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Volume 23 Number 1 January 2015Journal of Military and Veterans' Health Predicting bladder cancer death amongst Australian Veterans Army Malaria Institute – its Evolution and Achievements Rabies post-exposure prophylaxis in Australian Defence Force The Journal of the Australasian Military Medicine Association
AustrAlAsiAn MilitAry Medicine AssociAtion New Zealand Regional symposium Join us in wellington, NZ Register Now at www.amma.asN.au/woRkshops Venue: Trentham Military Camp Regional symposium Wellington, New Zealand Date: Saturday 21st March 2015 oN Ballistics aNd Time: 0900 - 1700 combat Facial trauma "Symposium will cover scenarios relating to Bomb, Blasts, Bullets, including response and management followed by trauma management and damage control surgery of facial trauma for the non head and neck clinician".
For further information visit www.amma.asn.au/workshops Dr Andrew Robertson
Dr Darryl Tong
AustrAlAsiAn MilitAry Medicine AssociAtion Table of Contents EditorialInside this edition . 3 New Zealand Regional symposium Original ArticlesPredicting bladder cancer death amongst Australian Veterans . 4 Army Malaria Institute - its evolution and achievements. Fourth decade (2nd half): 2000-2005 . 10 Review ArticlesVeterans with Co-morbid Posttraumatic Stress Disorder and Mild Traumatic Brain Injury: the Nurse Practitioners Role in Facilitating Treatment . 42 Short CommunicationRabies post-exposure prophylaxis in Australian Defence Force personnel in Afghanistan . 47 AMMA 2014 Conference Abstracts .52 Join us in wellington, NZ Venue: Trentham Military Camp Wellington, New Zealand Date: Saturday 21st March 2015 Time: 0900 - 1700 Cover photo: Courtesy of the Department of Deference Commonwealth of Australia 2015 Volume 23 Number 1; January 2015 Dr Andrew Robertson
Dr Darryl Tong
Journal of Military and Veterans' Health Dr Andrew Robertson (Editor in Chief) Dr Michael O'Connor Maj Gen Dato Mohd Zin Bidin BRIG Anne Campbell CDRE Michael Dowsett Australasian Military Medicine Association STATEMENT OF OBJECTIVES Air Vice Marshal Hugh Bartholomeusz, AM The Australasian Military Association is an Surgeon General Australian Defence Force Reserves independent, professional scientific organisation of health professionals with the objectives of: • Promoting the study of military medicine• Bringing together those with an interest in military medicine Dr Nader Abou-Seif • Disseminating knowledge of military medicine • Publishing and distributing a journal in military Dr Andrew Robertson • Promoting research in military medicine Mr Kerry Clifford Membership of the Association is open to doctors, dentists, nurses, pharmacists, paramedics and Mr Geoff Robinson anyone with a professional interest in any of the Ms Paula Leishman disciplines of military medicine. The Association is totally independent of the Australian Defence Force.
JMVH is published by the Australasian Military Medicine Association113 Harrington Street Ph: +61 3 62347844 ISSN No. 1835-1271 Journal of Military and Veterans' Health Inside this editionAs we move into 2015, we have a unique opportunity staff after the Bali Bombing, in his recent book "Air to look back to the origins of Australian Defence Force Force", (2) highlights both this continued dedication health services 100 years ago, the changes in Defence and the appreciation of these efforts by other non- healthcare in the intervening years and where we health ADF personnel. How we apply these lessons might expect to go into the future. The fundamentals in years to come will be of great interest.
of conflicts and wars themselves have changed – Some of the more perceptive of our readers may have from the set piece battles and trench warfare of the noticed that we did not publish a 4th issue in 2014. Great War to the highly mobile conflicts of the 21st This was to allow us to realign our publication dates century. The establishment of the No. 1 Australian and to get the first issue out early in 2015. Our first General Hospital (No. 1 AGH) is a case in point. issue has a tropical medicine theme, with excellent First sanctioned by the Commonwealth Defence articles on rabies and the more recent history of the Department in August 1914, the unit left Australia Army Malaria Institute. We also continue looking at as a General Hospital of 520 beds on board the S.S. cancer cases in serving members and veterans with Kyarra on 21 November 1914. Arriving in Egypt on a review of bladder cancer deaths among veterans. 14 January 1915, the No.1 AGH was set up in the This issue also looks at the nurse practitioners' role Heliopolis Palace Hotel. By June 1915, this 520 bed in facilitating treatment in post-traumatic stress hospital and surrounding buildings held nearly 2500 disorder. Finally, this issue includes all the abstracts patients, cared for by only 150 nurses. Needless to from our recent AMMA Conference in Sydney in say, hospital equipment and supplies were totally October 2014.
inadequate. (1) The sheer scale is daunting and, arguably, way beyond the worst nightmares of We continue to get a good range of articles, but other today's Defence health planners. The resilience of military and veterans' health articles are always very the medical, nursing and health support staff, the welcome and we would encourage all our readers to innovation in difficult situations and the dedication consider writing on their areas of military or veterans' to support the broader military forces continues health interest. on. Ian McPhedran's description of the life-saving Dr Andy Robertson, CSC health care provided by RAAF and other ADF health 1. Bassett J. Guns and Brooches: Australian Army Nursing from the Boer War to the Gulf War. Oxford; Melbourne: 1992.
2. McPhedran I. Air Force. HarperCollins; Australia: 2011.
Volume 23 Number 1; January 2015 Predicting bladder cancer death amongst Australian VeteransSophie Plagakis, Sheryl Edwards, Michael O'Callaghan, Darren Foreman Abstract
Background The purpose of this study was to compare the veteran and non-veteran cohorts of patients diagnosed
with bladder cancer in order to determine if veterans have a worse clinical outcome, as has previously been
demonstrated in prostate cancer.
Methods Using the Bladder Cancer Outcomes Database at the Repatriation General Hospital, South Australia,
all bladder cancer cases between January 1984 and December 2011 were identified. This data was used to
identify independent predictors of death in these populations and to contrast their five year bladder cancer-
specific and overall survival. A subgroup of muscle-invasive bladder cancer was also analysed. There were a
total of 1177 patients studied.
Results Overall, there was no significant difference in bladder cancer specific outcomes for veteran compared
to non-veteran subjects. In both groups, the staging of disease at diagnosis was the strongest independent
predictor of outcome, followed by the patient's age at diagnosis. Veterans were generally older at diagnosis than
non-veterans, and they did demonstrate worse all cause mortality outcomes.
In the muscle invasive bladder cancer subgroup, outcomes were similar between veterans and non-veterans but veterans were more likely to be treated with radiotherapy.
Conclusion The independent predictors of outcome and bladder cancer specific survival rates in our South
Australian cohort were similar to those described in the international literature and do not demonstrate poorer
outcomes in our veteran population. All cause mortality was worse in the veteran population, however, which
may be related to their older age at diagnosis and different treatments they may be offered as a consequence.
Keywords Bladder cancer, veteran, muscle invasive, survival
the non-veteran population.7 International studies have also demonstrated higher rates of bladder cancer Bladder cancer is the tenth most common malignancy in veterans from the USA and the United Kingdom ; diagnosed in Australia and has an annual incidence however there are no studies published reporting the of 2.0% among all newly diagnosed cancers.1 It is incidence of bladder cancer in Australian veterans.2,8 the seventh highest cause of cancer related death in the veteran population of the United States.2 It Analyses of the South Australian Prostate Cancer is predominantly diagnosed in older, male patients Outcomes Database have demonstrated that with almost 80% of patients being over 65 years of veterans have worse clinical disease profiles than age at the time of diagnosis. Since 1984, there has non-veterans with prostate cancer, and significantly been a decrease observed in the age-standardised lower prostate cancer-specific survival rates.9 This incidence of bladder cancer in both male and female study was designed to determine whether a similar Australians, and there has been a corresponding relationship exists with Australian veterans and increase in mortality of those who have been bladder cancer.
A further sub-group of patients with muscle-invasive There is a strong causal link with bladder cancer bladder cancer at diagnosis were identified within the and tobacco smoking.2-4 A study in 2011 found the veteran population. Their characteristics, treatment risk of bladder cancer to be four times higher in decisions and survival outcomes were compared smokers, compared with non-smokers5, and Kuper against a non-veteran population. et al. estimates a decrease of up to 60% in the risk of bladder cancer following cessation of smoking.6 In Materials and Methods the United States, it has been shown that the veteran Ethics approval for this project was obtained from population has a higher prevalence of smoking than the Southern Adelaide Clinical Human Research Ethics Committee. Journal of Military and Veterans' Health The Bladder Cancer Outcomes Database has been held a Department of Veteran's Affairs Gold Card maintained at the Repatriation General Hospital in at the time of diagnosis. Gold Card holders include South Australia since 1984, and contains almost ex-servicemen and women, and also include war 1500 patients. The database records all bladder widows and widowers and dependents of servicemen cancer diagnoses that have been treated at a single who were killed in the course of duty.10 public hospital, which caters for both veteran and A subgroup of patient with muscle-invasive bladder non-veteran patients within a large catchment area cancer were analysed separately using the additional in South Australia. Data is collected prospectively data of American Society of Anaesthesiologists and includes age, gender, disease stage and grade, (ASA) score and treatment modality. Comparisons treatment received, cytotoxic agent use, veteran between veteran and non-veteran groups were made. status and cause of death. The database was Distribution was compared with Kruskal Wallis tests originally conceived as a specialist nurse record of or a Chi-squared test (Fisher's exact test where patients' treatment to assist with the administration cell counts were low). Means were compared using of intravesical therapy and tracking ongoing a t-test. Independent predictors of survival were surveillance. It has since been approved for research analysed using a Cox proportional hazards model and five and ten year survival rates were obtained The Bladder Cancer Outcomes Database was used from a Kaplan-Meier curve. to identify patients who had been diagnosed between January 1984 and December 2011. Patient data extracted for this study included gender, age at The Bladder Cancer Outcomes Database identified diagnosis, stage and grade at diagnosis, and cause 1466 patients, however only 1176 had veteran status of death. Veterans were defined as patients who identified and were included in the study. There were Table 1: Patient characteristics in overall bladder cancer group and muscle-invasive bladder cancer sub-group Descriptors and Outcomes Mean Age at Diagnosis Five year bladder cancer specific survival (%) Ten year bladder cancer specific survival (%) Stage at Diagnosis Survival Outcomes Death – bladder cancer Death – other cause Lost to follow up Muscle-Invasive Bladder Cancer subgroup Proportion of cohort Average Age at Diagnosis Treatment modality *t-test; † Kruskal-Wallis test; ‡ Chi squared test. Volume 23 Number 1; January 2015 257 veterans and 919 non-veterans. The mean follow also evenly spread between the groups, and the p up time was 49 months for non-veterans (95% CI value between the groups was insignificant (p=0.75).
43-54) and 61 months for veterans (95% CI 49-72).
Independent predictors of survival were analysed in In total, 76.7% of the patient group were male, with a multivariable model and included age at diagnosis, a higher proportion of males when comparing the gender, veteran status, stage and grade of disease veteran group with non-veterans (90% compared at diagnosis. Veteran status was not a statistically significant predictor of death from bladder cancer (p = 0.96). However, age, gender and stage at diagnosis Mean age at diagnosis for veterans was 77 years were all significant predictors of death from bladder compared with 70 years for non-veterans (p value cancer. Increasing stage at diagnosis was associated <0.001). Almost 80% of veterans were diagnosed with increasingly worse outcomes. The hazard ratio between the ages of 70 and 89, whilst the majority for death from bladder cancer was 27.5 (95% CI 9.4- of non-veterans were diagnosed from 60 to 79 years 80.5) for T4 disease compared to 5.8 (95% CI 2.9- 11.8) for T1 disease.
Outcomes recorded in the database for all patients Bladder cancer specific survival was not significantly were: Alive, Dead from Bladder Cancer, Dead from different between veteran and non-veteran patients Other Cause and Lost to Follow Up. Non-veterans (p = 0.58). The longest a veteran lived post diagnosis were more likely to be alive. Veterans were more was 423 months, and the longest a non-veteran likely to have died from other cause compared with lived was for 364 months. Overall survival was non-veterans (50% compared with 24%, p <0.001). significantly worse among veterans compared with A higher proportion of veterans died from bladder cancer (18% compared with 13%, p <0.001).
Tumour stage at diagnosis was assigned by Muscle-invasive Bladder Cancer subgroup
pathological assessment as Ta, T1, T2, T3 and A subgroup of patients with muscle-invasive bladder T4. The tumour stage at diagnosis was similarly cancer was analysed. One hundred and fifty two distributed between both groups, with no significant patients were identified (28 veterans, 124 non- differences between the groups. Tumour grade was veterans, p = 0.33), and the average age at diagnosis Table 2: Cox proportional hazards model of survival from the time of diagnosis for bladder cancer patients and a subgroup of patients with muscle invasive disease (95% Confidence Interval) All Cases – bladder cancer specific survivalAge at Diagnosis 49.5 (20.1-122.1) Muscle-Invasive Bladder Cancer subgroup – overall survivalAge Treatment GroupSurgery 7.01 (3.86-12.76) Journal of Military and Veterans' Health Number at Risk
Number at Risk
was 82 years for the veteran group and 74 years The American Society of Anaesthesiologists (ASA) for the non-veteran group, which was significantly uses a physical status classification to record patient different (p <0.001). Veterans undergoing surgery fitness for an anaesthetic, which ranges from ASA had a higher median age than non-veteran patients 1, which is assigned to a healthy person, to ASA 4 (78 versus 68.5, p =0.13). There were a higher which is severe systemic disease that is a constant proportion of male patients in the veteran group. threat to life. The veteran group contained a higher proportion of patients with ASA 3 and 4 (p = 0.02). Veterans were three times more likely to have their muscle-invasive bladder cancer managed with There was no statistically significant difference radiotherapy (p <0.001), and were four times less in survival outcome of muscle-invasive bladder likely to have surgical excision of their bladder cancer patients between the two patient groups (p compared to the non-veteran group (Table 1). This is = 0.1). Neither age, veteran status nor gender were most likely reflective of their older age at diagnosis. A statistically significant predictors of death in the similar proportion in each group was managed with palliative intent. Volume 23 Number 1; January 2015 Number at Risk
specific mortality in patients diagnosed at an older In this South Australian population, we found that age, both because they are diagnosed with higher- the clinical descriptors of veteran and non-veteran risk tumours and are less likely to undergo aggressive patients with bladder cancer to be similar. The most treatment.14 We were not able to determine why marked differences occurred in age at diagnosis and veterans were diagnosed at an older age than non- gender. The gender difference between the groups was expected, due to the high male proportion within Female patients in our overall bladder cancer the veteran population. cohort did demonstrate poorer outcomes than Smoking history was not reliably recorded in the male patients. This trend is consistent with Bladder Cancer Outcomes Database and was not international literature.14-15 The reason for poorer used for analysis.
outcomes in females requires further investigation, and hypotheses include challenges staging disease Using the DVA Gold Card as the main identifier within the female pelvis, and delayed diagnosis for Veteran Status does mean that war widows due to symptoms being attributed to urinary tract and dependents have been included in our veteran infection or overactive bladder. It has also been population, however it was not possible to scrutinise suggested that women respond less effectively to their details after de-identification of data. We do intravesical treatments, but this is unsubstantiated acknowledge this as a weakness in our analysis. Bladder tumour grade was reported by our Veterans with muscle-invasive bladder cancer were pathologists according to Mostofi in 1973.11 more likely to be treated with radiotherapy than Modifications to grade occurred in 199812 and 2004,13 non-veterans, and this is most likely due to older age and these were also reported to allow for consistent at diagnosis and poorer anaesthetic fitness. There comparison between tumours within the database.
was no statistical difference between the groups in The stage and grade at diagnosis was comparable survival, although the sample size was small. between the groups. Considering the older age at In conclusion, this South Australian veteran diagnosis, the equivalent pathological stage suggests population did not demonstrate a worse clinical that there was no significant delay in diagnosis disease profile than the non-veteran population. Our within the veteran group. The older age at diagnosis cohort was predominantly male and diagnosed at may account for the higher proportion of death from an older age. However there was no statistically other causes in the veteran group. This contrasts significant difference in bladder cancer specific with recent studies that demonstrate worse cancer- survival, including the muscle-invasive disease Journal of Military and Veterans' Health subgroup, compared to the non-veteran group. Authors Affiliations: Veterans did however have worse all cause mortality Corresponding author: Dr Sophie Plagakis Department of outcomes. The most significant independent Urology, Repatriation General Hospital, Daw Park, SA 5041, Australia MBBS Contact details: 43 Ferry Ave, predictor of outcome in all patients is the stage of Plympton Park 5038 [email protected] disease at diagnosis, and this is consistent with the Ms Sheryl Edwards Department of Urology, Repatriation international literature. General Hospital, Daw Park, SA 5041, Australia Dr Michael O'Callaghan SA PCCOC and Department of Urology, Repatriation General Hospital, Daw Park, SA 5041, Australia. Also: University of Adelaide, Adelaide, SA Pinnock C and Walsh S for assistance with data analysis and Osei Tutu L for data collection.
Dr Darren Foreman Department of Urology, Repatriation General Hospital, Daw Park, SA 5041, AustraliaFlinders University, Bedford Park, SA 5000 Australia MBBS, FRACS (Urol) References1. Cancer incidence projections: Australia, 2011-2020, Australian Institute of Health and Welfare. Available at http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=10737421440 (Mar 2014) 2. McLaughlin JK, Hrubsec Z, Blot WJ et al. Smoking and cancer mortality among US veterans: a 26 year follow up. Int J Cancer 2005: 60; 190-193.
3. AIHW 2012. Cancer survival and prevalence in Australia: period estimates from 1982 to 2010. Cancer series no. 69. Cat. no. CAN 65. Canberra, AIHW.
4. Augustine A, Hebert JR, Kabat GC et al. Bladder cancer in relation to cigarette smoking. Can Res 1988: 48; 4405-4408.
5. Freedman ND, Silverman DT, Hollenbeck AR et al. Association between smoking and risk of bladder cancer among men and women. JAMA 2011:306; 737-745.
6. Kuper H, Boffetta P, Adami H-O. Tobacco use and cancer causation: association by tumour type. J Int Med 2002: 252; 206-224.
7. Zullig LL, Jackson GL, Dorn RA et al. Cancer incidence among patients of the U.S. Veterans Affairs health care system. Mil Med 2012:177; 693-701.
8. Muirhead C, Kendall GM, Darby SC et al. Epidemiological studies of UK test veterans. J Rad Prot 2004: 24; 9. Harbison J, Chopra S, Pinnock C et al. Clinical Profile of Veterans and Non-Veterans diagnosed with Prostate Cancer in the South Australian Prostate Cancer Outcomes Database. Abstract presented at the South Australia/Northern Territory Section USANZ Annual Scientific meeting, September 2010.
10. DVA Factsheet HSV59 Eligibility for the Repatriation Health Card – for All Conditions (Gold) [Internet]. Dept Veterans Affairs, Australian Government [updated 3 April 2014, cited 20 July 2014]. Available at: http://factsheets.dva.gov.au/factsheets/documents/HSV59%20Eligibility%20for%20Repatriation%20Health%20Card%20-%20For%20All%20Conditions%20%28Gold%29.pdf 11. Mostofi FK, Sobin LH, Torloni H. Histological typing of urinary bladder tumours. International Histological Classification of Tumours No.10. Geneva: World Health Organization, 1973.
12. The Bladder Consensus Conference Committee, Epstein JI, Amin MB, Reuter VE, et al. The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Am J Surg Pathol 1998; 12:1435-48.
13. Eble JN, Sauter G, Epstein JI et al. A World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press, 2004.
14. Noon AP, Albertsen PC, Thomas F et al. Competing mortality in patients diagnosed with bladder cancer: evidence of under treatment in the elderly and female patients. Br J Cancer 2013: 108; 1534 – 1540.
15. Mungan NA, Aben KK, Schoenberg MP et al. Gender differences in stage-adjusted bladder cancer survival. Urology 2000: 55(6); 876-880. Volume 23 Number 1; January 2015 Army Malaria Institute - its evolution and achievements. Fourth decade (2nd half): 2000-2005Karl H. Rieckmann, Qin Cheng, Stephen P. Frances, Scott J. Kitchener, Robert D. Cooper, Alyson Auliff, Michael D. Edstein The 2000-2005 quinquennium saw a marked drop in the number of Australian Defence Force (ADF) personnel suffering from malaria following the deployment of an Australian Army Malaria Institute (AMI) outbreak investigation team to Timor Leste and improved compliance with various prevention measures. The field evaluation of novel drug regimens using currently registered and new drugs also contributed to the reduced number of malaria cases overseas and after return to Australia. The main purpose of some of these studies was to determine the tolerability and effectiveness of more user friendly drug regimens, such as shorter courses of primaquine and 3-day courses of tafenoquine for post-exposure prophylaxis against vivax malaria. Clinical/field studies were also conducted with atovaquone/proguanil (Malarone®), loading doses of mefloquine, and a new artemisinin drug – artemisone. All of these investigations yielded positive results. Another landmark study – the first Phase III study in which weekly tafenoquine was taken for six months by non-immune individuals – showed that Australian soldiers could be protected against both falciparum and vivax malaria while in Timor Leste without having to take a post-exposure primaquine eradication course upon return to Australia. In addition to documenting increasing drug resistance of malaria parasites in various parts of the Asia/Pacific region, molecular markers and changes associated with parasite resistance to antimalarial drugs were identified. An in vitro field test for assessing the drug susceptibility of Plasmodium vivax was also developed and, for the first time, successful transfection of P. vivax genes to continuously cultured P. falciparum enabled antifolate drugs to be screened in vitro for their activity against P. vivax. Furthermore, various laboratory/epidemiological studies and mathematical models were developed to investigate factors involved in the evolution and spread of drug resistance, such as mutation patterns, antigenic variation, loss of fitness, and inappropriate treatment. In ongoing efforts to improve protection against mosquito bites, the effectiveness of various repellents/insecticides applied to skin, clothing and tents were evaluated in military training areas in Queensland and the Northern Territory. Mosquito control measures, including the use of newly-developed tools, were instrumental in controlling the outbreak of both malaria and dengue fever in Timor Leste. Furthermore, investigations in Australia, Vietnam and China indicated the potential value of novel molecular-based and other tests for identifying and controlling the spread of mosquitoes transmitting malaria, dengue and Japanese encephalitis. In view of the ADF's increasing exposure to arboviral diseases, further clinical studies were conducted to assess the tolerability and immunogenicity of dengue and Japanese encephalitis vaccines and prelicensure studies were started to determine the effectiveness of new vaccines.
By the mid-1960s, there were renewed concerns regarding the ability of antimalarial drugs to In 1943, an impressive medical and scientific provide adequate protection against malaria. In group was assembled by Brigadier Neil H. Fairley 1965, Professor Robert H. Black, Army Consultant in response to the devastating effects of malaria in Tropical Medicine and a previous investigator at being experienced by allied soldiers deployed to the the Cairns Unit, proposed that the Army should South Pacific. In just three years (1943-1946), the conduct malaria studies to address the growing drug ‘high priority' Land Headquarters Malaria Research resistance problem in Southeast Asia.2 As a result, a Unit, based at Cairns in North Queensland, obtained small research unit comprising two scientists and a considerable new information about the activity few technicians was established at the University of of drugs such as proguanil (Paludrine®) against Sydney in 1966. Although additional positions were different stages of the human malaria parasite and established later, research activities were hampered was able to protect soldiers remarkably well against by frequent staff changes and cramped facilities. malaria infections.1 Journal of Military and Veterans' Health The relocation of the unit to more spacious pre- effectiveness during ADF deployments overseas.5 fabricated quarters behind 2nd Military Hospital More recently it had shown that daily atovaquone/ at Ingleburn, Sydney in 1974 led to a gradual proguanil (Malarone®) could be used as an improvement in the scope and significance of alternative to doxycycline if required.6 Studies by research activities at the Army Malaria Research Unit AMI had also demonstrated that tafenoquine, a (AMRU), receiving a special boost when the number long-acting 8-aminoquinoline drug, might ultimately of unit staff positions was increased from 13 to 24 play a very useful role in malaria prophylaxis and in 1982.3 Commencing in the mid-1980s the pace of possibly replace primaquine for prevention of vivax research activities gathered momentum and greater malaria.6 Although higher doses appeared to be emphasis was placed on practical problems facing more effective,6 the very short elimination half-life Australian Defence Force (ADF) personnel deployed of primaquine and its toxicity (e.g. gastro-intestional to malarious areas.4,5 disturbances) would always remain a problem. With the growing threat of drug resistance, significant The unit continued to operate out of Sydney until progress was made in the non-clinical assessment of late 1996 when it was relocated to a new purpose various potential antimalarial drugs, including the built laboratory complex at Gallipoli Barracks, artemisinins, Mannich bases, and third generation Enoggera, Brisbane and known as the Australian Army Malaria Institute (AMI).6 The establishment of the Institute enabled the ADF to play a key global The establishment of a molecular parasitology role in the fight against malaria and other vector- laboratory broadened the scope of investigations in borne diseases (VBDs). Enhanced collaboration with malaria diagnosis and drug resistance.6 Early results Australian and overseas institutions empowered using DNA technology identified molecular markers AMI to make evermore significant contributions to for atovaquone resistance. These procedures also the more effective control of VBDs. This was further complemented various investigations with already facilitated by increased funding from non-Defence established in vitro and in vivo procedures and Health Service sources. enhanced AMI's fundamental commitment to improve malaria diagnosis and to monitor the evolution and Commencing in 1997, AMI deployed outbreak spread of drug resistance.
management teams to Bougainville, and later to Timor Leste (formerly known as East Timor), in In the continuing quest for improved personal response to scores of soldiers developing malaria protection against mosquito bites, field studies while on deployment to these areas.6 Without daily included the evaluation of two novel topical mosquito doxycycline prophylaxis, there is ample evidence repellents and a self-erecting, low profile bednet.6 that up to one thousand soldiers would have been The extensive survey of anopheline mosquitoes in 10 incapacitated by malaria, most of them infected provinces of PNG, started in 1992, was completed with potentially fatal falciparum malaria.6 Apart in 2000.6 Detailed analysis of collected specimens, from causing personal distress, this would have using DNA-based technology and monoclonal compromised operational capability, placed severe antibodies, revealed many hereto unknown facts of strain on the health services and may even have significant benefit to malaria control activities. One jeopardised the successful outcome of the peace- of these was groundbreaking information on the keeping missions. Despite the prescribed 14-day vectorial capacity of various genotypes and taxons of post-exposure primaquine course, several hundred Anopheles farauti. soldiers experienced their first attack of vivax AMI became involved with other mosquito-borne malaria after returning to Australia. Furthermore, diseases following its relocation to Brisbane.6 about one-fifth of them proceeded to have one to four After identifying Ross River virus in mosquitoes at relapses for up to a year after their initial attack. the Shoalwater Bay Training Area in Queensland This course of events was a rather sobering reminder during 1998, further observations highlighted the that malaria continued to be a serious threat to the importance of collecting serum specimens for IgG well being and fitness of military personnel deployed and IgM analysis during both acute and convalescent to malarious areas. In addition to highlighting the phases of the illness. In 1999/2000, AMI identified importance of adhering to prescribed antimalarial 160 cases of dengue (mostly serotype 3) among ADF measures, it emphasised the need for more effective personnel in Timor Leste and virus containment and user friendly tools to counter the ever increasing was successfully managed, when nine of them were problem of drug resistance.
medically evacuated to Townsville. In response to AMI had earlier on pioneered the use of doxycycline the shortage and cost of Japanese encephalitis for mass chemoprophylaxis and demonstrated its (JE) vaccine (Biken) in Australia, a series of studies was undertaken which revealed that low dose Volume 23 Number 1; January 2015 intradermal injections (one-fifth of the dose of the also had adjunct academic appointments with usual regimen) were able to provide good protection, the Faculty of Health Sciences of the Unversity of thereby extending the life of the vaccine stockpile. Queensland. Departmental activities were supported by an Administrative/Logistics section, a Quality By 2000, AMI had evolved from its humble beginnings Assurance section, and various committees, such in the mid-1960s to become a world centre of as Biosafety and Animal Ethics. All human studies excellence for malaria research. were reviewed by the Australian Defence Human Mission, Organisation and Staff Research Ethics Committee. AMI continued its mission to ensure that ADF Drug Resistance and Diagnostics (DRD). Dr Qin
personnel were able to have the best possible Cheng was the Head of the department. Members protection against malaria and other VBDs. This of her staff included Dr Nanhua Chen, Captain mission had become more important than ever with Alyson Auliff, Captain Bruce Russell (up to 2002), the increased deployment of military personnel Lieutenant Joanne Baker, and Lieutenant (Army to areas overseas with a high prevalence of VBDs. Reserve) Michael Korsinczky.
Recent deployments to Bougainville, Papua New Key functions of the department were (1) to monitor Guinea, and Timor Leste had demonstrated the drug susceptibility of malaria parasites in the field; (2) importance of adequate protection against these to better understand how and why parasites develop diseases for optimum performance under adverse drug resistance; (3) to determine host, parasite and environmental factors that might enhance or hinder During the 2000-2005 quinquennium, Professor Karl the development and spread of drug resistance; and Rieckmann continued to lead AMI's activities. In late (4) to improve the reliability and performance of 2002, Lieutenant Colonel Michael Edstein retired malaria diagnosis.
from full-time military service, and his position Responding to a call for applications by the National as Deputy Director and Commanding Officer was Institutes of Health, USA, a research proposal by filled by Lieutenant Colonel Robert Cooper. Both Dr Qin Cheng and Prof Allan Saul (QIMR) entitled scientists were long-standing members of AMRU/ "Evolution of drug resistance in Plasmodium AMI and they continued to remain actively involved falciparum" was submitted and subsequently funded in various laboratory and field activities throughout for three years commencing in March 2000. The this quinquennium.
project aimed to develop computer models, based Effective control of malaria parasites, arboviruses, on laboratory experiments and mathematical and their mosquito vectors relied heavily on modelling, which would mimic both the growth of an improved understanding of the biology and malaria parasites in people and the transmission epidemiology of these organisms. For example, the of parasites within communities. The models would ever-changing susceptibility of malaria parasites to then be used to investigate factors underlying the drugs could be tackled more effectively by a better development and spread of drug resistance, thereby insight into the mechanisms of drug resistance and helping to design better strategies for extending the by developing better surveillance techniques. In life of existing antimalarial drugs and for protecting addition to devising novel regimens and approaches future drugs. Following the departure of Prof Saul a to improving the effectiveness of currently few months after initiation of the project, Dr Cheng available agents, AMI was actively involved in the became the Principal Investigator, assisted by Dr development and/or evaluation of new antimalarial Michelle Gatton (mathematical modeller), Dr Beth drugs, vaccines and personal protection measures. Fowler (molecular geneticist), and Mrs Jenny Peters Although these investigations were generally tailored (molecular biologist). At the end of this first NIH grant to meet the requirements of the military sector, many funding period, a competitive renewal application of them were of benefit for controlling malaria and entitled "Antigenic variation and drug resistance in other VBDs in civilian populations.
P. falciparum" was prepared and submitted to NIH by Dr Qin Cheng (Principal Investigator) and Drs Objectives at AMI were primarily achieved through Michelle Gatton, Nanhua Chen and Dennis Kyle the activities of its five departments: Drug Resistance (Co-Investigators). Based on results obtained during and Diagnostics (DRD), Drug Evaluation (DE), the first grant, NIH provided support for a further Clinical Studies and Surveillance (CSS), Vector three years (2004-2007). Dr Darren Krause joned the Surveillance and Control (VSC), and Arbovirology research efforts in 2004.
(AV). Each department head had either a military or civilian appointment within the Australian Drug Evaluation (DE). Dr Michael Edstein was the Head
Defence Organisation. Some department heads of the department. Members of his staff included Dr Journal of Military and Veterans' Health Barbara Kotecka, Dr Marina Chavchich (from 2003), against VBDs by monitoring their occurrence and Sergeant Kerryn Rowcliffe, Mr Thomas Travers, Mr prevalence; (3) to provide clinical advice on VBDs to Wayne Lyons, and Sergeant Hamish Barbour (from ADF personnel; and (4) to maintain the ADF Central 2003). Veterinarians at the Institute's animal facility Malaria Register.
were: Major Ivor Harris, Captain (Army Reserve) Clair Vector Surveillance and Control (VSC). Major Stephen
Nussey (until 2001), Captain (Army Reserve) Narelle Frances replaced Major Robert Cooper as Head of Peach (until 2003), Captain (Army Reserve) Joanne the department in 2002 following Major Cooper's Beckett (from 2002), and Captain (Army Reserve) promotion to Commanding Officer. In addition to Amanda Perry (from 2004). Animal technicians both of these long-serving entomologists, other included Mr Zbigniew Kotecki and Mrs Julie Staley members of the department included Miss Cassie (until 2003).
Jansen (until 2004), Lieutenant Robert Marlow Key functions of the department were (1) to optimise (from 2004), Sergeant Stephen Mcleod-Robertson, drug regimens for malaria prophylaxis and treatment Corporal Brooke Wilson (2001-2002), Corporal by pharmacokinetic and pharmacodynamic studies; Raethea Huggins (2002-2005). (2) to support new antimalarial drug discovery Key functions of the department were (1) to conduct progams; (3) to assess the antimalaria activity risk assessment of exposure to VBDs by mosquito of promising candidate drugs using various surveys; (2) to provide field commanders with the best parasitological tools and animal models; and (4) to possible assessment of risk from VBDs and optimum manage the animal facility.
vector protection measures; (3) to identify potential Dr Edstein was intimately involved with the mosquito vectors of VBDs by using molecular-based establishment of the Vietnam Australia Defence technology; (4) to determine environmental factors Malaria Project (VADMP) and assumed primary affecting the distribution patterns of anopheline responsibility for operational administration of the mosquitoes; (5) to evaluate personal protection Australian component of the project. He also played measures against VBDs used by ADF personnel a leading role in contributing to the successful under field conditions, especially topical mosquito outcome of many of the clinical and field studies in repellents, impregnated military clothing and Vietnam and in organising the exchange visits by bednets; and (6) to evaluate the use of pyrethroid Vietnamese and Australian personnel. insecticides in military fabrics for protection against Clinical Studies and Surveillance (CSS).
nuisance and vector mosquitoes.
Colonel Peter Nasveld continued to be closely Arbovirology (AV). Major Stephen Frances was Head
involved in operations of several departments of of the department until 2002 when he relinquished the Institute, having been posted as Senior Medical the position to direct VSC activities. His position was Officer of the Third Brigade to the forward area of assumed by Major (Army Reserve)/Professor John operations in Timor Leste at the beginning of this Aaskov, an experienced virologist at QUT, who had period. Major Scott Kitchener (1999-2002) carried joined AMI in 2000. Members of his staff included on Lieutenant Colonel Nasveld's work as department Captain Mark Reid, Lieutenant Michael Reid (until head from late 1999 before being replaced by 2003), Cadet Lisa Baade, Sergeant Kerry Somerscales Lieutenant Commander Sonya Bennett (2002- (2002-2003), Corporal Natalie Lehmann (2003), and 2004). Following his departure and appointment Corporal Andrew Baron (from 2004).
as Lieutenant Colonel (Army Reserve), he became Key functions of the department were to improve the involved with the development of chimeric arborviral capacity of the ADF to detect, diagnose and prevent vaccines at Acambis Research (ACR) and provided a diseases caused by mosquito-borne viruses. During link for their subsequent clinical evaluation by AMI. this period, Captain Reid helped accredit AMI with Valuable support was also provided by Major (Army the Office of the Gene Technology Regulator and Reserve) Nathan Elmes (from 2003), Captain (Army manage the Physical Containment Level 3 arbovirus Reserve) Anne Jensen (from 2001), and Captain (Army Reserve) Tracy Carthew (from 2002). Other members included Warrant Officer John Staley (until Administrative/Logistic Section. Major Ivor Harris
2003), Warrant Officer Derek Davis (from 2004) and was the Head of the section except during his Sergeant (Army Reserve) Christine Atkins (from absence in Antarctica during 2003 when his duties were performed by Major Robin Gregory. Other members included Major (Army Reserve) Chrisopher Key functions of the department were (1) to conduct McCormack (from 2003), Sergeant (Army Reserve) clinical evaluations of antimalarial drugs and John Humphries, Corporal Anna Davis (until 2002) vaccines against VBDs; (2) to protect ADF personnel and Mr Kevin Anderson (from 2002) in Administration, Volume 23 Number 1; January 2015
and Corporal John Ross (until 2003) and Corporal Cameron Redman (from 2003) in Logistics.
Key functions of the section were (1) to provide personnel management, training and security support; (2) to manage internal and external financial affairs; (3) to prepare staff for courses, overseas visits and overseas deployments; (4) to manage the day-to-day administration of overseas visitors engaged in research activities at AMI; and (5) to order and account for equipment and supplies required by the departments and coordinate the maintenance and repair of equipment. During this period, the section maintained a considerable operational tempo of personnel movement and support for extended periods in several overseas operations.
Quality Management Section. Mr Ken Lilley was the
Head of the section and was assisted by Major (Army
Reserve) Robin Gregory.
Figure 1: Visit to AMI by US Army Surgeon General, July 2002. (L to R): Dr Q. Cheng, Lieutenant Colonel R.D. Key functions of the section were (1) to ensure Cooper, Lieutenant Colonel M.D. Edstein, Commander S. that laboratory equipment and procedures were Bennett, Professor K. H. Rieckmann, Lieutenant General maintained at the highest standard to produce J. B. Peake, Lieutenant Colonel D. E. Kyle, Lieutenant data with the greatest accuracy and validity; (2) Colonel S. Boos, Captain M. G. Reid, Major S. P. Frances, to implement and maintain accreditation and Colonel P. Alexander. certification with national and international authorities such as National Association of activities were closely integrated with work being Testing Authorities/Royal College of Pathologists carried out by the DRD and DE departments. of Australasia. (NATA/RCPA) and ISO 9001:2000; to conform to the relevant requirements of the Collaboration and engagement with military and Office of the Gene Technology Regulator (OGTR), civilian organisations the Australian Quarantine and Inspection Service (AQIS), and the animal use requirements of the Apart from close collaboration with medical research Commmonwealth Scientific and Industrial Research establishments within the US Army, as evidenced Organisation (CSIRO) and Queensland Department by the establishment of the WRAIR Laboratory at of Primary Industries (DPI); and (3) to promote a AMI, collaboration and engagement with various culture of continuous improvement in the pursuit of military and civilian organisations, both in Australia and overseas,5,6 was maintained and expanded during this quinquennium. This was of paramount Walter Reed Army Institute of Research (WRAIR)
importance in achieving AMI's objectives to improve the control of malaria and other VBDs. The WRAIR laboratory was established at AMI in Vietnam Australia Defence Malaria Project (VADMP)
2001 with the arrival of Lieutenant Colonel Dennis Kyle from WRAIR. He was part of the Engineer and Following several years of consultation, a vitally Scientist Exchange Program (ESEP) between the important relationship was established between the Australia Defence Organisation and the United ADF and the Vietnam People's Army (VPA) with the States Department of Defence. Just before his signing of a Memorandum of Understanding (MOU) departure in 2004, Major Michael O'Neil replaced in Hanoi in March 2000.6 This marked the start of the him for a further 3-year assignment by WRAIR to Vietnam Australia Defence Malaria Project (VADMP) AMI. They were assisted in their investigations by Dr which not only served to enhance malaria control Marina Chavchich (from 2003), Mrs Jennifer Peters activities within the defence forces of Vietnam and (from 2004) and Ms Karryn Grestey (from 2005).
Australia but also contributed to developing overall closer defence cooperation between both countries.6 Key functions of the laboratory were (1) to support This long-term collaborative project between the discovery of new antimalarial drugs; (2) to study AMI and the VPA Military Medicine Department drug resistance; and (3) to develop tools for controlling (MMD) had a strong and comprehensive focus on drug-resistant malaria more effectively. Most of their training, technological transfer, capacity building, Journal of Military and Veterans' Health
developing effective antimalarial drug regimens and malaria vectors of the Hyrcanus group of mosquitoes characterising malaria transmission. in central and southern China. Mr Ken Lilley acted as Rapporteur at a WHO Multiregional Workshop The principal collaborating institutions in on "Quality Assurance of Malaria Light Microscopy" Vietnam were the Military Institute of Hygiene held in Malaysia, in addition to conducting WHO- and Epidemiology (MIHE) and the Central Military sponsored malaria microscopy courses in the Hospital 108 in Hanoi, and the Military Preventative Philippines, Cambodia, Indonesia and the Solomon Medical Centre and Military Hospital 175 in Ho Islands. The purpose of these courses was to Chi Minh City. During this quinquennium six assesss the proficiency of provincial microscopists, Vietnamese officers spent 2 to 6 months at AMI. to identify qualified personnel as national trainers, Among them was Colonel Vu Quoc Binh, Deputy and to review draft quality assurance (QA) programs Director of MIHE, and later to become the Director and procedures for malaria microscopy and RDTs at of MMD and the Surgeon-General of VPA, and country peripheral levels.
Lieutenant Colonel Le Nogc Anh, Secretary of the Project Management Unit of VADMP in Vietnam. On 12 August 2002, the VADMP Laboratories were officially opened at MIHE, the ceremonies being attended by the Australian Ambassador to Vietnam and other dignitaries. Following the establishment of the Laboratories, successful laboratory and field studies were conducted, with some results being presented at the 14th and 15th Asia Pacific Military Medicine Conferences held in Brisbane (2004) and Hanoi (2005), respectively.
World Health Organization (WHO) Collaborating Centre
Professor Rieckmann continued to serve as Director
of the WHO Collaborating Centre for Malaria and, at
the end of the quinquennium, completed his 32-year
service as Member of the WHO Expert Advisory Panel
Figure 2: Inauguration of Vietnam Australia Defence on Malaria. Between 9-11 December, AMI hosted the Malaria Project laboratories, Hanoi, August 2002. "13th South-West Pacific Malaria Meeting – Roll Back Malaria in the Pacific". This meeting brought together Wide network of partnerships
nine national representatives from Governments in Interaction with other experts at national and the region, eleven Who staff members, five temporary international meetings continued to enhance AMIs advisers, and six observers from national and ability to achieve its objectives. For example, following international funding organisations to discuss many the outbreak of vivax malaria in ADF personnel different aspects of malaria control in the region. returning to Australia, AMI co-sponsored the first- AMI was also visited by several WHO staff during ever international conference on vivax malaria 2000-2005, including several visits by Dr David Bell research organised by the US-based Multilateral and Dr Jeffrey Hii. Initiative on Malaria (MIM). This 2002 conference Throughout this period, many AMI staff members in Bangkok provided AMI staff with the opportunity continued to contribute to, and benefit from, to interact with others who were also concerned participation in WHO activities. Dr Qin Cheng with the prevention of vivax malaria after leaving served as Temporary Adviser at WHO Workshops/ endemic areas. The second international conference Consultations in Shanghai and Manila, and was - "Vivax Malaria Research: 2005 and beyond" was the recipient of two WHO grants relating to rapid held in Washington DC, USA, with Dr Cheng being a diagnostic tests (RDTs) for malaria. She was also member of the organising committee.
a collaborating partner on a WHO funded project All departments were involved in continuing and to eliminate malaria from the Hainan Province in expanding their collaboration with other institutions. China. Ms Joanne Baker participated in WHO- These institutions included: sponsored field and laboratory evaluations of RDTs (1) AFRIMS - Armed Forces Research Institute of in the Philippines. Dr Robert Cooper, in collaboration Medical Sciences, Bangkok, Thailand. with Professor Gao Qi (JIPD) and Dr Nigel Beebe (UTS), received a WHO grant to study the potential (2) AP - Aventis Pasteur, France Volume 23 Number 1; January 2015 (3) ACR - Acambis Research, UK (4) BAY - Bayer AG, Germany Many of the objectives at AMI were achieved by joint (5) CDC - Center for Disease Control, USA efforts between two or more departments. Because of (6) GMI - Gorgas Memorial Institute of Health this, outcomes and achievements of each department are not presented under department headings. Rather, they are presented according to key objectives (7) JPC - Jacobus Pharmaceutical Company, USA pursued by AMI during this quinquennium. (8) JIPD - Jiangsu Institute of Parasitic Diseases, 1. MALARIA PREVALENCE AND SURVEILLANCE
(9) MAH - Mahidol University, Thailand Regular six-monthly updates on the malaria situation (10) MERLIN - Medical Emergency Relief in the ADF were issued during this quinquennium.7-9 International, UK They were based primarily on the analysis of data (11) MMV - Medicines for Malaria Venture, provided by health personnel to the ADF Central Malaria Register maintained at AMI.10 Malaria notifications in the ADF declined from almost 400 (12) MSHR - Menzies School of Health Research, cases in 2000 to 75 in 2001, and then to fewer than 20 per year over the next four years.11 As described (13) NAMRU-2 - ) US Naval Medical Research Unit previously,6 most of the malaria cases in 2000 were No. 2, Indonesia observed in soldiers who experienced their first acute (14) NIH - Laboratory of Parasitic Diseases, National attack of malaria in Australia because doxycycline Institutes of Health, USA had effectively suppressed their vivax infections (15) NIHRD - National Institute of Health Research while they were on peacekeeping duties in Timor and Development, Indonesia Leste. However, because more than 60 soldiers developed malaria (two-thirds of them falciparum (16) QH - Queensland State Health, Tropical Public malaria) soon after arrival in the forward area of Health Program, Australia operations,12 an AMI disease outbreak investigation (17) QIMR - Queensland Institute of Medical and management team was deployed to Timor Leste Research, Australia at the beginning of 2000.13 (18) QUT - Queensland University of Technology Major risk factors were poor compliance with (19) PNGIMR - Papua New Guinea Institute of doxycycline prophylaxis, involvement in night Medical Research, PNG operations, lack of preventive medicine support (20) RITM - Research Institute of Tropical Medicine, and higher risk locations selected by platoons. Following initial field assessments, the malaria (21) SMRU - Shoklo Malaria Research Unit, outbreak was brought under control by instituting various epidemiological surveillance and operational (22 UQ - University of Queensland, Department of activities (in collaboration with preventive medicine Parasitology, Australia personnel) and fostering improved compliance with personal protection and chemoprophylactic (23) UTS - University of Technology Sydney, measures.13-15 In addition, new tools were assessed for improved prevention and control of malaria (see (24) VBDCU - Vanuatu Malaria and Other Vector below). The marked reduction in the number of Borne Diseases Control Unit, Vanuatu malaria cases was achieved despite a significant level (25) VADMP - Vietnam Australia Defence Malaria of malaria transmission in the local villages.16 Apart from being infected with P. falciparum and P. vivax, a (26) WEHI - Walter and Eliza Hall Institute, few villagers were infected with P. malariae, possibly the first report of the presence of this Plasmodial species on the island of Timor Leste.17 (27) WHO - World Health Organization, Switzerland(28) WHO/WPRO - World Health Organization, 2. PROPHYLAXIS AND TREATMENT OF BLOOD
Western Pacific Regional Office, Philippines STAGE MALARIA PARASITES
(29) WRAIR - Walter Reed Army Institute of AMI continued its investigations to identify better Research, Experimental Therapeutics Division, tools for countering the threat posed by drug-resistant malaria. More than a decade ago AMI had pioneered (30) WRL - Wellcome Research Laboratories, the daily use of doxycycline for military contingents deployed to malarious areas. This tetracycline Journal of Military and Veterans' Health antibiotic continued to be effective against the blood view of the well known heightened vulnerability of stages of drug-resistant parasites and was the first- pregnant women to malaria infections, higher risk line drug for protecting ADF personnel against malaria of developing severe malaria, and the fact that no while they were overseas. Atovaquone/proguanil information was available on the extent to which the (Malarone®), a drug combination which had been extensive physiological changes during pregnancy investigated intensively at AMI for many years, had might affect the pharmacokinetics of this drug recently been approved for daily use by soldiers who were unable to take doxycycline. However, under The first study, carried out in healthy Karen women certain field conditions, better drug compliance during the second and third trimesters of pregnancy, might be achieved by using ADF's second-line drug, showed that plasma concentrations of cycloguanil, mefloquine, which had to be taken only once a week. the active triazine metabolite of proguanil, were Although mefloquine was being used widely overseas reduced by approximately 50% when proguanil as a first-line drug for malaria prophylaxis, further was administered alone.18 This suggested that information regarding mefloquine's tolerability, late pregnancy was associated with reduced safety and pharmacokinetics seemed desirable. biotransformation of proguanil. Although pregnancy Most drugs used for prophylaxis were also being did not affect the rate of proguanil absorption, used to treat drug-resistant malaria infections. But, it did increase plasma clearance and apparent increasingly, they were being used in combination volume of distribution of the drug, suggesting that with artemisinin drugs, a group of semi-synthetic pregnant women might need to receive a higher compounds derived from Artemisia annua. Apart from dose of proguanil. In the second study, serial an extremely rapid clinical response to treatment, plasma concentrations of atovaquone, proguanil and artemisinin-based combination therapy (ACT) was cycloguanil were measured in 24 malaria infected far more effective than mono-drug therapy in curing pregnant Karen women after completing a 3-day falciparum infections and reduced the likelihood of treatment regimen consisting of atovaquone (20 mg/ the emergence of drug-resistant parasites. During kg/day), proguanil (8 mg/kg/day) and artesunate the previous decade, AMI had developed in vitro (4 mg/kg/day).19 This ACT was well tolerated tests and bioassays to assist in the pharmacokinetic with no adverse effects in the pregnant women, evaluation of various artemisinin and antifolate birth outcomes, and other clinical and laboratory compounds.5,6 Investigations were now broadened parameters. Compared with previously reported to determine the pharmacokinetics of atovaquone/ blood maximum drug concentrations (Cmax) and proguanil, mefloquine and other compounds used area under the drug concentration versus time curve in ACTs. Furthermore, studies were carried out to (AUC) values of atovaquone, proguanil and cycloguanil assess the effects that pregnancy, gender or food in healthy women from the same population group, might have on the absorption and/or disposition of pregnancy caused a 50% reduction in the Cmax and these drugs, because they might ultimately affect AUC values, suggesting that the dose of atovaquone- their bioavailability and effectiveness. In view of the proguanil might need to be increased for malaria increasing role of artemisinin drugs in the treatment treatment during pregnancy.
of drug-resistant malaria, further studies were carried out with artemisone, a potent new drug with Prolonged persistence of atovaquone after
little or no neuro- or cyto-toxicity.
administration of atovaquone/proguanil (Malarone®)
Further information on the pharmacokinetics of
Atovaquone/proguanil (Malarone®) pharmacokinetics
atovaquone was obtained by determining plasma atovaquone concentrations collected from three Atovaquone/proguanil/artesunate was a well Caucasian volunteers after they had been treated tolerated and highly effective ACT that was being for three days with atovaquone/proguanil during investigated for the treatment of falciparum malaria. malaria investigations at QIMR.20 The average Earlier studies in collaboration with WRL had shown elimination half-life of atovaquone in the volunteers that the pharmacokinetics of individual components was much longer than expected at 5.9 days by high of this ACT were not altered when given in performance liquid chromatographic (HPLC) analysis combination with one another.6 As few antimalarial and 4.9 days by bioassay, and atovaquone was still drugs could be recommended during pregnancy, the present 35 days after treatment. These half-lives were SMRU on the western border of Thailand approached about twice as long as those obtained previously in AMI in 2001 to assess the pharmacokinetics of the African and Asian patients treated with atovaquone. proguanil and atovaquone components of this ACT Since proguanil has a half-life of less than one day, during pregnancy. This was especially important in proguanil would not be present to potentiate the Volume 23 Number 1; January 2015
antimalarial activity of atovaquone for about a month deployments on doxycycline prophylaxis. The three after treatment. Although the prolonged persistence soldiers who experienced serious adverse events of a of atovaquone would be of little consequence when neuropsychiatric nature, all revealed prior episodes used by short-term travellers, it could lead to the of either depression, hallucinations or epilepsy. All rapid selection of atovaquone-resistant parasites if soldiers were protected against malaria while in used widely by residents living in endemic areas Timor Leste and 94% of them indicated that they would use mefloquine again. Clinical assessment Effectiveness, tolerability and pharmacokinetics of
after the loading dose was found to be both positively mefloquine for malaria prophylaxis in Timor Leste
and negatively predictive of side effects associated Poor compliance by some soldiers with daily with mefloquine, simplifying its use for malaria doxycycline prophylaxis led to an appraisal of the chemoprophylaxis. Pharmacokinetic studies also wider use of mefloquine for ADF personnel because provided much useful information relating to the it had to be taken only once a week.21,22 Although use of this drug under operational conditions.25 mefloquine prophylaxis had been well tolerated After determining plasma mefloquine concentrations by British, Dutch, Indonesian, Italian and US by HPLC at various times during prophylaxis, the soldiers during two to five month deployments to pharmacokinetics of mefloquine could best be malarious areas, parasite resistance to mefloquine described as a two-compartment model: low plasma had been encountered in Cambodia and Indonesia. clearance (CL/F, 2.1 L/h) and a high central volume Furthermore, there were isolated reports of severe of distribution (V1/F, 528 L), with an elimination neuropsychiatric side-effects associated with the half-life of 14.0 days. Body weight had a positive use of mefloquine. Following a field study in Timor influence on central volume but was insufficient to Leste during which no severe adverse events were warrant adjustments to the drug regimen.
observed in the 162 Australian soldiers receiving mefloquine for six months,23 a large field study was Clinical studies in Vietnam on the influence of food on
undertaken in Timor Leste to determine whether a mefloquine and piperaquine pharmacokinetics
loading dose of mefloquine would (1) help to identify Food had been reported to increase the bioavailability individuals who might not tolerate the drug, and (2) of mefloquine in healthy Caucasian volunteers, but allow "steady-state" blood mefloquine concentrations it was unclear whether this was also the case in to be reached right at the start rather than several malaria patients. As part of a VADMP project, the weeks after commencing weekly medication.
pharmacokinetics of mefloquine was determined in Vietnamese malaria patients treated with mefloquine in the fasting and fed state.26 Blood mefloquine concentrations were compared in two cohorts of six malaria patients treated with mefloquine (15 mg/kg) and artesunate (8 mg/kg) and given either a low-fat (approximately 3 g fat) or high-fat (approximately 30 g fat) meal. The results showed no statistical differences (P<0.05) in the Cmax and AUC of mefloquine between these two groups of patients. These findings suggested that a high-fatty meal does not increase the bioavailability of mefloquine in malaria patients and should therefore not affect their response to treatment. This was not the case for piperaquine, another drug being considered as a partner with dihydroartemisinin for ACT in Vietnam and other countries of Southeast Asia. When 26 Figure 3: Captain B. Russell and Major S. Kitchener healthy Vietnamese soldiers were administered 0.5 taking off from Komoro airfield in Timor Leste to carry or 1.0 g of piperaquine, the bioavailability of the drug out field investigations. was increased by 41% after eating a moderately fatty meal (about 17 g of fat).27 In two successive contingents, 1,155 male soldiers received a loading dose of one 250 mg tablet of Artemisone - a new artemisinin compound for clinical
mefloquine every other day on three occasions, evaluation
followed by one tablet a week for six months.24 Artemisinin derivatives had by now been acknowleged Seventy-five soldiers (6.5%) experienced adverse to be the most rapidly acting drugs for the treatment responses to the drug and completed their of falciparum infections. However, infections were Journal of Military and Veterans' Health not being cured by 3-day courses of treatment due clindamycin (100 mg/kg/day) and artemisone (30 to the short pharmacological elimination half-lives mg/kg/day) was also effective in curing falciparum of the artemisinins. Since patient compliance with longer courses of treatment was poor, especially in In view of the encouraging results obtained in malarious areas with limited health facilities, various studies with non-human primates, Phase I human slower-acting but longer-lasting drugs (see above) safety and tolerability studies with artemisone were being investigated for use as partner drugs were initiated in healthy German volunteers.31 for ACT. Recently artemisone, a new semi-synthetic With the support of MMV and BAY, AMI assisted drug, had been developed which was relatively cheap by assessing the pharmacokinetic properties and to synthesise, and, unlike some other artemisinins, ex vivo pharmacodynamic antimalarial activity of displayed negligible neuro- and cytotoxicity. Early ex artemisone and its metabolites. Artemisone was vivo investigations with artemisone at AMI had also well tolerated, with no serious adverse events and indicated that the degree and duration of its activity no clinically relevant changes in laboratory and vital against multidrug-resistant P. falciparum was parameters, during and following administration significantly greater than that of artesunate following of single or multiple ascending doses (10-80 mg drug administration to non-infected Saimiri sciureus range) of artemisone to 56 healthy volunteers. The pharmacokinetics of artemisone demonstrated dose This was followed up by further studies at AMI linearity, with a Cmax of 140 ng/mL, an elimination with Aotus monkeys infected with the chloroquine- half-life of 2.8 hours, a high oral clearance of 284 resistant FVO strain of P. falciparum. Since many L/h, and a large apparent volume of distribution patients were not cured of their malaria infections of 14.5 L/kg following a single 80-mg dose. Plasma because they failed to complete 3-day courses of samples taken after multiple dosing showed marked treatment, might just a single dose of artemisone, ex vivo pharmacodynamic antimalarial activities combined with subcurative single doses of against two multidrug-resistant P. falciparum lines mefloquine, be sufficient to cure infected Aotus and confirmed the presence of active metabolites. monkeys? In a pilot study, three monkeys cleared Compared to other artemisinin derivatives, such as parasites within one day and two monkeys receiving artesunate and dihydroartemisinin, artemisone's only 10 mg/kg artemisone and 5 mg/kg mefloquine longer elimination half-life (2.8 hours versus 1.0 were cured.28 This was far below the curative hour for dihydroartemisinin) appeared to favour this mefloquine dose of 20 mg/kg for Aotus monkeys. artemisinin as a candidate ACT drug for treatment The remaining monkey that received 2.5 mg/kg of falciparum malaria. As a result of these findings, mefloquine had a recrudescence of parasitaemia 24 further clinical studies with artemisone were planned, days after treatment. The findings suggested that including Phase II efficacy studies in Thailand.
this ACT might eventually prove useful in areas with low malaria transmission but, because of 3. PROPHYLAXIS AND TREATMENT OF LIVER
mefloquine's very long persistence in the body, the HYPNOZOITES OF VIVAX MALARIA
likelihood of developing resistance to mefloquine The outbreak of vivax malaria among several would be increased in areas with high levels of hundred soldiers after returning to Australia during 2000 re-emphasised the need for improved measures Additional investigations were carried out in to prevent exposure to infected mosquitoes. But it collaboration with GMI in Panama, using a larger also highlighted the urgent need for antimalarial group (23 Aotus monkeys) than was available at AMI. drug regimens that would reduce the risk of this 29 Artemisone was administered in combination happening in the future. The fact that most of these with two other partner drugs – amodiaquine soldiers experienced their first attack of malaria and clindamycin. Although amodiaquine is a more than a month after leaving an endemic area 4-aminoquinoline drug, parasites were often indicated that inadequate drug suppression of blood less resistant to this inexpensive drug than to stage parasites was not the problem. Rather, the chloroquine.30 Clindamycin, an antibiotic, was outbreak of vivax malaria was due to the activation another drug which had been used in combination of dormant hypnozoites in the liver at different time with artemisone for treating malaria patients. intervals up to a year or more after leaving Timor Whereas monkeys failed to be cured after one day of treatment with amodiaquine (20 mg/kg) and Since it was unclear what determined the number artemisone (30 mg/kg), they were cured after three and timing of relapses, AMI attempted to investigate days treatment with amodiaquine (20 mg/kg/day) to what extent molecular diversity of parasites might and artemisone (10 mg/kg/day). A 3-day course of influence the relapse patterns experienced by soldiers Volume 23 Number 1; January 2015
after their return to Australia.32 Although high Poor compliance was also a problem in patients molecular diversity was observed, primary infections who were being treated with 14-day courses of and relapses were produced by the activation of a chloroquine/primaquine after developing malaria. single hypnozoite clone in 99% of cases. Even in This drug regimen had the additional handicap that patients with more than two genetically different chloroquine-resistant P. vivax, first identified at AMI,4 hypnozoites, 71% of them still experienced clonal was being reported from many areas of Asia, Oceania relapses. The activation of a single hypnozoite and South America. By contrast, P. vivax malaria genotype, when multiple genotypes were present in continued to be susceptible to the artemisinins. the liver, suggested that hypnozoites were activated Might a shorter treatment course of artesunate (200 according to a genetically determined biological clock mg twice a day for two days) followed by primaquine and not triggerrd by non-specific environmental (22.5 mg base twice a day for seven days) be the or host factors. The findings also suggested that multiple liver hypnozoite genotypes were associated Under the auspices of VADMP, this drug regimen with multiple replases. Therefore, any measures to was administered to 28 adult patients infected reduce exposure to mosquitoes would reduce not with P. vivax in Vietnam.36 All patients responded only the number of malaria infections but also the quickly to treatment with mean parasite and fever number of relapses. clearance times of 14.2 hours and 18.6 hours, While providing assistance with the diagnosis and respectively. The high daily dose of primaquine was management of these infections in Timor Leste, generally well tolerated, and only one patient (3.6%) it became obvious that, in attempting to deal with had a recurrence of parasitaemia during the 28 day the situation, soldiers were receiving a variety of follow-up period. As most patients infected with different treatment regimens.33,34 Although regimens Southeast Asian strains of P. vivax have their first with higher primaquine doses were more effective in relapse within 28 days after treatment with a rapidly preventing P. vivax relapses,6 the lengthy duration of eliminated blood schizonticide, such as quinine medication did not encourage drug compliance. More or artesunate, the failure to do so by 96% of the user friendly drug regimens would undoubtedly be patients suggested that this drug regimen was active more effective in eradicating the dormant hypnozoites against both blood and liver stages of vivax malaria. remaining in the liver after leaving an endemic area. These findings indicated the need for further studies With this in mind, clinical studies were initiated to to confirm that rapidly acting and short artesunate- evaluate the efficacy and safety of shorter courses of primaquine regimens are able to provide better primaquine and tafenoquine taken either during or patient compliance and treatment outcomes than after deployment overseas. standard chloroquine-primaquine regimens.
Shorter primaquine prophylactic and treatment
The very large number of vivax infections observed
in soldiers after their return to Australia from Timor
Leste6 emphasised the urgent need for better post-
exposure drug regimens to eradicate the residual
dormant hypnozoites of P. vivax malaria. Earlier
studies in ADF personnel returning from Timor
Leste had indicated that primaquine 30 mg (15
mg twice a day) was more effective than 22.5 mg
daily for 14 days in curing these infections.6 As the
lengthy 14-day regimens were contributing to poor
compliance, a pilot volunteer study was initiated to
assess the tolerability of higher dose, shorter courses
of primaquine.35 Australian soldiers tolerated Figure 4: Key contributors to the Vietnam Australia
primaquine 22.5 mg twice a day for 10 days and 30
Defence Malaria Project attending the 14th Asia mg twice a day for seven days just as well as 15 mg Pacific Military Medicine Conference, Brisbane, May 2004. Front row (L to R): Senior Colonel Nguyen Xuan twice a day for 14 days. The findings indicated that Thanh, Lieutenant General Cuong Tien Chu, Professor additional studies were desirable to further define Karl Rieckmann, Professor Bui Dai, Lieutenant Colonel the tolerability, safety and effectiveness of shorter, Michael Edstein, Senior Colonel Vu Quoc Binh. high dose courses of primaquine.
Journal of Military and Veterans' Health Influence of gender and food on primaquine
Tafenoquine post-exposure prophylaxis at end of
deployment to malarious area
Although primaquine had been used for 50 years A previous short report had already described for the radical cure of P. vivax dormant (hypnozoite) preliminary findings from a study in which 173 stages, little information was available on the Australian soldiers had received a 3-day course of effect of gender and food on the disposition of tafenoquine as post-exposure prophylaxis at the end primaquine. Earlier studies appeared to indicate of their peacekeeping duties in Bougainville, PNG.6,37 that female ADF personnel had a higher prevalence Since GI disturbances are a well known feature of gastro-intestinal (GI) disturbances than their male associated with the use of 8-aminoquinolines, 87 counterparts during post-exposure prophylaxis with volunteers (76 males; 11 females) received a single primaquine.37 This could have been due to higher tafenoquine dose (400 mg once a day) and 86 blood primaquine concentrations in females than in voluneers (73 males; 13 females) received a split males. Under the auspices of VADMP, a randomised, tafenoquine dose (200 mg twice a day) to determine two-phase cross-over study was conducted in which whether the split dose would lower the incidence 10 healthy male and 10 healthy female Vietnamese of side-effects. Although GI disturbances were soldiers were administered a single oral dose of 30 generally mild, self-limiting and not significantly mg primaquine in the fasting and fed states.38 The different between the two groups, the frequency of pharmacokinetics of primaquine was comparable nausea and abdominal distress in both groups was in both groups, with geometric mean ratios of more than two-fold higher in females than in males. Cmax = 0.89 and AUC = 0.80, although males had Furthermore, plasma tafenoquine concentrations a slightly higher plasma clearance than females. were significantly higher in females than in males When primaquine was taken in conjunction with a (mean values: 737 ± 118 ng/mL vs. 581 ± 113 fatty meal, the geometric mean Cmax of primaquine ng/mL) with similar body weight.40 Whilst little increased by 26% and the AUC by 14%. When the difference was observed in the way both sexes same dose of primaquine was given to nine healthy tolerated single and split doses, the findings did male and nine female ADF personnel, no significant suggest that there might be an association between differences in the pharmacokinetics of primaquine tafenoquine concentrations and GI disturbances and between the genders were observed.39 These findings that adjustments might have to be made in the dose suggested that, based on single dose assessment of of tafenoquine administered to women.
primaquine, there was no need to modify primaquine doses for women. However, the greater bioavailability Tafenoquine treatment of Plasmodium vivax malaria
of primaquine when consumed with a fatty meal Relapses of vivax malaria were common among ADF might lead to improved antimalarial effectiveness personnel after their return to Australia, despite post- irrespective of gender.
exposure prophylaxis and/or treatment with 14-day courses of primaquine. Following the successful Tafenoquine for the prevention and cure of vivax malaria
treatment of two patients with 3-day courses of Ground breaking investigations at AMI had shown tafenoquine,41 a further 27 patients were treated that tafenoquine might be more effective than with tafenoquine after their vivax infections had primaquine in the prevention and cure of vivax failed to be cured by chloroquine and primaquine.42 malaria.5,6 This new, long-acting synthetic analogue After a standard course of chloroquine (1,500 mg of primaquine might not only improve patient base over three days), they received a loading dose compliance with post-exposure prophylaxis and of tafenoquine (200 mg/day for three days) followed treatment regimens, but might provide protection by 200 mg a week for eight weeks. Only one of the against vivax and falciparum malaria if taken on a patients experienced a relapse during the next six weekly basis. Because of the potential importance months. Although further optimum dose-finding of this 8-aminoquinoline drug in reducing the studies are indicated, these findings suggested that malaria burden in ADF personnel, considerable intermittent weekly dosing with tafenoquine over time and effort was devoted to carrying out further several weeks might prove more effective than daily clinical studies with this drug in Australian soldiers dosing over a shorter period of time. The advantages contributing to peacekeeping duties. In addition to of such a tafenoquine regimen might be similar to pharmacokinetic studies involving male and female those observed following weekly doses of primaquine ADF personnel, several hundred soldiers deployed to administered over a period of eight weeks.43 Timor Leste participated in the first Phase III trial to determine the safety, tolerability and effectiveness of tafenoquine for malaria prophylaxis.
Volume 23 Number 1; January 2015 Tafenoquine prophylaxis during deployment to
recipients reporting that the drug did not allow them to complete their daily duties. Only three soldiers By 2000, doxycycline, Malarone® and mefloquine in the tafenoquine group discontinued prophylaxis were being used to protect ADF personnel against because of possible drug related adverse events (none malaria during their deployments overseas, but in the mefloquine group). Mild vortex keratopathy, they all had shortcomings, including their inability detected in 93% of a subset of 74 volunteers, was to prevent relapses and to radically cure P. vivax not associated with any visual disturbances and infections. Although post-exposure prophylaxis had fully resolved within one year after stopping with tafenoquine might prove to be more effective than using primaquine, could such prophylaxis be The population pharmacokinetics of tafenoquine was dispensed with altogether by taking tafenoquine determined in 476 male and 14 female participants throughout the time spent overseas? During a in this study by analysing plasma tafenoquine previous collaborative field study in Thailand, the concentrations in blood samples collected after the administration of tafenoquine (400 mg) at monthly last loading dose and then at weeks 4, 8, and 16.46 intervals for five months had been shown to be Analysis of specimens revealed that tafenoquine highly effective in preventing vivax and falciparum had a relatively low plasma clearance (CL/F) of infections.6 Based on various considerations, 4.5 L/h, a high apparent volume of distribution including tafenoquine analysis of Thai blood samples (V/F) of 1,896 L, suggesting that the drug was at AMI, it was decided to conduct the first Phase III widely distributed to body tissues and organs. As trial on the safety, tolerability and effectiveness of expected, the elimination half-life of tafenoquine tafenoquine in Australian soldiers, with reduced was long at 12.7 days. Pharmacokinetic data from doses of the drug being administered at shorter the four soldiers who developed vivax malaria time intervals. So in October 2000, a randomised after returning to Australia were similar to those double-blinded study was started which involved the who remained free of malaria. Neither could any participation of 654 soldiers during the entire period links be established between pharmacokinetic of their peacekeeping deployment to Timor Leste. 44,45 parameters and the prevalence or severity of GI During the six month period, 492 soldiers received disturbances or other adverse events, suggesting a loading dose of 200 mg tafenoquine daily for three that plasma tafenoquine concentrations were not the days followed by a weekly dose of 200 mg tafenoquine. primary predictor of tafenoquine tolerability. These A comparator group of 162 soldiers received a findings indicated that (1) the derived population weekly dose of 250 mg mefloquine. As the soldiers one-compartment pharmacokinetic model for had acquired no prior immunity to malaria, ethical tafenoquine satisfactorily described the disposition considerations obviously precluded incorporation and variability of tafenoquine in ADF personnel, and of a concurrent no-drug placebo group. After their (2) the pharmacokinetic properties of the drug were return to Australia, the mefloquine recipients were well suited for long-term weekly malaria prophylaxis administered primaquine (15 mg twice a day) for 14 during military deployments.
days whereas the tafenoquine recipients were given This study involving ADF personnel was the first and a placebo. While they were in Timor Leste, none only Phase III study to show that weekly tafenoquine of the 654 volunteers developed malaria, but four taken for six months was an effective prophylactic tafenoquine recipients (0.9%) and one mefloquine drug against both P. falciparum and P. vivax malaria recipient (0.7%) had acute attacks of P. vivax malaria in non-immune individuals.
within 16 to 20 weeks after returning home. This was in marked contrast to the 168 malaria cases 4. MALARIA DIAGNOSIS
observed in the 1,351 soldiers of two battalions that were deployed to the same area during the previous Rapid diagnostic tests (RDTs)
wet season between October 1999 and February Early diagnosis and treatment are critical to prevent 2000.6 Although the exposure of soldiers to malaria severe complications and death from malaria, could not be estimated directly without a placebo particularly in individuals with little or no prior control, malaria transmission continued to occur exposure to malaria. Although definitive diagnosis in several villages in close proximity to where the of malaria can only be established by microscopic soldiers were located.16 examination of blood films, the availability of a Drug-related adverse events were generally mild non-microscopic test would be a distinct advantage or moderate in severity and comparable in the two during the deployment of ADF personnel to remote groups. The most common drug related events were malarious areas where reliable malaria microscopy GI disturbances, with eight (<2%) of the tafenoquine might not be available.
Journal of Military and Veterans' Health In the mid-1990s, AMI had participated in the field Some of the RDTs were based on the detection of evaluation of the ICT Malaria Pf test card which was aldolase, a key enzyme in the glycolysis pathway the first immunochromatographic test card to detect of malaria parasites. Since RDTs targeting aldolase a specific antigen (PfHRP2) produced in patients were showing highly variable sensitivities, the infected with falciparum malaria.5 By 2004, about 25 genetic diversity of parasite isolates originating from branded malaria rapid diagnostic tests (RDTs) were geographically different areas were determined by commercially available; some of them detected P. sequencing the coding genes.50 The results showed falciparum only, while others detected P. falciparum that aldolases were highly conserved, indicating plus one or more other plasmodial species. However, that antigenic diversity was not a cause of variable the performance of these products (sensitivity, RDT sensitivity. However, in general, aldolase- specificity, heat durability, ease of use, etc) were detecting RDTs were less sensitive than their HRP2 reported to vary greatly between different products and between the same products used in different In their excellent article in ADF Health, Baker et al.51 reviewed the results of investigations carried In view of the variability observed in the performance out with RDTs at AMI and elsewhere, and pointed of these tests, WHO/WPRO organised an informal out their advantages and limitations. Although RDTs consultation on laboratory methods for the quality offered distinct advantages for early diagnosis and assurance of malaria RDTs. Following this meeting, treatment, especially when expert malaria microscopy to which Dr Qin Cheng had been invited, DRD was not available, ADF medical personnel needed became a key laboratory in the WHO malaria RDT to be aware that a patient might still have malaria Quality Assurance network, making significant despite a negative RDT result. This would be more contributions (described below) to the development of likely during the early stages of a malaria infection positive controls and the testing of various products when parasite densities were still at a low level. For and lots. As a WHO Collaborating Centre for Malaria, this reason, competent malaria microcopy remained AMI also collaborated with QIMR in examining the preferred method of arriving at a definitive several important parasite and host factors that species diagnosis of malaria. Patients with persisting could affect the performance of RDTs.
symptoms of malaria should have repeated RDTs within 24 hours of the initial test, and microscopy Since many RDTs were based on the detection of P. should be performed if at all possible.
falciparum histidine rich protein 2 (PfHRP2), might variability in RDT results be related to genetic diversity of PfHRP2 antigen? After amplifying and sequencing the pfhrp2 gene from 75 P. falciparum lines and isolates originating from 19 countries, extensive diversity in this antigen was observed both within and between countries. When a subset of parasite isolates was tested in two popular brands of RDTs, a correlation was observed between detection sensitivity and antigen structure. The results demonstrated for the first time that the variability of PfHRP2 could affect the detection sensitivity at parasite densities ≤250/µL blood.47 Significant differences were also observed between the reactivity of four PfHRP2 specific mononclonal antibodies to parasite PfHRP2 from a single isolate and also when one of the antibodies was tested against different isolates. When the target epitopes of these antibodies Figure 5: Lieutenant Joanne Baker assessing efficacy of malaria rapid diagnostic tests (RDTs). were determined they were found to vary in frequency in different isolates.48 These findings appeared to Polymerase chain reaction (PCR) test
indicate that variability in PfHRP2 antigen might have an effect on the sensitivity of PfHRP2-detecting Earlier efforts to employ sensitive and specific PCR- RDTs. However, further investigations including based methods for malaria detection6 were followed isolates from Africa and South America suggested up by the establishment of nested PCR and a that RDTs were not greatly affected by the diversity multiplex PCR to detect or verify Plasmodial species of PfHRP2 at parasite densities exceeding 200 in ADF personnel suspected of having malaria but in whom negative or discrepant results were obtained Volume 23 Number 1; January 2015 by microscopy or RDT. This could now be performed to determine whether genetic mutations could be using whole blood samples, plasma samples, detected in the dihydrofolate reductase (DHFR) of dried blood on filter papers and blood smears. In their parasites. Although 90% of these partially- combination with results obtained with microscopy immune patients were cured, 80% of them were or RDT, it ensured that accurate malaria information infected with parasites which carried double genetic was entered into the ADF Central Malaria Register. mutations (S108N/C59R) in SP's target molecule (Pfdhfr).54 This suggested that the useful life of SP 5. ASSESSMENT OF DRUG RESISTANCE
might be limited and that alternative drugs were Malaria control activities in the Asia-Pacific required to treat patients with lower levels of acquired region continued to be frustrated by the changing immunity to malaria.
susceptibility of parasites to standard antimalarial drugs. This also affected ADF operational and Susceptibility of Plasmodium falciparum and
peacekeeping activities. Many countries were using Plasmodium vivax to chloroquine (CQ) and sulfadoxine-
chloroquine (CQ) and sulfadoxine-pyrimethamine pyrimethamine (SP) in Indonesia
(SP) for first- and second-line treatments of Malaria epidemics in Central Java had increased uncomplicated malaria. CQ continued to be used concern about the re-emergence of endemic malaria because it was readily available and relieved which could threaten the island's 120 million symptoms in patients who were infected with vivax residents. AMI was approached by NAMRU-2 to malaria or had become partially immune to falciparum collaborate in a 28 day in vivo test of the efficacy malaria. When too many falciparum infections failed of CQ and SP among 167 villagers from Central to be cured, SP was usually introduced for malaria Java with 33% of 1,389 residents being infected treatment. Whereas both components of SP act prior to enrollment.55 Drug analysis was done at synergistically against P. falciparum, this is not the AMI to ensure that the patients had adequate case for P. vivax because of its innate resistance to blood concentrations of CQ and SP after starting the sulfadoxine component. In the presence of low to treatment. The study revealed CQ and SP to be moderate degrees of pyrimethamine resistance, this ineffective therapy for P. falciparum, with therapeutic meant that, unlike its activity against P. falciparum, failure rates of 47% and 22%, respectively, and 18% SP was often ineffective against P. vivax malaria.52 and 67% in the treatment of P. vivax. These findings Since P. falciparum could not be distinguished from suggested that the presence of CQ- and SP-resistant P. vivax in many malarious areas due to unavailable P. falciparum and P. vivax would compromise efforts or unreliable malaria microscopy, CQ was often to control resurgent malaria in Java and that ACTs co-administered with SP to increase the patient's should be introduced as soon as possible to improve likelihood of responding adequately to treatment irrespective of the infecting Plasmodial species. In addition to Central Java there had been a steady The response to treatment was of course far less rise in the number of reported cases of emerging satisfactory in areas with CQ-resistant vivax malaria. drug resistance in southern Papua, Indonesia. In Susceptibility of Plasmodium falciparum to sulfadoxine/
collaboration with MSHR, AMI carried out the drug pyrimethamine (SP) in Timor Leste
measurements in the assessment of the therapeutic efficacy of CQ monotherapy for P. vivax infections as When ADF personnel were deployed on peacekeeping well as CQ plus SP for P. falciparum infections.56 Of duties to Timor Leste in 1999 the efficacy of CQ and the 143 patients enrolled in the study (40 treated with SP for the treatment of uncomplicated P. falciparum CQ and 103 treated with CQ+SP), early treatment malaria was unknown. AMI was approached by the failures occurred in 15% of patients with P. vivax and non-government organisation, MERLIN, to assist in 4% of patients with P. falciparum The failure rates determining the efficacy of the antimalarial drugs by by days 28 and 42 were 65% for P. vivax and 48% genotyping for drug resistance and measuring blood for P. falciparum, respectively. These findings further drug concentrations. Earlier investigations at AMI confirmed the existence of a high prevalence of drug had already shown the value of molecular markers resistance of P. vivax and P. falciparum to both the for monitoring the resistance of P. falciparum to CQ first- and second-line treatments in Indonesia.
and atovaquone.6 Collaborative investigations with WEHI and PNGIMR had also indicated that the 76T Prevalence and extent of pyrimethamine resistance in
allele of the pfcrt gene was strongly associated with chloroquine resistance.53 After documenting a high The above mentioned study in Timor Leste exemplified level of CQ resistance in 48 patients,6 a further 40 the fact that genetic mutations in the dihydrofolate individuals infected with falciparum malaria were reductase (DHFR) of P. falciparum could also be used treated with SP following the collection of their blood Journal of Military and Veterans' Health to assess drug resistance to pyrimethamine and to various drugs.59 Using the WHO microtest, six P. SP. Furthermore, one to four genetic mutations in falciparum isolates showed a low level of resistance DHFR of P. vivax had been shown to confer various to CQ and pyrimethamine, but were sensitive to degrees of resistance to pyrimethamine and other mefloquine, cycloguanil, dihydroartemisinin and antifolate drugs. How prevalent might genetic amodiaquine. The parasites were also 50 to 400 mutations in Pvdhfr be in different areas of the Asia- times more active against WR99210, a remarkably Pacific region? In collaboration with QIMR, NAMRU active experimental antifolate drug,5,6 than against 2 and WRAIR, 70 P. vivax isolates from six countries pyrimethamine. Although patients with falciparum were examined for mutant genes.57 Overall, 74% of malaria on this island might have a recrudescence P. vivax isolates carried a mutant Pvdhfr, with the of parasitaemia following CQ treatment, the results prevalence of mutants being lower in isolates from indicated that they should be cured after SP China, Philippines, Timor Leste and Vietnam than treatment. No conclusions were possible regarding in those from PNG and Vanuatu. Furthermore, they the drug susceptibility of P.vivax because only two only carried single or double mutations whereas isolates were cultured. isolates from PNG and Vanuatu carried up to quadruple mutations. The data suggested that both the prevalence and degree of resistance of P. vivax to antifolate drugs was higher in the Southwest Pacific countries of PNG and Vanuatu than in their counterparts in Southeast Asia. Because sulfadoxine could not be expected to potentiate the activity of pyrimethamine, these findings indicated the limited value of SP for the treatment of vivax infections.
Efficacy of sulfadoxine-pyrimethamine (SP) combined
with artesunate or chloroquine (CQ) against
Plasmodium vivax malaria in Papua, Indonesia
Widespread CQ resistance of P. falciparum and P.
vivax in Papua, Indonesia, during the late 1990s led
to the use of CQ/SP combinations and the evaluation
of artesunate/SP. Since artesunate/SP proved highly
(96%) effective in curing falciparum infections,
NIHRD and MSHR conducted a study to compare
the efficacy of this combination with that of CQ/SP
in two groups of patients with vivax malaria.58 Not
unexpectedly, the treatment failure rate was higher
in the CQ/SP group (33%) than in the artesunate/SP
Figure 6: Captain Alyson Auliff examining malaria group (10%), and would have been higher in patient blood films. groups who were not partially immune to malaria. In fact, molecular analysis of parasite samples at AMI 6. NEW INSIGHTS AND TESTS FOR DRUG
revealed that 80% of these patients were infected RESISTANCE
with parasites carrying one to four genetic mutations in the P. vivax dihydrofolate reductase (pvdhfr) gene Drug susceptibility test for Plasmodium vivax
and that patients infected with parasites carrying In vitro assessment of drug activity against malaria quadruple mutations had a higher risk of treatment parasites had been an integral part of AMI activities failure. Although artesunate/SP was more effective for many years. The WHO in vitro field test (schizont than CQ/SP, it was obvious that an alternative maturation test) had proven to be a simple and drug, such as piperaquine, might prove to be more reliable means for determining the sensitivity of P. useful than SP as a partner for artemisinin-based falciparum to antimalarial drugs. However, early combination therapy (ACT).
attempts to use this test for P. vivax had proven unsuccessful because, unlike P. falciparum, parasite In vitro drug susceptibility of malaria parasites in
stages other than rings were usually present in the peripheral blood at the start of culture. With recent In collaboration with VBDCU and NAMRU-2, a advances in in vitro culture techniques, further efforts preliminary survey was conducted in Malo Island to were made at AMI and in Thailand (in collaboration assess the in vitro susceptibility of malaria parasites Volume 23 Number 1; January 2015 with MAH and AFRIMS), to develop an effective in resistance in P. falciparum, this might indicate similar vitro field test to determine the sensitivity of P. molecular mechanisms for P. vivax resistance to CQ. vivax to various drugs.60 Although the processing This study not only emphasised the need to further of freshly-collected parasitised blood samples was refine the in vitro test as a means of identifying the more complex than for P. falciparum, it was still presence of chloroquine resistance, but also raised considered possible to use this method in a field the possibility that the pvmdr1 polymorphism at setting. Chloroquine, sulfadoxine and tafenoquine Y976F might provide a useful tool to monitor the halted maturation of P. vivax at the late amoeboid emergence of CQ resistance.
or trophozoite stage, whereas dihydroartemisinin did so at the ring stage. As with the P. falciparum Identification of molecular markers for sulfadoxine
test, this field method avoided the use of expensive resistance in Plasmodium vivax
or dangerous reagents (monoclonal antibodies Although widely used for treating falciparum or radioisotopes) and expensive equipment (beta infections, SP was less effective against P. vivax counters or robotic plate washers and dispensers). because its sulfadoxine component was less able The whole 25-37 hour procedure also did not require to potentiate the activity of pyrimethamine against a biological safety hood. With increasing concern the parasite.52 To understand the mechanism of about the emergence of drug-resistant vivax malaria, this innate resistance to sulfadoxine, studies were it was felt that this field in vitro assay could be used undertaken to identify and sequence the P. vivax for assessing the true drug susceptibility of P. vivax dihydropteroate synthetase (DHPS) gene, construct in various areas, without being obscured by various a 3D homology model of the DHPS enzyme, and degrees of immunity acquired by malaria patients. investigate the interactions between sulfadoxine Furthermore, in view of the inability to maintain P. and DHPS.62 As a result, an amino acid residue vivax in long-term cultures, the test might also play (V585) unique to the P. vivax DHPS was identified a role in screening new antimalarial drugs for their causing a reduction in binding to sulfadoxine. This efficacy against this species. explained why P. vivax was innately less susceptible to sulfadoxine than P. falciparum. After examining Polymorphism of pmvdr1 possibly associated with
pvdhps in a number of P. vivax isolates collected Plasmodium vivax resistance to chloroquine
from different areas, mutations were identified in Unlike P. falciparum, no genetic markers for CQ some isolates which were likely to be responsible for resistance had yet been identified for P. vivax. A acquired resistance to sulfadoxine. These mutations collaborative effort attempted to shed further light were subsequently validated as molecular markers on this by examining the chloroquine susceptibilities for SP resistance in Thailand63 and other areas,57 (using a modification of the above mentioned in and have been used worldwide for monitoring SP vitro test) and molecular polymorphisms of P. vivax isolates collected in Papua, Indonesia, where high levels of clinical CQ resistance prevailed, and from Plasmodium falciparum cultures used to assess the
Thailand where CQ treatment was still generally activity of dihydrofolate reductase (DHFR) inhibitors on
effective.61 Isolates from Papua were considerably less susceptible to chloroquine than those from Thailand, As described above, treatment of most malaria although in vitro results raised the possibility of a patients in endemic areas was based on a clinical low level of CQ resistance along the western border diagnosis rather than a parasitological one. In areas where P. falciparum and P. vivax co-existed, Significantly, molecular analysis of the pvmdr1 gene this implied that the drug(s) used for treatment revealed that 96% of Indonesian isolates had the of multidrug-resistant falciparum malaria also Y976F allele compared to 25% in Thai isolates. It is needed to be effective against vivax malaria. With noteworthy that the 976 mutation was not always the increased prevalence of CQ-resistant and SP- associated with high IC50 CQ values, suggesting resistant P. vivax and the inability to culture P. vivax that other major molecular determinants were continuously, P. falciparum from continuous culture likely to be involved. Nevertheless, the predominant was transfected with functional P. falciparum and presence of the Y976F allele in Papua, known for P. vivax dhfr-ts alleles.64 The development of this P. its widespread clinical resistance to CQ treatment, falciparum expression system allowed for the first indicated that pvmdr1 played an important role in direct assessment of the effect of DHFR inhibitors on modulating the susceptibility of P. vivax to CQ. Since P. vivax DHFR.
gene amplification of the pfmdr1 gene had already Previous investigations at AMI with one of these been shown to be a major determinant of multidrug DHFR inhibitors, WR99210, had shown this Journal of Military and Veterans' Health new antifolate drug to be far more effective than mefloquine resistance. Finally, it was pointed out conventional antifolates against drug-resistant that the artemisinin-resistant mutants produced P. falciparum.5,6 How effective would it be against during these investigations constituted an important drug-resistant P. vivax? The results showed that resource in the further search for molecular markers the PvDHFR quadruple mutant conferred greater of artemisinin resistance. resistance to WR99210 than the PfDHFR quadruple mutant. This was also the case for cycloguanil and 7. EVOLUTION OF DRUG RESISTANCE
clociguanil, but not for pyrimethamine. Further The aim of these NIH-supported studies was to obtain work, including modeling of both P. vivax and P. a better understanding of how malaria parasites falciparum DHFR quadruple mutants suggested that developed drug resistance and what host, parasite mutations unique to P. vivax DHFR were responsible and environmental factors might enhance or hinder for differences observed in parasite susceptibility to the development and spread of drug resistance. antifolate drugs. Looking ahead, the development of the P. falciparum expression system appeared to be Origin and dissemination of chloroquine-resistant (CQR)
an important step forward in identifying potential P. Plasmodium falciparum in the Philippines
vivax drug-resistance markers and in investigating Following identification of the pfcrt gene as CQR the potency of existing and novel antimalarial drugs marker,6 mutation patterns were suggesting that against known or putative P. vivax gene targets.
CQR parasites had arisen independently in four different parts of the world: (1) Southeast Asia, then Molecular changes are associated with the development
spreading to Africa; (2) Peru in South America; (3) of Plasmodium falciparum resistance to artemisinin
Colombia, South America; and (4) Papua New Guinea. derivatives during in vitro cultures
However, it was not clear how CQR parasites had During the previous decade AMI had carried out developed and spread in Asia/Pacific countries other numerous studies relating to the in vitro and in than PNG. During the CQ efficacy study conducted vivo efficacy, and the pharmacokinetics of existing in Timor Leste,6 the pfcrt mutation patterns in P. and novel artemisinin derivatives. In view of the falciparum parasites indicated that CQR parasites increasing reliance of artemisinin-based combination shared a common origin with CQR parasites in PNG, therapy (ACT) for treating drug-resistant falciparum suggesting that CQR in Timor Leste had most likely malaria (see above), there was mounting concern spread from PNG. Further investigations, carried about the possible emergence of parasite resistance out in collaboration with RITM, revealed that 90% to the artemisinins. This prompted WRAIR and AMI of parasites sampled in Luzon Province, Philippines, to collaborate on investigating the development carried two novel mutations in their pfcrt gene which of artemisinin resistance in vitro.65 Applying had not been reported elsewhere in the world.66 discontinuous drug selection pressure, resistance to artemisinin derivatives was established in several To better understand the development and clones and lines of P. falciparum. Furthermore, dissemination of CQR P. falciparum in the Philippines, apart from parasites being also cross-resistant to a collaborative study was undertaken with QIMR to mefloquine and other artemisinin derivatives, they analyse mutation patterns in pfcrt and microsatellite were able to tolerate artemisinin concentrations patterns flanking pfcrt in 82 P. falciparum isolates equivalent to those usually found in plasma samples collected throughout the Philippines between 1989 after treatment of malaria patients. and 2002.67 While mutation patterns demonstrate CQR status, microsatellite patterns point to the The development of artemisinin-resistant parasites origin of CQR parasites. The results showed that the in vitro provided the opportunity to study various majority of CQR parasites in Luzon Province (in the aspects of artemisinin resistance, including the North) developed in situ while most CQR parasites in identification of putative molecular markers Mindanao and Palawan Provinces (in the South) had of resistance to these drugs. Preliminary data originated in PNG. These findings demonstrated that suggested that parasites could tolerate increasing CQ selection pressure could induce parasites with concentrations of artemisinin drugs by amplifying the different genetic backgrounds to become resistant to pfmdr1 gene, but they also suggested that this was CQ by mutating different positions in the pfcrt gene. not the central determinant of artemisinin resistance. Such new information should be helpful in gaining Nevertheless, since amplification of pfmdr1 was also a better insight into the evolutionary process of CQR associated with mefloquine resistance, attention and in preventing a similar process from occurring was drawn to the possibility that this might have following the introduction of newer drugs.
practical implications for the use of artesunate-mefloquine as an ACT in areas with high levels of Volume 23 Number 1; January 2015 of these genes was a result of their physical linkage to SP and CQ resistance markers and a probable outcome of the widespread use of SP and CQ in the region.69 This provided strong evidence that drug resistance can influence the shape of parasite populations. To understand how and how quickly parasites switch the expression of PfEMP1, the transcription of genes encoding PfEMP1 was studied in a number of human volunteers, infected with the 3D7 line of P. falciparum, who had participated in a vaccine trial conducted at QIMR in the early 1990s.70 The results demonstrated that the expression of PfEMP1 was reinitiated each time after mosquito inoculation Figure 7: Dr. Nanhua Chen determining mutation patterns of parasites. Parasites then switched away rapidly of malaria parasites. from the first expressed PfEMP1 likely to facilitate Role of antigenic variation in the evolution of drug
establishment of infection at a rate of about 18% per generation. Subsequent switching at later phases of infection occurred at much lower rates.71 It appeared Antigenic variation in malaria parasites is a well likely that a parasite requires a group of 15-20 fast known phenomenon hampering not only the switching genes to establish an infection and a group development of effective vaccines but also of effective of at least 20 slow switching genes to maintain the drugs. This is facilitated by a family of antigens, P. infection for transmission to mosquitoes.72 The falciparum erythrocyte membrane protein 1 (PfEMP1), results indicated that anything that might be able expressed by P. falciparum on the surface of infected to interrupt the switching of PfEMP1 would probably red cells which enables them to adhere to the wall interfere with the normal life cycle of the malaria of blood vessels and prevents them from being destroyed by the host spleen. Since each parasite expresses only one of its many member antigens at a Loss of fitness in drug resistant parasites
time, and regularly switches them around, it is able to evade host immunity. The number and diversity of Following the emergence of drug-resistant parasites, PfEMP1 antigens in each parasite and in a parasite would such parasites suffer a loss of fitness population are important for the survival of drug compared to their drug-sensitive siblings? The resistant parasites and determine the speed at which answer to this question could influence strategies humans develop immunity against parasites. After used to delay or even reverse the spread of drug examining the repertoires and genetic diversity of resistance. This was examined by comparing the genes encoding PfEMP1 in isolates collected from relative fitness of atovaquone resistant P. falciparum the Solomon Islands, Philippines, PNG and Africa, parasites to their atovaquone sensitive parent AMI demonstrated that generally each parasite parasites.73 An equal number of resistant and had genes encoding 40 – 50 members of PfEMP1.68 sensitive parasites were combined with each other However, each parasite had quite a distinct set of and, after 100 days of in vitro culture, the ratio of genes, with only 0-6 genes being shared between any resistant to sensitive parasites was measured. two parasite isolates. These findings suggested that Without any drug pressure, atovaquone resistant the global repertoire for PfEMP1 was immense and parasites that carried two mutations (M133I and could be potentially selected by the host's immune G280D) in their cytochrome b suffered a 5 to 9% response against PfEMP1. loss of fitness compared to their sensitive parents. Further molecular modelling revealed that the loss of Despite the high diversity of genes encoding PfEMP1 fitness was due to the mutation (G280D) weakening between parasites, five genes were identified that the binding of cytochrome b to ubiquinones. These were shared at relatively high frequency among 63 findings supported the concept that drug resistance genetically diverse P. falciparum isolates collected could be reversed if the old drug was withdrawn and from five islands in the Western Pacific region. Upon a new drug introduced long before the prevalence further examination, three of the five genes were of resistance prevalence reached fixation. They located on chromosome 4 near a mutant pfdhfr while also highlighted the importance of continuously two remaining genes were located on chromosome monitoring the prevalence of drug resistance so that 7 near a mutant pfcrt. Therefore, the conservation drug policy can be changed in a timely fashion. Journal of Military and Veterans' Health Establishing a P. falciparum in-host dynamics model
of treatment plays a role; and (c) treatment failures In addition to epidemiological and laboratory due to presence of highly resistant parasites. The studies, mathematical models were established to model output reaffirmed the importance of correct study the evolution of drug resistance. Mathematical treatment of confirmed malaria cases in slowing the modelling is a powerful tool for studying interactions development of SP resistance.77 of different factors in complex processes and for predicting the dynamics of changes resulting from 8. PERSONAL PROTECTION AGAINST MOSQUITOES
interventions that are difficult to study using laboratory or epidemiological tools. The first model was an in-host dynamic model which mimicked the Mosquito repellents are an important first line of dynamics of P. falciparum infections in naïve hosts.
defence against vector-borne diseases, such as The model was constructed using data collected malaria and dengue,78-80 but the ADF repellent during human malaria studies between the 1930s provided to ADF personnel was not being widely and 1970s and produced output mimicking the used by them. Although previous assessment of the infection dynamics of these infections. To ensure repellent (35% Deet in a gel preparation) by AMI had that the model prediction was biologically relevant, shown it to be effective in providing a broad spectrum several parameters were determined experimentally, of activity against mosquitoes, soldiers complained including PfEMP1 switching rates (see above), that it felt uncomfortable on the skin and melted pyrogenic threshold, development of clinical plastic and some other synthetic materials. During immunity, parasite susceptibility to antimalarial the 2000-2001 deployments to Timor Leste, AMI drugs, pharmacodynamics/pharmacokinetics of conducted further field observations on the use of drugs, and interactions between drugs. insect repellents by ADF personnel and asked them to complete a questionnaire. In their response, 84% of Pyrogenic threshold information was obtained by 955 soldiers indicated that they used repellents, but a retrospective statistical analysis of two existing they were mainly commercial repellents purchased human infection data sets to determine the by them.78,81 To ensure that ADF personnel were relationship of P. falciparum parasite density to the receiving suitable protection, laboratory and field onset of fever in naïve human hosts. The pyrogenic studies were conducted to assess the effectiveness threshold (parasite density triggering a fever) varied of commercial formulations available in Australia.82 significantly between different strains and host ethnicities and became progressively higher as Picaridin was a new repellent which was starting immunity developed following one and more attacks to be used in commercial preparations. In 2001, a collaborative study between AMI, WRAIR and 75 It was well known that individuals living in malaria endemic areas developed an acquired VADMP was carried out at Cowley Beach Training immunity to malaria, following repeated attacks of Area (CBTA) in northern Queensland to compare the malaria, which enabled them to remain asymptomatic effectiveness of picaridin and Deet preparations with while still carrying parasites. In developing the P. one another. In night-time tests, both 20% Picaridin falciparum in-host dynamics model, the acquisition and ADF 35% Deet in a gel provided >95% protection of clinical immunity was investigated under different conditions of malaria transmission conditions, levels of parasite diversity, and exposure to treatment.76 The time required to develop clinical immunity increased in areas where parasite diversity was high and decreased in areas where transmission intensity was high. Treatment of symptomatic infections did not prevent the development of immunity, only doubled the time required to develop immunity compared to circumstances where no treatment was available. The P. falciparum in-host dynamics model was used to investigate the evolutionary steps that were involved in the development of de novo SP resistance. The results indicated that the development of SP Figure 8: Collaborative investigation with mosquito resistance evolved in three steps: (a) SP selection repellents at Cowley Beach Training Area, Queensland, of existing mutant parasites, which is driven by the April 2001. (L to R) Major S. P. Frances (AMI), Dr N. Beebe long pharmacological half-life of SP; (b) SP selection (UTS) Major M. Debboun (WRAIR, USA), Senior Colonel of parasites with higher resistance, to which the time N.V. Dung (VADMP, Vietnam) preparing to test repellent effectiveness on themselves. Volume 23 Number 1; January 2015 against mosquito bites for 7-9 hours. Similar compared with one another.88 The results showed that protection was observed in day-time tests with 20% barrier tent treatment provided increased protection picaridin and 33% Deet in a polymer cream. However, against mosquitoes entering tents for at least four 10% picaridin provided >95% protection for only 2 weeks, and that both insecticides provided similar levels of protection.88 During further investigations, low concentrations of bifenthrin and permethrin, A further field study was conducted at Mt. Bundey applied to tent fabric, were discovered to inhibit egg Training area (MBTA) in the Northern Territory in hatching and larval survival of Aedes aegypti in water March 2003 which compared the effectiveness of accumulating in tent folds and, in addition, inhibit 20% picaridin with 20% Deet and ADF 35% Deet in bloodfeeding by host seeking adults.89 In view of the a gel against Anopheles spp. and Cx. annulirostris. previous long use of permethrin by the ADF and the The protection provided against Anopheles spp. was findings that it was just as effective as bifenthrin, relatively poor, with 20% picaridin and ADF Deet it was decided to continue using permethrin and providing >95% protection for only 1 hour. By contrast, to reserve bifenthrin for future use. The additional the repellents provided good protection against Cx. barrier protection against mosquitoes could have annulirostris, with 20% picaridin providing 5 hours important military and civilian applications, such as protection, and both Deet formulations providing might occur when the sheltering of refugees requires >95% protection for over 7 hours.84 A comparison the quick erection of tents.
of commercial formulations against primarily Cx. annulirostris was also undertaken in the same area 9. VECTOR SURVEILLANCE
during 2003. Autan Repel (containing 10% picaridin) provided 2 hours protection, RID (10% Deet) 7 Timor Leste
hours protection, and Bushman (80% Deet) 8 hours In 1999-2000, ADF forces deployed to Timor Leste protection. Commercial repellents containing higher on peacekeeping duties suffered from high infection concentrations of Deet provided better protection rates of malaria and dengue. The disease outbreak than picaridin.85 and management team deployed to Timor Leste in Synthetic pyrethroids as barrier treatment for military
2000 (see above) was involved not only in controlling the malaria situation but also contributed to monitoring the dengue outbreak6 and instituting Previous studies at AMI had established the best effective control measures. To guard against further methods for using permethrin insecticide in DPCU, outbreaks during subsequent deployments, surveys bednets and tentage.6 In 2000, after a new active were carried out around ADF installations along ingredient, bifenthrin, became available in Australia, the Timor Leste western border with Indonesia. The studies were undertaken to determine the potential vectors of dengue virus, Aedes aegypti and Aedes use of this insecticide within the ADF. Laboratory albopictus, were found both in the towns that were studies showed that uniforms treated with bifenthrin co-located with defence installations and within the and permethrin provided similar protection against defence installations themselves. The larvae of these Anopheles farauti and Aedes aegypti mosquitoes.86 container breeding mosquitoes were commonly found Chemical assays of ADF shirt fabrics showed that in portable water containers used by local residents. active ingredient was lost after cold water washing, Multiple breeding sites were also created following with 78.5 to 85% of the active ingredient lost after the establishment of defence installations, the most three cold water washes. Since bifenthrin did not common being water trapped in folds of plastic provide any additional protection, it was decided wraps and tarpaulins, and car and truck tyres. The to continue using permethrin, with bifenthrin findings of these surveys were communicated to the potentially available as an alternative insecticide.
deployed preventive medicine personnel who carried In early 2003, a field trial was conducted in MBTA out source reduction (physical removal of breeding to determine the effectiveness of spraying ADF tents sites) and larviciding.
with 0.1% bifenthrin as a means of protecting people Anopheline mosquitoes were surveyed to determine inside the tents from being bitten by mosquitoes.87 the soldiers' risk of exposure to malaria. The The treated tents provided an 81% increase in surveys were carried out in the ADF installations protection from mosquitoes entering the tents, and by conducting human landing catches. Using this 90.4% increase in protection from biting Culex simple technique the degree of exposure the soldiers annulirostris, an important arbovirus vector. In had to biting anopheles could be determined, the a subsequent study carried out in the Wide Bay specimens collected were identified using molecular Training Area in Queensland (WBTA) during 2005, based techniques and further tested for malaria the effectiveness of bifenthrin and permethrin in parasite antigen.
preventing mosquitoes from entering tents were Journal of Military and Veterans' Health Several species of anophelines were found biting of the 130 pools of mosquitoes showed any evidence humans: An. barbirostris, An. aconitus, An. annularis, of arboviral infection.88 A subsequent longitudinal An. maculatus, An. peditaeniatus, An. sundaicus, An. surveillance study commenced in 2005 revealed flavirostris and a newly discovered species An. vagus that, out of 348 pools of 9,380 mosquitoes (primarily genotype B. The most common species biting humans Ae. vigilax, Ae. multiplex, Ae. kochi and Culex were An. barbirostris and An. vagus genotype B and annulirostris), five were positive (two Edge Hill virus, specimens of both species were incriminated as one Stratford Virus, and two unidentified).93 vectors at the time of these surveys.90 Larval surveys were also conducted around the ADF installations, Incursion of dengue virus vectors into Australia
primarily to identify anopheline breeding sites In Australia the primary dengue virus vector for larviciding by preventive medicine personnel. Aedes aegypti is only found in far northeastern Detection of malaria parasites in mosquitoes is a Queensland, but another less efficient vector - Ae. laboratory based procedure requiring specialised albopictus - has recently been discovered moving equipment; so the surveys in Timor Leste provided south through Papua New Guinea and into the an opportunity to evaluate a novel diagnostic test Torres Strait islands.94 Because both species are that could be applied in the field.91 container breeders and can lay desiccant resistant During the deployment to Timor Leste, anti-filarial eggs they are easily transported from one country antibody levels were measured in 907 soldiers to another. Consequently, a continual threat existed to determine whether they had been exposed to that these dengue vectors could be introduced into mosquitoes infected with filarial parasites, the air and sea ports around Australia. A major problem causative agent of lymphatic filariasis.92 Initial testing in monitoring for possible incursions was that larvae using Dirofilaria immitis antigen demonstrated of both species, the most common stage encountered that 49 of them (5.4%) developed antifilarial IgG1 by preventive medicine and quarantine services, antibodies after deployment, and one out of 944 (0.1%) were very difficult to use for species identification. seroconverted to IgG4 antibodies. When a subsample To meet this problem, AMI, in collaboration with of 88 D. immitis reactive sera was subjected to a test UQ and QSH, developed molecular diagnostic tools using Brugia malayi antigen at NIH, 46 had elevated for identifying these species and for tracking their IgG antibodies and five had elevated IgG4 antibodies. movement into and within Australia.95-97 A total of 24 soldiers seroconverted to B. malayi IgG, and a single soldier seroconverted to IgG4. The study Studies on Culex annulirostris - a potential vector of
showed that a relatively low number of Australian Japanese encephalitis in Australia
soldiers seroconverted to B. malayi, indicating a low The Japanese encephalitis virus had been moving but measurable risk of exposure to human filarial down Southeast Asia through the Malay Archipelago parasites. This re-emphasised the importance of and into Papua New Guinea and, in 1995, there soldiers adhering to personal protective measures had been an outbreak in the Torres Strait islands against mosquito bites during their deployment to resulting in two deaths. Using sentinnel animals, tropical areas.
surveillance activities had indicated that the arbovirus was circulating on Cape York Peninsula in wild pig and bird populations though, as yet, there had only been one human case. Although the Ross River virus and Barmah Forest virus
Asian vector species for this virus is not present in In Australia, ADF personnel were at risk of acquiring Australia, vector competency studies had shown mosquito-borne infections not transmitted by that Culex annulirostris could readily transmit the anopheline mosquitoes. They were at greater risk of virus. However, this species was sometimes difficult becoming infected by arboviruses, such as Ross River to distinguish from Cx. sitiens and Cx. palpalis using (RR) and Barmah Forest (BF), than civilians because traditional morphological markers. To overcome this they deployed regularly to areas where the natural handicap, AMI collaborated with UQ and QSH in animal hosts and vector mosquitoes of these viruses examining the ribosomal DNA Internal Transcribed were in abundance. Concentration of soldiers within Spacer Region I to develop a molecular marker to training areas provided alternative human hosts, separate the three species reliably from one another.98 thereby facilitating the transmission and spread of The consistency of the procedure was documented these viral infections. During the evaluation of tent following the examination of specimens collected in barrier treatments with bifenthrin and permethrin Australia, PNG and the Solomon Islands. Further in WBTA, 3,497 mosquitoes (primarily Aedes vigilax) collections of field material in Cape York Peninsula were collected between January and March 2005 and the Northern Territory were analysed using the and processed for the presence of arboviruses. None CO1 gene of the mitochondrial DNA.99 Analysis of the Volume 23 Number 1; January 2015 specimens revealed that there are five independently 1990s there was a resurgence of vivax malaria in evolving haplotypes of Cx, annulirostris and three China involving millions of cases. The vector thought independently evolving haplotypes of Cx. palpalis, responsible for these epidemics was An. sinensis, and that these populations might differ in their but this species is primarily zoophilic, feeding mainly ability to transmit Japanese encephalitis on Cape on cattle, and therefore not a very efficient vector. York Peninsula.100 Field studies in Chinese provinces where the malaria outbreaks occurred revealed the presence of another anopheline which appeared morphologically similar to An. sinensis but which readily fed on humans. Malaria vectors and malaria transmission in rural
This mosquito was believed to be a new species and villages in Vietnam (2000-2005)
was named An. anthropophagus. The aim of the Under the auspices of VADMP, malaria transmission collaboration was to determine, using molecular was studied in rural communities in Vietnam. The tools, if An. anthropophagus was indeed a new species aim was to determine what anopheline species and not An. sinensis. Analysis and sequencing of were present, which were responsible for malaria the ribosomal DNA Internal Transcribed Spacer transmission, and to learn something of their biology Region II showed that An. anthropophagus and An. and ecology which might aid in their control and the sinensis were in fact different species.103 Following protection of military forces in the field. A field site the epidemics in China, the Korean Peninsula was selected at Truong Xuan Commune in Quang experienced severe epidemics of vivax malaria in the Binh Province, 500 km south of Hanoi, where malaria early 2000s. As in China, An. sinensis was at first transmission was perennial but where less than 15% thought to be responsible, but the vector was later of the villagers carried malaria parasites. This was found to be a closely related species - An. lesteri. primarily due to the fact that the anophelines in the Further studies revealed that An. anthropophagus area were not particularly efficient malaria vectors, and An. lesteri were in fact the same species, thus preferring to feed on cattle and buffalo.101 incriminating An. lesteri as the major malaria vector There was a perception in Vietnam that most responsible for the malaria epidemics in both China malaria was transmitted in the forest by An. dirus, a and the Korean Peninsula.
notoriously efficient malaria vector, and that people contracted the disease in the forest while hunting, 10. VACCINE DEVELOPMENT
timber cutting, and food gathering. At a second field site in Phuoc Chien Commune there was an The dengue outbreak among ADF personnel in Timor opportunity to study this concept of forest malaria. Leste provided the impetus for AMI to conduct the Although villagers in the commune lived in the valley first tetravalent dengue vaccine study in Australia floor where they were not exposed to any malaria involving 10 healthy volunteers admitted to the vectors, they spent several months of the year military hospital at Gallipoli Barracks, Brisbane. cultivating their crops on the surrounding hillsides. The Phase 1b study was designed to evaluate the Vector surveys conducted around these hillside immunogenicity and safety of two live attenuated communities showed that An. dirus was present vaccine formulations.104 After one injection, all and that a sufficient number of people spent enough subjects reported systemic reactions consistent time cultivating these crops to sustain malaria with a mild dengue-like syndrome. Seven volunteers transmission.102 These findings had implications developed dengue 3 viraemia after vaccination for community malaria control activities because and all of the volunteers developed a neutralizing indoor insecticide spraying and treated bed nets antibody response against serotype 3, with a partial were only supplied to village houses situated in the response against other serotypes. The study was valley floor, whereas little or no emphasis was placed terminated early due to formulation issues relating on preventing the acquisition of malaria at hillside to the dengue 3 vaccine component. Managing viral garden dwellings.
interference and balancing attenuation to produce acceptable tetravalent immunogenicity with minimal reactogenicity may be a recurring problem for future Malaria vectors associated with P. vivax epidemics in
multivalent live vaccines. This initial study with dengue vaccines led to a long-standing collaboration In 2003, AMI received a WHO grant, in collaboration between AMI, AP and ACR to evaluate chimeric with Dr Nigel Beebe, UTS and Professor Gao Qi arboviral vaccines using their envelope antigens (JIPD), to investigate the possible discovery of a combined with a core yellow fever vaccine.
new malaria vector in China. During the late mid- Journal of Military and Veterans' Health Japanese encephalitis
attenuated strain of the JE virus. Consequently, both With the spread of Japanese encephalitis (JE) vaccines shared antigenic determinants and non- throughout the region and even into mainland structural coding sequences which might boost or Australia, almost half of the ADF budget for suppress immune responses if these vaccines were vaccination was being spent on protecting its administered at the same time or in either order one military personnel against this mosquito-borne after the other. After administering two inoculations, disease.105 In efforts to extend the lifespan of the 30 days apart, using various JE-CV, YF-17D and Australian stockpile of the discontinued Biken JE placebo cross-overs, there were no serious adverse vaccine, previous studies at AMI had shown that events and seroconversion rates were above 90% in comparable serological levels of immunity could all the groups. Neutralising antibodies against the be attained by administering considerably lower JE and YF vaccines continued to be detected in 82- doses of the vaccine intradermally rather than by 100% of volunteers up to the last follow-up blood subcutaneous inoculation.6 Furthermore, cellular sample collected six months after immunisation. immunity continued to provide protection following The results suggested that both vaccines could be the decline of antibody levels.106,107 Although this given together, either concurrently or 30 days apart, inactivated, mouse brain-derived vaccine induced a without reducing their protective efficacy.
good immune response, there was uncertainty about In order to exclude the possibility that vaccinees the duration of protection and concern about some might transmit JEV to susceptible mosquitoes, Culex infrequent adverse events following immunisation, annulirostris, Culex gelidus, and Aedes vigilax were and production of the Biken JE vaccine was fed on Chimerivax™-JE.110 None of the mosquitoes completely discontinued in 2005.
fed on the vaccine became infected, in contrast In 2003, a randomised double-blind study involving to mosqitoes fed on JEV-Nakayama or the yellow 202 healthy ADF personnel was initiated to evaluate fever vaccine virus 17D. The findings indicated that the safety, immunogenicity and persistence of it was unlikely that transmission of JEV could be antibodies after administration of a live, attenuated established in Australia following vaccination with JE chimeric virus vaccine (JE-CV) - Chimerivax™- JE.108 To assess adverse events related to vaccination, volunteers were randomised to receive the vaccine 11. TECHNICAL ADVICE AND TRAINING
and placebo subcutaneously 28 days apart in a AMI continued to provide the Office of the Surgeon cross-over design. A subgroup of 98 participants were General with periodic updates regarding malaria and inoculated with a JE-CV booster six months later to other VBDs, including a review of Policy Directive determine whether this would prolong the protective 215 and subsequent issue of a new version in 2005. efficacy of the vaccine. Vaccination was well tolerated In addition to responding to frequent enquiries by and the incidence of reactions was comparable to medical staff regarding prevention and treatment of that observed after placebo inoculation. Almost all VBDs of ADF personnel, AMI was actively involved volunteers (99%) achieved seroprotective antibodies in providing assistance and training to preventive within 28 days of receiving the single dose of JE- medicine personnel during field deployments. In CV vaccine and 90% were still seroprotected two 2004 a new annual training course was initiated in years later. The seroprotection rate at this time was "Vector Borne Diseases Surveillance and Control". even higher (99%) for those JE-CV recipients who This one-week course for preventive medicine received a booster dose at six months. These findings technicians was administered by Army Logistic and indicated that JE-CV vaccination was safe and that Training Centre, and conducted by AMI staff. just a single dose provided prolonged immunity Following inauguration of the Vietnam Australia against JE infection. Plans were put in place to Defence Malaria Project, AMI hosted medical continue monitoring seroprotection for another three officers and scientists from Vietnam and trained years into the 2005-2010 quinquennium.
them in all aspects of work undertaken at the In 2004, a further randomised double-blind study Institute. Concurrently, AMI staff benefited greatly involving 108 volunteers was carried out to evaluate from experience gained during joint clinical and the safety and efficacy of concomitant or sequential field studies conducted in Vietnam. Apart from administration of JE-CV vaccine and yellow fever contributing to WHO-sponsored training projects in 17D vaccine (YF-17D).109 The rationale for this study various locations (see above), AMI staff continued to was based on the fact that JE-CV was produced by remain involved in other less structured efforts to removing the pre-membrane and envelope coding promote training and information on VBDs.
sequences from the yellow fever virus and replacing them with the corresponding sequences from an Volume 23 Number 1; January 2015 12) Evaluation of insecticides applied to skin, clothing The second half of the fourth decade (2000-2005) and tents to maintain optimum protection was characterised by the most wide-ranging and against mosquito bites.
significant activities yet undertaken by AMI. Many Entomological investigations in northern of them could not have been carried out without Australia with vectors of Ross River, Barmah the continued collaboration with other institutions Forest, Dengue and Japanese encephalitis in Australia and overseas. Significant events and achievements included: 14 Epidemiological investigations with malaria 1) Successful control of malaria and dengue vectors in Vietnam and China.
outbreak among Australian peacekeepers in 15) Inititation of dengue vaccine studies.
Timor Leste following various epidemiological, chemoprophylactic and mosquito control 16) Prolonged protection against Japanese measures instituted by AMI field teams. encephalitis obtained after administration of a single dose of a live, attenuated JE chimeric 2) Demonstration that currently-used regimens of virus vaccine (JE-CV).
antimalarial drugs, including mefloquine and primaquine, can be modified to provide more 17) Consolidation of close collaboration with US and effective protection against malaria under field Vietnamese Army investigators following the establishment of a Walter Reed Army Institute of Research laboratory at AMI and inauguration 3) Prospect that tafenoquine, a new, long-acting of Vietnam Australia Defence Malaria Project synthetic analogue of primaquine, might not (VADMP) laboratories in Hanoi.
only improve compliance with post-exposure prophylaxis and treatment regimens, but might 18) Redesignation of AMI as a WHO Collaborating provide protection against vivax and falciparum Centre for 4 years, with AMI hosting, participating malaria while in malarious areas.
in, or conducting several WHO-sponsored courses, conferences or workshops.
4) Assessment of the influence of food, gender and pregnancy on the effectiveness, tolerability and/or pharmacokinetics of various antimalarial Demonstration that artemisone, a new • Vietnam Australia Defence Malaria Project artemisinin derivative, is more active in vivo than (VADMP) established (2000-2005).
other artemisinins in curing falciparum malaria.
Walter Reed Army Institute of Research 6) Detailed evaluation of malaria rapid diagnostic laboratory established at AMI following arrival of tests (RDTs) and development of in vitro drug Lieutenant Colonel Dennis Kyle.
susceptibility test for P.vivax.
Investigations on "Evolution of drug resistance 7) Identification of molecular markers for P. vivax in P. falciparum" commence under three-year resistance to chloroquine and sulfadoxine.
NIH RO1 grant (2000-2003). 8) Documentation of worsening resistance of first- AMI field teams control malaria and dengue and second-line drugs used for malaria treatment outbreak in ADF personnel deployed to Timor in various parts of the Asia/Pacific region.
9) In vitro assessment of drug activity against P. vivax Shorter and higher dose primaquine regimens parasites enabled by successful transfection of P. evaluated to determine tolerability and vivax genes to P. falciparum. effectiveness for post-exposure prophylaxis and 10) Artemisinin resistance of P. falciparum in radical cure of P. vivax malaria.
vitro, produced by applying discontinuous Weekly tafenoquine prophylaxis during six- drug selection pressure, is associated with month deployments on peace keeping duties amplification of the pfmdr1 gene. in Timor Leste prevents falciparum and vivax 11) Investigation of factors influencing the evolution malaria both during and following deployments.
and spread of drug resistance in malaria Population pharmacokinetics of tafenoquine supports the use of a loading dose of 200 mg daily for 3 days followed by 200 mg weekly for six months for effective malaria protection. Journal of Military and Veterans' Health Mosquito repellents evaluated at Cowley Beach Field evaluation of picaridin as a mosquito Training Area, Queensland.
repellent and of bifenthrin as barrier treatment in military shirts and tents at Mount Bundey WHO in vitro test modified to assessof P. vivax Training area, Northern Territory.
susceptibility to antimalarial drugs. Food containing 30 g fat may enhance Entomological investigations in Timor Leste primaquine effectiveness by augmenting plasma identify potential malaria vectors and incriminate drug concentrations. a new vector species. New molecular diagnostic tools are developed to identify potential Japanese encephalitis vectors AMI hosts WHO-sponsored 13th Southwest in Australia.
Pacific Malaria meeting.
Immunisation with live, attenuated Japanese Official opening of VADMP laboratories in Hanoi.
encephalitis chimeric virus vaccine (JE- CV) is safe and induces seroprotection for at least two Large-scale study with mefloquine, including pharmacokinetic evaluation, indicates that 250 mg every other day during the first week followed by the same dose once a week is well tolerated High dose, shorter courses of primaquine are and effective in providing malaria protection for tolerated just as well as longer primaquine courses by glucose-6-phosphate dehydrogenase Artemisone is more effective than other normal Australian soldiers.
artemisinin drugs in curing falciparum infections Seven-day courses of primaquine (22.5 mg twice in Aotus monkeys. a day), preceded by two days of artesunate (200 Increased plasma clearance (50%) of atovaquone, mg twice a day) are well tolerated and effective in proguanil and cycloguanil in pregnant malaria Vietnamese patients infected with vivax malaria.
patients suggests that the dose of atovaquone- Pharmacokinetic studies with artemisone during proguanil might need to be increased for the Phase I human safety and toxicity studies treatment of malaria during pregnancy.
support the potential value of this drug for P. falciparum parasites process a highly diverse artemisinin combination therapy.
family of PfEMP1 on the surface of red cells P. vivax is both innately resistant and can and switch rapidly between these antigens to develop resistance to sulfadoxine due to variation establish an infection.
and mutation, respectively, of the parasite's Sulfadoxine/pyrimethamine treatment is less dihydropteroate synthetase (DHPS) enzyme.
effective in patients infected with P. vivax carrying Investigations on "Antigenic variation and drug a quadruple mutant dihydrofolate reductase resistance in P. falciparum" commence under second three-year NIH RO1 grant (2004-2007).
Atovaquone-resistant parasites are less fit than P. falciparum in-host dynamics model assists in sensitive parasites, suggesting reversal of drug understanding diverse factors influencing the resistance following use of alternative drugs.
development of host immunity and the evolution Molecular diagnostic tools are developed to of drug resistance.
identify larvae of dengue virus vectors and to Field evaluation of commercial repellents in prevent their importation into Australia. Entomological studies identify the malaria Lieutenant Colonel Robert Cooper replaces vectors in rural communities in north central Lieutenant Colonel Michael Edstein as Vietnam and investigate their biology and Commanding Officer.
Amplification of pfmdr1 gene plays an important Long-term persistence of neutralising antibodies role in the development of P. falciparum resitance after sequential administration of JE- CV and to artemisinin drugs.
yellow fever 17D vaccines suggest that both vaccines can be given together without reducing Chloroquine resistance in the Philippines is due their protective efficacy.
to mutations of both indigenous and imported parasites from Papua New Guinea. Volume 23 Number 1; January 2015 P. falciparum expression system established Food containing 17 g fat increases plasma to assess P. vivax response to dihydrofolate piperaquine concentrations in healthy reductase (DHFR) inhibitors.
Vietnamese soldiers, which may benefit malaria Drug resistance exerts a strong force in shaping patients receiving ACT using this drug and a parasite population.
dihydroartemisinin. Barrier treatment of tents with bifenthrin is just Relapses of P. vivax infections in ADF personnel as effective as permethrin in reducing exposure deployed to Timor Leste result from activation of to mosquitoes in the Wide Bay Training area, a single strain of hypnozoite in the liver.
Highly diverse target antigen HRP2 may cause Entomological aspects of forest malaria studied variable sensitivity of malaria RDT's, whereas in central Vietnam. highly conserved aldolase produces more reproducible test results but is less sensitive The opinions expressed are those of the authors and Pvmdr1 is a molecular marker for drug resistant do not necessarily reflect those of the Joint Health P. vivax, with mutant pvmdr1 predicting Command or any extant Australian Defence Force chloroquine resistance while multicopy pvmdr1 predicts mefloquine resistance.
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12. Kitchener S. Epidemiology of malaria from East Timor among Australian Defence Force personnel. Trans Royal Soc Trop Med Hyg 2002; 96: 376-377.
13. Kitchener S, Nasveld P, Russell B, Elmes N. An outbreak of malaria in a forward battalion on active service in East Timor. Mil Med 2003; 168(6): 457-459.
14. Kitchener S, Warwarek P. Operational Malaria in East Timor: six battalions later. Aust Mil Med 2002;11(1): 30-34. 15. Peragallo M, Croft, A, Kitchener, S. Malaria during a multinational military deployment: the comparative experience of the Italian, British and Australian Armed Force in East Timor. Trans Roy Soc Trop Med Hyg 2002; 96: 481-482.
16. Bragonier R, Reyburn H, Nasveld P, Edstein M, Auliff A. Rainy-season prevalence of malaria in Bobonaro district, East Timor. Ann Trop Med Parasitol 2002; 96 (7): 739-743.
Journal of Military and Veterans' Health 17. Bragonier R, Nasveld P, Auliff A. Plasmodium malariae in East Timor. Southeast Asia J Trop Med Public Hlth 2003; 33 (4): 689-690.
18. McGready R, Stepniewska K, Seaton E, Cho T, Cho D, Ginsberg A, Edstein MD, Ashley E, Looareesuwan S, White NJ, Nosten F. Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil. Eur J Clin Pharmacol 2003; 59: 553-557.
19. McGready R, Stepniewska K, Edstein MD, Cho T, Gilveray G, Looareesuwan S, White NJ, Nosten F. The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria. Eur J Clin Pharmacol 2003; 59: 545-552.
20. Edstein MD, Kotecka BM, Kyle DE, Rieckmann KH, Anderson KL, Pombo DJ, Good MF. Lengthy antimalarial activity of atovaquone in human plasma following atovaquone-proguanil administration. Antimicrob Ag Chemother 2005; 49: 4421-4422.
21. Kitchener S, Cunningham J, Jensen A. Mefloquine for malaria prophylaxis in the ADF. Aust Mil Med 2001;10(1): 4-5.
22. Kitchener S. The military experience of mefloquine malaria chemoprophylaxis. ADF Health 2003; 4(1): 34-38.
23. Nasveld P, Brennan L, Edstein M, Kitchener S, Leggat P, Rieckmann K. A randomised double-blind comparative study to evaluate the safety, tolerability and effectiveness of tafenoquine and mefloquine for the prophylaxis of malaria in non-immune Australian soldiers. Am J Trop Med Hyg 2002; 67(2): 255-256.
24. Kitchener S, Nasveld P, Gregory R, Edstein M. Mefloquine and doxycycline malaria prophylaxis in Australian soldiers in East Timor. Med J Aust 2005; 182: 168-171.
25. Charles B, Blomgren A, Nasveld PE, Kitchener S, Jensen A, Gregory RM, Robertson B, Harris IE, Reid MP, Edstein MD. Population pharmacokinetics of mefloquine in military personnel for prophylaxis against malaria infection during field deployment. Eur J Clin Pharm 2007; 63: 271-278 26. Dao NVH, Ngoa NP, Thuy LT, The ND, Bui Dai, Binh VQ, Anh LN, Rieckmann KH, Edstein MD. Fatty-food does not alter blood mefloquine concentrations in the treatment of falciparum malaria. Trans R Soc Trop Med Hyg 2005; 99: 927-931.
27. Nguyen Trong Chinh, Nguyen Ngoc Quang, Nguyen Xuan Thanh, Bui Dai, Travers T, Edstein MD. Short Report: Pharmacokinetics of the antimalarial drug piperaquine in healthy Vietnamese subjects. Am J Trop Med Hyg 2008; 79: 620-623.
28. Haynes RK, Fugmann B, Stetter J, Rieckmann K, Heilmann H-D, Chan H-W, Cheung M-K, Lam W-L, Wong H-N, Croft SL, Vivas L, Rattray L, Stewart L, Peters W, Robisnson BL, Edstein MD, Kotecka B, Kyle DE, Beckermann B, Gerisch M, Radtke M, Schmuck G, Steinke W, Wollborn U, Schmeer K, Roemer A. Artemisone – a highly active antimalarial drug of the artemisinin class. Angew Chem Int Ed 2006; 45: 2082-2088.
29. Nicanor O, Kotecka BM, Edstein MD, Haynes RK, Fugmann B, Kyle DE, Rieckmann KH. Evaluation of artemisone combinations in Aotus monkeys infected with Plasmodium falciparum. Antimicrob Ag Chemother 2009; 53: 3592-3594. 30. Rieckmann KH. Falciparum malaria. The urgent need for safe and effective drugs. Ann Rev Med 1983; 34: 321-335.
31. Nagelschmitz J, Voith B, Wensing G, Roemer A, Fugmann B, Haynes RK, Kotecka BM, Rieckmann KH, Edstein MD. First-Time-In-Humans safety, tolerability, pharmacokinetics and ex vivo pharmacodynamic antimalarial activity of the new artemisinin derivative, artemisone. Antimicrob Ag Chemother 2008; 52: 3085-91.
32. Chen N, Auliff A, Rieckmann K, Gatton LM, Cheng Q. Relapses of Plasmodium vivax infection result from clonal hypnozoites activated at predetermined intervals. J Infect Dis 2007; 195(7): 934-941.
33. Kitchener S, Ashford B. Self treated relapsing vivax malaria? Aust Mil Med 2002; 11(1): 19-20. 34. Kitchener S, Seidl I. Relapsing vivax malaria. Med J Aust 2002; 176: 502.
35. Bennett S, Elmes N, Nasveld P, Kitchener S. Proceedings of the 15th Asia Pacific Military Medicine Conference, Hanoi, Vietnam 2005.
36. Nguyen Van Hoang Dao, Bui Tri Cuong, Nguyen Dang Ngoa, Le Thi Thanh Thuy, Nguyen Duy The, Dinh Ngoc Duy, Bui Dai, Nguyen Xuan Thanh, Chavchich M, Rieckmann KH, Edstein MD. Vivax malaria: preliminary observations with a shorter course of treatment with artesunate plus primaquine. Trans Roy Soc Trop Med Hyg 2007; 101: 534-539.
37. Nasveld PE, Kitchener S, Edstein MD, Rieckmann KH. Comparison of tafenoquine (WR238605) and primaquine in the post exposure (terminal) prophylaxis of vivax malaria in Australian Defence Force personnel. Trans Roy Soc Trop Med Hyg 2002; 96: 683-684.
Volume 23 Number 1; January 2015 38. Bui Tri Cuong, Vu Quoc Binh, Bui Dai, Dinh Ngoc Duy, Lovell CM, Rieckmann K, Edstein MD. Does food and gender affect the pharmacokinetics of primaquine in healthy Vietnamese subjects? Br J Clin Pharm 2006; 61: 682-689.
39. Elmes NJ, Bennett SM, Abdalla H, Carthew TL, Edstein MD. The pharmacokinetics of primaquine in healthy Australian male and female volunteers. Am J Trop Med Hyg 2006; 74: 951-952.
40. Edstein MD, Nasveld PE, Kocisko DA, Kitchener SJ, Gatton ML, Rieckmann KH. Gender differences in gastrointestinal disturbances and plasma concentrations of tafenoquine in healthy volunteers after tafenoquine administration for post-exposure vivax malaria prophylaxis. Trans Roy Soc Trop Med Hyg 2007; 101: 226-230.
41. Nasveld P, Kitchener S. Treatment of acute vivax malaria with tafenoquine. Trans R Soc Trop Med Hyg 2005; 99: 2-5.
42. Kitchener S, Nasveld P, Edstein M. Tafenoquine in the treatment of recurrent Plasmodium vivax malaria. Am J Trop Med Hyg 2007; 76(6): 494-496.
43. Baird K, Rieckmann KH. Can primaquine therapy for vivax malaria be improved? Trends in Parasitology 2003; 19(3): 115-120.
44. Nasveld P, Brennan L, Edstein M, Kitchener S, Leggat P, Rieckmann K A randomised double-blind comparative study to evaluate the safety, tolerability and effectiveness of tafenoquine and mefloquine for the prophylaxis of malaria in non-immune Australian soldiers. Am J Trop Med Hyg 2002; 67(2): 255-256.
45. Nasveld PE, Edstein MD, Reid M, Brennan L, Harris IE, Kitchener SJ, Leggat PA, Pickford P, Kerr C, Ohrt C, Prescott W, et al. Randomized, double-blind study of the safety, tolerability and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects. Antimicrob Ag Chemother 2010; 54(2): 792-798.
46. Charles BG, Miller AK, Nasveld PE, Reid MP, Harris IE, Edstein MD Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects. Antimicrob Ag Chemother 2007; 51: 2709-2715.
47. Baker J, McCarthy J, Gatton ML, Kyle D, Belizario V, Luchavez J, Bell D, Cheng Q. Genetic Diversity of Plasmodium falciparum Histidine-Rich Protein 2 and its effect on the performance of PfHRP2-based Rapid Diagnostic Tests. J Infec Dis 2005; 192: 870-877.
48. Lee N, Baker J, Andrews K, Gatton M, Bell D, Cheng Q, McCarthy J. Effect of sequence variation in Plasmodium falciparum Histidine-Rich Protein 2 on the binding of specific monoclonal antibodies: implications for Rapid Diagnostic Tests for malaria. J Clin Microbiol 2006; 44(8): 2773-2778.
49. Baker J, Ho M-F, Pelecanos A, Gatton M, Chen N, Abdullah S, Albertini A, Ariey F, Barnwell J, Bell D, Cunningham J, Djalle D, Echeverry D, Gamboa D, Hii J, Kyaw MP, Luchavez1 J, Membi C, Menard D, Murillo C, Nhem S, Ogutu B, Onyor P, Oyibo W, Wang SQ, McCarthy J, Cheng Q. Global sequence variation in the histidine-richproteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests. Malaria Journal 2010; 9: 129.
50. Lee N, Baker J, Bell D, McCarthy J, Cheng Q. Assessing the genetic diversity of Plasmodium falciparum and Plasmodium vivax aldolases and its potential effect on the performance of aldolase-based Rapid Diagnostic Tests (RDTs). J Clin Microbiol 2006; 44(12): 4547-4549.
51. Baker J, McCarthy J, Gatton M, Lee N, Bell D, Peters J, Cheng Q. Rapid diagnostic tests for malaria: are they sufficiently reliable? ADF Health 2007; 8: 12-17. 52. Rieckmann K, Cheng Q. Pyrimethamin-sulfadoxine resistance in Plasmodium falciparum must be delayed in Africa. Trends in Parasitology 2002; 18(7): 293-4. 53. Nagesha AS, Casey GJ, Rieckmann KH, Fryauff DJ, Laksana BS, Reeder JC, Maguire JD, Baird JK. New haplotypes of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene among chloroquine-resistant parasite isolates. Am J Trop Med Hyg 2003; 68: 398-402.
54. Burns M, Baker J, Auliff AM, Gatton ML, Edstein MD and Cheng Q. Efficacy of sulfadoxine-pyrimethamine in the treatment of uncomplicated Plasmodium falciparum malaria in East Timor. Am J Trop Med Hyg 2006; 74(3): 361-366. 55. Maguire JD, Lacy MD, Sururi M, Sismadi P, Krisin, Wiady I, Laksana B, Bangs MJ, Masbar S, Susanti I, Basuki W, Barcus MJ, Marwoto H, Edstein MD, Tjokrosonto S, Baird JK. Chloroquine or sulfadoxine-pyrimethamine for the treatment of uncomplicated, Plasmodium falciparum malaria during an epidemic in Central Java, Indonesia. Ann Trop Med Parasitol 2002; 96(7): 655-68.
Journal of Military and Veterans' Health 56. Ratcliff A, Siswantoro H, Kenangalem E, Wuwung M, Brockman A, Edstein MD, Laihad F, Ebsworth EP, Anstey NM, Tjitra E and Price RN. Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to chloroquine and sulfadoxine–pyrimethamine in southern Papua, Indonesia. Trans R Soc Trop Med Hyg 2007; 101: 351-359.
57. Auliff A, Wilson DW, Russell B, Gao Q, Chen N, Anh LN, Maguire J, O'Neil M, Cheng Q. Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs. Am J Trop Med Hyg 2006; 75(4): 617-621. 58. Tjitra E, Baker J, Cheng Q, Anstey N. The therapeutic efficacy of artesunate plus sulfadoxine-pyrimethamine and chloroquine plus sulfadoxine-pyrimethamine for vivax malaria: relationship with Plasmodium vivax dhfr mutations. Antimicrob Ag Chemother 2002; 46(12): 3947-3953. 59. Auliff A. Personal communication 60. Russell BM, Udomsangpetch R, Rieckmann KH, Kotecka BM, Coleman RE, Sattabongkot J. Simple in vitro assay for determining the sensitivity of Plasmodium vivax isolates from fresh human blood to antimalarials where P. vivax is endemic. Antimicrob Ag Chemother 2003; 47(1): 170-173.
61. Suwanarusk R, Russell B, Chavchich M, Chalfein F, Kenangalem E, Kosaisavee V, Prasetyorini B, Piera KA, Barends M, Brockman A, Lek-Uthai U, Anstey NM, Tjitra E, Nosten N, Cheng Q and Price RN. (2007) Chloroquine resistant Plasmodium vivax: in vitro characterisation and association with molecular polymorphisms. PLOs One. 2007 Oct 31; 2(10): e1089. 62. Korsinczky M, Fisher K, Chen N, Rieckmann K, Cheng Q. Sulfadoxine resistance in Plasmodium vivax is associated with a DHPS sequence polymorphism altering the putative drug-binding site. Antimicrob Ag Chemother 2004; 48(6): 2214-2222.
63. Imwong M, Pukrittayakamee S, Cheng Q, Moore C, Looareesuwan S, Snounou G, White NJ and Day NP. Limited polymorphism in the dihydropteroate synthetase gene (dhps) of Plasmodium vivax isolates from Thailand. Antimicrob Ag Chemother 2005; 49(10): 4393-4395. 64. O'Neil, MT, Korsinczky MLJ, Gresty K, Auliff A, Cheng Q. A novel Plasmodium falciparum expression system for assessing antifolate resistance caused by mutant P. vivax dihydrofolate reductase-thymidylate synthase. J Infect Dis 2007; 196(3): 467-474.
65. Chavchich M, Gerena L, Peters J, Chen N, Cheng Q, Kyle DE. Role of pfmdr1 Amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum. Antimicrob Ag Chemother 2010; 54(6): 2455-2464.
66. Chen N, Kyle DE, Pasay CM, Fowler EV, Peters JM, Cheng Q. Pfcrt allelic types with novel amino acid mutations in chloroquine resistant Plasmodium falciparum from the Philippines. Antimicrob Ag Chemother 2003; 47(11): 3500-3505.
67. Chen N, Wilson D, Pasay CM, Bell D, Martin L, Kyle D, Cheng Q. The origin and dissemination of novel mutant Pfcrt allelic types of Plasmodium falciparum in the Philippines. Antimicrob Ag Chemother 2005; 49(5): 2102-2105. 68. Fowler E, Peters J, Gatton M, Chen N, Cheng Q. Genetic diversity of the DBL region in Plasmodium falciparum var genes among Asia-Pacific isolates. Mol Biochem Parasitol 2002; 120(1): 117-126.
69. Fowler EV, Chavchich M, Chen N, Peters JM, Kyle D, Gatton ML, Cheng Q. Physical linkage to drug resistance genes results in conservation of var genes among West Pacific Plasmodium falciparum isolates. J Infect Dis 2006; 194: 939-948. 70. Cheng Q, Lawrence G, Reed C, Stowers A, Ranford-Cartwright L, Creasey A, Saul A. Measurement of Plasmodium falciparum growth rate in vivo: a test of malaria vaccines. Am J Trop Med Hyg 1997; 57(4): 495-500. 71. Peters J, Fowler E, Gatton M, Chen N, Saul A, Cheng Q. High diversity and rapid changeover of expressed var genes during acute phase of Plasmodium falciparum infections in human volunteers. Proc Nat Acad Sci USA 2002; 99(16): 10689-10694. 72. Gatton ML, Peters J, Fowler E, Cheng Q. Switching rates of Plasmodium falciparum var genes: faster than we thought? Trends in Parasitology 2003; 19(5): 202-208. 73. Peters J, Chen N, Gatton M, Korsinczky M, Fowler E, Manzetti S, Saul A, Cheng Q. Mutations in cytochrome b resulting in atovaquone resistance are associated with a loss of fitness in Plasmodium falciparum. Antimicrob Ag Chemother 2002; 46(8): 2435-2441.
Volume 23 Number 1; January 2015 74. Gatton ML, Cheng Q. Investigating antigenic variation and other parasite-host interactions in Plasmodium falciparum infections in naïve hosts. Parasitololgy 2004; 128: 367-376. 75. Gatton ML, Cheng Q. Evaluation of the pyrogenic threshold for P. falciparum malaria in naïve individuals. Am J Trop Med Hyg 2002; 66(5): 467-473. 76. Gatton ML, Cheng Q. Modelling the development of acquired clinical immunity to Plasmodium falciparum. Infection and Immunity 2004; 72(11): 6538-6545. 77. Gatton ML, Martin LB, Cheng Q. Evolution of resistance to sulfadoxine / pyrimethamine in Plasmodium falciparum parasites. Antimicrob Ag Chemother 2004; 48(6): 2116-2123. 78. Frances SP, Cooper RD. Personal protection measures against mosquitoes - a brief history and current use of repellents by the Australian Defence Force. ADF Health 2002; 3: 58-63.
79. Hii J, Frances SP, Canyon D, Govere J. Personal protective measures against disease vectors. In: Leggat PA, Goldsmid JM (eds.). Primer of Travel Medicine, Third Edition, Brisbane, ACTM Publications, 2002; 163-174.
80. Frances SP, Wirtz RA. Repellents: Past, Present and Future. J. Am. Mosq. Control Assoc. 2005; 21 (Suppl.): 81. Frances SP, Auliff AM, Edstein MD, Cooper RD. Survey of personal protection measures against mosquitoes among Australian Defence Force personnel deployed to East Timor. Mil Med 2003; 168: 227-230.
82. Frances SP, Marlow RM, Jansen CC, Huggins RL, Cooper RD. Laboratory and field evaluation of commercial repellent formulations against mosquitoes (Diptera: Culicidae) in Queensland, Australia. Aust J Entomol 2005; 44: 431-436.
83. Frances SP, Dung NV, Beebe NW, Debboun M. Field evaluation of repellent formulations against day and night-time biting mosquitoes in a tropical rainforest in northern Australia. J Med Entomol 2002; 39: 541-544.
84. Frances SP, Waterson DGE, Beebe NW, Cooper RD. Field evaluation of repellent formulations containing deet and picaridin against mosquitoes in Northern Territory, Australia. J Med Entomol 2004; 41: 414-417.
85. Frances SP, Waterson DGE, Beebe NW, Cooper RD. Field evaluation of commercial repellent formulations against mosquitoes (Diptera: Culicidae) in Northern Territory, Australia. J Am Mosq Control Assoc 2005; 21: 480-482.
86. Frances SP, Watson K, Constable BG. Comparative toxicity of permethrin and bifenthrin treated fabrics for Anopheles farauti and Aedes aegypti. J Am Mosq Control Assoc 2003; 19: 275-278.
87. McGinn D, Frances SP, Sweeney AW, Brown MD, Cooper RD. Evaluation of Bistar 80SC (Bifenthrin) as a tent treatment for protection against mosquitoes in Northern Territory, Australia. J Med Entomol 2008; 45: 1087-1091.
88. Frances SP. Evaluation of bifenthrin and permethrin as barrier treatments for military tents against mosquitoes in Queensland, Australia. J Am Mosq Control Assoc 2007; 23: 208-212.
89. Frances SP, Huggins RL, Cooper RD. Evaluation of the inhibition of egglaying, larvicidal effects and bloodfeeding success of Aedes aegypti exposed to permethrin and bifenthrin treated military tent fabric. J Am Mosq Control Assoc 2008; 24: 598-600.
90. Cooper RD, Edstein MD, Frances SP, Beebe NW. Malaria vectors of Timor-Leste. Malaria J: 2010; 9: 40.
91. Ryan JR, Davé K, Collins KM, Hochberg L, Sattabongkot J, Coleman RE, Dunton RF, Bangs MJ, Mbogo CM, Cooper RD, Schoeler GB, Rubio-Palis Y, Magris M, Romer LI, Padilla N, Quakyi IA, Bigoga J, Leke RG, Akinpelu O, Evans B, Walsey M, Patterson P, Wirtz RA, Chan AS. Extensive multiple test centre evaluation of the VecTest malaria antigen panel assay. Med Vet Entomol 2002; 16: 321-327.
92. Frances SP, Baade LM, Kubofcik J, Nutman TB, Melrose WD, McCarthy JS, Nissen MD. Seroconversion to filarial antigens in Australian Defence Force personnel in Timor-Leste. Am J Trop Med Hyg 2008; 78: 560-563.
93. Frances SP, MacKenzie DO, Jones A, Cooper RD. Mosquitoes (Diptera: Culicidae) and arboviruses at Wide Bay Military Training Area, Queensland, Australia. Arbovirus Res Aus 2009; 10: 46-49.
94. Ritchie SA, Moore P, Carruthers M, Williams C, Montgomery B, Foley P, Ahboo S, van den Hurk A, Lindsay MD, Cooper RD, Beebe NW Russell RC. Discovery of a widespread infestation of Aedes albopictus in the Torres Strait, Australia. J Am Mosq Control Assoc 2006; 22: 358-365.
Journal of Military and Veterans' Health 95. Beebe WN, Whelan PI, van den Hurk A, Ritchie SA, Cooper RD. Genetic diversity of the dengue vector Aedes aegypti in Australia and implications for future surveillance and mainland incursion monitoring. Communicable Diseases Intelligence 2005; 29: 299-304.
96. Beebe, NW, Whelan PI, van den Hurk AF, Ritchie SA, Corcoran S, Cooper RD. A Polymerase Chain Reaction- Based diagnostic to identify larvae and eggs of container mosquito species from the Australian Region. J Med Entomol 2007; 44: 376-380.
97. Hill, LA, Davis J, Hapgood G, Whelan PI, Smith GA, Ritchie SA, Cooper RD, van den Hurk AF Rapid identification of Aedes albopictus, Aedes scutellaris and Aedes aegypti life stages using real-time polymerase chain reaction assays. Am J Trop Med Hyg 2008; 79: 866–875.
98. Beebe NW, van den Hurk AF, Chapman HF, Frances SP, Williams CR, Cooper RD. Development and evaluation of a species diagnostic PCR procedure for cryptic members of the Culex sitiens (Diptera: Culicidae) subgroup in Australia and the southwest Pacific. J Med Entomol 2002; 39: 362-369.
99. van den Hurk AF, Montgomery BL, Zborowski P, Beebe NW, Cooper RD, Ritchie SA. Does 1-Octen-3-ol enhance trap collections of Japanese encephalitis virus mosquito vectors in Northern Australia? J Am Mosq Control Assoc 2006; 22: 15-21.
100. Hemmenter S, Slapeta J, van den Hurk AF, Cooper RD, Whelan PI, Russell RC, Johansen CA, Beebe NW. A curious coincidence: mosquito biodiversity and the limits of the Japanese encephalitis virus in Australasia. BMC Evolutionary Biology 2007; 7: 100.
101. Cuong DM, Beebe NW, Hong NT, TaoVLQ, Chau TL, Van DN, Thanh NX, Anh L N, Cooper RD. Vectors and malaria transmission in deforested, rural communities in north-central Vietnam. Malaria J 2010; 9: 259.
102. Sanh NH, Dung NV, Thanh NX, Trung TN, Co TV, Cooper RD. Forest malaria in central Vietnam. Am J Trop Med Hyg 2008; 79: 652–654.
103. Gao Q, Beebe NW, Cooper RD. Molecular identification of the malaria vectors Anopheles anthropophagus and Anopheles sinensis (Diptera: Culicidae) in central China using PCR and appraisal of their position within the Hyrcanus Group. J Med Entomol 2004; 41: 5-11.
104. Kitchener S, Nissen M, Nasveld P, Forrat R, Yoksan S, Lang J, Saluzzo JF. Immunogencity and safety of two live-attenuated tetravalent dengue vaccine formulations in health Australian adults. Vaccine 2006; 24(9): 1238-1241.
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106. Kitchener S, Baade L, Brennan L, Nasveld P. Intradermal boosting of Japanese encephalitis vaccination. J Trav Med 2004; 11(3): 182-183.
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Volume 23 Number 1; January 2015 Veterans with co-morbid posttraumatic stress disorder and mild traumatic brain injury: the nurse practitioners role in facilitating treatmentLori Wheeler & Kathryn Puskar Abstract
Background: Many military veterans experience events during deployment that cause mild traumatic brain
injury (mTBI) and symptoms of Posttraumatic Stress Disorder (PTSD). Due to the inconsistencies in treatment
plans for patients with these co-morbid conditions, it is important that nurse practitioners and other mental
health care providers are aware of the options available and facilitate appropriate treatment in order to improve
outcomes for this patient population.
Purpose: To discuss standard evidence- based practice protocols to treat co-morbid PTSD and mTBI in veterans,
evidenced by the review of a case study, and to highlight the importance of the role of the nurse practitioner in
facilitating appropriate treatment.
Methods: A case study and article review of published literature related to treatment options for patients with
co-morbid mTBI and PTSD will be discussed.
Conclusion: This paper will illustrate the findings and discuss implications for the nurse practitioner's role in
facilitating appropriate treatment plans in order to improve outcomes for patients with co-morbid mTBI and
Keywords: Veterans, Posttraumatic Stress Disorder, Mild Traumatic Brain Injury, Nurse Practitioners,
Otis et al.3 describe the symptom profile of PTSD, PTSD can occur after someone experiences or which includes: 1) experiencing a traumatic event, witnesses a traumatic event in which their physical 2) re-experiencing the event via recurrent thoughts, or emotional well-being is threatened. Many veterans nightmares, or flashbacks, 3) avoidance of stimuli, experience traumatic events while deployed that thoughts or places associated with the traumatic cause symptoms of PTSD, ranging from combat event, and 4) emotional detachment and symptoms of related incidents, to training accidents or traffic hyper-arousal which cause increased startle reflex, collisions. Bogdanova and Verfaellie noted that problems with sleep, attention and concentration among combat deployed troops, there is a relatively problems, hypervigilance, and the presence of consistent prevalence of PTSD in the range of 10- irritability and anger.
17%.1 Richardson et al. noted that recent studies Sripada et al.4 define a mTBI as a traumatically have suggested combat related PTSD rates are induced physiological disruption of brain function, between 4-17%. Among different nations, the rates as manifested by at least one of the following: 1) vary, with the highest prevalence noted in the any period of loss of consciousness not exceeding United States at approximately 17%, compared to a 30 minutes, 2) any loss of memory for events 12% prevalence in Australian and United Kingdom immediately before or after the accident, 3) any veterans, and 7.2% of Canadian veterans.2 The alteration in mental state at the time of the accident highest rates of PTSD are reported among veterans such as feeling dazed, disoriented, or confused, and who also have a history of mTBI at a prevalence of 4) focal neurological deficits that may or may not be 33-39%,1 although it is debatable as to whether the transient such as weakness, loss of balance, and development of PTSD is related to the fact that the vision changes. The symptoms of mTBI can last days patient sustained a mTBI or if the condition would or weeks, but usually resolve before three months. have also occurred in the absence of a mTBI. When the symptoms last longer than three months, Journal of Military and Veterans' Health the patient is considered to have post concussive trauma focussed cognitive behavioural therapy- based treatments.7 CPT and PE are proven equally effective for treatment and have been established as Otis et al.3 cite The Diagnostic and Statistical the recommended protocols to reduce and eliminate Manual of Mental Disorders, 4th Edition, 2000 symptoms of PTSD.7 In CPT, clinicians rely on and describe PCS as a clinical syndrome where at cognitive processing techniques by working with least three symptoms of concussion persist after patients to address inconsistencies between trauma the initial three months following a head injury. generated thoughts and pre-existing belief systems. Symptoms of concussion include fatigue, difficulty On the other end of the spectrum, PE relies on sleeping, dizziness, persistent headaches, irritability, emotional processing through systematic exposure increased anxiety, depression, mood changes, and to memories or physical reminders of the trauma to reduce symptoms.7 Many of the symptoms of PTSD and mTBI overlap, Peterson et al.8 define CPT, which usually consists namely problems with executive functioning, of approximately twelve 60 minute sessions, and learning and memory, and attention. For this includes psycho-education about PTSD, cognitive reason, it is often difficult to distinguish whether or restructuring, and exposure. In the exposure not a patient's symptoms stem from PTSD, mTBI, component of CPT, the patient writes an account of or both. It is important that the patient is initially the event to read aloud in therapy and at home. The examined and a thorough work up is performed to cognitive therapy component begins with an impact rule out a more serious medical condition caused by statement in which the patient describes the impact the head injury during the traumatic event. Another of the event on his or her perspective of self, others, factor to consider is that the patient may not seek and the world, such as "it's all my fault". Throughout the care of a mental health care provider within the therapy, problematic cognitions are identified and first three months of their event. Identification of challenged through Socratic questioning until more PTSD specific symptoms, such as hyper-arousal and accurate beliefs replace any distorted thoughts. avoidance, which are typically not seen in civilian The last few sessions focus on cognitions that are mTBI, can be helpful for the differential diagnosis.1 troublesome in PTSD such as safety, trust, power, It is also important to consider the timeframe of the esteem, and intimacy.8 mTBI when implementing treatment plans. Residual symptoms of PCS may subside by one year after the Peterson et al. also define PE, which usually consists injury, while symptoms of PTSD may persist, and of ten to twelve 90 minute sessions, and includes the majority of cases are unlikely to resolve without psycho-education, breathing retraining, imaginal proper treatment.
exposure, and in vivo exposure. Patients are educated about the evolution and treatment of PTSD, are Treatment options for PTSD with mTBI taught breathing techniques to promote relaxation, Traditionally, there have been specialised clinical and practice imaginal and in vivo exposure to teams who treat each of these disorders separately. promote adaption to the feared trauma memory. Challenges have been identified by providers in PTSD patients usually avoid thoughts and situations regards to scheduling and engaging patients with co- that are reminders of the trauma, but PE requires occurring mTBI and PTSD in treatment, determining the patient to confront the memories by repeatedly the aetiology of patients' presenting problems, retelling the trauma story (imaginal exposure) coordinating services, and knowing whether or how and confront feared situations associated with the to alter standard treatments.6 With the evolving trauma (in vivo exposure).8 The major difference role of the nurse practitioner, and the increased between the two therapies is that CPT teaches the autonomy in practice, nurse practitioners are faced patient cognitive restructuring techniques to allow with treating some of these difficult cases. Although them to realise their distorted thoughts and develop little has been established in terms of evidence- coping mechanisms, and PE forces the patient to based practice guidelines for the treatment of these directly confront their situation over and over in co-morbid conditions, nurse practitioners must use order to desensitise the patient to their fear. current research to guide their practice. Findings Few studies have tested the effectiveness of these point to the need for further research on best treatments for co-morbidity in mTBI and PTSD, practices to assess and treat mTBI/PTSD.6 although the little evidence found suggests that The two primary non-pharmacologic treatments for these cognitive behavioural based therapies are PTSD are cognitive processing therapy (CPT) and almost equally effective for PTSD with mTBI and prolonged exposure therapy (PE), both of which are PTSD alone. Davis et al.9 found that treatment adherence was greater than 61% in both groups. The Volume 23 Number 1; January 2015 average attended sessions for the PTSD alone group was hit with an explosive missile, 2) the event was was 9.6 and for the mTBI/PTSD group was 7.9. re-experienced via nightmares and memories when Although the study did not evaluate the end outcome he witnessed or heard about violent acts, such as of effectiveness, it was noted that the treatment was news stories, violent television, or heard loud noises, tolerable for both groups. 3) he avoided turning on the television or radio, 4) Sripada et al.
he became less social and was detached from friends 4 investigated the utility of PE for individuals with and without a history of mTBI that he was close with prior to deployment, 5) he in a sample from a military hospital PTSD clinic. had trouble sleeping, difficulty concentrating, and As hypothesised, PE was highly efficacious for reported irritability, 6) he had been experiencing individuals with PTSD, and there was no evidence these symptoms for approximately 4 months to suggest that the presence of mTBI impacted the after he returned home from deployment. He also efficacy of PE. They compared their results to a experienced residual effects from his mTBI which study they found by Wolf and colleagues in 2012 included anxiety, dizziness, and frequent headaches that demonstrated a 45% post-PE reduction in PTSD almost every day. His symptoms of troubled symptoms in 10 veterans with PTSD plus mTBI. sleep, irritability, and difficulty concentrating are As stated previously, some providers have voiced overlapping symptoms that could have been caused concerns that individuals with a history of mTBI by either diagnosis mentioned above. are more likely to experience cognitive impairment Mr. A presented to the outpatient clinic stating and thus will not benefit from trauma-focussed "I can't take it anymore, I just want to be normal treatment. This study challenges these concerns, again". He stated that ever since the incident he had stating that PE utilises processes that depend been unable to maintain a normal lifestyle. As stated heavily on limbic and medial prefrontal circuits above, all of his symptoms were preventing him from that are conserved across species, and there is little getting a job, seeing friends and family, and doing reason to believe that minor impacts on the brain things that he used to do on a daily basis. He was would preclude them.4,10 living at home with his parents and younger sister, Aside from the cognitive behavioural approach, who were also very concerned for his well-being. He there are also medications that are prescribed to then decided to seek treatment and presented to an treat PTSD. Pharmacologic interventions that are outpatient mental health clinic for treatment. His frequently prescribed include antidepressants, parents accompanied him for emotional support.
antipsychotics, and sedative hypnotics. Some of the Prior to his traumatic event, Mr. A was a healthy prescribing trends are not supported by guidelines young male with no medical problems. He had developed for the treatment of PTSD. In fact, there never been on any medications. He had no history is suggestion that benzodiazepines may interfere of childhood illnesses, seizures, head trauma, or with psychotherapy treatments that are first-line surgeries. He denied use of nicotine, caffeine, or PTSD recommendations. The release of the updated herbal medications. He was taking ibuprofen to Clinical Practice Guideline(CPG) highlight the need relieve his headaches. He denied use of any illicit to investigate prescribing trends among veterans substances in the past or present. He was a social with PTSD to document changes in patterns, identify drinker, having 3-4 beers on Saturday nights when gaps between recommendations and practice, and he was out with his military buddies. He stated determine areas for clinical intervention.11,12 The CPG that he was never a big drinker, but that he would recommends a combination of cognitive behavioural find himself having 5-6 beers a night since he therapy, and a selective serotonin re-uptake returned home because he felt it numbed him and inhibitor(SSRI), specifically sertraline or paroxetine, helped him sleep better. He stated he had a great as first line interventions for combat related PTSD childhood, with loving family and many friends treated in specialty clinical settings.8,11 in high school and in the military. He was always interested in school and was an above average student. Since his return home after discharge, he Mr. A is a 23 year old single Caucasian male, found himself wanting to be alone, and had difficulty previously in the U.S. Marine Corp, who was deployed concentrating. He denied any suicidal ideation or to Afghanistan during his enlistment. He received a suicide attempts. His psychiatric review of systems general discharge after experiencing a primary blast was negative for hallucinations, delusions, mania, or injury which caused a mTBI. He was experiencing depressed mood. His family history was negative for symptoms of PTSD which included 1) involvement any serious medical problems, substance abuse, or in a traumatic event that caused physical harm, psychiatric history. After his initial injury, he was namely, being thrown from a tank when the rear evaluated by military medical specialists, before Journal of Military and Veterans' Health he was discharged. His blood work was normal, are also symptoms of PTSD, it is difficult to assess which included complete blood counts, chemistries, whether the medications and therapy improved thyroid studies, urinalysis, and drug screen. He had these symptoms, or if adequate time to recover from a computed tomography (CT) scan and magnetic the mTBI had an effect. Overall, this case shows resonance imaging (MRI) that showed normal brain a similar outcome when compared to results from images with no evidence of injury, which is typical studies that used CBT for treatment of PTSD along with co-morbid mTBI. Upon initial presentation to the psychiatric outpatient When a patient presents with history of mTBI clinic, he was evaluated by a psychiatric mental sustained during a traumatic event, the nurse health nurse practitioner. The patient was started on practitioner should follow specific protocols to ensure sertraline 25mg at bedtime for his PTSD symptoms. that the patient is receiving adequate treatment. A The dose was titrated up to 100mg by the third week. treatment algorithm can be followed, which consists He was also prescribed prazosin 1mg at bedtime for of a thorough medical workup including lab work, CT insomnia and nightmares, which was titrated up scan, and MRI. A comprehensive history and physical to 5mg by the third week. He attended 12 weekly examination, including psychiatric background, sessions of prolonged exposure therapy in which he should be performed in an initial interview with was initially educated about the development and the patient. The nurse practitioner or psychiatrist treatment of PTSD. He was then taught breathing should initiate approved medications. The FDA has retraining, which he was instructed to use any time approved the SSRI's paroxetine and sertraline for he felt anxious or when he was confronted with the treatment of PTSD. Sleep related complaints in a situation that reminded him of his traumatic PTSD have been poorly investigated, but prazosin experience. Imaginal exposure was initiated, where has been approved for the treatment of PTSD related he had to re-tell the event at each session, and utilise nightmares, and has shown promising results.(13) his breathing exercises to reduce his anxiety. He For treatment resistant patients, antipsychotic was also confronted with in vivo exposure, in which medications such as risperidone can be used off he engaged in watching devastating news stories, label for treating PTSD. As stated previously, avoid scenes from movies that had violent war scenes, and medications such as benzodiazepines and other was exposed to startling loud noises. sedative hypnotics because they may interfere with He was tolerating his medications with minimal the efficacy of therapy and other medications.11 side effects, and was progressing at a steady pace The nurse practitioner should refer the patient to a each week during his therapy sessions. By the end therapist who specialises in CBT programs that are of the twelve weeks, he was able to talk about his trauma focussed and include CPT or PE. Assessment traumatic experience with very little anxiety. He and management of medications should be performed had also begun to watch television at home without by the nurse practitioner every two weeks in the worrying about seeing something that would cause beginning stages of treatment, and should then panic. He started to see his friends again and enjoy follow the patient monthly after the first six weeks activities that he used to enjoy with them like fishing until the patient is stable. At the point where the and golfing. He had also stopped using alcohol as an patient is finishing therapy and has stabilised, three escape at night to decrease his anxiety, although he month follow ups are adequate. When the patient has admitted to social drinking on the weekends with his completed the recommended course of therapy, and friends. He very rarely experienced irritability and has been stable on their medications for one year, a his concentration improved. He also noticed that plan to titrate down medications can be discussed his headaches decreased from nearly every day to between the patient and the nurse practitioner. once or twice a week. He was no longer experiencing nightmares related to his traumatic event.
Implications for the Nurse Practitioner and other Mental Health Care Providers This case of Mr. A shows a patient who had severe symptoms of PTSD after a mTBI from a traumatic Psychiatric mental health nursing is a specialty event he experienced during military deployment. area that is dedicated to promoting the mental As shown in the research, CBT along with proper health of patients. The American Psychiatric Nurses medication management improved and helped to Association has developed standards of practice that alleviate his symptoms of PTSD. At the end of his relate to assessment and treatment for all areas of therapy sessions, Mr. A was approximately eight nursing practice. The standards of practice for nurses months post injury. His residual effects from his are followed when treating patients with PTSD and mTBI such as irritability, decreased concentration, mTBI, taking into account that the prevalence rates and headaches were also subsiding. Since these of these co-morbid conditions is high. There are six Volume 23 Number 1; January 2015 standards of practice, which include assessment, positive results that include standard treatment diagnosis, outcomes identification, planning, plans for PTSD with mTBI. Proper documentation implementation, and evaluation.14 All of equal and reporting of results can be used to support the importance, it is of particular interest to consider evidence- based practice data that currently exist. the implementation phase when treating a patient Nurse practitioners currently provide medication with co-morbid PTSD and mTBI. Although there is management for PTSD. They must encourage other very little evidence to support treatment of these co- practitioners to implement the use of approved CBT existing diagnoses as one, the few studies that have programs to reduce and eliminate PTSD symptoms, been completed show that PTSD symptoms can be regardless of whether they have sustained a mTBI or equally reduced with or without the presence of mTBI. not. By recognising the efficacy and facilitating the The Beck Institute for Cognitive Behavior Therapy use of these approved treatments, patients who have in Philadelphia, Pennsylvania recognises the high experienced a mTBI and suffer from PTSD have a incidence of PTSD in returning veterans, and offers significantly higher chance of recovering and living a three day workshop for advanced practice nurses more functional lives.
where the participants learn in depth cognitive behaviour techniques related to CPT and PE.15 Using Author's affiliation: University of Pittsburgh School of techniques from this workshop and other educational Nursing Corresponding author: Lori Wheeler programs, protocols must be established based on email: wheel[email protected] References1. Bogdanova Y, Verfaelle M. Cognitive sequelae of blast induced traumatic brain injury: recovery and rehabilitation. Neuropsychol Rev 2012; 22:4-20.
2. Richardson LK, Frueh BC, Acierno R. Prevalence estimates of combat-related PTSD: a critical review. Aust N Z J Psychiatry 2010 January; 44(1): 4-19.
3. Otis JD, McGlinchey R, Vasterling JJ et al. Complicating factors associated with mild traumatic brain injury: impact on pain and posttraumatic stress disorder treatment. J Clin Psychol Med Settings 2011; 18:145-154.
4. Sripada RK, Rauch SAM, Tuerk PW et al. Mild traumatic brain injury and treatment response in prolonged exposure for PTSD. J Trauma Stress 2013 Jun; 26:369-375.
5. American Psychological Association. Diagnostic and statistical manual of mental disorders (4th ed). Washington, DC: American Psychological Association; 2000.
6. Sayer NA, Rettmann NA, Carlson KF et al. Veterans with history of mild traumatic brain injury and posttraumatic stress disorder: challenges from provider prospective. J Rehabil Res Dev 2009; 46(6):703-716.
7. Kouchy EM, Dickstein BD, Chard KM. Cognitive behavioral treatments for posttraumatic stress disorder: empirical foundation and new directions. CNS Spectr 2013 Apr; 18(2):73-81.
8. Peterson AL, Luethcke CA, Borah EV et al. Assessment and treatment of combat related PTSD in returning war veterans. J Clin Psychol Med Settings 2011; 18:164-175.
9. Davis JJ, Walter KH, Chard KM et al. Treatment adherence in cognitive processing therapy for combat related PTSD with history of mild TBI. Rehabil Psychol 2013 Feb; 58(1):36-42.
10. Wolf GK, Strom TQ, Kehle SM et al. A preliminary examination of prolonged exposure therapy with Iraq and Afghanistan veterans with a diagnosis of posttraumatic stress disorder and mild to moderate traumatic brain injury. J Head Trauma Rehab 2012; 27:26-32.
11. Department of Veterans Affairs, Department of Defense. Clinical practice guideline for management of posttraumatic stress. http://www.healthquality.va.gov/PTSD-full-2010c.pdf. Published October 2010. Accessed June 5, 2013.
12. Bernardy NC, Lund BC, Alexander B et al. Prescribing trends in veterans with posttraumatic stress disorder. J Clin Psychiatry 2012; 73(3):297-303.
13. Van Liempt S, Vermetten E, Geuze E et al. Pharmacology for disordered sleep in post-traumatic stress disorder: a systematic review. Int Clin Psychopharmacol 2006 July; 21(4): 193-202.
14. American Psychiatric Nurses Association. Psychiatric mental health nursing: scope and standards of practice. Newington, VA: American Nurses Association; 2007.
15. The Beck Institute for Cognitive Behavior Therapy [homepage on the internet]. Available from: http://www.
Journal of Military and Veterans' Health Short Communication Rabies post-exposure prophylaxis in Australian Defence Force personnel in Leonard B. Brennan Abstract
Background: Australian Defence Force (ADF) personnel have been deployed to Afghanistan since 2002. The
2011 death of a US Army soldier from rabies raised the awareness of rabies in ADF personnel deployed in
Purpose: The study aims to review rabies exposure in ADF personnel supported by the Australian Role 1 health
facility in Tarin Kowt, Afghanistan during a 6 month period.
Materials and Methods: The Australian Role 1 rabies vaccination register and associated animal bite reports were
reviewed to identify rabies exposures and subsequent management.
Results: 21 ADF members reported a potential rabies exposure during the period.
Eighty five percent were due to a cat bite or scratch with an average delay of 51 days between exposure and
reporting, when 32% and 57% respectively were classified as a category II or III exposure. All exposures
were managed in accordance with National Health and Medical Research Council (NHMRC) post-exposure
prophylaxis (PEP) recommendations.
Conclusion: Rabies remains a disease of military significance for ADF personnel operating in Australia's area of
military interest. ADF health staff need to encourage military personnel to minimise contact with local animals
and report animal bites or scratches promptly in order to ensure that PEP is administered early.
Keywords: rabies, post-exposure prophylaxis, Afghanistan, Australian Defence Force
the mucous membranes are intact is very rare.1 Post- The rabies virus is a single-stranded RNA virus from exposure prophylaxis (PEP) involves treatment of the family Rhabdoviridae, genus Lyssavirus which the acute wound, administration of immunoglobulin also includes the Australian bat lyssavirus (ABLV).
and a course of rabies vaccination and approaches Humans exposed to saliva or any nerve tissue of an 100% effectiveness when conducted with complete animal infected with rabies may become infected, with the incubation period usually being 3-8 weeks, Rabies within the Indo-Pacific region although the range quoted in separate reports is as short as 1 week and as long as several years after The Australian Defence Force (ADF) is required to exposure. Rabies is almost invariably fatal, with contribute to contingency and security operations non-specific symptoms preceding the classical rabies in the Indo-Pacific region, with a priority for o symptoms of a progressive encephalopathy and Southeast Asia.3 Rabies remains endemic in most of hypersalivation. Death from cardiac or respiratory Asia and human deaths from rabies are estimated arrest usually occurs within 3 weeks of developing to be greater than 30,000 annually.2 Within Asia the only countries considered to be rabies-free are Hong Kong, Japan, Singapore, Taiwan, the Maldives, the Human exposure can occur via a scratch or bite that Malaysian state of Sabah and a number of India's has broken the skin, or via direct contact with the southern islands. In contrast, most countries in the mucosal surface of an infected animal. Most human Pacific Oceania region are considered to be rabies- cases of rabies occur after an animal bite(s). Cases free and include Australia, New Zealand, Papua New following animal scratches, the licking by animals of Guinea and the US state of Hawaii.4 The status can open wounds or contact with animal saliva when change however, as demonstrated in 2008 when Volume 23 Number 1; January 2015 Short Communication Figure 1. WHO map – Distribution of Risk levels for humans contacting rabies, worldwide, 2011 the previously ‘rabies-free' Indonesian island of Box 1. Case report of Death of US soldier from Rabies Bali reported rabies in local dogs and subsequently in humans.5 Figure 1 illustrates the World Health Organisation (WHO) 2011 world map detailing Death of US Soldier from Rabies
the risk levels for human contact with rabies, and "On August 19, 2011, a male U.S. Army soldier highlights the large areas within the region that are with progressive right arm pain, nausea, vomiting, at medium and high risk of rabies6.
ataxia, anxiety, and dysphagia was admitted to an emergency department (ED) in New York for Whilst the potential rabies reservoir within the region suspected rabies. Rabies virus antigens were includes a wide range of mammals, dog, monkey detected in a nuchal skin biopsy, rabies viral and cat bites or scratches were responsible for antibodies in serum and cerebrospinal fluid over 90% of potential rabies exposure in Australian (CSF), and rabies viral RNA in saliva and CSF travellers, with approximately 30% resulting from an specimens by state and CDC rabies laboratories. unprovoked contact.7,8 An Afghanistan canine rabies virus variant was During contingency or security operations, measures identified. The patient underwent an experimental must be taken to monitor and control rabies in treatment protocol but died on August 31. The endemic areas or to prevent its importation. Lack patient described a dog bite while in Afghanistan. of such control is likely to compromise the safety of However, he had not received effective rabies deployed personnel.
postexposure prophylaxis (PEP)." Extract from MMWR Morb Mortal Wkly Rep 2012 The Australian Afghan Experience May 4; 61(17):302-5 The ADF health support plans for deployment to Afghanistan recognised the threat of rabies and pre-deployment health briefs included advice to minimise contact with local animals, but did not emphasise the requirement to report and seek Journal of Military and Veterans' Health Short Communication Figure 2. ISAF Medical Alert on Prevention of rabies Materials and MethodsThe Australian Role 1 Tarin Kowt Master Rabies Vaccination register as at 22 January 2012 was used to identify ADF members who had reported a potential rabies exposure in the previous 6 months. The register was an excel spreadsheet compiled in December 2011 and based on monthly animal bite reports between August and November 2011. The ‘NATO-ISAF Report of Animal Attack – Potential Rabies Exposure' is required to be completed for rabies exposures in non-US personnel deployed to Afghanistan as part of ISAF. These reports were reviewed to establish the date of exposure, the animal species involved, the category of exposure and the date and type of treatment administered. PMKeyS, Defence's human resource management system, was utilised to access demographic and employment data.
ResultsThere were 23 reported exposures documented, involving 21 Australian Army members. The remaining 2 exposures were civilian contractors and were excluded from further analysis as ongoing treatment was transferred to another health facility. One exposure was reported after the offending animal had been observed for 10 days and PEP was no longer indicated. In all other cases the full PEP immediate treatment for animal bites or scratches. was completed as the offending animal was not Currently, preventive medicine personnel, military observed for the minimum 10 days or tested for the dog handlers and personnel trained in feral animal presence of the rabies virus.
capture and euthanasia are required to have rabies vaccination prior to deployment, although prior to A cat bite or scratch was responsible for 18 (85%) 2011 there were no predeployment rabies vaccination exposures, a dog bite for 2 (1%) and not specified in 1 requirements. All Australian military working dogs case.12 (57%) exposures were classified as grade III, are routinely vaccinated against rabies and have 8 (32%) graded as II and not specified in 1 case. The their immunity confirmed by a Rabies Neutralising reports do not differentiate between provoked and Antibody Titre Test (RNATT) prior to deployment.9 unprovoked exposures. All but 2 cases occurred in a forward operating base within the Uruzgan Province The death of a US Army soldier in 201110 (see box 1) with the remaining 2 cases occurring on the main from rabies, following a dog bite whilst deployed in operating base in Tarin Kowt. Table 1 summarises Afghanistan, resulted in the International Security the nature and treatment of the identified ADF Assistance Force (ISAF) in Afghanistan initiating a formal program of rabies awareness training, tracking, treatment and reporting requirements There was a significant delay between exposure and in September 2011. The ISAF Medical Alert notice, the seeking of medical advice, with an average of 51 see Figure 2, was issued as part of the program days and a median of 31 days; Only four cases highlighting the need to avoid animal contact and were treated within 1 week of exposure, all being to report any bite or scratch immediately. The managed within 24 hours. PEP was administered Australian post-deployment health screen includes in accordance with NHMRC guidelines, although a specific question on whether the member had three of the four cases received the shorter four suffered an animal bite or scratch during the dose vaccination course as recommended by the US deployment. A number of exposures were identified Center for Disease Control (CDC). from positive responses to this question.
Volume 23 Number 1; January 2015 Short Communication Table 1. Nature and treatment of ADF possible rabies exposure August 2011 - January 2012 commissioned Officers Category of bite II presentation (days) Source of bite or Dog Combat Service Support The knowledge and understanding of rabies by Despite the pre-deployment and health briefs given health staff was generally rudimentary prior to being at the destination, Australian soldiers of all ranks required to manage a clinical exposure. The deployed continued to suffer bites and scratches from local medical officers readily identified the requirement to animals. As the vast majority were related to a consider PEP and they provided the appropriate PEP cat bite or scratch occurring inside a patrol base, despite utilising protocols from a variety of different most of these exposures could have been avoided had the advice in the health briefs been heeded. Working in a multinational environment can result More importantly, the delay between exposure and in variations of the treatment protocols utilised. presentation may have had fatal consequences had There were subtle differences between ADF, the injuries resulted in viral transmission. There NHMRC, WHO and CDC policies and guidance at the were medical technicians on all the patrol bases time. Whilst the ADF policy refers to the NHMRC where exposures occurred and there were no cases guidelines, it does not draw the distinction between in which treatment was delayed because of lack of category II and III exposures, recommending access to medical assistance or PEP.
administration of human rabies immunoglobulin There were two cases, both preventive medicine (HRIG) for all exposures in non-immune individuals. technicians (now recognised as a high risk occupation), The ADF, NHMRC and WHO guidelines current whose PEP would have been significantly simplified at the time recommended a five dose vaccination by pre-exposure vaccination. A change in ADF course PEP, whereas the CDC had adopted a four policy to include rabies pre-exposure vaccination for dose schedule (which was subsequently adopted by preventive medicine personnel, military dog handlers the other agencies). The US military directed their and personnel trained in feral animal capture and staff to resume the five dose schedule on the basis euthanasia who are on short notice to deploy, that antimalarials may compromise the immune would be relatively inexpensive and consistent with system.11 All the major authorities recommended a NHMRC recommendations for personnel working fifth dose for immunocompromised individuals. The with terrestrial animals in rabies-enzootic areas.
US military directed their staff to resume the five Journal of Military and Veterans' Health Short Communication dose schedule on the basis that antimalarials may standard practice and efforts to specifically address compromise the immune system.11 Antimalarials interactions (or lack there of) with antimalarial are not normally associated immunocompromise medications should be made.
at chemoprophylactic dosages. There is evidence commissioned Officers that chloroquine specifically interacts with rabies vaccine to decrease its immunogenicity. This The views expressed in this paper are those of the has been extended by some sources apply also to author and do not necessarily reflect the official mefloquine, despite the available evidence failing to policy of the Australian Defence Force.
demonstrate any such interraction.12 In any case, the recommendation emphasised that the intramuscular route should be used rather than the intradermal The information presented in this paper was Category of bite II route.4 Antimalarial use should not impact on PEP.
collected and analysed as part of routine deployed public health surveillance and, in accordance with the Australian Defence Health Manual Volume 23, It is likely that rabies exposure will be a feature of does not constitute human research and therefore future ADF deployments and whilst pre-deployment does not require approval by the Australian Defence health briefs should highlight the risk, ADF health Human Research Ethics Committee (ADHREC).
staff needto be familiar with PEP and to promote early reporting of animal bites or scratches. ADF policy Author's affiliation: Leonard B. Brennan, CP3-6-009 should be revised to be consistent with NHMRC Campbell Park Offices Canberra ACT, Director Military Medicine, Mater Health Administration, Department of guidance, pre-exposure vaccination of high risk Source of bite or defence and University of Queensland, personnel on short notice to deploy should become [email protected], CP3-6-009 PO Box 7912 Canberra BC ACT 2610, (t) 02 61270247 (f) 02 62662143 1 National Health and Medical Research Council. Australian Government. The Australian Immunisation Combat Service Support Handbook 10th Edn. Canberra: Australian Government Department of Health and Ageing, 2013.
2 WHO Expert Consultation on Rabies: 2nd Report 2013.
3 Defence White Paper 2013 4 2014 Yellow Book: CDC Health Information for International Travellers 5 Gautret P, Lim PL, Shaw M. et al. Rabies post-exposure prophylaxis in travellers returning from Bali, Indonesia, November 2008 to March 2010. Clinical Microbiology and Infection 2011;17:445-447 6 World Health Organisation International http://www.who.int/rabies/Global_distribution_risk_humans_ contracting_rabies_2011.png?ua=1 accessed 30 Jun 2014 7 Mills DJ, Lau CL, Weinstein P. Animal bites and rabies exposure in Australian travellers. Med J Aust 2011; 8 Carroll HJ, McCall BJ, Christiansen JC. Surveillance of potential rabies exposure in Australian travellers returning to South East Queensland. Communicable Disease Intelligence (CDI) 2012; 36(2) E186-187 9 Information package for the importation of military dogs from Afghanistan. Australian Quarantine and Inspection Service. Updated May 2009 (accessed 13 Mar 14) 10 Center for Disease Control and Prevention (CDC) Imported human rabies in a U.S. Army soldier – New York 2011. MMWR Morb Mortal Wkly Rep 2012 May 4; 61(17):302-305 11 Center for Disease Control and Prevention (CDC) Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies. MMWR Morb Mortal Wkly Rep 2010 May 19; 59(RR02):1-9 12 Lau SC. Intradermal rabies vaccination and concurrent use of mefloquine. J Travel Med. 1999 Jun; Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts Resilience symposium - development of self- and social health of serving and ex-serving personnel and their families in order to ensure policy and management and resilience training resources for service delivery is responsive to future needs. The ADF members and veterans three studies included in this program are: The Kym Connolly & Nicole Sadler Health and Wellbeing Study, The Impact of Combat Study, and the Family and Wellbeing Study. Many younger serving and ex-serving Australian Together, the results from this program of research Defence Force (ADF) personnel are more likely to use will provide the Department of Veteran's Affairs online resources to seek information on mental (DVA) and the Department of Defence (Defence) with health support than through traditional print media. robust information about the re-adjustment process For this reason, the Department of Veterans' Affairs faced by contemporary veterans and their families (DVA) and Defence are working in partnership to who are in the process of transitioning from the develop a range of client and provider-driven Australian Defence Force (ADF), or have already left. initiatives aimed at improving awareness and The following symposium will describe the key aims understanding of mental health and the available and objectives and proposed methodology of each of support services. This includes the development of these three studies.
websites and smart phone applications (apps).
This presentation will outline the development of a Presentation 1:
suite of online products based on the ADF Self-Management and Resilience Training (SMART) The Health and Wellbeing Study: Investigating the mental, physical, and social health of serving and The 2013-14 Veterans' Affairs Budget package ex-serving Australian Defence Force (ADF) Veteran Mental Health Services – Expansion included the development of a resilience website that builds Miranda Van Hooff1, Alexander McFarlane1, on the SMART skills learned in the ADF. The SMART Stephanie Hodson2, Nicole Sadler3, Helen Benassi3, website, currently under development, will feature David Forbes4, Richard Bryant5, Malcolm Sim6, tools and information that build resilience, improve Helen Kelsall6, Jeffrey Rosenfeld6, Jane Burns7. mental health literacy and reduce stigma related to 1Centre for Traumatic Stress Studies, The University of seeking help for mental health conditions. The Adelaide, 2Department of Veterans Affairs, 3Department of website will target those with wellbeing concerns or Defence, 4Australian Centre for Posttraumatic Mental Health, 5The University of New South Wales, 6Monash seeking to renew the SMART skills learnt in the ADF. University, 7Young and Well Cooperative Research Centre. The website will be complemented by a self-help mobile app using interactive Cognitive Behavioural The Health and Wellbeing Study will target over Therapy (CBT) tools which are currently used in the 30,000 serving and ex-serving ADF personnel to ADF SMART program. determine their mental, physical and social health. It will provide a comprehensive picture of the mental DVA and Defence have worked closely to develop the health and wellbeing status of contemporary veterans online SMART resources to ensure they are consistent as well as particular subgroups within the ADF (i.e. with the SMART objectives, as well as being relevant ab initio reservists, a representative sample of 2014 to serving and ex-serving personnel and their regular ADF personnel). This study is the first of its families. Clinical practitioners have been involved in kind to use a two-phase design in order to provide the development of the online products to make sure prevalence estimates of lifetime, 12 month and 30 they are evidence-informed and can be used in day ICD-10 mental disorder in ADF personnel who conjunction with a treatment regime.
have recently transitioned from fulltime regular ADF service. Additionally it will examine the trajectory of The Transition and Wellbeing Programme – disorder and pathways to care for individuals previously diagnosed with a mental health disorder as well as investigate veteran use of technology and its utility for health and mental health programmes, The Transition and Wellbeing Research Program, including implications for future health service comprising a suite of three studies, will examine the impact of military service on the mental, physical Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts Presentation 2:
The Impact of Combat Study: Investigating the The Transition and Wellbeing Family Study: longitudinal trajectory of mental, physical, Investigating the social, physical, and emotional biological and neurocognitive profile in ADF health of family members of men and women who personnel deployed to a combat zone have recently transitioned out of the Australian Alexander McFarlane1, Miranda Van Hooff1, Defence Forces (ADF) Ellie Lawrence-wood1, Stephanie Hodson2, Nicole Sadler3, Benjamin Edwards1, Walter Forrest1, Jacqui Harvey1 Helen Benassi3, David Forbes4, Richard Bryant5, Malcolm Sim6, Helen Kelsall6, Jeffrey Rosenfeld6, 1Australian Institute of Family Studies, Melbourne, Australia Jane Burns7. Although there has been a great deal of research 1Centre for Traumatic Stress Studies, The University of investigating the welfare of veterans in Australia, Adelaide, 2Department of Veterans Affairs, 3Department of much less is known about the social, physical, and Defence, 4Australian Centre for Posttraumatic Mental Health, 5The University of New South Wales, 6Monash emotional health of their families. There is growing University, 7Young and Well Cooperative Research Centre. evidence, however, that military service can have both long-term effects on the partners and children The Impact of Combat Study will follow up all of service personnel after leaving the military. In individuals who participated in the Middle East Area turn, the social and emotional health of family of Operations (MEAO) Prospective Health Study members can have important implications for the (including current and ex-serving ADF members), health and welfare of veterans. The Transition and with the aim of examining the longitudinal trajectory Wellbeing Family Study (TWFS) is a new research and risk and protective factors for mental, physical, project that aims to address this gap by investigating and social health and wellbeing. In addition to the wellbeing of family members of men and women assessing mental health, pathways to care, who have recently transitioned out of the Australian psychosocial factors and physical health status, this Defence Forces (ADF). Part of the Transition and study will also examine the neurocognitive and Wellbeing Research Program (TWFP), the project is biological profiles of a subgroup identified as being being funded by the Department of Veterans' Affairs engaged in high-risk roles and who were likely to and is being managed by the Australian Institute of have been exposed to deployment-related trauma or Family Studies. It is based on an online survey of blast injury. This longitudinal study is the third approximately 30,000 family members of ex-ADF follow-up of 1871 personnel who were deployed to personnel who will be surveyed as part of the the MEAO between 2010 and 2012 and who were Transition and Wellbeing Program. In this previously assessed pre and post deployment. This presentation, we describe the aims and objectives of presentation will describe the aims and methodology the TWFP, briefly review the results of Australian of the study as well as review the current status of and international research on the social, physical, the neurobiological literature in relation to military and emotional health of military and veteran families, and discuss key aspects of the survey methodology, including its online administration, key concepts and measures, potential sources of data linkage, and possible ways of limiting the effects of sample selectivity.
How do we define ‘deployable'? Establishing a Army has moved over recent years to establish standard guide for clinicians to assess when a physical employment standards, in consultation soldier is fit for upgrade.
with the Defence Scientific and Technology Organisation, which are based on tests that soldiers Isaac Seidl are expected to undertake in their deployed roles, known as the Physical Employment Standards The ADF moved to a tri-service system for Medical Assessment (PESA). These are used to determine Employment Classification in the early 2000s. At readiness for deployment for many Army roles. that time, the single standard for assessing fitness However, it is hypothesised that they are not was based on ‘deployability'. Yet, there has continued appropriate to be used at the point of upgrade, that to be discussion about how to define this.
is, as a measure of effectiveness for rehabilitation. Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts Likewise, the Basic Fitness Assessment (BFA), holds documentary credentialing, but fewer may know of little basis in scientific evidence for predictability of Army Health Instruction 5 (Clinical Readiness Standards) which mandates military and clinical skills currency. However, even this does not This presentation will outline an ongoing discussion, guarantee competency to work in the deployed brought out in 2014, in which establishment of environment as well as, for example, the US Center clinical guidelines for practitioners and confirming for Sustainment of Trauma and Readiness Skills authorities, has become necessary, and propose (C-STARS) programme. ADF clinical courses such as appropriate tests that could be used, where the combined DSTC/MILAN, major exercises, and appropriate. This would necessitate setting out, civilian strategic alliances are increasingly filling this preferably in advance at the point of downgrade, the need. Clinicians are assessed by the 2GHB test that would be undertaken at the conclusion of credentialing committee to fill specific roles. Features rehabilitation, and offer a single Army Rehabilitation common in civilian healthcare, such as infection Fitness Assessment (ARFA) as one option. control, training, and patient safety officers, have Authors(s) affiliations: IS: Australian Army been appointed. Deployed hospital processes are Corresponding author: Isaac Seidl guided by doctrine and clinical practice guidelines, Corresponding author's email: [email protected] the expansion and revision of which are now high priorities recently resulting in, for example, Components of an effective deployed clinical HEALTHMAN 07 (Military Anaesthesia) and HEALTHMAN 16 (Transfusion). Hospital processes governance system for the ADF (albeit in simulation) have been audited against an LTCOL Michael C. Reade1,2 LTCOL Nicholas Duff 3 ADF modification of the UK military trauma Key COL Bradley McCall 3 Performance Indicators. The role of a Clinical Director Clinical governance is "the measurement and has been confirmed in doctrine, with responsibility benchmarking of clinical performance through for audit and continuous improvement as well as implementation of predefined standards and individual patient care. A morbidity and mortality established mechanisms that identify, address and committee operates in the field, ensuring continuously review problems or problematic trends that arise".1 Clinical governance comprises assessment of outcomes remains impossible without mechanisms to ensure and improve healthcare a sufficient number of patients, making conventional quality (for example, that the best treatments are indices (such as standardised mortality ratio) prescribed) and safety (for example, that treatments inapplicable. Nonetheless, the systems to collect prescribed are given as directed), along with oversight such data are under consideration – for example a of individuals, teams, systems and equipment; deployed trauma registry patterned on UK and US research; education; open disclosure; legislative models. The best quantitative measure of a deployed compliance; congruence with strategic intent; and governance framework might be the number of audit of results. Such features can be categorised as changes to inputs and processes that have been inputs, processes, and outcomes. The Australian achieved. By this metric, the 2nd General Health Government Commission on Safety and Quality in Battalion compares very favourably to the best Healthcare requires a system of clinical governance civilian trauma centres. as the first of ten National Standards.2 Applying these standards to deployable ADF hospitals is problematic – not least because infrequent 1. Health manual 25: Professional standards, deployments mean meeting many standards in governance and administration. 2009. Canberra, theory not practice. Further problems are imposed Department of Defence. by austerity (invalidating most civilian benchmarks), 2. National Safety and Quality Health Service frequent postings, and a peacetime exercise caseload Standards. 2012. Canberra, Australian that bears little resemblance to the high complexity Commission on Safety and Quality in Healthcare. trauma that ADF Role 2E hospitals are designed to Authors(s) affiliations: 1. Joint Health Command, Australian Defence Force, While accepting many standards are not applicable, Canberra, ACT. 2. Burns, Trauma and Critical Care Research Centre, deployed ADF hospitals are nonetheless obliged to University of Queensland, Brisbane, QLD implement the best possible clinical governance 3. 2nd General Health Battalion, Gallipoli Barracks, framework. Under a CO's directive, the 2nd General Enoggera, QLD. Health Battalion (2GHB), Army's only Role 2E Corresponding author: LTCOL Michael C. Reade hospital, has embraced this challenge. With respect Corresponding authors email: [email protected] to inputs, all ADF clinicians are familiar with annual Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts Captain B.g.pockley Aamc – A Hero Before "conspicuous gallantry in action and as a matter of fact he forfeited his life for those under his command." Michael Dowsett Most Australians are unaware of this important campaign in Australia's history as the events of that Last month at Rabaul a service was held to period have been overshadowed by Gallipoli, the commemorate the centenary of the Battle of Bita Western Front and Palestine. The New Guinea Paka at the graveside of Able Seaman Billy Williams campaign of 1914 saw a number of significant "firsts" and Captain Brian Pockley, the first Australians to for Australia including the first overseas military die in World War I.
expedition planned and coordinated by the new Captain Pockley enlisted as a medical officer in the nation, the first land operation of the war, the first AAMC as part of the Australian Naval and Military joint operation by the Navy and the Army, the loss of Expeditionary Force. His actions during the battle the RAN submarine AE1 and the first act of bravery that led to his death were described as those of by Australians in that war.
Effective Leadership on Operations: Perspectives be presented, which identified key themes of from Commanding Officers of NZDF deployments subordinate well-being, effective interpersonal style, performance management, motivations of leaders Lieutenant Christopher Liddell (Trainee Psychologist, New and command isolation. There will also be discussion Zealand Defence Force) on the utility of the research within NZDF and its use Over the last fifteen years the New Zealand Defence for development of a COs aid memoir for senior Force (NZDF) has deployed personnel in a number of leadership on operations. different operational settings including significant Corresponding author: MAJ Alana MacDonald (Senior contribution to the Middle East, Solomon Islands Psychologist Joint New Zealand Defence Force) and Timor Leste. As research across Allied Nations Corresponding authors email: [email protected] militaries suggest, the leadership behaviours of command teams on operations can significantly The Secrets of Very High Performance Medical impact deployment satisfaction and mental health outcomes for soldiers that deploy under their command. Leveraging off this research body, NZDF WGCDR David Cooksley1 (Emergency and Retrieval investigated leadership behaviours from the Physician) perspectives and experiences of its Commanding Medical teams that care for seriously ill or injured Officers who had deployed over the past 15 years. patients should, almost by definition, be high The roles of the Commanding Officer (CO) and Senior performance in nature. However there are some, National Officer (SNO) contain unique challenges such as the London Helicopter Emergency Medical and can be socially and professionally isolated. And Service (HEMS) and its military equivalent, the RAF whilst NZDF has a reasonable amount of Medical Emergency Response Team (MERT), that organisational knowledge and lessons learnt stand apart and are widely regarded as very high captured from our senior officers on operations, performance teams. They are selected and trained to recent information regarding effective and ineffective function expertly and consistently in hostile, operational command is not always readily available unpredictable and high consequence environments to new senior leaders on operations.
where there is little margin for error. This This presentation highlights research conducted presentation will examine some of their ‘secrets' with which sought to gather learnings from NZDFs recent regard to selection, training, clinical application and operational involvement by interviewing senior clinical governance that enable these teams to leaders of operations in CO or SNO positions. Twenty perform so well.
senior leaders were interviewed and provided Authors(s) affiliations: 1ADF Military Surgical Team, Royal information about the unique challenges senior Brisbane and Women's Hospital operational leaders face, as well as their perceptions Corresponding author: WGCDR David Cooksley1 of what created effective and ineffective senior Corresponding authors email: [email protected] command behaviours. The findings of this study will Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts Innovating change by encouraging rebels in the disabilities, who may have been out of the workforce Defence health workforce for extended periods. However, there it is vital that people are not placed into an environment which is Isaac Seidl detrimental to their physical and mental health. The What sets a rebel apart from a troublemaker is the work must be ‘good'. Just what is it the distinguishes ability to be creative, mission-focussed, passionate, ‘good work' and allows work participation to realise optimistic, energy-generating, see possibilities, its benefits? Much of it lies around workplace attract followers and work together.1 These are culture, management systems and the competence individuals who not only influence change, but drive of supervisors and managers. There is a fear that it, for the better, by ‘rocking the boat but staying in individuals could be required to work in it'.2 At a time when the Defence healthcare budget is circumstances that are detrimental and such an stretched, under pressure from increasing outcome needs to be avoided.
governance and crippling clinical workload arising The Australasian Faculty of Occupational and from 15 years of continuous operations, we need Environmental Medicine has, for the last 4 years, ‘rebels' at all levels to constantly ask, ‘how can we do been at the forefront of advocacy for the need for ways to ensure the potential of work to be a positive This presentation will examine how even John Kotter is realised. AFOEM has released a series of position has changed his view on change management. It will statements, initially ‘The Health benefits of Work' challenge attendees to move from the comfortable which states that ‘Good Work is generally good for centre, to the edge.2 It will define the difference you', and in 2013 two sister documents – ‘Health and between rebels and troublemakers, in order to Productivity' and ‘What is good Work'. These empower those who can, and often do, speak out, to documents speak to what is needed for a job to be do so in ways that lead innovation, rather than ‘good', and also how workplaces can readily improve compromise the organisation by throwing stones productivity through insightful, sensible approaches from the sidelines. We need to embrace change, which engage workers and negates potentially examining processes that we hold dear and critically negative outcomes.
evaluating whether they add value, or if, on the other This presentation will discuss some of the approaches hand, they stifle excellence in health care.
taken by AFOEM in engaging with Government, At the end of the presentation, attendees should be Regulators, Insurers, Industry, Unions and patient able to reflect on their practice, as clinicians, advocate groups, where the campaign is up to and managers, or indeed as consumers of Defence health what still needs to be done to truly see a return on care, in order to understand better, ways that their this program. It will also consider how such concepts engagement will improve outcomes.
are translatable into the Military environment.
1 Kelly, L. www.rebelsatwork.com 1 www.healthbenefitsofwork.com.au 2 Bevan, H., Transformational themes that will Corresponding author: James Ross shake the world of healthcare improvement. Corresponding authors email: [email protected] Presentation at International Forum on Quality and Safety in Health Care, Paris, 10 Apr 2014.
Valuing religious beliefs through the health care Authors(s) affiliations: IS: Australian Army Corresponding author: Isaac Seidl FLTLT Jenny Sutton Corresponding author's email: [email protected] The religious beliefs of patients has the ability to The Good Workplace: how management and greatly affect the delivery, success and ethical culture contribute to health and productivity acceptability of health care interventions. Australia has seen increasing multiculturalism in recent GPCAPT James Ross decades leading to a greater diversity in the religious Much has been written about the need to promote backgrounds within the Australian population, the value of early return to work after injury or reflected within the military population, and diverse illness. There are very important individual, family, spiritual beliefs amongst patients receiving enterprise and societal benefits from focussing on humanitarian aid, both within Australia and vocational rehabilitation. The value of being part of overseas. As health care professionals, the provision the workforce also relates to people with permanent of holistic, effective and appropriate interventions, includes the use of religiously sensitive knowledge, Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts provided through a greater understanding of the role care. Factors affecting the way spiritually sensitive of religion in our patient's experiences, the benefits holistic care is conducted, may be discussed to of spirituality and an overview of how religious beliefs provide a greater understanding of how patient care impact what and how health care is provided.
can be improved leading towards better patient outcomes and reduced morbidity. The discussion will aim to explore some of the factors and beliefs within various religions that may lead to Religious devotion can be at the core of our patients contradictions in the prevailing medical model understanding of both their own health status, the compared to the spiritual needs of the patient, whilst ways they wish health care to be provided as they exploring some of the barriers preventing religiously embark as an equal partner within the health setting sensitive care. The importance of religious values and also the positive outcomes achieved through the and beliefs for the patient is examined to explore the empathetic and cognisant, spiritually sensitive care holistic nature of spiritual care within the health of our patients. In order to provide patient centred, care setting, particularly in times of trauma, holistic care, the health care professional is aware of humanitarian crisis or disaster. the role of spiritual care and how their part in providing religiously sensitive health care enables Some of the various religions are reviewed to the best patient outcomes and better experiences for demonstrate the contradictions to care, which affect our patients within the health care setting.
the expectations, wishes and experiences of our patients, within the great variety of customs Authors(s) affiliations: Australian Society of Post associated with differing religions and even various Anaesthesia and anaesthesia nurses (ASPAAN) Australian College of Operating Room Nurses (ACORN) traditions within the same belief. Consideration of NSW Operating Theatre Association (OTA) how spiritual beliefs can contrast with prevailing Corresponding author: Jenny Sutton medical models can provide cues to the ethical and Corresponding author's email: [email protected] moral considerations within the provision of health Are the Current Priorities for the Control of Plague Because of its extreme pathogenicity, coupled with the fact that it is readily available in nature, simple to culture, and can be aerosolised, Y. pestis is Louise Gertner considered a potential agent for bioterrorism. This Plague is a highly virulent infection caused by the fear of a man-made plague outbreak has had a bacillus Yersinia pestis, from the family significant impact on research and control of plague Enterobacteriacea. Plague has been responsible for in the modern age, however not all of it has been the deaths of millions throughout history, and its very name is synonymous with pestilence and This presentation will provide an overview of the geographic distribution, clinical features, mode of After being largely absent for much of the 20th transmission, and treatment of human plague, along century, plague has re-emerged, and is now with an examination of the environmental, socio- considered endemic in a number of countries economic and cultural factors underlying its spread.
throughout Asia, Africa and the Americas. Along side The presentation then considers whether plague's the reoccurrence of wild plague, another threat also reputation as a destroyer of cities is warranted in the emerged in the early 21st century, that of modern age, and explores how strategies for the control of plague and research into the disease has Plague is primarily a zoonotic disease of rodents, been shaped by the construct of plague as a terrorist with human infection only occurring incidentally, threat, at the expense of other equally valid drivers of however when human cases do occur, the outcomes research, such as climate change, to the detriment of are often extremely poor for those infected. Plague is those most at risk.
one of the most virulent diseases known to man, with a complex pathogenicity derived from a combination of toxins, proteins, and plasmid-based 1. Anisimov, A. P. & Amoako, K. K. 2006. Treatment antigens. Without treatment, the mortality rate for of plague: promising alternatives to antibiotics. bubonic plague is approximately 50%. Untreated Journal of medical microbiology, 55, 1461-75.
septicaemic and pneumonic plague cases are almost 2. Bertherat, E. & Gage, K. L. 2008. Plague. In: always fatal, and even with early treatment mortality Heymann, D. L. (ed.) Control of communicable is between 10-20%.
diseases manual : an official report of the Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts American Public Health Association. Washington, 10. Meysick, K 2012. FDA media release 2012 DC: American Public Health Association 3. Burmeister RW, Tigertt WD, Overholt EL. Laboratory-acquired pneumonic plague. Report of a case and review of previous cases. Ann 11. Prentice, M. B. & Rahalison, L. 2007. Plague. Intern Med. 1962;56:789-800.
Lancet 369, 1196.
4. Dennis, D. T. & Staples, J. E. 2009. Plague. In: 12. Sivaramakrishnan, K. 2011. The return of Brachman, P. S. & Abrutyn, E. (eds.) Bacterial epidemics and the politics of global-local health. Infections of Humans. Boston, MA: Springer US. American Journal of Public Health, 101, 1032- 5. Feodorova, V. A. & Corbel, M. J. 2009. Prospects 13. Wagner D. et al 2014 Yersinia pestis and the for new plague vaccines. Expert Review of Plague of Justinian 541—543 AD: a genomic Vaccines, 8, 1721-38.
analysis. The Lancet Infectious Diseases, Volume 14, Issue 4, Pages 319 - 326, April 2014 6. Gani R, Leach S. Epidemiologic determinants for modeling pneumonic plague outbreaks. Emerg 14. WHO 2000. Report on Global Surveillance of Infect Dis 2004;10:608-14 Epidemic-prone Infectious Diseases – Ch.3 Plague. WHO/CDS/CSR/ISR/2000.1. Accessed 7. Kool, J. L. & Weinstein, R. A. 2005. Risk of Person-to-Person Transmission of Pneumonic Plague. Clinical Infectious Diseases, 40, 1166- 15. WHO 2006. Weekly Epidemiological Record No. 8. Mackenzie, D. 2003 New Scientist http://www.
28, 2006, 81, 273–284 at http://www.who.int/ 16. WHO 2010. Human plague: review of regional morbidity and mortality, 2004-2009/Peste 9. Massin, L., Legrand, J., Valleron, A. J. & humaine: examen de la morbidite et de la Flahault, A. 2007. Modelling outbreak control for pneumonic plague. Epidemiology and Epidemiological Record, 85, 40.
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Corresponding author: CAPT Louise Gertner Corresponding authors email: [email protected] ADF Clinical Handover Improvement Project A dedicated sub working group of the (GHCGWG) was formed. The inaugural ADF CHIP WG meeting was held in November 2012. Membership of the WG Dr Darrell Duncan & Ms Madeline Makeham includes representation from Joint Health Command, In 2012 it was identified through the Garrison Health Joint Operations Command, single Services and Clinical Governance Working Group, (GHCGWG) the Regional Health Services to facilitate an integrated need to adopt and implement an organisational approach to quality and safety in clinical handover system for structured clinical handover relevant to care across the ADF.
the ADF Healthcare setting. This was identified in The ADF CHIP WG is accountable to the Vice Chief of response to a recognised trend of adverse healthcare the Defence Force via the Surgeon General of the incidents related to issues with effective clinical Australian Defence Force. Terms of Reference and a project plan has been developed and was endorsed The primary aim of the project was to ensure there is by SGADF in July 2013.
timely, relevant and structured clinical handover The primary standard referenced to develop the that supports safe patient care in Defence healthcare systems and strategies for effective Clinical Handover in ADF healthcare environments was Standard The scope of this project applies to all health care 6-Clinical Handover of the Australian Commission services provided to Defence members in any Defence on Safety and Quality in Health Care.
Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts Outcomes of the project include: ADF Post-discharge GP health assessment • Identification of the key points of clinical handover Department of Veterans' Affairs /Discipline of General in the Defence health environment occurred. The Practice, Flinders University Adelaide ISOBAR framework was assessed for applicability This presentation will focus on a new Australian against the tool.
Defence Force post-discharge health assessment, to • Agreement by all members of the Working Group be conducted by GPs and funded under Medicare. A to use the ISOBAR framework as the standard new assessment tool has been developed by Flinders when undertaking Clinical Handover in Defence. University to help support this assessment, and the This tool is already used in the single Service presentation will work through this new tool. environments when using the Primary Care Tackling mental health challenges facing veterans Clinical Manual (PCCM) and is taught to Medics and their families is a pillar of the Government's plan as part of their basic training.
for veterans' affairs. The 2013-14 Veterans' Affairs • A baseline audit of current clinical handover Budget package Veteran Mental Health Services – practices was completed in garrison health Expansion included the introduction of the GP health assessment for former serving members of the ADF. • A JHC Health Instruction and ISOBAR intra In an effort to promote the importance of identifying facility and inter facility templates developed for health issues early, this health assessment has been use in clinical handover. These tools were trialled specially designed to help for former serving members and used by pilot sites in the garrison health and GPs identify and act on any physical and/or mental health issues before they become major • Outcomes from the JHC facilities who participated problems. The assessment is available to all former in the pilot phase of the project will be presented. ADF members, including former serving members of Next Steps to finalise the project will be: permanent and reserve forces, and supports them in • Evaluation of the pilot phase of the project. using primary health care after leaving Defence. • Implementation of the ISOBAR handover tools for DVA has worked with Flinders University, Discipline use in all JHC health facilities. of General Practice to design the ADF Post-discharge • Development of broader ADF guidance to ensure GP Health Assessment Tool. The tool assists GPs to consistency in the single Service and Operational assess their patient's current physical and environments using ISOBAR as the accepted psychological health, and includes specific screening clinical handover framework in Defence healthcare tools for alcohol and substance use disorder, posttraumatic stress disorder and psychological distress. References:
This presentation will outline the development and Standard 6 Clinical Handover, NSQHS Standards; implementation of the assessment and the specially Primary Clinical Care Manual, QLD Health designed assessment tool, including the consultation undertaken with medical practitioners and the Corresponding author: Madeline Makeham Department of Defence.
Authors(s) affiliations: Department of Veterans' Affairs / Discipline of General Practice, Flinders University Adelaide, Corresponding author: Matthew Jackson Corresponding authors email: [email protected] Operational Health Will an injury prevention program delivered during interested to know if an injury prevention program pre-week of Australian Defence Force (ADF) delivered during the pre-week of Infantry Initial Infantry training lead to a decrease in preventable Employment Training led to a decrease in preventable injuries through the 13 week program. We conducted injuries amongst trainees: a randomized a randomised controlled trial of 13 platoons with 403 controlled trial.
male Infantry Trainees randomly assigned to one of Carney Garland, Rebecca Sellwood, Dr Darrell Duncan two groups: the clinical education intervention group (n=251, 8 platoons), or the control group with no This presentation outlines some research undertaken education (n=152, 3 platoons). There were no at the School Of Infantry in 2012/13. We were significant differences between the groups in terms Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts of baseline characteristics. The intervention Forward Combat Critical Care – Time for a New consisted of an injury screening questionnaire, a theory and practical injury prevention education WGCDR David Cooksley1 (Emergency and Retrieval session as well as selected individual assessments. Physician) The education covered contributing factors to injuries, knowing the difference between an injury The recent military conflicts in Iraq and Afghanistan and a minor sprain or strain, biomechanics, basic have led to many changes in the care of the battle stretching, core stability and its role in maintaining casualty. Some of those, like haemostatic fitness and postural awareness. Based on the resuscitation, have even been adopted into civilian responses to the self reporting questionnaire within practice. One unique development by the British the intervention group we were able to identify Military is their Medical Emergency Response Team trainees who may benefit from a one off individual (MERT) created to provide very rapid, advanced and assessment with the Physiotherapist to assist them aggressive resuscitation and critical care far forward with self management strategies for any in the battlespace. The MERT comprises an musculoskeletal issues they may be experiencing. experienced critical care doctor, emergency nurse The primary outcome measure was the number of and two intensive care paramedics. The team preventable injuries. Secondary measures included undertakes considerable addition training and the number of trainees sustaining preventable operates within a strong clinical governance injuries that were subsequently removed from framework. They bring to the patient lifesaving training for rehabilitation, and the eventual capabilities normally only found within a hospital. disposition of injured trainees (completed infantry This paper will discuss the MERT rationale, training, training, Corps transfer or discharge). All trainees operational approach to dealing with critically unwell were offered the normal routine of medical and combat casualty and patient outcomes compared to physiotherapy assistance through the course of their conventional forward military care and evacuation. training regardless of the platoon they had been The author will give an example of how the MERT assigned to.
concept could be integrated into the ADF to enhance our current forward and tactical critical care Although the intervention showed no significant decrease in preventable injuries we did identify two strongly predictive risk factors for injury during Authors(s) affiliations: 1ADF Military Surgical Team, Royal training. These were: reported pain with pack Brisbane and Women's Hospital marching and having an injury at Kapooka, (rather Corresponding author: WGCDR David Cooksley1 Corresponding authors email: [email protected] than history of an earlier injury). Basic Fitness Assessment failure was close to a statistically significant predictor (p=0.08). Those trainees with Nurse Practitioners in Air Force Health these risk factors had a significantly higher chance Danny O'Neill and Matt Luther of being sent to the trainee rehabilitation wing in Work is underway within the Royal Australian Air Sydney for extended rehabilitation. The Injury Force to add capability to the current health care Prevention Program did not statistically make any model. In Australia Nurse Practitioners have been change to the number of preventable injuries providing a specific capability to the civilian presented during the infantry training, but the workforce, bridging many gaps in service provision predictive risk factors were able to provide the staff with great success. With this in mind, the global with early identification of those trainees who may be responsibility to support those in need, whether at a higher risk of sustaining an injury during arising from; political unrest and instability, environmental disaster or industrial incidents, will Authors(s) affiliations: Singleton Health Centre, Lone Pine continue to provide the Royal Australian Air Force Barracks, Singleton with ample opportunity to provide health care in Corresponding author: Rebecca Sellwood austere and complex environments. Taking on-board Corresponding authors email: [email protected] these issues, Air Force Health is beginning to embrace the challenges ahead with a well-trained and well equipped health care workforce.
Nurse Practitioners currently only exist in the reserve element of the Royal Australian Air Force. Whilst their advanced credentials are acknowledged they are not formally appointed in current health doctrine Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts as Nurse Practitioners. Work is underway to review References:
ways of applying this capability in to Air Force health O'Neill, D.R; Luther, M. 2013. Nurse Practitioner Led Health Facility (Role 1) on Exercise Precision The professional attributes of a Nurse Practitioner Support, 2011: A nurse practitioners that align it to a Defence application are those that observational report. JVMH. Vol 21. No3.
highlighted the role appropriate to fulfil the need for Authors(s) affiliations: SQNLDR Danny O'Neill, 3 AME SQN health care provision in rural and remote Australia, RAAFSR and Emergency Dept. Port Macquarie Base late in 1990s. Advanced practice within an autonomous, yet collaborative model, allows the SQNLDR Matt Luther, 3 AME SQN RAAFSR and Emergency Nurse Practitioner to immerse themselves in varied Dept. Calvary Hospital, Canberra. Corresponding author: Danny O'Neill health care environments, complementing the Corresponding authors email: Daniel.o'[email protected] existing structure, whilst bridging the historical gap between nursing and medicine. Nurse Practitioners are already a force multiplier, with significant impact, in many international military models and offer an Noise-Induced Hearing Loss in the Military attractive adjunct for Air Force Health. The robust Environment – a review of upcoming preventative nature of Nurse Practitioner accreditation ensures pharmacological agents that the Medical Officers (MOs) collaboratively FLTLT Patrick O'Neill working with a Nurse Practitioner, can rely on a competent, qualified and professional health care Personnel serving in the ADF will be exposed to high intensity noise from any number of sources including small arms fire, artillery, explosions, aircraft or During a recent review of the Nurse Practitioner engine noise. Without suitable hearing protection service, correlating the skill set of a civilian Nurse some of these personnel will go on to develop noise Practitioner to those required by Air Force in a induced hearing loss (NIHL).
military health facility, a best fit relationship can be found in the civilian Emergency Nurse Practitioner Good hearing is essential for safety in the military (ENP) role. An ENP brings specific skills and environment. Damage to hearing can lead directly to experience in the acute care setting, mapping across personnel becoming unsuitable for current to the identified health professional requirements of employment resulting in personal and financial a Role One or Two facility including; triage, acute consequences. The impact upon the ADF includes injury and trauma management, acute illness the loss of skilled and experienced personnel, the assessment, health promotion, resuscitation and financial costs associated with the retraining and primary health care. This professional profile replacement of personnel as well as any associated provides maximum capability for operational service compensation. To illustrate the magnitude of this within a single health care provider.
problem, for veterans of recent conflicts (East Timor, Solomon Islands, Afghanistan and Iraq) the third The subsequent assumption of Nurse Practitioners largest disease claim made to Veterans Affairs is being recognised as a significant health resource directly associated with noise induced hearing within Air Force health would lead to their effective damage with sensorineural hearing loss representing and efficient use during peacetime and combat/war 1,368 compensated cases. Furthermore amongst like operations. Reviewing and implementing other Vietnam veterans sensorineural hearing loss Nurse Practitioner skill sets such as primary health represents the largest claimed disability with 21,105 care, mental health and flight nursing will all benefit the future further capability in meeting service requires.
Until the mid-1990s it was believed that NIHL occurred primarily as a consequence of mechanical Utilising Nurse Practitioners in the nursing career trauma. Based on this paradigm the only existing structure could improve morale, retention and have strategies for reducing NIHL were use of mechanical benefits for Air Force and the greater Defence health devices.2 However there are limitations inherent in the sole use of mechanical interventions which This presentation will discuss the benefits, what has restricts their effectiveness in many circumstances. been done so far by RAAFSR Nurse Practitioners and Additionally it is now thought that NIHL occurs the future of Nurse Practitioners in the Air force.
largely as a result of metabolic not mechanical damage.3 This metabolic damage acts through various biochemical pathways, the foremost being Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts oxidative stress but with contributions from excess 6 Wong, A. C. Y., Froud, K. E., Hsieh, Y. S. Y., & glutamate concentrations and cochlea hypo- regarding Izumikawa, C. (2013). Noise-induced perfusion. By targeting these pathways with suitable hearing loss in the 21st century-a research and pharmacological agents there is potential to protect the ear against NIHL.4 Animal testing has identified a number of likely agents including MET, NAC, ebselen, Authors(s) affiliations: Patrick O'Neill conducted this literature review whilst completing a clinical rotation at the glutamate antagonists, magnesium and salicylic Institute of Aviation Medicine, advice and assistance was acid. Human clinical trials are already underway on provided by Dr Adrian Smith some of these agents. The results of these studies "have the potential to drive changes in evidence- Alphabet Soup: WHS, AME, SRCA, MRCA and based clinical practice."5 It is probable that within the 10-1-2-Metric – Providing a safe workplace for the next decade6 NIHL will be mitigated not only with mechanical means but also treated with a host of those left behind after withdrawal of operations (A pharmacological agents. In order to maximize the Case Study in Timor-Leste) safety of ADF personnel it is imperative that the ADF Miss Rachelle Warner be aware of these upcoming agents, their suitability to the military environment and the need to develop Following the withdrawal of Australian Forces from policy governing their use. Timor-Leste, a number of concerns regarding the safety of Defence personnel working in Timor-Leste have been raised. With the departure of the 1 Departments Veterans Affairs, Treatment International Stabilisation Force and the closure of Population Statistics Top 20 Accepted Conditions the Aspen medical facility in 2013, there is now an - September 2013 http://www.dva.gov.au/ increased risk for staff travelling outside of Dili to undertake Defence directed work, particularly in regards to medical support and evacuation. 2 Joseph, A., Punch, J., Stephenson, M., Paneth, The WHS legislation has extraterritorial application N., Wolfe, E., & Murphy, W. (2007). The effects of for international workers, as well as specific training format on earplug performance. requirements for remote and isolated workers, which International journal of audiology, 46(10), 609- are all applicable to workers in Timor-Leste. There is both an expectation and a legislative requirement to 3 Henderson D, Bielefeld EC, Harris KC, Hu BH look after our people, wherever they are in the world.
(2006) The role of oxidative stress in noise- This Case Study follows the comprehensive risk induced hearing loss. Ear Hear 27:1–19.
assessment, development and implementation of an 4 Wong, A. C. Y., Froud, K. E., Hsieh, Y. S. Y., & action plan to provide Defence personnel in Timor- regarding Izumikawa, C. (2013). Noise-induced Leste with an equivalent service of medical support hearing loss in the 21st century-a research and and access to medical evacuation to that they would expect in Australia.
5 Le Prell, C. G. (2012). Noise-induced hearing Authors(s) affiliations: Defence loss: from animal models to human trials. In The Corresponding author: Miss Rachelle Warner Effects of Noise on Aquatic Life (pp. 191-195). Corresponding authors email: [email protected] Springer New York.
NZ Peacekeepers in South Sudan: A Case Study peacekeeping campaign in South Sudan. New of Trauma Exposure and Impact on Mental Health Zealand Defence Force (NZDF) personnel deployed to South Sudan experience a range of additional Major Alana MacDonald (Senior Psychologist Joint, New stressors over and above typical deployment stressors Zealand Defence Force) many encounter on other NZDF deployments, which New Zealand has deployed approximately 50 include isolation, extreme environmental hardship, personnel to South Sudan since New Zealand's deprivation of food, exposure to severe illness, contribution began in 2005. New Zealand provides a constant and real threat, heightened involvement in small number of personnel on six-monthly rotations and exposure to psychological trauma, as well as to cover observation and liaison officer posts which severe restrictions around the ability to intervene contribute to the wider United Nations (UN) and use force. Since NZs involvement began, a Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts number of personnel returning from this deployment and units in the post deployment environment. have experienced reintegration difficulties on their Specific challenges such as support to reservists and return and been referred for clinical psychologist resource constraints will be discussed. treatment. In 2013, volatility within South Sudan Corresponding author: MAJ Michelle McInnes significantly rose, and as a response the type of Corresponding authors email: [email protected] psychological support provided to our personnel deployed in this area was reviewed. It was at this time that NZDF deemed our deployment to South The Provision of Psychological Support to HMNZS Sudan as a ‘Psychologically High Threat' mission TE MANA Personnel on an 8 month Anti-Piracy and a more intensive psychological support programme was implemented. This presentation serves to address some of the unique psychological New Zealand Defence Force Navy Psychological Service stressors NZDF personnel and other Nations The RNZN routinely deploy on operations within New peacekeepers face working in South Sudan and the Zealand's seas, which see personnel on ship and impact this appears to have placed on our previously away from their families for extended periods of time. deployed personnel. The presentation will review the Whilst psychological support is available to ships at criteria used in determining this mission as a high anytime, a structured psychological support psychological threat, as well as the provisions then programme is provided for deployments over four provided based on this assessment, for a months duration. In August 2013, HMNZS TE MANA comprehensive psychological support programme. A embarked on an eight month anti-piracy deployment brief case study will provide a review of MH screening in the Gulf of Aden and Arabian Sea, in support of data throughout a six month deployment to South the Combined Maritime Forces (CMF) multi-national Sudan over periods of heightened country volatility, naval partnership of 30 nations and NATO's anti- and into their reintegration period back home in New piracy mission Operation Ocean Shield. Due to both the length and nature of this operation, personnel of Corresponding author: MAJ Alana MacDonald (Senior HMNZS TE MANA were provided with a tailored Psychologist Joint New Zealand Defence Force) Psychological Support to Deployment Programme Corresponding authors email: [email protected] (PSDP) which is routinely provided to land and other Joint Forces missions. This presentation will outline The Changing Landscape of Operational Mental the components of the PSDP provided over the full deployment cycle to the 176 personnel and families of HMNZS TE MANA on their anti-piracy mission. LTCOL Andrew Cohn; MAJ Michelle McInnes This presentation will also provide a brief summary With the reduced operational tempo, both current of the psychological screening data, as well as and forecasted, the roles and tasking of the highlighting the strains experienced by personnel operational mental health workforce is evolving and and need for psychological support for our developing to better meet Army's requirements. In peacekeeping focused operations. response to the reduced operational tempo, 1st Corresponding author: MAJ Alana MacDonald (Senior Psychology Unit has developed a strategy to provide Psychologist Joint, New Zealand Defence Force) support to Army units across the spectrum of Corresponding authors email: [email protected] operational mental health. This support addresses the needs of units across all stages of the Force Participation in The Technical Cooperation Generation Cycle, from Readying to Ready and Reset. Program (TTCP) HUM Technical Panel 13: Areas in which 1st Psychology Unit is working closely with Joint Health Command to achieve this goal Psychological Health and Operational includes development and expansion of the Effectiveness: Perspectives and Learnings from psychological resilience training (BattleSMART), unit Australia and New Zealand climate measures (Profile of Unit Leadership, Colonel Nicole Sadler (Director Strategic and Operational Satisfaction and Effectiveness – PULSE), and Mental Health / Head of Corps Australian Army Psychology coordination of large scale Post Operational Corps) and Major Alana MacDonald (Senior Psychologist Psychology Screening (POPS) campaigns. This Joint, New Zealand Defence Force) presentation addresses the ways that 1st Psychology Psychological health is important in all military Unit is evolving to adapt to operational changes, operations (combat, peace support, humanitarian) including support to remote personnel via telephone and is an essential contributor to safety, productivity, and Internet, and meeting the needs of individual and efficiency both in garrison and in operating Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts environments. A great deal of research has been New Zealand. This presentation serves to highlight undertaken on ways to enhance psychological health some of the significant contributions developed within military forces in order to best prepare, through the workings of TP13 and how they have maintain and return from operations. The Technical influenced our respective strategies, policies and Cooperation Program (TTCP) is a collaborative practices, including in the areas of psychological military research and information exchange program health training, psychological resilience, management amongst five member nations – the United States, of cultural stigma and barriers to care and United Kingdom, Australia, Canada and New Zealand optimisation of mental health care. - to foster cooperation amongst member nations, so References:
as to facilitate effective research and policy development at reduced cost. TTCP Technical Panel The Technical Cooperation Program (TTCP) HUM 13: Psychological Health and Operational Technical Panel 13: Psychological Health and Effectiveness, conducts collaborative research and Operational Effectiveness Business Case May exchanges information and resources, that leads to the development of new strategies in the prediction, Authors(s) affiliations: COL N. Sadler, Joint Health prevention, treatment, optimisation, and Command, Department of Defence; MAJ A. MacDonald, management of psychological health factors that Senior Psychologist Joint, New Zealand Defence Force impact (positively and negatively) on military Corresponding author: Nicole Sadler Corresponding authors email: [email protected] activities. Involvement in TP13 has been one of the major forms of international engagement on psychological health research for both Australia and The Long Way Home Theatre Production – The Having the opportunity and privilege to be involved Military Nursing Perspective on Rehabilitating our in the ADF Theatre Project (ADF-TP) as a nurse was Wounded Injured and Ill through the Arts at times challenging but humbling and rewarding. Providing care is the effortless component of our LT Dianne Hutchinson and CAPT Emma Palmer RAANC profession however, this project came with its unique The Australian Defence Force (ADF) joined with the challenges because it was and continues to be, novel. Sydney Theatre Company (STC) to embark on an The greatest clinical opportunity of this project was historic event of national significance representing being involved in the development workshops servicemen and women's stories and experiences allowing us time to spend many hours with our through live theatre. The Long Way Home (TLWH) an group at the theatre. This provided the opportunity initiative of the Chief of Defence Force (CDF) saw to hear the soldier's stories, get to know them more service personnel perform live on stage alongside on a personal basis, build trust as well as gain a professional actors. This play represented their greater understanding of their health care experiences on operations in Iraq, Afghanistan and requirements. The importance of getting to know East Timor and the impact that these operations them intimately assisted us in recognising their have had on our members and their families. The triggers both physical and psychological and majority of the ADF cast members were wounded, therefore supporting them appropriately.
injured or ill (WII) and carried physical or Although there is no clinical evidence to support our psychological wounds and sometimes both. observations we have witnessed many positive The title was chosen long before the play was written, aspects from this project. Soldiers speaking ‘through none the less it appropriately represents the journey theatre' from the stage to their wives, parents and our members often encounter of returning home, families for the first time. Soldier's who came to the healing and recovery. TLWH provided an opportunity project with no sense of purpose and have left with for our members to tell their personal stories of the clear ideas about the future, hugely increased self challenges they faced and the sacrifices their families confidence and determination. Soldiers with the self- made to the author, who then wrote deeply moving assurance to confidently socialise outside of their interpretations of their experiences on operations. defence circle of friends and some who have Our defence members performed their very human reconnected with defence. While anecdotal, these story to the general public many times and the raw changes were so obvious that comments came from emotion was evident on their faces at the conclusion the members themselves, their colleagues and their Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts Where to from here? The anecdotal and observational spheres, including biological, social, psychological, evidence from this project is immeasurable and organisational and deployment-related factors. Our therefore it is incumbent upon us to design the next findings may be used to inform pre-deployment step ensuring that our methods in dealing with WII prevention programs for deployed personnel, soldiers are based on sound evidence in order to equipping them with the strengths and supports provide a variety of modalities for healing from the needed to cope with trauma, and disrupt pathways performing arts to sports and everything in between.
leading to disorder.
Corresponding author: Emma Palmer Authors(s) affiliations: ¹Centre for Traumatic Stress Studies, Corresponding authors email: [email protected] University of Adelaide Corresponding author: Amelia Searle Corresponding authors email: [email protected] Longitudinal predictors of ‘better than expected' post-deployment mental health among Australian Review of Mental Health Screening Data Defence Force (ADF) personnel.
Following Operational Deployment within the Searle A.¹, Lawrence-Wood E.¹, Van Hooff M.¹ & McFarlane A.¹ New Zealand Defence Force Experiencing deployment-related trauma like direct Captain Samuel Williams (Southern Regional Psychologist – combat and witnessing atrocities (rather than simply New Zealand Defence Force) having deployed) is associated with subsequent Psychological mental health screening is common mental disorder in military personnel. Furthermore, practice within Allied Nations militaries to identify cumulative trauma is more strongly associated with personnel with possible adverse mental health disorder than any one trauma type. However, there outcomes following deployment that might not is great variation in military personnel's response to otherwise be detected or treated. In 2008 New trauma; while personnel experience high levels of Zealand Defence Force (NZDF) implemented a new trauma during deployments to the Middle East Area Return to New Zealand (RTNZ) Psychological Screen of Operations (MEAO), only a minority develop which Service personnel completed upon their initial clinical-level mental disorder. Despite this, most RTNZ and at 4-6 months following return from research on deployed personnel focuses on predictors deployment. This presentation highlights the of disorder, and relatively few studies examine screening measures utilised at both administration factors that are associated with ‘better than expected' points, as well as an overview of the screening data functioning, or ‘resilience'. collected between 2008-2013 from deployed NZDF We analysed data from the MEAO Prospective Study personnel. Key findings from this review of the NZDF of Australian Defence Force members in order to deployment screening data have since been utilised examine the longitudinal predictors of resilience to further inform the review and development of following deployment. Participating personnel revised mental health screening tools administered reported their PTSD symptoms using the PCL at pre- following deployment, as well as informing best deployment and post-deployment, and also practice for the delivery of the NZDFs Psychological completed a detailed checklist of traumatic Support to Deployment Programme. Key findings deployment experiences. Overall, PTSD symptoms from this screening review will be highlighted, as well increased between pre- and post-deployment, with as how the findings were utilised in further traumatic deployment experiences significantly development and refinement of practices within associated with this increase. However, a number of personnel showed lower than predicted PTSD Corresponding author: MAJ Alana MacDonald (Senior symptoms (thus demonstrating resilience). In Psychologist Joint New Zealand Defence Force) accordance with ecological frameworks of resilience, Corresponding authors email: [email protected] we examine potential predictors from multiple Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts The Utilization of Computerized Balance only 1 of the equilibrium ratios. Next, comparing all Assessment to Examine the Physiologic Effects subjects with PTSD to those without PTSD, we found and Provide Differentiation Between Subjects with significant differences for the composite score and all equilibrium ratios.
Combat-Associated mTBI and PTSD We then examined differences between the four Dr David Cifu, Dr Joanna Wares, Dr William Carne, Dr Kathy mutually exclusive sets, Groups 0, 1, 2, and 3, and Hoke, Dr Steven West found significant differences for five of the measures Mild traumatic brain injury (mTBI) is common among (exception ratio 5). Post-hoc analyses demonstrated military combatants, particularly among those significant pairwise differences between Groups 0 Coalition Forces serving in Operations Enduring and and 3, the subjects without either disorder versus Iraqi Freedom. Common complaints post mTBI are the subjects with both disorders. This suggests that deficits in balance and orientation attributed to both the combined deficits from mTBI and PTSD cause mTBI and other medical concerns including post- large enough deficits for differences to be significant, traumatic stress disorder (PTSD). The objective of when compared with subjects that have neither this study was to examine the relationship of mTBI with balance deficits and to assess variations in Next, we compared measures of those diagnosed balance between four groups of combat exposed with PTSD and those without PTSD in first, the populations: (1) subjects with no history of either subgroup of subjects not diagnosed with mTBI and mTBI or PTSD, (2) subjects with a history of mTBI, next, in those diagnosed with mTBI. For subjects not (3) subjects with a PTSD diagnosis, and (4) subjects diagnosed with mTBI, significant differences between with both an mTBI and a PTSD diagnosis. Analyses PTSD groups (Group 0 and 2) were seen for 3 were performed on equilibrium scores, which equilibrium ratios and the composite measure. compare the most drastic anterior-posterior Amongst patients diagnosed with mTBI, differences movements of the subject over each trial to a were found for PTSD, Groups 1 and 3, for only 1 theoretical limit, from 6 computerized posturography equilibrium ratio, suggesting that mTBI lowers tasks. Statistical measures included 5 ratios of scores enough to mask the PTSD effect. Reversing equilibrium scores and a composite weighted average the roles of PTSD and mTBI, we found significant of the 6 equilibrium scores. differences in mTBI groups (Groups 0 and 1) in 2 Descriptive Data: A total of 166 subjects were measures. No differences differentiate mTBI for studied. 55 subjects had neither mTBI nor PTSD patients who are diagnosed with PTSD (Groups 2 (Group 0). 65 subjects were diagnosed only with and 3) suggesting that PTSD also lowers scores to a mTBI (Group 1). 25 were diagnosed with only PTSD level which masks any mTBI effect.
(Group 2). 21 subjects were diagnosed with both Summary: Computerized balance assessment offers mTBI and PTSD (Group 3).
an objective technique to examine the physiologic Results: Using a non-parametric approach, we effects and provide differentiation between subjects addressed the question, do people with mTBI or with combat-associated mTBI and PTSD.
PTSD exhibit balance deficits. First, we compared all subjects not diagnosed with mTBI to those diagnosed Authors(s) affiliations: Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, with mTBI and found them significantly different on University of Richmond Corresponding author: Dr Steven West Stigma and Accessing Mental Health Support in considerable stigma still exists for service personnel Military Organisations in relation to accessing mental health facilities. This presentation highlights research conducted by NZDF Lieutenant Christopher Liddell (Trainee Psychologist, New into factors that contribute to mental health stigma, Zealand Defence Force) as well as ways in which mental health facilities can In recent years, many military organisations have be made more accessible for service personnel. For had an increased focus on supporting the mental this study, NZDF personnel who have made use of wellbeing of their employees. However, despite this mental health support services provided through the increased awareness around mental health issues, NZDF were interviewed about their experiences. This Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts was done to provide real world accounts of accessing along with a collection of common tips, experiences mental health support through the NZDF, and by and advice for each stage of the ECOD from function of this, reveal some of the factors that can participants. The key findings from this research will make individuals reluctant to engage in help seeking be presented, as well as the further utility of this behaviours. Broadly speaking, two main barriers research for NZDF support to operations. existed for those who have made use of NZDF mental Corresponding author: MAJ Alana MacDonald (Senior health support services. Firstly, the potential effects Psychologist Joint, New Zealand Defence Force) that admitting mental health issues can have on Corresponding authors email: [email protected] one's career progression and/or deployment appeared as a barrier. Secondly, the perception that The Relationships Between Blast-Induced Mild accessing mental health support makes an individual Traumatic Brain Injury, Post-Concussive weak or inferior to others had a strong potential impact. This study indicates that accessing mental Symptomology, Depression, Post-Traumatic health services is often a positive and beneficial Stress Disorder, and Alcohol Use in Active Duty experience, but that making the decision to seek Military Personnel help can be difficult. To make mental health support Dr Steven West, Dr David Cifu, Captain Brett Hart, Mr Justin services more accessible, it is suggested that efforts be made to dispel myths around mental health. Additionally, further efforts need to be made to Nearly 250,000 U.S. military personnel have incurred increase the visibility of mental health support deployment-related mild traumatic brain injury services within the NZDF. (mTBI) during the Global War on Terrorism. Many of these individuals have subsequent post-concussion Corresponding author: MAJ Alana MacDonald (Senior syndrome (PCS). Occurrence of blast-induced mTBI Psychologist Joint, New Zealand Defence Force) is common in this population and has been Corresponding authors email: [email protected] hypothesized to alter the risk of PCS and presentation of individual symptoms particularly when repetitive. Emotional Cycle of Deployment: A Validation These individuals also present with a host of using NZDF Personnel and their families comorbid conditions including depression, PTSD, and increased risk of alcohol misuse. Recent research Sub Lieutenant Katherine Yardley (Trainee Psychologist, New Zealand Defence Force) has been conflictive in terms of the influence of these concomitant conditions on one another particularly Military Service places high demands on its with regard to select characteristics of service personnel, compounded through commitment to members involved. Likewise, debate on treatment operations, which can place significant strain on algorithms for these co-occurring conditions in both personnel who deploy and their families who patients with PCS concerns whether to focus on PCS remain at home. Currently, the NZDF provide a as the primary point of treatment or vice versa. range of resources designed for both personnel and Currently, little empirical support has appeared to their families prior to deployment in which an denote the impact of PCS on known corollaries of important model, the Emotional Cycle of Deployment mTBI such as PTSD, depression, and alcohol misuse (ECOD) is utilised. The ECOD is used as a framework and it is unclear if PCS modifies the relationships for both personnel and their families to describe and between known symptomolgies post mTBI. The goal understand the normal range of behaviours and of this study was to: (1) detail the rates of such emotions generated through the experience of conditions in a military population recently returned deployment. The ECOD first emerged in the late from combat operations, and (2) to determine if PCS 1980s from studies focusing on emotions and behaviours of US Navy wives during deployment of depression, PTSD, and alcohol misuse. Data were their husbands. In the late 1990s, the NZDF adopted obtained from 60 active duty service members within this model and gathered evidence from research for 90 days of return from theater. Analysis revealed no its use and implementation within NZDF. The ECOD group differences with respect to age, pay grade, has since been utilised in support resources for marital status, or race /ethnicity. All had a physician personnel since the 1990s and had not been reviewed confirmed diagnosis of blast-related mTBI. since that time. This present research validated the Measurement data were PCS as indicated by use of the ECOD model within the NZDF by collecting Rivermead Postconcussive Symptom Questionnaire, both quantitative and qualitative data from a mixed depressive symptomology from Center for sample of personnel and partners. The research Epidemiologic Studies Depression Scale, PTSD by investigated the models key components to ensure the PTSD Checklist, Military (PCL-M) and alcohol the ECOD was still a viable model to utilise for NZDF, Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts misuse as indicated by Alcohol Use Disorders 0.149, 95%CI -2.723, 0.423]. Regression-based path Identification Test (AUDIT). Data were analyzed to: analyses tested potential moderating and mediating (1) denote the rates of key variables, and (2) determine effects of PCS on the relationship between depression if PCS mediated or moderated the associations and alcohol use. No moderating [F (3, 56) = 2.3358, between depression, PTSD, and alcohol misuse. p = 0.0835] or mediating [F (1, 58) = 1.0619, p = Rates of depression and PTSD were near roughly 0.3071] effects were found. Although the overall 90% of the sample, and most (80%) engaged in at- model was significant [F (1, 58) = 26.6913, p = risk drinking. Results indicated that depression was 0.00001], only direct effects for depression were the primary predictor of drinking, with those having found (p = 0.00001), with depression explaining greater depressive symptoms drinking more than 31.52% of the variance in alcohol use. those who were not depressed [t (58) = 2.362, p = Authors(s) affiliations: Department of Physical Medicine and 0.022, 95%CI 3.151, 0.260, d = 0.609]. PTSD did not Rehabilitation, Virginia Commonwealth University predict drinking in this sample [t (58) = 1.464, p = Corresponding author: Dr Steven West The Post Deployment Transition Model: A Review veteran mental health service system. Along with of Experiences from NZDF Personnel DVA's strategic plan, DVA Towards 2020, it is transforming early intervention and mental health Sub Lieutenant Anna Hill (Trainee Psychologist, New Zealand treatment for a new generation of Australian Defence Force) veterans. Technology is integral in changing the way Returning from operations can often be a time of DVA engages with younger veteran clients as well as turbulence and change, as personnel transition back their mental health providers. DVA uses technology into their home environment. Common reintegration to support providers in improving their understanding issues within the Allied Nations research focus on of veterans and the use of evidence-based CBT relationship difficulties, as well as heightened risk treatments. In the past, DVA has sought to support taking behaviours and a general sense of providers through paper-based resources, face-to- disruptiveness settling back into routine. Currently face training and cooperative learning groups. Now, utilised in the NZDF return to New Zealand that same information is available through free psychological support resources, is an important online resources.
model to assist in normalising common behaviours In 2007, DVA released the Mental Health Advice and feelings during the transition process, called the Book, a resource for professionals treating veterans Post Deployment Transition Model (PDTM). The with common mental health problems. This PDTM was developed from the Kubler-Ross change specialized publication is designed to ensure curve, and was remodelled for use within a post consistency and utilisation of best practice, evidence- deployment context within NZDF. Since its first based procedures in the assessment and treatment implementation in the late 1990s, the PDTM had not of common mental health problems for veterans. The been reviewed for currency or relevancy with todays book contains information on understanding Service members. This present research reviewed the veterans and their families, summary advice for relevancy of the PDTM within NZDF by collecting General Practitioners and detailed information on qualitative information regarding each stage of the assessment, formulation and treatment of common PDTM. The key findings from this research will be mental health problems amongst veterans. presented, as well as the further utility of this research for NZDF support to operations. Since its release, the Mental Health Advice Book has become one of DVA's most sought after provider Corresponding author: MAJ Alana MacDonald (Senior resources. It was reviewed and updated in 2012/13. Psychologist Joint, New Zealand Defence Force) Corresponding authors email: [email protected] Feedback from users showed that the information and advice contained within the Mental Health Translating the Mental Health Advice Book into an Advice Book, while being a valuable resource, is not interactive electronic format always easy to access during a consultation. To aid providers in their screening and assessment of Kym Connolly, Olivia Mahn & Tim Adams (DVA) veterans with mental health concerns, an electronic The Department of Veterans' Affairs' (DVA) Veteran companion to the book has been developed. The Mental Health Strategy 2013-2023 is guiding Veteran Mental Health Consultation Companion is innovative policy and program delivery across the an application for tablet devices and enables a Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts practitioner to quickly navigate to relevant An Overview of the Development and Practice of assessment tools, outcome tools and patient Psychological Support to Operations within the handouts during a consultation. It is interactive and New Zealand Defence Force: Reflections on Past easy to navigate, making it more accessible to and Current Practice Captain Samuel Williams (Southern Regional Psychologist – The Veteran Mental Health Consultation Companion New Zealand Defence Force) is designed to complement the flow of a consultation The New Zealand Defence Force (NZDF) has utilised and assist with assessment tool calculations. uniformed psychologists in the provision of Practitioners who use the e-companion will have psychological support to operations since the early instant access to common assessment tools and will 1990s. Since that time, the components delivered at also receive information facilitating the interpretation each phase of the deployment cycle have developed of these results. All results can be printed or emailed, according to best practice and inclusion of Allied allowing them to be placed on a client's file. Patient Nations research and methodology. 2008 saw a handouts are also available, as are a range of online major review of NZDF psychological support to tools, such as psycho-educational videos. operations, largely drawing off the collaborative By using Veteran Mental Health Consultation relationships within The Technical Cooperation Companion during a consultation, practitioners can Program (TTCP) Technical Panel 13 (TP13) access the latest evidence-based tools for treating Psychological Health and Operational Effectiveness. veteran mental health conditions in a more This review saw the implementation of post- collaborative fashion. This encourages a recovery- deployment psychological screening more aligned focussed culture, as well as improving the efficiency with practices conducted within the Australian of their practice management. Defence Force (ADF). 2014 brings another review References: Australian Centre for Posttraumatic period of NZDFs practices of psychological support Mental Health (2012) Mental Health Advice Book for to operations and this presentation serves to Treating Veterans with Common Mental Health highlight the history of psychological support to Problems, Department of Veterans Affairs, Canberra.
operations within the NZDF, as well as its newly revised Psychological Support to Deployment Authors(s) affiliations: Department of Veterans' Affairs Programme (PSDP). Whilst covering the psychological Corresponding author: Kym Connolly support provided across the deployment cycle, the Corresponding authors email: [email protected] emphasis in this presentation will be to highlight the significant changes at post deployment and follow up, including an overview of the revised Initial Psychological Questionnaire (IPQ) and Follow-Up Questionnaire (FPQ) administered as part of psychological debriefing. Corresponding author: MAJ Alana MacDonald (Senior Psychologist Joint, New Zealand Defence Force) Corresponding authors email: [email protected] ADF Recovery and Rehabilitation New Initiatives: and service delivery initiatives to improve Progress and Evaluation Findings rehabilitation and recovery outcomes for serving Defence members.
Julie Wilson Key initiatives of the Simpson Assistance Program Mental health, rehabilitation and recovery are key focal areas for Defence. Defence currently has a successful occupational rehabilitation program but Development of the ADF Rehabilitation Strategy acknowledges that improvements can still be made. The Simpson Assistance Program (SAP) aims to Intensive Rehabilitation Teams; support and enhance the efforts of Defence to reduce A Rehabilitation Research Investment Program, the impact of serious injury or illness on Australian including the implementation of the ‘The role of Defence Force (ADF) personnel. Through SAP we the family in the rehabilitation of SWII ADF have identified and are developing strategic, enabling Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts Members' research initiative; A "Member and Families guide" and a "Commanders Guide to Rehabilitation and Assisting ADF personnel who cannot be gainfully employed during their rehabilitation programs with meaningful engagement options; This presentation will provide an update of program developments and evaluation findings which have Psychosocial support programs such as Mate to occurred to date, key learnings and the future of Mate Peer Visitation; and Defence's rehabilitation reform initiatives.
Corresponding author: Julie Wilson Corresponding authors email: [email protected] Clinical Placements – How do we maintain our within their clinical environment. The Defence currency of practice? individual of course, needs to comply with any requirements of the health service provider in respect CMDR Craig Spinks of for example, induction and credentialing. All three Services have a long history of working To continue to obtain effective outcomes for all hand in hand with public and private health systems parties however there needs to be a level of in times of both conflict and peace with Service communication associated with the use of these personnel working in civilian hospitals for as long as deeds that is perhaps greater than has been applied most of those currently serving can remember and in the past. Both Defence and the health service these relationships continue today. However, with provider are able to benefit from these relationships the increasing complexity of the professional clinical providing they are carefully and actively managed.
environment, Defence has sought to more appropriately formalise and standardise the basis The purpose of this presentation is to expand on this under which these placements occur.
program, inform the audience of its scope and purpose, and facilitate such communication.
To do this, since around 2011, Defence has established a system of deeds between on the one Corresponding author: CMDR Craig Spinks hand, the Commonwealth, and on the other, the relevant State, regional or local health service Experiences in the delivery of a flexible education provider. These deeds formalise clinical placement program to military students opportunities and set out the agreed terms under which Defence personnel may work in the civilian Dale Edwards, Anne-Marie Williams, Wayne Harris, health environment. They establish agreement in a David Lighton, Illya Selmes range of areas including professional liability, Background: The delivery of higher education and
conduct and expectations and provide a system professional development programs through a within which the parties may work to achieve their flexible online model has been increasing in clinical placement objectives. There are currently popularity for education providers and students some sixty deeds in place nationally, with a further alike for some time [Chitkushev Et.Al 2014]. The twenty under negotiation.
delivery of these programs to military students comes with a unique set of challenges, especially in the field Use of these deeds now enables the full spectrum of of health professions education. The University of Defence health personnel, from Medical Specialists, Tasmania (UTAS) offers a wide range of courses through to Medics, Environmental Health personnel through flexible delivery to military students, with and beyond to undertake such placements and has the Bachelor of Paramedic Practice receiving proven to be a successful method of enabling Defence increasing enrolments during the last 12 months. to maintain levels of clinical proficiency to ensure the The current evidence base underpinning education availability of appropriately experienced personnel in delivery to military personnel is limited, with the support of Operations and Exercises as required. majority of literature referring to the US military Once the deed is in place, typically for a period of two [Bunting 2013], which may have limited application to five years, then its schedules are completed that in the Australian military context. as well as identifying the individual undertaking a Aim: To investigate the issues affecting military
placement, identify the outcomes that are sought by personnel engaged in online education, with the aim Defence with acknowledgment by the health service of improving the delivery of services to this specific provider that those outcomes are able to be achieved student population Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts Methodology: The university undertook a review of
Introducing HOSPEX to Australia any cohort specific challenges faced by students LTCOL G Mathews, LTCOL G Gill, LTCOL M Reade, MAJ P enrolled in the Bachelor of Paramedic Practice Butt MAJ A Chalmers MAJ G Brown, CAPT D Innes, CAPT B (Conversion) in the first semester of 2014. Results: Currently 20% of the students enrolled in
This full one hour presentation from 3 speakers the Bachelor of Paramedic Practice at UTAS come introduces a wider ADF Health Service audience to from the Australian Defence Forces. A review of the Australian Concept of HOSPEX.
communication with students over the first semester of 2014 has identified a range of challenges faced by HOSPEX (Hospital Exercise) is a United Kingdom both the student population and the university. simulation exercise developed to validate the These challenges can be summarised under five competency of deploying hospital rotations to the domains; communication; flexibility in content fixed Role 3 field hospital at Camp Bastion in delivery; flexibility in assessment practices; access to Afghanistan. It is conducted utilising a large team of technology; flexibility in enrolment policies and assessors in a purpose built facility in York and assesses all hospital departments. The Australian Army has adapted the concept of HOSPEX to confirm Discussion: Whilst there are a number of issues that
that the personnel and clinical systems of its can be resolved internally within the faculty, there deployable Role 2 Extended medical facility, 2nd are a number of areas that require the development General Health Battalion (2 GHB), are sufficiently of new or updated policy relating to military students. competent to provide services on deployments likely A similar process occurs in the United States under to be requested of it.
the Military Friendly Colleges [Lederman 2008] program. This initial review reveals the need to As part of its role 3rd Health Support Battalion (3 further investigate the barriers and enablers for HSB) has assumed the responsibility for preparing military students in undertaking further education, personnel to conduct a HOSPEX type evaluation, to taking into consideration the unique nature of the develop simulated scenarios across the surgical military professional environment. services of 2 GHB, and to conduct the HOSPEX evaluation. Conclusion: Universities face challenges in the
provision of education to military personnel, due to
The Australian HOSPEX attempts to test 2 GHB their unique characteristics in comparison the wider under a variety of conditions and is conducted in the student body. In order to better support the military field. Preceding each HOSPEX the operator/trainer student, it is important to fully investigate the issues (OT) team, currently seven personnel, meet to develop facing this student cohort.
scenarios which will involve care across casualty reception, triage, initial resuscitation, first surgery, References:
admission to ward or to intensive care unit, and • Bunting, K.A. Military personnel: Perceptions of preparation for rearward evacuation. Some scenarios their experiences with online learning. Ph.D. will have involvement of primary care, psychological thesis, University of New Orleans support, dental and environmental health team in • Chitkushev, L., Vodenska, I., & Zlateva, T. (2014). providing care. Clinical findings, patient observations, Digital Learning Impact Factors: Student diagnostic imaging and pathology results are Satisfaction and Performance in Online Courses. prepared for each simulated casualty. Building on International Journal of Information & Education the British experience there is a strong emphasis on Technology, 4(4).
examining non-technical aspects of care, team situational awareness, clinical leadership, • Lederman, D. (2008) What Makes a College transmission of information during handover of care, ‘Military Friendly'?, Inside Higher Ed, Feb 2008.
and a general testing of 2 GHB administrative Authors(s) affiliations: University of Tasmania, School of processes around casualty movement, casualty notification, overall situational awareness and Corresponding author: Dale Edwards special logistic requirements.
Corresponding authors email: [email protected] The scenarios are difficult and intended to extend the knowledge and coping mechanisms of the treating teams. Casualties suddenly deteriorate and require emergency treatment. At the scenario conclusion, the treating teams will debrief themselves and if required there will be some input from the OT team.
Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts Before the HOSPEX activity the OT team is introduced concept, how it was adapted to suit local to2 GHB clinical personnel. Where possible at the circumstances, and how the concept may evolve to conclusion of the activity which generally lasts about meet the needs of the wider Australian Defence Force 36 hours personnel attend a presentation from the (ADF) and our allies.
OT team to ensure that the lessons identified are known to all, and an informal oral presentation is • Davies TJ, Nadin MN, McArthur DJ, Cox CW, made by the OT team to the CO of 2 GHB and his Roberts P. Hospex 2008. Journal of the Royal staff. A formal Post Activity Report is produced by Army Medical Corps. 2008;154(3):195-201.
the team project officer and officially is returned to the CO 2 GHB by the CO of 3 HSB, ensuring that the • Hayes L, Ryan J. An introduction to training lessons learnt are known to the full-time macrosimulation and Hospex. The clinical teacher. and reserve elements who will form the deployable Role 2 E facility.
Authors(s) affiliations: 3 Health Support Battalion The speakers will describe the reasons why the Corresponding author: Prof Gerard Gill Corresponding authors email: [email protected] Australian Army needed to adopt the HOSPEX ADF Military Medical ‘Dogma' – Teaching Our preventable battlefield deaths1, making the People New Tricks restoration of circulating blood volume and control of haemorrhage a clinical priority2. For the military, the WGCDR David Cooksley1 (Emergency and Retrieval Physician) and CAPT Kendall Crocker threat of disruption to supply chains has driven the 2 (Veterinarian) search for alternatives to refrigerated redblood cells ADF health personnel on deployment or exercise (RBCs), which have a shelf life of only 42 days. may be called upon to provide urgent medical care to Another, only recently recognised, problem with injured or ill military working dogs (MWDs) or other refrigerated RBCs is the development of a storage service dogs (such as police, customs, quarantine, lesion over a period of time that is well within the USAR or AUSMAT) when there is no immediate current shelf life and is associated with poor clinical veterinary support. Few ADF health personnel have had any formal training in the safe handling, assessment and management of these highly Cryopreservation of RBCs has emerged as the valuable service animal assets. This presentation favoured alternative to address these problems4. will outline what may be required in terms of training, Arresting metabolism by cryopreserving fresh blood equipment and policy to allow human healthcare should, in theory, deliver a storage lesion-free personnel to provide initial resuscitation and product that can be stored for up to 10 years. The evacuation of injured or ill MWDs and to communicate logistic advantage of prolonged shelf-life has been effectively with ADF veterinary members providing utilised by the US and Dutch armed forces for over remote support and/or subsequent ongoing care. It 15 years, and the ADF is acquiring this capability. will also address some of the concerns raised about From this limited use, we know that cryopreserved treating MWDs in human healthcare facilities.
RBCs do not cause severe transfusion reactions, but there is no controlled, comparative evidence for their Authors(s) affiliations: 1ADF Military Surgical Team, Royal efficacy as a resuscitation fluid.
Brisbane and Women's Hospital. 2School of Military Engineering, Steele Barracks, Australian Army Coagulation, Haemorrhage and Oxygenation in Corresponding author: WGCDR David Cooksley Resuscitation of Severe trauma – Phase II (CHORuS- Corresponding authors email: [email protected] II) will use a large animal model of acute traumatic coagulopathy to study the effects of aged RBCs, fresh The CHORuS study – using a large animal model RBCs, cryopreserved RBCs, albumin and fresh of acute traumatic coagulopathy to test the frozen plasma transfusion at an organ and cellular efficacy of cryopreserved red blood cells level in the severe trauma setting. The study follows compared to aged and fresh refrigerated red on from a successful pilot study (CHORuS-I) of twelve animals that demonstrated the development of acute blood cells.
traumatic coagulopathy from trauma and Milford EM1,2 van Zyl N1 Diab S1 Dunster K1,3 Tung, JP1,4 haemorrhage alone.
Reade MC5,6 Fraser JF1,7 The study will test the hypothesis that cryopreserved Haemorrhage is the primary reversible cause of RBCs are superior in efficacy to aged RBCs, and death after trauma, estimated to cause 80% of Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts equal in efficacy to fresh RBCs, using the following ideal for remote Australia. Anaesth Intensive Care 2013; 41(1): 10-9.
Organ level oxygenation – measured by tissue Authors(s) affiliations: 1Critical Care Research Group, The oxygen probes in liver, heart, kidney and brain.
Prince Charles Hospital, Brisbane, QLD, 22nd General Health Battalion, Australian Army, 3Science and Microcirculation blood flow – measured by tissue Engineering faculty, Queensland University of Technology, Doppler probes and sidestream darkfield camera Brisbane, QLD, 4Research and Development, Australian images in the same organs.
Red Cross Blood Service, Kelvin Grove, Brisbane, QLD, 5Joint Health Command, Australian Defence Force, Inflammation – measured by inflammatory Canberra, ACT, 6Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, QLD, 7Adult Intensive Care Services, The Prince Charles Hospital, Cardiac function – measured by echocardiography Brisbane, QLD and cardiac biomarkers.
Corresponding author: Elissa Milford Corresponding authors email: [email protected]; Acute traumatic coagulopathy – measured by ROTEM and MULTIPLATE as well as coagulation factor levels.
Do trauma operating theatres really need to be Endothelial glycocalyx damage – measured by electron microscopy imaging.
LTCOL Michael C. Reade The study will also contribute to understanding the The Clinical Practice Guidelines of the United States pathophysiology of acute traumatic coagulopathy, military Joint Theater Trauma System recommend and provide mechanistic data to support growing an operating room used for damage control clinical evidence suggesting aged red cells are resuscitation in military trauma should be heated to harmful, particularly for the trauma patient.
The results of this study will be of considerable recommendation is based on the repeatedly observed interest to Defence given its acquisition of a strong association between hypothermia in trauma cryopreserved RBC capability. In addition, the and greater mortality, conventionally taught as one nascent collaboration between the Critical Care component of the "lethal triad" (along with acidosis Research Group based at The Prince Charles Hospital and coagulopathy). However, there is only very weak in Brisbane and Defence will provide an enduring evidence2 that this association between core opportunity for Defence members to pursue research temperature and mortality is causative. It might be in pre-clinical and clinical areas of critical care.
that greater severity of injury independently causes both hypothermia and greater mortality. Even if the The study is planned to start in late June 2014, association is causative, this does not imply that finish in late 2014, with results published early rewarming once hypothermia has developed would be beneficial. Only a single trial, involving 33 trauma The study is supported by grants from the Defence patients, has ever shown benefit with active Health Foundation, the Queensland Emergency rewarming3 – which in this study involved an Medicine Foundation and the Intensive Care extracorporeal circuit. Even if rewarming is beneficial in trauma, the efficiency of heat transfer from the ambient air or even forced air warming devices is References:
poor,4 and at least within the range of ambient 1. Holcomb JB, McMullin NR, Pearse L, et al. temperatures 18-27°C there is no consistent effect Causes of death in U.S. Special Operations on patient core temperature.5 Very high ambient Forces in the global war on terrorism: 2001- temperatures almost certainly degrade the 2004. Ann Surg 2007; 245(6): 986-91.
performance of operating teams. Although this has 2. Evans JA, van Wessem KJ, McDougall D, et al. never been demonstrated in a clinical context, the Epidemiology of traumatic deaths: comprehensive ability to monitor complex information is known to population-based assessment. World J Surg be increasingly degraded at ambient temperatures 2010; 34(1): 158-63.
>25°C.6 Therefore, the current enthusiasm for very 3. Aubron C, Nichol A, Cooper DJ, Bellomo R. Age high ambient temperatures in operating theatres of red blood cells and transfusion in critically ill may be unwarranted and even detrimental. Indeed, patients. Ann Intensive Care 2013; 3(1): 2.
there is good animal evidence that induced hypothermia is beneficial in trauma,7 a concept that 4. Holley A, Marks DC, Johnson L, et al. Frozen will be familiar to military clinicians acquainted with blood products: clinically effective and potentially anecdotes of unexpected survival after prolonged Volume 23 Number 1; January 2015 AMMA 2014 Conference Abstracts severe hypothermia in battle casualties during the Enduring Freedom (OEF) and Operation Iraqi Falklands War.8 In short, the current feverish zeal Freedom (OIF) have sustained at least one traumatic with which we increase the temperatures of our brain injury (TBI), predominantly mild TBI (mTBI),1,2 deployed ADF operating theatres may, or may not, be and almost 8% of all OEF/OIF Veterans demonstrate detrimental to our patients. In the context of persistent post-TBI symptoms more than six months substantial uncertainty, a clinical trial of ambient post-injury.3,4 Similar issues are present in all operating theatre temperature in trauma is Coalition Forces personnel having served in these warranted. Such a trial would be quite simple and theaters of operation. Explosive munitions, inexpensive to conduct in Australian civilian trauma predominantly improvised explosive device' (IEDs), have caused the overwhelming majority of these identified cases. The incidence is likely even References:
significantly higher than reported, as many mTBIs 1. Damage control surgery at level IIb/III treatment may go unrecognized during and even after facilities. 1-2-2013. San Antonio, TX, United deployment because of more visible concomitant States Army Institute of Surgical Research. injuries capturing greater attention, clinicians' 2. Reynolds BR, Forsythe RM, Harbrecht BG et al. limited awareness of the often subtle initial findings, Hypothermia in massive transfusion: have we and patients' reduced subjective awareness related been paying enough attention to it? J Trauma to cognitive deficits in the acute period. Most Acute Care Surg 2012;73(2):486-491.
symptoms associated with mTBI are transient; however, in a small percentage of individuals, these 3. Gentilello LM, Jurkovich GJ, Stark MS, difficulties persist and even lead to lifelong disability. Hassantash SA, O'Keefe GE. Is hypothermia in In these individuals, additional chronic effects, the victim of major trauma protective or harmful? including neuroendocrinologic abnormalities, A randomized, prospective study. Ann Surg seizures and seizure-like disorders, fatigue, vision and hearing abnormalities, and numerous other 4. Gentilello LM, Moujaes S. Treatment of somatic symptoms are more common over time. The hypothermia in trauma victims: thermodynamic long-term effects from these single or repeated TBIs considerations. J Intensive Care Med on the persistence of these symptoms, on combat and trauma-related comorbidities, and on long-term 5. Inaba K, Berg R, Barmparas G et al. Prospective brain functioning are unknown. Increasing evidence evaluation of ambient operating room supports the linkage between both concussions and temperature on the core temperature of injured combat-related trauma with a degenerative patients undergoing emergent surgery. J Trauma neurologic disorder known as chronic traumatic Acute Care Surg 2012;73(6):1478-1483.
encephalopathy (CTE), which results in progressive 6. Hancock PA. Effect of environmental temperature cognitive and behavioral decline in sub-populations on display monitoring performance: an overview that are 5 to 50 years out from repeated or cumulative with practical implications. Am Ind Hyg Assoc J exposures.6,7,8 The possibility of a link between mTBI, persistent symptoms, and early dementia has 7. Tisherman SA. Hypothermia and injury. Curr widespread implications for SMs and Veterans; Opin Crit Care 2004;10(6):512-519.
however, these chronic and late-life effects of mTBI are poorly understood. The Chronic Effects of 8. Harbinson MJ. William harvey, hypothermia, Neurotrauma Consortium (CENC) is a research and battle injuries. BMJ 1999;319(7224):1561.
project sponsored by the U.S. Departments of Authors(s) affiliations: 1Joint Health Command, Australian Defense and Veterans Affairs devised to address the Defence Force, 2Burns, Trauma and Critical Care Research long-term effects of mild traumatic brain injury in Centre, University of Queensland military personnel and Veterans. The mission of the Corresponding author: LTCOL Michael C. Reade CENC is to fill the gaps in knowledge about the basic Corresponding authors email: [email protected] science of mild TBI (also termed concussion), to determine its effects on late-life outcomes and The Chronic Effects of Neurotrauma Consortium: neurodegeneration, to identify service members most Studying the Future Effects of Combat-Related susceptible to these effects, and to identify the most Brain Injury Today effective treatment strategies. The CENC is a multi-center Dr Steven West, Dr David Cifu translational, and clinical neuroscience researchers Nearly 20% of the more than 2.5 million U.S. Service from the DoD, VA, academic universities, and private Members (SMs) deployed since 2003 to Operation research institutes to effectively address the Journal of Military and Veterans' Health AMMA 2014 Conference Abstracts scientific, diagnostic, and therapeutic ramifications of mTBI and its long-term effects. This presentation will provide details of consortium's four research cores (1. Biorepository, 2. Biostatistics, Data Management and Study Management, 3. Neuroimaging, & 4. Neuropathology), and three principal studies (1. Longitudinal Cohort Study, 2. Tau Modification and Aggregation in Traumatic Brain Injury, and 3. Epidemiology of Chronic Comorbidities). Authors(s) affiliations: Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University Volume 23 Number 1; January 2015 JOURNAL OF MILITARY AND VETERANS' HEALTH
CALL TO AUTHORS
The Journal of Military and Veteran's Health is a peer reviewed quarterly publication published by the Australasian Military Medicine Association. The JMVH Editorial Board has indentified the following themes for future editions (please note these have been updated since previously communicated): Manuscript
Medical Aspects of Trauma Management July 2015 abstracts - Mental conference submission Categories for the above include:
Original Research/Original Articles, Short Communication, Review Articles, Reprinted Articles, Case Studies, Abstracts from the Literature, Biographies, History, Book Reviews, Commentary and View from the Front.
The Editor would be delighted to receive articles for consideration on these themes.
However, please note that although these are the suggested themes, we encourage
authors to continue to submit articles on a range of topics on military medicine and
veterans' health including operational articles.
Please submit your articles via the JMVH website www.jmvh.org where the ‘Instructions to Authors' can also be found.
Should you have any queries in relation to JMVH, please do not hesitate to contact the Editor via the JMVH Editorial Office on +61 3 6234 7844 or [email protected] Tailored medical and health services for Government at Auckland +64 9 359 1635Canberra +61 2 9372 2380Port Moresby +675 323 79 81Sydney +61 2 9372 2400www.internationalsos.com 25/09/2014 4:19:38 PM DISCLAIMERThe views expressed in this journal are those of the authors, and donot reflect in any way official Defence Force policy, or the views of theSurgeon General, Australian Defence Force, or any Military authority
Willdenowia 30 – 2000 The inclusion of adventive plants in the second edition of FloraPalaestina Danin, A.: The inclusion of adventive plants in the second edition of Flora Palaestina. – Willdenowia30: 305-314. 2000. – ISSN 0511-9618. Distribution maps for 19 prominent woody adventive gymnosperms, dicots and monocots, which areestablished in the Flora Palaestina area but not included in Flora Palaestina, ed. 1, are presented,showing their presence in grid areas of 5 7 5 km in Israel, and data on their introduction, habitats anddispersal modes are given in this preparatory contribution for the second edition of Flora Palaestina.