Jmvh.org
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
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Venue: Trentham Military Camp
Regional symposium
Wellington, New Zealand
Date: Saturday 21st March 2015
oN Ballistics aNd
Time: 0900 - 1700
combat Facial trauma
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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
for Malaria
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
regimens
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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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.
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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.
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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
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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.
105. Kitchener S. The military significance of Japanese encephalitis. Aust Mil Med 2003; 12(3): 126-131.
106. Kitchener S, Baade L, Brennan L, Nasveld P. Intradermal boosting of Japanese encephalitis vaccination.
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107. Kitchener S, Baade L, Brennan L. When should travelers from nonendemic areas for flaviviruses receive
booster vaccination for Japanese encephalitis? J Trav Med 2003; 10(1): 50-51.
108. Nasveld PE, Ebringer A, Elmes N, Bennett S, Yoksan S, Aaskov J, McCarthy K, Kanesa-thasan N, Meric
C, Reid M. Long term immunity to live attenuated Japanese encephalitis chimeric virus vaccine. Randomized, double-blind, 5-year phase II study in healthy adults. Human Vaccines 2010; 6(12): 1038-1046.
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110. Reid M, Mackenzie D, Baron A, Lehmann N, Lowry K, Aaskov J. Experimental infection of Culex
annulirostris, Culex gelidus, and Aedes vigilax with a yellow fever/Japanese encephalitis virus vaccine chimera (Chimerivax™-JE). Am J Trop Med Hyg 2006; 75(4): 659-663.
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
PTSD.
Keywords: Veterans, Posttraumatic Stress Disorder, Mild Traumatic Brain Injury, Nurse Practitioners,
Treatment
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: [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
Afghanistan.
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:
Presentation 3:
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.
References:
References:
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.
Infection, 135, 733-9.
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: michelle.mcinnes@defence.
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.[5] 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
Advertising
Submission
Submission
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]
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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
Source: http://jmvh.org/wp-content/uploads/2015/01/AMMA_JMVH_web-v4.pdf
ESTANDAR ECOCERT REFORESTACION SOLIDARIA Proyectos de reforestación solidaria y de agroforestería sostenible Versión 0 Fecha de publicación: 04/04/2012 El presente estándar esta protegido por las disposiciones del Código de propiedad intelectual, incluidas las disposiciones relativas a la propiedad literaria y artística y a los derechos de autor. Ecocert Environnement tiene la propiedad exclusiva sobre estos derechos. Toda reproducción integral o parcial, por cualquier medio, no autorizada por Ecocert Environnement o sus derechohabientes, está estrictamente prohibida.
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.
