Malaria in the Australian Defence Force: the Bougainville experience

During a 5-year period, almost 4000 Australian personnel served in the Papua New Guinean province of\ud Bougainville.\ud \ud 1.The first randomised, double-blind trial comparing Malarone (a combination of atovaquone and proguanil) with doxycycline was conducted during the deployment. Malarone was as effective as doxycycline and better tolerated.\ud \ud 2.Another trial compared a 3-day course of tafenoquine with the course of primaquine that was standard at that\ud time for post-exposure prophylaxis. There was no statistical difference in rates of malaria following either regimen.\ud \ud 3. There were 64 episodes of malaria affecting 50 individuals. This gave an attack rate of 41.6 malarious\ud episodes per 1000 man years. Most attacks occurred after the person had returned to Australia.\ud 4.The dosage of primaquine was increased partway through the deployment, from 22.5mg to 30mg per day.\ud \ud The attack rate fell from 67.1 to 13.2 per 1000 man years. The attack rate following tafenoquine post-exposure\ud ADF Health 2004; 5: 69-72 prophylaxis was 63.5 per 1000 man years

Mefloquine and doxycycline malaria prophylaxis in the Australian soldiers in East Timor

Objectives: To describe the tolerability of mefloquine in Australian soldiers for malaria prophylaxis, including a comparison with doxycycline.\ud \ud Design: Open-label, prospective study and cross-sectional questionnaire and interview.\ud \ud Setting and participants: Two contingents of Australian soldiers, each deployed to East Timor for peacekeeping duties over a 6-month period (April 2001–October 2001 and October 2001–May 2002).\ud \ud Outcome measures: Withdrawals during the study; adverse events relating to mefloquine prophylaxis; willingness to use mefloquine again on deployment.\ud \ud Results: Of 1157 soldiers starting on mefloquine, 75 (6.5%) withdrew because of adverse responses to the drug. There were three serious adverse events of a neuropsychiatric nature, possibly relating to mefloquine. Fifty-seven per cent of soldiers using mefloquine prophylaxis reported at least one adverse event, compared with 56% using doxycycline. The most commonly reported adverse effects of both drugs were sleep disturbance, headache, tiredness and nausea. Of the 968 soldiers still taking mefloquine at the end of their deployments, 94% indicated they would use mefloquine again. Of 388 soldiers taking doxycycline prophylaxis who were deployed with the first mefloquine study contingent, 89% indicated they would use doxycycline again.\ud \ud Conclusions: Mefloquine was generally well tolerated by Australian soldiers and should continue to be used for those intolerant of doxycycline

Comparison of self-reported and audiometrically-measured hearing loss in the Australian Defence Force

Objective: To investigate the relationship between self-reported and audiometrically-measured hearing loss in a sample of Australian Defence Force personnel. Design: Responses to a question regarding hearing problems were compared with contemporaneous audiometric data. Study sample: 3335 members of the Australian Defence Force for whom anonymised medical records were available. Results: The sensitivity of self-report data to identify higher-frequency hearing loss was lower than sensitivity at other frequencies, and positive predictive values were moderate to poor at all frequencies. Performance characteristics of self-report compared with audiometric data also varied with age, sex, and rank. Conclusions: While self-report hearing loss data have good performance characteristics for estimating prevalence of hearing loss as defined by audiometric criteria, this study indicates that the usefulness of self-report data in identifying individuals with hearing loss may be limited in this population

Advancing knowledge about the health issues of Australia's defence personnel and veterans

The Centre for Military and Veterans’ Health was established to specifically support the disciplines of military and veterans’ health in Australia. Key areas of research interest for CMVH include disease and injury prevention, wellness and rehabilitation, e-health and health services research. Of particular current interest are deployment and post-deployment physical and mental health of Australian Defence Force personnel, and the impact of deployment on their families

Population Pharmacokinetics of Tafenoquine during Malaria Prophylaxis in Healthy Subjects▿

The population pharmacokinetics of tafenoquine were studied in Australian soldiers taking tafenoquine for malarial prophylaxis. The subjects (476 males and 14 females) received a loading dose of 200 mg tafenoquine base daily for 3 days, followed by a weekly dose of 200 mg tafenoquine for 6 months. Blood samples were collected from each subject after the last loading dose and then at weeks 4, 8, and 16. Plasma tafenoquine concentrations were determined by liquid chromatography-tandem mass spectrometry. Population modeling was performed with NONMEM, using a one-compartment model. Typical values of the first-order absorption rate constant (Ka), clearance (CL/F), and volume of distribution (V/F) were 0.243 h−1, 0.056 liters/h/kg, and 23.7 liters/kg, respectively. The intersubject variability (coefficient of variation) in CL/F and V/F was 18% and 22%, respectively. The interoccasion variability in CL/F was 18%, and the mean elimination half-life was 12.7 days. A positive linear association between weight and both CL/F and V/F was found, but this had insufficient impact to warrant dosage adjustments. Model robustness was assessed by a nonparametric bootstrap (200 samples). A degenerate visual predictive check indicated that the raw data mirrored the postdose concentration-time profiles simulated (n = 1,000) from the final model. Individual pharmacokinetic estimates for tafenoquine did not predict the prophylactic outcome with the drug for four subjects who relapsed with Plasmodium vivax malaria, as they had similar pharmacokinetics to those who were free of malaria infection. No obvious pattern existed between the plasma tafenoquine concentration and the pharmacokinetic parameter values for subjects with and without drug-associated moderate or severe adverse events. This validated population pharmacokinetic model satisfactorily describes the disposition and variability of tafenoquine used for long-term malaria prophylaxis in a large cohort of soldiers on military deployment

Self-reported tinnitus and ototoxic exposures among deployed Australian defence force personnel

The objective of this study was to investigate the effect of chemical and environmental exposures during deployment on tinnitus among Australian Defence Force personnel previously deployed to Bougainville and East Timor. Participants were asked to self-report recent occurrence and severity of "ringing in the ears," and identify any chemical and environmental exposures during their deployment. Self-reported exposure to loud noises, heavy metals, intense smoke, engine exhaust, solvents and degreasing agents, and chemical spills increased the risk of self-assessed moderate or severe tinnitus. Daily exposure to 4 or more ototoxic factors was associated with 2- to 4-fold increase in the risk. In addition to loud noises, chemical exposures may also play a role in the development of tinnitus among Australian Defence Force personnel serving overseas

Randomized, Double-Blind Study of the Safety, Tolerability, and Efficacy of Tafenoquine versus Mefloquine for Malaria Prophylaxis in Nonimmune Subjects▿

This study represents the first phase III trial of the safety, tolerability, and effectiveness of tafenoquine for malaria prophylaxis. In a randomized (3:1), double-blinded study, Australian soldiers received weekly malaria prophylaxis with 200 mg tafenoquine (492 subjects) or 250 mg mefloquine (162 subjects) for 6 months on a peacekeeping deployment to East Timor. After returning to Australia, tafenoquine-receiving subjects received a placebo and mefloquine-receiving subjects received 30 mg primaquine daily for 14 days. There were no clinically significant differences between hematological and biochemical parameters of the treatment groups. Treatment-related adverse events for the two groups were similar (tafenoquine, 13.4%; mefloquine, 11.7%). Three subjects on tafenoquine (0.6%) and none on mefloquine discontinued prophylaxis because of possible drug-related adverse events. No diagnoses of malaria occurred for either group during deployment, but 4 cases (0.9%) and 1 case (0.7%) of Plasmodium vivax infection occurred among the tafenoquine and mefloquine groups, respectively, up to 20 weeks after discontinuation of medication. In a subset of subjects recruited for detailed safety assessments, treatment-related mild vortex keratopathy was detected in 93% (69 of 74) of tafenoquine subjects but none of the 21 mefloquine subjects. The vortex keratopathy was not associated with any effect on visual acuity and was fully resolved in all subjects by 1 year. Tafenoquine appears to be safe and well tolerated as malaria prophylaxis. Although the volunteers' precise exposure to malaria could not be proven in this study, tafenoquine appears to be a highly efficacious drug for malaria prophylaxis

Long term immunity to live attenuated Japanese encephalitis chimeric virus vaccine: Randomized, double-blind, 5-year phase II study in healthy adults

In a randomized, double-blind study, 202 healthy adults were randomized to receive a live, attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) and placebo 28 days apart in a cross-over design. A subgroup of 98 volunteers received a JE-CV booster at month 6. Safety, immunogenicity and persistence of antibodies to month 60 were evaluated

Concomitant or sequential administration of live attenuated japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine: Randomized double-blind phase II evaluation of safety and immunogenicity

A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever (YF) vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered sequentially