Influenza Outbreak During Exercise Talisman Sabre, Queensland, Australia, July 2019.

Influenza appeared in Queensland, Australia during Exercise Talisman Sabre (TS-19) in July 2019 with an early focus within the New Zealand Defence Force members arriving in Australia aboard HMNZS Canterbury. A total of 76 cases of influenza-like illness (ILI) were reported, of which 43 were confirmed by rapid diagnostic tests to be influenza A (n=32) and B (n=11). Australia's influenza season (starting in March, peaked in July 2019) exposed large numbers of military members to a virus for which they had been suboptimally immunized either because of low uptake of the Southern Hemisphere vaccine by Australians/New Zealanders who were not mandated to be immunized, or because U.S. soldiers had received only the Northern Hemisphere vaccine for the 2018-2019 season. A low-intensity clinical unit separate from the main exercise was used as a means of isolating ILI cases both to facilitate their treatment and limit disease spread. Despite disease rates of <1%, influenza still had a major impact on TS-19 mostly in terms of the considerable medical resources required to manage ILI.

Assessment of revised recruitment standards for asthma in the Australian Defence Force.

OBJECTIVE: To assess the impact of relaxed asthma recruitment standards adopted by the Australian Defence Force in 2007. METHODS: A retrospective audit was conducted on clinical and administrative data for recruits, with and without mild asthma, in their first year of service. RESULTS: There was no evidence that mild asthmatics experienced worse outcomes than nonasthmatic recruits. Mild asthmatics had fewer illnesses and restricted duty days and were less costly compared to other recruits. There was no difference in the rate of discharge (attrition) between those with and without mild asthma. CONCLUSIONS: The revised recruitment standards for asthma in the Australian Defence Force have not resulted in unanticipated medical or administrative costs to the organization. Health and administrative outcomes differed little between mild asthmatics and nonasthmatic recruits in their first 12 months of service.

Self-management and rehabilitation in osteoarthritis: is there a place for internet-based interventions?

The electronic databases Cochrane, MEDLINE, and SCOPUS were searched to collect evidence on the impact of community-based Internet interventions for adult patients with osteoarthritis (OA) on health outcomes. Five studies met our review criteria. We found that Internet-based OA self-management interventions modestly but significantly improved four of six health status measures compared with usual care and have been met with high acceptance and high user satisfaction. Preventive physiotherapy exercise delivered via videoconferencing for patients with OA-related knee pain significantly improved health measures including pain, stiffness, and physical function compared with the initial health status. Postoperative rehabilitation performed by a physical therapist via videoconferencing and "in-person" resulted in similar health measure improvements. The review findings show that the Internet may be successfully used as a medium for providing community-based self-management and rehabilitation interventions in OA.

The health and cost implications of high body mass index in Australian defence force personnel.

BACKGROUND: Frequent illness and injury among workers with high body mass index (BMI) can raise the costs of employee healthcare and reduce workforce maintenance and productivity. These issues are particularly important in vocational settings such as the military, which require good physical health, regular attendance and teamwork to operate efficiently. The purpose of this study was to compare the incidence of injury and illness, absenteeism, productivity, healthcare usage and administrative outcomes among Australian Defence Force personnel with varying BMI. METHODS: Personnel were grouped into cohorts according to the following ranges for (BMI): normal (18.5 - 24.9 kg/m2; n = 197), overweight (25-29.9 kg/m2; n = 154) and obese (≥30 kg/m2) with restricted body fat (≤28% for females, ≤24% for males) (n = 148) and with no restriction on body fat (n = 180). Medical records for each individual were audited retrospectively to record the incidence of injury and illness, absenteeism, productivity, healthcare usage (i.e., consultation with medical specialists, hospital stays, medical investigations, prescriptions) and administrative outcomes (e.g., discharge from service) over one year. These data were then grouped and compared between the cohorts. RESULTS: The prevalence of injury and illness, cost of medical specialist consultations and cost of medical scans were all higher (p < 0.05) in both obese cohorts compared with the normal cohort. The estimated productivity losses from restricted work days were also higher (p < 0.05) in the obese cohort with no restriction on body fat compared with the normal cohort. Within the obese cohort, the prevalence of injury and illness, healthcare usage and productivity were not significantly greater in the obese cohort with no restriction on body fat compared with the cohort with restricted body fat. The number of restricted work days, the rate of re-classification of Medical Employment Classification and the rate of discharge from service were similar between all four cohorts. CONCLUSIONS: High BMI in the military increases healthcare usage, but does not disrupt workforce maintenance. The greater prevalence of injury and illness, greater healthcare usage and lower productivity in obese Australian Defence Force personnel is not related to higher levels of body fat.

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.

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.

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. There were no unexpected adverse events (AEs) and the incidence of AEs between JE-CV and placebo were similar. There were three serious adverse events (SAE) and no deaths. A moderately severe case of acute viral illness commencing 39 days after placebo administration was the only SAE considered possibly related to immunization. 99% of vaccine recipients achieved a seroprotective antibody titer ≥ 10 to JE-CV 28 days following the single dose of JE-CV, and 97% were seroprotected at month 6. Kaplan Meier analysis showed that after a single dose of JE-CV, 87% of the participants who were seroprotected at month 6 were still protected at month 60. This rate was 96% among those who received a booster immunization at month 6. 95% of subjects developed a neutralizing titer ≥ 10 against at least three of the four strains of a panel of wild-type Japanese encephalitis virus (JEV) strains on day 28 after immunization. At month 60, that proportion was 65% for participants who received a single dose of JE-CV and 75% for the booster group. These results suggest that JE-CV is safe, well tolerated and that a single dose provides long-lasting immunity to wild-type strains.

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 vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

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.

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 (K(a)), 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.

Tafenoquine for the treatment of recurrent Plasmodium vivax malaria.

Tafenoquine was used to treat Plasmodium vivax malaria cases who had previously failed treatment with chloroquine and primaquine. Chloroquine was followed by a loading dose of tafenoquine (200 mg base/day for 3 days) and 200 mg a week was given for 8 weeks. One of 27 treated patients relapsed after 6 months of observation. A standard course of chloroquine administered with 8 weeks of tafenoquine may be more effective than chloroquine with primaquine (22.5 mg/day for 14 days) in preventing additional P. vivax relapses. Larger studies are required to optimize the combination, but our findings suggest that an extended use of tafenoquine may be required to prevent relapses of primaquine-tolerant strains of P. vivax malaria.

Immunogenicity and safety of two live-attenuated tetravalent dengue vaccine formulations in healthy Australian adults.

We conducted a Phase 1b study to evaluate the immunogenicity and safety of two live attenuated tetravalent dengue vaccines in healthy adult volunteers. After one injection, all subjects reported systemic reactions consistent with a mild dengue-like syndrome. Seven volunteers developed dengue 3 viraemia after vaccination. All subjects developed a neutralizing antibody response against serotype 3 with partial response against other serotypes. The trial was stopped early (after 10 subjects enrolled) due to formulation issues, which were related to the dengue 3 vaccine component. Managing viral interference and balancing attenuation to produce acceptable tetravalent immunogenicity with minimal reactogenicity may be a recurring problem for future multivalent live vaccines.

Comparative safety and efficacy of subcutaneous and intradermal administration of inactivated Japanese encephalitis vaccine during predeployment preparations in the Australian Defence Force.

Japanese encephalitis is a viral disease emerging in areas of influence for the Australian Defence Force immediately north of the continent, including the Torres Strait border of Australia and Papua, New Guinea. Only the mouse brain-derived, inactivated, Nakayama strain vaccine is commercially available to the Australian Defence Force. This vaccine has a high cost and significant adverse event profile, requiring restricted duties after administration. To address these issues, intradermal vaccination (either single intradermal administration or two intradermal injections at two separate sites) was assessed, compared with the conventional subcutaneous vaccination method, in a randomized controlled trial among soldiers preparing for deployment. Dual intradermal vaccination (0.1 mL at two sites) was found to have a slightly more favorable adverse event profile while maintaining comparable serological efficacy and reduced cost. An expansion of the concept and a test of logistics were conducted by vaccinating a battalion formation during predeployment medical preparations. The method of vaccination was well accepted and retained comparable immunogenicity.

Adequate primaquine for vivax malaria.

BACKGROUND: Treatment of vivax malaria with primaquine prevents the relapse of infection from residual liver stages of the parasite. Inadequate dosage is related to a higher relapse risk. METHODS: A comparison was made of vivax malaria relapse-prevention treatments with primaquine 22.5 mg or 30 mg daily for 14 days on 146 reports to the Australian Army Central Malaria Register. RESULTS: The lower dose of primaquine was found to carry a relative risk of 6.63 for a relapse of vivax malaria compared with the higher dose. CONCLUSIONS: The available data presented here suggest that vivax malaria in this region is increasingly tolerant of the 22.5 mg daily treatment regimen of primaquine and that the greater dose of at least 30 mg daily is more effective.

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

OBJECTIVES: To describe the tolerability of mefloquine in Australian soldiers for malaria prophylaxis, including a comparison with doxycycline. DESIGN: Open-label, prospective study and cross-sectional questionnaire and interview. 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). OUTCOME MEASURES: Withdrawals during the study; adverse events relating to mefloquine prophylaxis; willingness to use mefloquine again on deployment. 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. CONCLUSIONS: Mefloquine was generally well tolerated by Australian soldiers and should continue to be used for those intolerant of doxycycline.

Treatment of acute vivax malaria with tafenoquine.

Tafenoquine is an 8-aminoquiniline related to primaquine with pre-clinical activity against a range of malaria species. We treated two acute cases of vivax malaria with tafenoquine (800 mg over three days) alone, instead of conventional chloroquine (1500 mg over three days) and primaquine (420 mg over 14 days). In addition to the convenience of this regimen, the rapid parasite clearances observed, coupled with a good clinical response and lack of recrudescence or relapse, indicate that further investigation of tafenoquine in the treatment of vivax malaria is warranted.

An outbreak of malaria in a forward battalion on active service in East Timor.

An outbreak of malaria first developed within Second Battalion Royal Australian Regiment, a forward (Australian) Battalion of the International Force in East Timor in October 1999. Before the Battalion redeployed to Australia, 17 cases had occurred and in the 12 months following return to Australia another 89 cases have occurred, including 18 single recurrences and 2 second recurrences. The overall attack rate for this deployment of 4 months, mostly including the wet season of Timor, has been 13.5%. The attack rate for the Battalion (5/7 Royal Austarlian Regimen) subsequently occupying this ground (for approximately 4 months and including the 12 months following redeployment) was 5.2%. Investigation of the initial outbreak and comparisons with the subsequent Battalion suggest major risk factors for contracting malaria were side effects from doxycycline, involvement in night operations, lack of preventive medicine support, and the location of platoon positions.