Tafenoquine is being developed for radical cure and post-exposure prophylaxis of Plasmodium vivax malaria. In an open-label study, 1512 Australian Defence Force personnel received one of three tafenoquine 3 d regimens [400 mg once daily (od), 200 mg twice daily (bid), 200 mg od] or daily primaquine (22.5 mg) plus doxycycline (100 mg) over 14 d in Bougainville and in Timor-Leste for post-exposure prophylaxis. The relapse rate of subjects treated in Bougainville with tafenoquine (n=173) was 1.2% (200 mg bid x 3 d) and 2.3% (400 mg od x 3 d), while primaquine plus doxycycline (n=175) was 3.4%. For subjects treated in Timor-Leste with tafenoquine (n=636), the relapse rate was 4.9% (200 mg od x 3 d), 5.3% (200 mg bid x 3 d) and 11.0% (400 mg od x 3d), while primaquine plus doxycycline (n=289) was 10.0%. The most frequent adverse events reported across all groups were nausea, abdominal distress and diarrhoea. There was a dose-dependent reduction in adverse events with a reduced dose of tafenoquine, with the lowest dose (total 600 mg over 3 d) producing rates of adverse events equivalent to that of primaquine plus doxycycline. The much shorter dosing regimen of tafenoquine should increase compliance, which is often suboptimal with primaquine after leaving an endemic area. [Australian New Zealand Clinical Trials Registry Number 12607000588493].

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The pharmacokinetics of primaquine have been well defined in male volunteers, but there is little data on the disposition of the drug in women. We compared the kinetics of primaquine in nine male and nine female healthy Australian volunteers after the administration of a single oral dose (30 mg base) of primaquine. No statistical differences were observed in the following kinetic parameters of primaquine between men and women, respectively: maximum plasma concentration (93 +/- 26 and 115 +/- 38 ng/mL; 95% confidence interval [CI] of the mean difference: -55 to 10 ng/mL; P = 0.16), area under the curve (1.1 +/- 0.5 and 1.2 +/- 0.4 microg x h/mL; 95% CI: -0.6 to 0.3 microg x h/mL; P = 0.54), and clearance (0.34 +/- 0.12 and 0.39 +/- 0.14 L/h/kg; 95% CI: -0.17 to 0.08 L/h/kg; P = 0.46). The clinical relevance of such findings would suggest that sex does not have to be taken into account as a factor when prescribing primaquine for radical cure or terminal prophylaxis of Plasmodium vivax malaria.

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.

We report here a retrospective analysis of all malaria cases in military personnel reported to the Australian Defence Force (ADF) Central Malaria Register from 1998 to 2007. A total of 637 cases of malaria were notified affecting 487 individuals. Of these 85.9% (547) were infected with Plasmodium vivax malaria and 10.2% (65) with P. falciparum malaria. The majority of cases were from Timor Leste (78.5%, 501/637). Malaria attack rates of 0.9% (369/40 571), 1.1% (52/4776) and 0.4% (20/5345) were seen in Timor Leste, Bougainville and the Solomon Islands, respectively. The median period following departure from a malarious country to presentation of P. falciparum was 17 d (range 1-47 d) and for a primary presentation of P. vivax malaria was 86 d (range 1-505 d). Increasing the dose of primaquine from 22.5 mg daily to 30 mg daily for 14 d for radical cure of P. vivax malaria reduced the failure rate from 46.6% (35/75) to 9.4% (17/181) in subjects returning from Timor Leste. Malaria remains a serious problem for ADF soldiers deploying to malarious areas, particularly the incidence of relapsing vivax malaria and the tolerance of these vivax strains to primaquine.