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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].

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.

Objective: To assess the causal prophylactic activity (activity against the pre-erythrocytic liver stage) of a daily regimen of doxycycline combined with low dose primaquine against malaria in Australian Defence Force personnel deployed to Papua New Guinea (PNG)., Participants and Setting: A 53-strong Australian Army engineer detachment deployed to the north coast of PNG for 42 days starting in July 1993., Interventions: The soldiers took doxycycline (100 mg) and primaquine (7.5 mg) daily, starting at least two days before they entered the endemic area and continuing for three days after their return to Australia. No primaquine eradication course was given at that time., Main Outcome Measures: The number of soldiers who developed malaria, plasma drug concentrations and drug side effects., Results: None of the 53 men developed malaria while in PNG. Three developed falciparum malaria two to three weeks after leaving the endemic area, although one of them had taken doxycycline alone because of glucose-6-phosphate dehydrogenase deficiency. Nine men developed vivax malaria between three and 40 weeks after leaving PNG, and three had relapses. Doxycycline was generally well tolerated, with only three of the men requiring a change of medication to mefloquine because of adverse gastrointestinal symptoms., Conclusions: Although doxycycline generally provides good protection against malaria infection, it cannot be relied on for causal prophylaxis, even when combined with low dose primaquine. Because the malaria infections occurred only after return to Australia, doxycycline appears to be effective in suppressing malaria while the drug is being taken. Intense, repeated exposure to malaria may require an extended period of chemoprophylaxis on return from an endemic area.

In 1980, the incidence of malaria among Southeast-Asian refugees arriving in South Australia rose substantially to 22.0 cases/1000 arrivals. All these cases were caused by Plasmodium vivax, and the majority occurred in the small proportion of refugees who had arrived by way of Indonesian camps of asylum (59.2 cases/1000 arrivals). The commencement of an eight-week prophylactic regimen with primaquine (22.5 mg/week) and chloroquine (300 mg/week; 600 mg first dose) by 1388 refugees proved significantly effective in reducing the incidence of malaria among this population. The regimen was administered without the assessment of glucose-6-phosphate dehydrogenase levels, and a transient haemoglobinuria occurred in only one refugee. Other side-effects were minimal when the administration of drugs was delayed until several days after the arrival of the refugee in Australia.