Because anti-malarial medications used for prevention are not 100% effective (no medication is) it is possible that someone might be infected with malaria but not show symptoms until they stop taking their anti-malarial medication. This is called relapsing malaria. To reduce the risk posed to ADF members returning from malarious areas at the end of their deployments they are prescribed additional medication to kill off any malaria parasites that may be in the body.
Primaquine is particularly good at killing any residual malaria that may be present and preventing a relapse of malaria. Because of this it is commonly used by troops returning from deployment to malarious areas. However there has been evidence to suggest that malaria parasites may have developed resistance to primaquine, making it less effective. As such the Army Malaria Institute (AMI) has studied alternative dosing schedules and medications (tafenoquine) to try to optimise the protection against malaria for ADF personnel.
Evaluation of tafenoquine for the post-exposure prophylaxis of vivax malaria in Australian soldiers 1998-2000
The aim of this study was to compare the effectiveness and tolerability (side effects) of tafenoquine and primaquine in preventing malaria relapses. Participants either took the standard 14 day eradication course of primaquine (three doses per day) or three days of tafenoquine (either as a single or a split dose). They were followed up for 12 months after completion of the eradication course to see if they became ill with malaria.
This study was reviewed and approved by the Australian Defence Medical Ethics Committee (now the Australian Defence Human Research Ethics Committee) and ADF personnel deployed to Bougainville (PNG) in 1998/1999 and Timor Leste in early 2000 were invited to participate in this study. These personnel were briefed about the study, given a written information sheet and the opportunity to ask questions. Those who chose to participate then signed the study consent form and were provided a copy. The consent form included information on their right to withdraw from the study at any time without any consequences.
Those who chose not to participate received the standard primaquine eradication course. Those who agreed to participate were randomly assigned primaquine or tafenoquine for malaria eradication (1,017 ADF members took tafenoquine). Participants were given an ID card which had information for their doctor in the event that they became unexpectedly unwell.
For both primaquine and tafenoquine, the most common reported side effects were gastro-intestinal; nausea, abdominal cramps and diarrhoea. Other side effects reported were headache and lethargy. These side effects were generally mild or moderate, and did not interfere with daily activities.
During the 12 month follow up period of personnel returning from Bougainville, the proportion of participants who developed malaria was 3% of the group taking primaquine and 2% of the group taking tafenoquine. The malaria rates in Timor Leste participants were similar. In this study, tafenoquine was shown to be neither more nor less effective in preventing relapsing malaria than primaquine, but the feedback received suggested it was generally preferred by the participants as it was a much shorter course of tablets than the primaquine schedule.
Use of tafenoquine for treatment of malaria
During the East Timor deployments from 1999, more than 400 cases of malaria occurred in ADF personnel, mostly after returning to Australia (see History). These personnel had taken doxycycline for malaria prophylaxis and primaquine for eradication. For those personnel whose malaria was treated with the standard chloroquine and primaquine treatment schedule, just over 50% were cured. As the decreasing effectiveness of primaquine had become a concern, an alternative treatment regimen using chloroquine and tafenoquine was identified to see if it could be a more effective way of treating malaria.
ADF personnel who had a confirmed diagnosis of vivax (relapsing) malaria were given the option of taking tafenoquine after previous treatments had failed. Because tafenoquine is not registered in Australia, approval to use this medication was obtained from the Therapeutic Goods Administration (TGA). Each participant gave informed consent before taking tafenoquine. Of the 31 personnel who commenced this treatment regimen, 27 completed the full eight week course of treatment. Treatment was stopped early for 4 participants when the tafenoquine prophylaxis trial being done at the same time in East Timor identified a previously unknown side-effect (vortex keratopathy – a benign eye condition which resolves completely after the medication is stopped).
During the treatments with tafenoquine, no adverse events were reported and the medication was well tolerated. One patient had a further relapse of malaria after completing treatment, meaning the cure rate recorded was 96%. The outcomes of the treatment trial were published in an article which is available here.