Malaria is endemic in much of our region, including Timor-Leste, and military personnel face a very real threat when deploying into malarious areas. During the first few weeks of Operation Warden in Timor-Leste in 1999, several malaria outbreaks occurred, directly impacting the fighting strength of Australia forces. In the first five months of the deployment, there were 64 cases of malaria detected in ADF personnel.
In 2000 and 2001 the Army Malaria Institute (AMI) conducted a trial of tafenoquine in Timor-Leste. In the years prior to that the US Army had been developing tafenoquine as a new anti-malarial drug to treat and prevent malaria in their soldiers, however the AMI needed to ensure that tafenoquine was also effective and well-tolerated in the ADF population. The AMI study was a double-blind, randomised controlled trial which is required for drug registration as it that provides a high level of evidence. Mefloquine was chosen as the comparator drug as, like tafenoquine, it is taken as a once weekly dose. At the time of this study, the principal drugs available for malaria prevention were doxycycline and mefloquine.
Participation in the study was offered to a battalion group deploying to Timor-Leste for a six month period. It was optional and voluntary. Efforts were made to ensure deploying personnel were fully informed of the risks and benefits of participation before they made their decision. They were given a written information sheet, a verbal briefing and were asked to sign a consent form. Those who chose to participate were also advised of the option to opt out or withdraw from the trials at any time with no detriment to their career or future health care.
Participation in the trials was not a pre-requisite for deployment. To provide deploying personnel with appropriate protection against malaria, those who chose to not participate in the trials were prescribed anti-malarial medication in accordance with extant health policy, which included doxycycline and mefloquine.
Three quarters of trial participants took tafenoquine, and one quarter took mefloquine. Mefloquine was already registered and in use in Australia at that time; tafenoquine was not. The study protocol was reviewed and approved by the then Australian Defence Medical Ethics Committee (ADMEC) before it was allowed to go ahead.
In all, 654 ADF personnel participated in this study: 492 took tafenoquine and 162 took mefloquine. These personnel were monitored closely during the study and for six months afterwards. Monitoring included blood tests to look for malaria and to check general health. A sub-group of 100 people were randomly chosen for more detailed assessment of their eyes and respiratory function.
The number of adverse events reported was similar in both groups. The most common event reported was gastrointestinal upset. An eye condition (vortex keratopathy) was seen in some people taking tafenoqine. This is a benign condition that does not affect vision and in all reported cases it resolved completely after the medication was stopped. This condition is also seen with other medications, including chloroquine and medications that are used in heart disease and cancer. No neurological or psychiatric side effects were reported, although 12% of both groups reported headaches.
Overall, the study found that tafenoquine appeared to be safe and well tolerated as malaria prophylaxis. This study has been published and is available at http://aac.asm.org/content/54/2/792.full.