The Army Malaria Institute (AMI), then known as the Army Malaria Research Unit (AMRU), was involved in several studies in 1989 that compared existing anti-malarial medications with newer anti-malarials in different dosing schedules. By the late 1980s it had become clear that anti-malarial measures of the time were failing and something had to be done to ensure that Australian soldiers would be protected from malaria. Chloroquine, folate and primaquine resistance was increasing and standard anti-malarial prophylaxis regimens were losing their effectiveness. The studies in 1989 sought to find a more effective and suitable prophylaxis regimen.
The Special Air Service Regiment (SASR) regularly conducted field exercises in Papua New Guinea (PNG) in the l980s where the incidence of malaria was high (around 20%) despite the use of protective measures, including anti-malarial medication. At that time, the usual anti-malarials taken for malaria prevention (prophylaxis) were chloroquine and Maloprim (dapsone/pyrimethamine). These were taken together once a week commencing two weeks before departure and continuing for four weeks after return. A two week course of primaquine would also be taken when leaving the malarious area to eradicate any malaria parasites that might still have been present in the body. Other malaria prevention measures used included the use of long sleeves and trousers after dark, mosquito nets, and insect repellents applied to skin and clothing.
In 1988 the SASR deployed 99 soldiers to PNG for a field exercise. One soldier became sick with malaria while taking prophylaxis and 22 suffered malaria attacks after completing prophylaxis and the eradication course of primaquine. Several soldiers were infected with two types of malaria. These attack rates (25%) despite taking the assigned medications were similar to those seen in WWII in the Pacific, and higher than that during the Vietnam War (see History).
The timing and type of malaria strongly suggested that the weekly Maloprim/chloroquine was no longer protective against malaria and that the current primaquine eradication regimen was becoming less effective in preventing relapses (malaria occurring after return to Australia).
Anti-malarial comparison studies
In 1989, AMI (then AMRU) participated in a study involving troops deploying to PNG, Malaysia and Thailand. This study aimed to answer questions about whether the problem was drug resistance or failure of soldiers to take the anti-malarial medications properly. The study included field testing of the anti-malarial medication mefloquine (which had been registered in Australia for malaria treatment the year before in1988) to determine its effectiveness in preventing malaria compared to Maloprim and chloroquine. Doxycycline was also tested in a similar manner, as there was evidence that it had anti-malarial properties and was becoming more commonly used for malaria prophylaxis. The 1989 Australian National Health and Medical Research Council Malaria Guidelines for Medical Practitioners recommended both mefloquine and doxycycline for areas with drug resistant malaria. Primaquine was taken for malaria eradication on return to Australia.
The outcomes of the studies are detailed in an article published in the Medical Journal of Australia. The study concluded that both doxycycline and mefloquine were very effective in preventing malaria while deployed as no one taking either of these medications got malaria while overseas. After return to Australia, 10% of those who had taken mefloquine and 20% of those who had taken doxycycline got malaria (relapsing malaria). Of those who took doxycycline and primaquine together for prophylaxis, no one got malaria, either during deployment or after return to Australia. Blood testing confirmed that all the medications were being taken properly (blood levels of the medications were in the protective range).
These outcomes suggested that primaquine alone as eradication was not effective in preventing malaria on return to Australia, but that in combination with doxycycline it might be. This study recommended that further studies be done to define the optimal anti-malarial prophylaxis.
The most significant finding of this study was that everyone on doxycycline/primaquine prophylaxis was protected against relapsing malaria. It has since become ADF practice to continue malaria prophylaxis during the primaquine eradication course. The challenge of complying with the full eradication course has led to further studies to work out the most suitable primaquine dosing schedule, as well as the development of alternatives to primaquine, such as tafenoquine.
While both doxycycline and mefloquine were shown to be effective in preventing malaria while deployed, doxycycline was subsequently chosen to be the first line (routine first choice) anti-malarial for the ADF. Doxycycline was a well established medicine with many years of experience in its use and a known range of side effects. As an antibiotic, it was also effective against other infections commonly seen in the field, such as leptospirosis and scrub typhus. Mefloquine was a much newer drug with a smaller experience base and a risk, albeit small, of neuropsychiatric adverse effects. Mefloquine was therefore the second choice for malaria prophylaxis. Later, after Malarone (atovaquone/proguanil) became available, mefloquine became the third line anti-malarial for the ADF.