Objective: To assess the causal prophylactic activity (activity agains
t the pre-erythrocytic liver stage) of a daily regimen of doxycycline
combined with low dose primaquine against malaria in Australian Defenc
e 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. Intervention
s: The soldiers took doxycycline (100 mg) and primaquine (7.5mg) daily
, starting at least two days before they entered the endemic area and
continuing for three days after their return to Australia. No primaqui
ne eradication course was given at that time. Main outcome measures: T
he number of soldiers who developed malaria, plasma drug concentration
s and drug side effects, Results: None of the 53 men developed malaria
while in PNG. Three developed falciparum malaria two to three weeks a
fter leaving the endemic area, although one of them had taken doxycycl
ine alone because of glucose-6-phosphate dehydrogenase deficiency. Nin
e 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 meflo
quine because of adverse gastrointestinal symptoms. Conclusions: Altho
ugh doxycycline generally provides good protection against malaria inf
ection, it cannot be relied on for causal prophylaxis, even when combi
ned 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.