Primaquine Prophylaxis for Malaria
Abstract & Commentary
Synopsis: Although mefloquine and doxycycline are highly effective for malaria prophylaxis, the actual or perceived toxicity of such agents, as well as growing mefloquine resistance, have prompted the evaluation of alternative prophylactic regimens.
Source: Soto J, et al. Primaquine prophylaxis against malaria in nonimmune Colombian soldiers: Efficacy and toxicity. Ann Intern Med 1998;129:241-244.
This recent study of prophylactic antimalarial therapy involved a double-blind, placebo-controlled evaluation of primaquine prophylaxis in nonimmune Colombian soldiers performed by Soto and associates and the Walter Reed Army Institute of Research (WRAIR).
The study was performed in 176 male soldiers during a 15-week patrol in a malarious region, after which they returned to barracks duty in a nonmalarious area. Subjects were randomly allocated to prophylaxis with 30 mg daily of oral primaquine diphosphate (2 tablets of 15 mg base each) or identical-appearing placebo tablets—during the 15 weeks of malaria exposure and for one week upon return to a nonmalarious area. Thick and thin smears were obtained either weekly or earlier, if participants had symptoms of malaria, and follow-up smears were continued for four weeks. The protective efficacy of primaquine (122 soldiers) was 89% (95%; CI 75-96%) against all types of malaria (i.e., 94% against P. falciparum malaria and 85% [CI 57-95%] against P. vivax malaria). Six primaquine recipients had mild-to-moderate gastrointestinal distress.
Comment by Michele Barry, MD
Although the efficacy demonstrated in this study of primaquine prophylaxis at preventing P. falciparum and P. vivax infection is similar to that reported in another study performed in Indonesia,1 there are some serious problems with the short-term follow-up period of three weeks after primaquine was discontinued. Clearly, parasitemia can occur with both P. falciparum and P. vivax infections after three weeks, so a larger question remains as to whether Soto et al simply achieved impressive suppression with primaquine, rather than malaria prevention per se. Moreover, each participant was classified as having malaria if he or she demonstrated either a parasitemia level of at least 1500 organisms/mL or a lower parasitemia level associated with two symptoms compatible with malaria, such as fever, headache, or nausea. A low level of parasitemia without symptoms was not considered a study end point, which may be an unacceptable scenario for a nonimmune traveler, as most travelers with low-level parasitemia will eventually declare themselves with the appearance of clinical malaria.
Thus, although travelers may be reluctant to take doxycycline or mefloquine, it is not clear to this reviewer that this study proves primaquine to be as efficacious as Soto et al have concluded in both their summary and discussion.
Reference
1. Fryayff DJ, et al. Randomized placebo-controlled trial of primaquine for prophylaxis of falciparum and vivax malaria. Lancet 1995;346:1190-1193.
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