Recent military experience with malaria chemoprophylaxis

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Abstract
Objective To assess the value of various drug regimens for malaria prophylaxis under circumstances where dapsone and pyrimethamine (combined as Maloprim) and chloroquine, followed by the 14‐day primaquine eradication course, were no longer effective in protecting military personnel against falciparum and vivax malaria. Design, setting and participants Various drug regimens given to four groups of healthy male members of the Australian Army during training exercises in malarious countries. Interventions Four groups of soldiers were given different regimens for 3–12 weeks: Group 1 — mefloquine (250 mg weekly); Group 2 — doxycycline (100 mg daily); Group 3 — doxycycline (100 mg daily) and primaquine (7.5 mg daily); and Group 4 — doxycycline (50 mg daily) and chloroquine (300 mg weekly). Except in Group 3, each of these regimens was followed by a 7.5 mg dose of primaquine three times a day for two weeks. Main outcome measures The proportion of participants in the various prophylactic drug groups who developed falciparum or vivax malaria during or after the intervention. Results Group 1: 40 men receiving mefloquine were all protected against falciparum malaria but four (10%) developed vivax malaria. These results were not statistically different from those obtained for either falciparum (P = 0.28) or vivax (P = 0.36) malaria in the control group of 64 men receiving Maloprim and chloroquine. Group 2: 60 men receiving doxycycline (no control group) were all protected against falciparum malaria but two developed vivax malaria. Group 3: 124 men, of whom 55 received doxycycline and 69 primaquine in addition to doxycycline, were all protected against falciparum malaria. However, 13 men taking only doxycycline developed vivax malaria two to three weeks after prophylaxis, whereas no vivax infections were observed in the men taking the drug combination (P = 0.0001). Group 4: no malaria infections were observed in 125 men receiving doxycycline and chloroquine for 13 weeks, probably because of the low prevalence of malaria in the training area. Conclusions These studies confirm that doxycycline is very effective in preventing falciparum malaria and, for the first time, also suggest that doxycycline used in combination with small doses of primaquine may prevent (not only suppress) vivax malaria. If further studies confirm these findings, the use of such a drug combination would reduce the incidence of both vivax and falciparum malaria in returning travellers. For individuals with a high risk of exposure to malaria, it would also forestall the need to take the bothersome primaquine eradication course.