Objective: To determine whether azithromycin, 250 mg/d, is effective prophylaxis for liver infection or for both liver and subsequent blood infection with Plasmodium falciparum.
Design: Controlled phase II trial with two cohorts entered sequentially.
Setting: Clinical trials center of Walter Reed Army Institute of Research, Washington, D.C.
Patients: Each of the two cohorts consisted of 12 normal adult volunteers who had not had malaria during the previous 2 years: 10 who received azithromycin prophylaxis and 2 controls who did not receive treatment.
Intervention: For cohort 1, prophylactic efficacy against liver infection alone during the initial 7 days of the infection was determined by loading participants with azithromycin before challenge with P. falciparum-infected mosquitoes on day 0 and by then giving the drug for 7 days after the challenge. The regimen was 500 mg on day 14 before the challenge, followed by 250 mg/d from day 13 before the challenge through day 7 after the challenge. For cohort 2, prophylactic efficacy against both the liver infection and the subsequent blood infection was determined by continuing drug administration for 28 days after the challenge.
Measurements: Plasmodium falciparum infection was diagnosed through peripheral blood smears obtained up to 70 days after challenge. Malarial symptoms and adverse drug reactions were also monitored.
Results: In cohort 1, 4 of 10 volunteers who received azithromycin prophylaxis (40%) did not develop parasitemia. In cohort 2, none of the 10 volunteers receiving azithromycin prophylaxis (100%) developed parasitemia. For each cohort, both control volunteers became parasitemic on days 9 through 13 after the challenge. Adverse drug reactions were few and mild.
Conclusions: In this model, prophylaxis with azithromycin (250 mg/d) was partially effective against liver parasites and completely successful against the combination of liver and blood parasites. These data suggest that azithromycin has the potential to be an effective, well-tolerated clinical prophylactic agent for P. falciparum malaria.