PROPHYLAXIS OF PLASMODIUM-FALCIPARUM MALARIA WITH AZITHROMYCIN ADMINISTERED TO VOLUNTEERS

Objective: To determine whether azithromycin, 250 mg/d, is effective p rophylaxis for liver infection or for both liver and subsequent blood infection with Plasmodium falciparum. Design: Controlled phase II tria l with two cohorts entered sequentially. Setting: Clinical trials cent er of Waiter Reed Army Institute of Research, Washington, D.C. Patient s: Each of the two cohorts consisted of 12 normal adult volunteers who had not had malaria during the previous 2 years: 10 who received azit hromycin prophylaxis and 2 controls who did not receive treatment. Int ervention: For cohort 1, prophylactic efficacy against liver infection alone during the initial 7 days of the infection was determined by lo ading participants with azithromycin before challenge with P falciparu m-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 chall enge, followed by 250 mg/d from day 13 before the challenge through da y 7 after the challenge. For cohort 2, prophylactic efficacy against b oth the liver infection and the subsequent blood infection was determi ned by continuing drug administration for 28 days after the challenge. Measurements: Plasmodium falciparum infection was diagnosed through p eripheral blood smears obtained up to 70 days after challenge. Malaria l 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 thro ugh 13 after the challenge. Adverse drug reactions were few and mild. Conclusions: In this model, prophylaxis with azithro-mycin (250 mg/d) was partially effective against liver parasites and completely success ful against the combination of liver and blood parasites. These data s uggest that azithromycin has the potential to be an effective, well-to lerated clinical prophylactic agent for P. falciparum malaria.