Taylor, W.R.J.; (2004) Clinical trials of new strategies for the prevention and treatment of Plasmodium falciparum and Plasmodium vivax malaria in north eastern Papua, Indonesia. Doctoral thesis , University of London.

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Abstract

New drug regimens are needed for effective prophylaxis and treatment of drug resistant Plasmodium falciparum and Plasmodium vivax malaria in northeastern Papua. Mefloquine and doxycycline, two standard prophylactic drugs, had high prophylactic efficacy in northeastern Papua but they have limited application for two vulnerable groups, young children and pregnant women. Azithromycin, an azalide antibiotic, had a prophylactic efficacy of 83% against P. falciparum in malaria immune Kenyans. If successful in non immunes, it would be a significant addition to the current prophylactic drugs. Chloroquine, the current first line drug in northeastern Papua, is associated with high rates of treatment failure for falciparum and vivax malaria. Cure rates might be improved by combining with chloroquine with doxycycline, two drugs that are inexpensive and widely available. Methods. Two clinical trials were conducted. (1). The prophylactic efficacy of azithromycin against P. falciparum and P. vivax was determined in a double blind, placebo-controlled trial in Indonesian adults with limited immunity. After radical cure, three hundred randomised subjects received azithromycin (n=T48, 750mg loading dose, 250mg/day), placebo (n=77), or doxycycline (n=75, 100mg/day). The end point was slide proven parasitaemia. (2). In an open trial chloroquine plus doxycycline (CQD) was compared to chloroquine or doxycycline alone for treating falciparum and vivax malaria. Eight nine falciparum patients were randomised to standard dose chloroquine (n=30), doxycycline 100 mg 12 hourly (7 days), n=20 , or chloroquine plus doxycycline (n=39) corresponding numbers for vivax patients were 23, 16, 24. Endpoints were parasite sensitivity (S) or resistance (RI, RII, and RIII) assessed by Day 28. Findings. (1). There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Based on incidence rates, the prophylactic efficacy of azithromycin relative to placebo was 71.6% (95% CI 50.3-83.8) against P. falciparum, and 98.9% (93.1-99.9) against P. vivax. Corresponding figures for doxycycline were 96.3% (85.4-99.6) and 98% (88.0- 99.9).

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