Response of falciparum malaria to chloroquine and three second line antimalarial drugs in a Kenyan coastal school age population.
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Ambulatory rural school children in the Mombasa area with P. falciparum parasitaemia were examined and randomly assigned to treatment with one of three second-line antimalarials--amodiaquine, pyrimethamine/sulphadoxine (P/SD) and pyrimethamine/sulfalene (P/SL). Clinical signs and parasitaemia were followed daily for the first week and on days 14 and 28. WHO Mark II schizont inhibition tests were performed for all the above 3 drugs and chloroquine. The total number of cases was 73. The mean parasite density was 142.1 +/- 207; 102.7 +/- 166; 82.74 +/- 93 parasites per 300 WBC for amodiaquine, P/SD, and P/SL, respectively. In vitro tests showed a chloroquine resistance rate of 60% and no resistance to all of the second line drugs. Also, all children treated successfully cleared their parasitaemia with mean clearance rates of 2.05 +/- 0.57; 1.86 +/- 0.47; 2.05 +/- 0.50 days for amodiaquine, P/SD and P/SL, respectively. Even though, no difference in the effectiveness between the second line drugs used was found, reinfection rates as depicted by day 28 parasitaemia differed--amodiaquine 16%; P/SD 0%; and P/SL4.35%. This difference could be attributed to the difference in the pharmacokinetic properties of the drugs. PIP: In Kenya, in May-June 1990, clinicians screened 728 primary school children in Mazeras, a coastal village, for Plasmodium falciparum parasitemia and randomly assigned them to receive 1 of 3 second-line antimalarials (amodiaquine, pyrimethamine/sulfadoxine [P/SD], and pyrimethamine/sulfalene [P/SL] to treat malaria. Laboratory personnel at the Coast Provincial General Hospital conducted WHO Mark II schizont inhibition tests for all 3 antimalarials and chloroquine. The clinicians followed the children every day for the first week and at 2 and 4 weeks. 10.44% (76) of the children had falciparum malaria (=or 40 asexual parasites/300 WBC). 3 were lost to follow-up, so 73 children were part of the in vivo study. Prior to treatment, mean parasite densities were 142.1/300 WBC for the amodiaquine group, 102.7/300 WBC for the P/SD group, and 82.74/300 WBC for the P/SL group. The mean clearance time for 2.05 days for amodiaquine, 1.86 days for P/SD, and 2.05 days for P/SL. By day 14, none of the children had parasitemia and no differences in mean body temperatures existed. On day 28, 16% of the children in the amodiaquine group and 4.35% of those in the P/SL group were reinfected compared to none in the P/SD group (p .05). Differences in the pharmacokinetic properties of these second line antimalarials may account for the difference in reinfection rates. 60% of the isolates were resistant to chloroquine. None were resistant to the second line drugs. Isolates were highly sensitive to both P/SD and P/SL. These findings show the need for the Kenyan Ministry of Health to reexamine chloroquine as a treatment for falciparum malaria in areas of confirmed high chloroquine resistance.