DISTINCTION OF RECRUDESCENCES FROM NEW INFECTIONS BY PCR-RFLP ANALYSIS IN A COMPARATIVE TRIAL OF CGP-56697 AND CHLOROQUINE IN TANZANIAN CHILDREN

OBJECTIVE TO test the efficacy of a new compound drug (CGP 56697) agai nst acute, uncomplicated falciparum malaria. METHOD Reappearing parasi tes were analysed by PGR-RFLP within a randomized controlled trial. 13 0 patients received chloroquine and 130 patients were treated with CGP 56697. Samples from 36 patients with parasitological failure were tes ted by PCR-RFLP for MSP2 of Plasmodium falciparum. Seven days after tr eatment 32 patients of the chloroquine control group with reappearing parasites were tested by PCR and one infection was unequivocally deter mined as a new infection. After 7 days, in the CGP 56697 group, 6 samp les were tested in which one new infection was identified. Similar obs ervations were made one and three weeks later in both groups. RESULTS Although a high multiplicity of infections on admission was observed, there was no significant correlation between multiplicity and either r ecrudescence or new infection. patients in both treatment groups with subsequent recrudescent parasites had higher initial mean parasite den sities than patients who cleared. Those of the patients with recrudesc ent parasites who were treated with CGP 56697 had higher initial paras ite densities than those treated with chloroquine. The rate of re-infe ction increased with time as effected in holoendemic areas and appeare d to be higher in chloroquine patients. Generally CGP 56697 showed. a superior clearance rate, successfully cleared higher parasite densitie s and suppressed new infections over a longer period of time. CONCLUSI ON The PCR analysis confirmed char reinfections beyond day 7 are signi ficant in areas highly endemic for malaria and showed the necessity of excluding these when estimating 14 day clearance rates. provided new infections are excluded. the 28-day clearance rate can also be used to determine the efficacy of antimalarial drugs in highly endemic areas, and adds to our knowledge of drug resistance and dynamics of infectio ns in people living in such areas.