EX-VIVO ANTIMALARIAL ACTIVITY OF PROGUANIL COMBINED WITH DAPSONE AGAINST CYCLOGUANIL-RESISTANT PLASMODIUM-FALCIPARUM ISOLATES

The ex vivo antimalarial activity of plasma samples obtained from 20 h ealthy Caucasian volunteers following daily proguanil (200 mg) plus da psone (8 mg) for malaria chemoprophylaxis inhibited five cycloguanil-r esistant Thai isolates of Plasmodium falciparum. All volunteers were p henotyped as extensive metabolisers (EMs) of proguanil. Three of the f ive isolates were obtained from Thai soldiers who had failed malaria p rophylaxis on daily proguanil (200 mg) plus dapsone (4.0 or 12.5 mg). The Thai soldiers were also classified as EMs, but had relatively lowe r plasma cycloguanil concentrations compared to values reported in the literature for Caucasians and black Kenyans. Although the high level of parasite resistance to cycloguanil was the most likely explanation for the Thai soldiers failing prophylaxis on proguanil plus dapsone, t heir low cycloguanil concentrations may have also contributed to their lack of protection. However, in areas where parasites are more suscep tible to cycloguanil, such as in certain regions of Africa, proguanil plus dapsone may still be an effective chemoprophylactic drug combinat ion. (C) 1997 Elsevier Science B.V.