Mefloquine-halofantrine cross-resistance in Plasmodium falciparum induced by intermittent mefloquine pressure.

The study was designed to evaluate how exposure of Plasmodium falciparum to mefloquine modifies the sensitivity of the parasite to four major antimalarial drugs. A recently culture-adapted strain of P. falciparum was subjected to intermittent drug pressure at three different mefloquine concentrations (2.34, 4.68, and 9.37 ng/ml). Growth was monitored by daily evaluation of parasitemia on thin smears. Drug sensitivity tests were done weekly, using a radioisotope microdilution method. Mefloquine was removed from culture media when decreasing parasitemia was observed, and reintroduced when multiplication reoccurred. Parasite survival was inversely proportional to drug concentrations. The parasites tolerated progressively higher concentrations of mefloquine with prolonged exposure to the drug. Throughout this adaptation, the 50% inhibitory concentration for chloroquine and quinine showed no modification, but it increased considerably for mefloquine, exceeding known levels of resistance. Furthermore, a parallel increased resistance to halofantrine was observed, surpassing the normal range of sensitivity. Cross-resistance between mefloquine and halofantrine shown in this study has now been confirmed by epidemiologic in vitro surveys and clone analysis. These findings may have important in vivo consequences and eventually affect the choice of antimalarial therapy.

Primary and secondary dapsone resistance of M. leprae in Martinique, Guadeloupe, New Caledonia, Tahiti, Senegal, and Paris between 1980 and 1985.

Primary and secondary dapsone resistance were studied among lepromatous patients living in Martinique, Guadeloupe, New Caledonia, Tahiti, Senegal, and Paris. Four hundred fifteen biopsies were taken from clinically active and bacteriologically positive (bacterial index greater than 2) patients in the 6-year period of 1980-1985. Among these, 280 biopsies that contained 5 x 10(4) acid-fast bacilli per ml with a morphological index of at least 0.10 were inoculated into the mouse foot pad, and 229 harbored infective Mycobacterium leprae. Among the 129 infective M. leprae isolated from new cases, 54% had some degree of dapsone resistance, a low degree being prominent in all cases. Among the 100 infective M. leprae isolated from relapsed cases, 79% had a high or an intermediate degree of dapsone resistance. The annual incidence of secondary dapsone resistance was estimated to be about 0.55% in Guadeloupe.