Antibiotics for prophylaxis of Plasmodium falciparum infections: In vitro activity of doxycycline against Senegalese isolates

The in vitro activities of doxycycline, chloroquine, quinine, amodiaquine, artemether, pyrimethamine, and cycloguanil were evaluated against Plasmodiu m falciparum isolates from Senegal (Dielmo and Ndiop), using an isotopic, m icro, drug susceptibility test. The 71 50% inhibitory concentration (IC,,) values for doxycycline ranged from 0.7 to 108.0 mu M and the geometric mean IC50 for the 71 isolates was 11.3 mu M (95% confidence interval = 9.5-13.4 mu M). The activity of doxycycline did not differ significantly (P = 0.085 8) between the chloroquine-susceptible isolates and the chloroquine-resista nt isolates. There was no in vitro correlation between the responses to dox ycycline and those to artemether, chloroquine, quinine, amodiaquine, pyrime thamine, and cycloguanil, suggesting no in vitro cross-resistance among the se drugs. Potency was increased by prolonged exposure. In 96-hr incubations . the activity of doxycycline was 4-5-fold more increased than in 48-hr inc ubations. The in vitro activity of doxycycline against intraerythrocytic st ages of multidrug-resistant P. falciparum, its: action against the preeryth rocytic forms, the lack of correlation between the responses in vitro of P. falciparum to doxycycline and the ether antimalarial drugs, and its origin al potential site of action are factors that favor its use as antimalarial drug.