Suscetibilidade in vitro de isolados de Plasmodium falciparum da Amazônia brasileira às drogas antimaláricas convencionais e ao antibiótico tigeciclina

Abstract

The present study aimed to evaluate the in vitro efficacy of drugs used for the treatment of P. falciparum in Brazil and of the antibiotic tigecycline, in order to suggest this as an alternative for the treatment of severe and complicated malaria. ELISA quantification of histidine-rich protein 2 of P. falciparum in culture with and without the presence of drugs were performed to determine the in vitro susceptibility of clinical isolates and reference parasite strains (DW2 - chloroquine-resistant and 3D7 - chloroquine-sensitive) for each drug tested. The in vitro efficacy of each drug was evaluated by determining its EC50% which was compared to previously standardized cut-offs. Furthermore, analysis of correlation was made between the EC50% calculated for each drug, in order to evaluate the potential for cross-resistance between them. Chloroquine did not show in vitro activity for all isolates of P. falciparum evaluated. However, two regional clinical isolates showed evidence of in vitro susceptibility to P. falciparum, suggesting rescue of the efficacy of chloroquine against this parasite species. The quinine, mefloquine, lumefantrine, artemisinin and artesunate showed satisfactory antimalarial in vitro activity against clinical and reference strains of P. falciparum. Tigecycline was shown to be effective against all P. falciparum isolates. Lumefantrine has potential to develop cross-resistance to artemisinin. Our findings showed that the drug components of conventional antimalarial regimens recommended in Brazil for the treatment of P. falciparum exhibit good in vitro antimalarial activity. Since tigecycline is an exclusively injectable drug, it may represent an alternative for the treatment of severe and complicated P. falciparum malaria. Is of concern, however, the observation of potential cross-resistance between artemisinin and lumefantrine, since these drugs are components of the first-line schedule for the treatment of P. falciparum in Brazil.