Limited ability of Plasmodium falciparum Pfcrt, Pfmdr1, and Pfnhe1 polymorphisms to predict quinine in vitro sensitivity or clinical effectiveness in Uganda

Authors: Frederick N. Baliraine, Samuel L. Nsobya, Jane Achan, James K. Tibenderana, Ambrose O. Talisuna, Bryan Greenhouse, Philip J. Rosenthal

Abstract

Quinine is a standard drug for treating severe malaria in Africa, and it is also increasingly used to treat uncomplicated disease. However, failures of quinine therapy are common, and it is unknown if failures in Africa are due to drug resistance. Recent studies have identified associations between in vitro quinine sensitivity and polymorphisms in genes encoding putative transporters, including well-described polymorphisms in pfcrt and pfmdr1 and varied numbers of DNNND or DDNHNDNHNND repeats in microsatellite 4760 (ms4760) of the predicted sodium-hydrogen exchanger, pfnhe1. This study aims to better characterise the mediators of quinine response. It assesses associations between genetic polymorphisms, in vitro quinine sensitivity, and quinine treatment responses in Kampala, Uganda.

Citation: Antimicrobial Agents and Chemotherapy, 2011; 55(2):615.