Susceptibility of human Plasmodium knowlesi infections to anti-malarials

Farrah A Fatih,Janet Cox-Singh,Mohammed Atique Ahmed,Erica M Pasini,Henry M Staines,Balbir Singh,Angela Siner,Clemens Hm Kocken,Sanjeev Krishna,Lu Chan Woon

doi:10.1186/1475-2875-12-425

Abstract

BackgroundEvidence suggests that Plasmodium knowlesi malaria in Sarawak, Malaysian Borneo remains zoonotic, meaning anti-malarial drug resistance is unlikely to have developed in the absence of drug selection pressure. Therefore, adequate response to available anti-malarial treatments is assumed.MethodsHere the ex vivo sensitivity of human P. knowlesi isolates in Malaysian Borneo were studied, using a WHO schizont maturation assay modified to accommodate the quotidian life cycle of this parasite. The in vitro sensitivities of P. knowlesi H strain adapted from a primate infection to in vitro culture (by measuring the production of Plasmodium lactate dehydrogenase) were also examined together with some assays using Plasmodium falciparum and Plasmodium vivax.ResultsPlasmodium knowlesi is uniformly highly sensitive to artemisinins, variably and moderately sensitive to chloroquine, and less sensitive to mefloquine.ConclusionsTaken together with reports of clinical failures when P. knowlesi is treated with mefloquine, the data suggest that caution is required if using mefloquine in prevention or treatment of P. knowlesi infections, until further studies are undertaken.

Highlights

Evidence suggests that Plasmodium knowlesi malaria in Sarawak, Malaysian Borneo remains zoonotic, meaning anti-malarial drug resistance is unlikely to have developed in the absence of drug selection pressure
The incidence of P. knowlesi malaria is increasing in geographic areas where Plasmodium falciparum and Plasmodium vivax are coming under control, thereby threatening the aim of eliminating malaria [5]
Mefloquine, used as a partner drug in certain artemisinin-based combinations and in prophylaxis against malaria, and chloroquine that is recommended for treatment of Plasmodium malariae were included

Summary

Introduction

Evidence suggests that Plasmodium knowlesi malaria in Sarawak, Malaysian Borneo remains zoonotic, meaning anti-malarial drug resistance is unlikely to have developed in the absence of drug selection pressure. From its natural simian hosts in Southeast Asia, Plasmodium knowlesi has emerged as a significant human pathogen, in Malaysian Borneo [1,2,3]. The drug sensitivity profiles of P. knowlesi isolates obtained from patients being recruited into a study of the pathophysiology of knowlesi malaria in an endemic area of Sarawak, Malaysian Borneo were investigated. Insights into the drug susceptibility patterns of this important emerging parasite, may prove useful in guiding the best choice of anti-malarial treatment regimens for P. knowlesi infection

Methods

Results

Conclusion