Plasmodium falciparum drug resistance gene status in the Horn of Africa: A systematic review

Abstract

Antimalarial drug resistance monitoring is the key factor in malaria control policy for early detection and subsequent prevention of drug resistance spread. This review was performed to collate all available data of P. falciparum resistant genes in the Horn of Africa as a baseline for future appraisal of the regional malaria control policy. The search of this review was performed in January 2018 using the scientific databases Pub Med and Google Scholar. The search terms used included: Plasmodium falciparum AND drug resistance genes OR molecular marks AND Somalia OR Ethiopia OR Eritrea OR Djibouti. The majority of studies (9 of 18 studies, 50%) examined pfdhfr, pfcrt and pfmdr 1 genes. Eight (44%), 4 (22%), and 2 (11%) studies analyzed pfdhps, pfk 13 and pfatp 6 genes, respectively. The Pfcytbc1 associated with atovaquone resistance is the only gene with no mutation detected. High frequencies of pfdhfr and pfdhps mutations were reported with an association to treatment failure after the artemisinin-based combination therapy (ACT) - artesunate + sulfadoxine/pyrimethamine. The aminoquinoline resistance genes such as pfmdr1, and pfatp 6 were only reported with low frequency. The 76T mutation of pfcrt ranged from 4 to 100%, while pfmdr1 mutations at codon 86 and 184 varied depending on geographical locations. The 402V and 431K mutations of pfatp 6 were found highly prevalent at 93% and 58% in Southwestern Ethiopia, respectively. The pfk13 gene mutation at codon 622I was 2.4%, with an association to artemether-lumefantrine efficacy and delay of parasite clearance on day 3.