Novel Potential Drug-Resistant Mutations in P. falciparum in the Democratic Republic of Congo (2013)

Undergraduate: Alejandro Antonia

Faculty Advisor: Steve Meshnick
Department: Biology

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Within a decade of the first use of Chloroquine (CQ) to treat malaria, P. falciparum developed resistance to CQ (CQR). Throughout much of Africa CQR is conferred by a mutant CVIET haplotype in codons 72-76 of pfcrt rather than the chloroquine sensitive (CQS) wildtype CVMNK. Alternative genotypes at these loci, such as the Amodiaquine resistance associated SVMNT, have recently been reported in Africa as well. In order to describe the epidemiology of these genetic markers of CQR in the Democratic Republic of Congo (DRC), parasites were genotyped from 180 parasitemic individuals sampled in the 2007 Demographic and Health Survey. These parasitemias were genotyped at pfcrt codons 72-76 using PCR amplification and direct sequencing. Of 166 (92.2%) samples successfully genotyped: 73 (44.0%) harbored pure wild-type CVMNK parasites, 55 (33.1%) harbored pure CVIET parasites, 31 (18.7%) harbored a mix of CVMNK/CVIET parasites, and 7 (4.4%) harbored minority genotypes. The SVMNT haplotype was not observed. Of the minority genotypes, 4 contained a novel lysine to glutamine substitution at codon 76 (K76Q), instead of the usual K76T. The novel mutations warrant additional investigation to assess their potential role in drug resistance to CQ and other drugs. This snapshot of the genetic landscape of pfcrt in the DRC at a single time point highlights the importance of continued surveillance of the genetic markers of drug resistance to effectively inform public health decisions about drug use.