The landscape of drug resistance in Plasmodium falciparum malaria in the Democratic Republic of Congo: a mapping systematic review

Author:

Kayiba Nadine Kalenda,Tshibangu-Kabamba Evariste,Rosas-Aguirre Angel,Kaku Natsuko,Nakagama Yu,Kaneko Akira,Makaba Dieudonné Mvumbi,Malekita Doudou Yobi,Devleesschauwer Brecht,Likwela Joris Losimba,Zakayi Pius Kabututu,DeMol Patrick,Lelo Georges Mvumbi,Hayette Marie-Pierre,Dikassa Paul Lusamba,Kido YasutoshiORCID,Speybroeck Niko

Abstract

Abstract Context The Democratic Republic of Congo (DRC), one of the most malaria-affected countries worldwide, is a potential hub for global drug-resistant malaria. This study aimed at summarizing and mapping surveys of malaria parasites carrying molecular markers of drug-resistance across the country. Methods A systematic mapping review was carried out before July 2023 by searching for relevant articles through seven databases (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline and Web of Science). Results We identified 1541 primary studies of which 29 fulfilled inclusion criteria and provided information related to 6385 Plasmodium falciparum clinical isolates (collected from 2000 to 2020). We noted the PfCRT K76T mutation encoding for chloroquine-resistance in median 32.1% [interquartile interval, IQR: 45.2] of analyzed malaria parasites. The proportion of parasites carrying this mutation decreased overtime, but wide geographic variations persisted. A single isolate had encoded the PfK13 R561H substitution that is invoked in artemisinin-resistance emergence in the Great Lakes region of Africa. Parasites carrying various mutations linked to resistance to the sulfadoxine–pyrimethamine combination were widespread and reflected a moderate resistance profile (PfDHPS A437G: 99.5% [IQR: 3.9]; PfDHPS K540E: 38.9% [IQR: 47.7]) with median 13.1% [IQR: 10.3] of them being quintuple IRNGE mutants (i.e., parasites carrying the PfDHFR N51IC59RS108N and PfDHPS A437GK540E mutations). These quintuple mutants tended to prevail in eastern regions of the country. Among circulating parasites, we did not record any parasites harboring mutations related to mefloquine-resistance, but we could suspect those with decreased susceptibility to quinine, amodiaquine, and lumefantrine based on corresponding molecular surrogates. Conclusions Drug resistance poses a serious threat to existing malaria therapies and chemoprevention options in the DRC. This review provides a baseline for monitoring public health efforts as well as evidence for decision-making in support of national malaria policies and for implementing regionally tailored control measures across the country.

Funder

Academy of Research and Higher Education

Japan Society for the Promotion of Science (JSPS) KAKENHI

Japan Agency for Medical Research and Development

Publisher

Springer Science and Business Media LLC

Subject

Infectious Diseases,Public Health, Environmental and Occupational Health

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