Spatial and molecular mapping of PfKelch13 gene polymorphism in Africa in the era of emerging Plasmodium falciparum resistance to artemisinin: A systematic review
[en] The spread of Plasmodium falciparum (Pf) isolates carrying mutations in the kelch 13 (PfK13) gene associated with artemisinin resistance (PfART-R) in Southeast Asia (SEA) threatens malaria control and elimination efforts. An eventual emergence of PfART-R in Africa would result in a major public health problem. We conducted a systematic review to investigate the frequency and spatial distribution of PfK13 mutants in Africa, including mutants linked to PfART-R in SEA. Seven databases were searched for relevant articles published before January, 2019 following PRISMA guidelines, identifying 53 studies that sequenced the PfK13 gene of 23100 sample isolates in 41 Sub-Saharan African countries. The PfK13 sequence was highly polymorphic (292 alleles, including 255 in the PfK13-propeller domain) but with mutations occurring at very low relative frequencies. Nonsynonymous mutations were found in only 626 isolates (2·7%) from Western, Central, and Eastern Africa. Nine different mutations linked to PfART-R in SEA according to the WHO (F446I, C469Y, M476I, R515K, S522C, P553L, V568G, P574L, and A675V) were detected, mainly in Eastern Africa. Several other PfK13 mutations such as those structurally mimicking SEA PfART-R mutations were also identified, but their relevance for drug resistance is still unknown. This review shows that Africa, thought to be spared from PfART-R, has reported resistance-related mutants in recent years. Surveillance using PfART-R molecular markers can provide valuable decision-making information to sustain the effectiveness of ART in the continent.
Disciplines :
Immunology & infectious disease Public health, health care sciences & services
Author, co-author :
Kayiba, Nadine
Yobi, Doudou
Tshibangu-Kabamba, Evariste
Phuoc Tuan, Vo
Yamaoka, Yoshio
Devleeschauwer, Brecht
Mvumbi, Dieudonné
Okitolonda, Emile
De Mol, Patrick ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Mvumbi, Georges
Hayette, Marie-Pierre ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Bactériologie, mycologie, parasitologie, virologie
Spatial and molecular mapping of PfKelch13 gene polymorphism in Africa in the era of emerging Plasmodium falciparum resistance to artemisinin: A systematic review
Alternative titles :
[en] Cartographie spatiale et moléculaire du polymorphisme du gène PfKelch13 en Afrique à l'époque de l'émergence de la résistance de P. falciparum à l'artémisinine: revue systématique
Publication date :
2021
Journal title :
The Lancet Infectious Diseases
ISSN :
1473-3099
eISSN :
1474-4457
Publisher :
The Lancet Publishing Group, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Mise en place d'un système de surveillance de la résistance de Plasmodium falciparum aux antipuludéens en RD Congo
Funders :
ARES - Académie de Recherche et d'Enseignement Supérieur
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