Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2021
Historique:
received: 30 01 2021
accepted: 05 08 2021
entrez: 19 8 2021
pubmed: 20 8 2021
medline: 17 12 2021
Statut: epublish

Résumé

The spread of Plasmodium falciparum resistant parasites remains one of the major challenges for malaria control and elimination in Sub Saharan Africa. Monitoring of molecular markers conferring resistance to different antimalarials is important to track the spread of resistant parasites and to optimize the therapeutic lifespan of current drugs. This study aimed to evaluate the prevalence of known mutations in the drug resistance genes Pfcrt, Pfmdr1, Pfdhfr and Pfdhps in two different epidemiological settings in Cameroon. Dried blood spots collected in 2018 and 2019 from asymptomatic individuals were used for DNA extraction and then the Plasmodium infection status was determined byPCR. Detection of SNPs was performed by nested PCR followed by allele-specific restriction analysis (ASRA). The prevalence of each genotype was compared between sites using the Chi square and Fisher's exact tests. A high prevalence of the Pfcrt K76 wild type allele was found in both sites (88.5 and 62.29% respectively; P< 0,0001). The prevalence of Pfmdr1 mutations 86Y and 1246Y was respectively 55.83 and 1.45% in Mfou and 45.87 and 5.97% in Tibati, with significant difference between the studied areas (P<0.0001). Overall, the Pfdhfr triple-mutant genotype (51I/59R/108N) was highly prevalent (> 96%), however no SNP was detected at codon 164. In Pfdhps, the prevalence of the 437G mutation reached (90%) and was at higher frequency in Mfou (P< 0.0001). Overall, the Pfdhps mutations 540E and 581G were less common (0.33 and 3.26%, respectively). The quadruple resistant genotype (Pfdhfr 51I/59R/108N+Pfdhp437G) was found almost 90% of the samples. The wild-type genotype (Pfdhfr N51/C59/S108/164I+Pfdhps A437/K540/A581) was never identified and the sextuple mutant (Pfdhfr 51I/59R/108N+Pfdhp437G/540E/581G), kwon as super resistant appeared in two samples from Tibati. These findings demonstrate declining trends in the prevalence of mutations conferring resistance to 4-aminoquinolines, especially to chloroquine. However, a high level of mutations in P. falciparum genes related to SP resistance was detected and this raises concerns about the future efficacy of IPTp-SP and SMC in Cameroon.

Identifiants

pubmed: 34411157
doi: 10.1371/journal.pone.0256343
pii: PONE-D-21-03307
pmc: PMC8376100
doi:

Substances chimiques

Antimalarials 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0256343

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Aline Gaelle Bouopda Tuedom (AGB)

Department of Biological Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon.
Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroun.

Elangwe Milo Sarah-Matio (EM)

Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroun.
UMR MIVEGEC, IRD, CNRS, Institut de Recherche pour le Développement, Université Montpellier, Montpellier Cedex, France.

Carole Else Eboumbou Moukoko (CEE)

Department of Biological Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon.
Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroun.

Brice Lionel Feufack-Donfack (BL)

Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroun.
CNRS UPR9022, INSERM U963, Strasbourg, France.

Christelle Ngou Maffo (CN)

Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroun.
UMR MIVEGEC, IRD, CNRS, Institut de Recherche pour le Développement, Université Montpellier, Montpellier Cedex, France.

Albert Ngano Bayibeki (AN)

Université Catholique d'Afrique Centrale, Yaoundé-Campus Messa Cameroun, Yaoundé, Cameroun.

Hermann Parfait Awono-Ambene (HP)

Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), Yaoundé, Cameroun.

Lawrence Ayong (L)

Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroun.

Antoine Berry (A)

Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire de Toulouse et UMR152 UPS-IRD, Université de Toulouse, Toulouse, France.

Luc Abate (L)

UMR MIVEGEC, IRD, CNRS, Institut de Recherche pour le Développement, Université Montpellier, Montpellier Cedex, France.

Isabelle Morlais (I)

UMR MIVEGEC, IRD, CNRS, Institut de Recherche pour le Développement, Université Montpellier, Montpellier Cedex, France.

Sandrine Eveline Nsango (SE)

Department of Biological Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon.
Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroun.

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