Pfkelch13 Plasmodium falciparum Mutations in Huambo, Angola

Pathogens. 2022 May 8;11(5):554. doi: 10.3390/pathogens11050554.

Abstract

Artemisinin (ART) is recommended as the first-line drug for P. falciparum infections combined with a long-acting partner drug. The emergence of P. falciparum resistance to ART (ARTR) is a concern for malaria. The most feared threat remains the spread of ARTR from Southeast Asia to Africa or the independent emergence of ARTR in Africa, where malaria accounts for 93% of all malaria cases and 94% of deaths. To avoid this worst-case scenario, surveillance of Pfkelch13 mutations is essential. We investigated mutations of Pfkelch13 in 78 P. falciparum samples from Huambo, Angola. Most of the parasites had a wild-type Pfkelch13 allele. We identified one synonymous mutation (R471R) in 10 isolates and one non-synonymous mutation (A578S) in two samples. No Pfkelch13 validated or candidate ARTR mutants were identified. The finding suggests that there is little polymorphism in Pfkelch13 in Huambo. Since cases of late response to ART in Africa and the emergence of ARTR mutations in Rwanda and Uganda have been reported, efforts should be made toward continuous molecular surveillance of ARTR. Our study has some limitations. Since we analyzed P. falciparum parasites from a single health facility, the study may not be representative of all Angolan endemic areas.

Keywords: ACTs; Angola; Plasmodium falciparum; artemisinin; malaria; pfk13; resistance.

Grants and funding

This work was supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; http://www.cnpq.br/, accessed on 10 March 2022) by fellowship that A.B.B.R. and R.d.A.-F. are recipients, and by Research Productivity Fellowships whom C.T.D.-R. (310445/2017-5) and M.d.F.F.-d.-C. (306025/2018-3) are recipients; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado de Rio de Janeiro (FAPERJ; http://www.faperj.br/, accessed on 10 March 2022) by postdoctoral Fellowship that N.K.A.-d.-O. is recipient, and by “Cientistas do Nosso Estado” whom C.T.D.-R. (E-26/202.921/2018) and M.d.F.F.-d.-C. (E-26/203.295/2015) are recipients. This work was also supported by Departamento de Ciência e Tecnologia em Saúde/ Ministério da Saúde (DECIT/MS), Programa Nacional de Controle da Malária/ Secretaria de Vigilância em Saúde/Ministério da Saúde (SVS/MS), Fiocruz, and the Angolan Ministry of Health (MINSA). The World Academy of Sciences (TWAS) also provided funding for the advancement of science in developing countries (Grant fellowship 17-368 RG/BIO/AF/AC_I).