Temporal evolution of the resistance genotypes of Plasmodium falciparum in isolates from Equatorial Guinea during 20 years (1999 to 2019)

Malaria Journal

Irene Molina de la Fuente¹  Matilde Riloha²  Luz García³  Pedro Berzosa³  Agustin Benito³  Ramón Díaz-Regañón³  Laura Cerrada-Gálvez³  Vicenta González³  Rosario Galán³  Thuy-Huong Ta-Tang³  Ana Rodríguez-Galet⁴  Policarpo Ncogo⁵ 

[1] Department of Biomedicine and Biotechnology, University of Alcalá and National Centre of Tropical Medicine-Institute of Health Carlos III, Madrid, Spain;Ministry of Health and Social Welfare-Malaria National Programme of Equatorial Guinea, Malabo, Equatorial Guinea;National Centre of Tropical Medicine-Institute of Health Carlos III, Madrid, Spain;National Centre of Tropical Medicine-Institute of Health Carlos III, Madrid, Spain;HIV Molecular Epidemiology Laboratory, Ramón y Cajal-IRyCIS Hospital, Madrid, Spain;State Foundation, Health, Childhood and Social Welfare FSP, Madrid, Spain;

关键词: Malaria;    Resistance;    Genes;    Artemisinin combination therapy;    Equatorial Guinea;   

DOI  :  10.1186/s12936-021-04000-w

来源: Springer

【 摘 要 】

BackgroundMalaria is one of the deadliest diseases in the world, particularly in Africa. As such, resistance to anti-malarial drugs is one of the most important problems in terms of global malaria control. This study assesses the evolution of the different resistance markers over time and the possible influence of interventions and treatment changes that have been made in Equatorial Guinea.MethodsA total of 1223 biological samples obtained in the period 1999 to 2019 were included in the study. Screening for mutations in the pfdhfr, pfdhps, pfmdr1, and pfcrt genes was carried out by nested PCR and restriction-fragment length polymorphisms (RFLPs), and the study of pfk13 genes was carried out by nested PCR, followed by sequencing to determine the presence of mutations.ResultsThe partially and fully resistant haplotypes (pfdhfr + pfdhps) were found to increase over time. Moreover, in 2019, the fully resistant haplotype was found to be increasing, although its super-resistant counterpart remains much less prevalent. A continued decline in pfmdr1 and pfcrt gene mutations over time was also found. The number of mutations detected in pfk13 has increased since 2008, when artemisinin-based combination therapy (ACT) were first introduced, with more mutations being observed in 2019, with two synonymous and five non-synonymous mutations being detected, although these are not related to resistance to ACT. In addition, the non-synonymous A578S mutation, which is the most frequent on the African continent, was detected in 2013, although not in the following years.ConclusionsWithdrawal of the use of chloroquine (CQ) as a treatment in Equatorial Guinea has been shown to be effective over time, as wild-type parasite populations outnumber mutant populations. The upward trend observed in sulfadoxine-pyrimethamine (SP) resistance markers suggest its misuse, either alone or in combination with artesunate (AS) or amodiaquine (AQ), in some areas of the country, as was found in a previous study conducted by this group, which allows selective pressure from SP to continue. Single nucleotide polymorphisms (SNPs) 540E and 581G do not exceed the limit of 50 and 10%, respectively, thus meaning that SP is still effective as an intermittent preventive treatment (IPT) in this country. As for the pfk13 gene, no mutations have been detected in relation to resistance to ACT. However, in 2019 there is a greater accumulation of non-synonymous mutations compared to years prior to 2008.Graphical Abstract

【 授权许可】

CC BY