Molecular epidemiology of drug-resistant Plasmodium falciparum in Benguela province, Angola

Malaria Journal

Research

Joseph Allico Djaman¹  Vincent Foumane Ngane²  Pierre Carnevale³  Patrick Besnard³  Filomeno Fortes⁴  Cécile Culeux⁵  Nathalie Piette⁵  Rachida Tahar⁵  Leonardo K Basco⁶ 

[1] Laboratoire de Pharmacodynamie Biochimique, Unité de Formation et de Recherche (UFR) Biosciences, Université Félix Houphouët-Boigny (Cocody), 22 BP 582, 22, Abidjan, Côte d’Ivoire;Département de Biochimie, Institut Pasteur de Côte d’Ivoire, 01 BP 490, 01, Abidjan, Côte d’Ivoire;Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), B. P. 288, Yaoundé, Cameroon;Malaria Control Programme, Société nationale de métallurgie (Sonamet), rua 1 de Dezembro, caixa postal 479, Lobito, Provincia de Benguela, Angola;Plano National Contra Malaria, Ministry of Health, Luanda, Angola;Unité Mixte de Recherche 216 Mère et Enfant Face aux Infections Tropicales, Institut de Recherche pour le Développement (IRD), Unité de Formation et de Recherche (UFR) de Pharmacie, Université Paris Descartes, 4 avenue de l’Observatoire, 75270, Paris, France;Unité de Recherche 198-Institut de Recherche pour le Développement (IRD), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine La Timone, Aix-Marseille Université, 27 boulevard Jean Moulin, 13385, Marseille, France;

关键词: Plasmodium falciparum;    Drug resistance;    Antifolate drugs;    Chloroquine;    Molecular markers;   

DOI  :  10.1186/s12936-015-0634-2

 received in 2014-11-21, accepted in 2015-03-02,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe malaria situation has been worsening in Angola, partly due to armed conflict until the recent past and drug-resistant Plasmodium falciparum. Malaria transmission is heterogeneous within the country, and data on drug-resistant malaria in different parts of the country are incomplete. The aim of the present study was to evaluate resistance to 4-aminoquinolines and antifolate drugs in P. falciparum isolates collected in Benguela province, central Angola, using molecular markers.MethodsFingerprick capillary blood was collected from asymptomatic children aged less than 15 years old during a household survey in and around Balombo town in 2010–2011. Samples were screened for P. falciparum by nested PCR. Molecular markers (P. falciparum dihydrofolate reductase [pfdhfr], P. falciparum dihydropteroate synthase [pfdhps], P. falciparum chloroquine resistance transporter [pfcrt], and P. falciparum multidrug-resistance gene 1 [pfmdr1]) were sequenced to determine the key codons associated with drug resistance.ResultsA total of 60 blood samples were positive for P. falciparum. Most isolates with successful PCR amplification had mutant pfdhfr alleles, with either double mutant AICNI (69%) or triple mutant AIRNI (21%) haplotypes. A16V, S108T, and I164L substitutions were not found. Many of the isolates were carriers of either SGKAA (60%) or AGKAA (27%) pfdhps haplotype. K540E substitution was absent. There were only two pfcrt haplotypes: wild-type CVMNK (11%) and mutant CVIET (89%). Wild-type pfmdr1 NYSND haplotype was found in 19% of the isolates, whereas single mutant pfmdr1 YYSND and NFSND haplotypes occurred in 48% and 11%, respectively. Double mutant pfmdr1 haplotypes (YFSND and YYSNY) occurred rarely.ConclusionsThe results suggest that the high prevalence of mutant pfcrt CVIET haplotype is in agreement with low clinical efficacy of chloroquine observed in earlier studies and that the double pfdhfr mutant AICNI and single pfdhps mutant SGKAA are currently the predominant haplotypes associated with antifolate resistance in Benguela province. The hallmark of clinical resistance observed in East Africa, i.e. triple pfdhfr mutant haplotype (AIRNI) and double pfdhps mutant haplotype (SGEAA), was absent. These molecular findings need to be further evaluated in parallel with clinical studies, in particular with the efficacy of intermittent preventive treatment using sulphadoxine-pyrimethamine in pregnant women and artesunate-amodiaquine for uncomplicated malaria.

【 授权许可】

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© Foumane Ngane et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.