Profile of molecular mutations in pfdhfr, pfdhps, pfmdr1, and pfcrt genes of Plasmodium falciparum related to resistance to different anti-malarial drugs in the Bata District (Equatorial Guinea)

Malaria Journal

Research

María Santana-Morales¹  Marisa Navarro²  Andrés Esteban-Cantos²  Zaida Herrador²  Taiomara Fernández²  Pedro Berzosa³  María Romay-Barja³  Luz García³  Agustín Benito³  Vicenta González³  Matilde Riloha⁴  Policarpo Ncogo⁵  José Miguel Rubio⁶  Basilio Valladares⁷ 

[1] Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de la Laguna, Tenerife, Spain;Malaria Laboratory, National Centre of Tropical Medicine, Institute of Health Carlos III, C/Monforte de Lemos 5, 28029, Madrid, Spain;Malaria Laboratory, National Centre of Tropical Medicine, Institute of Health Carlos III, C/Monforte de Lemos 5, 28029, Madrid, Spain;Network Collaborative Research in Tropical Diseases, RICET, Madrid, Spain;Ministry of Health and Social Welfare of Equatorial Guinea, Malabo, Equatorial Guinea;Ministry of Health and Social Welfare of Equatorial Guinea, Malabo, Equatorial Guinea;Malaria Laboratory, National Centre of Tropical Medicine, Institute of Health Carlos III, C/Monforte de Lemos 5, 28029, Madrid, Spain;National Centre of Microbiology, Institute of Health Carlos III, Madrid, Spain;Network Collaborative Research in Tropical Diseases, RICET, Madrid, Spain;Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de la Laguna, Tenerife, Spain;

关键词: Equatorial Guinea;    Malaria;    P. falciparum;    Resistance;    Mutations;    Antimalarial drugs;   

DOI  :  10.1186/s12936-016-1672-0

 received in 2016-09-20, accepted in 2016-12-30,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe emergence of drug resistance in Plasmodium falciparum has been a major contributor to the global burden of malaria. Drug resistance complicates treatment, and it is one of the most important problems in malaria control. This study assessed the level of mutations in P. falciparum genes, pfdhfr, pfdhps, pfmdr1, and pfcrt, related to resistance to different anti-malarial drugs, in the Continental Region of Equatorial Guinea, after 8 years of implementing artesunate combination therapies as the first-line treatment.ResultsA triple mutant of pfdhfr (51I/59R/108N), which conferred resistance to sulfadoxine/pyrimethamine (SP), was found in 78% of samples from rural settings; its frequency was significantly different between urban and rural settings (p = 0.007). The 164L mutation was detected for the first time in this area, in rural settings (1.4%). We also identified three classes of previously described mutants and their frequencies: the partially resistant (pfdhfr 51I/59R/108N + pfdhps 437G), found at 54% (95% CI 47.75–60.25); the fully resistant (pfdhfr 51I/59R/108N + pfdhps 437G/540E), found at 28% (95% CI 7.07–14.93); and the super resistant (pfdhfr 51I/59R/108N + pfdhps 437G/540E/581G), found at 6% (95% CI 0.48–4.32). A double mutation in pfmdr1 (86Y + 1246Y) was detected at 2% (95% CI 0.24–3.76) frequency, distributed in both urban and rural samples. A combination of single mutations in the pfmdr1 and pfcrt genes (86Y + 76T), which was related to resistance to chloroquine and amodiaquine, was detected in 22% (95% CI 16.8–27.2) of samples from the area.ConclusionsThe high level of mutations detected in P. falciparum genes related to SP resistance could be linked to the unsuccessful withdrawal of SP treatment in this area. Drug resistance can reduce the efficacy of intermittent prophylactic treatment with SP for children under 5 years old and for pregnant women. Although a high number of mutations was detected, the efficacy of the first-line treatment, artemisinin/amodiaquine, was not affected. To avoid increases in the numbers, occurrence, and spread of mutations, and to protect the population, the Ministry of Health should ensure that health centres and hospitals are supplied with appropriate first-line treatments for malaria.

【 授权许可】

CC BY   
© The Author(s) 2017