Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes

Malaria Journal

Research

Nabil A. Nasr¹  Yee-Ling Lau¹  Hany Sady¹  Johari Surin²  Wahib M. Atroosh³  Hesham M. Al-Mekhlafi⁴  Adel Al-Jasari⁵  Georges Snounou⁶ 

[1] Department of Parasitology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia;Department of Parasitology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia;Centre for Research and Innovation, Taylor’s University, 47500, Subang Jaya, Selangor, Malaysia;Department of Parasitology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia;Department of Microbiology and Parasitology, Faculty of Medicine and Health Sciences, University of Aden, Aden, Yemen;Department of Parasitology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia;Endemic and Tropical Diseases Unit, Medical Research Center, Jazan University, Jazan, Kingdom of Saudi Arabia;Department of Parasitology, Faculty of Medicine and Health Sciences, Sana’a University, Sana’a, Yemen;National Malaria Control Programme, Ministry of Public Health and Population, Sana’a, Yemen;UPMC Université Paris 06, Inserm (Institut National de la Santé et de la Recherche Medicale), Centre d’Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, ERL CNRS 8255 (Centre National de la Recherche Scientifique), Sorbonne Universités, 91 Boulevard de l’Hôpital, F-75013, Paris, France;

关键词: Artemisinin-based combination therapy;    Sulfadoxine-pyrimethamine;    Drug resistance;    Malaria;    Plasmodium falciparum;    Gametocytaemia;    Kelch 13-propeller;    Yemen;   

DOI  :  10.1186/s12936-016-1344-0

 received in 2016-03-16, accepted in 2016-05-13,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundIn Yemen, artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been used as first-line treatment for uncomplicated falciparum malaria, which accounts for about 99 % of malaria cases. There is evidence that resistance to SP is increasing, with potential negative impact on efficacy, and in particular on curbing transmission. This study aims: (a) to evaluate the therapeutic efficacy of AS + SP treatment for uncomplicated falciparum malaria in Yemen; (b) to investigate the frequency of mutations in Plasmodium falciparum genes associated with resistance to AS (Kelch 13 propeller domain, pfK13) and SP (dihydrofolate reductase, pfdhfr, and dihydropteroate synthase, pfdhps); and (c) to assess the adequacy of this ACT to clear gametocytes.MethodsA 28-day in vivo evaluation of the clinical and parasitological response to three-day course of AS + SP was carried out in two areas of high endemicity (Hodeidah and Al-Mahwit provinces, Tehama region) in Yemen according to standard WHO protocol 2009. Clinical and parasitological indices were monitored over a 28-day follow-up, and the outcome was PCR-corrected. The frequencies of mutations in the pfdhfr, pfdhps, and pfK13 genes were obtained by sequencing following amplification.ResultsEighty-six patients completed the study, with a cure rate of 96.5 % (94.2 % PCR-uncorrected). Whereas four (4.7 %) patients still showed parasitaemia on day 2 post-treatment, all were found negative for asexual malaria stages on days 3 and 7. The efficacy of gametocyte clearance was poor (14.5, 42.5 and 86.0 % on days 7, 14 and 28, respectively), with gametocytes persisting throughout the study in some patients. All the isolates sequenced had the pfk13 propeller domain wild-type allele, and mutations associated with SP failure were observed only for pfdhfr with the double mutation (S108N + N51I) found in 65.4 % of the isolates sequenced.ConclusionIn Yemen, AS + SP therapy remains effective for the treatment of uncomplicated falciparum malaria. Mutations were not detected in pfk13 or pfdhps, though double mutations were observed for pfdhfr. The observed persistent gametocytaemia re-enforces calls to add a single dose primaquine to this ACT in order to minimizes the potential for transmission and enhance regional efforts to eliminate malaria.

【 授权许可】

CC BY   
© The Author(s) 2016