Effect of three years’ seasonal malaria chemoprevention on molecular markers of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine and amodiaquine in Ouelessebougou, Mali

Malaria Journal

Boubacar N. Diarra¹  Brandt Levitt²  Betsy Freedman²  Kelsey M. Sumner³  Steve M. Taylor⁴  Patrick E. Duffy⁵  Michal Fried⁵  Adama B. Dembele⁶  Amadou Barry⁶  Aliou Traore⁶  Abdoulaye Djimde⁶  Issaka Sagara⁶  Almahamoudou Mahamar⁶  Djibrilla Issiaka⁶  Oumar Attaher⁶  Alassane Dicko⁶  Moussa B. Kanoute⁶ 

[1] Centre de Santé de Référence de Ouelessebougou, Koulikoro, Mali;Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA;Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA;Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC, USA;Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA;Duke Global Health Institute, Duke University, Durham, NC, USA;Laboratory of Malaria Immunology and Vaccinology (LMIV), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA;Malaria Research & Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Science, Techniques and Technologies (USTT), Bamako, Mali;

关键词: Seasonal malaria chemoprevention;    Plasmodium falciparum;    Molecular markers of resistance;    Sulfadoxine-pyrimethamine;    Amodiaquine;   

DOI  :  10.1186/s12936-022-04059-z

来源: Springer

【 摘 要 】

BackgroundIn 2012, seasonal malaria chemoprevention (SMC) was recommended as policy for malaria control by the World Health Organization (WHO) in areas of highly seasonal malaria transmission across the Sahel sub-region in Africa along with monitoring of drug resistance. We assessed the long-term impact of SMC on Plasmodium falciparum resistance to sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) over a 3-year period of SMC implementation in the health district of Ouelessebougou, Mali.MethodsIn 8 randomly selected sub-districts of Ouelessebougou, Mali, children aged 0–5 years were randomly selected during cross-sectional surveys at baseline (August 2014) and 1, 2 and 3 years post-SMC, at the beginning and end of the malaria transmission season. Blood smears and blood spots on filter paper were obtained and frequencies of mutation in P. falciparum genes related to resistance to SP and AQ (Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt) were assessed by PCR amplification on individual samples and PCR amplification followed by deep sequencing on pooled (by site and year) samples.ResultsAt each survey, approximately 50–100 individual samples were analysed by PCR amplification and a total of 1,164 samples were analysed by deep sequencing with an average read depth of 18,018–36,918 after pooling by site and year. Most molecular markers of resistance did not increase in frequency over the period of study (2014–2016). After 3 years of SMC, the frequencies of Pfdhps 540E, Pfdhps 437G and Pfcrt K76T remained similar compared to baseline (4.0 vs 1.4%, p = 0.41; 74.5 vs 64.6%, p = 0.22; 71.3 vs 67.4%, p = 0.69). Nearly all samples tested carried Pfdhfr 59R, and this proportion remained similar 3 years after SMC implementation (98.8 vs 100%, p = 1). The frequency of Pfmdr1 N86Y increased significantly over time from 5.6% at baseline to 18.6% after 3 years of SMC (p = 0.016). Results of pooled analysis using deep sequencing were consistent with those by individual analysis with standard PCR, but also indicated for the first time the presence of mutations at the Pfdhps A581G allele at a frequency of 11.7% after 2 years of SMC, as well as the Pfdhps I431V allele at frequencies of 1.6–9.3% following 1 and 2 years of SMC, respectively.ConclusionTwo and 3 years of SMC implementation were associated with increased frequency of the Pfmdr1 N86Y mutation but not Pfdhps 540E, Pfdhps 437G and Pfcrt K76T. The first-time detection of the Pfdhps haplotype bearing the I431V and A581G mutations in Mali, even at low frequency, warrants further long-term surveillance.

【 授权许可】

CC BY