NDLI: Prevalence of molecular markers of sulfadoxine–pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan

Content Provider	Springer Nature : BioMed Central
Author	Yaqoob, Adnan Khattak, Aamer Ali Nadeem, Muhammad Faisal Fatima, Huma Mbambo, Gillian Ouattara, Amed Adams, Matthew Zeeshan, Nadia Takala-Harrison, Shannon
Abstract	Background In Pakistan, artesunate (AS) in combination with sulfadoxine–pyrimethamine (SP) is the recommended treatment for uncomplicated Plasmodium falciparum malaria. Monitoring molecular markers of anti-malarial drug resistance is crucial for early detection and containment of parasite resistance to treatment. Currently, no data are available on molecular markers of artemisinin resistance (K13 mutations) in P. falciparum isolates from Pakistan. In this study, the prevalence of mutations associated with SP and artemisinin resistance was estimated in different regions of Pakistan. Methods A total of 845 blood samples that were positive for malaria parasites by microscopy or rapid diagnostic test were collected from January 2016 to February 2017 from 16 different sites in Pakistan. Of these samples, 300 were positive for P. falciparum by PCR. Polymorphisms in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes were identified by pyrosequencing while polymorphisms in the propeller domain of the pfk13 gene were identified by Sanger sequencing. Results The prevalence of the PfDHFR 108N and 59R mutations was 100% and 98.8%, respectively, while the prevalence of PfDHFR 50R and 51I mutations was 8.6%. No mutation was observed at PfDHFR position 164. In PfDHPS, the prevalence of mutations at positions 436, 437, and 613 was 9.9%, 45.2%, and 0.4%, respectively. No mutations were found at PfDHPS positions 540 and 581. The prevalence of double PfDHFR mutants (59R + 108N) ranged from 93.8% to 100%, while the prevalence of parasites having the PfDHFR 59R + 108N mutations in addition to the PfDHPS 437G mutation ranged from 9.5% to 83.3% across different regions of Pakistan. Nine non-synonymous and four synonymous mutations were observed in the PfK13 propeller domain, none of which correspond to mutations validated to contribute to artemisinin resistance. Conclusion The absence of the highly resistant PfDHFR/PfDHPS quintuple mutant parasites and the lack of PfK13 mutations associated with artemisinin resistance is consistent with AS + SP being effective in Pakistan.
Related Links	https://malariajournal.biomedcentral.com/counter/pdf/10.1186/s12936-018-2620-y.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
ISSN	14752875
DOI	10.1186/s12936-018-2620-y
Journal	Malaria Journal
Issue Number	1
Volume Number	17
Language	English
Publisher	BioMed Central
Publisher Date	2018-12-17
Access Restriction	Open
Subject Keyword	Parasitology Tropical Medicine Infectious Diseases Entomology Microbiology Public Health Plasmodium falciparum Malaria Drug resistance Pakistan
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology
Journal Impact Factor	2.4/2023
5-Year Journal Impact Factor	2.6/2023

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