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Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India

Das S 1 , Kar A 2 , Manna S 3 , Mandal S 3 , Mandal S 4 , Das S 4 Show all authors , Saha B 5 , Hati AK 6

Affiliations 

  • 1 Department of Physiology, Faculty of Medicine, Manipal University College Malaysia, Jalan Batu Hampar, Bukit Baru, 75150, Melaka, Malaysia. Sabyasachi.das@manipal.edu.my
  • 2 Department of Biotechnology, Centre for Research in Infectious Diseases, School of Chemical and Biotechnology, Sastra University, Thanjavur, Tamil Nadu, India
  • 3 Department of Human Physiology, Vidyasagar University, Midnapore, West Bengal, India
  • 4 Medicare, Bhilai, Chhattisgarh, India
  • 5 Lab 5, National Centre for Cell Science, Ganeshkhind, Pune, India
  • 6 Department of Medical Entomology and Parasitology, Calcutta School of Tropical Medicine, Kolkata, West Bengal, India
Sci Rep, 2021 05 11;11(1):9946.
PMID: 33976269 DOI: 10.1038/s41598-021-89295-0

Abstract

Artemisinin is the frontline fast-acting anti-malarial against P. falciparum. Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Therefore, the objective of our study is to evaluate the artesunate-sulfadoxine-pyrimethamine efficacy in Central India. 180 monoclonal P. falciparum-infected patients received standard ASSP therapy during August 2015-January 2017, soon after diagnosis and monitored over next 42-days. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC1/2), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch13 and other candidate gene (pfcrt, pfmdr1, pfatpase 6, pfdhfr and pfdhps). Of 180 P. falciparum positive patients, 9.5% showed increased PC1/2 (> 5.5 h), among them eleven isolates (6.1%) showed reduced sensitivity to RSA. In 4.4% of cases, parasites were not cleared by 72 h and showed prolonged PC1/2(5.6 h) (P 

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