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

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 effica...

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Autores principales:	Sabyasachi Das, Amrita Kar, Subhankar Manna, Samaresh Mandal, Sayantani Mandal, Subhasis Das, Bhaskar Saha, Amiya Kumar Hati
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a0a431df835a4e7d8266cb3aaccbd591
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spelling	oai:doaj.org-article:a0a431df835a4e7d8266cb3aaccbd5912021-12-02T15:36:31ZArtemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India10.1038/s41598-021-89295-02045-2322https://doaj.org/article/a0a431df835a4e7d8266cb3aaccbd5912021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89295-0https://doaj.org/toc/2045-2322Abstract 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 < 0.005) along with significantly higher RSA (2.2%) than cured patients (0.4%). None of day-3 positive isolates contained the pfkelch13 mutation implicated in artemisinin resistance. Parasite recrudescence was observed in 5.6% patients, which was associated with triple dhfr–dhps (A16 I 51 R 59 N 108I164–S436 G 437K540 G 581 T 613 ) combination mutation. Emergence of reduced sensitivity to artesunate-sulfadoxine-pyrimethamine, in central India highlighted the risk toward spread of resistant parasite across different parts of India. Day-3 positive parasite, featuring the phenotype of artemisinin-resistance without pfkelch13 mutation, suggested kelch13-independent artemisinin-resistance.Sabyasachi DasAmrita KarSubhankar MannaSamaresh MandalSayantani MandalSubhasis DasBhaskar SahaAmiya Kumar HatiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sabyasachi Das Amrita Kar Subhankar Manna Samaresh Mandal Sayantani Mandal Subhasis Das Bhaskar Saha Amiya Kumar Hati Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India
description	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 < 0.005) along with significantly higher RSA (2.2%) than cured patients (0.4%). None of day-3 positive isolates contained the pfkelch13 mutation implicated in artemisinin resistance. Parasite recrudescence was observed in 5.6% patients, which was associated with triple dhfr–dhps (A16 I 51 R 59 N 108I164–S436 G 437K540 G 581 T 613 ) combination mutation. Emergence of reduced sensitivity to artesunate-sulfadoxine-pyrimethamine, in central India highlighted the risk toward spread of resistant parasite across different parts of India. Day-3 positive parasite, featuring the phenotype of artemisinin-resistance without pfkelch13 mutation, suggested kelch13-independent artemisinin-resistance.
format	article
author	Sabyasachi Das Amrita Kar Subhankar Manna Samaresh Mandal Sayantani Mandal Subhasis Das Bhaskar Saha Amiya Kumar Hati
author_facet	Sabyasachi Das Amrita Kar Subhankar Manna Samaresh Mandal Sayantani Mandal Subhasis Das Bhaskar Saha Amiya Kumar Hati
author_sort	Sabyasachi Das
title	Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India
title_short	Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India
title_full	Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India
title_fullStr	Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India
title_full_unstemmed	Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India
title_sort	artemisinin combination therapy fails even in the absence of plasmodium falciparum kelch13 gene polymorphism in central india
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a0a431df835a4e7d8266cb3aaccbd591
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Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India

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