Systematic Review and Geospatial Modeling of Molecular Markers of Resistance to Artemisinins and Sulfadoxine–Pyrimethamine in Plasmodium falciparum in India

Author:

Nain Minu1,Dhorda Mehul2345,Flegg Jennifer A.6,Gupta Apoorv1,Harrison Lucinda E.6,Singh-Phulgenda Sauman35,Otienoburu Sabina D.237,Harriss Eli8,Bharti Praveen K.1,Behera Beauty1,Rahi Manju1910,Guerin Philippe J.235,Sharma Amit111

Affiliation:

1. ICMR-National Institute of Malaria Research, New Delhi, India;

2. WorldWide Antimalarial Resistance Network, Oxford, United Kingdom;

3. Infectious Diseases Data Observatory, Oxford, United Kingdom;

4. Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;

5. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;

6. School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria, Australia;

7. College of STEM, Johnson C. Smith University, Charlotte, North Carolina;

8. The Knowledge Centre, Bodleian Health Care Libraries, University of Oxford, Oxford, United Kingdom;

9. Indian Council of Medical Research, New Delhi, India;

10. Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh;

11. Molecular Medicine, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

Abstract

ABSTRACT. Surveillance for genetic markers of resistance can provide valuable information on the likely efficacy of antimalarials but needs to be targeted to ensure optimal use of resources. We conducted a systematic search and review of publications in seven databases to compile resistance marker data from studies in India. The sample collection from the studies identified from this search was conducted between 1994 and 2020, and these studies were published between 1994 and 2022. In all, Plasmodium falciparum Kelch13 (PfK13), P. falciparum dihydropteroate synthase, and P. falciparum dihydrofolate reductase (PfDHPS) genotype data from 2,953, 4,148, and 4,222 blood samples from patients with laboratory-confirmed malaria, respectively, were extracted from these publications and uploaded onto the WorldWide Antimalarial Resistance Network molecular surveyors. These data were fed into hierarchical geostatistical models to produce maps with a predicted prevalence of the PfK13 and PfDHPS markers, and of the associated uncertainty. Zones with a predicted PfDHPS 540E prevalence of >15% were identified in central, eastern, and northeastern India. The predicted prevalence of PfK13 mutants was nonzero at only a few locations, but were within or adjacent to the zones with >15% prevalence of PfDHPS 540E. There may be a greater probability of artesunate–sulfadoxine–pyrimethamine failures in these regions, but these predictions need confirmation. This work can be applied in India and elsewhere to help identify the treatments most likely to be effective for malaria elimination.

Publisher

American Society of Tropical Medicine and Hygiene

Reference48 articles.

1. Global Technical Strategy for Malaria 2016–2030: 2021 Update,2021

2. A Framework for Malaria Elimination,2017

3. World Malaria Report 2022,2022

4. Guidelines for Diagnosis and Treatment of Malaria in India 2014,2014

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