Kelch13 mutations in Plasmodium falciparum and risk of spreading in Amazon basin countries

Author:

Mathieu Luana C12,Singh Prabhjot3,Monteiro Wuelton Marcelo45,Magris Magda6,Cox Horace7,Lazrek Yassamine1,Melo Gisely C45,Marchesini Paola8,Alexandre Jean S F9,Alvarez Angel Manuel10,Demar Magalie1112,Douine Maylis1213,Ade Maria-Paz3,Lacerda Marcus V G414,Musset Lise1ORCID

Affiliation:

1. Laboratoire de parasitologie, Centre Nationale de Référence du Paludisme, World Health Organization Collaborating Center for surveillance of antimalarial drug resistance, Institut Pasteur de la Guyane, 97306 Cayenne, French Guiana

2. Ecole Doctorale n°587 « Diversités, Santé, et Développement en Amazonie », Université de Guyane, 97300 Cayenne, French Guiana

3. Department of Communicable Diseases and Environmental Determinants of Health, Pan American Health Organization/World Health Organization, Washington, DC 20037, USA

4. Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, 69040-200 Manaus, Amazonas, Brazil

5. Escola de Ciências da Saúde, Universidade do Estado do Amazonas, 69050-010 Manaus, Amazonas, Brazil

6. Amazonic Center for Research and Control of Tropical Diseases “Simón Bolívar”, 7101, Puerto Ayacucho, Amazonas State, Venezuela

7. National Malaria Program, Ministry of Public Health, 0592 Georgetown, Guyana

8. Malaria Technical Group, Vector Transmissible and Zoonotic Diseases Coordination, Ministry of Health, 70058-900 Brasilia, Brazil

9. Pan American Health Organization, Georgetown, Guyana

10. Pan American Health Organization, Caracas, Venezuela

11. Service de Maladies Infectieuses et Tropicales, Centre Hospitalier Andrée Rosemon, 97300 Cayenne, French Guiana

12. Ecosystèmes Amazoniens et Pathologie Tropicale (EPAT), EA3593, Université de Guyane, 97300 Cayenne, French Guiana

13. Centre d'Investigation Clinique Antilles-Guyane (Inserm 1424), Hôpital de Cayenne, 97300 Cayenne, French Guiana

14. Instituto Leônidas & Maria Deane, Fiocruz, 69057-070 Manaus, Brazil

Abstract

Abstract Background The first potential focus for artemisinin resistance in South America was recently confirmed with the presence of the C580Y mutation in the Plasmodium falciparum kelch 13 gene (pfk13) in Guyana. Objectives This study aimed to strengthen pfk13 monitoring in the Amazon basin countries, to compile the available data and to evaluate the risk of spreading of mutations. Methods Sanger sequencing was done on 862 samples collected between 1998 and 2019, and a global map of pfk13 genotypes available for this region was constructed. Then, the risk of spreading of mutations based on P. falciparum case importation between 2015 and 2018 within countries of the Amazon basin was evaluated. Results No additional pfk13 C580Y foci were identified. Few mutations (0.5%, 95% CI = 0.3%–0.8%) in the propeller domain were observed in the general parasite population of this region despite a high proportion of K189T mutations (49.1%, 95% CI = 46.2%–52.0%) in the non-propeller domain. Case information revealed two patterns of intense human migration: Venezuela, Guyana and the Roraima State in Brazil; and French Guiana, Suriname and the Amapá State in Brazil. Conclusions There are few pfk13 mutant foci, but a high risk of dispersion in the Amazon basin, mainly from the Guiana Shield, proportionate to mining activities. Therefore, access to prompt diagnosis and treatment, and continuous molecular monitoring is essential in these geographical areas.

Funder

Global Malaria Program (World Health Organization), Communicable Diseases and Environmental Determinants of Health Department

Guyamazon 3 Program

French Ministry for Research

European Commission Grant (Regional Fund for Development

Santé Publique France as National Reference Centre for Malaria and Investissement d’Avenir grant managed by Agence Nationale de la Recherche [CEBA

Centre National d’Etudes Spatiales

Fundação de Amparo à Pesquisa do Estado do Amazonas-FAPEAM (PAPAC

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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