Are pvcrt-o and pvmdr1 Gene Mutations Associated with Plasmodium vivax Chloroquine-Resistant Parasites?

Author:

Abreu-Fernandes Rebecca de12,Almeida-de-Oliveira Natália Ketrin12,de Lavigne Mello Aline Rosa12,Queiroz Lucas Tavares de1,Barros Jacqueline de Aguiar13ORCID,Baptista Bárbara de Oliveira1,Oliveira-Ferreira Joseli4ORCID,Souza Rodrigo Medeiros de5ORCID,Pratt-Riccio Lilian Rose1ORCID,Brasil Patrícia26ORCID,Daniel-Ribeiro Cláudio Tadeu12,Ferreira-da-Cruz Maria de Fátima12ORCID

Affiliation:

1. Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21041-361, Brazil

2. Centro de Pesquisa, Diagnóstico e Treinamento em Malária (CPD-Mal), Reference Laboratory for Malaria in the Extra-Amazonian Region for the Brazilian Ministry of Health, Secretaria de Vigilância Sanitária & Fiocruz, Rio de Janeiro 21041-361, Brazil

3. Núcleo de Controle da Malária/Departamento de Vigilância Epidemiológica/Coordenação Geral de Vigilância em Saúde/SESAU-RR, Boa Vista 69305-080, Brazil

4. Laboratório de Imunoparasitologia, IOC, Fiocruz, Rio de Janeiro 21041-361, Brazil

5. Laboratório de Doenças Infecciosas da Amazônia Ocidental, Universidade Federal do Acre, Campus Floresta, Cruzeiro do Sul 69980-000, Brazil

6. Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro 21040-361, Brazil

Abstract

(1) Background: Malaria remains a significant global public health issue. Since parasites quickly became resistant to most of the available antimalarial drugs, treatment effectiveness must be constantly monitored. In Brazil, up to 10% of cases of vivax malaria resistant to chloroquine (CQ) have been registered. Unlike P. falciparum, there are no definitive molecular markers for the chemoresistance of P. vivax to CQ. This work aimed to investigate whether polymorphisms in the pvcrt-o and pvmdr1 genes could be used as markers for assessing its resistance to CQ. (2) Methods: A total of 130 samples from P. vivax malaria cases with no clinical and/or parasitological evidence of CQ resistance were studied through polymerase chain reaction for gene amplification followed by target DNA sequencing. (3) Results: In the pvcrt-o exons, the K10 insert was present in 14% of the isolates. Regarding pvmdr1, T958M and F1076L haplotypes showed frequencies of 95% and 3%, respectively, while the SNP Y976F was not detected. (4) Conclusions: Since K10-pvcrt-o and F1076L/T958M-pvmdr1 polymorphisms were detected in samples from patients who responded well to CQ treatment, it can be concluded that mutations in these genes do not seem to have a potential for association with the phenotype of CQ resistance.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado de Rio de Janeiro

Departamento de Ciência e Tecnologia em Saúde/Ministério da Saúde

Programa Nacional de Controle e Prevenção da Malária/Secretaria de Vigilância em Saúde/Ministério da Saúde (SVS/MS) and Fiocruz

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

Reference56 articles.

1. World Health Organization (2022). World Malaria Report 2022, World Health Organization. Available online: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022.

2. Plasmodium vivax Malaria across South America: Management Guidelines and Their Quality Assessment;Olivera;Rev. Soc. Bras. Med. Trop.,2020

3. Population Genomic Evidence of Plasmodium vivax Southeast Asian Origin;Daron;Sci. Adv.,2021

4. Tableau Public (2023, December 14). Tableau Public Dados Para Cidadão. Available online: https://public.tableau.com/app/profile/mal.ria.brasil/viz/Dadosparacidado_201925_03_2020/Incio.

5. Emerging Plasmodium vivax Resistance to Chloroquine in South America: An Overview;Cravo;Mem. Inst. Oswaldo Cruz,2014

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