Investigation of Mutations in the and Genes of for the Molecular Surveillance of Chloroquine Resistance in Parasites from Gold Mining Areas in Roraima, Brazil

Overview

Journal Microorganisms

Specialty Microbiology

Date 2024 Aug 29

PMID 39203521

Authors

Jacqueline de Aguiar Barros

Fabiana Granja

Rebecca de Abreu-Fernandes

Lucas Tavares de Queiroz

Daniel da Silva E Silva

Arthur Camurca Cito

Natalia Ketrin Almeida-de-Oliveira Mocelin

Claudio Tadeu Daniel-Ribeiro

Maria de Fatima Ferreira-da-Cruz

Affiliations

Soon will be listed here.

Abstract

causes the largest malaria burden in Brazil, and chloroquine resistance poses a challenge to eliminating malaria by 2035. Illegal mining in the Roraima Yanomami Indigenous territory can lead to the introduction of resistant parasites. This study aimed to investigate mutations in the and genes to determine their potential as predictors of chloroquine-resistant phenotypes. Samples were collected in two health centers of Boa Vista. A questionnaire was completed, and blood was drawn from each patient. Then, DNA extraction, PCR, amplicon purification, and DNA sequencing were performed. After alignment with the Sal-1, the amplified fragment was analyzed. Patients infected with the mutant parasites were queried in the Surveillance Information System. Among the patients, 98% (157/164) of participants were from illegal mining areas. The was sequenced in 151 samples, and the K10 insertion was identified in 13% of them. The was sequenced in 80 samples, and the YF haplotype (958) was detected in 92% of them and the TYF was detected in 8%, while the Y was absent. No cases of recrudescence, hospitalization, or death were found. Mutations in the and genes have no potential to predict chloroquine resistance in .

References

Brega S, Meslin B, de Monbrison F, Severini C, Gradoni L, Udomsangpetch R . Identification of the Plasmodium vivax mdr-like gene (pvmdr1) and analysis of single-nucleotide polymorphisms among isolates from different areas of endemicity. J Infect Dis. 2004; 191(2):272-7. DOI: 10.1086/426830. View

Spotin A, Mahami-Oskouei M, Ahmadpour E, Parsaei M, Rostami A, Emami S . Global assessment of genetic paradigms of Pvmdr1 mutations in chloroquine-resistant Plasmodium vivax isolates. Trans R Soc Trop Med Hyg. 2020; 114(5):339-345. DOI: 10.1093/trstmh/traa002. View

Bray P, Martin R, Tilley L, Ward S, Kirk K, Fidock D . Defining the role of PfCRT in Plasmodium falciparum chloroquine resistance. Mol Microbiol. 2005; 56(2):323-33. DOI: 10.1111/j.1365-2958.2005.04556.x. View

Schousboe M, Ranjitkar S, Rajakaruna R, Amerasinghe P, Morales F, Pearce R . Multiple Origins of Mutations in the mdr1 Gene--A Putative Marker of Chloroquine Resistance in P. vivax. PLoS Negl Trop Dis. 2015; 9(11):e0004196. PMC: 4634971. DOI: 10.1371/journal.pntd.0004196. View

Lacerda M, Llanos-Cuentas A, Krudsood S, Lon C, Saunders D, Mohammed R . Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria. N Engl J Med. 2019; 380(3):215-228. PMC: 6657226. DOI: 10.1056/NEJMoa1710775. View

Baird J . Neglect of Plasmodium vivax malaria. Trends Parasitol. 2007; 23(11):533-9. DOI: 10.1016/j.pt.2007.08.011. View

Phillips E, Keystone J, Kain K . Failure of combined chloroquine and high-dose primaquine therapy for Plasmodium vivax malaria acquired in Guyana, South America. Clin Infect Dis. 1996; 23(5):1171-3. DOI: 10.1093/clinids/23.5.1171. View

Murta F, Marques L, Santos A, Batista T, Mendes M, Silva E . Perceptions about malaria among Brazilian gold miners in an Amazonian border area: perspectives for malaria elimination strategies. Malar J. 2021; 20(1):286. PMC: 8236171. DOI: 10.1186/s12936-021-03820-0. View

Buyon L, Elsworth B, Duraisingh M . The molecular basis of antimalarial drug resistance in Plasmodium vivax. Int J Parasitol Drugs Drug Resist. 2021; 16:23-37. PMC: 8113647. DOI: 10.1016/j.ijpddr.2021.04.002. View

10.

Abreu-Fernandes R, Almeida-de-Oliveira N, Mello A, de Queiroz L, de Aguiar Barros J, Baptista B . Are and Gene Mutations Associated with Chloroquine-Resistant Parasites?. Biomedicines. 2024; 12(1). PMC: 10812985. DOI: 10.3390/biomedicines12010141. View

11.

Ketema T, Getahun K, Bacha K . Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Halaba district, South Ethiopia. Parasit Vectors. 2011; 4:46. PMC: 3076248. DOI: 10.1186/1756-3305-4-46. View

12.

Gomes M, Vieira J, Machado R, Nacher M, Stefani A, Musset L . Efficacy in the treatment of malaria by Plasmodium vivax in Oiapoque, Brazil, on the border with French Guiana: the importance of control over external factors. Malar J. 2015; 14:402. PMC: 4600333. DOI: 10.1186/s12936-015-0925-7. View

13.

Leang R, Barrette A, Mey Bouth D, Menard D, Abdur R, Duong S . Efficacy of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010. Antimicrob Agents Chemother. 2012; 57(2):818-26. PMC: 3553743. DOI: 10.1128/AAC.00686-12. View

14.

Veiga M, Dhingra S, Henrich P, Straimer J, Gnadig N, Uhlemann A . Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies. Nat Commun. 2016; 7:11553. PMC: 4873939. DOI: 10.1038/ncomms11553. View

15.

de Aguiar Barros J, Granja F, Pequeno P, Marchesini P, de Fatima Ferreira da Cruz M . Gold miners augment malaria transmission in indigenous territories of Roraima state, Brazil. Malar J. 2022; 21(1):358. PMC: 9706895. DOI: 10.1186/s12936-022-04381-6. View

16.

Zhao Y, Wang L, Soe M, Aung P, Wei H, Liu Z . Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China-Myanmar border. Malar J. 2020; 19(1):281. PMC: 7409419. DOI: 10.1186/s12936-020-03354-x. View

17.

Alecrim M das G, Alecrim W, Macedo V . Plasmodium vivax resistance to chloroquine (R2) and mefloquine (R3) in Brazilian Amazon region. Rev Soc Bras Med Trop. 1999; 32(1):67-8. DOI: 10.1590/s0037-86821999000100013. View

18.

Simoes L, Alves Jr E, Ribatski-Silva D, Gomes L, Nery A, Fontes C . Factors associated with recurrent Plasmodium vivax malaria in Porto Velho, Rondônia State, Brazil, 2009. Cad Saude Publica. 2014; 30(7):1403-17. DOI: 10.1590/0102-311x00169312. View

19.

Nomura T, Carlton J, Baird J, del Portillo H, Fryauff D, Rathore D . Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria. J Infect Dis. 2001; 183(11):1653-61. DOI: 10.1086/320707. View

20.

Tantiamornkul K, Pumpaibool T, Piriyapongsa J, Culleton R, Lek-Uthai U . The prevalence of molecular markers of drug resistance in Plasmodium vivax from the border regions of Thailand in 2008 and 2014. Int J Parasitol Drugs Drug Resist. 2018; 8(2):229-237. PMC: 6039358. DOI: 10.1016/j.ijpddr.2018.04.003. View