Chloroquine and mefloquine resistance profiles are not related to the circumsporozoite protein (CSP) VK210 subtypes in field isolates of Plasmodium vivax from Manaus, Brazilian Amazon

BACKGROUND The central repetitive region (CRR) of the Plasmodium vivax circumsporozoite surface protein (CSP) is composed of a repetitive sequence that is characterised by three variants: VK210, VK247 and P. vivax-like. The most important challenge in the treatment of P. vivax infection is the possibility of differential response based on the parasite genotype. OBJECTIVES To characterise the CSP variants in P. vivax isolates from individuals residing in a malaria-endemic region in Brazil and to profile these variants based on sensitivity to chloroquine and mefloquine. METHODS The CSP variants were determined by sequencing and the sensitivity of the P. vivax isolates to chloroquine and mefloquine was determined by Deli-test. FINDINGS Although five different allele sizes were amplified, the sequencing results showed that all of the isolates belonged to the VK210 variant. However, we observed substantial genetic diversity in the CRR, resulting in the identification of 10 different VK210 subtypes. The frequency of isolates that were resistant to chloroquine and mefloquine was 11.8 and 23.8%, respectively. However, we did not observe any difference in the frequency of the resistant isolates belonging to the VK210 subtypes. MAIN CONCLUSION The VK210 variant is the most frequently observed in the studied region and there is significant genetic variability in the CRR of the P. vivax CSP. Moreover, the antimalarial drug sensitivity profiles of the isolates does not seem to be related to the VK210 subtypes.

The frequency of HLA-DRB1 polymorphisms in Brazilian Plasmodium vivax malaria patients and in blood donors from the Amazon Region / Frequência de polimorfismos HLA-DRB1 em pacientes brasileiros com malária por Plasmodium vivaxe em doadores de sangue da Região Amazônica

We evaluated the frequency of different HLA-DRB1 alleles in Plasmodium vivax-infected individuals and in healthy blood donors from malaria endemic areas of Brazil. Low-resolution human leukocyte antigen-DRBl genotyping was performed for 73 malaria patients and 29 healthy blood donors. The most frequent alleles in individuals from northern Brazil were human leukocyte antigen-DRB1*04, *08, *07 and *13. The frequency of human leukocyte antigen-DRB1*07 was higher in malaria-infected individuals than in the control group, which reinforces the theory that this allele plays an important role in susceptibility to malaria. This study offers new information about a potential susceptibility factor for P. vivax malaria in a Brazilian population that is naturally exposed to malaria.

Este estudo avaliou a frequência de diferentes alelos HLA-DRB1 em indivíduos infectados por Plasmodium vivax e em doadores de sangue saudáveis provenientes de áreas endêmicas de malária do Brasil. Foi realizada uma genotipagem de baixa resolução dos alelos HLA-DRB1 em 73 pacientes com malária e em 29 doadores de sangue saudáveis. Os alelos mais frequentes em indivíduos do norte do Brasil foram HLA-DRB1 *04, *08, *07 e *13. A frequência de HLA-DRB1 *07 foi maior nos indivíduos infectados com malária do que no grupo controle, o que reforça a hipótese de que esse alelo desempenha um papel importante na suscetibilidade à malária. Esta pesquisa fornece novas informações sobre um fator potencial de suscetibilidade à malária por P. vivax em uma população brasileira naturalmente exposta à doença.