Abstract
BackgroundPlasmodium vivax is the most widespread human malaria parasite outside Africa and is the predominant parasite in the Americas. Increasing reports of P. vivax disease severity, together with the emergence of drug-resistant strains, underscore the urgency of the development of vaccines against P. vivax. Polymorphisms on DBP-II-gene could act as an immune evasion mechanism and, consequently, limited the vaccine efficacy. This study aimed to investigate the pvdbp-II genetic diversity in two Brazilian regions with different epidemiological patterns: the unstable transmission area in the Atlantic Forest (AF) of Rio de Janeiro and; the fixed malaria-endemic area in Brazilian Amazon (BA).Methods216 Brazilian P. vivax infected blood samples, diagnosed by microscopic examination and PCR, were investigated. The region flanking pvdbp-II was amplified by PCR and sequenced. Genetic polymorphisms of pvdbp-II were estimated based on the number of segregating sites and nucleotide and haplotype diversities; the degree of differentiation between-regions was evaluated applying Wright’s statistics. Natural selection was calculated using the rate of nonsynonymous per synonymous substitutions with the Z-test, and the evolutionary distance was estimated based on the reconstructed tree.Results79 samples from AF and 137 from BA were successfully sequenced. The analyses showed 28 polymorphic sites distributed in 21 codons, with only 5% of the samples Salvador 1 type. The highest rates of polymorphic sites were found in B- and T cell epitopes. Unexpectedly, the nucleotide diversity in pvdbp-II was higher in AF (0.01) than in BA (0.008). Among the 28 SNPs detected, 18 are shared between P. vivax isolates from AF and BA regions, but 8 SNPs were exclusively detected in AF—I322S, K371N, E385Q, E385T, K386T, K411N, I419L and I419R—and 2 (N375D and I419M) arose exclusively in BA. These findings could suggest the potential of these geographical clusters as population-specific-signatures that may be useful to track the origin of infections. The sample size should be increased in order to confirm this possibility.ConclusionsThe results highlight that the pvdbp-II polymorphisms are positively selected by host’s immune pressure. The characterization of pvdbp-II polymorphisms might be useful for designing effective DBP-II-based vaccines.
Highlights
Plasmodium vivax is the most widespread human malaria parasite outside Africa and is the predomi‐ nant parasite in the Americas
The first and most important occurs inside the Brazilian Amazon Basin (BA), where more than 99% of malaria cases were recorded; the second one involves imported malaria cases, which corresponds to infections that are acquired in Brazilian endemic areas different from where the individual lives or the diagnosis has been done, or from other endemic countries
One group of 177 individuals (95 from BA and 82 from Atlantic Forest (AF)) who attended to the Reference Centre for Malaria Diagnosis CPD-Mal/ Fiocruz in Rio de Janeiro (S 22° 54′ W 43° 12′) from January 2011 to March 2018; the other group of 50 individuals who sought for diagnosis at the Unit Health of Tucuruí (S 3o 46′ W 49o 40′), a municipality from Pará State, located in the Brazilian Amazon region during 2011
Summary
Plasmodium vivax is the most widespread human malaria parasite outside Africa and is the predomi‐ nant parasite in the Americas. Increasing reports of P. vivax disease severity, together with the emergence of drugresistant strains, underscore the urgency of the development of vaccines against P. vivax. Plasmodium vivax is the most widespread human malaria parasite outside sub-Saharan Africa. Plasmodium vivax causes significant morbidity, as well as social and economic burden, becoming a public health challenge in endemic countries [2]. The evidence of severe vivax malaria around the world, including Brazil [3], together with the emergence of drug-resistant strains [4], underscore the urgency to reduce the infection burden and malaria elimination [5, 6]. The development of vaccines that protect against P. vivax blood stages is a priority to prevent disease and onward transmission. The Duffy Binding Protein–DBP, a 140-kDa protein expressed in the micronemes of the P. vivax surface in the asexual blood-stage, interacts with the Duffy antigen/ receptor for chemokines (DARC) on the host erythrocytes [7], making this molecule an attractive vaccine candidate against vivax malaria
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