Frequency of Plasmodium vivax circumsporozoite protein genotypes in humans and anopheline mosquitoes in an endemic area of southeastern Pará State, Brazil

Santos, Erian de Almeida; Primo, Deocleciano Galiza; Sucupira, Izis Mônica Carvalho; Cassiano, Gustavo Capatti; Barbosa, Danielle Regina Lima; Viana, Giselle Maria Rachid; Machado, Ricardo Luiz Dantas; Póvoa, Marinete Marins

doi:10.5123/s2176-62232016000300007

Cited by 6 publications

(11 citation statements)

References 39 publications

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“…The motif known as Region II was also found conserved in previous studies on the Brazilian Amazon [65], Peru [66], Iran, Sri Lanka, India [67], Cambodia, and Colombia [29]. This constrained variation in terminal regions reinforces such protein structures importance for its interaction with Anopheles mosquito salivary gland and human hepatocytes during the invasion processes [52]. Conversely, CR diversity could reflect the host's immune system's evasion mechanism, as already observed for other surface antigens as pvdbp gene [12,68].…”

Section: Discussionsupporting

confidence: 70%

Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest

et al. 2020

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Circumsporozoite protein (CSP) is the primary pre-erythrocytic vaccine target in Plasmodium species. Knowledge about their genetic diversity can help predict vaccine efficacy and the spread of novel parasite variants. Thus, we investigated pvcsp gene polymorphisms in 219 isolates (136 from Brazilian Amazon [BA], 71 from Rio de Janeiro Atlantic Forest [AF], and 12 from non-Brazilian countries [NB]). Forty-eight polymorphic sites were detected, 46 in the central repeat region (CR), and two in the C-terminal region. Also, the CR presents InDels and a variable number of repeats. All samples correspond to the VK210 variant, and 24 VK210 subtypes based on CR. Nucleotide diversity (π = 0.0135) generated a significant number of haplotypes (168) with low genetic differentiation between the Brazilian regions (Fst = 0.208). The haplotype network revealed similar distances among the BA and AF regions. The linkage disequilibrium indicates that recombination does not seem to be acting in diversity, reinforcing natural selection’s role in accelerating adaptive evolution. The high diversity (low Fst) and polymorphism frequencies could be indicators of balancing selection. Although malaria in BA and AF have distinct vector species and different host immune pressures, consistent genetic signature was found in two regions. The immunodominant B-cell epitope mapped in the CR varies from seven to 19 repeats. The CR T-cell epitope is conserved only in 39 samples. Concerning to C-terminal region, the Th2R epitope presented nonsynonymous SNP only in 6% of Brazilian samples, and the Th3R epitope remained conserved in all studied regions. We conclude that, although the uneven distribution of alleles may jeopardize the deployment of vaccines directed to a specific variable locus, a unique vaccine formulation could protect populations in all Brazilian regions.

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Section: Discussionsupporting

confidence: 70%

Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest

et al. 2020

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“…However, the genotype distribution profile has been changing overtime due to the gradual increase of P. vivax VK247 in Amapá, Pará and Roraima States. These findings can be reinforced for what has already been described on these genotypes distribution in Acre 11,12 , Amapá 7 , Pará 13,26–28 and Roraima 5 .…”

Section: Discussionsupporting

confidence: 81%

“…In addition to signs of adaptation of VK247 in mosquitoes, this variant also presented some changes in clinical profile in humans that may be related to its evolution. Other findings show that P. vivax VK247 is associated with higher parasite density levels in malaria patients in the Brazilian Amazon 28,29 , and the association with increased immune responses related to the disease’s clinical complications 29 , highlighting the importance of epidemiological studies in monitoring the process of adaptation of this genotype to mosquitoes.…”

Section: Discussionmentioning

confidence: 99%

“…The first report of infection by P. vivax VK247 in A. albitarsis s.l. from Brazilian Amazon was from the municipality of Marabá (PA) 13 , and later, it was detected in the municipality of Goianésia do Pará (PA) 28 . These data, together to the fact that the frequency of this genotype in Pará state is increasing, indicate that this genotype may be adapting not only in this Anopheles species, but also in A. darlingi .…”

Section: Discussionmentioning

confidence: 99%

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VK210 and VK247 genotypes of Plasmodium vivax in anopheline mosquitoes from Brazilian Amazon

Santos

Sucupira

Martins

et al. 2019

Sci Rep

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Plasmodium vivax sporozoites are differenced by circumsporozoite protein. Studies on the circulation of P. vivax VK210 and P. vivax VK247 in anopheline mosquitoes are important to verify the adaptability of these parasites on mosquitoes in different locations and periods. This study aimed to describe and compare the distribution of these genotypes in anopheline mosquitoes from four states of the Brazilian Amazon. Epidemiological databases about CSP infections on mosquitoes from Pará (2000–2015), Amapá (2000–2010), Roraima (2000–2003 and 2009–2011) and Acre States (2012–2015) were used for analysis. A total of 895 specimens were found infected mainly by P. vivax VK210. We showed that the distribution of P. vivax VK247 changed over time in the main malaria vectors on the Brazilian Amazon. We note that A. darlingi was abundant in certain localities while A. albitarsis s.l. in anothers, which highlights the importance of entomological studies for the control of human malaria.

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“… 21 These findings are consistent with results from previous studies reporting that the VK210 variant is the most frequent in malaria-endemic areas of the Brazilian Amazon. 12 , 13 , 22 In fact, Machado and Póvoa 12 suggested that VK210 is the best-adapted variant in Brazil as well as the world, as this variant has also been reported to be predominant in cases from Afghanistan, Iran, Azerbaijan, India, Thailand and Guiana.…”

Section: Discussionmentioning

confidence: 99%

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

Pratt-Riccio

Baptista

Torres

et al. 2019

Mem. Inst. Oswaldo Cruz

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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.

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Frequency of Plasmodium vivax circumsporozoite protein genotypes in humans and anopheline mosquitoes in an endemic area of southeastern Pará State, Brazil

Abstract: Frequência de genótipos da proteína circunsporozoíta de Plasmodium vivax em seres humanos e mosquitos anofelinos em área endêmica da região sudeste do Estado do Pará, Brasil Frecuencia de genotipos de la proteína circunsporozoíta de Plasmodium vivax en seres humanos y mosquitos

Cited by 6 publications

References 39 publications

Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest

Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest

VK210 and VK247 genotypes of Plasmodium vivax in anopheline mosquitoes from Brazilian Amazon

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

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