Plasmodium vivax infection in Anajás, State of Pará: no differential resistance profile among Duffy-negative and Duffy-positive individuals

Abstract

BackgroundThere is large body of evidence that states that invasion of Plasmodium vivax requires the Duffy antigen, but the universality of this specificity is certainly now under question with recent reports showing that in some parts of the world P. vivax infects and causes disease in Duffy-negative people. These findings reinforce the idea that this parasite is rapidly evolving, being able to use other receptors than Duffy to invade the erythrocytes, which may have an enormous impact in P. vivax current distribution. The presence of P. vivax infection in Duffy-negative individuals was investigated in a cross-sectional study conducted in Anajás, Archipelago of Marajó, State of Pará, which is an area of malaria transmission in the Brazilian Amazonia.MethodsDuffy genotyping and Plasmodium species diagnostic assays were performed successfully in 678 individuals. An allele-specific primer polymerase chain reaction (PCR) technique was used for Duffy blood group genotyping. Identification of Plasmodium species was achieved by conventional blood smear light microscopy and a TaqMan-based real-time PCR method to detect mitochondrial genome of Plasmodium falciparum and P. vivax.ResultsPlasmodium spp. infection was detected in 137 samples (20.2%). Prevalence of each Plasmodium species was 13.9% P. vivax, 5.8% P. falciparum, and 0.6% P. vivax plus P. falciparum. Overall, 4.3% (29/678) were genotyped as Duffy-negative (FY*BES/*BES). Among Duffy-negative individuals 6.9% were P. vivax PCR positive and among Duffy-positive 14.2% were P. vivax PCR positive. Although lower, the risk of Duffy-negatives to experience a P. vivax blood stage infection was not significantly different to that of Duffy-positives. Furthermore, the genotypic and allelic frequencies of the Duffy blood group among P. vivax-infected patients and in the control group did not differ significantly, also suggesting no reduction in infection rates among the carriers of FY*BES allele.ConclusionsThe data obtained in Anajás showed no differential resistance vivax malaria among Duffy-negative and Duffy-positive individuals. This result needs additional confirmation through a deeper evaluation in a larger sample of patients with P. vivax malaria and molecular parasite characterization. Nonetheless, this genetic profile of the parasite may be contributing to the high incidence of malaria in the municipality.

Population Genetic Analysis of the DARC Locus (Duffy) Reveals Adaptation from Standing Variation Associated with Malaria Resistance in Humans

“…It has been proposed that due to the near-fixation of FY Ã O, P. vivax infection in humans is largely absent from equatorial Africa. An important recent discovery suggests low levels of P.vivax infection in FY Ã O homozygotes [13][14][15][16][17], which indicates that P. vivax might be evolving escape variants able to overcome the protective effect of FY Ã O. Phenotypic effects of the FY Ã A mutation are less clear than FY Ã O; however, there is evidence of natural selection and reduced P. vivax infection in individuals with this genotype ( [18,19], with conflicting reports in the Brazilian Amazon however [12,20,21]). …”

“…Individuals with the FY Ã O allele do not express the Duffy receptor in red blood cells resulting in immunity to P.vivax [6,10] and individuals with the FY Ã A allele may have lower infectivity rates [11,12,[18][19][20][21]. Unlike P. falciparum, the most common and deadly malaria protozoan in Africa that uses multiple entry receptors, P.vivax's one mode of entry allows the possibility of resistance with only one SNP.…”

Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans

“…It has been proposed that due to the near-fixation of FY*O, P. vivax infection in humans is largely absent from equatorial Africa. An important recent discovery suggests low levels of P.vivax infection in FY*O homozygotes [13–17], which indicates that P. vivax might be evolving escape variants able to overcome the protective effect of FY*O. Phenotypic effects of the FY*A mutation are less clear than FY*O; however, there is evidence of natural selection and reduced P. vivax infection in individuals with this genotype ([18, 19], with conflicting reports in the Brazilian Amazon however [12, 20, 21]).…”

The hide and seek of Plasmodium vivax in West Africa: report from a large-scale study in Beninese asymptomatic subjects

“…To date, this has been mainly accounted for by the absence of the red blood cell surface Duffy antigen among Africans living in this area [4]. Meanwhile, however, P. vivax infections were documented in Duffy-negative subjects in Brazil [5, 6], Ethiopia [7, 8], Madagascar [9], but also in West African countries, such as Mauritania [10], Cameroon [11, 12], Equatorial Guinea, and Angola [13]. According to these different studies, the prevalence of P. vivax in West-Africa is probably underestimated and large-scale epidemiological studies are thus required to investigate the burden of P. vivax infections [3].…”