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.

Increased levels of fetal hemoglobin (HbF, α2γ2) may reduce sickle cell anemia severity due to its ability to inhibit HbS polymerization and also reduce the mean corpuscular HbS concentration. We have investigated the influence of three known major loci on the HbF trait (HBG2, rs748214; BCL11A, rs4671393; and HBS1L-MYB, rs28384513, rs489544 and rs9399137) and HbF levels in SCA patients from the State of Pará, Northern Brazil. Our results showed that high levels of HbF were primarily influenced by alleles of BCL11A (rs4671393) and HMIP (rs4895441) loci, and to a lesser extent by rs748214 Gγ-globin (HBG2) gene promoter. The SNPs rs4671393 and rs4895441 explained 10% and 9.2%, respectively, of the variation in HbF levels, while 4.1% of trait variation was explained by rs748214. The results can be considered as in accordance with the pattern of ancestry displayed by the SCA patients: 39.6% European, 29.6% African and 30.8% Native American, and reinforce the suggestion that studies of association between genetic modifiers and clinical and laboratory manifestations in Brazil must be controlled by ancestry.

The spectrum of β-thalassemia (β-thal) mutations was investigated for the first time in a cohort of 33 unrelated patients from the Brazilian Amazon attending the Center for Hemotherapy and Hematology of the Pará Foundation (HEMOPA), in Belém, the state capital of Pará, Northern Brazil. Identification of the β-thal mutations was made by direct genomic sequencing of the β-globin gene. Mutations were identified in all patients, corresponding to a spectrum of 10 different point mutations and a total of 37 alleles studied. HBB: c.92 + 5G > A [IVS-I-5 (G > A)], was the most common β-thal mutation, followed by HBB: c.118C > T [codon 39 (C > T)], HBB: c.-138C > T [-88 (C>T)], HBB: c.92 + 1G > A [IVS-I-1 (G > A)] and HBB: c.92 + 6T > C [IVS-I-6 (T > C)] mutations. These five mutations (four Mediterranean origin and one African origin) accounted for 86.5% of the β-thal alleles. The profile of β-thal mutations found in northern Brazil is different from those described in other regions of the country. In the southeast and south, the nonsense mutation HBB: c.118C > T is the most prevalent, followed by HBB: c.93-21G > A [IVS-I-110 (G > A)], whereas in the northeast, HBB: c.92 + 6T > C has been identified as the most common mutation, followed by HBB: c.92 + 1G > A. This heterogeneous geographical distribution is certainly related to the ancestry of Brazilian populations because they have similar genetic backgrounds (European, African and Amerindian), although with slightly different admixture proportions. Furthermore, the European contribution in the southeast and south was largely made up of immigrants of other nationalities, such as Italian and Spanish, in addition to Portuguese.