Influence of trem-1 gene polymorphisms on cytokine levels during malaria by Plasmodium vivax in a frontier area of the Brazilian Amazon.

BACKGROUND: The immunopathology during malaria depends on the level of inflammatory response generated. In this scenario, the TREM-1 has been associated with the severity of infectious diseases and could play an important role in the inflammatory course of malaria. We aimed to describe the allelic and genotypic frequency of four polymorphisms in the trem-1 gene in Plasmodium vivax-infected patients and to verify the association of these polymorphisms with clinical and immunological factors in a frontier area of the Brazilian Amazon. METHODS: We included 76 individuals infected with P. vivax and 144 healthy controls living in the municipality of Oiapoque, Amapá, Brazil. The levels of TNF-α, IL-10, IL-2, IL-4, IL-5, and IFN-γ were measured by flow cytometry, while IL-6, sTREM-1, and antibodies against PvMSP-119 were evaluated by ELISA. The SNPs were genotyped by qPCR technique. Polymorphisms analysis, allelic and genotype, frequencies, and HWE calculation were determined by x2 test in R Software. The association between the parasitemia, gametocytes, antibodies, cytokines, and sTREM-1 with the genotypes of malaria and control groups was performed using the Kruskal-Wallis test, these analyzes were conducted in SPSS Software, at 5% significance level. RESULTS: All SNPs were successfully genotyped. Allelic and genotypic distribution was in Hardy-Weinberg Equilibrium. Furthermore, several associations were identified between malaria and control groups, with increased levels of IL-5, IL-6, IL-10, TNF-α, and IFN-γ in the infected individuals with rs6910730A, rs2234237T, rs2234246T, rs4711668C alleles compared to the homozygous wild-type and heterozygous genotypes of the controls (p-value < 0.05). No association was found for these SNPs and the levels of IL-2, and sTREM-1. CONCLUSIONS: The SNPs on the trem-1 gene are associated with the effector molecules of the innate immunity and may contribute to the identification and effective participation of trem-1 in the modulation of the immune response. This association may be essential for the establishment of immunization strategies against malaria.

Polymorphisms in Toll-Like receptors genes and their associations with immunological parameters in Plasmodium vivax malaria in the Brazil-French Guiana Border.

BACKGROUND: The innate immune response plays an important role during malaria. Toll-like receptors (TLR) are capable of recognizing pathogen molecules. We aimed to evaluate five polymorphisms in TLR-4, TLR-6, and TLR-9 genes and their association with cytokine levels and clinical parameters in malaria from the Brazil-French Guiana border. METHODS: A case-control study was conducted in Amapá, Brazil. P. vivax patients and individuals not infected were evaluated. Genotyping of five SNPs was carried out by qPCR. Circulating cytokines were measured by CBA. The MSP-119 IgG antibodies were performed by ELISA. RESULTS: An association between TLR4 A299G with parasitemia was observed. There was an increase for IFN-ɤ, TNF-ɑ, IL-6, and IL-10 in the TLR-4 A299G and T3911, TLR-6 S249P, and TLR-9 1486C/T, SNPs for the studied malarial groups. There were significant findings for the TLR-4 variants A299G and T3911, TLR-9 1237C/T, and 1486C/T. For the reactivity of MSP-119 antibodies levels, no significant results were found in malaria, and control groups. CONCLUSIONS: The profile of the immune response observed by polymorphisms in TLRs genes does not seem to be standard for all types of malaria infection around the world. This can depend on the human population and the species of Plasmodium.

Efficacy in the treatment of malaria by Plasmodium vivax in Oiapoque, Brazil, on the border with French Guiana: the importance of control over external factors.

BACKGROUND: Plasmodium vivax malaria is an important public health issue in the Amazon region, and it accounts for approximately 84 % of cases of the disease. Migration across the border between Brazil and French Guiana contributes to the maintenance of the disease. The aim of this study was to evaluate the therapeutic and parasitological responses of patients with P. vivax malaria treated with chloroquine and primaquine in the socio-environmental context of cross-border interactions between Brazil and French Guiana. The factors controlled were diagnostic agreement, adherence, adjustment of primaquine doses for patient weight, and quality of the drugs used. METHODS: A prospective study was conducted in 2011 with 103 individuals aged 10-60 years with a positive diagnosis of P. vivax treated with chloroquine (10 mg base/kg on the first day, followed by 7.5 mg/kg on the second and third days) and primaquine for 7 days, who were followed for 28 days. The primaquine doses were adjusted for the patients' weight. A number of factors were determined: epidemiological characteristics, origin of patients, signs and symptoms, initial parasitaemia and parasitaemia clearance time, blood concentrations of chloroquine and primaquine, quality of anti-malarial drugs and diagnostic agreement. RESULTS: Ninety-five patients were followed for 28 days. There was a 100 % agreement in microscopic diagnosis between field laboratory and reference centre. The adhesion to the treatment was 100 %. Of these patients, 32.6 % received a weight-adjusted dose of primaquine. The chloroquine and primaquine tablets were consistent with the optimal quality limits for human consumption. The investigated patients achieved optimal blood exposure to anti-malarial drugs. The parasitological and therapeutic response was adequate in 99.0 % of cases. CONCLUSIONS: In the municipality of Oiapoque, the therapeutic regime used for the treatment of P. vivax malaria using chloroquine combined with primaquine remains effective, when external factors are controlled, such as the quality of anti-malarial drugs, the adhesion to the treatment prescribed, the correct diagnostic and the adjustment of primaquine dose for patient body weight.