RESUMO
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-É, 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.
Assuntos
Malária Vivax , Malária , Humanos , Malária Vivax/genética , Receptor Toll-Like 9 , Receptor 4 Toll-Like/genética , Receptor 6 Toll-Like/genética , Estudos de Casos e Controles , Brasil , Guiana Francesa , Proteína 1 de Superfície de Merozoito/genética , Genótipo , Predisposição Genética para Doença , Receptores Toll-Like/genética , Polimorfismo de Nucleotídeo Único/genética , Plasmodium vivax/genéticaRESUMO
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.
Assuntos
Malária Vivax , Malária , Humanos , Citocinas/genética , Plasmodium vivax/genética , Interleucina-10/genética , Brasil , Receptor Gatilho 1 Expresso em Células Mieloides/genética , Fator de Necrose Tumoral alfa/genética , Interleucina-6/genética , Interleucina-2/genética , Interleucina-5/genética , Malária Vivax/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: Dengue virus (DENV) and Zika virus (ZIKV) have a severe impact on human health worldwide. To understand the dynamics of these viruses in mosquito populations, it is necessary to maintain surveillance during non-epidemic years. METHODS: We aimed to assess the presence of DENV and ZIKV in Aedes aegypti females in the state of Sergipe, northeastern Brazil, during a non-epidemic year. The Ae. aegypti females collected were sectioned, and the heads and thorax were used to analyze the infection rate. Each female was first analyzed to detect Flavivirus using RT-PCR. Flavivirus-positive samples were further screened to detect ZIKV and DENV types 1, 2, 3 and 4. RESULTS: A total of 184 females were collected. ZIKV was identified in 5.4% of the sample and DENV in 7.1%, with the DENV-positive samples belonging to subtypes 2, 3 and 4. The presence of coinfected vectors was also observed. Of the four cities tested, only one was negative for all viruses. CONCLUSIONS: These results show that the maintenance of vigilance during non-epidemic years can provide data on viruses circulating before the onset of outbreaks. This can enable the planning and implementation of local control measures to prevent the appearance of new outbreaks.
Assuntos
Aedes , Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Animais , Brasil/epidemiologia , Vírus da Dengue/genética , Feminino , Humanos , Mosquitos Vetores , Zika virus/genéticaRESUMO
BACKGROUND: Chikungunya (CHIKV) is an arbovirus transmitted mainly by Aedes aegypti females. CHIKV has been highlighted as the pathogen with the greatest impact due to the high morbidity caused by the infection. In 2016, Brazil experienced an outbreak that affected almost 272 000 people. Here, we performed a molecular characterization and phylogenetic analysis of the CHIKV circulating in 2016 in the state of Sergipe, Brazil. METHODS: A partial region of the E1 gene of 16 CHIKV-positive samples from Sergipe State was amplified and sequenced. RESULTS: All sequences belonged to the East-Central-South-African genotype and three point mutations were verified. Two of them were silent mutations and one was a non-synonymous mutation, which changed lysine to threonine at position 211 in the E1 protein. This mutation was present in 81.2% of the sequences, as well as in other five Brazilian sequences from previous studies. This study found that CHIKV strains circulating in Sergipe during the 2016 outbreak belonged to two different haplotypes. CONCLUSIONS: The strains circulating in Sergipe are phylogenetically close to other Brazilian samples circulating in the northeast and southeast of the country, as well as viruses circulating during the same period in Haiti, indicating the rapid spread of these haplotypes.