Kynurenine elevation correlates with T regulatory cells increase in acute plasmodium vivax infection : a pilot study

Disease-tolerance mechanisms limit infection severity by preventing tissue damage; however, the underlying mechanisms in human malaria are still unclear. Tryptophan (TRP), an essential amino acid, is catabolized into tolerogenic metabolites, kynurenines (KYN), by indoleamine 2,3-dioxygenase 1 (IDO1), which can induce Foxp3+ T regulatory cells (Tregs). In this study, we evaluated the relationship of these metabolites with Treg-mediated tolerance induction in acute malaria infections. We performed a cross-sectional study that evaluated asymptomatic, symptomatic malaria patients and endemic control patient groups. We assessed plasmatic concentration of cytokines by ELISA. Plasmatic TRP and KYN levels were measured by HPLC. Peripheral T regulatory cells were measured and phenotyped by flow cytometry. The KYN/TRP ratio was significantly elevated in asymptomatic and symptomatic Plasmodium infection, compared to healthy controls. Also, Th1 and Th2 cytokines were elevated in the acute phase of malaria disease. IFN-gamma increase in acute phase was positively correlated with the KYN/TRP ratio and KYN elevation was positively correlated with the increase of peripheral FoxP3+ T regulatory cells. Additional studies are needed not only to identify innate mechanisms that increase tryptophan catabolism but also the role of Tregs in controlling malaria-induced pathology and malaria tolerance by the host423CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO AMAZONAS - FAPEAM470315/2012-1; 462245/2014-4; 436097/2018-42010/52146-0não te

Epidemiology and control of frontier malaria in Brazil: lessons from community-based studies in rural Amazonia

We describe the epidemiology of malaria in a frontier agricultural settlement in Brazilian Amazonia. We analysed the incidence of slide-confirmed symptomatic infections diagnosed between 2001 and 2006 in a cohort of 531 individuals (2281.53 person-years of follow-up) and parasite prevalence data derived from four cross-sectional surveys. Overall, the incidence rates of Plasmodium vivax and P. falciparaum were 20.6/100 and 6.8/100 person-years at risk, respectively, with a marked decline in the incidence of both species (81.4 and 56.8%, respectively) observed between 2001 and 2006. PCR revealed 5.4-fold more infections than conventional microscopy in population-wide cross-sectional surveys carried out between 2004 and 2006 (average prevalence, 11.3 vs. 2.0%). Only 27.2% of PCR-positive (but 73.3% of slide-positive) individuals had symptoms when enrolled, indicating that asymptomatic carriage of low-grade parasitaemias is a common phenomenon in frontier settlements. A circular cluster comprising 22.3% of the households, all situated in the area of most recent occupation, comprised 69.1% of all malaria infections diagnosed during the follow-up, with malaria incidence decreasing exponentially with distance from the cluster centre. By targeting one-quarter of the households, with selective indoor spraying or other house-protection measures, malaria incidence could be reduced by more than two-thirds in this community. (C) 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)[470067/2004-7]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao de Amparo Pesquisa do Estado de Sao Paulo (FAPESP)[03/09719-6]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao de Amparo Pesquisa do Estado de Sao Paulo (FAPESP)[05/51988-0]FAPESP (MdSN and RRD`A)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CNPqConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CAPESCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES