Abstract
Emerging and re-emerging diseases are a major public health problem. In the past years, the world has been threatened by several important emerging or re-emerging infectious diseases, such as Ebola, Avian Influenza A, Yellow Fever (YFV), Dengue (DENV), West Nile Fever (WNV) among others. In Brazil, the emerging infections caused by arboviruses such as DENV and YIF are historical and have been causing serious sequels along years. More recently, the health problems caused by zika (ZIKV) and chikungunya (CHIKV) viruses have been reported. It's well known that emerging infections caused by arboviruses are a great concern because of the large dimensions that epidemics can take and, due to the problems caused and the rapidity with which they spread, it is increasingly necessary to search for effective forms of prevention and treatment. The CHIKV is an emerging arbovirus present in tropical and subtropical regions transmitted by the arthropod vector A. aegypti. Although CHIKV infection may be asymptomatic, it usually leads to the development of chikungunya fever, a disease characterized by the onset of fever, rashes and arthralgia. While many of the symptoms disappear within one week, arthralgia may persist in almost 50% of patients for up to a few years. The molecular mechanisms of chronicity development of this disease are very complex and remain unknow. To contribute to the understanding of the natural course of this disease from infection, chronicity to resolution intentions, this project aims to evaluate the establishment of one international scientific web to study genetic, immunological and metabolomic pathways and factors associated with chronic arthritis in patients previously exposed to CHIKV. The proposal is divided into: (i) ex vivo studies using samples from naturally CHIKV-infected patients from a cohort of the National Clinical Research Network in CHIKV (CNPq 421724/2017); (ii) in vivo/vitro studies for the evaluation of immunologic/metabolic processes associated with the initiation of innate/adaptive immune response and (iii) biotechnological approach for construction of a prototype for treatment or diagnosis. We will characterize the disease course by collecting viral load, cytokines, metabolics, antibody isotypes, haematology (cells), genotype and anti-inflammatory drug levels during acute infection, convalescence, and chronic phases. Of interest is to understand whether CHIKV alters the metabolism of immune cells and impairs subsequent initiation of adaptive immune response. Moreover, this project will be the first initiative to provide insight into the natural history of CHIKV infection and enable identification of patients at risk of chronicity. It's important to know that these objectives are able to be executed because this project is part of the multicenter and multidisciplinary study funded by the Ministry of Health of Brazil entitled "Rede de Pesquisa Clínica e Aplicada em CHIKV - REPLICK" (CNPq 421724/2017, coordinated by André M. Siqueira, participant of this project and vice-coordinated by this proponent), which aims to characterize the clinical and molecular evolution of CHIKV infection in Brazil. This initiative is allowed to access a biobank of well-characterized clinical samples of 10 sites in 10 Brazilian States, from North to South. (AU)
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