RESUMO
Oral transmission of Chagas disease has been increasing in Latin American countries. The present study aimed to investigate changes in hepatic function, coagulation factor levels and parasite load in human acute Chagas disease (ACD) secondary to oral Trypanosoma cruzi transmission. Clinical and epidemiological findings of 102 infected individuals attended in the State of Pará from October 2013 to February 2016 were included. The most common symptoms were fever (98%), asthenia (83.3%), face and limb edema (80.4%), headache (74.5%) and myalgia (72.5%). The hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of 30 ACD patients were higher compared with controls, and this increase was independent of the treatment with benznidazole. Moreover, ACD individuals had higher plasma levels of activated protein C and lower levels of factor VII of the coagulation cascade. Patients with the highest parasite load had also the most increased transaminase levels. Also, ALT and AST were associated moderately (r = 0.429) and strongly (r = 0.595) with parasite load respectively. In conclusion, the present study raises the possibility that a disturbance in coagulation and hepatic function may be linked to human ACD.
Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Doença de Chagas/fisiopatologia , Fator VIIa/análise , Fígado/fisiopatologia , Proteína C/análise , Doença Aguda , Adulto , Biomarcadores/sangue , Brasil/epidemiologia , Estudos de Casos e Controles , Doença de Chagas/sangue , Doença de Chagas/enzimologia , Doença de Chagas/transmissão , Feminino , Humanos , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Carga Parasitária , Estudos ProspectivosRESUMO
Previous work showed that the thymus can be infected by RNA viruses as HIV and HTLV-1. We thus hypothesized that the thymus might also be infected by the Zika virus (ZIKV). Herein we provide compelling evidence that ZIKV targets human thymic epithelial cells (TEC) in vivo and in vitro. ZIKV-infection enhances keratinization of TEC, with a decrease in proliferation and increase in cell death. Moreover, ZIKV modulates a high amount of coding RNAs with upregulation of genes related to cell adhesion and migration, as well as non-coding genes including miRNAs, circRNAs and lncRNAs. Moreover, we observed enhanced attachment of lymphoblastic T-cells to infected TEC, as well as virus transfer to those cells. Lastly, alterations in thymuses from babies congenitally infected were seen, with the presence of viral envelope protein in TEC. Taken together, our data reveals that the thymus, particularly the thymic epithelium, is a target for the ZIKV with changes in the expression of molecules that are relevant for interactions with developing thymocytes.