Interleukin (IL)‐22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate immunity, tissue protection, and repair. IL‐22 may also cause inflammation and abnormal cell proliferation. The binding of IL‐22 to its receptor is competed by IL‐22 binding protein (IL‐22BP), which may limit the deleterious effects of IL‐22. The role of IL‐22 and IL‐22BP in chronic liver diseases is unknown. We addressed this question in individuals chronically infected with schistosomes or hepatitis C virus (HCV). We first demonstrate that schistosome eggs stimulate production of IL‐22 transcripts and inhibit accumulation of IL22‐BP transcripts in schistosome‐infected mice, and that schistosome eggs selectively stimulate production of IL‐22 in cultures of blood leukocytes from individuals chronically infected with Schistosoma japonicum. High IL‐22 levels in cultures correlated with protection against hepatic fibrosis and portal hypertension. To test further the implication of IL‐22/IL‐22BP in hepatic disease, we analyzed common genetic variants of IL22RA2, which encodes IL‐22BP, and found that the genotypes, AA, GG of rs6570136 (P = 0.003; odds ratio [OR] = 2), and CC, TT of rs2064501 (P = 0.01; OR = 2), were associated with severe fibrosis in Chinese infected with S. japonicum. We confirmed this result in Sudanese (rs6570136 GG [P = 0.0007; OR = 8.2], rs2064501 TT [P = 0.02; OR = 3.1]), and Brazilians (rs6570136 GG [P = 0.003; OR = 26], rs2064501 TC, TT (P = 0.03; OR = 11]) infected with S. mansoni. The aggravating genotypes were associated with high IL22RA2 transcripts levels. Furthermore, these same variants were also associated with HCV‐induced fibrosis and cirrhosis (rs6570136 GG, GA [P = 0.007; OR = 1.7], rs2064501 TT, TC (P = 0.004; OR = 2.4]). Conclusions: These results provide strong evidence that IL‐22 protects against and IL‐22BP aggravates liver fibrosis and cirrhosis in humans with chronic liver infections. Thus, pharmacological modulation of IL‐22 BP may be an effective strategy to limit cirrhosis. (Hepatology 2015;61:1321–1331)

Background: Dengue fever is an arthropod-borne viral disease caused by dengue virus (DENV) and transmitted by Aedes mosquitoes. The Northeast region of Brazil is characterized by having one of the highest dengue rates in the country, in addition to being considered the poorest region. Here, we aimed to identify spatial clusters with the highest dengue risk, as well as to analyze the temporal behavior of the incidence rate and the effects of social determinants on the disease transmission dynamic in Northeastern Brazil. Methods: This is an ecological study carried out with all confirmed cases of dengue in the Northeast Brazil between 2014 and 2017. Data were extracted from the National Notifiable Diseases Information System (SINAN) and the Brazilian Institute of Geography and Statistics (IBGE). Local empirical Bayesian model, Moran statistics and spatial scan statistics were applied. The association between dengue incidence rate and social determinants was tested using Moran’s bivariate correlation. Results: A total of 509 261 cases of dengue were confirmed in the Northeast during the study period, 53.41% of them were concentrated in Pernambuco and Ceará states. Spatial analysis showed a heterogeneous distribution of dengue cases in the region, with the highest rates in the east coast. Four risk clusters were observed, involving 815 municipalities (45.45%). Moreover, social indicators related to population density, education, income, housing, and social vulnerability showed a spatial correlation with the dengue incidence rate. Conclusions: This study provides information on the spatial dynamics of dengue in northeastern Brazil and its relationship with social determinants and can be used in the formulation of public health policies to reduce the impact of the disease in vulnerable populations.

Introduction: Tuberculosis is one of the ten leading causes of death and the leading infectious cause worldwide. The disease represents a challenge to health systems around the world. In 2018, it is estimated that 10 million people were affected by tuberculosis, and approximately 1.5 million people died due to the disease worldwide, including 251,000 patients coinfected with HIV. In Brazil, the disease caused 4,490 deaths, with rate of 2.2 deaths per 100,000 inhabitants. The objective of this study was to analyze the time behavior, spatial, spatial-temporal distribution, and the effects of social vulnerability on the incidence of TB in Brazil during the period from 2001 to 2017. Materials and methods: A spatial-temporal ecological study was conducted, including all new cases of tuberculosis registered in Brazil during the period from 2001 to 2017. The following variables were analyzed: incidence rate of tuberculosis, the Social Vulnerability Index, its subindices, its 16 indicators, and an additional 14 variables available on the Atlas of Social Vulnerability. The statistical treatment of the data consisted of the following three stages: a) time trend analysis with a joinpoint regression model; b) spatial analysis and identification of risk areas based on smoothing of the incidence rate by local empirical Bayesian model, application of global and local Moran statistics, and, finally, spatial-temporal scan statistics; and c) analysis of association between the incidence rate and the indicators of social vulnerability. Results: Brazil reduced the incidence of tuberculosis from 42.8 per 100,000 to 35.2 per 100,000 between 2001 and 2017. Only the state of Minas Gerais showed an increasing trend, whereas nine other states showed a stationary trend. A total of 326 Brazilian municipalities were classified as high priority, and 22 high-risk spatial-temporal clusters were identified. The overall Social Vulnerability Index and the subindices of Human Capital and Income and Work were associated with the incidence of tuberculosis. It was also observed that the incidence rates were greater in municipalities with greater social vulnerability. Conclusions: This study identified clusters with high risk of TB in Brazil. A significant association was observed between the incidence rate of TB and the indices of social vulnerability.

Brazil ranks second in the number of confirmed cases of COVID-19 worldwide. In spite of this, coping measures differ throughout the national territory, as does the disease's impact on the population. This cross-sectional observational study, with 59 695 cases of COVID-19 registered in the state of Alagoas between March and August 2020, analysed clinical-epidemiological variables, incidence rate, mortality rate, case fatality rate (CFR) and the social indicators municipal human development index (MHDI) and social vulnerability index (SVI). Moran statistics and regression models were applied. Logistic regression analysis was applied to determine the predictors of death. The incidence rate was 1788.7/100 000 inhabitants; mortality rate was 48.0/100 000 and CFR was 2.7%. The highest incidence rates were observed in municipalities with better human development (overall MHDI (I = 0.1668; p = 0.002), education MHDI (I = 0.1649; p = 0.002) and income MHDI (I = 0.1880; p = 0.005)) and higher social vulnerability (overall SVI (I = 0.0599; p = 0.033)). CFR was associated with higher social vulnerability (SVI human capital (I = 0.0858; p = 0.004) and SVI urban infrastructure (I = 0.0985; p = 0.040)). Of the analysed cases, 55.4% were female; 2/3 were Black or Brown and the median age was 41 years. Among deaths, most were male (919; 57.4%) and elderly (1171; 73.1%). The predictors of death were male sex, advanced age and the presence of comorbidities. In Alagoas, Brazil, the disease has undergone a process of interiorisation and caused more deaths in poorer municipalities. The presence of comorbidities and advanced age were predictors of death.