Basic sanitation: a new indicator for the spread of COVID-19?

BACKGROUND: Basic sanitation could be a potential indicator of the spread of coronavirus disease-2019 (COVID-19) and, in this context, space-time patterns are important tools with which to elucidate the spread of disease and identify risk factors. The aim of this study was to assess a possible association between basic sanitation indices and COVID-19 rates in all the 5570 municipalities of Brazil and its spatial distribution. METHODS: Data of COVID-19 cases registered in Brazil from 28 February until 31 May 2020 and independent variables associated with basic sanitation were included. RESULTS: High incidence rates were significantly associated with precarious water service index (0-25% coverage) and offstandard faecal coliforms index for tap water (5-50% and 75-100% of samples tested). A significant association between high mortality rates and sewage collection (0-25% coverage)/treatment (25-50% coverage) indices was also verified. In addition, clusters with significant spatial autocorrelation were identified mainly in the North and Northeast regions for mortality and incidence rates (high-high risk areas) and for offstandard faecal coliforms index. Those regions are considered the poorest in Brazil, presenting with low incomes, human agglomerations, as well as a poor basic sanitation system, which also hinder the implementation of COVID-19-preventative measures. CONCLUSIONS: A precarious basic sanitation infrastructure could potentially be associated with the high transmission of severe acute respiratory syndrome coronavirus-2 in Brazil.

Macrophages From Subjects With Isolated GH/IGF-I Deficiency Due to a GHRH Receptor Gene Mutation Are Less Prone to Infection by Leishmania amazonensis.

Isolated growth hormone (GH) deficiency (IGHD) affects approximately 1 in 4,000 to 1 in 10,000 individuals worldwide. We have previously described a large cohort of subjects with IGHD due to a homozygous mutation in the GH releasing hormone (GHRH) receptor gene. These subjects exhibit throughout the life very low levels of GH and its principal mediator, the Insulin Growth Factor-I (IGF-I). The facilitating role of IGF-I in the infection of mouse macrophages by different Leishmania strains is well-known. Nevertheless, the role of IGF-I in Leishmania infection of human macrophages has not been studied. This study aimed to evaluate the behavior of Leishmania infection in vitro in macrophages from untreated IGHD subjects. To this end, blood samples were collected from 14 IGHD individuals and 14 age and sex-matched healthy controls. Monocytes were isolated and derived into macrophages and infected with a strain of Leishmania amazonensis. In addition, IGF-I was added to culture medium to evaluate its effect on the infection. Cytokines were measured in the culture supernatants. We found that macrophages from IGHD subjects were less prone to Leishmania infection compared to GH sufficient controls. Both inflammatory and anti-inflammatory cytokines increase only in the supernatants of the control macrophages. Addition of IGF-I to the culture medium increased infection rates. In conclusion, we demonstrated that IGF-I is crucial for Leishmania infection of human macrophages.

sCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis.

BACKGROUND: CD163, receptor for the haptoglobin-hemoglobin complex, is expressed on monocytes/macrophages and neutrophils. A soluble form of CD163 (sCD163) has been associated with the M2 macrophage phenotype, and M2 macrophages have been shown to down-modulate inflammatory responses. In particular, previous studies have shown that M2 is closely associated with the most severe clinical presentation of leprosy (i.e. lepromatous leprosy (LL)), as well as tuberculosis. We hypothesized that sCD163 correlates with severity of diseases caused by intracellular pathogens. METHODOLOGY/PRINCIPAL FINDINGS: To assess this hypothesis, sCD163 levels were measured in the serum of leprosy and visceral leishmaniasis (VL) patients stratified by severity of the clinical presentation. sCD163 levels were significantly higher in patients with these diseases than those observed in healthy control individuals. Further analyses on infection and disease status of leprosy and VL patients revealed a clear association of sCD163 levels with clinical parameters of disease severity. In vitro culture assays revealed that Leishmania infection induced CD163 expression on the surface of both monocyte/macrophages and neutrophils, suggesting these cells as possible sources of sCD163. FACS analyses shows that the cells expressing CD163 produces both TNF-α and IL-4. CONCLUSIONS/SIGNIFICANCE: Taken together, our results reveal sCD163 as a potential biomarker of severity of diseases caused by intracellular pathogens M. leprae and Leishmania spp. and have a modulatory role, with a mix of an inflammatory property induced by TNF-α release, but that potentially induces an anti-inflammatory T cell response, related to IL-4 release.