Dynamics of Transmission of Urban Arbovirus Dengue, Zika and Chikungunya in Southwestern Region of Bahia, Brazil.

Arboviral diseases are disseminated all over the world. In Brazil, they remain neglected, alerting public authorities to possible outbreaks. Over here, we report the epidemiological indicators of Dengue from 2010 to 2015, Zika between 2015 and 2016, and Chikungunya from 2014 to 2016, within 19 municipalities of Southwestern Region of Bahia, Brazil. The data were collected from Brazilian national public information systems (SISFAD, SINAN, and IBGE) and by Endemic Control Agents. The analysis consisted of a description of vector characteristics, Home Infestation Index and characterization of human reported cases. The years 2011 and 2013 were recorded as having the highest frequencies of positive properties for the presence of the arboviruse vectors. Most municipalities presented high annual values of Home Infestation Index indicating an alert situation (62.28%). In the evaluated period, there were (i) 9,196 cases of Dengue, (ii) 636 cases of Zika and (iii) 224 cases of Chikungunya reported. This is the first report of the epidemiological characteristics of these arboviruses in the 19 municipalities of Bahia. It is believed that the data collected may contribute to public health policies aimed at controlling future epidemics of these arboviruses.

The Combined Use of Melatonin and an Indoleamine 2,3-Dioxygenase-1 Inhibitor Enhances Vaccine-Induced Protective Cellular Immunity to HPV16-Associated Tumors.

Immunotherapy has become an important ally in the fight against distinct types of cancer. However, the metabolic plasticity of the tumor environment frequently influences the efficacy of therapeutic procedures, including those based on immunological tools. In this scenario, immunometabolic adjuvants arise as an alternative toward the development of more efficient cancer therapies. Here we demonstrated that the combination of melatonin, a neuroimmunomodulator molecule, and an indoleamine 2,3-dioxygenase (IDO) inhibitor (1-methyl-DL-tryptophan, DL-1MT) improves the efficacy of an immunotherapy (gDE7) targeting human papillomavirus (HPV)-associated tumors. Melatonin or IDO inhibitors (D-1MT and DL-1MT) directly reduced proliferation, migration, adhesion and viability of a tumor cell line (TC-1), capable to express the HPV-16 E6 and E7 oncoproteins, but could not confer in vivo antitumor protection effects. Nonetheless, combination of gDE7 with melatonin or D-1MT or DL-1MT enhanced the antitumor protective immunity of gDE7-based vaccine in mice. Notably, expression of IDO1 in stromal cells and/or immune cells, but not in tumor cells, inhibited the antitumor effects of the gDE7, as demonstrated in IDO1-deficient mice. Finally, co-administration of gDE7, melatonin and DL-1MT further improved the protective antitumor effects and the numbers of circulating E7-specific CD8+ T cells in mice previously transplanted with TC-1 cells. The unprecedented combination of melatonin and IDO inhibitors, as immunometabolic adjuvants, thus, represents a new and promising alternative for improving the efficacy of immunotherapeutic treatments of HPV-associated tumors.