BackgroundYellow fever (YF) is endemic in the Brazilian Amazon Basin, and sporadic outbreaks take place outside the endemic area in Brazil. Since 2016, YF epidemics have been occurring in Southeast Brazil, with more than 1,900 human cases and more than 1,600 epizooties of non-human primates (NHPs) reported until April 2018. Previous studies have demonstrated that Yellow fever virus (YFV) causing outbreaks in 2017 formed a monophyletic group.Methodology/Principal findingsAiming to decipher the origin of the YFV responsible for the recent epidemics, we obtained nucleotide sequences of YFV detected in humans (n = 6) and NHPs (n = 10) from Minas Gerais state during 2017–2018. Next, we performed evolutionary analyses and discussed the results in the light of epidemiological records (official numbers of YFV cases at each Brazilian Federative unit, reported by the Brazilian Ministry of Health). Nucleotide sequences of YFV from Southeast Brazil from 2016 to 2018 were highly conserved and formed a monophyletic lineage (BR-YFV_2016/18) within the genotype South America I. Different clusters were observed within lineage BR-YFV_2016/18, one containing the majority of isolates (from humans and NHPs), indicating the sylvatic transmission of YFV. We also detected a cluster characterized by two synapomorphies (amino acid substitutions) that contained YFV only associated with NHP what should be further investigated. The topology of lineage BR-YFV_2016/18 was congruent with epidemiological and temporal patterns of the ongoing epidemic. YFV isolates detected in 2016, in São Paulo state were located in the most basal position of the lineage, followed by the isolates from Minas Gerais and Espírito Santo obtained in 2017 and 2018. The most recent common ancestor of the lineage BR-YFV_2016/18 dated to 2015 (95% credible intervals = 2014–2016), in a period that was coincident with the reemergence of YFV in the Midwest region of Brazil.ConclusionsThe results demonstrated a single introduction of YFV in the Southeast region and the silent viral circulation before the onset of the outbreaks in 2016. Evolutionary analyses combined with epidemiological records supported the idea that BR-YFV_2016/18 was probably introduced from the Midwest into the Southeast region, possibly in São Paulo state. The persistence of YFV in the Southeast region, causing epidemics from 2016 to 2018, suggests that this region presents suitable ecological and climatic conditions for YFV maintenance during the epidemic and interepidemic seasons. This fact poses risks for the establishing of YF enzootic cycles and epidemics, outside the Amazon Basin in Brazil. YF surveillance and studies of viral dynamics deserve particular attention, especially in Midwest, Southeast and neighbor regions which are the main areas historically associated with YF outbreaks outside the Amazon Basin. YFV persistence in Southeast Brazil should be carefully considered in the context of public health, especially for public health decision-makers and researchers.

Cutaneous leishmaniasis affects millions of people around the world. Several species ofLeishmaniainfect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO−) in the control of parasites by macrophages, which are both the host cells and the effector cells. We also discuss the role of neutrophil-derived oxygen and nitrogen reactive species during infection withLeishmania. We emphasize the role of these cells in the outcome of leishmaniasis early after infection, before the adaptive Th-cell immune response.

Background: Yellow fever outbreaks have re-emerged in Brazil during 2016-18, with mortality rates up to 30%. Although urban transmission has not been reported since 1942, the risk of re-urbanization of yellow fever is significant, as Aedes aegypti is present in most tropical and sub-tropical cities in the World and still remains the main vector of urban YFV. Although the YFV vaccine is safe and effective, it does not always reach populations at greatest risk of infection and there is an acknowledged global shortage of vaccine supply. The introgression of Wolbachia bacteria into Ae. aegypti mosquito populations is being trialed in several countries (www.worldmosquito.org) as a biocontrol method against dengue, Zika and chikungunya. Here, we studied the ability of Wolbachia to reduce the transmission potential of Ae. aegypti mosquitoes for Yellow fever virus (YFV). Methods: Two recently isolated YFV (primate and human) were used to challenge field-derived wild-type and Wolbachia-infected (wMel +) Ae. aegypti mosquitoes. The YFV infection status was followed for 7, 14 and 21 days post-oral feeding (dpf). The YFV transmission potential of mosquitoes was evaluated via nano-injection of saliva into uninfected mosquitoes or by inoculation in mice. Results: We found that Wolbachia was able to significantly reduce the prevalence of mosquitoes with YFV infected heads and thoraces for both viral isolates. Furthermore, analyses of mosquito saliva, through indirect injection into naïve mosquitoes or via interferon-deficient mouse model, indicated Wolbachia was associated with profound reduction in the YFV transmission potential of mosquitoes (14dpf). Conclusions: Our results suggest that Wolbachia introgression could be used as a complementary strategy for prevention of urban yellow fever transmission, along with the human vaccination program.

Abstract. Dengue is responsible for a wide range of clinical manifestations, ranging from asymptomatic infections to severe cases. The alteration of cytokine levels correlated with clinical characteristics can help determine prognostic markers of the disease and the identification of targets for immunotherapy. We measured the viral load, serotype, and cytokine levels of 212 serum samples from patients with acute dengue infection during days 1-4 after the onset of symptoms. The patients were classified as either with hemorrhagic manifestations (HM) or with no hemorrhagic manifestations (NHM). The cytokines interleukin-6 (IL-6), IL-8, and IL-10 were increased (P < 0.05) in the dengue virus+ group, compared with the control group. A higher viral load (P < 0.05) and IL-6 was detected in the HM group compared with the NHM group. Interestingly, the NHM group demonstrated a significant positive correlation between inflammatory (IL-6 and 8) and anti-inflammatory (IL-10) cytokines, whereas the HM group did not. These findings suggest that a disturbance in the balance of inflammatory cytokines IL-6 and IL-8 with the anti-inflammatory cytokine, IL-10, combined with the high levels of IL-6 and viral load, characterize possible mechanisms related to the formation of HM.

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BACKGROUNDThe heat-labile nature of Dengue virus (DENV) in serum samples must be considered when applying routine diagnostic tests to avoid issues that could impact the accuracy of test results with direct implications for case management and disease reporting.OBJECTIVES To check if pre-analytical variables, such as storage time and temperature, have an impact on the accuracy of the main routine diagnostic tests for dengue.METHODS Virus isolation, reverse transcription real-time polymerase chain reaction (RT-PCR) and NS1 enzyme-linked immunosorbent assay (ELISA) were evaluated using 84 samples submitted to different pre-analytical conditions. FINDINGS Sensitivity and negative predictive value were directly affected by sample storage conditions. RT-PCR and virus isolation showed greater dependence on well-conserved samples for an accurate diagnosis. Interestingly, even storage at -30ºC for a relatively short time (15 days) was not adequate for accurate results using virus isolation and RT-PCR tests. On the other hand, NS1 ELISA showed no significant reduction in positivity for aliquots tested under the same conditions as in the previous tests. MAIN CONCLUSIONSOur results support the stability of the NS1 marker in ELISA diagnosis and indicate that the accuracy of routine tests such as virus isolation and RT-PCR is significantly affected by inadequate transport and storage conditions of serum samples.