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Flaviviruses are agents of a major emerging human public health issue and members of this genus have been associated with central nervous system (CNS) infections. In Brazil, a country endemic for some arboviruses, the most clinically relevant neurotropic flaviviruses include Dengue virus and Zika virus. Flaviviruses cause diseases ranging from mild or sub-clinical infections to severe cases as CNS infections. There is a lack of data about the incidence of flaviviruses in the CNS of children in Brazil. In this review, we provide a general overview of several flaviviruses that cause CNS infections in Brazilian children and explore the importance of epidemiological surveillance of CNS infections in cases of flavivirus infections.

RESUMO

Flaviviruses are agents of a major emerging human public health issue, and members of the Flavivirus genus have been associated with central nervous system (CNS) infections. In Brazil, a country endemic for some arboviruses, the most clinically relevant neurotropic flaviviruses include dengue virus and Zika virus. Flaviviruses cause diseases ranging from mild or subclinical infections to severe cases as CNS infections. There is a lack of data about the incidence of flaviviruses in the CNS of children in Brazil. In this review, we provide a general overview of several flaviviruses that cause CNS infections in Brazilian children and explore the importance of epidemiologic surveillance of CNS infections in cases of Flavivirus infections.

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At the end of 2016, Brazil experienced an unprecedented yellow fever (YF) outbreak. Clinical, molecular and ecological aspects of human and non-human primate (NHP) samples collected at the beginning of the outbreak are described in this study. Spatial distribution analyses demonstrated a strong overlap between human and NHP cases. Through molecular analyses, we showed that the outbreak had a sylvatic origin, caused by the South American genotype 1 YFV, which has already been shown to circulate in Brazil. As expected, the clusters of cases were identified in regions with a low vaccination coverage. Our findings highlight the importance of the synchronization of animal surveillance and health services to identify emerging YF cases, thereby promoting a better response to the vulnerable population.

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A cross-sectional serosurvey was performed to identify environmental features or practices of dairy farms associated with risk for exposure to vaccinia-like viruses in dairy cattle in Brazil. Sera from 103 cows from 18 farms in Minas Gerais state were examined for Orthopoxvirus-neutralizing antibodies. A database of 243 binary or multiple-selection categorical variables regarding the physical features and surrounding ecology of each property was obtained. Thirteen of 46 presumptive predictor variables were found to be significantly associated with Orthopoxvirus serostatus by univariate logistic regression methods. Use of teat sanitizer and having felids on the property were independently associated with virus exposure by multivariable analysis. Rodents have long been suspected of serving as maintenance reservoirs for vaccinia-like viruses in Brazil. Therefore, domestic felids are not only effective predators of small rodent pests, but also their urine can serve as a deterrent to rodent habitation in buildings such as stables and barns. These results corroborate previous evidence of the high significance of rodents in the Vaccinia virus transmission cycle, and they also raise questions regarding the common use of teat sanitizers in dairy production areas.

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Vaccinia virus (VACV) is an important pathogen. Although studies have shown relationships between probiotics and viruses, the effect of probiotics on VACV infection is unknown. Therefore, this work aims to investigate the probiotics effects on VACV infection. Mice were divided into four groups, two non-infected groups, one receiving the probiotic, the other one not receiving it, and two groups infected intranasally with VACV Western Reserve (VACV-WR) receiving or not receiving the probiotic. Viral titres in organs and cytokine production in the lungs were analysed. Lung samples were also subjected to histological analysis. The intake of probiotic results in reduction in viral spread with a significant decrease of VACV titer on lung, liver and brain of treated group. In addition,treatment with the probiotic results in attenuated mice lung inflammation showing fewer lesions on histological findings and decreased lethality in mice infected with VACV. The ingestion of Lactobacillus paracasei ST11 (LPST11) after VACV infection resulted in 2/9 animal lethality compared with 4/9 in the VACV group. This is the first study on probiotics and VACV interactions, providing not only information about this interaction, but also proposing a model for future studies involving probiotics and other poxvirus.

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We describe what is to our knowledge the first fatal case of central nervous system Enterovirus infection in Brazil. Molecular and phylogenetic characterization revealed that Enterovirus A was the aetiologic agent of this case.

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The objective of this study was to assess the effectiveness of BG-Sentinel (BGS) traps for mass trapping at the household level to control the dengue vector, Aedes aegypti (L.), in Manaus (Brazil) by performing a cluster randomized controlled trial. After an initial questionnaire and baseline monitoring, 6 out of 12 clusters were randomly allocated to the intervention arm, where participating premises received one BGS trap for mass trapping. The other six clusters did not receive traps and were considered as the control arm. Biweekly monitoring with BGS in both arms assessed the impact of mass trapping. At the end of the study, a serological survey was conducted and a second questionnaire was conducted in the intervention arm. Entomological monitoring indicated that mass trapping with BGS traps significantly reduced the abundance of adult female Ae. aegypti during the first five rainy months. In the subsequent dry season when the mosquito population was lower, no effect of mass trapping was observed. Fewer Ae. aegypti females were measured in the intervention arm during the next rainy period, but no significant difference between arms was observed. The serological survey revealed that in participating houses of mass trapping areas recent dengue infections were less common than in control areas, although this effect was not statistically significant. The majority of participants responded positively to questions concerning user satisfaction. Our results suggest that BGS traps are a promising tool which might be deployed as part of dengue control programs; however, further investigations and larger scale studies are necessary.

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Bovine vaccinia (BV), a zoonosis caused by Vaccinia virus (VACV), affects dairy cattle and milkers, causing economic, veterinary and human health impacts. Despite such impacts, there are no experimental studies about the pathogenesis of BV in cows to assess whether there is a systemic spread of the virus and whether there are different ways of VACV shedding. Trying to answer some of these questions, a study was proposed using experimental inoculation of VACV in cows. All experimentally infected cows developed lesions compatible with VACV infection in cattle. Two of the six animals presented VACV DNA in blood and faecal samples, starting at the 2nd and the 3rd day post-infection (d.p.i.), respectively, and lasting until the 36th d.p.i., in an intermittent way. This study provides new evidence that VACV can be detected in blood and faeces of infected cows, suggesting that BV could be a systemic disease, and also bringing new information about the epidemiology and pathogenesis of BV.

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Orf virus (ORFV), the prototype of the genus Parapoxvirus, is the aetiological agent of contagious ecthyma (CE), a pustular dermatitis that afflicts domestic and wild small ruminants. CE is one of the most widespread poxvirus diseases in the world, causing public health impacts. Outbreaks of ORFV have been observed in all geographical regions of Brazil, affecting ovine and caprine herds. The origins, epidemiology and identity of Brazilian ORFVs are unknown, and no comparative or phylogenetic studies of these viruses have been performed. In the present study, we revisited CE outbreaks which occurred until 32 years ago, and we assessed, genetically, five viral isolates. We performed the sequencing and analysis of the three ORFV molecular markers: B2L gene, virus interferon resistance gene (VIR) and the vascular endothelial growth factor gene. Nucleotide and amino acid analysis of the analysed genes demonstrated that Brazilian ORFVs do not form a unique cluster, and presented more similarity to other worldwide ORFV samples than with each other. These data raise the questions of whether there are different worldwide ORFVs circulating in Brazil, or if all the Brazilian ORFV samples are of the same virus taken at distinct time points.

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AIMS: To investigate the in vitro antiviral activity of Distictella elongata (Vahl) Urb. ethanol extracts from leaves (LEE), fruits (FEE), stems and their main components. METHODS AND RESULTS: The antiviral activity was evaluated against human herpesvirus type 1 (HSV-1), murine encephalomyocarditis virus (EMCV), vaccinia virus Western Reserve (VACV-WR) and dengue virus 2 (DENV-2) by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. LEE presented anti-HSV-1 [EC(50) 142.8 ± 5.3 µg ml(-1); selectivity index (SI) 2.0] and anti-DENV-2 activity (EC(50) 9.8 ± 1.3 µg ml(-1) ; SI 1.5). The pectolinarin (1) isolated from LEE was less active against HSV-1 and DENV-2. A mixture of the triterpenoids ursolic, pomolic and oleanolic acids was also obtained. Ursolic and oleanolic acids have shown antiviral activity against HSV-1. A mixture of pectolinarin (1) and acacetin-7-O-rutinoside (2) was isolated from FEE and has presented anti-DENV-2 activity (EC(50) 11.1 ± 1.6 µg ml(-1) ; SI > 45). Besides the antiviral activity, D. elongata has disclosed antioxidant effect. CONCLUSIONS: These data shows that D. elongata has antiviral activity mainly against HSV-1 and DENV-2, besides antioxidant activity. These effects might be principally attributed to flavonoids isolated. SIGNIFICANCE AND IMPACT OF THE STUDY: Distictella elongata might be considered a promising source of anti-dengue fever phytochemicals.

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