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BACKGROUND Despite efforts to mitigate the impact of dengue virus (DENV) epidemics, the virus remains a public health problem in tropical and subtropical regions around the world. Most DENV cases in the Americas between January and July 2019 were reported in Brazil. São Paulo State in the southeast of Brazil has reported nearly half of all DENV infections in the country. OBJECTIVES To understand the origin and dynamics of the 2019 DENV outbreak. METHODS Here using portable nanopore sequencing we generated20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities of São Paulo State, Araraquara and São José do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. FINDINGS The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Our analysis shows that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. MAIN CONCLUSIONS Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.

The disease caused by each of the four serotypes of dengue virus (DENV) have plagued humans since last century. Symptoms of dengue virus (DENV) infection range from asymptomatic to dengue fever (DF) to severe dengue disease (SDD). One third of the world's population lives in regions with active urban DENV transmission, and thousands of serologically naïve travelers visit these areas annually, making a significant portion of the human population at risk of being infected. Even though lifelong immunity to the homotypic serotype is achieved after a primary DENV infection. Heterotypic DENV infections may be exacerbated by a pre-existing immune memory to the primary infection and can result in an increased probability of severe disease. Not only, age, comorbidities and presence of antibodies transferred passively from dengue-immune mother to infants are considered risk factors to dengue severe forms. Plasma leakage and multiple organ impairment are well documented in the literature, affecting liver, lung, brain, muscle, and kidney. However, unusual manifestation, severe or not, have been reported and may require medical attention. This review will summarize and discuss the increasing reports of unusual manifestations in the clinical course of dengue infection., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: We aimed to report the first 54 cases of pregnant women infected by Zika virus (ZIKV) and their virologic and clinical outcomes, as well as their newborns' outcomes, in 2016, after the emergence of ZIKV in dengue-endemic areas of São Paulo, Brazil., Methods: This descriptive study was performed from February to October 2016 on 54 quantitative real-time PCR ZIKV-positive pregnant women identified by the public health authority of São José do Rio Preto, São Paulo, Brazil. The women were followed and had clinical and epidemiologic data collected before and after birth. Adverse outcomes in newborns were analysed and reported. Urine or blood samples from newborns were collected to identify ZIKV infection by reverse transcription PCR (RT-PCR)., Results: A total of 216 acute Zika-suspected pregnant women were identified, and 54 had the diagnosis confirmed by RT-PCR. None of the 54 women miscarried. Among the 54 newborns, 15 exhibited adverse outcomes at birth. The highest number of ZIKV infections occurred during the second and third trimesters. No cases of microcephaly were reported, though a broad clinical spectrum of outcomes, including lenticulostriate vasculopathy, subependymal cysts, and auditory and ophthalmologic disorders, were identified. ZIKV RNA was detected in 18 of 51 newborns tested and in eight of 15 newborns with adverse outcomes., Conclusions: Although other studies have associated many newborn outcomes to ZIKV infection during pregnancy, these same adverse outcomes were rare or nonexistent in this study. The clinical presentation the newborns we studied was mild compared to other reports, suggesting that there is significant heterogeneity in congenital Zika infection., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Yellow fever virus (YFV) replication is highly dependent on host cell factors. YFV NS4B is reported to be involved in viral replication and immune evasion. Here interactions between NS4B and human proteins were determined using a GST pull-down assay and analyzed using 1-DE and LC-MS/MS. We present a total of 207 proteins confirmed using Scaffold 3 Software. Cyclophilin A (CypA), a protein that has been shown to be necessary for the positive regulation of flavivirus replication, was identified as a possible NS4B partner. 59 proteins were found to be significantly increased when compared with a negative control, and CypA exhibited the greatest difference, with a 22-fold change. Fisher's exact test was significant for 58 proteins, and the p value of CypA was the most significant (0.000000019). The Ingenuity Systems software identified 16 pathways, and this analysis indicated sirolimus, an mTOR pathway inhibitor, as a potential inhibitor of CypA. Immunofluorescence and viral plaque assays showed a significant reduction in YFV replication using sirolimus and cyclosporine A (CsA) as inhibitors. Furthermore, YFV replication was strongly inhibited in cells treated with both inhibitors using reporter BHK-21-rep-YFV17D-LucNeoIres cells. Taken together, these data suggest that CypA-NS4B interaction regulates YFV replication. Finally, we present the first evidence that YFV inhibition may depend on NS4B-CypA interaction.

Public health concerns exist surrounding the epidemic of the Zika virus (ZIKV) and the rapid growth of transplantation in developing countries, including endemic zones of active arbovirus transmission, as well as travel to such regions by potential organ donors and recipients. Few data exist regarding the clinical characteristics of ZIKV infection in immunocompromised hosts. Laboratory screening protocols for transplantation to differentiate ZIKV infections from other endemic viral diseases and for the detection of possible donor-derived infection have not been stated. The diagnosis of ZIKV infection remains a challenge, fueled by the lack of standardized commercially available diagnostic tests and validated reference diagnostic laboratories, as well as the limited duration of ZIKV viremia. In this small series, ZIKV infection in renal and liver recipients presented without rash, conjunctivitis, or neurological symptoms, and with abnormal graft function, thrombocytopenia, and bacterial superinfection. We report the first case series of ZIKV infection in solid organ recipients, with a description of clinical and laboratory features and therapeutic management., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Dengue fever is the most common arbovirus disease, and presents with a large spectrum of clinical manifestations ranging from asymptomatic disease through to the development of dengue hemorrhagic fever. These extreme cases can lead to dengue shock syndrome, and sometimes death. Spinal cord involvement in dengue virus (DENV) infections is rare. Here, we report a case in which the patient developed acute transverse myelitis (TM) without paraparesis following a DENV infection. This case highlights the importance of physicians' awareness of the possible link between DENV and TM in endemic areas., (© The American Society of Tropical Medicine and Hygiene.)

Zika virus (ZIKV) infection acquired during pregnancy is associated with congenital microcephaly. We describe 2 cases of ZIKV infection in women in their 36th week of pregnancy whose fetuses had preserved head circumference at birth and findings of subependymal cysts and lenticulostriate vasculopathy in postnatal imaging. These represent the first signs of congenital brain injury acquired due to ZIKV in the third trimester., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Arboviruses pose a serious threat to public health worldwide, overloading the healthcare system and causing economic losses. These viruses form a very diverse group, and in Brazil, arboviruses belonging to the families Flaviviridae and Togaviridae are predominant. Unfortunately, the number of arboviruses increases in proportion with factors such as deforestation, poor sanitation, climate changes, and introduction of new viruses like Chikungunya virus and Zika virus. In Brazil, dengue is endemic, along with the presence of other arboviruses. The situation is complicated by the scarcity of diagnostic infrastructure and the absence of approved vaccines for these diseases. Disease control, thus, relies solely on vector control. Therefore, enhanced clinical knowledge and improved general awareness about these arboviruses are indispensable to tackle diagnostic inadequacies., (Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Background: The Zika virus (ZIKV) is an emerging arthropod-borne virus related to the dengue virus (DENV), and shows a similar clinical profile as other arboviral diseases, such as dengue and chikungunya virus (CHIKV). Historically, ZIKV has been associated with sporadic cases of human infection, but is now responsible for outbreaks worldwide. In Brazil, cases have been reported since 2015, with some cases causing severe disease., Objective: To identify clinical symptoms of Zika in patients in Dengue suspected patients., Study Design: Description of a series of cases, wherein we analyzed 100 clinical samples collected from patients who exhibited acute febrile disease for ≤5days, from January to February 2016., Results: In this study, we report 13 cases of ZIKV infection in adults presenting dengue-like symptoms in a DENV endemic area. All patients presented with fever, with myalgia being the second most frequently observed symptom. Two patients had rashes, but none of them had conjunctivitis. Other less frequent manifestations included headache, arthralgia, diarrhea, and nausea., Conclusion: The co-circulation of ZIKV and DENV is a serious public health concern, since it represents both a clinical and diagnostic challenge in endemic areas, as well as in the field of travel medicine., (Copyright © 2016 Elsevier B.V. All rights reserved.)

St. Louis encephalitis virus (SLEV), a member of the family Flaviviridae, genus Flavivirus, is a causative agent of encephalitis in the Americas. In Brazil, sporadic cases of SLEV infection have been reported since 1953, but the first outbreak of SLEV in Brazil was identified only in 2007, concomitant with an outbreak of dengue virus (DENV) serotype 3. This finding, along with other reports, indicates that SLEV circulation in Brazil is largely unknown, and there may be epidemiological implications of the co-circulation of SLEV, DENV and other flaviviruses in Brazil. Here, we describe the first complete genome sequence of an SLEV strain isolated from a human patient in Brazil, strain BeH 355964. Phylogenetic analysis was performed to determine the genotype of BeH 355964 using the full-length genome and envelope (E) gene sequences separately. Both analyses showed that BeH 355964 could be classified as genotype V. Although the number of single gene sequences available is greater (such as for the E gene), the phylogenetic tree based on the complete genome sequence was better supported and provided further information about the virus.

Mayaro virus (MAYV) is widely distributed throughout South America and is the etiologic agent of Mayaro fever, an acute febrile illness often presenting with arthralgic manifestations. The true incidence of MAYV infection is likely grossly underestimated because the symptomatic presentation is very similar to that of dengue fever and other acute febrile tropical diseases. We report the complete genome sequence of a MAYV isolate detected from an Acrelândia patient presenting with fever, chills, and sweating, but with no arthralgia. Results show that this isolate belongs to genotype D and is closely related to Bolivian strains. Our results suggest that the Acre/Mayaro strain is closely related to the progenitor of these Bolivian strains that were isolated between 2002 and 2006., (© The American Society of Tropical Medicine and Hygiene.)

Background: Yellow fever virus (YFV) belongs to the Flavivirus genus and causes an important disease. An alarming resurgence of viral circulation and the expansion of YFV-endemic zones have been detected in Africa and South America in recent years. NS5 is a viral protein that contains methyltransferase and RNA-dependent RNA polymerase (RdRp) domains, which are essential for viral replication, and the interactions between NS5 and cellular proteins have been studied to better understand viral replication. The aim of this study was to characterize the interaction of the NS5 protein with eukaryotic translation initiation factor 3 subunit L (eIF3L) and to evaluate the role of eIF3L in yellow fever replication., Methods: To identify interactions of YFV NS5 with cellular proteins, we performed a two-hybrid screen using the YFV NS5 RdRp domain as bait with a human cDNA library, and RNApol deletion mutants were generated and analyzed using the two-hybrid system for mapping the interactions. The RNApol region involved was segmented into three fragments and analyzed using an eIF3L-expressing yeast strain. To map the NS5 residues that are critical for the interactions, we performed site-direct mutagenesis in segment 3 of the interaction domain (ID) and confirmed the interaction using in vitro assays and in vivo coimmunoprecipitation. The significance of eIF3L for YFV replication was investigated using eIF3L overexpression and RNA interference., Results: In this work, we describe and characterize the interaction of NS5 with the translation factor eIF3L. The interaction between NS5 and eIF3L was confirmed using in vitro binding and in vivo coimmunoprecipitation assays. This interaction occurs at a region (the interaction domain of the RNApol domain) that is conserved in several flaviviruses and that is, therefore, likely to be relevant to the genus. eIF3L overexpression and plaque reduction assays showed a slight effect on YFV replication, indicating that the interaction of eIF3L with YFV NS5 may play a role in YFV replication., Conclusions: Although the precise function of eIF3L on interactions with viral proteins is not entirely understood, these results indicate an interaction of eIF3L with YF NS5 and that eIF3L overexpression facilitates translation, which has potential implications for virus replication.

Arboviruses are frequently associated with outbreaks in humans and represent a serious public health problem. Among the Brazilian arboviruses, Mayaro virus, Dengue virus (DENV), Yellow Fever virus, Rocio virus, Saint Louis Encephalitis virus (SLEV), and Oropouche virus are responsible for most of human cases. All these arboviruses usually produce undistinguishable acute febrile illness, especially in the acute phase of infection. In this study we investigated the presence of arboviruses in sera of 519 patients presenting acute febrile illness, during a dengue outbreak in São José do Rio Preto City (São Paulo, Brazil). A multiplex-nested RT-polymerase chain reaction assay was applied to detect and identify the main Brazilian arboviruses (Flavivirus, Alphavirus, and Orthobunyavirus genera). The molecular analysis showed that 365 samples were positive to DENV-3, 5 to DENV-2, and 8 to SLEV. Among the positive samples, one coinfection was detected between DENV-2 and DENV-3. The phylogenetic analysis of the SLEV envelope gene indicated that the virus circulating in city is related to lineage V strains. These results indicated that during that large DENV-3 outbreak in 2006, different arboviruses cocirculated causing human disease. Thus, it is necessary to have an efficient surveillance system to control the dissemination of these arboviruses in the population.

Introduction: The Amazon region has extensive forested areas and natural ecosystems, providing favorable conditions for the existence of innumerous arboviruses. Over 200 arboviruses have been isolated in Brazil and about 40 are associated with human disease. Four out of 40 are considered to be of public health importance in Brazil: Dengue viruses (1-4), Oropouche, Mayaro and Yellow Fever. Along with these viruses, about 98% of the malaria cases are restricted to the Legal Amazon region., Methods: This study aimed to investigate the presence of arboviruses in 111 clinical serum samples from patients living in Novo Repartimento (Pará), Plácido de Castro (Acre), Porto Velho (Rondônia) and Oiapoque (Amapá). The viral RNA was extracted and RT-PCR was performed followed by a Multiplex-Nested-PCR, using Flavivirus, Alphavirus and Orthobunyavirus generic and species-specific primers., Results: Dengue virus serotype 2 was detected in two patients living in Novo Repartimento (Pará) that also presented active Plasmodium vivax infection., Conclusions: Despite scant data, this situation is likely to occur more frequently than detected in the Amazon region. Finally, it is important to remember that both diseases have similar clinical findings, thus the diagnosis could be made concomitantly for dengue and malaria in patients living or returning from areas where both diseases are endemic or during dengue outbreaks.

A comparison of dengue virus (DENV) antibody levels in paired serum samples collected from predominantly DENV-naive residents in an agricultural settlement in Brazilian Amazonia (baseline seroprevalence, 18.3%) showed a seroconversion rate of 3.67 episodes/100 person-years at risk during 12 months of follow-up. Multivariate analysis identified male sex, poverty, and migration from extra-Amazonian states as significant predictors of baseline DENV seropositivity, whereas male sex, a history of clinical diagnosis of dengue fever, and travel to an urban area predicted subsequent seroconversion. The laboratory surveillance of acute febrile illnesses implemented at the study site and in a nearby town between 2004 and 2006 confirmed 11 DENV infections among 102 episodes studied with DENV IgM detection, reverse transcriptase-polymerase chain reaction, and virus isolation; DENV-3 was isolated. Because DENV exposure is associated with migration or travel, personal protection measures when visiting high-risk urban areas may reduce the incidence of DENV infection in this rural population.

Objective: To investigate the impact of parental disorder in the life of adult offspring by evaluating education, current employment and marital status of a sample of offspring of patients with schizophrenia and comparing findings with population rates., Methods: A sample of 489 patients with DSM-IV diagnoses of schizophrenia was identified in the public outpatient mental health services of the city of Cuiabá, Brazil. Of these patients, 294 had children, and a total of 828 offspring were identified. Data for 431 offspring aged 18 years or older were collected using a structured questionnaire answered by the patient-parent and a family member., Results: The percentage of age-grade discrepancy for offspring aged 18 and 19 years was 59.2% (95%CI 45.4-73.0), not significantly different from the discrepancy rate for the same age group in the general population, which was 71.1%. Offspring of patients with schizophrenia had a significantly poorer employment situation than the general population (66.7% and 75.6%; 95%CI 62.1-71.3). Fewer male offspring were married than males in the general population (54.7% and 66.0%; 95%CI 48.2-61.2)., Conclusion: Adult offspring of patients with schizophrenia had social adjustment problems that were markedly reflected in employment and marital status.

Objective: To determine reproductive rates among patients with schizophrenia who attended the outpatient clinic at the Universidade Federal de São Paulo., Method: All patients with schizophrenia completed a semi-standardized questionnaire, and data from the Brazilian census was used for comparing population rates., Results: 167 patients completed the questionnaires and of these 33 (19.8%) were or had been married and 32 reported being a parent. The fertility rate (number of individuals who had had at least one child divided by the total number of individuals) was 19.4% (25% for females, 15.8% for males, p = 0.14). Fecundity rate was 1.75 for males and 1.69 for females (p = 0.85). A logistic regression analysis identified an association between the later date of the onset of illness and higher rate of marriage (p = 0.003). Gender and the interaction between gender and marital status were significant predictors for fertility (p < 0.05 and p = 0.024, respectively)., Conclusions: Patients with schizophrenia showed lower rates for marital status, fertility and fecundity when compared to standard population rates. However, many patients will become parents during their life time. Therefore, it is imperative to develop services that fulfill their needs, mainly in Brazil, a middle-income country, where resources are scarce and there is no policy for dealing with this reality.