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Orthobunyavirus oropouche ense virus (OROV), the causative agent of Oropouche fever, is widely dispersed in Brazil and South America, causing sporadic outbreaks. Due to the similarity of initial clinical symptoms caused by OROV with other arboviruses found in overlapping geographical areas, differential diagnosis is challenging. As for most neglected tropical diseases, there is a shortage of reagents for diagnosing and studying OROV pathogenesis. We therefore developed and characterized mouse monoclonal antibodies and, one of them recognizes the OROV nucleocapsid in indirect immunofluorescent (IFA) and immunohistochemistry (IHC) assays. Considering that it is the first monoclonal antibody produced for detecting OROV infections, we believe that it will be useful not only for diagnostic purposes but also for performing serological surveys and epidemiological surveillance on the dispersion and prevalence of OROV in Brazil and South America. [ABSTRACT FROM AUTHOR]

Adherence to treatment and use of co-medication, but also molecular factors such as CYP2D6 genotype, affect tamoxifen metabolism, with consequences for early breast cancer prognosis. In a prospective study of 149 tamoxifen-treated early-stage breast cancer patients from Brazil followed up for 5 years, we investigated the association between the active tamoxifen metabolite (Z)-endoxifen at 3 months and event-free survival (EFS) adjusted for clinico-pathological factors. Twenty-five patients (16.8%) had recurred or died at a median follow-up of 52.3 months. When we applied a putative 15 nM threshold used in previous independent studies, (Z)-endoxifen levels below the threshold showed an association with shorter EFS in univariate analysis (p = 0.045) and after adjustment for stage (HR 2.52; 95% CI 1.13–5.65; p = 0.024). However, modeling of plasma concentrations with splines instead of dichotomization did not verify a significant association with EFS (univariate analysis: p = 0.158; adjusted for stage: p = 0.117). Hence, in our small exploratory study, the link between impaired tamoxifen metabolism and early breast cancer recurrence could not be unanimously demonstrated. This inconsistency justifies larger modeling studies backed up by mechanistic pharmacodynamic analyses to shed new light on this suspected association and the stipulation of an appropriate predictive (Z)-endoxifen threshold. [ABSTRACT FROM AUTHOR]

We documented fetal death associated with intrauterine transmission of severe acute respiratory syndrome coronavirus 2. We found chronic histiocytic intervillositis, maternal and fetal vascular malperfusion, microglial hyperplasia, and lymphocytic infiltrate in muscle in the placenta and fetal tissue. Placenta and umbilical cord blood tested positive for the virus by PCR, confirming transplacental transmission. [ABSTRACT FROM AUTHOR]

Abstract: Hantaviruses are rodent-borne RNA viruses that cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). From the first detection of infection in Brazil in 1993 until 2009, 1161 cases of HPS have been reported, with mortality rates of around ∼40%. Currently, due to the absence of a vaccine or specific antiviral therapy, the only way to reduce mortality by hantavirus infection is a fast and precise diagnosis that allows for supportive clinical health care. To improve the detection of hantavirus infection, we developed monoclonal antibodies (Mabs) against the nucleoprotein (rNΔ85) of the Araucaria hantavirus strain (ARAUV). The specificity of generated Mabs for rNΔ85 was demonstrated by western blot, indirect immunofluorescence and immunohistochemistry. These are the first monoclonal antibodies to be produced and characterized against the South American hantavirus strain, and may be of special interest in the development of diagnostic assays and epidemiological studies. [Copyright &y& Elsevier]

Since the beginning of the pandemic, few papers describe the placenta's morphological and morphometrical features in SARS-CoV-2-positive pregnant women. Alterations, such as low placental weight, accelerated villous maturation, decidual vasculopathy, infarcts, thrombosis of fetal placental vessels, and chronic histiocytic intervillositis (CHI), have been described., Objective: To analyze clinical data and the placental morphological and morphometric changes of pregnant women infected with SARS-CoV-2 (COVID-19 group) in comparison with the placentas of non-infected pregnant women, matched for maternal age and comorbidities, besides gestational age of delivery (Control group)., Method: The patients in the COVID-19 and the Control group were matched for maternal age, gestational age, and comorbidities. The morphological analysis of placentas was performed using Amsterdam Placental Workshop Group Consensus Statement. The quantitative morphometric evaluation included perimeter diameter and number of tertiary villi, number of sprouts and knots, evaluation of deposition of villous fibrin, and deposition of intra-villous collagen I and III by Sirius Red. Additionally, Hofbauer cells (HC) were counted within villi by immunohistochemistry with CD68 marker., Results: Compared to controls, symptomatic women in the COVID-19 group were more likely to have at least one comorbidity, to evolve to preterm labor and infant death, and to have positive SARS-CoV-2 RNA testing in their concepts. Compared to controls, placentas in the COVID-19 group were more likely to show features of maternal and fetal vascular malperfusion. In the COVID-19 group, placentas of symptomatic women were more likely to show CHI. No significant results were found after morphometric analysis., Conclusion: Pregnant women with symptomatic SARS-CoV-2 infection, particularly with the severe course, are more likely to exhibit an adverse fetal outcome, with slightly more frequent histopathologic findings of maternal and fetal vascular malperfusion, and CHI. The morphometric changes found in the placentas of the COVID-19 group do not seem to be different from those observed in the Control group, as far as maternal age, gestational age, and comorbidities are paired. Only the deposition of villous fibrin could be more accentuated in the COVID-19 group (p = 0.08 borderline). The number of HC/villous evaluated with CD68 immunohistochemistry did not show a difference between both groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rebutini, Zanchettin, Stonoga, Prá, de Oliveira, Dezidério, Fonseca, Dagostini, Hlatchuk, Furuie, Longo, Cavalli, Dino, Dias, Percicote, Nogueira, Raboni, de Carvalho, Machado-Souza and de Noronha.)

Objectives: Screening for genes differentially expressed in placental tissues, aiming to identify transcriptional signatures that may be involved in ZIKV congenital pathogenesis., Methods: Transcriptome data from placental tissues of pregnant women naturally infected with Zika virus during the third trimester were compared to those from women who tested negative for Zika infection. The findings were validated using both a cell culture model and an immunohistochemistry/morphological analysis of naturally infected placental tissues., Results: Transcriptome analysis revealed that Zika virus infection induces downregulation of insulin-like growth factor II (IGF2) gene, an essential factor for fetal development. The Caco-2 cell culture model that constitutively expresses IGF2 was used for the transcriptome validation. Asiatic and African Zika virus strains infection caused downregulated IGF2 gene expression in Caco-2 cells, whereas other flaviviruses, such as dengue serotype 1, West Nile and wild-type yellow fever viruses, had no effect on this gene expression. Immunohistochemical assays on decidual tissues corroborated our transcriptome analysis, showing that IGF2 is reduced in the decidua of Zika virus-infected women., Conclusions: Our results draw attention to IGF2 modulation in uterine tissues, and this finding is expected to support future studies on strategies to ameliorate the harmful effects of Zika virus infection during pregnancy., Competing Interests: Declaration of Competing Interest The authors have declared that no conflict of interest exists., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent systemic mycosis among immunocompetent patients in Latin America; it is rare in immunocompromised patients. The estimated frequency of central nervous system (CNS) involvement in the HIV/PCM population was 2.5%. We report a case of HIV/P. brasiliensis co-infection, with neurological (NPCM) and multiple organ involvement, indicating a diagnosis of AIDS. PCM diagnosis was established during the autopsy. This is the first described case of HIV/P. brasiliensis co-infection with CNS involvement diagnosed at autopsy. In conclusion, the diagnosis of NPCM is challenging, and it must be considered in the differential diagnosis in HIV-positive patients who reside in or have visited areas in which the condition is endemic and who present with neurological symptoms.

Background/aim: Acute respiratory infections are an important cause of childhood morbidity and mortality throughout the world, and viruses have often been reported to be an aetiological agent. This study aimed to identify respiratory viruses in paraffin-embedded samples of paediatric lung necropsy specimens, using immunohistochemistry on tissue microarray slides., Methods: Retrospective study in 200 lung tissue samples from children who had died from severe respiratory infections during 1985-2005. Immunoperoxidase assay was performed to detect the viruses that were most commonly associated with respiratory tract infections: influenza virus A (FLU A), influenza virus B (FLU B), respiratory syncytial virus (RSV), adenovirus (AdV) and parainfluenza virus (PIV) types 1, 2 and 3., Results: Viruses were detected in 71 (35.5%) cases. Most positive cases were observed in children younger than 6 months. In 42.3% of cases, only one virus was detected: 11 (36.7%) RSV; 7 (23.3%) AdV; 4 (13.3%) PIV2; 3 (10%) FLU A; 2 (6.7%) FLU B; 2 (6.7%) PIV3; and 1 (3.3%) PIV1. Co-infection with more than one virus was observed in 41 (57.7%) cases. No positive correlations were observed between the presence of viral antigens and seasonality of the infection, sex, age or histopathological findings., Conclusions: Non-pandemic seasonal respiratory viruses are involved in a significant number of deaths in paediatric patients; these findings highlight the importance of laboratory investigation of these agents in patients hospitalised with severe acute respiratory infections.

Background: Hantavirus pulmonary syndrome has been reported with increasing frequency in some Brazilian regions, but information about viral genetic identification is still limited. Recently, the state of Mato Grosso, in the Legal Amazon of Brazil, experienced a growing number of hantavirus pulmonary syndrome (HPS) cases but the genetic characterization of the causative hantavirus is still missing., Objectives: Our goal was to identify the hantavirus strain involved in a fatal HPS case in the Central region of Brazil., Study Design: Nested RT-PCR was conducted on blood clot samples from an HPS patient from Mato Grosso. PCR-positive samples were sequenced, and the resulting sequences were compared with reference samples. Viral antigens were detected by immunohistological analyses in lung and liver tissues., Results: Analyses of the viral RNA isolated from the patient identified a Laguna Negra (LN)-like virus as the causative agent and histological analysis of lung sections were compatible with the genetic characterization., Conclusions: This is the first report of circulation and human infection by a Laguna Negra-like hantavirus in Brazil.

Infections of the respiratory system are responsible for the majority of hospitalizations and deaths in pediatric patients in developing countries. We selected 177 necropsies of pediatric patients who died as a result of serious respiratory infections. The histopathological findings and epidemiological data were reviewed, and lung tissue samples were separated for immunohistochemistry testing. Conventional immunohistochemistry techniques were used to detect viral antigens in formalin-fixed, paraffin-embedded (FF-PE) lung tissue samples using a pool of monoclonal antibodies against respiratory viruses (respiratory syncytial virus, influenza A and B, adenovirus, and parainfluenza 1, 2, and 3 viruses) as primary antibodies. The histopathological findings were classified into bronchopneumonia (BCP) and interstitial pneumonitis (IP) patterns. The immunohistochemistry results were compared with histopathological patterns and epidemiological data. Positive results for viruses were found in 34% and 62.5% of the BCP and IP cases, respectively. Males and infants below 1 year of age were more frequent in the group that had positive results for viruses. Acute enteritis was the main cause of hospitalization and sepsis the most frequent cause of death in this group. A clear seasonal distribution was observed, with the majority of cases occurring in the 2nd and 3rd trimesters (autumn and winter) of each year in the period studied. Immunohistochemistry is an affordable and easy-to-perform method for viral-antigen detection in FF-PE tissue samples. Although BCP is a classic histopathological pattern found in bacterial infections, it is possible that children with serious respiratory infections had concomitant viral and bacterial infections, regardless of their previous immunologic state.