Genetic diversity in the partial sequence of the HIV-1 gag gene among people living with multidrug-resistant HIV-1 infection.

The group-specific antigen (gag) plays a crucial role in the assembly, release, and maturation of HIV. This study aimed to analyze the partial sequence of the HIV gag gene to classify HIV subtypes, identify recombination sites, and detect protease inhibitor (PI) resistance-associated mutations (RAMs). The cohort included 100 people living with HIV (PLH) who had experienced antiretroviral treatment failure with reverse transcriptase/protease inhibitors. Proviral HIV-DNA was successfully sequenced in 96 out of 100 samples for gag regions, specifically matrix (p17) and capsid (p24). Moreover, from these 96 sequences, 82 (85.42%) were classified as subtype B, six (6.25%) as subtype F1, one (1.04%) as subtype C, and seven (7.29%) exhibited a mosaic pattern between subtypes B and F1 (B/F1), with breakpoints at p24 protein. Insertions and deletions of amino acid at p17 were observed in 51 samples (53.13%). The prevalence of PI RAM in the partial gag gene was observed in 78 out of 96 PLH (81.25%). Among these cases, the most common mutations were R76K (53.13%), Y79F (31.25%), and H219Q (14.58%) at non-cleavage sites, as well as V128I (10.42%) and Y132F (11.46%) at cleavage sites. While B/F1 recombination was identified in the p24, the p17 coding region showed higher diversity, where insertions, deletions, and PI RAM, were observed at high prevalence. In PLH with virological failure, the analysis of the partial gag gene could contribute to more accurate predictions in genotypic resistance to PIs. This can aid guide more effective HIV treatment strategies.

SARS-CoV-2 shedding, infectivity, and evolution in an immunocompromised adult patient.

This study aimed to provide further insight into the evolutionary dynamics of SARS-CoV-2 by analyzing the case of a 40-year-old man who had previously undergone autologous hematopoietic stem cell transplantation due to a diffuse large B-cell lymphoma. He developed a persistent SARS-CoV-2 infection lasting at least 218 days and did not manifest a humoral immune response to the virus during this follow-up period. Whole-genome sequencing and viral cultures confirmed a persistent infection with a replication-positive virus that had undergone genetic variation for at least 196 days after symptom onset.

Ocular manifestations of Monkeypox virus (MPXV) infection with viral persistence in ocular samples: A case series.

OBJECTIVE: We describe the clinical presentation and ocular viral dynamics in patients with Monkeypox virus-related ophthalmic disease (MPXROD). METHODS: In this case series, we investigated five consecutive patients with confirmed mpox, diagnosed through a positive Monkeypox virus (MPXV) Polymerase Chain Reaction (PCR) test and presenting with ocular symptoms. They were referred from the Reference Center for Sexually Transmitted Infections in São Paulo (CRT) to the Uveitis Sector at the Federal University of São Paulo, between August and December 2022. We performed PCR testing on ocular samples and culture supernatants for MPXV in all patients. Viral sequencing was conducted in one of the cases. RESULTS: Replicating MPXV was identified in at least one ocular sample of all patients, between day 31 and day 145 after the onset of skin lesions. All patients presented with keratitis, 3 with uveitis (60%) and two exhibited hypopyon (40%). The onset of ocular symptoms occurred at a mean of 21.2 days after the appearance of the first skin lesion and persisted, on average, for 61,.6 days, with a worsening trend observed until the initiation of tecovirimat treatment. Tecovirimat treatment was administered to all patients, with initiation occurring between 31 and 145 days after the onset of skin lesions. MPXV genome sequencing of an isolate from one patient classified it as belonging to lineage B1 in clade IIb. CONCLUSION: This study reveals a late onset and persistence of sight threatening ocular disease, along with potential viral infectivity even after systemic resolution in mpox cases. These findings highlight the risk of ongoing transmission from individuals with prolonged ocular manifestations, particularly through ocular discharge.

Nutraceutical blends predict enhanced health via microbiota reshaping improving cytokines and life quality: a Brazilian double-blind randomized trial.

Nutraceutical interventions supporting microbiota and eliciting clinical improvements in metabolic diseases have grown significantly. Chronic stress, gut dysbiosis, and metainflammation have emerged as key factors intertwined with sleep disorders, consequently exacerbating the decline in quality of life. This study aimed to assess the effects of two nutraceutical formulations containing prebiotics (fructooligosaccharides (FOS), galactooligosaccharides (GOS), yeast ß-glucans), minerals (Mg, Se, Zn), and the herbal medicine Silybum marianum L. Gaertn., Asteraceae (Milk thistle or Silymarin). These formulations, namely NSupple (without silymarin) and NSupple_Silybum (with silymarin) were tested over 180 days in overweight/obese volunteers from Brazil's southeastern region. We accessed fecal gut microbiota by partial 16S rRNA sequences; cytokines expression by CBA; anthropometrics, quality of life and sleep, as well as metabolic and hormonal parameters, at baseline (T0) and 180 days (T180) post-supplementation. Results demonstrated gut microbiota reshaping at phyla, genera, and species level post-supplementation. The Bacteroidetes phylum, Bacteroides, and Prevotella genera were positively modulated especially in the NSupple_Silybum group. Gut microbiota modulation was associated with improved sleep patterns, quality-of-life perception, cytokines expression, and anthropometric parameters post-supplementation. Our findings suggest that the nutraceutical blends positively enhance cardiometabolic and inflammatory markers. Particularly, NSupple_Silybum modulated microbiota composition, underscoring its potential significance in ameliorating metabolic dysregulation. Clinical trial registry number: NCT04810572. 23/03/2021.

Analysis of chlorhexidine, antibiotics and bacterial community composition in water environments from Brazil, Cameroon and Madagascar during the COVID-19 pandemic.

The widespread of chlorhexidine and antibiotics in the water bodies, which grew during the global COVID-19 pandemic, can increase the dispersion of antibiotic resistance. We assessed the occurrence of these pharmaceutical compounds as well as SARS-CoV-2 and analysed the bacterial community structure of hospital and urban wastewaters from Brazil, Cameroon, and Madagascar. Water and wastewater samples (n = 59) were collected between January-June 2022. Chlorhexidine, azithromycin, levofloxacin, ceftriaxone, gentamicin and meropenem were screened by Ultra-High-Performance Liquid Chromatography coupled with mass spectrometer. SARS-CoV-2 was detected based on the nucleocapsid gene (in Cameroon and Madagascar), and envelope and spike protein-encoding genes (in Brazil). The total community-DNA was extracted and used for bacterial community analysis based on the 16S rRNA gene. To unravel likely interaction between pharmaceutical compounds and/or SARS-CoV-2 with the water bacterial community, multivariate statistics were performed. Chlorhexidine was found in hospital wastewater effluent from Brazil with a maximum concentration value of 89.28 µg/L. Additionally, antibiotic residues such as azithromycin and levofloxacin were also present at concentrations between 0.32-7.37 µg/L and 0.11-118.91 µg/L, respectively. In Cameroon, azithromycin was the most found antibiotic present at concentrations from 1.14 to 1.21 µg/L. In Madagascar instead, ceftriaxone (0.68-11.53 µg/L) and levofloxacin (0.15-0.30 µg/L) were commonly found. The bacterial phyla statistically significant different (P < 0,05) among participating countries were Proteobacteria, Patescibacteria and Dependentiae which were mainly abundant in waters sampled in Africa and, other phyla such as Firmicutes, Campylobacterota and Fusobacteriota were more abundant in Brazil. The phylum Caldisericota was only found in raw hospital wastewater samples from Madagascar. The canonical correspondence analysis results suggest significant correlation of azithromycin, meropenem and levofloxacin with bacteria families such as Enterococcaceae, Flavobacteriaceae, Deinococcaceae, Thermacetogeniaceae and Desulfomonilaceae, Spirochaetaceae, Methanosaetaceae, Synergistaceae, respectively. Water samples were also positive for SARS-CoV-2 with the lowest number of hospitalized COVID-19 patients in Madagascar (n = 7) and Brazil (n = 30). Our work provides new data about the bacterial community profile and the presence of pharmaceutical compounds in the hospital effluents from Brazil, Cameroon, and Madagascar, whose limited information is available. These compounds can exacerbate the spreading of antibiotic resistance and therefore pose a risk to public health.

Modulation of the gut microbiome and Firmicutes phylum reduction by a nutraceutical blend in the obesity mouse model and overweight humans: A double-blind clinical trial.

Overweight and obesity are closely linked to gut dysbiosis/dysmetabolism and disrupted De-Ritis ratio [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio], which may contribute to chronic noncommunicable diseases onset. Concurrently, extensive research explores nutraceuticals, and health-enhancing supplements, for disease prevention or treatment. Thus, sedentary overweight volunteers were double-blind randomized into two groups: Novel Nutraceutical_(S) (without silymarin) and Novel Nutraceutical (with silymarin). Experimental formulations were orally administered twice daily over 180 consecutive days. We evaluated fecal gut microbiota, based on partial 16S rRNA sequences, biochemistry and endocrine markers, steatosis biomarker (AST/ALT ratio), and anthropometric parameters. Post-supplementation, only the Novel Nutraceutical group reduced Clostridium clostridioforme (Firmicutes), Firmicutes/Bacteroidetes ratio (F/B ratio), and De-Ritis ratio, while elevating Bacteroides caccae and Bacteroides uniformis (Bacteroidetes) in Brazilian sedentary overweight volunteers after 180 days. In summary, the results presented here allow us to suggest the gut microbiota as the action mechanism of the Novel Nutraceutical promoting metabolic hepatic recovery in obesity/overweight non-drug interventions.

Temporal and spatial analysis of over 7,000 measles cases outbreak from 2018 to 2019 in the Brazilian Amazon.

OBJECTIVE: This study aimed to present a temporal and spatial analysis of the 2018 measles outbreak in Brazil, particularly in the metropolitan city of Manaus in the Amazon region, and further introduce a new tool for spatial analysis. METHODS: We analyzed the geographical data of the residences of over 7,000 individuals with measles in Manaus during 2018 and 2019. Spatial and temporal analyses were conducted to characterize various aspects of the outbreak, including the onset and prevalence of symptoms, demographics, and vaccination status. A visualization tool was also constructed to display the geographical and temporal distribution of the reported measles cases. RESULTS: Approximately 95% of the included participants had not received vaccination within the past decade. Heterogeneity was observed across all facets of the outbreak, including variations in the incubation period and symptom presentation. Age distribution exhibited two peaks, occurring at one year and 18 years of age, and the potential implications of this distribution on predictive analysis were discussed. Additionally, spatial analysis revealed that areas with the highest case densities tended to have the lowest standard of living. CONCLUSION: Understanding the spatial and temporal spread of measles outbreaks provides insights for decision-making regarding measures to mitigate future epidemics.

Temporal trends of severity and outcomes of critically ill patients with COVID-19 after the emergence of variants of concern: A comparison of two waves.

BACKGROUND: The emergence of SARS-CoV-2 variants led to subsequent waves of COVID-19 worldwide. In many countries, the second wave of COVID-19 was marked by record deaths, raising the concern that variants associated with that wave might be more deadly. Our aim was to compare outcomes of critically-ill patients of the first two waves of COVID-19. METHODS: This retrospective cohort included critically-ill patients admitted between March-June 2020 and April-July 2021 in the largest academic hospital in Brazil, which has free-access universal health care system. We compared admission characteristics and hospital outcomes. The main outcome was 60-day survival and we built multivariable Cox model based on a conceptual causal diagram in the format of directed acyclic graph (DAG). RESULTS: We included 1583 patients (1315 in the first and 268 in the second wave). Patients in the second wave were younger, had lower severity scores, used prone and non-invasive ventilatory support more often, and fewer patients required mechanical ventilation (70% vs 80%, p<0.001), vasopressors (60 vs 74%, p<0.001), and dialysis (22% vs 37%, p<0.001). Survival was higher in the second wave (HR 0.61, 95%CI 0.50-0.76). In the multivariable model, admission during the second wave, adjusted for age, SAPS3 and vaccination, was not associated with survival (aHR 0.85, 95%CI 0.65-1.12). CONCLUSIONS: In this cohort study, patients with COVID-19 admitted to the ICU in the second wave were younger and had better prognostic scores. Adjusted survival was similar in the two waves, contrasting with record number of hospitalizations, daily deaths and health system collapse seen across the country in the second wave. Our findings suggest that the combination of the burden of severe cases and factors such as resource allocation and health disparities may have had an impact in the excess mortality found in many countries in the second wave.

An electrochemical genomagnetic assay for detection of SARS-CoV-2 and Influenza A viruses in saliva.

Viral respiratory infections represent a major threat to the population's health globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 disease and in some cases the symptoms can be confused with Influenza disease caused by the Influenza A viruses. A simple, fast, and selective assay capable of identifying the etiological agent and differentiating the diseases is essential to provide the correct clinical management to the patient. Herein, we described the development of a genomagnetic assay for the selective capture of viral RNA from SARS-CoV-2 and Influenza A viruses in saliva samples and employing a simple disposable electrochemical device for gene detection and quantification. The proposed method showed excellent performance detecting RNA of SARS-CoV-2 and Influenza A viruses, with a limit of detection (LoD) and limit of quantification (LoQ) of 5.0 fmol L-1 and 8.6 fmol L-1 for SARS-CoV-2, and 1.0 fmol L-1 and 108.9 fmol L-1 for Influenza, respectively. The genomagnetic assay was employed to evaluate the presence of the viruses in 36 saliva samples and the results presented similar responses to those obtained by the real-time reverse transcription-polymerase chain reaction (RT-PCR), demonstrating the reliability and capability of a method as an alternative for the diagnosis of COVID-19 and Influenza with point-of-care capabilities.

Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency. Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output. Results: Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19. Discussion: Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.

Gastrointestinal Manifestations of Chagas Disease: A Systematic Review with Meta-Analysis.

The aims of this study were to estimate the prevalence of gastrointestinal manifestations among individuals with positive serology for Chagas disease (ChD) and to describe the clinical gastrointestinal manifestations of the disease. A systematic review with meta-analysis was conducted based on the criteria and recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The PubMed, Scopus, Virtual Health Library, Web of Science, and Embase databases were used to search for evidence. Two reviewers independently selected eligible articles and extracted data. RStudio® software was used for the meta-analysis. For subgroup analysis, the studies were divided according to the origin of the individuals included: 1) individuals from health units were included in the health care service prevalence analysis, and 2) individuals from the general population were included in the population prevalence analysis. A total of 2,570 articles were identified, but after removal of duplicates and application of inclusion criteria, 24 articles were included and 21 were part of the meta-analysis. Most of the studies were conducted in Brazil. Radiological diagnosis was the most frequent method used to identify the gastrointestinal clinical form. The combined effect of meta-analysis studies showed a prevalence of gastrointestinal manifestations in individuals with ChD of 12% (95% CI, 8.0-17.0%). In subgroup analysis, the prevalence for studies involving health care services was 16% (95% CI, 11.0-23.0%), while the prevalence for population-based studies was 9% (95% CI, 5.0-15.0%). Megaesophagus and megacolon were the main forms of ChD presentation in the gastrointestinal form. The prevalence of gastrointestinal manifestations of ChD was 12%. Knowing the prevalence of ChD in its gastrointestinal form is an important step in planning health actions for these patients.

Comparing plasma and skin imprint metabolic profiles in COVID-19 diagnosis and severity assessment.

As SARS-CoV-2 continues to produce new variants, the demand for diagnostics and a better understanding of COVID-19 remain key topics in healthcare. Skin manifestations have been widely reported in cases of COVID-19, but the mechanisms and markers of these symptoms are poorly described. In this cross-sectional study, 101 patients (64 COVID-19 positive patients and 37 controls) were enrolled between April and June 2020, during the first wave of COVID-19, in São Paulo, Brazil. Enrolled patients had skin imprints sampled non-invasively using silica plates; plasma samples were also collected. Samples were used for untargeted lipidomics/metabolomics through high-resolution mass spectrometry. We identified 558 molecular ions, with lipids comprising most of them. We found 245 plasma ions that were significant for COVID-19 diagnosis, compared to 61 from the skin imprints. Plasma samples outperformed skin imprints in distinguishing patients with COVID-19 from controls, with F1-scores of 91.9% and 84.3%, respectively. Skin imprints were excellent for assessing disease severity, exhibiting an F1-score of 93.5% when discriminating between patient hospitalization and home care statuses. Specifically, oleamide and linoleamide were the most discriminative biomarkers for identifying hospitalized patients through skin imprinting, and palmitic amides and N-acylethanolamine 18:0 were also identified as significant biomarkers. These observations underscore the importance of primary fatty acid amides and N-acylethanolamines in immunomodulatory processes and metabolic disorders. These findings confirm the potential utility of skin imprinting as a valuable non-invasive sampling method for COVID-19 screening; a method that may also be applied in the evaluation of other medical conditions. KEY MESSAGES: Skin imprints complement plasma in disease metabolomics. The annotated markers have a role in immunomodulation and metabolic diseases. Skin imprints outperformed plasma samples at assessing disease severity. Skin imprints have potential as non-invasive sampling strategy for COVID-19.

Temporal and spatial analysis of over 7,000 measles cases outbreak from 2018 to 2019 in the Brazilian Amazon

ABSTRACT Objective: This study aimed to present a temporal and spatial analysis of the 2018 measles outbreak in Brazil, particularly in the metropolitan city of Manaus in the Amazon region, and further introduce a new tool for spatial analysis. Methods: We analyzed the geographical data of the residences of over 7,000 individuals with measles in Manaus during 2018 and 2019. Spatial and temporal analyses were conducted to characterize various aspects of the outbreak, including the onset and prevalence of symptoms, demographics, and vaccination status. A visualization tool was also constructed to display the geographical and temporal distribution of the reported measles cases. Results: Approximately 95% of the included participants had not received vaccination within the past decade. Heterogeneity was observed across all facets of the outbreak, including variations in the incubation period and symptom presentation. Age distribution exhibited two peaks, occurring at one year and 18 years of age, and the potential implications of this distribution on predictive analysis were discussed. Additionally, spatial analysis revealed that areas with the highest case densities tended to have the lowest standard of living. Conclusion: Understanding the spatial and temporal spread of measles outbreaks provides insights for decision-making regarding measures to mitigate future epidemics.

Lessons from a Multilaboratorial Task Force for Diagnosis of a Fatal Toxoplasmosis Outbreak in Captive Primates in Brazil.

Toxoplasmosis is an important zoonotic disease caused by the parasite Toxoplasma gondii and is especially fatal for neotropical primates. In Brazil, the Ministry of Health is responsible for national epizootic surveillance, but some diseases are still neglected. Here, we present an integrated investigation of an outbreak that occurred during the first year of the COVID-19 pandemic among eleven neotropical primates housed at a primatology center in Brazil. After presenting non-specific clinical signs, all animals died within four days. A wide range of pathogens were evaluated, and we successfully identified T. gondii as the causative agent within four days after necropsies. The liver was the most affected organ, presenting hemorrhage and hepatocellular necrosis. Tachyzoites and bradyzoite cysts were observed in histological examinations and immunohistochemistry in different organs; in addition, parasitic DNA was detected through PCR in blood samples from all specimens evaluated. A high prevalence of Escherichia coli was also observed, indicating sepsis. This case highlights some of the obstacles faced by the current Brazilian surveillance system. A diagnosis was obtained through the integrated action of researchers since investigation for toxoplasmosis is currently absent in national guidelines. An interdisciplinary investigation could be a possible model for future epizootic investigations in animals.

Chagas disease and perceived quality of life: a cross-sectional study.

BACKGROUND: Chagas disease (ChD) is a neglected tropical disease that is caused by the protozoan parasite Trypanosoma cruzi and can negatively impact quality of life (QoL). This study aimed to assess and compare QoL between individuals with and without ChD. METHODS: This cross-sectional study was performed within a concurrent cohort study (REDS). The participants were derived from two blood donation centers: São Paulo capital and Montes Claros, Minas Gerais, Brazil. Participants with ChD were identified in blood donations by serological diagnosis between 2008 and 2010, and those without ChD were donors with negative serology identified during the same period. QoL was assessed using the World Health Organization Quality of Life-BREF questionnaire. Logistic regression was used to compare sociodemographic and clinical characteristics between the groups, and mean, standard deviation, and beta regression were used to compare QoL. RESULTS: In total, 611 individuals participated in the study (328 with ChD and 283 without ChD). Participants with ChD had lower QoL in the physical (p=0.02) and psychological (p<0.01) domains than did individuals without CD. CONCLUSIONS: Individuals with ChD had worse QoL perceptions. These results provide a comprehensive understanding of the impact of ChD on individuals' QoL, while also highlighting potential opportunities for improving the care and treatment of those affected.

Overview of Chagas disease surveillance in an endemic region in Southeastern Brazil.

Chagas disease (CD) is a neglected disease caused by the protozoan Trypanosoma cruzi. It has high morbidity and mortality rates and mainly affects socially vulnerable populations. This is a cross-sectional study, with retrospective and prospective data collection. Using questionnaires applied to environmental surveillance coordinators, we characterized the status of CD surveillance activities in municipalities endemic for the disease in Northern Minas Gerais State (MG) and Jequitinhonha Valley (Vale do Jequitinhonha). Moreover, we spatialized the vulnerability index for chronic CD in the study area. The population consisted of 22 environmental surveillance coordinators, active in 2020, from Northern MG and Jequitinhonha Valley, 21 municipalities included in the SaMi-Trop research project, and Montes Claros municipality. After applying the questionnaires to the coordinators, a descriptive analysis of the variables was performed. To characterize the active municipalities, the explanatory variables collected in the questionnaire were compared with the dichotomous variable. Bivariate descriptive analysis was performed. Finally, geoprocessing techniques were used to spatialize the data and prepare maps. Regarding the team of endemic combat agents (ECA), 90.9% reported the lack of a specific team for CD vector control actions. Of the 22 municipalities participating in this study, nine were active (41.1%). Only 25% (n=2) of active municipalities (9% of the municipalities studied) met the target of visiting 50% of households per year. Finally, 81.1% of the coordinators stated that in their municipality, they developed actions linked to primary health care (PHC). The implementation of CD surveillance activities weakened in the endemic region. Few municipalities have a surveillance team, with low regularity of active surveillance and noncompliance with the program's goal. The results suggest insufficient recording of activities in the information system, considering that there are municipalities that report performing the activities, but no production record was observed in the system.

Survival analysis over a 20-year period of a Brazilian cohort of blood donors coinfected HIV-HCV.

Among individuals coinfected with HCV and HIV, studies of mortality from non-hepatic causes have shown inconsistent results. The aim of this study was to investigate the contribution of HCV and HIV co-infection to mortality from hepatic and non-hepatic causes in Brazil. This retrospective cohort study included blood donors from Fundação Pró-Sangue de São Paulo (FPS) who were followed from 1994 to 2016 to compare mortality and its causes between HIV-HCV coinfected individuals versus those seronegative for all tested infections. Records from the FPS database and the Mortality Information System were linked through a probabilistic record Relationship (RL). The Hazard Ratio (HR) was estimated using Cox multiple regression models. HCV-HIV coinfected individuals compared to seronegative individuals had a higher risk of death from all causes (HR = 14.54), non-liver neoplasms (HR = 2.55), infections (HR = 10.37) and liver disease (HR = 7.0). In addition, HCV mono-infected individuals compared to seronegative individuals had a higher risk of death from all causes (HR = 2.23), liver cancer (HR = 32.21), liver disease (HR = 14.92), infection (HR = 3.22), and trauma (HR = 1.68). Individuals coinfected with HCV and HIV have increased overall mortality and death due to infections, liver diseases and non-liver neoplasms as compared to those uninfected with HCV and HIV.

Clinical Aspects and Etiologic Investigation of Pediatric Patients With Acute Liver Failure.

A new outbreak of hepatitis of unknown origin raised awareness in the international community. A few reports have attempted to associate new cases with adenovirus infection and the immunologic effects of previous SARS-CoV-2 infections through a superantigen mechanism. Moreover, according to a case series, viral isolates were identified in 7 of 10 cases of pediatric patients with hepatitis of unknown origin and acute liver failure. Adenovirus was detected by respiratory secretion polymerase chain reaction in 2 patients, with neither presenting with SARS-CoV-2 acute infection. Clinical and laboratory descriptions and cross-referencing epidemiologic and pathophysiological data can help identify possible disease etiologies.

Genetic differences of dengue virus 2 in patients with distinct clinical outcome.

The genetic diversity of the dengue virus is characterized by four circulating serotypes, several genotypes, and an increasing number of existing lineages that may have differences in the potential to cause epidemics and disease severity. Accurate identification of the genetic variability of the virus is essential to identify lineages responsible for an epidemic and understanding the processes of virus spread and virulence. Here, we characterize, using portable nanopore genomic sequencing, different lineages of dengue virus 2 (DENV-2) detected in 22 serum samples from patients with and without dengue warning signs attended at Hospital de Base of São José do Rio Preto (SJRP) in 2019, during a DENV-2 outbreak. Demographic, epidemiological, and clinical data were also analyzed. The phylogenetic reconstruction and the clinical data showed that two lineages belonging to the American/Asian genotype of DENV-2-BR3 and BR4 (BR4L1 and BR4L2)-were co-circulating in SJRP. Although preliminary, these results indicate no specific association between clinical form and phylogenetic clustering at the virus consensus sequence level. Studies with larger sample sizes and which explore single nucleotide variants are needed. Therefore, we showed that portable nanopore genome sequencing could generate quick and reliable sequences for genomic surveillance to monitor viral diversity and its association with disease severity as an epidemic unfolds.