High Levels of NfL, GFAP, TAU, and UCH-L1 as Potential Predictor Biomarkers of Severity and Lethality in Acute COVID-19.

Few studies showed that neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tubulin-associated unit (TAU), and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) may be related to neurological manifestations and severity during and after SARS-CoV-2 infection. The objective of this work was to investigate the relationship among nervous system biomarkers (NfL, TAU, GFAP, and UCH-L1), biochemical parameters, and viral loads with heterogeneous outcomes in a cohort of severe COVID-19 patients admitted in Intensive Care Unit (ICU) of a university hospital. For that, 108 subjects were recruited within the first 5 days at ICU. In parallel, 16 mild COVID-19 patients were enrolled. Severe COVID-19 group was divided between "deceased" and "survivor." All subjects were positive for SARS-CoV-2 detection. NfL, total TAU, GFAP, and UCH-L1 quantification in plasma was performed using SIMOA SR-X platform. Of 108 severe patients, 36 (33.33%) presented neurological manifestation and 41 (37.96%) died. All four biomarkers - GFAP, NfL, TAU, and UCH-L1 - were significantly higher among deceased patients in comparison to survivors (p < 0.05). Analyzing biochemical biomarkers, higher Peak Serum Ferritin, D-Dimer Peak, Gamma-glutamyltransferase, and C-Reactive Protein levels were related to death (p < 0.0001). In multivariate analysis, GFAP, NfL, TAU, UCH-L1, and Peak Serum Ferritin levels were correlated to death. Regarding SARS-CoV-2 viral load, no statistical difference was observed for any group. Thus, Ferritin, NFL, GFAP, TAU, and UCH-L1 are early biomarkers of severity and lethality of SARS-COV-2 infection and may be important tools for therapeutic decision-making in the acute phase of disease.

Clinical Profile and Risk Factors for Severe COVID-19 in Hospitalized Patients from Rio de Janeiro, Brazil: Comparison between the First and Second Pandemic Waves.

Since COVID-19 was declared a pandemic, Brazil has become one of the countries most affected by this disease. A year into the pandemic, a second wave of COVID-19 emerged, with a rapid spread of a new SARS-CoV-2 lineage of concern. Several vaccines have been granted emergency-use authorization, leading to a decrease in mortality and severe cases in many countries. However, the emergence of SARS-CoV-2 variants raises the alert for potential new waves of transmission and an increase in pathogenicity. We compared the demographic and clinical data of critically ill patients infected with COVID-19 hospitalized in Rio de Janeiro during the first and second waves between July 2020 and October 2021. In total, 106 participants were included in this study; among them, 88% had at least one comorbidity, and 37% developed severe disease. Disease severity was associated with older age, pre-existing neurological comorbidities, higher viral load, and dyspnea. Laboratory biomarkers related to white blood cells, coagulation, cellular injury, inflammation, renal, and liver injuries were significantly associated with severe COVID-19. During the second wave of the pandemic, the necessity of invasive respiratory support was higher, and more individuals with COVID-19 developed acute hepatitis, suggesting that the progression of the second wave resulted in an increase in severe cases. These results can contribute to understanding the behavior of the COVID-19 pandemic in Brazil and may be helpful in predicting disease severity, which is a pivotal for guiding clinical care, improving patient outcomes, and defining public policies.

Neuroinvasive chikungunya in a liver transplant recipient.

The influence of chronic immunosuppression on the course of chikungunya virus (CHIKV) infection in recipients of solid organ transplantation (SOT) is still unsettled. Scarce data suggest that the course of CHIKV infection is generally benign in this population. In addition, the occurrence of severe atypical manifestations associated with CHIKV has not been well documented among SOT recipients. In this report, we describe a 64-year-old male liver transplant recipient who was admitted with fever, headache, arthralgia, left palpebral ptosis, mydriasis, and right hemiparesis. Cranial magnetic resonance imaging did not reveal any alteration suggestive of acute infection. Nevertheless, CHIKV was detected in the cerebrospinal fluid (CSF) with a real-time reverse transcriptase assay. Other PCR assays carried out in CSF were negative for HSV-1 and 2, cytomegalovirus, dengue virus (DENV), and Zika virus (ZIKV). CHIKV viremia was also detected while PCR assays for ZIKV and DENV in the blood were negative. ZIKV viruria was simultaneously present in this case. All neurologic manifestations waned within 2 weeks after the onset. This report shows that chikungunya must be considered in the differential diagnosis of acute neurologic disease in SOT recipients who live in or have recently traveled to endemic areas.

Schistosoma mansoni Coinfection Attenuates Murine Toxoplasma gondii-Induced Crohn's-Like Ileitis by Preserving the Epithelial Barrier and Downregulating the Inflammatory Response.

Background and aims: Mice orally infected with T. gondii develop Crohn's disease (CD)-like enteritis associated with severe mucosal damage and a systemic inflammatory response, resulting in high morbidity and mortality. Previously, helminthic infections have shown therapeutic potential in experimental colitis. However, the role of S. mansoni in T. gondii-induced CD-like enteritis has not been elucidated. Our study investigated the mechanisms underlying T. gondii-induced ileitis and the potential therapeutic effect of S. mansoni coinfection. Methods: C57BL/6 mice were infected by subcutaneous injection of cercariae of the BH strain of S. mansoni, and 7-9 weeks later, they were orally infected with cysts of the ME49 strain of T. gondii. After euthanasia, the ileum was removed for histopathological analysis; staining for goblet cells; immunohistochemistry characterizing mononuclear cells, lysozyme expression, apoptotic cells, and intracellular pathway activation; and measuring gene expression levels by real-time PCR. Cytokine concentrations were measured in the serial serum samples and culture supernatants of the ileal explants, in addition to myeloperoxidase (MPO) activity. Results:T. gondii-monoinfected mice presented dense inflammatory cell infiltrates and ulcerations in the terminal ileum, with abundant cell extrusion, apoptotic bodies, and necrosis; these effects were absent in S. mansoni-infected or coinfected animals. Coinfection preserved goblet cells and Paneth cells, remarkably depleted in T. gondii-infected mice. Densities of CD4- and CD11b-positive cells were increased in T. gondii- compared to S. mansoni-infected mice and controls. MPO was significantly increased among T. gondii-mice, while attenuated in coinfected animals. In T. gondii-infected mice, the culture supernatants of the explants showed increased concentrations of TNF-alpha, IFN-gamma, and IL-17, and the ileal tissue revealed increased expression of the mRNA transcripts for IL-1 beta, NOS2, HMOX1, MMP3, and MMP9 and activation of NF-kappa B and p38 MAPK signaling, all of which were counterregulated by S. mansoni coinfection. Conclusion:S. mansoni coinfection attenuates T. gondii-induced ileitis by preserving mucosal integrity and downregulating the local inflammatory response based on the activation of NF-kappa B and MAPK. The protective function of prior S. mansoni infection suggests the involvement of innate immune mechanisms and supports a conceptually new approach to the treatment of chronic inflammatory diseases, including CD.

Reprint of "Neurocysticercosis-related mortality in Brazil, 2000-2011: Epidemiology of a neglected neurologic cause of death".

Neurocysticercosis (NCC) is an important cause of severe neurological disease mainly in low- and middle-income countries, but data on NCC mortality from endemic areas are scarce. Here we analysed the epidemiological patterns of NCC-related mortality in Brazil. We included all deaths recorded in Brazil between 2000 and 2011, in which NCC was mentioned on death certificates, either as underlying or as associated cause of death. NCC was identified in 1829/12,491,280 deaths (0.015%), 1130 (61.8%) as underlying cause, and 699 (38.2%) as associated cause. Overall age-adjusted mortality rate for the period was 0.97 deaths/1,000,000 inhabitants (95% confidence interval [CI]: 0.83-1.12). The highest NCC-related mortality rates were found in males, elderly, white race/colour and residents in endemic states/regions. Age-adjusted mortality rates at national level decreased significantly over time (annual percent change [APC]: -4.7; 95% CI: -6.0 to -3.3), with a decrease in the Southeast, South and Central-West regions, and a non-significant increasing trend in the North and Northeast regions. We identified spatial and spatiotemporal high-risk mortality clusters located mainly in NCC-endemic areas. Conditions related to the nervous system were the most commonly associated causes of death when NCC was mentioned as an underlying cause, and HIV/AIDS was the main underlying cause when NCC was an associated cause. NCC is a neglected and preventable cause of severe neurologic disease and death with high public health impact in Brazil. There is a clear need to strengthen nationwide epidemiological surveillance and control for the taeniasis/cysticercosis complex.

Molecular and serological techniques to detect co-circulation of DENV, ZIKV and CHIKV in suspected dengue-like syndrome patients.

BACKGROUND: Arboviruses are important emerging viruses worldwide. The signs and symptoms of Zika virus (ZIKV) infection are similar to those presented by infections with dengue virus (DENV) and chikungunya virus (CHIKV). Furthermore, diagnosis of ZIKV infection is particularly challenging in dengue endemic regions and with co-circulation of DENV, CHIKV, and ZIKV, making diagnosis based solely on clinical and epidemiological data unreliable. As these three viral infections share similar clinical manifestations, differential diagnosis is crucial. OBJECTIVES: In this study, diagnoses of ZIKV, CHIKV and DENV infections were investigated in 30 patients with suspected dengue fever residing in the area of co-circulation of these three arboviruses. STUDY DESIGN: The study included whole blood and/or serum samples obtained from 30 patients with suspected dengue fever. All patients were tested for DENV infection as well as for CHIKV and ZIKV infections. Assays for detecting anti-DENV IgM and DENV RNA by semi-nested RT-PCR and ZIKV and CHIKV RNA by real-time RT-PCR were performed. RESULTS: DENV RNA was not detectable in any of the clinical samples, whereas ZIKV RNA was detectable in 17 samples (56.7%). Co-infection by ZIKV and CHIKV was documented in one case. Of the 17 ZIKV-positive individuals, 8 showed reactivity for anti-DENV IgM, which suggested recent DENV infection, cross-reactivity or co-infection. CONCLUSION: Our findings confirm that accurate laboratory testing is of paramount importance for differential diagnosis in areas of simultaneous transmission of different arboviruses with similar clinical presentations.

A Luminex-based single DNA fragment amplification assay as a practical tool for detecting and serotyping dengue virus.

Dengue is a mosquito-borne viral infection that can evolve from subclinical to severe forms of disease. Early recognition during initial primary and secondary infections correlates with a reduced case-fatality rate in susceptible groups. The aim of this study was to standardize a DNA hybridization assay based on the Luminex technology for detecting and serotyping dengue virus (DENV). Reference DENVs representing the four different serotypes were used as controls to standardize the test. For validation, 16 DENV isolates obtained from a reference laboratory were analyzed in a double-blind manner to validate the test. Sixty blood samples from patients suspected of having dengue fever were used to evaluate the methodology after the validation step, and the results were compared with the reference semi-nested RT-PCR. Additionally, five human samples of each Zika and Chikungunya confirmed patients were used for specificity analysis. The Luminex-based assay correctly identified all 16 DENV isolates. In the evaluation step, the results of the RT-PCR/Luminex assay showed a concordance of 86.7% with those of the semi-nested RT-PCR. None of other virus infection samples was amplified. This is the first description of a hybridization assay that can discriminate the four DENV serotypes using probes against a single DENV sequence. The results indicated that the RT-PCR/Luminex DENV assay designed and evaluated in this study is a valuable additional tool for the early and rapid detection and serotyping of DENV, which could, in the future, be applied to new targets such as the Zika and Chikungunya viruses.

Neurocysticercosis-related mortality in Brazil, 2000-2011: Epidemiology of a neglected neurologic cause of death.

Neurocysticercosis (NCC) is an important cause of severe neurological disease mainly in low- and middle-income countries, but data on NCC mortality from endemic areas are scarce. Here we analysed the epidemiological patterns of NCC-related mortality in Brazil. We included all deaths recorded in Brazil between 2000 and 2011, in which NCC was mentioned on death certificates, either as underlying or as associated cause of death. NCC was identified in 1829/12,491,280 deaths (0.015%), 1130 (61.8%) as underlying cause, and 699 (38.2%) as associated cause. Overall age-adjusted mortality rate for the period was 0.97 deaths/1,000,000 inhabitants (95% confidence interval [CI]: 0.83-1.12). The highest NCC-related mortality rates were found in males, elderly, white race/colour and residents in endemic states/regions. Age-adjusted mortality rates at national level decreased significantly over time (annual percent change [APC]: -4.7; 95% CI: -6.0 to -3.3), with a decrease in the Southeast, South and Central-West regions, and a non-significant increasing trend in the North and Northeast regions. We identified spatial and spatiotemporal high-risk mortality clusters located mainly in NCC-endemic areas. Conditions related to the nervous system were the most commonly associated causes of death when NCC was mentioned as an underlying cause, and HIV/AIDS was the main underlying cause when NCC was an associated cause. NCC is a neglected and preventable cause of severe neurologic disease and death with high public health impact in Brazil. There is a clear need to strengthen nationwide epidemiological surveillance and control for the taeniasis/cysticercosis complex.

Acute schistosomiasis mansoni: the pathophysiological cycle of the schistosoma mansoni and the granulomas as egg of columbus / Esquistossomose mansônica aguda: o ciclo fisiopatológico do Schistosoma mansoni e o granuloma como ovo de colombo*

Background and objectives: Schistosomiasis has a wide geographical distribution, and is found in many countries including Brazil, where it is endemic in some states. This study aimed to describe the main pathogenic aspects of the Homo sapiens sapiens / Shistosoma mansoni interaction, focusing on the acute phase of illness. Accordingly, we reviewed the literature using a with a defined search strategy, using PubMed. The selected papers were read and the information organized into two sections, focusing on (1) the pathophysiological human-helminth interaction "cycle" and (2) the role of granuloma in the disease. Content: The pathologic process begins with the penetration of the cercariae into the skin, from which point the response mechanisms to infection are triggered - linked to the biological cycle of the helminth in the human body - and justifying the development of acute and chronic forms of the disease. The acute phase is characterized by the formation of necrotic-exudative granulomas around the eggs. Continuous oviposition allows for modulation of the immune response, the histopathological significance of which is the disappearance of the necrotic areas and size reduction of the granulomas surrounding the eggs. Conclusion: An understanding of the Homo sapiens sapiens/Schistosoma mansoni interaction is essential in order to think of ways to intervene with the natural history of the disease, avoiding the emergence of severe forms - especially in the context of evolution to chronic disease -, and, perhaps, corroborating for a better coexistence between man and helminth, in the best spirit of cohabitology...

Tuberculose em hospital geral / Tuberculosis in general hospital

No Hospital Universitário (Faculdade de Medicina) da Universidade Federal do Rio de Janeiro, onde näo säo internados pacientes sabidamente portadores de tuberculose pulmonar, foram diagnosticados 166 casos desta enfermidade, no período compreendido entre 1978 e setembro de 1984. A tuberculose, assim, é um problema para o Hospital Geral: a) deve ser um problema sua internaçäo eletiva e o Hospital deve estar preparado para recebê-la, diagnosticá-la e tratá-la em todas as suas formas; b) deve estar apto a reconhecê-la após a internaçäo e, para isto, tem que se adaptar por todos os meios modernos de diagnóstico, para identificá-la rápida e seguramente; c) ao lado dos equipamentos radiológico, bacteriológico, imunológico e outros, deve ter seu pessoal médico e paramédico constantemente instruído e alertado para a importância, os riscos e a responsabilidade no tratamento da tuberculose