Exploring the Profile of Cell Populations and Soluble Immunological Mediators in Bothrops atrox Envenomations.

Bothrops atrox envenomations are common in the Brazilian Amazon. The venom of B. atrox is highly inflammatory, which results in severe local complications, including the formation of blisters. Moreover, there is little information on the immune mechanisms associated with this condition. Thus, a longitudinal study was carried out to characterize the profile of the cell populations and soluble immunological mediators in the peripheral blood and blisters in B. atrox patients s according to their clinical manifestations (mild and severe). A similar response in both B. atrox patient groups (MILD and SEV) was observed, with an increase in inflammatory monocytes, NKT, and T and B cells, as well as CCL2, CCL5, CXCL9, CXCL10, IL-1ß and IL-10, when compared with the group of healthy blood donors. After the administration of antivenom, the participation of patrolling monocytes and IL-10 in the MILD group was observed. In the SEV group, the participation of B cells was observed, with high levels of CCL2 and IL-6. In the blister exudate, a hyperinflammatory profile was observed. In conclusion, we revealed the involvement of cell populations and soluble mediators in the immune response to B. atrox envenomation at the local and peripheral level, which is related to the onset and extent of the inflammation/clinical manifestation.

Case Report: Adrenal Pathology Findings in Severe COVID-19: An Autopsy Study.

Although high mortality has been reported in many COVID-19 studies, very limited postmortem information from complete autopsies is available. We report the findings in the adrenal glands in 28 autopsies with confirmed SARS-CoV-2 infection. Microscopic lesions were identified in the adrenal glands in 12/28 patients (46%). Seven cases showed necrosis, generally ischemic; four showed cortical lipid degeneration; two showed hemorrhage; and one unspecific focal adrenalitis. Vascular thrombosis in one patient and focal inflammation in association with other findings in three patients were observed. No case presented adrenal insufficiency. In conclusion, adrenal lesions are frequent in patients with severe COVID-19. The lesions are mild but could contribute to the lethal outcome.

Confirmed Invasive Pulmonary Aspergillosis and COVID-19: the value of postmortem findings to support antemortem management.

We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.

Confirmed Invasive Pulmonary Aspergillosis and COVID-19: the value of postmortem findings to support antemortem management

Abstract We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.

An Immunological Stairway to Severe Tissue Complication Assembly in Bothrops atrox Snakebites.

Snakebites are a serious public health problem and, in the Amazon, the Bothrops atrox snake is the most frequent cause of envenomation. B. atrox venom (BaV) causes pathophysiological changes with intense, local inflammatory processes, such as severe tissue complication (STC). However, mechanisms associated with the inflammatory process in humans are still poorly understood. Thus, in this study, we sought to describe the profile of local and systemic immunological soluble molecules in Bothrops envenomation patients treated at a specialist tertiary healthcare unit in the Brazilian Amazon. An analytical and prospective study was performed with patients who had snakebites with different clinical outcomes (STC and Mild Tissue Complication-MTC) using venous blood and blister exudate in order to measure immunological soluble molecules present in the response process. Twenty STC patients and 20 MTC patients were eligible for the study. In addition, 20 healthy donors (HD) who had never been bitten by a snake were used as controls. The biomarkers CXCL-8, CCL-5, CXCL-9, CCL-2 and CXCL-10; C3a, C4a, and C5a; IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, TNF, IFN-γ and IL-17A were quantified using flow cytometry and ELISA. The circulating response profile differs between the studied groups, with MTC patients presenting a mixed profile and STC patients presenting a more polarized profile for Th1 response. In addition, individuals who develop STC have a more intense local immune response, because the tissue response differs from the circulating immunological soluble molecules and presents Th1/Th2/Th17 response polarization. Furthermore, these results suggest that CCL-2 and CXCL-10 are biomarkers for STC and the response profile they assume against Bothrops snakebite should reflect in the clinical practice for the patient.

Low Health System Performance, Indigenous Status and Antivenom Underdosage Correlate with Spider Envenoming Severity in the Remote Brazilian Amazon.

BACKGROUND: A better knowledge of the burden and risk factors associated with severity due to spider bites would lead to improved management with a reduction of sequelae usually seen for this neglected health problem, and would ensure proper use of antivenoms in remote localities in the Brazilian Amazon. The aim of this study was to analyze the profile of spider bites reported in the state of Amazonas in the Western Brazilian Amazon, and to investigate potential risk factors associated with severity of envenomation. METHODOLOGY/PRINCIPAL FINDINGS: We used a case-control study in order to identify factors associated with spider bite severity in the Western Brazilian Amazon from 2007 to 2014. Patients evolving to any severity criteria were considered cases and those with non-severe bites were included in the control group. All variables were retrieved from the official Brazilian reporting systems. Socioeconomical and environmental components were also included in a multivariable analysis in order to identify ecological determinants of incidence and severity. A total of 1,181 spider bites were recorded, resulting in an incidence of 4 cases per 100,000 person/year. Most of the spider bites occurred in males (65.8%). Bites mostly occurred in rural areas (59.5%). The most affected age group was between 16 and 45 years old (50.9%). A proportion of 39.7% of the bites were related to work activities. Antivenom was prescribed to 39% of the patients. Envenomings recorded from urban areas [Odds ratio (OR) = 0.40 (95%CI = 0.30-0.71; p<0.001)] and living in a municipality with a mean health system performance index (MHSPI >median [OR = 0.64 (95%CI = 0.39-0.75; p<0.001)] were independently associated with decreased risk of severity. Work related accidents [OR = 2.09 (95%CI = 1.49-2.94; p<0.001)], Indigenous status [OR = 2.15 (95%CI = 1.19-3.86; p = 0.011)] and living in a municipality located >300 km away from the state capital Manaus [OR = 1.90 (95%CI = 1.28-2.40; p<0.001)] were independently associated with a risk of severity. Living in a municipality located >300 km away from the state capital Manaus [OR = 1.53 (95%CI = 1.15-2.02; p = 0.003)] and living in a municipality with a MHSPI 300 km away from the state capital Manaus could be contributing factors to higher severity of spider envenomings in this area, as well as to antivenom underdosage.

HPV Infection and Cervical Screening in Socially Isolated Indigenous Women Inhabitants of the Amazonian Rainforest.

OBJECTIVE: Indigenous women from the Amazon regions have some of the highest rates of cervical cancer in the world. This study evaluated cervical cytology and human papillomavirus (HPV) in native women that differ by lifestyle and interaction with western society. Yanomami women are isolated deep in the Amazon with a hunter/gatherer lifestyle. Macuxi and Wapishana women live in proximity to western society. METHODS: To select a representative group of women from each district, random cluster sampling was used, considering each registered village as a cluster. Cervical samples were collected for cytology and HPV detection and typing by PCR amplification and next generation sequencing. The study was approved by the National IRB and by tribal leaders. RESULTS: 664 native women were enrolled from 13 indigenous villages (76% participation rate). Yanomami women had higher rates of abnormal cytology (5.1% vs. 1.8%, p = 0.04) and prevalent HR-HPV (34.1% vs. 19.2%, p<0.001). Yanomami women >35 y of age were significantly more likely to have HR-HPV, whereas women ≤ 35 y did not significantly differ between groups. Prevalence of HPV was significantly different amongst geographically clustered Yanomami women (p<0.004). The most prevalent HPV types in the entire group were HPV31 (8.7%), HPV16 (5.9%) and HPV18 (4.4%). CONCLUSION: Isolated endogenous Yanomami women were more likely to be HPV+ and rates increased with age. Study of HPV in isolated hunter-gather peoples suggests that long-term persistence is a characteristic of prehistoric humans and patterns reflecting decreased prevalence with age in western society represents recent change. These studies have implications for cervical cancer prevention and viral-host relationships.

Glioblastoma Multiforme in an HIV-Infected Patient: An Unexpected Diagnosis.

We reported a case of glioblastoma multiforme in a 42-year-old female patient with HIV infection, who had a rapid progression to AIDS. She was diagnosed with an intracerebral mass and treated as neurotoxoplasmosis with improvement in the first week of therapy. On the fourth week she had a clinical worsening evolving to death, receiving the diagnosis at necropsy.

Reproducibility of histopathologic diagnosis of skin diseases by digital photomicrographs versus conventional optical microscopy.

BACKGROUND: Telepathology is considered a good alternative for a second opinion consultation. Its implementation is desirable, but studies to confirm its practical application are required. OBJECTIVES: To evaluate the reproducibility of histopathologic diagnoses of skin diseases obtained through digital photomicrographs compared with conventional microscopy. METHODS: We evaluated the surgical specimens of 135 patients using an optical microscope. After 4 weeks, the same consultants independently evaluated a total of 1,738 digital photomicrographs obtained from the histopathological slides. We estimated the overall rate of intra and interobserver agreement, and the Kappa coefficient was obtained with the categorization of the skin diseases: neoplastic skin diseases, infectious-contagious skin diseases and non-infectious-contagious skin diseases. RESULTS: Consultant 1 obtained an agreement of 88.1% (95% CI = 81.5% - 93.1%) between conventional microscopy and images. Consultant 2 obtained an agreement of 80.7% (95% CI = 73.1% - 87%). The interobserver agreement for the microscopy analysis was 81.5% (95% CI = 73.9% - 87.6%). The same analysis using microphotography showed an agreement of 85.9% (95% CI = 78.9% - 91.3%). The Kappa coefficient, which evaluated the categorized skin diseases, was 98.6% for Consultant 1, 93.1% for Consultant 2, 95.8% for interconsultant analyses of images and 95.9% for interconsultant analyses using conventional optical microscopy. All of these values are considered optimal. CONCLUSION: The evaluation of microphotographs shows a good level of reproducibility when compared to traditional microscopy and, therefore, is a viable option for a second opinion consultation in dermatopathology.

Reprodutibilidade do diagnóstico histopatológico de dermatoses por fotomicrografias digitais versus microscopia óptica convencional / Reproducibility of histopathologic diagnosis of skin diseases by digital photomicrographs versus conventional optical microscopy

FUNDAMENTOS: A telepatologia é considerada boa alternativa para consultas de segunda opinião. Sua implementação é desejável, mas estudos que confirmem sua aplicação prática são necessários. OBJETIVOS: Analisar a concordância entre os diagnósticos histopatológicos de dermatoses feitos com base em microfotografias digitais em comparação com a microscopia convencional. MÉTODOS: As lâminas de 135 pacientes foram avaliadas por dois consultores por meio de microscópio. Após quatro semanas, os mesmos consultores avaliaram 1.738 microfotografias digitais obtidas dessas lâminas. Estimou-se a taxa geral de concordância intraobservadores e interobservadores e obteve-se o índice Kappa com a categorização das dermatoses: dermatoses neoplásicas, dermatoses infectocontagiosas e não infectocontagiosas. RESULTADOS: A concordância do Consultor 1, que analisou lâminas ao microscópio versus imagens, foi de 88,1 por cento (IC 95 por cento = 81,5 por cento - 93,1 por cento). O Consultor 2 obteve concordância de 80,7 por cento (IC 95 por cento = 73,1 por cento - 87 por cento). A concordância interconsultores ao microscópio foi de 81,5 por cento (IC 95 por cento = 73,9 por cento - 87,6 por cento). A mesma análise por meio de microfotografias mostrou concordância de 85,9 por cento (IC 95 por cento = 78,9 por cento - 91,3 por cento). O índice Kappa, que avalia as dermatoses categorizadas, foi de 98,6 por cento para o Consultor 1, de 93,1 por cento para o Consultor 2, de 95,8 por cento para interconsulta por imagens e de 95,9 por cento para interconsultas ao microscópio óptico. Todos esses valores são considerados ótimos. CONCLUSÃO: A avaliação das microfotografias apresentou ótimo nível de reprodutibilidade quando comparada à microscopia tradicional, sendo uma opção viável para consultas de segunda opinião em dermatopatologia.

BACKGROUND: Telepathology is considered a good alternative for a second opinion consultation. Its implementation is desirable, but studies to confirm its practical application are required. OBJECTIVES: To evaluate the reproducibility of histopathologic diagnoses of skin diseases obtained through digital photomicrographs compared with conventional microscopy. METHODS: We evaluated the surgical specimens of 135 patients using an optical microscope. After 4 weeks, the same consultants independently evaluated a total of 1,738 digital photomicrographs obtained from the histopathological slides. We estimated the overall rate of intra and interobserver agreement, and the Kappa coefficient was obtained with the categorization of the skin diseases: neoplastic skin diseases, infectious-contagious skin diseases and non-infectious-contagious skin diseases. RESULTS: Consultant 1 obtained an agreement of 88.1 percent (95 percent CI = 81.5 percent - 93.1 percent) between conventional microscopy and images. Consultant 2 obtained an agreement of 80.7 percent (95 percent CI = 73.1 percent - 87 percent). The interobserver agreement for the microscopy analysis was 81.5 percent (95 percent CI = 73.9 percent - 87.6 percent). The same analysis using microphotography showed an agreement of 85.9 percent (95 percent CI = 78.9 percent - 91.3 percent). The Kappa coefficient, which evaluated the categorized skin diseases, was 98.6 percent for Consultant 1, 93.1 percent for Consultant 2, 95.8 percent for interconsultant analyses of images and 95.9 percent for interconsultant analyses using conventional optical microscopy. All of these values are considered optimal. CONCLUSION: The evaluation of microphotographs shows a good level of reproducibility when compared to traditional microscopy and, therefore, is a viable option for a second opinion consultation in dermatopathology.

Paracoccidiodomicose enzóotica em tatus (Dasypus novemcinctus) no Estado do Pará / Enzootic paracoccidioidomycosis in armadillos (Dasypus novemcinctus) in the state of Pará

Paracoccidioides brasiliensis foi encontrado, por inoculaçäo de triturado de fígado e baço em hamsters, em 4 de 20 tatus (Dasypus novemcinctus) examinados na regiäo de Tucuruí, Pará. Hamsters inoculados por via intradérmica e peritoneal com o parasito desenvolveram infecçöes generalizadas e morreram em 1 1/2 a 13 meses. A diagnose do fungo foi confirmada por histopatologia e cultura. Näo se observaram sinais macroscópios de doenças nos tatus. A distribuiçäo geográfica de D. novemcinctus abrange a área endêmica de paracoccidioidomicose humana, sugerindo-se que o tatu tenha algum papel na ecologia do fungo

Hepatite fulminante e febre negra de Lábrea: estudo de 5 casos procedentes de Codajás, Amazonas, Brasil

São descritas as manifestações clinicas, laboratoriais e aspectos evolutivos de cinco pacientes procedentes de Codajás-Amazonas, atendidos no Instituto de Medicina Tropical de Manaus devido ao quadro de hepatopatia grave, com período médio de doença de quatro dias. Quatro destes pacientes evoluiram para óbito, com uma média de cinco dias desde o inicio dos pródromos. A sorologia para hepatite B mostrou que o Ag HBs estava presente em quatro e o Anti - HBc em todos. Dos pacientes que foram ao óbito, através da necropsia a histopatologia do fígado revelou quadro de hepatite fulminante em dois e de febre de Lábrea nos outros dois.

We have described the clinical and laboratory manifestations and evolutiortal aspects of five patients from Codajás, state of Amazonas, Brasil. These patients were treated at the Instituto de Medicina Tropical de Manaus with a picture of acute liver failure with an average period of evolution of 4 days. Of these patients, four died, within an average time of five days since the prodromal phase. Serology for hepatitis B showed that HBAg was present in four, and the HBc antigen in all patients. An autopsy was perfomed on the four patients who died, and the liver histopathology revealed a picture of fulminant hepatitis in two, and Lábrea fever (febre negra), in the other two.