INTERPRETANDO O LÍQUOR – COMO DADOS EPIDEMIOLÓGICOS PODEM AJUDAR NO RACIOCÍNIO CLÍNICO

Introdução: A meningite bacteriana sofreu grandes mudanças epidemiológicas após a introdução dos antibióticos e vacinas, passando de uma condição letal para tratável e prevenível. Compreender essas mudanças no perfil epidemiológico em nível local permitem planejar estratégias de terapia empírica. As alterações de líquor possuem papel fundamental nessa avaliação. Metodologia: Foi realizado um estudo transversal dos casos notificados de meningite entre janeiro de 2010 e junho de 2015 no Complexo Hospital de Clínicas – Universidade Federal do Paraná. Foram analisados a celularidade e citologia do líquor e os agentes etiológicos. Para as etiologias bacterianas, foi avaliado dados epidemiológicos. Resultados: Foram notificados 504 casos de meningite no período avaliado. A meningite asséptica foi a classificação epidemiológica mais comum. As meningites bacterianas com confirmação etiológica causadas por Neisseria meningitidis, Streptococcus pneumoniae ou Haemophilus influenzae ocorreram em 8,7% dos casos notificados, sendo que 30% delas ocorreram em menores de 1 ano. A N. meningitidis correspondeu a 61% desses casos, enquanto que S. pneumoniae a 34%. As meningites neutrofílicas com mais de 75% de neutrófilos são causadas por tais bactérias em mais da metade (53%). A meningite asséptica é a segunda principal etiologia (20%) seguida de perto pela meningite tuberculosa (17%). Os casos de meningite meningocócica se concentram em crianças até 1 ano (56% dos casos), a meningite pneumocócica se concentra nos adultos entre 18 e 50 anos (46%) e idosos (27%). Conclusões: O conhecimento da epidemiologia local através da interpretação do líquor, somada à avaliação da faixa etária são importantes aliados da avaliação clínica para determinação do agente etiológico mais provável e podem ajudar na decisão terapêutica

Differential Regional Immune Response in Chagas Disease

Following infection, lymphocytes expand exponentially and differentiate into effector cells to control infection and coordinate the multiple effector arms of the immune response. Soon after this expansion, the majority of antigen-specific lymphocytes die, thus keeping homeostasis, and a small pool of memory cells develops, providing long-term immunity to subsequent reinfection. The extent of infection and rate of pathogen clearance are thought to determine both the magnitude of cell expansion and the homeostatic contraction to a stable number of memory cells. This straight correlation between the kinetics of T cell response and the dynamics of lymphoid tissue cell numbers is a constant feature in acute infections yielded by pathogens that are cleared during the course of response. However, the regional dynamics of the immune response mounted against pathogens that are able to establish a persistent infection remain poorly understood. Herein we discuss the differential lymphocyte dynamics in distinct central and peripheral lymphoid organs following acute infection by Trypanosoma cruzi, the causative agent of Chagas disease. While the thymus and mesenteric lymph nodes undergo a severe atrophy with massive lymphocyte depletion, the spleen and subcutaneous lymph nodes expand due to T and B cell activation/proliferation. These events are regulated by cytokines, as well as parasite-derived moieties. In this regard, identifying the molecular mechanisms underlying regional lymphocyte dynamics secondary to T. cruzi infection may hopefully contribute to the design of novel immune intervention strategies to control pathology in this infection

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Fatores de risco para diárreia persistente em lactentes Risk factors to persistent diarrhea in infants

RACIONAL: A diarréia persistente é uma doença multicausal. A análise do risco para o prolongamento do quadro diarréico envolve variáveis ambientais, biológicas e do manejo clínico. OBJETIVO: Identificar fatores de risco para a diarréia persistente em crianças hospitalizadas na fase aguda do quadro diarréico. PACIENTES E MÉTODOS: O estudo foi do tipo caso-controle. A amostra consistiu de 216 crianças menores de 24 meses hospitalizadas por diarréia de início abrupto, no Instituto Materno-Infantil de Pernambuco, Recife, PE. O grupo de casos incluiu as crianças com diarréia persistente e o de controles aquelas com diarréia aguda. Foram analisadas variáveis socioeconômicas, biológicas, de morbidade anterior, clínicas e do manejo terapêutico prévio à admissão. Utilizou-se o odds ratio não ajustado e ajustado, com seus respectivos intervalos de confiança de 95%, observando-se o nível de significância de 5%. A análise multivariada foi feita através de regressão logística. RESULTADOS: O risco de persistência da diarréia foi maior nas crianças com: disenteria, febre no início do quadro, dieta suspensa e uso de antibiótico à admissão hospitalar. O risco de diarréia persistente foi cerca de três vezes maior para crianças sem geladeira no domicílio e que apresentavam hiperemia perianal ao exame físico na admissão hospitalar, sendo estas as variáveis que apresentaram significância estatística após o ajuste para fatores de confusão. CONCLUSÕES: A melhoria das condições ambientais e o manejo adequado e individualizado da criança hospitalizada por diarréia pode contribuir para a redução da morbidade da doença.<br>BACKGROUND: Persistent diarrhea is a multicausal disease. The analysis of risk factors for persistent diarrhea includes environmental and biological variables as well as therapeutical management. AIM: To identify risk factors for persistent diarrhea among children hospitalized with acute diarrhea. PATIENT AND METHODS: This is a case-control study. The sample consisted of 212 infants under 24 months, hospitalized with acute diarrhea, at the "Instituto Materno-Infantil de Pernambuco", Recife, PE, Brazil. Cases were infants with persistent diarrhea and controls those with acute diarrhea. Cases and controls were compared to a series of socio-economic, biological and clinical variables, previous morbidities and therapeutic management prior to hospital admission. Unadjusted and adjusted odds ratio were used with the respective 95% confidence intervals. It was adopted the level of significance of 5%. Logistic regression analysis was conducted to control for potential confounding factors. RESULTS: The risk of persistent diarrhea was higher for infants with: dysentery, fever at the onset of diarrhea, fasting and taking antibiotics prior to hospital admission. The variables that showed the highest adjusted odds ratios for persistent diarrhea were infants living in households without refrigerator and perianal hyperemia at hospital admission. CONCLUSIONS: The improvement of environmental conditions and an adequate clinical management of diarrhea for hospitalized infants may contribute to the reduction of diarrhea morbidity