MULTISYSTEM INFLAMMATORY SYNDROME IN A CHILD ASSOCIATED WITH CORONAVIRUS DISEASE 19 IN THE BRAZILIAN AMAZON: FATAL OUTCOME IN AN INFANT.

OBJECTIVE: Recently, there have been reports of children with severe inflammatory syndrome and multiorgan dysfunction associated with elevated inflammatory markers. These cases are reported as presenting the Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19. In this study, we describe with parental permission a case of MIS-C in an infant with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CASE DESCRIPTION: A seven-month-old infant, with SARS-CoV-2 infection and a history of extreme preterm birth and very low weight at birth, with an initial course of mild respiratory symptoms and abrupt progression to vasoplegic shock, myocarditis and hyperinflammation syndrome, shown by high levels of troponin I, ferritin, CRP, D-dimer and hypoalbuminemia. Despite the intensive care provided, the child developed multiple organ dysfunction and died. COMMENTS: Patients with a history of extreme prematurity may present with MIS-C in the presence of COVID-19 and are a group of special concern.

Multisystem inflammatory syndrome in a child associated with coronavirus disease 19 in the brazilian amazon: fatal outcome in an infant / Síndrome inflamatória multissistêmica em criança associada à doença do coronavírus 19 na amazônia brasileira: evolução fatal em lactente

ABSTRACT Objective: Recently, there have been reports of children with severe inflammatory syndrome and multiorgan dysfunction associated with elevated inflammatory markers. These cases are reported as presenting the Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19. In this study, we describe with parental permission a case of MIS-C in an infant with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Case description: A seven-month-old infant, with SARS-CoV-2 infection and a history of extreme preterm birth and very low weight at birth, with an initial course of mild respiratory symptoms and abrupt progression to vasoplegic shock, myocarditis and hyperinflammation syndrome, shown by high levels of troponin I, ferritin, CRP, D-dimer and hypoalbuminemia. Despite the intensive care provided, the child developed multiple organ dysfunction and died. Comments: Patients with a history of extreme prematurity may present with MIS-C in the presence of COVID-19 and are a group of special concern.

RESUMO Objetivo: Recentemente, foram descritos relatos de crianças com exame positivo para o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2) associado à disfunção de múltiplos órgãos, secundária à hiperinflamação, denominada de síndrome inflamatória multissistêmica pediátrica (do inglês multisystem inflammatory syndrome in children - MIS-C). O objetivo deste relato é descrever um caso de MIS-C em lactente com infecção por SARS-CoV-2 e com evolução fatal abrupta, a despeito do suporte de terapia intensiva pediátrica. Descrição do caso: Lactente de sete meses, com infecção por SARS-CoV-2 e antecedentes de prematuridade extrema, com quadro inicial de síndrome gripal e progressão abrupta para choque vasoplégico, miocardite e síndrome de hiperinflamação, evidenciados por níveis elevados de troponina I, ferritina, proteína C reativa (PCR), dímero D e hipoalbuminemia. Não obstante o suporte de terapia intensiva instituído, a criança evoluiu com disfunção de múltiplos órgãos e morte. Comentários: Pacientes com antecedentes de prematuridade extrema podem apresentar MIS-C na vigência de doença do coronavírus 19 (COVID-19) e constituir um grupo de preocupação especial.

Norovirus RNA in serum associated with increased fecal viral load in children: Detection, quantification and molecular analysis.

Worldwide, norovirus (NoV) is a major cause of acute gastroenteritis (AGE) responsible for pandemics every ~3 years, and over 200,000 deaths per year, with the majority in children from developing countries. We investigate the incidence of NoV in children hospitalized with AGE from Belém, Pará, Brazil, and also correlated viral RNA levels in their blood and stool with clinical severity. For this purpose, paired stool and serum samples were collected from 445 pediatric patients, ≤9 years between March 2012 and June 2015. Enzyme-linked immunosorbent assay (EIA) was used to detect NoV in stool and reverse transcription quantitative PCR (RT-qPCR) used to quantify NoV RNA levels in sera (RNAemia) and in the positive stool. Positives samples were characterized by the partial ORF1/2 region sequence of viral genome. NoV antigen was detected in 24.3% (108/445) of stool samples, with RNAemia also present in 20.4% (22/108). RNAemia and a high stool viral load (>107 genome copies/gram of faeces) were associated with longer hospitalizations. The prevalent genotypes were GII.4 Sydney_2012 (71.6%-58/81) and New Orleans_2009 (6.2%-5/81) variants. Eight other genotypes belonging to GII were detected and four of them were recombinant strains. All sera were characterized as GII.4 and shared 100% similarity with their stool. The results suggest that the dissemination of NoV to the blood stream is not uncommon and may be related to increased faecal viral loads and disease severity.

Astrovirus infection in hospitalized children: Molecular, clinical and epidemiological features.

BACKGROUND: Astrovirus (HAstV) is a common viral pathogen that causes gastroenteritis worldwide. It is classified into eight classical human types (HAstV-1/8) and seven other less prevalent types, described as HAstV VA1, VA2, VA3, VA4, MLB-1, MLB-2 and MLB-3. During outbreaks, the elderly and children are the most affected, and the spread of the virus is associated with person-to-person contact, food ingestion and contaminated water. OBJECTIVES: The aim of the present study was to investigate the prevalence of infection and genetic diversity of HAstV strains. Samples were collected from children with acute gastroenteritis admitted to a large pediatric hospital during a surveillance period of three years (2008-2011) in Belém city, Pará State, Amazon Region, Northern Brazil. STUDY DESIGN: Screening and genotyping tests were conducted using RT-PCR to detect the classical and non-classical HAstV types using specific primers. A semi-nested RT-PCR protocol was developed to improve viral detection in samples with a low viral load. RESULTS: The overall positivity observed in this study was 3.9% (19/483). The age distribution showed a high prevalence of positive cases in children under one year old (5.3%). We found vomiting associated with 75% of the positive cases, fever with 82.3%, and dehydration with 76.9%. Most patients with positive cases demonstrated two to five days of diarrhea, two to three episodes of vomiting during hospitalization, and three bowel movements per day. Co-infection with HAstV and norovirus was observed in three cases (15.8%), and no pattern of seasonality or any relationship between the HAstV positivity rate and climate variables was observed. Eighteen positive samples (94.7%-18/19) were genotyped based on the ORF 2 region, and the greatest prevalence was of HAstV-1a (66.6%-12/18), followed by HAstV-2 (22.2%-4/18, comprising two type-2b and two type-2c genotypes), HAstV-3c (5.6%-1/18) and HAstV-4c (5.6%-1/18). No non-classical types were detected in the clinical samples analyzed. CONCLUSIONS: The present study showed that although HAstV infections occur at low frequency, they are involved in severe pediatric cases of acute gastroenteritis presenting with a high diversity of strains, including the lineages 3c and 4c, which were never before detected in Brazil.

Detection and genetic characterization of the emergent GII.17_2014 norovirus genotype among children with gastroenteritis from Northern Brazil.

Norovirus is the most important cause of viral gastroenteritis outbreaks worldwide. Recently, a novel GII.17 norovirus variant emerged and caused epidemics in Asian countries, replacing the GII.4 Sydney 2012 strain in hospitalized cases. In this study we describe the emergence of this novel NoV GII.17_2014 strain in Brazil.

Characterization of novel intragenotype recombination events among norovirus pandemic GII.4 variants.

Recently, there has been an increase in the number of children hospitalized due to norovirus infection in Brazil. This is due both to the occurrence of more severe norovirus-related gastroenteritis cases after the introduction of the rotavirus vaccine and an increase in the tools for the detection of the disease. This pathogen is transmitted by the fecal-oral route, and the illness is characterized by diarrhea, vomiting, nausea and abdominal cramps. The genome of the virus is organized into three open reading frames showing strong mutation rates. Additionally, homologous recombination events, which can increase the virulence of the virus and lead to genotyping mistakes in molecular epidemiological studies, frequently occur. The purpose of this study was to describe two recombination events among different GII.4 variants that infected children who were hospitalized for severe acute gastroenteritis during distinct periods of time in Belém, Brazil. The recombination among the variants US95_96/Kaiso_2003 and Den Haag_2006b/Yerseke_2006a were observed in May 2003 and February 2009, respectively. In both cases, the association between the dominant variant at that point in time and another that was circulating at a low frequency in the population of Belém was demonstrated. Interestingly, the position of the breakpoint of the recombination event in the genome was the polymerase gene and was located at the nucleotide positions 4.834 and 5.002, which is an unusual location for the occurrence of recombination as other studies have previously reported the junction region as a breakpoint. In this study, both recombinant variant strains were related to severe cases of diarrhea that lead to hospitalization, demonstrating the viral evolution of GII.4 in response to selective pressures, which ultimately lead to the emergence of novel viral types in the pediatric population. The cases discussed here reinforce the need for continuous norovirus surveillance. To our knowledge, these two GII.4 variant recombinations have not yet been previously described.

Group A rotavirus and norovirus display sharply distinct seasonal profiles in Belém, northern Brazil.

Several viruses have been associated with acute gastroenteritis (AGE), and group A rotavirus (RVA) and norovirus (NoV) are the most prevalent. This study aimed to assess their prevalence among children hospitalised for diarrhoea during a three-year surveillance study. From May 2008-April 2011, overall positivity rates of 21.6% (628/2904) and 35.4% (171/483) were observed for RVA and NoV, respectively. The seasonality observed indicated distinct patterns when both viruses were compared. This finding may explain why hospitalisation for AGE remains constant throughout the year. Continuous AGE monitoring is needed to better assess the patterns of infection.

Group A rotavirus and norovirus display sharply distinct seasonal profiles in Belém, northern Brazil

Several viruses have been associated with acute gastroenteritis (AGE), and group A rotavirus (RVA) and nor-ovirus (NoV) are the most prevalent. This study aimed to assess their prevalence among children hospitalised for diarrhoea during a three-year surveillance study. From May 2008-April 2011, overall positivity rates of 21.6% (628/2904) and 35.4% (171/483) were observed for RVA and NoV, respectively. The seasonality observed indicated distinct patterns when both viruses were compared. This finding may explain why hospitalisation for AGE remains constant throughout the year. Continuous AGE monitoring is needed to better assess the patterns of infection.

Norovirus infection in children admitted to hospital for acute gastroenteritis in Belém, Pará, Northern Brazil.

Noroviruses are the leading cause of epidemic, non-bacterial outbreaks of acute gastroenteritis, and are also a major cause of sporadic acute gastroenteritis in infants. The aim of the present study was to identify norovirus infections in children not infected by rotavirus admitted to hospital for acute gastroenteritis in Belém. A total of 348 fecal specimens were obtained from children with diarrhea aged less than 5 years, all of whom had tested negative for rotavirus, between May 2008 and April 2010. Fecal samples were screened for norovirus antigen using enzyme-immunoassay (EIA). Specimens were subjected to reverse-transcription polymerase chain reaction (RT-PCR) using the primers Mon432/434-Mon431/433 for detection of the GI and GII norovirus strains, respectively. Based on both methods, the overall norovirus positivity rate was 36.5% (127/348). Of the 169 samples collected in the first year, 44.4% (n = 75) tested positive for norovirus using both methods, 35.5% (n = 60) by EIA and 40.8% (n = 69) by RT-PCR. Using RT-PCR as a reference standard, a sensitivity of 78.3%, specificity of 94%, and agreement of 87.6% were recorded. Genome sequencing was obtained for 22 (31.9%) of the 69 positive samples, of which 90.9% (20/22) were genotype GII.4d and 9.1% (2/22) were genotype GII.b. Norovirus infection was most frequent in children under 2 years of age (41.5%-115/277). The peak incidence (62.1%) of norovirus-related acute gastroenteritis in these patients (not infected by rotavirus) was observed in February 2010. These findings emphasize the importance of norovirus as a cause of severe acute gastroenteritis among children in Belém, Pará, Northern Brazil.

Efetividade da vacina oral contra rotavírus humano espécie A e monitoramento das amostras v irais circulantes em Belém, Pará, Brasil / Effectiveness of oral vaccine against human rotavirus type A and monitoring of samples v irais circulating in Belém, Pará, Brazil

Globalmente, os rotavírus da espécie A (RVA) são a principal causa de doença diarreica aguda grave em crianças abaixo de cinco anos de idade, sendo responsáveis por mais de um terço de todas as hospitalizações por diarreia e 453.000 óbitos a cada ano, principalmente nos países em desenvolvimento. Ensaios clínicos multicêntricos envolvendo aproximadamente 100.000 crianças na América Latina, Europa, África e Ásia demonstraram a segurança e a eficácia da vacina monovalente contra RVA de origem humana (Rotarix ® , GlaxoSmithKline, Bélgica), em prevenir gastroenterite grave causada por esse agente viral em crianças. No Brasil essa vacina foi introduzida no Programa Naci onal de Imunizações em 6 de março de 2006, sob a denominação de Vacina Oral contra Rotavírus Humano (VORH). Realizou-se estudo caso-controle de base hospitalar que avaliou a efetividade da vacina através da vigilância diária das hospitalizações por gastroenterite ocorridas entre crianças nascidas após seis de março de 2006, em quatro clínicas selecionadas em Belém, Pará. Consentimento por escrito foi obtido dos pais/responsável legal pela criança antes de sua inclusão no estudo. Após a hospitalização, amostras de fezes dessas crianças foram coletadas e enviadas à Seção de Virologia do Instituto Evandro Chagas para detecção dos RVA por ensaio imunoenzimático (ELISA). As amostras positivas foram posteriormente genotipadas por reação em cadeia da polimerase precedida de transcrição reversa (RT-PCR). No primeiro ano (2008-2009), 538 crianças foram incluídas no estudo como casos (gastroenterite grave por RVA) e pareadas, de acordo com a idade, a 507 controles hospitalares e 346 domiciliares; estes, sem quaisquer sintomas de gastroenterite. Haviam recebido esquema vacinal completo quanto a VORH (duas doses) 54 por cento, 61 por cento e 74 por cento dos casos, controles hospitalares e domiciliares, respectivamente...

Os resultados obtidos nesse estudo demonstraram a boa efetividade da vacina VORH frent e aos casos graves de gastroenterite causada por RVA em condições reais na população est udada, inclusive contra genótipo distinto daquele contido na composição da vacina. A lém disso, permitiu o monitoramento da circulação de amostras virais no período de três anos consecutivos em Belém, Pará, demonstrando variação nos genótipos circulantes ao longo do estudo; o que corrobora a hipótese de flutuação natural das amostras circulantes ao longo do tempo...

Prevalence and clinical features of respiratory syncytial virus in children hospitalized for community-acquired pneumonia in northern Brazil.

BACKGROUND: Childhood pneumonia and bronchiolitis is a leading cause of illness and death in young children worldwide with Respiratory Syncytial Virus (RSV) as the main viral cause. RSV has been associated with annual respiratory disease outbreaks and bacterial co-infection has also been reported. This study is the first RSV epidemiological study in young children hospitalized with community-acquired pneumonia (CAP) in Belém city, Pará (Northern Brazil). METHODS: With the objective of determining the prevalence of RSV infection and evaluating the patients' clinical and epidemiological features, we conducted a prospective study across eight hospitals from November 2006 to October 2007. In this study, 1,050 nasopharyngeal aspirate samples were obtained from hospitalized children up to the age of three years with CAP, and tested for RSV antigen by direct immunofluorescence assay and by Reverse Transcription Polymerase Chain Reaction (RT-PCR) for RSV Group identification. RESULTS: RSV infection was detected in 243 (23.1%) children. The mean age of the RSV-positive group was lower than the RSV-negative group (12.1 months vs 15.5 months, p<0.001) whereas gender distribution was similar. The RSV-positive group showed lower means of C-reactive protein (CRP) in comparison to the RSV-negative group (15.3 vs 24.0 mg/dL, p<0.05). Radiological findings showed that 54.2% of RSV-positive group and 50.3% of RSV-negative group had interstitial infiltrate. Bacterial infection was identified predominantly in the RSV-positive group (10% vs 4.5%, p<0.05). Rhinorrhea and nasal obstruction were predominantly observed in the RSV-positive group. A co-circulation of RSV Groups A and B was identified, with a predominance of Group B (209/227). Multivariate analysis revealed that age under 1 year (p<0.015), CRP levels under 48 mg/dL (p<0.001) and bacterial co-infection (p<0.032) were independently associated with the presence of RSV and, in the analyze of symptoms, nasal obstruction were independently associated with RSV-positive group (p<0.001). CONCLUSION: The present study highlights the relevance of RSV infection in hospitalized cases of CAP in our region; our findings warrant the conduct of further investigations which can help design strategies for controlling the disease.

Síndrome Dubin-Johnson: importante causa de icterícia colestática na infância / Dubin-Johnson syndrome: an important cause of obstructive jaundice in children na infância

A síndrome Dubin-Johnson é caracterizada clinicamente por episódios de icterícia colestática recorrente, de caráter benigno e familiar, sendo definida pela presença de pigmento melânico nos hepatócitos. Os autores relatam um caso de síndrome Dubin-Johnson em uma criança portadora de icterícia e hepatoesplenomegalia, cujo diagnóstico foi confirmado pela presença do pigmento castanho escuro à microscopia hepática realizada a partir de biópsia, e alertam para a necessidade de suspeição dessa síndrome em casos de icterícia colestática flutuante na infância.

The Dubin-Johnson syndrome is clinically characterized by recurrent episodes of benign and familiar obstructive jaundice. It is identified by the presence of melanin pigment in the hepatocytes. The authors report a case of Dubin-Johnson syndrome in a child with jaundice and hepatosplenomegaly, whose diagnosis was confirmed by the presence of dark brown pigment on microscopy of liver biopsy. They suggest the suspicion of this syndrome in cases of fluctuating obstructive jaundice in children.