Impact of PCV10 on pediatric pneumococcal disease burden in Brazil: time for new recommendations?

Abstract Objective: To describe the impact of the 10-valent pneumococcal conjugate vaccine on the pediatric burden of pneumococcal infections, carriage, serotype replacement, and antimicrobial resistance in Brazil since its introduction in 2010. Data source: A narrative review of English, Spanish, and Portuguese articles published in online databases and in Brazilian epidemiological surveillance databases was performed. The following keywords were used: Streptococcus pneumoniae, pneumococcal disease, conjugate vaccine, PCV10, antimicrobial resistance, and meningitis. Summary of the findings: Declines in hospitalization rates of all-cause pneumonia occurred in the target age groups and some age groups not targeted by vaccination early after the use of PCV10. Large descriptive studies of laboratory-confirmed pneumococcal meningitis and hospital-based historical series of hospitalized children with IPD have evidenced a significant impact on disease burden, in-hospital fatality rates, and admission to the intensive care unit before and after the inclusion of the vaccine. Impact data on otitis media is limited and inconsistent; the main benefit remains the prevention of complicated diseases. During the late post-vaccine years, a significant and progressive increase in high-level penicillin non-susceptibility pneumococci has been described. Since 2014 serotype 19A has been the leading serotype in all ages and was responsible for 28.2%-44.6% of all IPD in children under 5 yrs. Conclusions: PCV10 has performed a significant impact on IPD in Brazil since 2010, however, progress has been continuously hampered by replacement. Broader spectrum PCVs could provide expanded direct and indirect protection against ST19A and other additional serotypes of increasing importance if administered to children in the Brazilian National Immunization Program.

First report of two consecutive respiratory syncytial virus outbreaks by the novel genotypes ON-1 and NA-2 in a neonatal intensive care unit / Primeiro relato de dois surtos consecutivos de vírus sincicial respiratório pelos novos genótipos ON-1 e NA-2 em uma unidade de terapia intensiva neonatal

Abstract Objective: Respiratory syncytial virus is a pathogen frequently involved in nosocomial outbreaks. Although several studies have reported nosocomial outbreaks in neonatal intensive care units, molecular epidemiology data are scarce. Here, the authors describe two consecutive respiratory syncytial virus outbreaks caused by genotypes ON-1 and NA-2 in a neonatal intensive care unit in São Paulo, Brazil. Methods: A prospective search for respiratory syncytial virus was performed after diagnosing the index case and four other symptomatic newborns in the neonatal intensive care unit. Nasopharyngeal aspirate samples of all patients in the neonatal intensive care unit were tested for 17 respiratory viruses using real-time reverse transcriptase polymerase chain reaction. Genotyping was performed using nucleotide sequencing. Results: From May to August 2013, two different outbreaks were detected in the neonatal intensive care unit. A total of 20 infants were infected with respiratory syncytial virus-A (ten and 14 with ON-1 and NA-2 genotypes, respectively). The mean age of the infants was 10 days, mean birth weight was 1,961 g, and the mean gestational age was 33 weeks. Risk factors (heart disease, lung disease, and prematurity) were present in 80% and 85.7% of infants in the ON-1 and NA-2 groups, respectively. In total, 45.8% of infants were asymptomatic and 20.8% required mechanical ventilation. Coinfections were not detected during the outbreaks. Conclusions: Infants in a neonatal intensive care unit who develop abrupt respiratory symptoms should be tested for respiratory viruses, especially respiratory syncytial virus. Even in the absence of severe symptoms, respiratory syncytial virus detection can prevent nosocomial transmission through infection control measures. A better understanding of respiratory syncytial virus molecular epidemiology is essential for developing new vaccines and antiviral drugs against respiratory syncytial virus.

Resumo Objetivo O vírus sincicial respiratório é um patógeno frequentemente envolvido em surtos nosocomiais. Embora vários estudos tenham relatado tais surtos em unidades de terapia intensiva neonatal, os dados epidemiológicos moleculares são escassos. Neste artigo, descrevemos dois surtos consecutivos de vírus sincicial respiratório causados pelos genótipos ON-1 e NA-2 em uma unidade de terapia intensiva neonatal em São Paulo, Brasil. Métodos Uma busca prospectiva por vírus sincicial respiratório foi realizada após o diagnóstico do caso índice e outros quatro recém-nascidos sintomáticos na unidade de terapia intensiva neonatal. Amostras de aspirado nasofaríngeo de todos os pacientes da unidade de terapia intensiva neonatal foram testadas para 17 vírus respiratórios com reação em cadeia da polimerase via transcriptase reversa em tempo real. A genotipagem realizada utilizando sequenciamento de nucleotídeos. Resultados De maio a agosto de 2013, foram detectados dois surtos diferentes na unidade de terapia intensiva neonatal. Vinte e quatro crianças foram infectadas com vírus sincicial respiratório-A (10 e 14 com os genótipos ON-1 e NA-2, respectivamente). A média da idade dos lactentes era de 10 dias, o peso médio ao nascer foi de 1961 g e a idade gestacional média de 33 semanas. Fatores de risco (doença cardíaca, doença pulmonar e prematuridade) estavam presentes em 80% e 85,7% dos bebês nos grupos ON-1 e NA-2, respectivamente. No total, 45,8% dos lactentes eram assintomáticos e 20,8% necessitaram de ventilação mecânica. Não foram detectadas coinfecções durante os surtos. Conclusões Bebês em unidade de terapia intensiva neonatal que desenvolvem sintomas respiratórios abruptos devem ser testados para vírus respiratórios, especialmente o vírus sincicial respiratório. Mesmo na ausência de sintomas graves, a detecção de vírus sincicial respiratório pode prevenir a transmissão nosocomial através de medidas de controle de infecção. Um melhor entendimento da epidemiologia molecular do vírus sincicial respiratório é essencial para o desenvolvimento de novas vacinas e drogas antivirais contra o vírus sincicial respiratório.

Imported hepatopulmonary echinococcosis: first report of Echinococcus granulosus sensu stricto (G1) in Bolivia

Abstract Hepatopulmonary hydatidosis in young children is a rare and atypical presentation of Echinococcus granulosus infection. We report the first case of cystic echinococcosis caused by a microvariant of E. granulosus sensu stricto. Chemotherapy and systemic corticoids were administered before curative surgery was performed. Recurrence was not observed for more than 24 months of follow-up.

Parainfluenza virus as a cause of acute respiratory infection in hospitalized childrens

Background: Human parainfluenza viruses account for a significant proportion of lower respiratory tract infections in children.Objective: To assess the prevalence of Human parainfluenza viruses as a cause of acute respiratory infection and to compare clinical data for this infection against those of the human respiratory syncytial virus.Methods: A prospective study in children younger than five years with acute respiratory infection was conducted. Detection of respiratory viruses in nasopharyngeal aspirate samples was performed using the indirect immunofluorescence reaction. Length of hospital stay, age, clinical history and physical exam, clinical diagnoses, and evolution (admission to Intensive Care Unit or general ward, discharge or death) were assessed. Past personal (premature birth and cardiopathy) as well as family (smoking and atopy) medical factors were also assessed.Results: A total of 585 patients were included with a median age of 7.9 months and median hospital stay of six days. No difference between the HRSV+ and HPIV+ groups was found in terms of age, gender or length of hospital stay. The HRSV+ group had more fever and cough. Need for admission to the Intensive Care Unit was similar for both groups but more deaths were recorded in the HPIV+ group. The occurrence of parainfluenza peaked during the autumn in the first two years of the study.Conclusion: Parainfluenza was responsible for significant morbidity, proving to be the second-most prevalent viral agent in this population after respiratory syncytial virus. No difference in clinical presentation was found between the two groups, but mortality was higher in the HPIV+ group.

Association of X4 tropism with disease progression in antiretroviral-treated children and adolescents living with HIV/AIDS in São Paulo, Brazil

Management of children with HIV/AIDS is specially challenging. Age-related issues do not allow for direct transposition of adult observations to this population. CXCR4 tropism has been associated with disease progression in adults. The geno2pheno web-base is a friendly tool to predict viral tropism on envelope V3 sequences, generating a false positive rate for a CXCR4 prediction. We evaluated the association of HIV-1 tropism prediction with clinical and laboratory outcome of 73 children with HIV/AIDS in São Paulo, Brazil. The CXCR4 tropism was strongly associated with a lower (nadir) CD4 documented during follow-up (p < 0.0001) and with disease severity (clinical event and/or CD4 below 200 cells/mm3) at the last observation, using commonly applied clinical cutoffs, such as10%FPRclonal (p = 0.001). When variables obtained during follow-up are included, both treatment adherence and viral tropism show a significant association with disease severity. As for viremia suppression, 30% (22/73) were undetectable at the last observation, with only adherence strongly associated with suppression after adjustment. The study brings further support to the notion that antiretroviral treatment adherence is pivotal to management of HIV disease, but suggests that tropism prediction may provide an additional prognostic marker to monitor HIV disease in children.

Bacterial Colonization of Mechanical Ventilation Circuits in a Pediatric Intensive Care Unit.

To identify the onset time of bacterial proliferation in mechanical ventilator circuits in a pediatric intensive care unit (PICU) and the colonizing agents involved, as well to verify any possible pre-use contamination, we conducted a prospective microbiological analysis of the circuits of 30 patients, with a total of 342 cultures. Bacterial colonization of the mechanical ventilator circuits in the studied PICU was confirmed. Microorganisms were present in 39% of expiratory branch cultures: K. pneumoniae (77%), A. baumannii (65%), and S. aureus (42%). The inspiratory branch registered a smaller number of positive culture: A. baumannii (51%), S. aureus, coagulase-negative (38%) and K. pneumoniae (32%). As to the colonization onset time, 23% of the cultures collected on the 1st day from the inspiratory branch were positive, versus 30% of those collected from the expiratory branch, which lead us to conclude that bacteria can be present within the first hours of use. The sequential analysis of bacterial colonization over the course of circuit usage and the observation that the number of positive cultures becomes progressively higher on the 5th, 6th and 7th days in the expiratory branch both suggest that the systems should be replaced more often.

Análise crítica das recomendações do uso das vacinas meningocócicas conjugadas / A critical appraisal of the recommendations for the use of meningococcal conjugate vaccines

OBJETIVOS: Analisar a epidemiologia da doença meningocócica no Brasil e o impacto que as recentes evidências acumuladas com a incorporação das vacinas meningocócicas C conjugadas nos programas de imunização podem ter nas diferentes estratégias de uso dessas vacinas. FONTES DOS DADOS: Revisão nas bases de dados MEDLINE, SciELO e LILACS no período de 2000 a 2011. SÍNTESE DOS DADOS: No Brasil, a doença meningocócica é endêmica, com ocorrência periódica de surtos. Os maiores coeficientes de incidência ocorrem em lactentes, sendo o sorogrupo C responsável pela maioria dos casos, motivando a introdução da vacina meningocócica C conjugada no Programa Nacional de Imunizações, em 2010, para crianças menores de 2 anos. A introdução das vacinas meningocócicas C conjugadas nos programas de imunização na Europa, Canadá e Austrália mostrou-se efetiva, com dramática redução na incidência de doença causada pelo sorogrupo C, não apenas nos vacinados, mas também em não vacinados. A efetividade em longo prazo dessas vacinas mostrou-se dependente de uma combinação de persistência de anticorpos, memória imunológica e proteção indireta. Recentes evidências indicando que a persistência de anticorpos não é duradoura em crianças pequenas imunizadas e que a memória imunológica não é rápida o suficiente para protegê-las contra a doença enfatizam a importância da proteção indireta para manutenção da população protegida. CONCLUSÕES: A rápida queda de títulos de anticorpos em crianças vacinadas nos primeiros anos de vida sugere a necessidade de incorporarmos doses de reforço antes da adolescência, especialmente em locais como o Brasil, onde ainda não contamos com o efeito da proteção indireta da população.

OBJECTIVES: To assess the epidemiology of meningococcal disease (MD) in Brazil and the impact that recent evidence and lessons learned from the introduction of meningococcal C conjugate (MCC) vaccines into immunization programs may have on different strategies of vaccine use. SOURCES: Non-systematic review of the MEDLINE, SciELO and LILACS databases covering the period from 2000 to 2011. SUMMARY OF THE FINDINGS: Meningococcal disease is endemic in Brazil, with periodic occurrence of outbreaks. Most cases are associated with serogroup C and the highest incidence rates are observed in infants, encouraging the introduction of MCC vaccine in the National Immunization Program in 2010 for children under 2 years old. The introduction of MCC vaccines into immunization programs in Europe, Canada and Australia proved to be effective, with dramatic reduction in the incidence of serogroup C meningococcal disease, not only in the vaccinated, but also in the unvaccinated individuals. Long-term effectiveness of MCC vaccines was dependent on a combination of antibody persistence, immunologic memory and herd protection. Recent evidence indicating that antibody persistence is not long-lasting in young immunized children, and that immunologic memory is not fast enough to protect them against the disease, emphasize the importance of herd protection to maintain the population protected. CONCLUSIONS: The rapid decline of antibody titers in children vaccinated in the first years of life suggests the need to incorporate booster doses before adolescence, especially in locations like Brazil, where the immunization program did not incorporate catch-up campaigns including adolescents, lacking the herd immunity effect.

Evaluation of the incidence of occult bacteremia among children with fever of unknown origin

We reviewed the incidence of occult bacteremia, to identify the most frequent etiological agents of bacteremias in otherwise healthy children from one month to 10 years old, who had fever of unknown origin attended at the emergency ward of an urban, university-affiliated pediatric referral center. This was a retrospective medical record review, evaluating children with fever. Data were collected from the initial visit, when blood cultures, hematological properties and hemosedimentation rates were examined. Fever was considered as the highest temperature assessed in the hospital or reported by the responsible adult. Occult bacteremia was discovered in 1.4 percent of the 1,051 children evaluated, and the most common etiologic agent was Streptococcus pneumoniae. Total leukocyte count and blood sedimentation rates greater than 30 mm³ were not predictive factors for occult bacteremia. Fever greater than 39°C was the most important factor for predicting occult bacteremia (P<0.001). The presence of occult bacteremia was significantly correlated with patient hospitalization.

Empiemas pleurais pneumocócicos: distribuição dos sorotipos de Streptococcus pneumoniae e sensibilidade à penicilina / Pneumococcic pleural empyema: streptococcus pneumoniae serotypes and their sensitivity to penicillin

Estudo prospectivo de 50 crianças portadoras de empiema pleural pneumocócico adquirido na comunidade, hospitalizadas no Departamento de Pediatria da Santa Casa de São Paulo, no período de janeiro de 1998 a dezembro de 2000. Foram identificados os sorotipos dos Streptococcus pneumoniae e sua sensibilidade à penicilina. Observou-se que os empiemas pleurais pneumocócicos ocorreram em número significativo durante todo o ano, 50 por cento dos casos em crianças menores de 2 anos e predomínio do sexo masculino. O melhor local para o isolamento do Streptococcus pneumoniae foi o líquido pleural, sendo responsável por 86,0 por cento dos isolados. Os sorotipos de Streptococcus pneumoniae isolados foram em ordem decrescente de freqüência: 14 = 23 casos; 1 = 10 casos; 5 = 7 casos; 4 = 3 casos; 6B = 2 casos e os sorotipos 3, 8, 9V, 15A, e 23F com um caso cada. Os sorotipos 14, 1 e 5 foram responsáveis por 80,0 por cento dos isolados, dados estes que se assemelham a outros estudos realizados na cidade de São Paulo em pacientes com pneumonia. Resistência à penicilina foi identificada em oito cepas (16,0 por cento), sendo sete (14 por cento) moderadamente resistentes e uma (2 por cento) com resistência plena. Dos Streptococcus pneumoniae resistentes, 6/8 dos casos foram do sorotipo 14 e os sorotipos 1 e 6B com um caso cada.

Estudo da persistência de colonizaçäo em pacientes infectados por Salmonella / Persistence of colonization time in patients infected by Salmonella

A salmonela näo-typhi tem se constituído em importante causa de infecçäo nosocoial no Brasil, atingindo níveis endêmicos em alguns Estados na década de 70 e 80, alcançando principalmente lactentes jovens. Neste trabalho, estudamos prospectivamente 25 lactentes de idade variando de quatro a 180 dias de vida para verificar a duraçäo do período de portador da infecçäo e suas repercussöes clínicas. Após o diagnóstico, estas crianças foram acompanhadas mensalmente, com exames clínicos e com cultura de material obtido de pele, orofaringe, urina, fezes, aparelho geniturinário, narina e conduto auditivo. Dezoito (72%) dos pacientes persistiam colonizados com quatro semanas, dez (40%) persistiam com oito, sete (28%) com 12, quatro (16%) com 16, quatro (16%) com 20 e um (4%) com 24 semanas. Em 11 casos foi feito estudo seriado das amostras isoladas quanto ao biotipo e sensibilidade antimicrobiana. Em todos os casos, os biotipos das bactérias isoladas foram os mesmos durante todo o seguimento, caracterizando-a como da mesma cepa. Concluímos que existe uma persitência de excreçäo da salmonela pelo organismo que pode atingir até 24 semanas. Esta excreçäo pode se constituir em uma fonte de disseminaçäo, tanto através do pessoal de saúde, como no contato interpessoal, intra-hospitalar ou domiciliar. O uso de agentes antimicrobianos näo erradica a salmonela, apesar de melhorar o estado clínico dos pacientes durante a doença aguda

Desnutriçäo: imunidade e infecçäo / Malnutrition: immunity and infection

O trabalho trata das inter-relaçöes entre desnutriçäo, imunidade e infecçäo, estudando os mecanismos inespecíficos e específicos de defesa do organismo infantil contra as infecçöes, a imunidade de natrueza humoral e celular e, por outro lado, os efeitos da infecçäo sobre a nutriçäo e o metabolismo da criança

Experiência com hidrataçäo oral em crianças desnutridas no Pronto-Socorro Infantil da Santa Casa de Säo Paulo / Experience with oral hidration in malnourished children at the child Emergency Service of the Santa Casa of Säo Paulo

Setenta e cinco lactantes provenientes de famílias de baixa renda, com diagnóstico de diarréia e desidrataçäo, foram hidratados por via oral com a soluçäo glicoeletrolítica proposta pela OMS. Noventa e três por cento das crianças hidrataram-se somente com a soluçäo oral e näo necessitaram de hidrataçäo endovenosa nas primeiras 24 horas. Os vômitos näo se constituiram obstáculo para a hidrataçäo oral. No retorno, após 24 horas, seis (8%) das crianças necessitaram de hidrataçäo endovenosa. A hidrataçäo oral mostrou ser um método seguro para o tratamento da desidrataçäo mesmo em pacientes desnutridos

Leite humano - estudo das imunoglobulinas no colostro de maes de prematuros e de maes de criancas a termo. / Human milk - study of immunoglobulins in the colostrum of mothers of premature and full term infants

A composicao proteica e imunologica do colostro humano foi analisada em termos comparativos entre as maes de recem-nascidos prematuros e recem-nascidos a termo. Nenhuma diferenca estatisticamente significativa foi encontrada em termos de imunoglobulinas e proteinas