Enfermedad invasiva por Haemophilus influenzae: reporte de 14 casos luego de un año de iniciada la pandemia por COVID-19 / Invasive Haemophilus influenzae disease: A report of 14 cases one year after the COVID-19 pandemic outbreak

El Haemophilus influenzae (Hi) causa enfermedad invasiva (EI). Se distinguen cepas capsuladas, como el serotipo b (Hib), y cepas no tipificables (HNT). Al año de declarada la pandemia por COVID-19, observamos un aumento de casos. Se describen las características clínico-epidemiológicas de niños con EI por Hi internados en el hospital (julio 2021-julio 2022). Hubo 14 casos; 12 previamente sanos. Aislamientos: Hib (n = 6), Hi serotipo a (n = 2), HNT (n = 5), 1 no se tipificó. Mediana de edad: 8,5 meses (RIC 4-21). Manifestaciones: meningitis (n = 5), neumonía (n = 6), celulitis (n = 2), artritis (n = 1). Nueve presentaron vacunación incompleta para Hib. Observamos un incremento de EI por Hi de 2,5 veces respecto a años previos. Estos datos sugieren el resurgimiento de Hib por la caída de las coberturas de vacunación y porque otras cepas de Hi no b están en aumento.

Haemophilus influenzae (Hi) causes invasive disease. There are encapsulated strains, such as serotype b (Hib), and non-typeable strains (NTHi). One year after the outbreak of the COVID-19 pandemic, the number of cases increased. In this report we describe the clinical and epidemiological characteristics of children hospitalized with invasive Hi disease (July 2021-July 2022). There were 14 cases; 12 were previously healthy children. Isolations: Hib (n = 6), Hi serotype a (n = 2), NTHi (n = 5); 1 case was not typified. Median age: 8.5 months (IQR: 4­21). Manifestations: meningitis (n = 5), pneumonia (n = 6), cellulitis (n = 2), arthritis (n = 1). Incomplete Hib immunization was observed in 9 children. Invasive Hi disease increased 2.5 times from previous years. These data suggest the reemergence of Hib due to a decline in vaccination coverage and an increase in other non-b-type Hi serotypes.

Características clínicas de adultos mayores con neumonía adquirida en la comunidad / Clinical characteristics of older adults with community-acquired pneumonia

La neumonía adquirida en la comunidad es una enfermedad infecciosa común que causa una morbilidad y mortalidad sustanciales. Las personas mayores son las más frecuentemente afectadas, y se deben considerar varios aspectos relacionados con el cuidado de esta condición en los ancianos. El patógeno más común en esta patología sigue siendo Streptococcus pneumoniae, seguido de Haemophilus influenzae, Mycoplasma pneumoniae. El objetivo de este estudio fue determinar las características clínicas de adultos mayores con esta patología en el hospital "Alfredo Noboa Montenegro". Para las variables cualitativas fue empleada la frecuencia absoluta y el por ciento. Para la asociación entre variables cualitativas se utilizó la prueba Jicuadrado de independencia. En caso de las tablas de contingencia 2x2 cuando tuvo alguna celda con frecuencia esperada menor que 5 se utilizó el test exacto de Fisher. Más del 54% de los pacientes estudiados fue clasificado como grado II; de ellos el mayor porcentaje (66,7%) correspondió a los hombres. Le siguió en orden de frecuencia el grado III con 25% y alrededor del 83% fue del sexo femenino. No se obtuvo asociación estadística entre el sexo y el grado de los pacientes estudiados por lo que se pude afirmar que ambas variables fueron independientes. En la mayoría de casos los pacientes resultan infra diagnosticados desde los niveles primarios de atención al confundirlos con otro tipo de patologías, lo que provoca un retraso en la identificación y tratamiento del paciente que en el futuro influye en un pronóstico negativo de este(AU)

Community-acquired pneumonia is a common infectious disease that causes substantial morbidity and mortality. Elderly people are frequently affected, and several issues related to care of this condition in the elderly have to be considered. The most common pathogen in this pathology is still Streptococcus pneumoniae, followed by other pathogens such as Haemophilus influenzae, Mycoplasma pneumonia. The objective of this study was to determine the clinical characteristics of older adults with this disease in hospital "Alfredo Noboa Montenegro". For the qualitative variables the absolute frequency and the percent were used. For the association between qualitative variables, the Chi-square independence test was used. In the case of the 2x2 contingency tables, when Fisher had an expected cell shorter than 5, Fisher's exact test was used. More than 54% of the patients studied were classified as grade II; of them, the highest percentage (66.7%) corresponded to men. Next in order of frequency was grade III with 25% and about 83% was female. There was no statistical association between sex and the degree of the patients studied, so we could say that both variables were independent. In the majority of cases, patients are diagnosed from the primary care levels when they are confused with other types of pathologies, which causes a delay in the identification and treatment of the patient that in the future influences a negative prognosis(AU)

Sentinel surveillance for bacterial pneumonia and meningitis in children under the age of 5 in a tertiary pediatric hospital in Colombia - 2016 / Vigilancia centinela de neumonías y meningitis bacterianas en menores de 5 años en un hospital pediátrico de tercer nivel en Colombia - 2016

Abstract | Introduction: Bacterial pneumonia and meningitis are vaccine-preventable diseases. Sentinel surveillance provides relevant information about their behavior. Objective: To present the data from sentinel surveillance carried out at the Fundación HOMI, Fundación Hospital Pediátrico La Misericordia in 2016. Materials and methods: We conducted a descriptive study from January 1 to December 31, 2016, on the daily surveillance of patients under 5 years of age diagnosed with pneumonia or bacterial meningitis according to PAHO's definitions. We identified the microorganisms using the automated VITEKTM 2 system. Bacterial isolates were sent to the Microbiology Group at the Colombian Instituto Nacional de Salud for confirmation, serotyping, phenotypic, and genotypic characterization. Antimicrobial susceptibility profiles were established. Results: From 1,343 suspected cases of bacterial pneumonia, 654 (48.7%) were probable, 84% had complete Hib vaccination schedules, and 87% had complete pneumococcal vaccination schedules for age. Blood culture was taken in 619 (94.6%) and 41 (6.6%) were positive while S. pneumoniae was isolated in 17 (41%) of them. The most frequent serotype was 19A in five cases (29.4%), and four 19A serotypes were associated with the reference isolate ST320. The incidence rate of probable bacterial pneumonia was 7.3 cases/100 hospitalized patients, and lethality was 2.1%. As for bacterial meningitis, 22 suspected cases were reported, 12 (54%) were probable, four (33%) were confirmed: two by Escherichia coli and two by group C N. meningitidis. The incidence of probable bacterial meningitis was 0.14 cases/100 hospitalized patients. Conclusion: Streptococcus pneumoniae serotypes 19A and 3 were the most frequent cause of pneumonia. Spn19A is related to the multi-resistant clone ST320. Strengthening and continuing this strategy will allow understanding the impact of vaccination.

Resumen | Introducción. La neumonía y la meningitis bacterianas son enfermedades inmunoprevenibles; la vigilancia centinela aporta información relevante acerca de su comportamiento. Objetivo. Presentar los resultados de la vigilancia centinela de neumonía y meningitis llevada a cabo en la HOMI, Fundación Hospital Pediátrico La Misericordia. Materiales y métodos. Se hizo un estudio descriptivo entre el 1 de enero y el 31 diciembre del 2016, de la vigilancia diaria de pacientes menores de 5 años con diagnóstico de neumonía o meningitis bacteriana, según las definiciones de la Organización Panamericana de la Salud (OPS). Los microorganismos fueron identificados usando el sistema automatizado VITEK TM2. Los aislamientos se enviaron al grupo de microbiología del Instituto Nacional de Salud para confirmación, serotipificación, y caracterización genotípica y fenotípica. Asimismo, se establecieron los perfiles de sensibilidad antimicrobiana. Resultados. De 1.343 casos sospechosos de neumonía bacteriana, 654 (48,7 %) fueron probables, el 84 % tenía el esquema de vacunación completo para la edad contra Haemophilus influenzae de tipo b, y el 87 %, contra neumococo. En 619 (94,6 %) pacientes se hizo hemocultivo y 41 (6,6 %) fueron positivos. S. pneumoniae se aisló en 17 (41 %) casos. El serotipo más frecuente fue el 19A, en cinco pacientes (29,4 %), en tanto que cuatro aislamientos de spn19A fueron relacionados con el clon ST320. La tasa de incidencia de neumonía bacteriana probable fue de 7,3 casos/100 pacientes hospitalizados. La letalidad fue de 2,1 %. Hubo 22 casos sospechosos de meningitis bacteriana, 12 (54 %) probables, y cuatro (33 %) confirmados: dos por Escherichia coli y dos por Neisseria meningitidis del grupo C. La incidencia de meningitis bacteriana probable fue de 0,14/100 pacientes hospitalizados. Conclusión. Los serotipos 19A y 3 de S. pneumoniae fueron la causa más frecuente de neumonía. El Spn19A se relacionó con el clon ST320 mulitirresistente. El fortalecimiento continuo de la vigilancia centinela permitirá entender el impacto de la vacunación.

Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data

Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. Methods In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 434 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27­0·37]) and 82% at 8 weeks (0·18 [0·14­0·23]) following the week in which significant changes in population movements were recorded. Interpretation The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide. Funding Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).

Endoftalmitis endógena como primera manifestación de meningitis por Haemophilus influenza: reporte de un caso / Endogenous endophthalmitis as the initial presentation of Haemophilus influenzae meningitis

La endoftalmitis endógena es responsable del 2-15 % de las endoftalmitis, se relaciona con una infección sistémica hasta en un 52-90% de los casos, en el contexto de infecciones sistémicas como abscesos hepáticos, neumonia, infecciones de vias urinarias, meningitis, usurios de drogas endovenosas y fungémias. Haemophilus influenzae es un agente etiológico inusual de esta patología, hay pocos casos reportados a nivel mundial y no se han reportado casos en nuestro país; las endoftalmitis por Haemophilus se caractererizan por tener un pronóstico visual sombrio, ya que pueden presentar complicaciones severas y comprometer permanentemente la visión. A continuación, se describe un caso de endoftalmitis endogéna como primera manifestación de meningitis asociada a H. Influenzae en una paciente inmunocompetente y sin factores de riesgo.

Endogenous endophthalmitis is responsible for 2-15% of endophthalmitis, it is associated with a systemic infection in up to 52-90% of cases, in the context of systemic infections such as liver abscesses, pneumonia, urinary tract infections, meningitis, intravenousdrug users and fungaemia. Haemophilus influenzae is an unusual etiologic agent of this pathology, there are few cases reported worldwide and no cases have been reported in our country. The endophthalmitis due to Haemophilus are characterized by having a somber visual prognosis, since they can present severe complications and can permanently affect vision. Mentioned hereinafter, a case of endogenous endophthalmitis is described as the first manifestation of meningitis associated with H.Influenzae in an immunocompetent patient with no risk factors.

Bacterial meningitis in patients with sickle cell anemia in Salvador, Bahia, Brazil: a report on ten cases

ABSTRACT Sickle cell anemia (SCA) is a common genetic blood disorder, affecting millions worldwide. According to current evidence, individuals with SCA have more than 300 times greater risk to develop bacterial meningitis (BM) than the general population. Herein we have described the characteristics of a series of BM cases in SCA patients in Salvador, Brazil, during 13 years of hospital-based surveillance. Data on clinical presentation, laboratory parameters and outcomes were collected retrospectively by reviewing medical records. From 1999 to 2011, ten SCA patients were identified among the 2511 cases of BM (10/2511; 0.40%). These patients were more likely to be male (90%) and to be younger (median age 8.5 years). The causative agents were Streptococcus pneumoniae (n = 5) and Haemophilus influenzae (n = 1). The most frequent pneumococcal serotypes were 23 F (2 cases), 14, 18 F, 23B (one case each). Common medical complications were stroke (n = 3); heart failure (n = 2), respiratory problems (n = 2), renal dysfunctions (n = 2) and leg ulcers (n = 1). This study highlights the importance of S. pneumoniae as a causative agent of meningitis in individuals with SCA and shows the diversity of comorbidities associated with this condition.

Impacto do uso da reação em cadeia da polimerase para o diagnóstico de meningite bacteriana em substituição a contraimunoeletroforese / Impact of using polymerase chain reaction for the diagnosis of bacterial meningitis in substitution for counterimmunoelectrophoresis

Introdução: a meningite bacteriana é um grave problema de Saúde Pública mundial, tendo como principais agentes: Neisseria meningitidis, Streptococcus pneumoniae e Haemophilus influenzae. A metodologia de diagnóstico empregada no Instituto Adolfo Lutz ­ Centro de Laboratório Regional Santo André até o ano de 2011 era a contraimunoeletroforese (CIE), depois foi substituída pela reação em cadeia da polimerase em tempo real (qPCR), que apresenta maior sensibilidade. Objetivo: este trabalho objetivou comparar ambas as metodologias no período de 2009 a 2018, para avaliação do impacto da introdução da qPCR no diagnóstico das meningites bacterianas nos 7 municípios da região do ABC do Estado de São Paulo. Metodologia: foram avaliadas a quantidade total de exames realizados, a média mensal, a positividade no período, os municípios requisitantes e a prevalência das bactérias causadoras de meningite, no período de abril/2009 até dezembro/2018. Resultados: Foram 377 exames de CIE e 1305 de qPCR, com média anual de 230 exames em 2010-2013 e 130 exames em 2014-2018. Observou-se aumento da positividade entre as técnicas, 17,8% para CIE e 33,8% para qPCR. N. meningitidis foi responsável pela maioria dos casos entre 2011 e 2013, cerca de 61% dos casos positivos, enquanto que entre 2014 e 2018 foi S. pneumoniae, cerca de 53%. Conclusão: os resultados indicaram que a qPCR foi mais eficiente em detectar os agentes causadores de meningite bacteriana na região do que a técnica de CIE. Por fim, este trabalho suporta a implantação da metodologia de qPCR para diagnóstico de meningite em substituição de técnicas menos sensíveis.

Introduction: bacterial meningitis is still a serious worldwide public health problem, and the main etiological agents are: Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. The diagnostic methodology employed at the Adolfo Lutz Institute ­ Santo André Regional Laboratory Center until 2011 was the ounterimmunoelectrophoresis (CIE), then it was replaced by the real-time polymerase chain reaction (qPCR), which is more sensitivity. Objective: this study aimed to compare both methodologies from 2009 to 2018 to evaluate the impact of the introduction of qPCR in the diagnosis of bacterial meningitis in the 7 cities of the ABC region of São Paulo State. Methodology: the total number of tests performed, the month average, the positivity in the period, the requesting cities and the prevalence of bacteria causing meningitis were evaluated from April/2009 to December/2018. Results: there were 377 CIE exams and 1305 qPCR exams, with an annual average of 230 exams in 2010-2013 and 130 exams in 2014-2018. There was an increase in positivity between the performed techniques, 17.8% for CIE and 33.8% for qPCR. N. meningitidis accounted for most cases of bacterial meningitis between 2011 and 2013, about 61% of positive cases, whereas between 2014 and 2018 it was S. pneumoniae, with about 53%. Conclusion: the results indicated that qPCR was more efficient in detecting the agents that cause bacterial meningitis in the region than the CIE technique. Finally, this work supports the implementation of qPCR methodology for diagnosis of meningitis in replacement of less sensitive techniques.

Deficiência de anticorpos específicos antipolissacarídeos / Specific polysaccharide antibody deficiency

A deficiência de anticorpos específicos antipolissacarídeos é um dos erros inatos da imunidade predominantemente de anticorpos, destacando-se entre os defeitos mais frequentes. É caracterizada por uma permanência de imaturidade da resposta imunológica a antígenos polissacarídeos, estando normais linfócitos B, classes e subclasses de imunoglobulinas. O paciente apresenta maior suscetibilidade a infecções por bactérias encapsuladas, especialmente Streptococcus pneumoniae e Haemophilus influenzae. As principais manifestações clínicas são otites, sinusites, traqueobronquites e pneumonias de repetição; pode haver meningite pneumocócica e septicemia. A investigação é feita por titulação de anticorpos antipolissacarídeos antes e após a aplicação da vacina pneumocócica não conjugada. Até dois anos, há imaturidade fisiológica desse setor da imunidade, por isso, o diagnóstico não pode ser feito antes desta idade. O tratamento, além de antibiótico precoce em vigência de quadros infecciosos, inclui antibióticos profiláticos, aplicação de vacina conjugada com proteínas e/ou reposição de imunoglobulina humana endovenosa ou subcutânea. O diagnóstico e o tratamento precoce melhoram a qualidade de vida do paciente, diminuindo o risco de sequelas e até de óbito por infecção, e quando não são precoces, é possível que haja sequelas como bronquiectasias, hipoacusia ou danos neurológicos.

Specific polysaccharide antibody deficiency is an inborn error of immunity predominantly affecting antibodies, being one of the most frequent primary immunodeficiencies of childhood. It is characterized by persistent immaturity of the immune response to polysaccharide antigens, with normal levels of B lymphocytes, immunoglobulin classes and subclasses. Patients are more susceptible to infections by encapsulated bacteria, especially Streptococcus pneumoniae and Haemophilus influenzae. The main clinical manifestations are recurrent otitis, sinusitis, tracheobronchitis and pneumonia; there may be pneumococcal meningitis and septicemia. The investigation is done by dosages of polysaccharide antibodies before and after unconjugated pneumococcal vaccination. As this area of immunity is physiologically immature until two years of age, diagnosis cannot be made earlier. Treatment, in addition to antibiotics as soon as infections are detected, includes prophylactic antibiotic therapy, use of pneumococcal vaccine conjugated to protein and/or replacement of intravenous or subcutaneous human immunoglobulin. Early diagnosis and treatment improve patients' quality of life, reducing the risk of sequelae and even death from infection, while lack of early measures can lead to sequelae such as bronchiectasis, hearing loss and neurological damage.

Invasive non-type b haemophilus influenzae disease: report of eight cases / Doença invasiva causada por haemophilus influenzae não tipo b: relato de oito casos

ASTRACT Objective: To describe eight cases of invasive non-type b Haemophilus influenzae disease in children admitted to Hospital de Clínicas of Universidade Estadual de Campinas. Cases description: In 2015, there were eight cases of invasive non-type b H. influenzae disease. We tested the ampicillin sensitivity and beta-lactamase production of the strains identified and performed the genotyping. Molecular typing was determined by Pulsed-Field Gel Electrophoresis. Four patients were diagnosed with bacteremia; in two cases, H. influenzae was detected in the pleural fluid, and two patients had meningitis. Patients with comorbidities represented 37.5% of cases. Except for the strain of one patient - not sent to the reference laboratory -, all were ampicillin-sensitive and non-beta-lactamase-producing. Genotyping identified four non-capsular, one type c, and two type a strains. Molecular typing ruled out nosocomial transmission since all serotypes were distinct regarding genotype. Comments: The rise in cases of invasive non-type b H. influenzae infection was real. There was no nosocomial transmission, and we found no justification for the increase. These data indicate the need for surveillance to correctly diagnose, monitor, and understand the spectrum of non-type b H. influenzae disease.

ABSTRACT Objetivo: Descrever oito casos de doença invasiva por Haemophilus influenzae não tipo b em crianças internadas no Hospital de Clínicas da Universidade Estadual de Campinas. Descrição dos casos: Em 2015, ocorreram oito casos de doença invasiva por H. influenzae não tipo b. Nas cepas identificadas, testou-se a sensibilidade à ampicilina e a produção de betalactamase, e realizou-se a genotipagem. A tipagem molecular foi feita por Pulsed Field Gel Electrophoresis. Em quatro pacientes, o diagnóstico foi de bacteremia; em dois casos, H. influenzae foi identificado em líquido pleural, e dois pacientes tiveram meningite. Comorbidades foram encontradas em 37,5% dos pacientes. Com exceção da cepa de um dos pacientes (que não foi enviada ao laboratório de referência), todas eram sensíveis à ampicilina e não produtoras de betalactamase. A genotipagem identificou quatro cepas não capsulares, uma cepa tipo c e duas cepas tipo a. A tipagem molecular descartou a transmissão intra-hospitalar, já que todos os sorotipos eram distintos quanto ao genótipo. Comentários: O aumento dos casos de infecção invasiva por H. influenzae não tipo b foi real. Não houve transmissão intra-hospitalar e não foi encontrada justificativa para o aumento. Esses dados indicam a necessidade de vigilância para diagnosticar corretamente, monitorar e entender o espectro da doença causada por H. influenzae não tipo b.

Bacterial and Viral Identification Rate in Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Korea

PURPOSE: The most common cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is respiratory infection. Most studies of bacterial or viral cause in AECOPD have been conducted in Western countries. We investigated bacterial and viral identification rates in AECOPD in Korea. MATERIALS AND METHODS: We reviewed and analyzed medical records of 736 cases of AECOPD at the Korea University Guro Hospital. We analyzed bacterial and viral identification rates and classified infections according to epidemiological factors, such as Global Initiative for Chronic Obstructive Lung Disease stage, mortality, and seasonal variation. RESULTS: The numbers of AECOPD events involving only bacterial identification, only viral identification, bacterial-viral co-identification, and no identification were 200 (27.2%), 159 (21.6%), 107 (14.5%), and 270 (36.7%), respectively. The most common infectious bacteria identified were Pseudomonas aeruginosa (13.0%), Streptococcus pneumoniae (11.4%), and Haemophilus influenzae (5.3%); the most common viruses identified were influenza virus (12.4%), rhinovirus (9.4%), parainfluenza virus (5.2%), and metapneumovirus (4.9%). The bacterial identification rate tended to be higher at more advanced stages of chronic obstructive pulmonary disease (p=0.020 overall, p=0.011 for P. aeruginosa, p=0.048 for S. pneumoniae). Staphylococcus aureus and Klebsiella pneumoniae were identified more in mortality group (p=0.003 for S. aureus, p=0.009 for K. pneumoniae). All viruses were seasonal (i.e., greater prevalence in a particular season; p < 0.050). Influenza virus and rhinovirus were mainly identified in the winter, parainfluenza virus in the summer, and metapneumovirus in the spring. CONCLUSION: This information on the epidemiology of respiratory infections in AECOPD will improve the management of AECOPD using antibiotics and other treatments in Korea.

Colloidal gold immunochromatographic strip for rapid detection of Haemophilus influenzae / 生物工程学报

To establish a novel colloidal gold immunochromatography assay (GICA) for rapid, sensitive and accurate detection of Haemophilus influenzae infection by using the outer membrane protein P6 as detection target. First, the linear antigen epitope located in the extracellular domain of the P6 protein (GenBank accession number: AGH02799) was predicted by bioinformatics analysis. The region (62-75 aa of the protein) with strong antigen specificity was chosen and synthesized. Two rabbits were then immunized by the polypeptides (14 aa) for production of polyclonal antibodies. Then, the recombinant P6 proteins were also obtained to produce polyclonal antibodies. Finally, based on the two antibodies, a novel colloidal GICA for detection of Haemophilus influenzae infection was established and the specificity, sensitivity, repeatability and stability of this method were evaluated. At the same time, the method was tested in clinical simulation, and the plate culture method was used to verify its accuracy. The test strip for Haemophilus influenzae infection was successfully prepared. The detection limit of the test strip was as low as 1×105 CFU/mL and the whole process can be completed within 15 minutes. The strip specifically recognized Haemophilus influenzae and did not react with nine of other common respiratory pathogens such as Streptococcus pneumoniae, Moraxella catarrhalis, Mycoplasma pneumonia, and Legionella pneumophila. And the strips could be stored at 25 °C for at least 6 months without losing sensitivity or specificity. The coincidence rate between the results of 200 clinical samples and the plate culture method was 90.5%. Haemophilus influenzae protein P6, which possessed a high degree of surface antigen accessibility and antigencity, could be used as a marker for Haemophilus influenzae detection. The immunochromatographic colloidal gold test strip which bears the features of rapidity, convenience and sensitivity provides a unique tool for the on-site surveillance and diagnosis of Haemophilus influenzae infection in clinical test.

Pathogens in bronchoalveolar lavage fluid of children with lower respiratory tract infection / 中国当代儿科杂志

OBJECTIVE@#To study the features of pathogens in children with lower respiratory tract infection.@*METHODS@#A total of 108 children who were hospitalized due to lower respiratory tract infection and underwent fiber bronchoscopy between January 2017 and June 2018 were enrolled. Bronchoalveolar lavage fluid samples were collected. Multiple quantitative real-time PCR was performed to detect pathogens.@*RESULTS@#Of the108 children, 85 (78.7%) were found to have pathogens, among whom 52 (48.1%) had single pathogen infection and 33 (30.6%) had multiple pathogen infections. Mycoplasma pneumoniae was detected in 38 children (35.2%), and was the most common pathogen. The children aged 36 - <72 months had the highest detection rate of Mycoplasma pneumoniae. Both Streptococcus pneumoniae and Haemophilus influenzae were detected in 29 children (26.9%) and Streptococcus pneumoniae was mainly detected in children aged <24 months. Each of Acinetobacter baumannii, Candida albicans and Klebsiella pneumoniae was detected in 3 children. Among the 31 children with bronchopneumonia, 9 were found to have Haemophilus influenza, with the highest detection rate of 29%. Among the 34 children with lobar pneumonia, 22 were found to have Mycoplasma pneumoniae, with the highest detection rate of 65%. Among the 22 children with bronchial foreign bodies and bronchopneumonia, 10 were found to have Streptococcus pneumoniae, with the highest detection rate of 45%.@*CONCLUSIONS@#In children with lower respiratory tract infection, Mycoplasma pneumoniae is the most common pathogen, followed by Streptococcus pneumoniae and Haemophilus influenzae. There are differences in the detection rates of pathogens between children with different ages and different types of lower respiratory tract infection.

Cerebral Venous Sinus Thrombosis with Meningitis and Septicemia due to Haemophilus influenzae Type f in an Immunocompetent Child

Since the implementation of conjugate Haemophilus influenzae serotype b (Hib) vaccine, the rate of infections caused by Hib has dramatically decreased, and the proportion of infections caused by non-type b H. influenzae has increased. Cerebral venous sinus thrombosis (CVST) is rare; however, it should be considered as a potential complication of bacterial meningitis. Herein, we report about a child who developed CVST after being diagnosed with H. influenzae serotype f meningitis.

Bacteriologic profile and drug resistance in children with respiratory infection from 2016 to 2018 / 中国当代儿科杂志

OBJECTIVE@#To study the bacteriologic profile and drug resistance of respiratory infection in children, and to provide a basis for etiological diagnosis and rational use of antimicrobial agents.@*METHODS@#A retrospective analysis was performed for 15 047 children who attended the hospital due to respiratory infection from January 2016 to December 2018. Their sputum samples were collected, and the Phoenix-100 automatic microbial identification system was used for the identification and drug sensitivity analysis of the isolated pathogenic bacteria.@*RESULTS@#Of all 17 174 sputum samples detected, there were 2 395 positive samples, with a positive rate of 13.95%; a total of 2 584 strains of pathogenic bacteria were isolated, among which there were 1 577 (61.03%) Gram-negative strains, 967 (37.42%) Gram-positive strains, and 40 (1.55%) fungal strains. The most common pathogen was Haemophilus influenzae (33.90%), followed by Streptococcus pneumoniae (33.55%), Moraxella catarrhalis (19.20%), and Staphylococcus aureus (3.64%). Among the 2 331 children with positive infection, 251 had mixed infection, most commonly with Haemophilus influenzae and Streptococcus pneumoniae. The detection rate of pathogenic bacteria was higher in winter and spring and lower in summer and autumn. There was a significant difference in the detection rate of pathogenic bacteria between different age groups (P<0.05), with the highest detection rate in infants aged 1 month to <1 year. Streptococcus pneumoniae and Staphylococcus aureus had a sensitivity rate of 100% to vancomycin, linezolid, and teicoplanin, and Haemophilus influenzae had a lower sensitivity rate to ampicillin, compound sulfamethoxazole and cefuroxime and a higher sensitivity rate to other drugs.@*CONCLUSIONS@#Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis are the main pathogenic bacteria of respiratory infection in children, and mixed infection is the most common type of infection. The detection rate of pathogenic bacteria varies across seasons and ages. Different pathogenic bacteria have different features of drug resistance, and antibiotics should be selected based on drug sensitivity results.

Haemophilus influenzae no tipificable: mecanismo de destrucción del biofilm / Non-typeable Haemophilus influenzae: mechanism of biofilm destruction

INTRODUCCIÓN: Haemophilus influenzae tiene como hábitat el aparato respiratorio humano. No existe vacuna contra la variante no tipificable (NTHi) de este, por lo que se ha mostrado una tendencia al incremento de casos en los últimos años. La patogenicidad de NTHi se debe a su habilidad para formar biofilms, por lo que se pretende analizar mecanismos de destrucción del biofilm formado por NTHi. METODOLOGÍA: Se realizó una revisión bibliográfica mediante consultas en las bases de datos, Hinari, MEDLINE y el motor de búsqueda PubMed. Se tomaron en consideración artículos originales, ensayos clínicos y artículos de revisión bibliográfica dando prioridad a aquellos publicados en los últimos 5 años. DESARROLLO: NTHi tiene la capacidad de formar biofilms por medio de proteínas del pili y elementos estabilizadores del ADN extracelular, entre los más importantes están: DNA BII, pili tipo IV, Nucleasa extracelular 2019 y adhesinas de alto peso molecular. El uso de chalconas, EDTA y ADN como quelante de cationes, antisueros contra DNBII y maquinaria luxS más anticuerpos contra Pili IV han demostrado que pueden ser útiles para la erradicación del biofilm. CONCLUSIÓN: Se proponen dos tratamientos novedosos que podrían contribuir en la eliminación del biofilm formado por NTHi, uno es el uso de EDTA y otro los anticuerpos dirigidos a proteínas esenciales en la formación y adhesión del biofilm. Es necesario profundizar en otros estudios con estas propuestas terapéuticas para determinar su uso en el área clínica en un futuro.

INTRODUCTION: Haemophilus influenzae has the human respiratory system as habitat. There's no vaccine against the non-typeable group (NTHi), as a consequence there has been an increase in the number of cases in the past few years. The pathogenesis of NTHi is caused by its ability to form biofilms, for this reason we pretend to analyze the destruction mechanisms of biofilms formed by NTHi. METHODOLOGY: A review was made using the databases Hinari, MEDLINE and PubMed. Original articles, clinical trials and reviews that had been published in the last five years were taken in count. RESULTS: NTHi has the capacity to form biofilms through pilus proteins and extracellular DNA stabilizers; among the most important we have: DNA BII, type IV pilus, 2019 extracellular nuclease and adhesins of high molecular weight. The use of chalcone, EDTA, DNA as cation chelant, antiserum against DNA BII and luxS plus antibodies against Pili IV has shown potential to eradicate biofilms. DISCUSSION: Two new treatments, that could contribute to the removal of biofilms formed by NTHi, are proposed: one of them is the use of EDTA and the other one is the use of antibodies against essential proteins that the bacteria uses in the formation and adhesion of biofilms. Never the less, it is necessary to deepen more in studies about these therapeutic alternatives to determine their use in the clinical area in the future.

Infection by Streptococcus pneumoniae in children with or without radiologically confirmed pneumonia / Infecção por Streptococcus pneumoniae em crianças com ou sem pneumonia radiologicamente confirmada

Abstract Objective: Community-acquired pneumonia is an important cause of morbidity in childhood, but the detection of its causative agent remains a diagnostic challenge. The authors aimed to evaluate the role of the chest radiograph to identify cases of community-aquired pneumonia caused by typical bacteria. Methods: The frequency of infection by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis was compared in non-hospitalized children with clinical diagnosis of community acquired pneumonia aged 2-59 months with or without radiological confirmation (n = 249 and 366, respectively). Infection by S. pneumoniae was diagnosed by the detection of a serological response against at least one of eight pneumococcal proteins (defined as an increase ≥2-fold in the IgG levels against Ply, CbpA, PspA1 and PspA2, PhtD, StkP-C, and PcsB-N, or an increase ≥1.5-fold against PcpA). Infection by H. influenzae and M. catarrhalis was defined as an increase ≥2-fold on the levels of microbe-specific IgG. Results: Children with radiologically confirmed pneumonia had higher rates of infection by S. pneumoniae. The presence of pneumococcal infection increased the odds of having radiologically confirmed pneumonia by 2.8 times (95% CI: 1.8-4.3). The negative predictive value of the normal chest radiograph for infection by S. pneumoniae was 86.3% (95% CI: 82.4-89.7%). There was no difference on the rates of infection by H. influenzae and M. catarrhalis between children with community-acquired pneumonia with and without radiological confirmation. Conclusions: Among children with clinical diagnosis of community-acquired pneumonia submitted to chest radiograph, those with radiologically confirmed pneumonia present a higher rate of infection by S. pneumoniae when compared with those with a normal chest radiograph.

Resumo Objetivo: Avaliar o papel do raios X de tórax na identificação de casos de pneumonia adquirida na comunidade (PAC) causada por agentes bacterianos. Métodos: A frequência de infecção por Streptococcus pneumoniae, Haemophilus influenzae e Moraxella catarrhalis em crianças com PAC não hospitalizadas foi comparada com a presença de confirmação radiológica da pneumonia (n = 249 crianças com pneumonia radiologicamente confirmada e 366 crianças com raios X de tórax normal). Infecção por S. pneumoniae foi diagnosticada com base na resposta sorológica a pelo menos uma dentre oito proteínas pneumocócicas investigadas (aumento ≥ 2 vezes nos níveis de IgG em relação a Ply, CbpA, PspA1 e 2, PhtD, StkP-C e PcsB-N ou aumento≥ 1,5 vez em relação aPcpA). Infecção por H. influenzae e M. catarrhalis foi definida por aumento ≥ 2 vezes nos níveis de IgG específica a antígenos de cada agente. Resultados: Crianças com pneumonia radiologicamente confirmada apresentaram maior taxa de infecção pelo pneumococo. Além disso, a presença de infecção pneumocócica foi um fator preditor de pneumonia radiologicamente confirmada, o que aumenta sua chance de detecção em 2,8 vezes (IC 95%: 1,8-4,3). O valor preditivo negativo do raios X normal para a infecção por S. pneumoniae foi 86,3% (IC95%: 82,4%-89,7%). Não houve diferença nas frequências de infecção por H. influenzae e M. catarrhalis entre crianças com PAC com ou sem confirmação radiológica. Conclusão: Crianças com diagnóstico clínico de PAC submetidas a um raios X de tórax que apresentam confirmação radiológica têm maior taxa de infecção por S. pneumoniae comparadas com as crianças com raios X normal.

Recurrent Guillain-Barré Syndrome Following Urinary Tract Infection by Escherichia coli

Recurrent Guillain-Barré syndrome (GBS) is a rare, immune-mediated disease of the peripheral nervous system. It has been reported to occur at intervals ranging from four months to 10 years; published case studies suggest that 1%–6% of patients who have had GBS will experience recurrent attacks. The most commonly identified infections coinciding with GBS are Campylobacter jejuni, Haemophilus influenzae, Mycoplasma pneumonia, and cytomegalovirus, while an antecedent infection with Escherichia coli is very uncommon. In this case report, we present a rare episode of recurrent GBS, which followed a urinary tract infection (UTI) by E. coli, and an accompanying literature review. A 75-year-old woman with a prior history of acute motor axonal neuropathy (AMAN), a subtype of GBS, presented with subsequent weakness of limbs and areflexia following 10 days of fever, frequency, and dysuria. Base on nerve conduction studies, cerebrospinal fluid analysis and other clinical investigation, we diagnosed the patient with recurrent GBS caused by E. coli. The patient recovered with mild subjective weakness following treatment of intravenous immunoglobulin with ceftriaxone. We suggest that E. coli causes UTI could be one of the diverse trigger factors involved in recurrent GBS.

Influence of Vitamin D Deficiency on Progression of Experimental Otitis Media in Rats

BACKGROUND: Vitamin D plays an important role in the immune response against infection. The purpose of the present study was to investigate the influence of vitamin D deficiency on the progression of otitis media (OM) using an experimental rat model. METHODS: Four-week-old male Sprague-Dawley rats (n=72) were divided into two groups based on their diet: a control diet group (n=36) and a vitamin D-deficient diet group (n=36). After 8 weeks of diet, experimental OM was induced by inoculation of non-typeable Haemophilus influenzae in the middle ear cavity. The rats were evaluated with otomicroscopy to determine the inflammation in the middle ear mucosa on days 1, 2, 4, 7, and 14 post-inoculation. Bullae from sacrificed rats were collected and analyzed histologically. RESULTS: The middle ear mucosa from rats with vitamin D deficiency showed a significantly higher thickness than that of controls during the course of OM. The maximum mucosal thickness was 56.0±9.1 µm in the vitamin D deficiency group, and 43.9±9.8 µm in the control group, although there was no significant difference in the tympanic membrane score between the two groups evaluated with otomicroscopy. An immunohistochemical study showed increased expression of interleukin 6 (IL-6) and tumor necrosis factor α in rats manifesting vitamin D deficiency and decreased expression of IL-10 compared with controls. CONCLUSION: Our results showed that vitamin D deficiency may exacerbate the pathophysiological changes of OM via altered cytokine production. Therefore, maintaining vitamin D status in the optimal range may be beneficial for proper management of OM.

Microbiological Results From Middle Ear Effusion in Pediatric Patients Receiving Ventilation Tube Insertion: Multicenter Registry Study on the Effectiveness of Ventilation Tube Insertion in Pediatric Patients With Chronic Otitis Media With Effusion: Part

OBJECTIVES: The aim of this multicenter registry study was to investigate the effectiveness of ventilation tube insertion and the microbiology of otitis media with effusion (OME) in children. This part I study was conducted to evaluate the microbiological profile of children with OME who needed ventilation tube insertion. METHODS: Patients < 15 years old who were diagnosed as having OME and received ventilation tube insertion were prospectively enrolled in 16 tertiary hospitals from June 2014 to December 2016. After excluding patients with missing data, the data of 397 patients were analyzed among a total of 433 enrolled patients. The clinical symptoms, findings of the tympanic membrane, hearing level, and microbiological findings were collected. RESULTS: In 103 patients (25.9%), antibiotics were used within 3 weeks before surgery. Ventilation tube insertion was performed in a total of 710 ears (626 in both ears in 313 patients, 55 in the left ear only, and 29 in the right ear only). Culture of middle ear effusion was done in at least one ear in 221 patients (55.7%), and in a total of 346 ears. Only 46 ears (13.3%) showed positive results in middle ear effusion culture. Haemophilus influenzae (17.3%, followed by coagulase-negative Staphylococcus and Staphylococcus auricularis) was the most common bacteria detected. CONCLUSION: H. influenzae was the most commonly found bacteria in middle ear effusion. Relatively low rates of culture positivity were noted in middle ear effusion of patients with OME in Korea.