Estado de vacunación en pacientes con riesgo de enfermedades invasoras por bacterias capsuladas en un hospital pediátrico de Buenos Aires / Vaccination status in patients at risk for invasive disease with encapsulated bacteria at a children's hospital in the City of Buenos Aires

Introducción. El Ministerio de Salud contempla vacunas específicas para personas con riesgo elevado de infecciones invasoras por bacterias capsuladas (BC). En la actualidad se desconoce el cumplimiento del programa. El objetivo fue evaluar el estado de vacunación para BC en ≤ 18 años con factores de riesgo. Población y métodos. Estudio observacional, analítico, mediante encuesta a padres de ≤ 18 años con VIH, asplenia y/o déficit de complemento que concurrieron al vacunatorio de un hospital pediátrico de octubre de 2020 a septiembre de 2021. Se recabaron datos sociodemográficos y clínicos. Se evaluó el estado de vacunación para BC: neumococo, meningococo y Haemophilus influenzae b (Hib), calendario regular y antigripal. Se administró la escala de reticencia a la vacunación (ERV): rango 10-50. Se analizó la asociación entre las variables estudiadas y la vacunación para BC mediante regresión logística (OR, IC95%). Se utilizó la base datos REDCap® y STATA vs14®. Resultados. Participaron 104 sujetos, media 9,9 años (DE 4,4). Asplenia: 91,3 %, VIH: 7,6 % y déficit de complemento: 0,9 %. Nivel socioeconómico: pobreza relativa: 38,4 %, seguido por clase media: 37,5 %. Estado de vacunación completa para meningococo: 45 %, neumococo: 42 %, Hib: 97 %. El 77,9 % tenía al día el calendario regular y el 61,5 %, el antigripal. Media ERV: 41,9 (DE 3,2). No se encontraron asociaciones significativas entre las variables y el estado de vacunación para BC. Conclusiones. Un elevado porcentaje no tenía vacunación completa para BC, tampoco el calendario regular y antigripal. La confianza en la vacunación de los cuidadores fue elevada.

Introduction. The Ministry of Health has established specific vaccines for people at high risk for invasive infections with encapsulated bacteria (EB). There is currently no information about compliance with the vaccination schedule. Our objective was to assess EB vaccination status in subjects ≤ 18 years with risk factors. Population and methods. Observational, analytical study with a survey to parents of subjects aged ≤ 18 years with HIV, asplenia and/or complement deficiency attending a vaccination center at a children's hospital between October 2020 and September 2021. Sociodemographic and clinical data were collected. Their vaccination status for the EB pneumococcus, meningococcus, and Haemophilus influenzae type b (Hib), their regular vaccination and flu vaccination schedules were assessed. The vaccine hesitancy scale (VHS) was administered: range 10­50. The association between the study variables and EB vaccination was analyzed using logistic regression (OR, 95% CI). The REDCap® database and the STATA® v.14 software were used. Results. A total of 104 subjects participated; mean age: 9.9 years (SD: 4.4). Asplenia: 91.3%, HIV: 7.6%, and complement deficiency: 0.9%. Socioeconomic level: relative poverty: 38.4%, followed by middle class: 37.5%. Complete vaccination status: meningococcal vaccine 45%, pneumococcal vaccine: 42%, Hib: 97%. The regular vaccination and flu vaccination schedules were up-to-date in 77.9% and 61.5% of cases, respectively. Mean VHS score: 41.9 (SD: 3.2). No significant associations were observed between variables and EB vaccination status. Conclusions. A high percentage of subjects had not completed neither their EB vaccination nor their regular or their flu vaccination schedules. Caregivers' confidence in vaccines was high.

Niveles de protección contra Haemophilus influenzae tipo b en niños, adolescentes y adultos cubanos / Levels of protection against Haemophilus influenzae type b in Cuban children, adolescents and adults

La concentración de los anticuerpos contra el polisacárido capsular polirribosilribitol fosfato del Haemophilus influenzae tipo b se considera un buen indicador serológico para evaluar protección contra la enfermedad invasiva. Existen pocos reportes que estudien la inmunidad serológica en Cuba. El objetivo general de este estudio fue determinar los niveles de protección séricos contra Haemophilus influenzae tipo b en niños, adolescentes y adultos cubanos, en una muestra de 575 individuos. Se cuantificó la concentración de IgG anti-polirribosilribitol fosfato de Haemophilus influenzae tipo b mediante un inmunoensayo enzimático estandarizado y validado en el laboratorio de inmunología del Centro Nacional de Genética Médica, La Habana, Cuba. Se determinaron las concentraciones medias geométricas de anticuerpos y los niveles de protección frente a la enfermedad invasiva por Haemophilus influenzae tipo b. La concentración media geométrica de IgG anti-polirribosilribitol fosfato fue de 1,94 μg/mL (IC95 por ciento 1,80; 2,08) y fue mayor en el grupo de 16 a 22 años. El porcentaje con protección de larga duración fue mayor para el sexo femenino que para el masculino (82,2 por ciento vs 71,4 por ciento; p=0,0339) entre los que poseían inmunidad natural. El grupo de sujetos nacidos en el periodo en que se vacunó con la vacuna conjugada cubana QUIMI-HIB® presentó concentraciones medias geométricas superiores (2,75 μg/mL, IC95 por ciento 2,00; 3,79). El 99,1 por ciento de los participantes presentó protección frente a la enfermedad invasiva por Haemophilus influenzae tipo b, el 19,8 por ciento a corto plazo y el 79,3 por ciento protección de larga duración. El inmunoensayo validado para la cuantificación de IgG anti-polirribosilribitol fosfato podría emplearse en estudios de seroprevalencia. En los sujetos estudiados, se encontró un predominio de elevadas concentraciones de IgG anti- polirribosilribitol fosfato del Haemophilus influenzae tipo b que confieren protección de larga duración(AU)

The levels of antibodies directed against the capsular polysaccharide polyribosylribitol phosphate of Haemophilus influenzae type b are considered a good serological indicator to assess the immunity against invasive disease. In Cuba, there are few reports that study serological immunity. The general objective was to determine serum protection levels against Haemophilus influenzae type b in Cuban children, adolescents and adults, in a sample of 575 Cuban individuals. The concentration of IgG against Haemophilus influenzae type b was quantified by means of an indirect ELISA standardized and validated in the immunology laboratory of the National Center of Medical Genetics, Havana, Cuba. The geometric mean concentration of IgG anti- polyribosylribitol phosphate and the levels of protection against invasive Haemophilus influenzae type b disease were determined. The geometric mean concentration of IgG anti- polyribosylribitol phosphate was 1.94 μg/mL (95percentCI 1.80;2.08) and the group from 16 to 22 years old presented the highest. Among those with natural immunity, the percentage with long-term protection was higher for females vs. males (82.2percent vs. 71.4percent; p=0.0339). The group of subjects born in the period in which they were vaccinated with the Cuban conjugate vaccine QUIMI-HIB® presented higher geometric mean concentration (2.75 μg/mL, CI95percent 2.00; 3.79). The 99.1percent of the participants had protection against invasive Haemophilus influenzae type b disease, 19.8percent short-term and 79.3percent long-term protection. The ELISA for the quantification of anti- Haemophilus influenzae type b IgG antibodies, developed and validated, could be used in seroprevalence studies. In the subjects studied, there was a predominance of high IgG anti- Haemophilus influenzae type b polyribosylribitol phosphate concentration values that confer long-term protection(AU)

Atraso na vacina tetravalente (DTP+Hib) em crianças de 12 a 23 meses de idade: Pesquisa Nacional de Saúde, 2013 / Delay in quadrivalent vaccine (DTP+Hib) in children 12 to 23 months of age: Brazilian National Health Survey, 2013 / Retraso en la vacuna tetravalente (DTP+Hib) en niños de 12 a 23 meses de edad: Encuesta Nacional de Salud, 2013

Resumo: O objetivo foi estimar a prevalência do atraso nas três doses da vacina tetravalente (DTP+Hib) em crianças de 12 a 23 meses de idade, no Brasil, por meio dos dados da Pesquisa Nacional de Saúde (PNS) de 2013 e descrever o atraso em cada uma das doses segundo variáveis sociodemográficas, utilização de serviços e intervenções públicas de saúde. Foram utilizados dados da PNS, estudo transversal realizado em 2013. O desfecho foi o atraso pelo menos em uma das três doses da vacina tetravalente. Considerou-se como atraso a dose recebida pelo menos 30 dias após a data preconizada, segundo informação da caderneta de vacinação. A prevalência do atraso foi descrita segundo variáveis sociodemográficas e utilização de serviços de saúde. Realizou-se análise descritiva obtendo-se frequências absolutas e relativas e seus respectivos intervalos de 95% de confiança. Das 2.016 crianças com informações coletadas, 1.843 foram analisadas. A prevalência de atraso de pelo menos uma dose da vacina foi de 44%. Observou-se atraso de 14,8% na primeira, 28,8% na segunda e 45,4% na terceira dose, sendo que 10% das crianças tiveram atraso nas três doses. Maiores prevalências de atraso foram encontradas em crianças do sexo masculino, de cor da pele parda, pertencentes ao quintil mais pobre de riqueza, moradores da zona rural e da Região Norte do Brasil. Evidenciou-se alta prevalência de atraso na vacina tetravalente (DTP+Hib) em crianças de 12 a 23 meses do Brasil, sendo maior na terceira dose.

Abstract: The study aimed to estimate the prevalence of delay in the three doses of quadrivalent vaccine (DTP+Hib) in children 12 to 23 months of age in Brazil, based on data from the Brazilian National Health Survey (PNS) of 2013 and to analyze the delay in each of the doses according to sociodemographic variables and use of health services and public health interventions. The data are from the PNS a cross-sectional study performed in 2013. The outcome was delay in at least one of the three doses of the quadrivalent vaccine. Delay was defined as a dose received at least 30 days after the recommended date according to information on the child's vaccination card. Prevalence of delay was analyzed according to sociodemographic variables and use of health services. A descriptive analysis was performed to obtain absolute and relative frequencies and their respective 95% confidence intervals. Of the 2,016 children with information collected, 1,843 were analyzed. The prevalence of delay in at least one dose of the vaccine was 44%. There was a delay of 14.8% in the first dose, 28.8% in the second, and 45.4% in the third, and 10% of the children had delays in all three doses. Higher prevalence of delay was associated with male gender, brown skin color, the poorest income quintile, and residence in rural areas and the North of Brazil. The study revealed high prevalence of delay with the quadrivalent vaccine (DTP+Hib) in children 12 to 23 months of age in Brazil, with the highest delay in the third dose.

Resumen: El objetivo fue estimar la prevalencia del atraso en las tres dosis de la vacuna tetravalente (DTP+Hib) en niños de 12 a 23 meses de edad, en Brasil, mediante los datos de la Encuesta Nacional de Salud (PNS) de 2013 y describir el retraso en cada una de las dosis, según variables sociodemográficas, utilización de servicios e intervenciones públicas de salud. Se trata de un estudio transversal, realizado en 2013, con datos de la PNS. El resultado fue el retraso por lo menos en una de las tres dosis de la vacuna tetravalente. Se consideró como un atraso la dosis recibida por lo menos 30 días tras la fecha prefijada, según la información de la cartilla de vacunación. La prevalencia del atraso fue descrita según variables sociodemográficas y utilización de servicios de salud. Se realizó un análisis descriptivo, obteniéndose frecuencias absolutas y relativas, así como sus respectivos intervalos de 95% de confianza. De los 2016 niños con información recogida, se analizaron 1843. La prevalencia de atraso de por lo menos una dosis de la vacuna fue de un 44%. Se observó un retraso de 14,8% en la primera, un 28,8% en la segunda y un 45,4% en la tercera dosis, siendo que un 10% de los niños sufrieron atraso en las tres dosis. Las mayores prevalencias de atraso se encontraron en niños de sexo masculino, mestizos, pertenecientes al quintil más pobre de riqueza, habitantes de la zona rural y de la Región Norte de Brasil. Se evidenció una alta prevalencia de atraso en la vacuna tetravalente (DTP+Hib) en niños de 12 a 23 meses de Brasil, siendo mayor en la tercera dosis.

Sistema de seguimiento y control eProtect infecciones respiratorias / eProtect respiratory infection monitoring and control system

Las infecciones del tracto respiratorio (ITR) son una de las principales causas de morbilidad y mortalidad en todo el mundo, y representan el 4,4 % de las muertes en todas las edades. A nivel mundial, se han observado disminuciones en la mortalidad causada por las ITR después de la introducción de las vacunas conjugadas contra Haemophilus influenzae tipo b, tos ferina y neumocócica. Sin embargo, las ITR siguen siendo una de las principales causas de mortalidad entre los niños pequeños y los ancianos en los países de ingresos bajos y medios. Se planteó un estudio donde se aplicó un sistema de seguimiento que sirvan para monitorear la vigilancia de las infecciones respiratorias agudas (IRA) en servicios de salud, por laboratorio y en unidades centinela en Perú. Participaron 67 médicos generales o cirujanos de 8 servicios de pediatría. 1453 casos de las IRA fueron de etiología viral, identificando al virus sincitial respiratorio (63,94%), Influenza AH1N1 (16,59%); en el caso de las neumonías bacterianas se aislaron Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae y Streptococcus beta hemolyticus. Durante la última década de reforma del sistema de salud, Perú ha hecho de la construcción de su sistema de APS una prioridad. Sin embargo, el sistema se enfrenta actualmente a desafíos para proporcionar atención de alta calidad y valor a la población debido a deficiencias en varias dimensiones. El sistema de APS ayudará a responder a la transición epidemiológica actual y futura epidemia brotes de manera más eficaz(AU)

Respiratory tract infections (RTIs) are one of the leading causes of morbidity and mortality worldwide, accounting for 4.4% of deaths in all ages. Globally, declines in mortality from RTIs have been observed after the introduction of Haemophilus influenzae type b, pertussis, and pneumococcal conjugate vaccines. However, RTIs remain a leading cause of mortality among young children and the elderly in low- and middle-income countries. A study was proposed where a monitoring system was applied to monitor the surveillance of acute respiratory infections (ARI) in health services, by laboratory and in sentinel units in Peru. A total of 67 general practitioners or surgeons from 8 pediatric services participated. 1453 cases of ARI were of viral aetiology, identifying the respiratory syncytial virus (63.94%), Influenza AH1N1 (16.59%); in the case of bacterial pneumonia, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus beta hemolyticus were isolated. During the last decade of health system reform, Peru has made building its PHC system a priority. However, the system currently faces challenges in providing high quality and value care to the population due to deficiencies in several dimensions. The PHC system will help respond to current epidemiological transition and future epidemic outbreaks more effectively(AU)

Epiglotite na era pós-vacinal ao Haemophilus influenzae tipo B / Epiglottitis in the post Haemophilus influenzae type B vaccine era

A epiglotite, conhecida recentemente como supraglotite, é uma infecção grave da epiglote e estruturas supraglóticas, com consequente obstrução da via aérea superior e risco iminente de morte. Trata-se de emergência médica, e a via aérea do paciente deve ser garantida o mais breve possível. Com o desenvolvimento e introdução da vacinação contra o Haemophilus influenzae tipo B (Hib), houve queda expressiva de sua incidência e mortalidade na faixa etária pediátrica, principalmente em crianças menores de cinco anos, porém, tal redução não foi tão significativa em adultos. A doença passou a ser mais comum em crianças acima de cinco anos e na faixa etária adulta, e agentes como Streptococcus e Staphylococcus tornaram-se os principais responsáveis. Embora rara, ela ainda não foi eliminada, fazendo-se necessário o seu rápido reconhecimento e tratamento, a fim de evitar mortalidade. (AU)

Epiglottitis, recently known as supraglottitis, is a severe infection of the epiglottis and supraglottic structures, leading to upper airway obstruction and imminent risk of death. It is considered a medical emergency and the patient's airway must be cleared as soon as possible. With the development and introduction of the vaccination against Haemophilus influenzae type B (Hib), there has been a significant decline in its incidence and mortality in the pediatric age range, especially in children younger than five years old, yet not so much in adults. The disease has become more common in children older than five years old and in adults, with Streptococcus and Staphylococcus being the main responsible pathogens. Although it is a rare condition, it has not yet been eradicated, making its fast recognition and treatment necessary to decrease the chance of mortality. (AU)

Epiglotitis por Haemophilus influenzae tipo b en la era de la vacunación: caso clínico pediátrico / Epiglottitis due to Haemophilus influenzae type b in the vaccination era: pediatric clinical case

La epiglotitis aguda infecciosa es infrecuente en la actualidad, debido a la vacunación contra su principal agente etiológico, el Haemophilus influenzae b. Se requiere alto índice de sospecha ante el cuadro clínico de dificultad respiratoria, estridor, disfonía y fiebre. Se presenta a un niño de 2 años, previamente sano, con esquema de vacunas completas, con dificultad respiratoria aguda y estridor laríngeo, en el que, al momento de realizar la intubación, se realizó el diagnóstico de epiglotitis aguda. Con hemocultivos positivos para Haemophilus influenzae b, cumplió 13 días de tratamiento con ceftriaxona, con hemocultivos de control y cultivo de líquido cefalorraquídeo negativo.

Acute infectious epiglottitis is infrequent at present due to vaccination for its main etiologic agent, Haemophilus influenzae b (Hib). It must be taken into account when we make a differential diagnosis in a child whose clinical symptoms are respiratory distress, stridor, dysphonia and fever. We report a 2-year-old child, previously healthy, whose vaccination calendar was complete, and whose clinical presentation included respiratory distress and stridor; at the moment of the intubation the laryngoscopy showed an acute epiglottitis. Blood cultures were taken, which were positive for Hib. He was treated with ceftriaxone during 13 days, and the control blood cultures and cerebrospinal fluid were negative.

Epidemiología de las meningitis bacterianas en niños en un hospital pediátrico: 2011-2016 / Epidemiology of bacterial meningitis in children at a pediatric hospital: 2011-2016

Introducción: Las meningitis bacterianas en niños son causa de importante morbimortalidad. Los principales agentes etiológicos son Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae. En los últimos años, luego de la introducción sucesiva de vacunas conjugadas al calendario nacional de inmunizaciones, se ha visto un cambio en la epidemiología de estas infecciones. Objetivo: Describir las características clínicas, epidemiológicas y evolutivas de los niños hospitalizados con meningitis bacteriana confirmada microbiológicamente entre 2011 y 2016 en un hospital de tercer nivel de complejidad. Materiales y métodos: Cohorte retrospectiva. Se incluyeron niños entre 1 mes de vida y 17 años con cuadro clínico compatible con meningitis bacteriana y cultivo positivo y/o PCR en líquido cefalorraquídeo y/o hemocultivos positivos para Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae b. Se registraron las características demográficas, clínicas y evolutivas hasta los 30 días del egreso. Se utilizó mediana y rango intercuartilo (RIC) para variables continuas y porcentaje para variables categóricas. Se utilizó Stata 10. Resultados: n=65. Edad: mediana de 9 meses (RIC 4-35). Varones: 58% (n=38). Se identificó Neisseria meningitidis en un 48% (n=31), Haemophilus influenzae b en un 26% (n=17) y Streptococcus pneumoniae en un 26% (n=17). El 26% (n=17) de los pacientes presentaba alguna comorbilidad. Tuvieron hemocultivos positivos el 62% (n = 40) de los pacientes y 86% (n=55) de los líquidos cefalorraquídeos. Todos los pacientes recibieron tratamiento antimicrobiano con ceftriaxona tanto como tratamiento empírico como definitivo y 92% (n=60) recibieron corticoides empíricos. La mediana de días de internación fue de 11 (RIC 8-17). El 28% (n=18) requirió cuidados intensivos, y el 8% (n=5) falleció. Durante el período de estudio se observó que la frecuencia de meningitis por Streptococcus pneumoniae disminuyó en el final del estudio (9% en 2016 vs 60% en 2011), mientras que la frecuencia de meningitis por Neisseria meningitidis en 2016 fue mayor que al inicio del período (64% en 2016 vs. 40% en 2011). La frecuencia de identificación de Haemophilus influenzae b se mantuvo estable. Conclusiones: Las meningitis bacterianas confirmadas por Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae b prevalecieron en niños menores de 12 meses. En esta cohorte se observó un predominio de las infecciones por Neisseria meningitidis en los últimos años, y una disminución en la frecuencia de meningitis por Streptococcus pneumoniae en el período post introducción de la vacuna conjugada 13 valente al calendario nacional de inmunizaciones. (AU)

Introduction: In children, bacterial meningitis is an important cause of morbidity and mortality. The main etiological agents are Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Over the last years, the successive introduction of conjugated vaccines in the national immunization calendar has led to a change in the epidemiology of these infections. Objective: To describe the clinical and epidemiological features and outcome of children admitted because of microbiologically confirmed meningitis seen between 2011 and 2016 at a tertiary care hospital. Material and methods: A retrospective cohort study was conducted. Children between 1 month of life and 17 years of age with clinical features compatible with bacterial meningitis and positive cultures and/or PCR in cerebrospinal fluid (CSF) and/or positive blood cultures for Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae b were included. Demographic, clinical, and outcome features were recorded until 30 days after discharge. Median and interquartile range (IQR) were calculated for continuous variables and percentages for categorical variables. The Stata 10 program was used. Results: n=65. Age: median was 9 months (IQR 4-35). Boys: 58% (n=38). Neisseria meningitidis was identified in 48% (n=31), Haemophilus influenzae b in 26% (n=17), and Streptococcus pneumoniae in 26% (n=17). Overall, 26% (n=17) of the patients presented with comorbidities. Positive blood cultures were found in 62% (n = 40) and positive CSF cultures in 86% (n=55) of the patients. All patients received antimicrobial treatment with ceftriaxone both empirically and as final treatment and corticosteroids were empirically started in 92% (n=60). Median hospital stay was 11 days (IQR 8-17). Overall, 28% (n=18) required intensive care and 8% (n=5) of the patients died. The incidence of meningitis due to Streptococcus pneumoniae was observed to diminish at the end of the study period (9% in 2016 vs 60% in 2011), while the incidence of meningitis due to Neisseria meningitidis in 2016 was higher than at the end of the study period (64% in 2016 vs. 40% in 2011). The frequency of identification of Haemophilus influenzae b remained stable. Conclusions: Confirmed bacterial infections due to Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae b were prevalent in infants younger than 12 months of age in this cohort of patients. Infections due to Neisseria meningitidis predominated over the last years and the incidence of meningitis due to Streptococcus pneumoniae diminished after the introduction of the 13 valent conjugated vaccine was introduced in the national immunization calendar.(AU)

Detección de virus influenza A, B y subtipos a (H1N1) pdm09, A (H3N2) por múltiple rt-pcr en muestras clínicas / Detection of influenza A, B and subtypes A (H1N1) pdm09, A (H3N2) viruses by multiple qrt-pcr in clinical samples

RESUMEN Objetivos. Estandarizar la técnica de reacción en cadena de la polimerasa en tiempo real (RT-PCR) múltiple para la detección de virus influenza A, B y tipificación de subtipos A (H1N1) pdm09, A (H3N2) en muestras clínicas. Materiales y métodos. Se analizaron 300 muestras de hisopado nasofaríngeo. Esta metodología fue estandarizada en dos pasos: la primera reacción detectó el gen de la matriz del virus de influenza A, gen de la nucleoproteína del virus influenza B y el gen GAPDH de las células huésped. La segunda reacción detectó el gen de la hemaglutinina de los subtipos A (H1N1) pandémico (pdm09) y A (H3N2). Resultados. Se identificaron 109 muestras positivas a influenza A y B, de las cuales 72 fueron positivas a influenza A (36 positivas a influenza A (H1N1) pdm09 y 36 positivos a influenza A (H3N2)) y 37 muestras positivas a influenza B. 191 fueron negativas a ambos virus mediante RT-PCR en tiempo real multiplex. Se encontró una sensibilidad y especificidad del 100% al analizar los resultados de ambas reacciones. El límite de detección viral fue del rango de 7 a 9 copias/µL por virus. Los resultados no mostraron ninguna reacción cruzada con otros virus tales como adenovirus, virus sincitial respiratorio, parainfluenza (1,2 y 3), metapneumovirus, subtipos A (H1N1) estacional, A (H5N2) y VIH. Conclusiones. La RT-PCR múltiple demostró ser una prueba muy sensible y específica para la detección de virus influenza A, B y subtipos A (H1N1, H3N2) y su uso puede ser conveniente en brotes estacionales.

ABSTRACT Objectives. To describe the clinical and epidemiological characteristics of patients diagnosed with epidermolysis bullosa (EB) at the Instituto Nacional de Salud (INSN) in Lima, Peru; a National Reference Center for this disease. Material and methods . Observational, descriptive and transversal study. We reviewed the clinical histories and laboratory tests of patients diagnosed with EB treated in INSN from 1993 to 2015. Results. 93 patients were registered. The average age was 7.9 ± 5.6 years; 53.8% (n = 50) were boys. Clinical forms corresponded to dystrophic EB with 41 (44.1%) cases, simple EB with 39 (41.9%) union EB cases with 8 (8.6%) and Kindler syndrome with 4 (4.3%) cases. The clinical form could not be identified in a case. A total of 48 cases (51.6%) came from Lima and Callao, and 45 cases (48.4%) from other provinces of the country. Extracutaneous manifestations involved gastrointestinal (44.1%), ocular (37.6%), odontogenic (87.1%), and nutritional (79.6%) involvement, as well as pseudosindactilia (16.1%). Chronic malnutrition (71.6%), acute malnutrition (17.6%) and anemia (62.4%) were found. Mortality corresponded to 6 cases (6.5%). Conclusions. 93 cases of EB were reported in INSN, the predominant clinical presentation was the dystrophic form.

Evaluation of Haemophilus influenzae type b carrier status among children 10 years after the introduction of Hib vaccine in Brazil

The aim of the present study was to assess the prevalence of Haemophilus influenzaetype b (Hib) nasopharyngeal (NP) colonisation among healthy children where Hib vaccination using a 3p+0 dosing schedule has been routinely administered for 10 years with sustained coverage (> 90%). NP swabs were collected from 2,558 children who had received the Hib vaccine, of whom 1,379 were 12-< 24 months (m) old and 1,179 were 48-< 60 m old. Hi strains were identified by molecular methods. Hi carriage prevalence was 45.1% (1,153/2,558) and the prevalence in the 12-< 24 m and 48-< 60 m age groups were 37.5% (517/1,379) and 53.9% (636/1,179), respectively. Hib was identified in 0.6% (16/2,558) of all children in the study, being 0.8% (11/1,379) and 0.4% (5/1,179) among the 12-< 24 m and 48-< 60 m age groups, respectively. The nonencapsulate Hi colonisation was 43% (n = 1,099) and was significantly more frequent at 48-< 60 m of age (51.6%, n = 608) compared with that at 12-< 24 m of age (35.6%, n = 491). The overall resistance rates to ampicillin and chloramphenicol were 16.5% and 3.7%, respectively; the co-resistance was detected in 2.6%. Our findings showed that the Hib carrier rate in healthy children under five years was very low after 10 years of the introduction of the Hib vaccine.

Aislamientos invasivos de Haemophilus influenzae en menores de 5 años: distribución de los serotipos y de la sensibilidad antimicrobiana, SIREVA II Colombia 2002-2013 / Invasive Haemophilus influenzae isolates in children younger than 5 years: Distribution of serotypes and antimicrobial sensitivity, SIREVA II Colombia 2002-2013

Objetivo: Analizar del 2002 al 2013 los datos de la vigilancia de los serotipos y sensibilidad antimicrobiana de los aislamientos invasivos de Haemophilus influenzae ( H. influenzae ) en niños menores de 60 meses. Materiales y métodos: Se analizaron los datos demográficos, fuente y enfermedad asociada de los aislamientos invasivos de H. influenzae recibidos entre 2002 y 2013. Todos los aislamientos habían sido confirmados bacteriológicamente, tenían el dato del serotipo, el cual fue determinado por el método de aglutinación en lámina y PCR y los patrones de sensibilidad antimicrobiana por concentración inhibitoria mínima a ampicilina, SXT, cloranfenicol, cefuroxima y ceftriaxona. El análisis se realizó por periodos de 3 años. Resultados: Por enfermedad invasiva el 50,5% eran de pacientes con meningitis, 23,5% de neumonías, 19,5% de sepsis y bacteriemia, 2,0% de otros y 4,5% sin dato. Por procedencia se recibieron de Bogotá y Antioquia 55 aislamientos de cada uno, de Risaralda 24, de Valle 15, de Santander 11 y 40 de 14 departamentos. El serotipo predominante fue el Hib (40,5%), seguido de HiNT (38,0%), Hia (17,5%), Hid (2,0%), Hif (1,5%) y Hie (0,5%). Del total de los aislamientos, 12,0% eran resistentes a ampicilina; 16,5% a SXT; 1,0% a cloranfenicol y 0,5% a ceftriaxona. Todos los aislamientos fueron sensibles a cefuroxima y a rifampicina. Conclusiones: La vigilancia por el laboratorio es una vigilancia pasiva voluntaria pero, no obstante el número reducido de aislamientos, permite determinar que Hib continúa circulando en esta población y que hay otros serotipos de H. influenzae que causan enfermedad invasiva. Por tanto es necesario mantener y fortalecer la vigilancia de este patógeno.

Objective: To analyze 2002-2013 surveillance data on the serotypes and antimicrobial sensitivity of invasive Haemophilus influenzae ( H. influenzae ) isolates in children younger than 60 months. Materials and methods: We analyzed the demographic data, source and associated diseases ofinvasive HI isolates from cases recorded from 2002-2013. All isolates had been bacteriologically confirmed and had data on their serotype, which was determined by the slide agglutination method and polymerase chain reaction. The antimicrobial sensitivity patterns were determined by minimum inhibitory concentration of ampicillin, trimethoprim-sulfamethoxazole, chloramp-henicol, cefuroxime and ceftriaxone. The analysis was conducted in 3-year periods. Results: According to invasive disease, 50.5% of patients had meningitis, 23.5% had pneumonia,19.5% had sepsis and bacteremia, 2.0% had other diseases and 4.5% lacked data. By origin, 55 isolates each were received from Bogota and Antioquia, 24 were from Risaralda, 15 were from Valle, 11 were from Santander and 40 came from 14 departments. The predominant serotype was Hib (40.5%), followed by HiNT (38.0%), Hia (17.5%), Hid (2.0%), Hif (1.5%) and Hie (0.5%). Ofthe total isolates, 12.0% were resistant to ampicillin; 16.5% to trimethoprim-sulfamethoxazole,1.0% to chloramphenicol and 0.5% to ceftriaxone. All isolates were sensitive to cefuroxime andrifampicin. Conclusions: Laboratory surveillance is a voluntary passive surveillance; however, the low number of isolates helped determine that Hib continues to circulate in this population and that there are other H. influenzae serotypes that cause invasive disease. Therefore, surveillance of this pathogen needs to be maintained and reinforced.

Avaliação do impacto do programa de vacinação contra o Haemophilus influenzae tipo b (Hib) no Estado de São Paulo e município de São Paulo, após dez anos de introdução da vacina / Evaluation of the impact of the anti Haemophilus influenzae type b (Hib) vaccine program in the state of São Paulo and the city of São Paulo, ten years after vaccine introduction

Objetivos: Avaliar o impacto global, direto, indireto e a tendência da duração de proteção da vacinação contra o Haemophilus influenzae tipo b (Hib), no estado de São Paulo (ESP) e no município de São Paulo (MSP), na população de 0 - 59 meses, comparando os períodos pré-vacinal (1996 - 1998) e pós-vacinal (2001 - 2009). Métodos: estudo com componente descritivo e de cunho analítico, retrospectivo. A população de estudo incluiu os menores de cinco anos residentes no ESP e no MSP. Adotou-se como definição de caso confirmado o menor de cinco anos identificado como positivo para o Hib em cultura e/ou contraimunoeletroforese e/ou látex e/ou RT-PCR, em amostra de LCR e sangue, e/ou vínculo epidemiológico. Os dados foram obtidos a partir do SINAN, SIGH-Web Instituto Adolfo Lutz e Fundação IBGE. As variáveis de estudo incluíram as demográficas, clínicas e relativas ao agente, apresentadas em séries temporais e períodos estabelecidos para parametrização e comparabilidade. O parâmetro das avaliações de impacto foi a magnitude da variação da incidência de meningite causada pelo Hib. Para cada estimativa de impacto construiu-se um Intervalo de Confiança (IC) de 95 por cento a partir do cálculo de Risco Relativo (RR). As estimativas do risco relativo (RR) e os respectivos intervalos de 95 por cento de confiança foram analisados utilizando-se o software R. Resultados: nos períodos considerados, foram descritos 1.561 casos confirmados de meningites por Hib no ESP, sendo 27,16 por cento (424/1.561) no MSP, e 80,78 por cento (1.261/1.561) dos casos foram registrados em menores de cinco anos. A maioria dos casos foi confirmada por cultura, com percentual médio de 65 por cento no ESP e 66 por cento no MSP. As taxas médias de incidência de meningites por Hib mais significativas no período pré-vacinal verificaram-se nos menores de um ano (30,56/105- ESP; 32,06/105 - MSP), considerada a faixa etária de maior risco de adoecimento...

Objectives: To evaluate global impact, direct and indirect, as well as the tendency of the duration of vaccine protection against Haemophilus influenzae type b (Hib) in the state of São Paulo (ESP) and in the city of São Paulo (MSP), amongst the population between 0-59 months of age during the periods pre-vaccine (1996-1998) and post vaccine (2001-2009). Methods: a retrospective study with a descriptive component and with analytic venue. Studied population included children under five years old, dwelling in ESP and MSP. Criteria adopted as definition of confirmed case was child under five years of age identified as positive for Hib in culture and/or counterimmunelectroforesis and/or latex and/or RT/PCR, in LCR sample and blood. and/or epidemiologic link. Data were obtained from the SINAN, SIGH-Web Instituto Adolfo Lutz and IBGE Foundation. Variables under study included socio-demographic and clinical ones, and those related to the agent; they were presented in temporal series and periods established in order to allow parametric and comparison. Impact evaluation was established upon the variation of incidence magnitude of meningitis caused by Hib. For each impact estimate a Confidence Interval (IC) of 95 per cent from the calculus of Relative Risk (RR). Estimates of relative risk (RR) and the respective intervals of 95 per cent confidence were analyzed employing the R software. Results: During the analyzed periods 1561 confirmed cases of meningitis caused by Hib were described in the state of São Paulo, 27.16 per cent of which (424/1561) in MSP; 80.78 per cent (1261/1561) of the registered cases occurred in children under five years of age. The majority of the cases were confirmed by culture, with an average percentage of 65 per cent in ESP and 66 per cent in MSP...

Vigilancia de serotipos en infecciones invasivas por Haemophilus influenzae en la Argentina en la era de la vacuna conjugada contra el serotipo b durante el período 2005-2010 / Surveillance of Haemophilus influenzae serotypes in Argentina from 2005 to 2010 during the Haemophilus influenzae type b conjugate vaccine era

La introducción de la vacuna contra Haemophilus influenzae tipo b en los programas de inmunización de muchos países produjo una reducción marcada en la incidencia de enfermedad invasiva causada por este serotipo y en su portación y un incremento de otros tipos capsulares y de aislamientos no capsulados. Se estudiaron 313 aislamientos de H. influenzae recuperados de sitio estéril, provenientes de pacientes pediátricos y adultos con enfermedad invasiva atendidos en 90 hospitales de la Red Nacional de Laboratorios para Meningitis e Infecciones Respiratorias Agudas Bacterianas durante el período 2005-2010. Las patologías más frecuentes fueron neumonía, 40,3 % (n = 126), meningitis, 30,0 % (n = 94) y bacteriemia, 26,5 % (n = 83). En los pacientes pediátricos (n = 279), la mayor frecuencia de aislamientos correspondió a menores de 2 años, 74,5 % (n = 208). Con respecto a la distribución de tipos, el 61,3 %, correspondió a H. influenzae no capsulados (n = 192); el 20,1 % al b (n = 63); 11,2 % al a (n = 35); 4,8 % al f y 2,6 % a otros. En meningitis predominaron H. influenzae capsulados mientras que en neumonía y bacteriemia resultaron dominantes los tipos no capsulados. Se determinó el biotipo en 306 aislamientos. Todos los aislamientos de tipo a correspondieron al biotipo II; el 66,7 % de los tipo b pertenecieron al biotipo I. Mediante las técnicas de aglutinación en lámina y PCR se estudiaron 220 aislamientos; la concordancia entre ambas fue de 0,982 (IC: 0,92-1,00). En el último año se encontró un aumento significativo del tipo b, lo cual indica la importancia de mantener la vigilancia clínica y laboratorial de la enfermedad invasiva por H. influenzae.

The introduction of the Haemophilus influenzae type b vaccine in the immunization programs of many countries has greatly reduced this invasive disease and the carriage caused by this serotype, also increasing other capsular types and non-capsular isolations. There were 313 isolations of H. influenzae under study, which were recovered from a sterile site coming from pediatric and adult patients carrying the invasive disease. Patients were treated at 90 different hospitals belonging to the Red Nacional de Laboratorios para Meningitis e Infecciones Respiratorias Agudas Bacterianas (National Lab Network for Meningitis and Acute Bacterial Respiratory Infections) from 2005 to 2010 for the following disorders: pneumonia, 40.3% (n = 126), meningitis, 30.0% (n = 94) and bacteremia, 26.5% (n = 83). In pediatric patients (n = 279), the highest frequency of isolations corresponded to children under the age of 2 years, 74.5% (n = 208). Regarding type distribution, 61.3% corresponded to non-capsular H. influenzae (n = 192), 20.1% to type b (n = 63), 11.2% to type a (n = 35), 4.8% to type f, and 2.6% to other types. Capsular H. influenzae was predominant in meningitis whereas non-capsular H. influenzae in pneumonia and bacteremia. The biotype was determined in 306 isolations. The totality (100%) of type a (n = 35) was biotype II whereas 66.7% of type b (n = 63) was biotype I. Slide agglutination and PCR tests were used in 220 isolations. There was a match of 0.982 (IC: 0.92-1.00) between them. During the last year, there was a great increase in type b, showing the importance of clinical and laboratory-based surveillance of the invasive disease caused by H. influenzae.

Incidência de meningite por Haemophilus influenzae no RS 1999-2010: impacto da cobertura vacinal / Incidence of meningitis caused by Haemophilus influenzae in the state of Rio Grande do Sul 1999-2010: impact of vaccination campaign

O objetivo deste artigo é analisar e verificar a situação epidemiológica das meningites causadas pelo agente Haemophilus influenzae tipo b nos últimos 10 anos no Rio Grande do Sul. Estudo retrospectivo, descritivo, utilizando o sistema de dados de notificação de meningites, e cobertura vacinal, armazenados em base on line Tabnet - Tabulação de dados Epidemiológicos - CEVS/SES/RS, abrangendo o período de 1999 a 2010. Foram utilizados casos notificados e confirmados, tendo como critério de seleção o ano de inicio dos sintomas, idade, diagnostico e evolução. Foi analisado o Estado do Rio Grande do Sul, representado por 19 coordenadorias de saúde. Comparações entre proporções foram avaliadas pelo teste de z. No RS foram notificados 3043 casos confirmados de meningite bacteriana, sendo 6,77% dos casos causados por H. influenzae. O coeficiente de incidência da meningite por H. influenzae, sem considerar faixa etária, caiu significativamente (95,6%) após 1999, assim como a mortalidade. Crianças menores de um ano continuam sendo as mais acometidas (52%), não havendo alteração na letalidade. Os resultados apresentados revelaram um impacto positivo das estratégias de vacinação contra Hib no Estado do Rio Grande do Sul nos últimos dez anos.

This article seeks to analyze and update the epidemiological situation of meningitis caused by Haemophilus influenzae type b in the past 10 years in the state of Rio Grande do Sul (RS). It is a retrospective, descriptive study, which used the data notification system of meningitis and vaccination campaign coverage, stored in the Epidemiological TABNET online database, for the period from 1999 to 2010. Cases notified and confirmed were used and the selection criteria were the year when the symptoms were detected, age, diagnosis, and evolution. Nineteen health centers in the state of Rio Grande do Sul were analyzed. The z-test was used to evaluate comparisons between the proportions. In the period studied, 3043 confirmed cases of bacterial meningitis were reported, of which 6.77% were caused by H. influenzae. The incidence and mortality rates of meningitis caused by H. influenzae, without taking age group into consideration, fell significantly (95.6%) after 1999. Children under one year old continue to be the most affected (52%), there being no change in lethality. The results presented revealed a positive impact of Hib vaccination strategies in the state of Rio Grande do Sul over the past ten years.

Prevención / Prevention

En la actualidad, se cuenta con un grupo de vacunas desarrolladas para la prevención de infecciones bacterianas, incluso para realizar profilaxis. En la década de los 80 del siglo XX apareció la primera vacuna contra Haemophilus influenzae tipo b que redujo y prácticamente eliminó la enfermedad invasiva por esta bacteria. A inicios del año 2000 se observó una dramática reducción de enfermedad invasiva por neumococo, gracias a la introducción de la vacuna PCV-7 contra este germen. Sin embargo, surgieron serotipos no incluidos en esta vacuna, por lo cual se desarrollaron la PHiD-CV 10 y la PCV-13, con 10 y 13 serotipos, respectivamente. En contra del meningococo se han desarrollado vacunas polisacáridas que han demostrado efectividad, así como las conjugadas que pueden ser monovalentes y tetravalentes. La quimioprofilaxis se indica en casos específicos que se explican en forma detallada en este capítulo

Nowadays, several vaccines have been developed for the prevention of bacterial infections, and also for prophylaxis. In the 80's of the twentieth century came the first vaccine against Haemophilus influenzae type b, which reduced and virtually eliminated invasive disease by this bacterium. In early 2000, there was a dramatic reduction in invasive pneumococcal disease, with the introduction of PCV-7 vaccine against this germ. However, there were serotypes not included in the vaccine, which was developed by the Phido-CV 10 and PCV-13, 10 and 13 serotypes, respectively. Against meningococcus, polysaccharide vaccines have been developed that have demonstrated effectiveness, as well as the conjugate vaccines, which may be monovalent and tetravalent. Chemoprophylaxis is indicated in specific cases that are reviewed in detail in this chapter

Identificación y tipificación de Haemophilus influenzae mediante PCR múltiple / Use of multiplex PCR for detection and identification of Haemophilus influenzae

Se diseñó una estrategia metodológica para la detección simultánea entre Haemophilus influenzae serotipo b (Hib) y no tipificable (HiNT), así como para discriminar entre H. influenzae, Moraxella catarrhalis y Streptococcus pneumoniae. El estudio se realizó en una recolección de 64 cepas, las cuales se sometieron a amplificación por PCR utilizando ADN genómico o directamente el cultivo bacteriano como plantilla. La PCR se realizó en dos fases: 1) PCR triple para discriminar entre H. influenzae y M. catarrhalis empleando oligonucleótidos específicos para los genes del ARNr 16S y de la neumolisina (Ply) para identificar S. pneumoniae; 2) PCR doble para la identificación simultánea de Hib y HiNT, utilizando oligonucleótidos específicos de los genes cap y hmw. Se logró la amplificación del gen ARNr 16S en las 64 cepas de H. influenzae, sin obtenerse amplificación en las cepas control. La secuencia Bex A se amplificó en 29 de 32 cepas de Hib, y la secuencia HMWA se amplificó en 29 de 30 cepas de HiNT. La amplificación con los oligonucleótidos específicos para M. catarrhalis y S. pneumoniae no mostró productos con ninguna cepa de H. influenzae. Estos resultados permiten proponer la aplicación de esta herramienta metodológica para discriminar entre M. catarrhalis y S. pneumoniae, e identificar H. influenzae directamente a partir de muestras clínicas.

Immunogenicity, reactogenicity and consistency of production of a Brazilian combined vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type b

A randomized, double-blinded study evaluating the immunogenicity, safety and consistency of production of a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine entirely produced in Brazil by Bio-Manguinhos and Instituto Butantan (DTP/Hib-BM) was undertaken. The reference vaccine had the same DTP vaccine but the Hib component was produced using purified materials supplied by GlaxoSmithKline (DTP/Hib-GSK), which is registered and has supplied the Brazilian National Immunization Program for over more than five years. One thousand infants were recruited for the study and received vaccinations at two, four and six months of age. With respect to immunogenicity, the vaccination protocol was followed in 95.6 percent and 98.4 percent of infants in the DTP/Hib-BM and DTP/Hib-GSK groups, respectively. For the Hib component of the study, there was 100 percent seroprotection (>0.15 µg/mL) with all three lots of DTP/Hib-BM and DTP/Hib-GSK. The geometric mean titer (GMT) was 9.3 µg/mL, 10.3 µg/mL and 10.3 µg/mL for lots 1, 2 and 3 of DTP/Hib-BM, respectively, and the GMT was 11.3 g/mL for DTP/Hib-GSK. For diphtheria, tetanus and pertussis, seroprotection was 99.7 percent, 100 percent and 99.9 percent, respectively, for DTP/Hib-BM, three lots altogether and 99.2 percent, 100 percent and 100 percent for DTP/Hib-GSK. GMTs were similar across all lots and vaccines. Adverse events rates were comparable among the vaccine groups. The Brazilian DTP/Hib vaccine demonstrated an immunogenicity and reactogenicity profile similar to that of the reference vaccine.