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.

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.

Caracterización del polirribosilribitol fosfato por cromatografía de exclusión molecular de alta eficacia con detección ultravioleta / Characterization of polyribosylribitol phosphate by high efficiency size exclusion chromatography with ultraviolet detection

Haemophilus influenzae tipo b es un importante patógeno del hombre causante de varias de las enfermedades invasivas en niños menores de cinco años, contra el cual fueron autorizadas las vacunas glicoconjugadas a partir del polirribosilribitol fosfato. Quimi-Hib® es la primera y única vacuna contra este patógeno que utiliza el polisacárido obtenido por síntesis química. El Ingrediente Farmacéutico Activo es producido por el Centro de Ingeniería Genética y Biotecnología y se obtiene a partir de su conjugación al toxoide tetánico. En el presente reporte se hizo una caracterización del polirribosilribitol fosfato mediante la técnica de cromatografía de exclusión molecular de alta eficacia con detección ultravioleta a 215 nm. En el estudio se evaluaron tres lotes y se determinó el perfil de elución en una columna SuperdexTM 75 10/300 GL Increase con un porciento de pureza de 77,42 ± 8,97 y una masa molar promedio de 7.381 Da ± 210,93. La principal impureza presente en el polirribosilribitol fosfato es el dimetilsulfóxido, disolvente utilizado en la reacción de activación con el éster N-hidroxisuccinimidilo del ácido β-maleimidopropiónico. El polirribosilribitol fosfato se purificó por filtración con un Amicon Ultra-15 de 2.000 Da hasta una pureza de 99,1 por ciento y se conjugó al toxoide tetánico. El rendimiento de la reacción de conjugación con el polisacárido purificado fue de 30,0 por ciento 1,77 el cual no muestra diferencias significativas con el control que fue 33,7 por ciento ± 3,57 demostrándose que el dimetilsulfóxido no afecta el desempeño de la reacción de conjugación(AU)

Haemophilus influenzae type b is an important human pathogen causing some invasive diseases in children less than five years of age. Glycoconjugate vaccines based on polyribosylribitol phosphate have been licensed against this bacterium. Quimi-Hib® is the first and only vaccine against this pathogen using the chemically synthesized polysaccharide. The Active Pharmaceutical Ingredient is produced by the Center for Genetic Engineering and Biotechnology and is obtained from its conjugation to tetanus toxoid. In the present report a characterization of polyribosylribitol phosphate was performed by high performance molecular exclusion chromatography with ultraviolet detection at 215 nm. Three batches were evaluated in the study and the elution profile was determined on a SuperdexTM 75 10/300 GL Increase column with a purity percentage of 77.42 ± 8.97 and an average molecular weight of 7,381 Da ± 210.93. The main impurity present in polyribosylribitol phosphate was dimethylsulfoxide, the solvent used in the activation reaction with N-hydroxysuccinimidyl ester of β-maleimidopropionic acid. Polyribosylribitol phosphate was purified by filtration using a 2,000 Da cut-off Amicon Ultra-15 to a purity of 99.1 percent and conjugated to tetanus toxoid. The yield of the conjugation reaction with the purified polysaccharide was 30.0 percent ± 1.77 which shows no significant difference with the control which was 33.7 percent ± 3.57 demonstrating that dimethylsulfoxide does not affect the performance of the conjugation reaction(AU)

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.

Invasive Haemophilus influenzae disease in the vaccine era in Rio de Janeiro, Brazil

BACKGROUND Haemophilus influenzae (Hi) serotype b (Hib) conjugate vaccine was incorporated into the infant immunisation schedule in Brazil in 1999, where Hib was one of the major etiologic sources of community-acquired bacterial meningitis. OBJECTIVES The purpose of this study is to describe the molecular epidemiology of invasive Hi disease in Rio de Janeiro state, Brazil, before and after vaccine introduction. METHODS Surveillance data from 1986 to 2014 were analysed. Hi isolates recovered from cerebrospinal fluid (CSF) or blood from 1993 to 2014 were serotyped by slide agglutination, genotyped by multilocus sequence typing (MLST), and the capsule type evaluation, differentiation of serologically non-typeable isolates, and characterisation of the capsule (cap) locus was done by polymerase chain reaction. Antimicrobial susceptibility testing was performed using E-test. FINDINGS From 1986 to 1999 and from 2000 to 2014, 2580 and 197 (42% without serotype information) confirmed cases were reported, respectively. The case fatality rate was 17% and did not correlate with the strain. Hib and b- variant isolates belonged to ST-6, whereas serotype a isolates belonged to the ST-23 clonal complex. Serotype a appeared to emerge during the 2000s. Non-encapsulated isolates were non-clonal and distinct from the encapsulated isolates. Ampicillin-resistant isolates were either of serotype b or were non-encapsulated, and all of them were β-lactamase-positive but amoxicillin-clavulanic acid susceptible. MAIN CONCLUSIONS Although Hi meningitis became a relatively rare disease in Rio de Janeiro after the introduction of the Hib conjugate vaccine, the isolates recovered from patients have become more diverse. These results indicate the need to implement an enhanced surveillance system to continue monitoring the impact of the Hib conjugate vaccine.

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.

Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines / Distribución de serotipos de neumococos aislados de pacientes pediátricos con otitis media aguda e infecciones invasivas y su cobertura potencial a través de vacunas conjugadas

A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AÜM) and invasive infections (INV). Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326) were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.

Se realizó un estudio prospectivo descriptivo sobre la distribución de serotipos de neumococos aislados de niños con otitis media aguda (OMA) y con infecciones invasivas (INV) en un período de 16 meses. Se incluyeron 89 niños con INV neumocócicas y 324 con un primer episodio de OMA. Trescientos cuarenta y seis patógenos se aislaron de las secreciones de oído medio obtenidas de 250 pacientes. Se identificaron 30 serotipos y los más prevalentes fueron el 14, 19A, 9V, 3, 19F, 6A, 23F y 18C en OMA y el 14, 1, 19A, 5, 12F, 6B y 18C en INV. La cobertura potencial con la vacuna PCV10 sería de 46,5 % y 60,7 % para neumococos involucrados en OMA y en INV, respectivamente; con la PCV13, esta sería de 71,7 % y 73 %. La PCV10 conjugada con una proteína de Haemophilus tendría una cobertura inmunológica del 39,9 % para OMA, contra una cobertura del 18,5 % de la PCV13. Sin embargo, las diferencias en la prevención de INV fueron determinantes a la hora de considerar incorporarla al calendario nacional de vacunación para niños menores de 2 años en la Argentina.

Streptomycin induced protein expression analysis in Mycobacterium tuberculosis by two-dimensional gel electrophoresis & mass spectrometry.

Background & objectives: The resistance of Mycobacterium tuberculosis to streptomycin, a core drug for treatment of category II tuberculosis (TB) has posed a major challenge to the health providers as well as research workers worldwide and has severely compromised the therapeutic options. A significant proportion of streptomycin resistant M. tuberculosis isolates failed to show mutations in conventional targets like rpsL and rrs. Although efflux, permeability, etc. are also known to contribute, yet a substantial proportion of isolates remains resistant suggesting involvement of other unknown mechanism. A resistant isolate may show altered gene as well as protein expression under drug induced conditions and a whole cell proteome analysis under induced conditions might help in further understanding the mechanisms of drug resistance. The present study was therefore designed with the objective to identify proteins related to streptomycin resistance in M. tuberculosis isolate grown in presence and absence of streptomycin (SM). Methods: A clinical isolate of M. tuberculosis from Mycobacterial Repository Centre at the Institute (NJIL & OMD), Agra was grown in Sauton’s medium for 36 h with/without subinhibitory concentration of the drug (2 μg/ml) and the cell lysate of isolates was prepared by sonication and centrifugation. Two-dimensional (2D) gel electrophoresis was employed to study the protein profile. The selected proteins were finally identified by MALDI-TOF mass spectrometry. Results: Our study revealed eight inducible proteins (DnaK, fabG4, DNA-binding, hypothetical, two 14 kDa antigen and two 10 kDa chaperonin) that were upregulated in the presence of drug. Interpretation & conclusion: This preliminary study has thrown light on whether or not and how the resistant isolate responds to streptomycin at its non-toxic but sub-inhibitory concentration. An in-depth study of the upregulated proteins will give an insight into probable sites of drug action other than established primary sites.

Relación costo-efectividad de la vacuna contra Haemophilus influenzae tipo b en niños menores de dos años de edad en Colombia / The cost-effectiveness of Haemophilus influenzae type b vaccine for children under 2 years of age in Colombia

OBJETIVOS: Las vacunas conjugadas contra Haemophilus influenzae tipo b (Hib) son la herramienta más importante para prevenir la mayoría de las enfermedades invasoras producidas por dicho patógeno, pero debido a su costo, aún no se han introducido mundialmente de manera masiva. En el presente estudio se determinó la relación costo-efectividad de una vacuna contra Hib para prevenir la neumonía y la meningitis bacterianas en niños menores de 2 años en Colombia. MÉTODOS: Se estimaron los costos directos e indirectos de la neumonía y la meningitis hospitalaria y siguiendo las recomendaciones de la Organización Mundial de la Salud (OMS), la relación costo-efectividad de los programas de vacunación contra Hib. Se estimaron también las razones de costos por caso evitado de enfermedad invasora por Hib y el costo por año de vida salvado en dos situaciones hipotéticas: con vacunación contra Hib (cobertura vacunal: 90 por ciento) y sin vacunación. RESULTADOS: El costo medio del tratamiento hospitalario de un caso de neumonía fue de 611,5 dólares estadounidenses (US$) (intervalo de confianza del 95 por ciento [IC95 por ciento]: 532,2 - 690,8), el costo medio del tratamiento hospitalario de un caso de meningitis fue de US$ 848,9 (IC95 por ciento: 716,8 - 981,0) y el costo por caso evitado de enfermedad invasora por Hib, de US$ 316,7 (IC95 por ciento: 294,2 - 339,2). La relación costo-efectividad en la hipótesis con vacunación fue de 2,38, frente a 3,81 en la hipótesis sin vacunación. CONCLUSION: La aplicación de un programa adecuado de vacunación contra Hib en Colombia puede prevenir cerca de 25 000 casos de enfermedad invasora por año, lo que representa un ahorro de por lo menos US$ 15 millones anuales. Además, puede evitar cerca de 700 defunciones y salvar anualmente 44 054 años de vida.

OBJECTIVE: Conjugate vaccines are the best public health tools available for preventing most invasive diseases caused by Haemophilus influenzae type b (Hib), but the high cost of the vaccines has so far kept them from being introduced worldwide. The objective of this study was to estimate the cost-effectiveness of introducing Hib conjugate vaccines for the prevention of meningitis and pneumonia among children under 2 years of age in Colombia. METHODS: We estimated the direct and indirect costs of managing in-hospital pneumonia and meningitis cases. In addition, following the recommendations of the World Health Organization, we assessed the cost-effectiveness of Hib vaccination programs. We also estimated the costs for preventing Hib cases, and the cost per year of life saved in two hypothetical situations: (1) with vaccination against Hib (with 90 percent coverage) and (2) without vaccination. RESULTS: The average in-hospital treatment costs were US$ 611.50 (95 percent confidence interval (95 percent CI) = US$ 532.2 to US$ 690.8) per case of pneumonia and US$ 848.9 (95 percent CI = US$ 716.8 to US$ 981.0) per case of meningitis. The average cost per Hib case prevented was US$ 316.7 (95 percent CI = US$ 294.2 to US$ 339.2). In terms of cost-effectiveness, the cost would be US$ 2.38 per year of life saved for vaccination, versus US$ 3.81 per year of life saved without vaccination. CONCLUSION: Having an adequate Hib vaccination program in Colombia could prevent around 25 000 cases of invasive disease per year, representing a cost savings of at least US$ 15 million annually. Furthermore, the program could prevent some 700 deaths per year and save 44 054 years of life per year.

Acute bacterial meningitis in Qatar

To study the changes in the epidemiology, clinical and bacteriological profiles of bacterial meningitis in the era of the Haemophilus influenzae type b [Hib]vaccine and pneumococcus resistance. This is a retrospective study of children aged <12 years admitted to the Hamad Medical Corporation, Qatar between January 1998 through December 2002 with positive cerebrospinal fluid culture. We described 64 patients with culture proven bacterial meningitis. In infants <3 months [n=29 [45%]], the most common organism was Group B Streptococcus [GBS] [20%]. Children >3 months [n=35 [55%]]; Hib [25%] and Streptococcus pneumoniae [STP] [20%] were the most common organisms before introduction of Hib vaccination. A significant drop of Hib infections were noticed after introduction of the vaccine. Fever, neck stiffness, seizure, vomiting, and bulging fontanel were the most frequent presenting features. Group B Streptococcus were sensitive to ampicillin and cefotaxime with no resistance detected. Forty percent of STP isolates were resistant to penicillin and 12% were resistant to ceftriaxone. Fifty percent of Hib were resistant to ampicillin; while none of Hib were resistant to ceftriaxone. No case of Listeria monocytogenes meningitis was diagnosed. Morbidity was 28%, and one patient expired [2%] after Klebsiella pneumoniae meningitis. Streptococcus pneumoniae was associated with the highest morbidity [62%] while Hib had zero morbidity in our patients. Bacterial meningitis is a serious illness with a significant morbidity and mortality. Haemophilus influenzae type b infection decreased which indicated an effective vaccination. As there is 12% bacterial resistance of STP reported against ceftriaxone; We recommend Cefotaxime for infants <3 months while ceftriaxone plus vancomycin as empiric therapy for older patients with community acquired bacterial meningitis. A pneumococcal vaccination may further decrease the incidence of meningitis in our community. A continuos surveillance to detect changes in the microbiology of organisms causing bacterial meningitis or their sensitivity in our community is essential to update these recommendations

Introducing new vaccines in developing countries: concepts and approaches to estimating burden of Haemophilus influenzae type b-associated disease.

In the past 30 years, great strides have been made in immunizing infants and children routinely in developing countries under the Expanded Programme on Immunization. Despite this, the introduction of Haemophilus influenzae type b (Hib) vaccines has progressed rather slowly compared to previously-introduced vaccines for infant immunizations. This slower uptake has been attributed partly to the need for data on the burden of invasive Hib disease. To understand this need, conceptual underpinnings and prerequisites were explored for Hib disease-burden studies. Methodological approaches were also reviewed for conducting Hib disease-burden studies that may be considered in developing countries. Potential studies span a range of designs that provide varying levels of clinical, laboratory and epidemiologic evidence of the burden of invasive Hib disease. Carefully-conducted studies can lay the foundation for complementary studies of long-term disability due to invasive Hib disease, national economic analysis, and field evaluations of vaccine. Studies done in collaboration with national agencies and clinical investigators will maximize study value and provide critical data for national decision-makers who make choices regarding the introduction of Hib vaccines.

Aislamiento de distintos serotipos de Haemophilus influenzae en muestras profundas de pacientes pediátricos / Isolation of Haemophilus influenzae serotypes from sterile sites in sick children

Haemophilus influenzae (Hi) es responsable de diversas enfermedades humanas como sepsis, meningitis, celulitis y osteoartritis. En este trabajo se investigó la recuperación de distintos serotipos de Hi en muestras profundas de pacientes pediátricos. Se estudiaron 179 aislamientos de 146 niños durante el periodo 1996-2002 en el Laboratorio de Microbiología del Hospital de Niños Superiora Sor María Ludovica, Argentina. La distribución de los serotipos fue la siguiente: 1 a, 112 b, 1 c,1 d, 4 e, 3 f y 24 no tipificables. A partir del establecimiento de la estrategia de vacunación universal anti Hi b en 1998 se observa una disminución notable del serotipo b y un aumento relativo de otros y no tipificables.

Haemophilus influenzae (Hi) is the causative agent of several human diseases such as sepsis, meningitis, celulitis, and osteoarthritis. We investigated the isolation of Hi serotypes from sterile sites in sick children. One hundred and seventy nine strains from 146 patients were studied, period 1996-2002, at the Microbiology Laboratory, Hospital de Niños Superiora Sor María Ludovica, Argentina. The serotype distribution was:1 a, 112 b,1 c,1 d, 4 e, 3 f y 24 no typable. Since the beginning of universal Hi b vaccination in 1998, we have observed the fast decrease of serotype b and a relative increase of other serotypes.

El uso de la radiografía de tórax para la vigilancia de neumonías bacterianas en niños latinoamericanos / The use of chest X-rays for surveillance of bacterial pneumonias in children in Latin America

La División de Vacunas e Inmunización de la Organización Panamericana de la Salud (OPS) está promoviendo la vigilancia epidemiológica de neumonías bacterianas en niños latinoamericanos, con el objetivo de generar pruebas científicas que sustenten futuras decisiones de control mediante vacunas en los países de la Región. Como es poco frecuente que el diagnóstico de estas enfermedades abarque la documentación bacteriológica del agente causal, los estudios de este tipo que se realizan en el mundo aceptan la imagen radiológica de consolidación alveolar como criterio confirmatorio de una neumonía presuntamente bacteriana. En este informe se examinan la racionalidad teórica y los requisitos necesarios para utilizar la radiología de tórax como instrumento para la vigilancia epidemiológica de neumonías bacterianas. Además, se ofrece un resumen de las actividades realizadas en dos años de trabajo conjunto entre el Centro para Vacunas en Desarrollo, en Chile, y la División de Vacunas e Inmunización de la OPS. Durante ese período se fomentó el estudio epidemiológico de las neumonías bacterianas en niños latinoamericanos utilizando los criterios y definiciones acordados a escala internacional, así como herramientas y soluciones prácticas ajustadas a la realidad de la Región. Las actividades desarrolladas hasta ahora evidencian la necesidad y factibilidad de estandarizar la interpretación de las radiografías de tórax para utilizarlas en estudios epidemiológicos

Haemophilus influenzae type b diseases in children: a pre-vaccination study

Haemophilus influenzae type b [Hib] can now be prevented by vaccination. We present the clinical and laboratory characteristics of acute invasive H. influenzae diseases in children admitted over a 4-year period to a tertiary paediatric ward of the Al-Ain medical district hospital, before vaccination became available in the United Arab Emirates. In all, 38 children had bacteriologically proven H. influenzae invasive diseases and all the isolates were serotype b. Meningitis was diagnosed in 60.5% of the children and 66% of the studied children were under 12 months. There were no deaths but substantial morbidity occurred in 12 children

A review of Hib epidemiology in Asia.

Meningitis due to an invasive Haemophilus influenzae type b (Hib) infection, has been previously perceived to be relatively uncommon in Asia. However, the incidence of disease and its impact may have been underestimated. In addition to a lack of microbiological facilities in some hospitals, difficulties in culturing the organism and the widespread use of antibiotics may have hidden the true incidence of the disease in some countries. Furthermore, the reported disease burden probably underestimates the incidence of Hib pneumonia. The epidemiology of invasive Hib disease for various Asian nations is reviewed in this paper. Hospital-based studies show that Hib is a major cause of bacterial meningitis and/or pneumonia in the Philippines, India, Thailand, Malaysia, Indonesia and Vietnam. Singapore and Hong Kong have a low incidence of infection compared with Western and other Asian nations. This low incidence is not due to a higher level of natural protective antibodies, but may be related to an interaction between environmental and genetic factors. Therefore the widespread belief that Hib infection is unimportant in Asia does not refer to Asia as a whole and possibly to Chinese patients only, and failure to recognize this has serious implications. The inclusion of Hib vaccine in the routine infant immunization schedule in many industrialized nations has significantly reduced the incidence of invasive disease. Recent studies have shown Hib vaccination is also effective in preventing invasive disease in children in developing countries. While population-based data may be required to confirm the need for public-funded infant Hib immunization in Asia, its introduction in countries with a high incidence of Hib meningitis and/or pneumonia has the potential to significantly improve pediatric health and survival.