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.

Inflammatory response of Haemophilus influenzae biotype aegyptius causing Brazilian Purpuric Fever

The Brazilian Purpuric Fever (BPF) is a systemic disease with many clinical features of meningococcal sepsis and is usually preceded by purulent conjunctivitis. The illness is caused by Haemophilus influenza biogroup aegyptius, which was associated exclusively with conjunctivitis. In this work construction of the las gene, hypothetically responsible for this virulence, were fusioned with ermAM cassette in Neisseria meningitidis virulent strains and had its DNA transfer to non BPF H. influenzae strains. The effect of the las transfer was capable to increase the cytokines TNFα and IL10 expression in Hec-1B cells line infected with these transformed mutants (in eight log scale of folding change RNA expression). This is the first molecular study involving the las transfer to search an elucidation of the pathogenic factors by horizontal intergeneric transfer from meningococci to H. influenzae.

Tipificación capsular mediante PCR de aislamientos de Haemophilus influenzae no tipificables por aglutinación / PCR-based capsular typing of Haemophilus influenzae isolates non-typeable by agglutination

Haemophilus influenzae es reconocido como un agente patógeno responsable de infecciones localizadas y sistémicas. Se han descrito 6 tipos de polisacáridos capsulares antigénicamente distintos (a, b, c, d, e, y f ) que se pueden identificar por aglutinación en lámina con antisueros específicos. También existen cepas no capsuladas (NC) fenotípicamente no tipificables (NT). La introducción de la vacuna conjugada produjo una marcada disminución de las enfermedades invasivas causadas por H. influenzae tipo b. En este contexto, la tipificación capsular mediante PCR es el método más apropiado para distinguir las cepas no capsuladas de las mutantes b deficientes en cápsula (b-) y detectar la presencia de cepas pertenecientes a otros serotipos que no puedan ser tipificables por aglutinación. Se determinó el genotipo capsular a 38 aislamientos de Haemophilus influenzae no tipificables por aglutinación, derivados al servicio de Bacteriología Clínica del INEI-ANLIS "Dr. Carlos G. Malbrán" en el período 2002-2004. El 78,9% de los aislamientos provenían de hemocultivos y la mayor parte de ellos estaban asociados a foco respiratorio. El 100% de los aislamientos fueron identificados como H. influenzae no capsulados mediante la técnica de PCR.

Haemophilus influenzae is recognized as a pathogenic agent responsible of localized and systemic infections. Six antigenically different capsular polysaccharide types have been described (a, b, c, d, e, and f ) which can be identified by slide agglutination with specific antisera. Besides there are non capsulated strains that cannot be typed by slide agglutination. The introduction of the conjugated vaccine produced an important reduction of invasive diseases caused by H. influenzae type b. Capsular typing by PCR is the most appropriated method for distinguishing non capsulated strains from capsule deficient type b mutants (b-) and for detecting strains of other serotypes that cannot be detected by slide agglutination. Capsular genotype was studied in 38 isolates of non-typeable Haemophilus influenzae received at INEIANLIS "Dr. Carlos G. Malbrán" between 2002-2004. Of the isolates included in this study 78.9% of them were recovered from blood cultures and most of them were associated with a respiratory focus. By PCR technique 100% of the isolates were identified as non-capsulate H. influenzae and genotype b-was not detected.

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.

Vaccines: World Health Organization versus Federal Drug Administration recommended formula

Vaccines produced in accordance with WHO formulas, differ in concentration from those used in United States according to FDA formulas. We aimed to compare the immunogenicity of both formulas. Infants who were 6 weeks old were randomly put into 3 groups to receive 3 doses of vaccines at 6 weeks, 3 months and 5 months of age. The vaccines consisted of Haemophilus influenzae type b vaccine, diphtheria-tetanus-pertussis and oral polio vaccine. Antibody levels for polyribosylribitol phosphate [PRP], tetanus, diphtheria and poliovirus were measured 1 month after the third dose of vaccines. Although diphtheria and tetanus antigens in the FDA formula are half the concentration of the WHO formula, anti-tetanus and anti-diphtheria antibodies were significantly higher. No difference was found between groups regarding oral poliovirus vaccine

Analise critica sobre o uso das vacinas conjugadas contra o Haemophilus influenzae do tipo b em diferentes paises / Critical analysis about the use of Haemophylus influenzae type b conjugate vaccines in different countries

O Haemophylus influenzae do tipo b (Hib) e um dos principais agentes causadores de doencas invasivas em criancas, tais como meningite, epiglotite, pneumonia e bacteremia. Desde 1987, as vacinas conjugadas contra o Hib vem sendo amplamente utilizadas em diversos paises desenvolvidos, e o sucesso da imunizacao pode ser comprovado pelo rapido desaparecimento das infeccoes graves causadas pelo Hib, apos a introducao da vacinacao de rotina contra o Hib para todas as criancas com idade entre 2 meses e 5 anos. Neste artigo, a autora apresenta uma revisao sobre o impacto epidemiologico da vacinacao contra o Hib, em 4 paises desenvolvidos - Finlandia, Estados Unidos, Inglaterra e Suecia - e analisa as dificuldades relacionadas a introducao desta vacina nos paises em desenvolvimento

Immunogenicity study of Haemophilus influenzae type B conjugate vaccine in Indian infants.

OBJECTIVE: To assess the immunogenicity in Indian infants to Haemophilus influenzae b oligosaccharide conjugate vaccine (HbOC). DESIGN: Prospective multicenter study. SETTING: Pediatric Out Patient Department of general hospitals in Pune and Mumbai. SUBJECTS: 124 full term healthy infants brought for routine DPT/OPV immunization. METHODS: Infants were administered 3 doses of 0.5 ml of HbOC, on the same day as their DPT/OPV immunization, injected intramuscularly on the limb opposite to that where DPT vaccine was administered. Data on local reactions and general symptoms was collected for three days after every dose. The children had their blood collected for assay of anti PRP (polyribosil ribitol phosphate) antibody titers, along with the first injection and one month after the third injection. One hundred and three infants completed the study protocol with two blood collections. RESULTS: The initial geometric mean titers (GMT) of 0.124 mcg/ml rose by 37 times to 4.552 mcg/ml. Ninety eight children (95.1%) had a final titer of > or = 0.15 mcg/ml, the minimum level associated with protection, and 77 children (74.8%) had a final level of > or = 1.0 mcg/ml, a level associated with long term protection. CONCLUSION: HbOC is immunogenic in Indian infants when used as per the locally recommended DPT/OPV immunization schedule.

Evaluation of immunogenicity and tolerance of single dose haemophilus influenzae type B (PRP-T) vaccine.

OBJECTIVE: Evaluation of immunogenicity and acceptability of PRP-T vaccine among the Indian children. DESIGN: Multicentric, open, parallel group, comparative study of Haemophilus influenzae type B vaccine, given as single (Group I) or associated (Group II) with DPT vaccine. SETTING: Five different vaccination clinics. SUBJECTS: 125 children between the age group of 18-24 months. PARAMETERS: Measurement of (i) pre and post vaccination antibody titres of Haemophilus influenze type B specific antibody; (ii) Adverse events; and (iii) Tolerance as graded by the physician. RESULTS: Prevaccination antibody levels were > 0.15 mcg/ml in 56.3% in Group I and 35.7% in Group II. Post-seroconversion was seen in 97% in Group II receiving single and all in Group II (P > 0.05). The vaccine was well tolerated. CONCLUSIONS: The probability of subclinical infection or cross immunity is high in India. ACTHIB vaccine has a good immunogenicity and tolerance and association with DPT does not modify the immunogenicity of ACTHIB vaccine.

Doença invasiva por Haemophilus influenzae B: perspectiva em vacinaçäo / Invasive disease by Haemophilus influenzae B: vaccination's perspective

Os autores apresentam uma revisao da literatura mais recente, quanto aos aspectos clínicos e fisiopatológicos da doença evasiva por Haemophilus influenzae B assim como, consideraçoes a respeito de sua prevençao através de vacinas conjugadas enfatizando a necessidade do engajamento dos profissionais pediatras e infoctologistas na sua indicaçao em nosso meio, assim como hoje rotineiramente é feito nos países desenvolvidos.

La meningitis por haemophilus influenzae tipo b (Hib), su prevención inmunologica una necesidad? / Haemophilus infuenzae type B (HIB) meningitis, immunologic prevention:a necesity

El Hib fue la causa más común de meningitis bacteriana en niños menores de cinco años en los Estados Unidos, antes de ellos disponer de una vacuna efectiva. El H. influenzae es el principal agente causal de meninguitis (50 - 52 por ciento ) en los pacientes admitidos a la clínica infantil Dr. Robert Reid Cabral. El tipo b representa el 90 por ciento de todas las bacterias aisladas en LCR. El 98 por ciento son menores de 5 años y de estos el 90 por ciento tienen menos de 15 meses de edad; este microorganismo produce un 7 por ciento de mortalidad y un 38 por ciento de secuelas neurológicas. El desarrollo de una vacuna efectiva (1970) y su introducción en E.U.A. (1985) además de su aprobación para uso en niños de 2 meses de edad en adelante (1990) provocó un dramático descenso en las infecciones por Hib (85 por ciento 90 por ciento ). Resultados demuestran que la vacunación debe ser considerada en República Dominicana en niños menores de 5 años, ya que es una vacuna segura y efectiva

Reaction of the sera of the Korean children free from Hib invasive diseases against H. influenzae type B capsular polysaccharide antigen

The purpose of our experiment is to examine the level of anti-Haemophilus influenza polysaccharide antibody titer in the Korean population. Using ELISA, the level of Hib-PS antibodies in 384 infants and children who were all free from Hib invasive diseases, was tested. And the blood of 50 mothers within 24 hours of delivery and cord blood from their respective full-term neonates was also tested. The transport of Hib-PS IgG and IgG subclasses in paired sera from mothers and neonates was also measured. The titer of Hib-PS IgG varies with age. At birth the mean optical density of cord blood was 1.028; however, it declined to 0.609 up to 6 months and further decline was noted up to 2 years to 0.488. Then the mean O.D. remained around 0.5 from 3 to 14 years of age. The mean O.D. of Hib-PS IgG in the mothers blood was 0.856. The ratio of mean O.D. of anti-Hib PS IgG antibody in the cord blood to that in the maternal blood was 1.20. The mean optical densities of IgG subclasses were: 1.18 for anti-Hib PS IgG1, 1.07 for anti-Hib PS IgG2, 1.01 for anti-Hib PS IgG3, and 1.09 for anti-Hib PS IgG4. The sera from Korean children of almost all age groups reacted to Hib-PS antigen on ELISA. Also the active transport of anti-Hib PS IgG antibody through placenta was observed. Among four IgG subclasses, only IgG1 transport had significant experimental meaning.

Caracteres biológicos de Hemophilus influenzae aislado de diferentes poblaciones infantiles / Biological characteristics of Haemophilus influenzae isolated from different infantile populations

Las características biológicas de Hemophilus influenzae aisladas de áreas normalmente estériles o de la orofaringe de niños, no han sido descritas en el Uruguay. Esta información tiene importante implicancia en la comprensión de la patogenia de esas infecciones y en los requisitos para lograr una vacuna adecuada. Con tal fin se determinaron los serotipos y biotipos en 54.3 por ciento de las cepas aisladas entre 1986 y 1992. Además en la totalidad de las cepas conservadas (n=311) se investigó la producción de ß lactamasas. Se demostró que la resistecia a los ß lactámicos era poco frecuente (5.9 por ciento ). Las cepas invasivas, recuperadas de la sangre, derrame pleural o LCR, pertenecían en su mayoría, al serotipo b y al biotipo I (83.4 por ciento ). En las infecciones del oído medio predominaron los H. influenzae no tipificables, así como entre las cepas que colonizaban la orofaringe de pacientes y niños sanos, pero en estos casos los biotipos fueron diversos, con 38 por ciento correspondiendo al biotipo II. Las vacunas conjugadas conteniendo polisacárido capsular del serotipo b, prevendrían los cuadros invasivos, pero no se lograría el control de infecciones por otros serotipos y por cepas no tipificables

Deteccao de antigenos bacterianos em pneumonia aguda: metodos de preparacao das amostras de urina, soro e liquido pleural para os testes de imunodiagnostico / Detection of bacterial antigens in acute pneumonia: methods of preparing the urine, serum and pleural fluid samples for immunodiagnostic assays

Foi desenvolvido um metodo de precipitacao de antigenos polissacaridicos de S. pneumoniae e H influenzae tipo b na urina, atraves do tratamento com uma solucao de etnol-acetona 1:1 seguido de um tratamento a quente com EDTA 0,1M. Foram empregadas as tecnicas de contra-imunoeletroforese e latex aglutinacao para a deteccao de antigenos polissacarideos em amostras pareadas de urina e soro e ainda de liquido pleural, de criancas com diagnostico clinico e radiologico de pneumonia aguda. Contra-imunoeletroforese e latex aglutinacao apresentaram melhores indices de sensibilidade em urina do que em soro e tiveram otimo desempenho tanto para urina de volume inicial relativamente pequeno como de grande volume, colhidas antes ou durante os primeiros dias de antibioticoterapia. Os resultados obtidos em contra-imunoeletroforese e latex aglutinacao mostraram que a solucao etanol-acetona 1:1 fornece melhor rendimento na precipitacao de antigeno polissacaridico enquanto que o aquecimento com EDTA diminui a probabilidade de ocorrencia de resultados falso-positivos e de reatividade cruzada entre S. pneumoniae e H. influenzae tipo b. A urina mostrou-se como importante meio de deteccao de antigenos bacterianos no diagnostico de pneumonia bacteriana aguda, principalmente se a antibioticoterapia previa obstrui o crescimento bacteriano nos meios de cultura.

Counter immuno electrophoresis for the early diagnosis of acute pyogenic meningitis.

A total of 123 cases of acute pyogenic meningitis were studied to investigate whether counter current immunoelectrophoresis (CIEP) would facilitate rapid etiological diagnosis when used with other routine methods in a clinical bacteriology laboratory. Of the 123 cases, 53 (43.08 percent) were culture positive. Streptococcus pneumoniae was the commonest etiological agent accounting for 30 (56.6 percent) of the isolates. There were four isolates of Haemophilus influenzae and one of Neisseria meningitidis. High rates of isolation were found from turbid CSF samples, those showing a high polymorphonuclear cellular reaction and from those with a high protein and a low sugar level. CIEP detected antigen in 50 percent of cases of Haemophilus influenzae and 76.7 percent of cases of Streptococcus pneumoniae.