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.

The immunological response of Thai infants to haemophilus influenzae type B polysaccharide-tetanus conjugate vaccine co-administered in the same syringe with locally produced diphtheria-tetanus-pertussis vaccine.

OBJECTIVE: Comparing the immunogenicity and reactogenicity of three vaccine combinations. These were GlaxoSmithKline Biologicals' (GSK) Haemophilus influenzae type b vaccine (Hib-TT, Hiberix) administered with the local Government Pharmaceutical Organization's (GPO) diphtheria-tetanus-pertussis whole cell (DTPw) vaccine, Hib-TT mixed with GPO's DTPw vaccine, or Hib-IT mixed with GSKs' DTPw vaccine (Tritanrix). MATERIAL AND METHOD: An open, randomized, controlled, single center study of three hundred and sixty infants. They were randomized into three groups to receive either Hib-TT Hiberix mix with GPOs' DTPw vaccine (group 1), Hib-TT mixed with GPO's DTPw vaccine (group 2), or Hib-TT mixed with GSKs' DTPw vaccine (Tritanrix; group 3) at two, four and six months of age. RESULT: One month after the third dose, all subjects had antibodies level against Hib polyribosylribitol phosphate (PRP) > or = 0.15 microg/ml. All 11 subjects except two (in group 2) had anti-PRP levels > or = 1.0 microg/ml. The geometric mean concentrations were similar in all three groups. Over 96% of the subjects in all three groups demonstrated an immunological response to diphtheria, tetanus, and pertussis antigens. There was no diference among the three groups in terms of severe local reaction and fever. CONCLUSION: The present study showed that the combined vaccines produced an effective antibody response with no increase in reactogenicity compared to separately administrated vaccines.

Vacinação contra Haemophilus influenzae tipo b: proteção a longo prazo / Haemophilus influenzae type b vaccination: long term protection

OBJETIVO: Identificar as evidências sobre o impacto da vacina conjugada para Haemophilus influenzae tipo b (Hib) na epidemiologia da doença invasiva por Hib. FONTE DOS DADOS: Pesquisa nas bases de dados do MEDLINE, LILACS, publicações técnicas de organizações internacionais, diretrizes nacionais e internacionais, nos últimos 15 anos (1991-2005), utilizando os seguintes unitermos: Haemophilus influenzae type b, immunization, impact, effectiveness. Foram incluídas as publicações que apresentaram informação para atender o objetivo deste artigo. Artigos publicados em período anterior ao da pesquisa e citados em referências dos artigos incluídos foram analisados quanto à apresentação de informação de interesse. SíNTESE DOS DADOS: A introdução da vacina conjugada para Hib produziu grande declínio na incidência de casos de doença invasiva por Hib nos diversos países em que seu uso foi incorporado à rotina de vacinação das crianças. No entanto, o ressurgimento de casos com doença invasiva por Hib tem mobilizado vários investigadores na busca das possíveis explicações para esses eventos, bem como a identificação das medidas a serem implementadas para evitar o reaparecimento da doença. CONCLUSÕES: O uso da vacina conjugada para Hib em escala populacional tem sido extremamente efetivo. No entanto, mudanças no esquema vacinal poderão ser necessárias para a manutenção do controle da doença invasiva por Hib, frente ao atual cenário epidemiológico das infecções pelo Hib.

An epidemiological study of Haemophilus influenzae at a Brazilian Day Care Center

Day care centers are a relatively new phenomenon in Brazil that bring together large numbers of young children susceptible to contagious diseases. Haemophilus influenzae (Hi) is an important infection in the age range of those attending day care centers. In the present study, the carriage rate of haemophilus influenzae was identified in 38 day care attendees age 6 to 37 months, and 23 staff members, at a day care center in Ribeirao Preto - Sao Paulo, in 1997. To identify the carriers, two nasopharyngeal swabs were collected; one in july and one in december. The rate of H. influenzae carriers among the children was 77 percent. Only 2 of 23 staff members (9 percent) had Hi. Among the children, there were 58 isolates in the two sampling periods; 6 of the Hi were serotype b, 1 was serotype e, and 48 isolates were non-typeable. Two were identified as H. parainfluenzae. One adult had a non-typeable Hi and 1 had H. paraphrohaemolyticus. Three of the 6 children with type B had received a conjugate vaccine against H. influenzae type b, but they still carried this bacterium in the nasopharynx (50 percent). Forty ribotype patterns were found among the isolates, showing a high exchange rate of nontypeable H. influenzae carriers. The results indicate that, because of the high and changing biotype of Hi carriage, day care centers should be carefully monitored as potential point source of Hi disease in the community.

Age- and cause-specific childhood mortality in Lombok, Indonesia, as a factor for determining the appropriateness of introducing Haemophilus influenzae type b and pneumococcal vaccines.

Using age and cause-specific childhood mortality in Lombok, Indonesia, as a factor for determining the appropriateness of introducing Haemophilus influenzae type b (Hib) and pneumococcal vaccines, the study describes a cross-sectional, hamlet-level mortality survey in 40 of 305 villages in Lombok Island, Indonesia. Causes of death were assessed with a standardized verbal-autopsy questionnaire. One thousand four hundred ninety-nine births and 141 deaths occurring among children aged less than 2 years were identified, with 43% of deaths occurring during the first 2 months of life. The infant mortality rate was 89 (95% CI: 75, 104) per 1,000 live-births. All mortality rates are reported per 1,000 live-births. To examine children whose deaths could potentially have been prevented through vaccination with Hib or pneumococcal vaccine, deaths due to acute respiratory infection (ARI) and central nervous system (CNS) infections among children, aged 2-23 months, were analyzed. ARI and CNS infections caused 58% (mortality rate: 31 per 1,000 live-births; 95% CI: 23, 41) and 17% (mortality rate: 9 per 1,000 live-births; 95% CI: 5, 16), respectively, of all deaths within this age group. Between the ages of 2 and 23 months, 5% of all babies born alive died of ARI, and another 1% died of CNS infections. Our results indicate that current efforts to reduce childhood mortality should focus on reducing ARI and meningitis. These efforts should include evaluating the impact of Hib and pneumococcal vaccines within the routine Expanded Programme on Immunization system.

Immunogenicity and tolerance of H. influenzae type b, tetanus toxoid conjugate vaccine given concurrently or in combination.

The present prospective, open, controlled, randomised comparative trial was undertaken to evaluate the sero response and side effects of PRP-T Conjugate Vaccine (ACT-HIB) in infants and children aged 2 months and 16-24 months. Fifty four babies aged 2 months formed group A, 56 children aged 16-24 months formed group B. Groups A and B were further subdivided into two sub groups each destined to receive either PRP-T vaccine in association with DPT vaccine at different sites (I) or PRP-T and DPT both vaccines at the same site mixed in the same syringe (II). Group A received 3 doses at 2, 3 and 4 months of age and group B received one dose between 16-24 months. The Geometric mean titres of Anti PRP antibodies observed in primary immunisation schedule (A) and single dose vaccination schedule (B) were comparable and significantly higher to prevaccination titres. A serum anti PRP level of > 1.0 mcg/ml after immunisation is believed to correlate with long term protection. Ninety-six percent of infants in Group A and 98% in Group B achieved titres > 1.0 mcg/ml. The side effects were minimal, local and were comparable between the study and control groups, suggesting that PRP-T vaccine is highly immunogenic and well tolerated in Indian infants and children.

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.

Haemophilus influenzae type b vaccine in India: need and timing, immunogenecity and tolerance.

OBJECTIVE: (i) To assess the natural immunity and susceptibility to Haemophilus influenzae type b (Hib) infections in children in India. (ii) To study the immunogenecity and tolerance of Hib vaccine (ACTHIB) in young infants. DESIGNS: (i) Cross sectional study. (ii) Prospective trial. SETTING: Well baby and immunization clinics. METHODS: (i) PRP antibody titers against Hib estimated in 172 healthy infants and children aged 1 month to 10 years. (ii) Antibody titres estimated before and after ACTHIB vaccine given with primary immunization (age group 6 to 8 weeks) in 50 babies. RESULTS: (i) Naturally protective levels of Hib antibodies found in less than 20% of infants under one year, but in over 80% above 4 years. (ii) Seroconversion after ACTHIB vaccination was 100% with very high protective levels. There were no significant adverse reactions. CONCLUSIONS: ACTHIB vaccine proved to be safe and highly immunogenic. As susceptibility to Hib is highest in the first year of life, the vaccine should be recommended in the primary immunization schedule (combined with DPT). The very high titers achieved suggest the possibility of decreasing the number of doses or the amount of antigen to reduce the prevalent high cost.

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.

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

Infecciones severas por Haemophilus influenzae / Haemiphilus influenzae: severe systemic diseases

Haemophilus influenzae es el más importante microorganismo que causa serias infecciones bacterianas en niños. Un importante factor asociado con el riesgo de enfermedad invasiva es la edad, con un pico de incidencia entre los 6 y 23 meses. Esta revisión tiene como finalidad presentar al médico pediatra una actualización sobre el amplio espectro de infecciones invasivas por haemophilus influenzae.