RESUMO
We evaluated the functional activities of antibodies, serum bactericidal activity (SBA), and immunoglobulin G (IgG) antibody avidity indices, using sodium thiocyanate (NaSCN) elution, elicited after vaccination with fractional doses of the Haemophilus influenzae type b conjugate (polyribosylribitol phosphate [PRP] conjugated to tetanus toxoid [PRP-T]) vaccine. A cohort of 600 infants from the Dominican Republic were randomized to receive one of three regimens of the PRP-T vaccine at ages 2, 4, and 6 months: full doses (10 microg of PRP antigen), one-half doses (5.0 microg), and one-third doses (3.3 microg) (J. Fernandez et al., Am. J. Trop. Med. Hyg. 62:485-490, 2000). Sixty serum samples, collected at age 7 months, with > or =2.0 microg of anti-PRP IgG per ml were randomly selected for avidity determinations. Geometric mean IgG concentrations were 13, 14, and 17 microg/ml for infants who received the full-dose (n = 19), one-half-dose (n = 19), and one-third-dose (n = 22) regimens, respectively. SBA geometric mean titers (1/dilution) were 85.0, 82.0, and 76.1 in sera from infants receiving the full-, one-half-, and one-third-dose regimens, respectively. Avidity indices (mean +/- standard error weighted average of NaSCN molar concentration x serum dilution factor) were 71.9 +/- 9.4, 123.6 +/- 26.8, and 150.9 +/- 24.9 for the full-, one-half-, and one-third-dose regimens, respectively. Upon comparison, the only significant difference (P = 0.024) found was a greater avidity index for sera from infants receiving the one-third-dose regimen than for sera from infants receiving the the full-dose regimen. We conclude that fractional doses elicit similar functional antibody activities in infants with > or = 2 microg of anti-PRP IgG per ml, corresponding to 89, 90, and 97% of infants receiving three doses of either the full concentration or one-half or one-third of the labeled concentration, respectively. This approach offers an alternative strategy for the prevention of H. influenzae type b disease in countries with limited resources.
Assuntos
Anticorpos Antibacterianos/sangue , Toxoide Diftérico/administração & dosagem , Toxoide Diftérico/imunologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Haemophilus influenzae/imunologia , Estudos de Coortes , Países em Desenvolvimento , Toxoide Diftérico/economia , República Dominicana , Infecções por Haemophilus/imunologia , Vacinas Anti-Haemophilus/economia , Custos de Cuidados de Saúde , Humanos , Imunoglobulina G/sangue , LactenteRESUMO
Concentrations of serum anti-Haemophilus influenzae type b (anti-Hib) capsular polysaccharide (CPS) >/=0.15 and >/=1.0 microgram/mL are widely used as surrogates for protection against invasive Hib disease. However, the relationship between serum anti-Hib CPS following immunization and protection against colonization is not known, making it difficult to evaluate new Hib vaccines or combination vaccines. In the Dominican Republic, nasopharyngeal swabs were collected from 546 9-month-old infants who had received Hib conjugate vaccine at ages 2, 4, and 6 months and from 600 unvaccinated infants of the same age. The prevalence of Hib colonization was lower among vaccinated infants than among unvaccinated infants (0.9% vs. 2.3%). Among vaccinated infants, protection against colonization was significantly correlated with anti-Hib CPS concentrations >/=5 microgram/mL 1 month following the third dose of vaccine. These results suggest that the concentration of serum anti-Hib CPS needed for protection against colonization is greater than that needed for protection for invasive disease.
Assuntos
Anticorpos Antibacterianos/sangue , Cápsulas Bacterianas/imunologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/imunologia , Haemophilus influenzae/imunologia , Imunoglobulina G/sangue , Polissacarídeos Bacterianos/imunologia , Humanos , Lactente , VacinaçãoRESUMO
OBJECTIVES: To report the epidemiology of invasive Haemophilus influenzae type b (Hib) disease in high-risk Alaska Native infants before and after universal infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996 after changing Hib vaccine type. STUDY DESIGN: Statewide laboratory surveillance for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib carriage studies were conducted in 1997 and 1998. RESULTS: The invasive Hib disease rate in Alaska Natives decreased from 332 cases per 100,000 children <5 years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as 9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native children was <1%. CONCLUSIONS: Although Hib disease has decreased in Alaska, the rate of Hib disease and carriage in rural Alaska Natives did not decrease to the same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol phosphate-outer-membrane protein conjugate vaccine for the first vaccine dose is critical to disease control in this population with continued transmission in infants <6 months of age. The ability to eliminate Hib carriage and disease may be affected by population characteristics, vaccination coverage, and Hib vaccine type used. This may pose a challenge to global elimination of Hib.
Assuntos
Portador Sadio , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus , Haemophilus influenzae tipo b , Orofaringe/virologia , Vacinas Conjugadas , Adolescente , Alaska/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/etnologia , Humanos , Lactente , Inuíte/estatística & dados numéricos , Vigilância da População , Fatores de Risco , Saúde da População Rural , VacinaçãoRESUMO
Quantifying the local burden of disease is an important step towards the introduction of new vaccines, such as Haemophilus influenzae type b (Hib) conjugate vaccine. We adapted a generic protocol developed by the World Health Organization for population-based surveillance of bacterial meningitis. All hospitals that admit paediatric patients with meningitis in the National District, Dominican Republic were included in the system and standard laboratory methods were used. The system identified 111 cases of confirmed bacterial meningitis. Hib was the leading cause of bacterial meningitis, followed by group B streptococcus, S. pneumoniae, and N. meningitidis. Unlike hospital-based case series, this population-based system was able to calculate incidence rates. The incidence of Hib meningitis was 13 cases per 100,000 children < 5 years old. The data from this study were used by the Ministry of Health to support the introduction of routine Hib vaccination and will be used to monitor its effectiveness.
Assuntos
Vacinas Anti-Haemophilus , Haemophilus influenzae , Meningite por Haemophilus/epidemiologia , Pré-Escolar , República Dominicana/epidemiologia , Feminino , Haemophilus influenzae/imunologia , Política de Saúde , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Meningite por Haemophilus/prevenção & controle , Formulação de Políticas , Vigilância da PopulaçãoRESUMO
To assess the immunogenicity of more economical regimens of Haemophilus influenzae type b (Hib) conjugate vaccine, a randomized trial of fractional doses of polyribosylribitol phosphate-tetanus toxoid (PRP-T) Hib vaccine was undertaken in the Dominican Republic. Six hundred children were assigned to one of six regimens with PRP-T vaccine: full-dose, half-dose, and one-third-dose of Hib vaccine given separately or combined with diphtheria, tetanus, and pertussis (DTP) vaccine at ages 2, 4, and 6 months. Regimens that elicited antibody levels > 1.0 microg/mL in >70% of children and < or = 0.15 microg/mL in > 90% of children were considered acceptable. At 1 month post Dose 3, all regimens met the criteria for acceptable response. Among those who received Hib as a separate injection, geometric mean concentrations of anti-PRP bodies (GMCs) at age 1 month post Dose 3 were 11.2, 11.9, and 16.3 in the full, half, and one-third dose groups, respectively. Among those who received Hib and DTP combined, the GMCs were 6.4, 5.2, and 5.7 in the full-, half-, and one-third-dose groups respectively.
Assuntos
Anticorpos Antibacterianos/biossíntese , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/imunologia , Anticorpos Antibacterianos/sangue , Relação Dose-Resposta Imunológica , Ensaio de Imunoadsorção Enzimática , Humanos , Lactente , Método Simples-Cego , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologiaRESUMO
OBJECTIVES: To determine the burden of pneumonia requiring hospitalization in infants and young children preventable by vaccination against Haemophilus influenzae type b (Hib). DESIGN: Vaccination centers in Santiago, Chile, were randomly selected to administer PRP-T, an Hib conjugate vaccine, combined with diphtheria-tetanus toxoids-pertussis (DTP) vaccine or DTP alone. SUBJECTS: Infants who received > or =2 doses of DTP or DTP and Hib conjugate vaccine combined. MAIN OUTCOME MEASURES: Pneumonia episodes leading to hospitalization accompanied by indicators of likely bacterial infection including radiologic evidence of alveolar consolidation or pleural effusion, an elevated erythrocyte sedimentation rate (> or =40 mm/h) or bronchial breath sounds on auscultation. RESULTS: In participants age 4 to 23 months, PRP-T reduced the incidence of pneumonia associated with alveolar consolidation or pleural effusion by 22% (95% confidence interval, -7 to 43) from 5.0 to 3.9 episodes per 1000 children per year. When the pneumonia case definition included any of the following, alveolar consolidation, pleural effusion, erythrocyte sedimentation rate > or =40 mm/h or bronchial breath sounds, PRP-T provided 26% protection (95% confidence interval, 7 to 44) and prevented 2.5 episodes per 1000 children per year. CONCLUSIONS: Hib vaccine provides substantial protection against nonbacteremic pneumonia, particularly those cases with alveolar consolidation, pleural effusion or other signs of likely bacterial infection. Hib vaccination prevented approximately 5 times as many nonbacteremic pneumonia cases in infants as meningitis cases, thus indicating that the largest part of the effect of Hib vaccination might be undetectable by routine culture methods.
Assuntos
Vacinas Anti-Haemophilus , Hospitalização/estatística & dados numéricos , Pneumonia/epidemiologia , Toxoide Tetânico , Vacinas Conjugadas , Chile/epidemiologia , Efeitos Psicossociais da Doença , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacinas Anti-Haemophilus/administração & dosagem , Humanos , Incidência , Lactente , Pneumonia/fisiopatologia , Pneumonia/prevenção & controle , Estatísticas não Paramétricas , Toxoide Tetânico/administração & dosagem , Vacinas Conjugadas/administração & dosagemRESUMO
Hib conjugate vaccines are widely used in the industrialized world, but are just now beginning to be introduced into other countries. To identify factors facilitating rapid global introduction, we evaluated the decision-making process, mode of introduction, effectiveness, and impact on the immunization program of Hib conjugate vaccine introduction in four non- industrialized countries through site visits and use of a standardized questionnaire. The key promoters of Hib introduction were the pediatric community and ministries of health. Local surveillance and severity data were critical in the decision to adopt Hib vaccine. Assistance with surveillance, introduction guidelines, educational material, tenders, and funding is needed to accelerate wider adoption.
Assuntos
Países em Desenvolvimento , Vacinas Anti-Haemophilus/administração & dosagem , Programas de Imunização , Chile , Tomada de Decisões , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Saúde Global , Infecções por Haemophilus/prevenção & controle , Haemophilus influenzae/imunologia , Humanos , Lactente , Recém-Nascido , Kuweit , Catar , Uruguai , Vacinas Conjugadas/administração & dosagemRESUMO
OBJECTIVE: To determine the burden of Haemophilus influenzae type b (Hib) disease, the safety and immunogenicity of Hib conjugate vaccine, the practicality of combining Hib conjugate and diphtheria-tetanus-pertussis vaccines and the effectiveness of routine vaccination. STUDY DESIGNS: A series of studies were carried out involving infants and children in Santiago, Chile. The study designs included retrospective surveillance, cost-benefit analysis, randomized placebo-controlled trials of safety and immunogenicity and a Phase IV postlicensure evaluation of vaccine effectiveness. RESULTS: The studies included in this stepwise process showed that Hib invasive disease was a significant public health problem with a substantial economic burden; that combining Hib conjugate and diphtheria-tetanus-pertussis vaccines was practical, safe and elicited a strong immunologic response; and that the combined formulation afforded a high level of protection against invasive Hib disease (90% effectiveness). CONCLUSIONS: In July, 1996, Chile became only the third newly industrializing country to introduce routine Hib conjugate vaccination. New vaccines, such as Hib conjugates, will be more expensive than existing ones. The stepwise process used in Chile may serve as an example for the evaluation of new vaccines in nonindustrialized countries.
Assuntos
Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/imunologia , Haemophilus influenzae tipo b/imunologia , Toxoide Tetânico/imunologia , Vacinação/estatística & dados numéricos , Vacinas Conjugadas/imunologia , Pré-Escolar , Chile/epidemiologia , Análise Custo-Benefício , Países Desenvolvidos , Infecções por Haemophilus/economia , Infecções por Haemophilus/epidemiologia , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/economia , Humanos , Lactente , Ensaios Clínicos Controlados Aleatórios como Assunto , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/economia , Vacinação/economia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/economiaRESUMO
BACKGROUND: Whether herd immunity will occur with widespread Haemophilus influenzae type b (Hib) vaccination in developing countries is dependent on whether the vaccines are capable of reducing carriage in these settings. However, few population-based studies of Hib carriage in developing countries exist. METHODS: To study Hib carriage in the Dominican Republic, we collected nasopharyngeal swab specimens from a population-based sample of 983 children 0 to 47 months old in a periurban area of Santo Domingo. RESULTS: Nasopharyngeal swabs of 76 (7.7%) children were positive for Hib. Hib carriage varied by age group with a low of 1.5% among 0 to 5 month olds, a peak of 12.5% in 6 to 11 month olds and prevalence rates of 6.0, 7.9 and 9.8% among 1-, 2- and 3-year-olds, respectively. Hib carriage was 51% lower among currently breast-fed 6 to 11 month olds than among those not currently breast-fed (18.2% vs. 9.0%; P=0.08). CONCLUSIONS: Infants and young children in Santo Domingo have high rates of Hib carriage, characterized by an early peak in carriage that corresponds with the peak of risk for Hib meningitis. The ability of Hib vaccines to diminish carriage to levels that will effectively reduce transmission and lead to herd immunity in this setting needs to be determined.
Assuntos
Portador Sadio/epidemiologia , Infecções por Haemophilus/epidemiologia , Haemophilus influenzae tipo b , Pré-Escolar , Países em Desenvolvimento , República Dominicana/epidemiologia , Haemophilus influenzae tipo b/isolamento & purificação , Humanos , Lactente , Nasofaringe/microbiologiaRESUMO
BACKGROUND: The cost of Haemophilus influenzae type b (Hib) conjugate vaccines has limited their use in non-industrialised countries. To identify more economical vaccination schedules, we carried out a randomised trial of the immunogenicity of alternative regimens to the standard three-dose series. METHODS: 627 Chilean infants were randomly allocated to one of four regimens with either Hib polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) or Hib oligosaccharide-diphtheria mutant toxoid conjugate vaccine (PRP-CRM197), for a total of eight groups. All infants receive diphtheria-tetanus-pertussis (DTP) vaccine at ages 2, 4, and 6 months. The regimens included three full doses, three fractional doses consisting of one half or one third of the full dose, and a regimen of two full doses (at age 4 and 6 months). The primary outcome was the proportion of infants with serum anti-polyribosylribitol phosphate (PRP, the type b capsular polysaccharide) concentrations of 0.15 microg/mL or more at age 8 months. FINDINGS: 93% (95% CI 85-98) of infants vaccinated with three full doses of PRP-T or PRP-CRM197 (95% CI 84-98) achieved anti-PRP concentrations of 0.15 microg/mL or more at age 8 months, compared with 91% (83-96) to 100% (95-100) of infants immunised with any fractional-dose regimen. Of the infants vaccinated with two doses of PRP-T or PRP-CRM197, 99% (93-100) and 87% (77-93) developed anti-PRP concentrations of 0.15 microg/mL or more, respectively. INTERPRETATION: 91% (83-96) to 100% (95-100) of infants immunised with one-half or one-third of a full dose of Hib conjugate developed protective antibody concentrations. Carrier priming with DTP may make two-dose schedules an option in some places. These alternative regimens could bring the cost of Hib vaccines within reach of countries that currently cannot afford them.