Introduction of a hexavalent vaccine containing acellular pertussis into the national immunization program for infants in Peru: a cost-consequence analysis of vaccination coverage.

BACKGROUND: Infant vaccination coverage rates in Peru have declined in recent years, exacerbated by the COVID-19 pandemic. Introduction of the fully-liquid diphtheria, tetanus, and acellular pertussis (DTaP)-inactivated polio vaccine (IPV)-hepatitis B (HB)-Haemophilus influenzae type B (Hib) hexavalent vaccine (DTaP-IPV-HB-Hib) in Peru's infant National Immunization Program may help improve coverage. We evaluated costs and healthcare outcomes, including coverage, of switching from a pentavalent vaccine containing whole-cell pertussis component (DTwP-HB-Hib) plus IPV/oral polio vaccine (IPV/OPV) to the hexavalent vaccine for the primary vaccination scheme (2, 4 and 6 months). METHODS: The analysis was performed over a 5-year period on a cohort of children born in Peru in 2020 (N = 494,595). Four scenarios were considered: the pentavalent plus IPV/OPV scheme (S1); replacing the pentavalent plus IPV/OPV scheme with the hexavalent scheme (S2); expanded delivery of the pentavalent plus IPV/OPV scheme (S3); expanded delivery of the hexavalent scheme (S4). Vaccine coverage and incidence of adverse reactions (ARs) were estimated using Monte Carlo simulations and previous estimates from the literature. Cases of vaccine-preventable diseases were estimated using a Markov model. Logistical and healthcare costs associated with these outcomes were estimated. Impact of key variables (including coverage rates, incidence of ARs and vaccine prices) on costs was evaluated in sensitivity analyses. RESULTS: The overall cost from a public health payer perspective associated with the pentavalent plus IPV/OPV vaccine scheme (S1) was estimated at $56,719,350, increasing to $61,324,263 (+ 8.1%), $59,121,545 (+ 4.2%) and $64,872,734 (+ 14.4%) in scenarios S2, S3 and S4, respectively. Compared with the status quo (S1), coverage rates were estimated to increase by 3.1% points with expanded delivery alone, and by 9.4 and 14.3% points, if the hexavalent vaccine is deployed (S2 and S4, respectively). In both scenarios with the hexavalent vaccine (S2 and S4), pertussis cases would also be 5.7% and 8.7% lower, and AR rates would decrease by 32%. The cost per protected child would be reduced when the hexavalent vaccine scheme. Incidence of ARs was an important driver of cost variability in the sensitivity analysis. CONCLUSIONS: Implementation of the hexavalent vaccine in Peru's National Immunization Program has a positive public health cost consequence.

Religious affiliation as a driver of immunization coverage: Analyses of zero-dose vaccine prevalence in 66 low- and middle-income countries.

Background: The literature on the association between religion and immunization coverage is scant, mostly consisting of single-country studies. Analyses in low and middle-income countries (LMICs) to assess whether the proportions of zero-dose children vary according to religion remains necessary to better understand non-socioeconomic immunization barriers and to inform interventions that target zero-dose children. Methods: We included 66 LMICs with standardized national surveys carried out since 2010, with information on religion and vaccination. The proportion of children who failed to receive any doses of a diphtheria-pertussis-tetanus (DPT) containing vaccine - a proxy for no access to routine vaccination or "zero-dose" status - was the outcome. Differences among religious groups were assessed using a test for heterogeneity. Additional analyses were performed controlling for the fixed effect of country, household wealth, maternal education, and urban-rural residence to assess associations between religion and immunization. Findings: In 27 countries there was significant heterogeneity in no-DPT prevalence according to religion. Pooled analyses adjusted for wealth, maternal education, and area of residence showed that Muslim children had 76% higher no-DPT prevalence than Christian children. Children from the majority religion in each country tended to have lower no-DPT prevalence than the rest of the population except in Muslim-majority countries. Interpretation: Analyses of gaps in coverage according to religion are relevant to renewing efforts to reach groups that are being left behind, with an important role in the reduction of zero-dose children.

Tétanos generalizado en un niño parcialmente inmunizado

Resumen El tétanos continúa siendo un problema de salud pública, y que afecta a todas las edades. La mortalidad aumenta por bajas coberturas de vacunación y escasez de recursos para un tratamiento temprano. Es causado por la toxina de Clostridium tetani (tetanoespasmina) el cual ingresa al organismo a través de heridas contaminadas por cuerpos extraños. La clínica más frecuente del tétanos es del tipo generalizado y se caracteriza por la contracción tónica de músculos esqueléticos, espasmos musculares intensos, dolorosos, e hiperactividad autonómica. El diagnóstico es principalmente clínico. Se presenta el caso clínico de un tétanos generalizado en un niño con vacunación incompleta. Se discute la importancia de la vacunación y el diagnóstico y tratamiento precoz para mejorar el pronóstico de la enfermedad.

Abstract Tetanus continues to be a public health problem, which affects all age groups. Mortality increases when immunization programs have low coverage and there is a lack of resources for early treatment. This disease is caused by the toxin of Clostridium tetani (tetanospasmin) which enters the body via wounds contaminated by foreign bodies. The most common symptoms of tetanus are of the generalized type and are characterized by tonic contraction of skeletal muscles, intense, painful muscle spasms, and autonomic hyperactivity. The diagnosis is clinical and the previous vaccination history becomes important. We report the case of generalized tetanus in a child with incomplete immunizations. Highlight the importance of vaccination and early diagnosis and treatment.

Vaccine coverage in children born to migrant mothers in Australia: A population-based cohort study.

BACKGROUND: Overall, infant immunisation coverage is currently >90% in Australia, but there are pockets of under-immunised children including children from migrant backgrounds. This study aimed to examine whether on-time vaccination coverage of diphtheria-tetanus-pertussis dose 3 (DTP3) for children born in Australia differed by mother's region of birth and if so, what factors were associated with these differences. METHODS: We conducted a population-based cohort study using linked data on perinatal, immunisation and birth records for 2 million children born in Western Australia and New South Wales between 1996 and 2012. We assessed on-time coverage of DTP3 (vaccination from 2 weeks prior to, and up until 30 days after, the due date) in children with mothers born overseas. Logistic regression models were developed to determine factors associated with on-time coverage for each maternal region of birth and all regions combined, adjusting for a range of demographic factors. Adjusted estimates of coverage were calculated for the different regions of birth. RESULTS: On-time DTP3 coverage was 76.2% in children of Australian born mothers, lower in children of mothers from Oceania (66.7%) and North America (68%), and higher in children born to mothers from South-East Asia (79.9%) and Southern Asia (79.3%). While most variables were consistently associated with lower coverage in all regions of birth, higher socioeconomic status and jurisdiction of birth showed varied results. Adjusted estimates of DTP3 coverage increased in children born to mothers from Australia (78.3%), Oceania (70.5%), Northern Africa (81.5%) and the Middle East (79.6%). DTP3 coverage decreased in children born to mothers from Europe and former USSR (74.6%), North-east Asia (75.2%), Southern Asia (76.7%), North America (65.5) and South/Central America and the Caribbean (73.2%). CONCLUSIONS: On-time vaccination rates differed by mother's region of birth. More research is needed to determine the main reasons for these remaining differences to improve vaccine uptake and also help guide policy and practice.

Systematic review and meta-analysis of pertussis epidemiology in Latin America and the Caribbean: 1980-2015 / Examen sistemático y metanálisis de las características epidemiológicas de la tos ferina en América Latina y el Caribe: 1980-2015 / Revisão sistemática e metanálise da epidemiologia da coqueluche na América Latina e Caribe: 1980 a 2015

Objectives In Latin America and the Caribbean (LAC), pertussis disease incidence has reportedly increased since 2000 despite high vaccine coverage. A systematic review of pertussis literature and a meta-analysis was conducted to understand the burden of disease in LAC. Methods A systematic literature review was completed, using relevant search terms. Original articles describing pertussis epidemiology and vaccine coverage in LAC published between 1980 and 2015 were identified. Applying a Bayesian meta-analysis random-effects model, we calculated pooled estimates and corresponding 95% credible intervals (95% CrIs) for pertussis incidence, case fatality ratio (CFR), pertussis prevalence among contacts, and coverage with three doses of diphtheria, tetanus, and pertussis (DTP) vaccine (DTP3). Results A total of 59 studies meeting our selection criteria were identified, representing 15 countries. Of the 59, 15 of them provided incidence data, with 7 of the 15 reporting a pertussis case definition. The pertussis incidence estimate for the 1980-1999 period was 17.8 cases per 100 000 persons (95% CrI: 5.9-29.7); for the 2000-2015 period, it was 2.5 cases per 100 000 persons (95% CrI: 1.8-3.2). For the 1980-2015 period, the CFR, in 19 studies reviewed, was 3.9% (95% CrI: 2.9%-4.9%); for that same period, in 5 studies reviewed, pertussis prevalence among contacts was 24.9% (95% CrI: 13.7%-36.1%). Pooled DTP3 vaccine coverage estimates, in a total of 20 studies reviewed for the following three time periods, were: 1980-1990, 72.4% (95% CrI: 64.6%-80.2%); 1991-2000, 79.0% (95% CrI: 66.1%-91.9%); and 2001-2015, 90.0% (95% CrI: 87.7%-92.3%). Conclusion A decrease in pertussis incidence and an achievement of moderately high DTP3 vaccine coverage since the early 2000s was observed. The review highlights the need for increased publication of pertussis data at the country level and for LAC as a whole in order to better understand the true burden of the disease. Application of a standardized case definition and use of active case finding would aid in obtaining more accurate estimates of the disease burden in LAC.

RESUMEN Objetivos En América Latina y el Caribe, la incidencia de la tos ferina habría aparentemente aumentado desde el 2000, a pesar de la alta cobertura de vacunación. Se realizó una revisión sistemática de la bibliografía sobre tos ferina y un metanálisis para conocer la carga de esta enfermedad en América Latina y el Caribe. Métodos. La revisión bibliográfica sistemática se realizó utilizando términos de búsqueda pertinentes. Se encontraron artículos originales que describían las características epidemiológicas de la tos ferina y la cobertura de vacunación en América Latina y el Caribe publicados entre 1980 y el 2015. Aplicando un modelo bayesiano de efectos aleatorios para el metanálisis, se obtuvieron estimaciones combinadas y los correspondientes intervalos de credibilidad del 95% (ICr) para la incidencia, la tasa de letalidad y la prevalencia entre contactos de la tos ferina, y la cobertura con tres dosis de vacuna contra la difteria, el tétanos y la tos ferina (DTP3). Resultados Se encontraron en total 59 estudios de 15 países que cumplían con los criterios de selección. De ellos, 15 proporcionaban datos sobre incidencia. Siete de estos 15 contenían una definición de caso de tos ferina. La incidencia estimada de tos ferina para el período 1980-1999 fue de 17,8 casos por 100 000 (ICr 95%: 5,9-29,7) y para el período 2000-2015, de 2,5 casos por 100 000 (ICr 95%: 1,8-3,2). En cuanto a la tasa de letalidad, para el período 1980-2015 en 19 estudios examinados fue de 3,9% (ICr 95%: 2,9%-4,9%); en el mismo período, en 5 estudios examinados la prevalencia de tos ferina entre los contactos fue de 24,9% (ICr 95%: 13,7%-36,1%). Las estimaciones combinadas de cobertura con DTP3 en un total de 21 estudios examinados para los siguientes tres períodos fueron: en 1980-1990, 72,4% (ICr 95%: 64,6%-80,2%); en 1991-2000, 79,0% (ICr 95%: 66,1%-91,9%) y en el 2001-2015, 90,0% (ICr 95%: 87,7%-92,3%). Conclusiones Se observó una disminución de la incidencia de la tos ferina y el logro de una cobertura moderadamente alta con la vacuna DTP3 desde principios del siglo XXI. En el examen se subraya la necesidad de incrementar la publicación de datos sobre la tos ferina en los países y en América Latina y el Caribe en su conjunto, para conocer mejor la verdadera carga de enfermedad. La adopción de una definición de caso normalizada y la búsqueda activa de casos ayudarán a obtener estimaciones más precisas de la carga de enfermedad en América Latina y el Caribe.

RESUMO Objetivos Há relatos de que a incidência de coqueluche na América Latina e Caribe (ALC) tem aumentado desde o ano 2000, apesar da alta cobertura vacinal. Realizamos uma revisão sistemática e metanálise da literatura sobre a coqueluche para compreender a carga da doença na ALC. Métodos. Fizemos uma revisão sistemática da literatura usando termos de pesquisa relevantes. Identificamos artigos originais, publicados entre 1980 e 2015, que descrevessem a epidemiologia da coqueluche e a cobertura vacinal na ALC. Aplicando um modelo Bayesiano de efeitos aleatórios para a metanálise, calculamos estimativas agrupadas e seus correspondentes intervalos de credibilidade de 95% (CrIs 95%) para a incidência de coqueluche, a taxa de letalidade, a prevalência de coqueluche entre os contatos e a cobertura com três doses da vacina combinada para difteria, tétano e coqueluche (DTP3). Resultados Identificamos um total de 59 estudos que cumpriram os nossos critérios de seleção, representando 15 países. Destes 59, 15 apresentaram dados sobre a incidência, e 7 dos 15 apresentaram uma definição de "caso de coqueluche". A incidência estimada da coqueluche no período de 1980 a 1999 foi de 17,8 casos por 100.000 pessoas (CrI 95%: 5,9-29,7); no período de 2000 a 2015, foi de 2,5 casos por 100.000 pessoas (CrI 95%: 1,8-3,2). No período de 1980 a 2015, a taxa de letalidade, em 19 estudos revistos, foi de 3,9% (CrI 95%: 2,9%-4,9%); neste mesmo período, em 5 estudos revistos, a prevalência de coqueluche entre os contatos foi de 24,9% (CrI 95%: 13,7%-36,1%). A cobertura vacinal agrupada com DTP3, em um total de 21 estudos examinados nos seguintes três períodos, foi estimada em: 1980 a 1990, 72,4% (CrI 95%: 64,6%-80,2%); 1991 a 2000, 79,0% (CrI 95%: 66,1%-91,9%); 2001 a 2015, 90,0% (CrI 95%: 87,7%-92,3%). Conclusões Foi observada uma redução na incidência de coqueluche e uma cobertura vacinal com DTP3 relativamente alta desde o início da década de 2000. Esta revisão destaca a necessidade de melhorar a publicação de dados sobre a coqueluche ao nível nacional e na ALC como um todo, a fim de promover uma melhor compreensão sobre a verdadeira carga da doença. O uso de uma definição padronizada de "caso de coqueluche" e a busca ativa de casos ajudaria na obtenção de estimativas mais precisas da carga da doença na ALC.

Assessing vaccine data recording in Brazil / Avaliação de dados vacinais no Brasil

ABSTRACT: Objectives: Vaccines represent an important advancement for improving the general health of a population. The effective recording of vaccine data is a factor for the definition of its supply chain. This study investigated vaccine data recording relatively to data collected from vaccination rooms and data obtained from a government-developed Internet platform. Methods: The monthly recorded total number of diphtheria and tetanus toxoids and pertussis vaccine (alone or in combination with the Haemophilus influenzae type b conjugate vaccine) doses administered in a medium-sized city of the Southeast region of Brazil was collected for the period January/2006 through December/2010 from two sources: City level (directly from vaccination rooms, the study "gold standard"), and Federal level (from an Internet platform developed by the country government). Data from these sources were compared using descriptive statistics and the Percentage error. Results: The data values made available by the Internet platform differed from those obtained from the vaccination rooms, with a Percentage error relatively to the actual values in the range [-0.48; 0.39]. Concordant values were observed only in one among the sixty analyzed months (1.66%). Conclusions: A frequent and large difference between the number of diphtheria and tetanus toxoids and pertussis vaccine doses administered in the two levels was detected.

RESUMO: Objetivos: Vacinas representam um importante avanço para melhorar a saúde de uma população. O registro adequado dos dados vacinais é um fator crítico para a programação da distribuição de vacinas. Este estudo investiga os registros de uma vacina aplicada à população, de acordo com dados coletados nas salas de vacinação e dados obtidos a partir de uma plataforma governamental de Internet. Métodos: O número mensal total de doses aplicadas da vacina contra difteria, tétano e coqueluche (isolada ou combinada à vacina contra Haemophilus influenzae tipo b) de uma cidade de médio porte da Região Sudeste do Brasil foi coletado no período de Janeiro/2006 a Dezembro/2010, de duas fontes: a nível Local (diretamente de salas de vacinação, o "padrão ouro") e a nível Federal (a partir de uma plataforma governamental de Internet). Os dados dessas fontes foram comparados utilizando estatística descritiva e a Percentagem de erro. Resultados: Os valores dos dados disponibilizados pela plataforma governamental diferem daqueles obtidos nas salas de vacinação, com uma Percentagem de erro compreendida no intervalo [-0,48; 0,39]. Valores concordantes foram observados somente em um dentre os sessenta meses analisados (1,66%). Conclusões: Detectou-se uma frequente e acentuada diferença entre o número de doses aplicadas da vacina observada relativamente às duas fontes de dados da pesquisa.

Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants.

BACKGROUND: The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants. METHODS: Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1-7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%). RESULTS: A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI -0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference -0.1% [95% CI -4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups. CONCLUSION: In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone.

Distribution of aluminum in hair of Brazilian infants and correlation to aluminum-adjuvanted vaccine exposure.

BACKGROUND: Nursing children are exposed to dietary aluminum (in breast milk and/or infant formulas) and through aluminum-adjuvanted vaccines (AAVs). We studied total hair-Al concentrations of nursing children that had been immunized with hepatitis B, DTP, and meningococcal vaccines. METHODS: We studied the hair of 37 young children (aged 26 to 824 days) who were exposed to cumulative doses of Al ranging from 0.63 to 6.88 mg from AAVs. Graphite furnace atomic absorption spectrometry was used to reliably measure total Al concentrations in hair samples. RESULTS: The analytical method proved sensitive enough to quantify Al in the hair of nursing children. At current levels of exposure it is possible to determine total Al in hair sample of 1.65 mg. Cumulative doses of AAV in children ranged from 0.63 to 6.88 mg Al. Median hair-Al was 47.7 µg g⁻¹ (ranging from 12.2 to 221.9 µg g⁻¹). There was no statistically significant correlation between hair-Al concentration and age of child (r=-0.049; p=0.774), total exposure from vaccine (r=-0.078; p=0.643), or the time elapsed after the last AAVs (r=0.015; p=0.931). CONCLUSION: Aluminum in children's hair can be reliably measured but we are still uncertain how representative it can be of the Al body burden.

A fully liquid DTPw-HepB-Hib combination vaccine for booster vaccination of toddlers in El Salvador / Vacuna líquida combinada DTPw-HepB-Hib como dosis de refuerzo en infantes de El Salvador

Objectives:To compare the safety and immunogenicity of a booster dose of a fully liquid diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HepB-Hib) vaccine to the separate administration of commercially available DTPw and Hib vaccines in healthy toddlers. Methods:An open-label, randomized, parallel-group, Phase III study conducted at six centers in San Salvador, El Salvador, during February-June 2006. Toddlers (15-24 months of age) were eligible to participate if they had received primary immunization at 2, 4, and 6 months of age with a commercial DTPw-HepB/Hib vaccine requiring reconstitution. Participants received either one booster dose of DTPw-HepB-Hib fully liquid vaccine or DTPw and Hib vaccines administered separately. Blood samples were taken immediately prior to and at 1 month post-vaccination. For a 5-day period following vaccination, solicited adverse events were collected in subject diaries and assessed. Results:The combined DTPw-HepB-Hib fully liquid vaccine was non-inferior to the separately administered DTPw and Hib vaccines, in terms of seroprotection/seroconversion rates for all antigens evaluated. The combination vaccine elicited a strong booster response as demonstrated by a large increase in antibodies against all vaccine antigens. The geometric mean concentrations (GMCs) of all antibodies in the DTPw-HepB-Hib group exceeded the seroprotection/seroconversion thresholds by very large margins, although for some antigens they were somewhat lower than the corresponding titers in the comparator group. With the combination vaccine, considerably fewer solicited local and systemic adverse events, such as fever and irritability, were reported than with the comparator vaccines. Conclusions:This study demonstrates that the fully liquid combined DTPw-HepB-Hib vaccine is highly immunogenic and has a favorable safety profile when given as a booster vaccination to toddlers who have received...

Objetivos:Comparar la seguridad y la inmunogenicidad en infantes saludables de una dosis de refuerzo de una vacuna líquida combinada contra la difteria, el tétanos, la tosferina (de células enteras), la hepatitis B y Haemophilus influenzae tipo b (DTPw-HepB-Hib), con la aplicación por separado de vacunas DTPw y Hib disponibles comercialmente. Métodos:Se realizó un estudio de fase III abierto, aleatorizado, con grupos paralelos, en seis centros de San Salvador, El Salvador, en febrero-junio de 2006. Los infantes (de 15-24 meses) habían recibido la inmunización primaria a los 2, 4 y 6 meses de edad con una vacuna comercial DTPw-HepB/Hib que necesitaba reconstitución. Los lactantes recibieron una dosis de refuerzo con la vacuna DTPw-HepB-Hib o las vacunas DTPw y Hib por separado. Se tomaron muestras de sangre inmediatamente antes de la vacunación y un mes después. Las reacciones adversas en los cinco días siguientes a la vacunación se anotaron en diarios individuales y se evaluaron. Resultados:Según las tasas de seroprotección/seroconversión de todos los antígenos evaluados, la vacuna DTPw-HepB-Hib no fue inferior que las vacunas DTPw y Hib administradas por separado. La vacuna combinada produjo una fuerte respuesta de refuerzo, reflejada en el gran aumento de anticuerpos contra todos los antígenos presentes. Con respecto al grupo de comparación, en el grupo vacunado con DTPw-HepB-Hib las concentraciones geométricas medias de todos los anticuerpos superaron ampliamente los umbrales de seroprotección/seroconversión -aunque con títulos menores en algunos antígenos- y hubo mucho menos reacciones adversas locales y sistémicas, como fiebre e irritabilidad. Conclusiones:Se demostró que la vacuna líquida combinada DTPw-HepB-Hib es altamente inmunógena y satisfactoriamente segura cuando se aplica como dosis de refuerzo a infantes inmunizados primariamente con una vacuna pentavalente diferente que requiere reconstitución.

Reacciones adversas a vacuna DPT del Programa Nacional de Inmunizaciones / Adverse reactions to diphtheria-pertussis-tetanus vaccine in the Chilean Immunization Program

Background: During 2005, the surveillance system of the Chilean Immunization Program detected an increased number of adverse reaction notifications associated to diphtheria, pertussis and tetanus whole-cell vaccine (DPT), coincidentiy with a change in the vaccine manufacturer. Aim: To compare the reactogenicity of two DPT formulations (vaccines 1 and 2) in 18-month-old infants and 4-year-old children. Material and methods: Severe adverse reactions to DPT were studied at the emergency room of two hospitals of Santiago in a case-control study (110 cases and 171 controls, who consulted for other causes). Simultaneously the incidence of total adverse reactions (mild and severe) for vaccine 1 and 2 was estimated in a cohort of 1,017 children vaccinated in an ambulatory health center of the same área. The formulation of DPT received by all participants was verífied, as well as the temporal relation with consultation or symptoms referred by their caregivers. Results: There was a greater probability of consulting at the emergency rooms for severe adverse reactions among children who received vaccine 1 (odds ratio (OR) =7.1; p <0.001), being greater among 4-year-old children (OR =18.9; p <0.001). Coincidentiy, in the cohort of vaccinated children, those who received vaccine 1 had a higher risk of presenting adverse reactions (RR =2.9; p <0.001), being high fever the commonest. Conclusions: We confirmed that vaccine 1 was associated to a higher risk of adverse reactions, especially among 4-year-old children. These results allowed the sanitary authority to adopt an informed decisión. The usefulness of observational studies in vaccine adverse reactions is confirmed.

A new DTPw-HB/Hib combination vaccine for primary and booster vaccination of infants in Latin America / Nueva vacuna combinada DTPw-HB/Hib para la vacunación primaria y de refuerzo de menores de un año en América Latina

Objectives. In 1998 the World Health Organization (WHO) recommended the inclusion of Haemophilus influenza type B (Hib) conjugate vaccines in infant immunization programs, whenever in accordance with national priorities. GlaxoSmithKline Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib (DTPwHB/Hib) vaccine containing 5 µg of polyribosylribitol phosphate (PRP), and we assessed the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with this new vaccine compared with a reference regimen consisting of the licensed DTPw-HB (Tritanrix) and Hib (Hiberix) vaccines given as simultaneous concomitant injections. Methods. We performed a randomized, double-blind study from September 1998 to August 1999 to establish the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with the new pentavalent combined DTPw-HB/Hib vaccine given as a single injection, compared with the reference regimen. Results. Both vaccination regimens elicited excellent immune responses, with all subjects in both groups achieving seroprotective anti-PRP antibody concentrations of ≥ 0.15 µg/mL one month after primary vaccination. The combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms of seroprotection/seropositivity/vaccine response rates for all antigen components. Persistence of antibodies against all study vaccine antigens up to the time of booster vaccination was comparable between groups, and a marked increase of all antibody concentrations was observed after the booster dose. Both vaccine regimens were similar in terms of their overall reactogenicity profiles. Conclusions. Our results indicate that the new DTPw-HB/Hib pentavalent combination vaccine provides an efficient and reliable way of implementing WHO recommendations for controlling hepatitis B and Hib infections on a worldwide basis.

OBJETIVOS: En 1998, la Organización Mundial de la Salud (OMS) recomendó que se incluyeran vacunas conjugadas contra Haemophilus influenzae tipo B (Hib) en los programas de vacunación de niños menores de un año, siempre que ello estuviera en consonancia con las prioridades nacionales. La compañía GlaxoSmithKline Biologicals ha creado una nueva vacuna pentavalente que es una combinación de la vacuna contra la difteria (D), el tétanos (T) y la tos ferina (P) (con antígeno tosferínico a base de células completas) y las vacunas contra la hepatitis B (HB) y contra Haemophilus influenzae tipo B (Hib) (DTPw-HB/Hib), con un total de 5 µg de fosfato de polirribosilrribitol (FPR). Hemos evaluado la inmunogenia y reactogenia observadas al aplicarse las dosis primaria y de refuerzo de esta nueva vacuna a niños sanos y las hemos comparado con las observadas al aplicar un régimen de referencia a base de las vacunas autorizadas DTPw-HB (Tritanrix) y antiHib (Hiberix) en forma de inyecciones simultáneas. MÉTODOS: Llevamos a cabo un estudio aleatorizado y con doble enmascaramiento de septiembre de 1998 a agosto de 1999 para establecer la inmunogenia y reactogenia observadas al administrarles a niños sanos la nueva vacuna combinada pentavalente (DTPw-HB/Hib) en una sola inyección, y compararlas con las observadas con el régimen de referencia. RESULTADOS: Se obtuvieron excelentes respuestas inmunitarias con ambos regímenes. Todos los niños vacunados en ambos grupos alcanzaron concentraciones séricas protectoras de anticuerpos antiFPR > 0,15 µg un mes después de recibir la dosis primaria. La vacuna combinada DTPw-HB/Hib no dio resultados inferiores a los obtenidos con las vacunas autorizadas en términos de los porcentajes de seroprotección, seropositividad y respuesta frente a todos los componentes antigénicos de la vacuna. La persistencia de anticuerpos contra todos los antígenos contenidos en ella hasta el momento en que se administró la dosis de refuerzo fue parecida en ambos grupos, y se observó un marcado aumento de las concentraciones de todos los anticuerpos después del refuerzo. La reactogenia general observada con ambos regímenes de vacunación fue parecida. CONCLUSIONES: Nuestros resultados indican que la nueva vacuna combinada pentavalente DTPw-HB/Hib ofrece una manera eficiente y confiable de poner en práctica las recomendaciones de la OMS para el control de la hepatitis B y de las infecciones por Hib en el mundo entero.