Cost-effectiveness analysis of the pediatric 20-valent pneumococcal conjugate vaccine compared with lower-valent alternatives in Argentina.

OBJECTIVES: The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants in Argentina's national immunization program (NIP) in a 2 + 1 schedule since 2012. Licensure of the 15-valent vaccine (PCV15) is anticipated soon, and the 20-valent vaccine (PCV20) recently received regulatory approval. This cost-effectiveness analysis examined the public health and economic implications of transitioning from PCV13 to either PCV15 or PCV20 in Argentina's pediatric NIP. METHODS: A decision-analytic Markov model was used with a 10-year time horizon and a 3.0% annual discount rate for costs and benefits. Vaccine effectiveness estimates were derived from Argentinian surveillance data, PCV13 clinical effectiveness and impact studies, and PCV7 efficacy studies. Population, epidemiologic, and economic inputs were obtained from literature and Argentinian-specific data. The study adopted a healthcare system perspective; sensitivity and scenario analyses were conducted to assess input parameters and structural uncertainty. RESULTS: Compared with PCV13, PCV20 was estimated to avert an additional 7,378, 42,884, and 172,389 cases of invasive pneumococcal disease (IPD), all-cause pneumonia, and all-cause otitis media (OM), respectively, as well as 3,308 deaths, resulting in savings of United States Dollars (USD) 50,973,962 in direct medical costs. Compared with PCV15, PCV20 was also estimated to have greater benefit, averting an additional 6,140, 35,258, and 142,366 cases of IPD, pneumonia, and OM, respectively, as well as 2,624 deaths, resulting in savings of USD 37,697,868 in direct medical costs. PCV20 was associated with a higher quality-adjusted life year gain and a lower cost (i.e., dominance) versus both PCV13 and PCV15. Results remained robust in sensitivity analyses and scenario assessments. CONCLUSION: Over a 10-year horizon, vaccination with PCV20 was expected to be the dominant, cost-saving strategy versus PCV13 and PCV15 in children in Argentina. Policymakers should consider the PCV20 vaccination strategy to achieve the greatest clinical and economic benefit compared with lower-valent options.

Cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban national immunization programme.

OBJECTIVES: To evaluate the cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban National Immunization Program (NIP). METHODS: We compared PCV7-TT given at two, four and six months of age to a scenario without PCV7-TT, over a ten-year period (2020-2029). We calculated the cost (Cuban pesos - CUP) per Disability Adjusted Life Year (DALY) averted from a Government perspective. We compared results from a static cohort model and a parsimonious prediction model informed by the serotype distribution among pneumococcal carriers and cases. We ran probabilistic and deterministic uncertainty analyses. RESULTS: PCV7-TT could prevent 6897 (95% uncertainty interval, 4344-8750) hospitalizations and 189 (115-253) deaths in children <5 years of age, over the period 2020-2029. This could cost around 25 million (20-31) discounted CUP but would be offset by treatment cost savings of around 23 million (14-31). A parsimonious model predicted less favourable impact and cost-effectiveness but the cost per DALY averted was still less than 0.4 times the current GDP per capita. CONCLUSIONS: PCV7-TT is likely to be cost-effective in Cuba. The impact of the vaccine would need to be carefully monitored following its introduction into the NIP.

Cost-Utility Study of PCV13 Versus PPSV23 in Adults in Chile.

INTRODUCTION: Pneumococcal infections are a public health problem in older adults. In Chile there are two vaccines at this time, PPSV23 and PCV13. The first has lower immunogenicity and effectiveness in preventing pneumococcal pneumonia and a lower cost than PCV13. OBJECTIVE: To determine the cost-effectiveness of PCV13 versus PPSV23 in adults 18 years old and over in the Chilean Health System. MATERIAL AND METHOD: A cost-utility study was performed using the Markov model (population data for a time horizon of 10 years). Utilities and epidemiological data were obtained from the literature and costs from the Chilean Public sector. Vaccine's costs and quality-adjusted life years (QALYs) were determined and compared. RESULTS: PCV13 vaccination program in adults (≥18 years), generated savings of $42,195 USD and an increase of 6,820 QALYs, avoiding 107 cases of bacteremia, 13 meningitis, 6,706 inpatient pneumonia, 4,509 outpatient pneumonia and 1,189 deaths compared to PPSV23 without variation on sensitivity analysis on high impact variables. For the subgroup of patients over 65 years old PCV13 generates savings of $ 32,105.94USD and produces 5,430 QALYs more compared to PPSV23. CONCLUSION: PCV13 is dominant. A PCV13 vaccination program saves costs to the public system, reduces mortality and morbidity; these results are robust.

Postintroduction Study of Cost-Effectiveness of Pneumococcal Vaccine PCV10 from Public Sector Payer's Perspective in the State of Santa Catarina, Brazil.

OBJECTIVES: To evaluate cost-effectiveness of 10-valent pneumococcal conjugate vaccine in the routine immunization program for children younger than 5 years in Brazil by a postintroduction study. METHODS: Ecological study of prevaccine (2006-2009) versus postvaccine (2011-2014) period related the changes in mortality rate and hospitalization rate to direct cost of pneumonia treatment from the payer's perspective to estimate the cost-effectiveness regarding lives saved, life-years gained, and disability-adjusted life-year for children younger than 5 years in the southern Brazilian state of Santa Catarina. All-cause pneumonia (ICD-10 J12-J18) deaths, hospital admissions, and associated costs were retrieved from the Brazilian Ministry of Health official Web site. Life expectancy at birth, population, ambulatory costs, cost savings, and plausible range of these parameters were used from published sources. Computer simulations with sensitivity analysis were performed to obtain the cost-effectiveness estimates. RESULTS: About 27 lives were saved and 2573 hospitalizations averted by the 10-valent pneumococcal conjugate vaccine vaccination in the 2011 to 2014 period at the cost of US $24,348 per life-year gained and US $27,748 per disability-adjusted life-year. The latter cost is 81% of Brazilian gross domestic product per capita over the same period. CONCLUSIONS: The vaccine was very cost-effective according to the World Health Organization criterion.

Cost-Effectiveness Analysis of Pneumococcal and Influenza Vaccines Administered to Children Less Than 5 Years of Age in a Low-Income District of Bogota, Colombia.

BACKGROUND: The Colombian health authorities introduced the pneumococcal conjugated vaccine and the seasonal influenza vaccine into the national immunization schedule for children in 2009 and 2007, respectively. Despite this, the health authorities continue to be concerned about the high economic and disease burden among children from low-income households caused by these vaccine-preventable diseases. OBJECTIVES: 1) To evaluate the potential health outcomes of four vaccination strategies for subsidized children younger than 5 years in a low-income district in Colombia from a public, direct medical health care perspective. 2) To perform univariate, multivariate, and probabilistic sensitivity analysis to evaluate the robustness of these results. METHODS: We built a Markov deterministic cohort model to evaluate five consecutive cohorts across four alternative situations: 1) no vaccination; 2) vaccination with the 10-valent pneumococcal conjugate vaccine (PCV10 vaccine); 3) vaccination with the trivalent inactivated vaccine (TIV) annually; and 4) combined vaccination with PCV10 vaccine and TIV. RESULTS: The introduction of PCV10 vaccine and TIV and their combined use in particular would be highly cost-effective in comparison to no vaccination. For the combined vaccination with PCV10 vaccine and TIV, the incremental cost-effectiveness ratio would be $1,280 per disability-adjusted life-year (DALY) averted, the total incremental cost of the vaccination program would be $776,800, and it would avert four deaths and 332 DALYs for the five cohorts. CONCLUSIONS: The introduction of PCV10 vaccine and TIV would be highly cost-effective from a public, direct medical health care perspective. Despite these results, we have not observed decreases in severity or hospitalizations. Our findings highlight the need for further studies of the immunization campaign indicators and socioeconomic indicators for this low-income community.

From individual to herd protection with pneumococcal vaccines: the contribution of the Cuban pneumococcal conjugate vaccine implementation strategy.

A new pneumococcal conjugate vaccine is currently undergoing advanced clinical evaluation prior to its planned introduction in Cuba. The implementation of the pneumococcal vaccination strategy has been designed with consideration of the need to maximize both its direct and indirect effects. A novel approach is suggested, which addresses preschool children as the first-line target group to generate herd immunity in infants and to have an impact on transmission at the community level. The clinical evaluation pipeline is described herein, including evaluations of effectiveness, cost-effectiveness, and impact. The scientific contribution of the Cuban strategy could support a paradigm shift from individual protection to a population effect based on a rigorous body of scientific evidence.

Cost-effectiveness and cost utility analysis of three pneumococcal conjugate vaccines in children of Peru.

BACKGROUND: The clinical and economic burden associated with invasive and non-invasive pneumococcal and non-typeable Haemophilus influenzae (NTHi) diseases is substantial in the Latin America and Caribbean region, where pneumococcal vaccines have only been introduced to a few countries. This study analyzed the cost-effectiveness and cost utility of three different pneumococcal conjugate vaccines (PCVs) for Peru. METHODS: A Markov model that simulated the disease processes in a birth cohort over a lifetime, within 1,128 month cycles was used to evaluate the cost-effectiveness of 10-valent pneumococcal NTHi protein D conjugate vaccine (PHiD-CV) and 7- and 13-valent PCVs (PCV-7 and PCV-13). Expected quality-adjusted life years (QALYs), cost-savings and incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: Without vaccination, pneumonia was associated with the greatest health economic burden (90% of QALYs lost and 63% of lifetime direct medical costs); while acute otitis media (AOM) was responsible for 1% of QALYs lost and 25% of direct medical costs. All vaccines were predicted to be cost-effective for Peru, with PHiD-CV being most cost-effective. PHiD-CV was predicted to generate 50 more QALYs gained and required a reduced investment (-US$ 3.4 million) versus PCV-13 (discounted data), and was therefore dominant and cost saving. The probabilistic sensitivity analysis showed that PHiD-CV generated more QALYs gained at a reduced cost than PCV-13 in 84% of the simulations and less QALYs gains at a reduced cost in 16%. Additional scenarios using different assumptions on vaccine efficacies based on previous evidence were explored, but no significant change in the overall cost-effective results were observed. CONCLUSIONS: The results of this modeling study predict that PCVs are likely to be a cost-effective strategy to help relieve the epidemiological and economic burden associated with pediatric pneumococcal and NTHi diseases for Peru. PHiD-CV is likely to be a dominant (better health gains at a reduced net cost) intervention compared to PCV-13 or PCV-7. The most significant drivers for these results are the better health and economic profile of PHiD-CV against AOM and its reduced cost per dose available through the PAHO Revolving Fund in the LAC region.

Cost-effectiveness of Haemophilus influenzae type b conjugate vaccine in low- and middle-income countries: regional analysis and assessment of major determinants.

OBJECTIVES: To estimate the cost-effectiveness of Haemophilus influenzae type b (Hib) conjugate vaccine in low- and middle-income countries and identify the model variables, which are most important for the result. STUDY DESIGN: A static decision tree model was developed to predict incremental costs and health impacts. Estimates were generated for 4 country groups: countries eligible for funding by the GAVI Alliance in Africa and Asia, lower middle-income countries, and upper middle-income countries. Values, including disease incidence, case fatality rates, and treatment costs, were based on international country estimates and the scientific literature. RESULTS: From the societal perspective, it is estimated that the probability of Hib conjugate vaccine cost saving is 34%-53% in Global Alliance for Vaccines and Immunization eligible African and Asian countries, respectively. In middle-income countries, costs per discounted disability adjusted life year averted are between US$37 and US$733. Variation in vaccine prices and risks of meningitis sequelae and mortality explain most of the difference in results. For all country groups, disease incidence cause the largest part of the uncertainty in the result. CONCLUSIONS: Hib conjugate vaccine is cost saving or highly cost-effective in low- and middle-income settings. This conclusion is especially influenced by the recent decline in Hib conjugate vaccine prices and new data revealing the high costs of lost productivity associated with meningitis sequelae.

Impact and cost-effectiveness of Haemophilus influenzae type b conjugate vaccination in India.

OBJECTIVE: To estimate the potential health impact and cost-effectiveness of nationwide Haemophilus influenzae type b (Hib) vaccination in India. STUDY DESIGN: A decision support model was used, bringing together estimates of demography, epidemiology, Hib vaccine effectiveness, Hib vaccine costs, and health care costs. Scenarios favorable and unfavorable to the vaccine were evaluated. State-level analyses indicate where the vaccine might have the greatest impact and value. RESULTS: Between 2012 and 2031, Hib conjugate vaccination is estimated to prevent over 200 000 child deaths (∼1% of deaths in children <5 years of age) in India at an incremental cost of US$127 million per year. From a government perspective, state-level cost-effectiveness ranged from US$192 to US$1033 per discounted disability adjusted life years averted. With the inclusion of household health care costs, cost-effectiveness ranged from US$155-US$939 per discounted disability adjusted life year averted. These values are below the World Health Organization thresholds for cost effectiveness of public health interventions. CONCLUSIONS: Hib conjugate vaccination is a cost-effective intervention in all States of India. This conclusion does not alter with plausible changes in key parameters. Although investment in Hib conjugate vaccination would significantly increase the cost of the Universal Immunization Program, about 15% of the incremental cost would be offset by health care cost savings. Efforts should be made to expedite the nationwide introduction of Hib conjugate vaccination in India.

Estimating health service utilization for treatment of pneumococcal disease: the case of Brazil.

BACKGROUND: Health service utilization (HSU) is an essential component of economic evaluations of health initiatives. Defining HSU for cases of pneumococcal disease (PD) is particularly complex considering the varying clinical manifestations and diverse severity. OBJECTIVE: We describe the process of developing estimates of HSU for PD as part of an economic evaluation of the introduction of pneumococcal conjugate vaccine in Brazil. METHODS: Nationwide inpatient and outpatient HSU by children under-5 years with meningitis (PM), sepsis (PS), non-meningitis non-sepsis invasive PD (NMNS), pneumonia, and acute otitis media (AOM) was estimated. We assumed that all cases of invasive PD (PM, PS, and NMNS) required hospitalization. The study perspective was the health system, including both the public and private sectors. Data sources were obtained from national health information systems, including the Hospital Information System (SIH/SUS) and the Notifiable Diseases Information System (SINAN); surveys; and community-based and health care facility-based studies. RESULTS: We estimated hospitalization rates of 7.69 per 100,000 children under-5 years for PM (21.4 for children <1 years of age and 4.3 for children aged 1-4 years), 5.89 for PS (20.94 and 2.17), and 4.01 for NMNS (5.5 and 3.64) in 2004, with an overall hospitalization rate of 17.59 for all invasive PD (47.27 and 10.11). The estimated incidence rate of all-cause pneumonia was 93.4 per 1000 children under-5 (142.8 for children <1 years of age and 81.2 for children aged 1-4 years), considering both hospital and outpatient care. DISCUSSION: Secondary data derived from health information systems and the available literature enabled the development of national HSU estimates for PD in Brazil. Estimating HSU for noninvasive disease was challenging, particularly in the case of outpatient care, for which secondary data are scarce. Information for the private sector is lacking in Brazil, but estimates were possible with data from the public sector and national population surveys.

The pharmacoeconomics of pneumococcal conjugate vaccines in Latin America.

Streptococcus pneumoniae continues to be the most important causative agent of invasive bacterial infections in children and is the most common cause of vaccine-preventable deaths in children less than 5 years of age. Due to some conditions in the Latin America region, economic assessments of pneumococcal conjugate vaccines (PCVs) have unique characteristics. First, distribution of S. pneumoniae serotypes, and thus coverage by vaccines that incorporate certain serotypes, varies within the region and compared with other parts of the world. Second, the mortality rate of pneumococcal infections in developing countries is significantly higher than in the US and Europe. Third, the economies of the Latin American region are very different from those of developed countries. For these reasons, the Pan American Health Organization (PAHO) is promoting the need for economic valuation studies of the impact of pneumococcal vaccines Latin America. Given the importance of pneumonia in the burden of pneumococcal disease in Latin America, the number of pneumonia cases prevented by the vaccine has a large impact on the economic valuation of PCVs, due to a strong correlation with numbers of deaths averted, quality-adjusted life-years (QALYs) gained or disability-adjusted life-years (DALYs) avoided. In terms of cost, analysis of impact on acute otitis media (short-term) and sequelae (long-term) show a significant and important expenditure avoided by vaccination. Cost-effectiveness is significantly modified by vaccine cost, mortality due to pneumonia, vaccine efficacy/effectiveness and herd immunity. Finally the validity of certain assumptions based on the uncertainty of the data should be considered in economic assessments of new PCVs. These include assumptions related to the impact on otitis media, estimates of efficacy/effectiveness based on measured antibody levels and the extrapolation to PCV10 and PCV13 of previous experience with PCV7.

[Economic evaluation of an infant immunization program in Mexico, based on 13-valent pneumococcal conjugated vaccines]. / Evaluación económica de un programa de inmunización infantil en México basado en la vacuna neumocócica conjugada 13-valente.

OBJECTIVES: Vaccination is an effective intervention for reduce child morbidity and mortality associated to pneumococcus. The availability of new anti-pneumococcal vaccines makes it necessary to evaluate its potential impact on public health and costs related to their implementation. The aim of this study was to estimate the cost-effectiveness and cost-utility of immunization strategies based on pneumococcal conjugated vaccines (PCV's) currently available in Mexico from a third payer perspective. MATERIAL AND METHODS: A decision tree model was developed to assess both, economic and health impact, of anti-pneumococcal vaccination in children <2 years (lifetime time horizon, discount rate: 5% annual). Comparators were: no-vaccination (reference) and strategies based on 7, 10 and 13-valent PCV's. Effectiveness measures were: child deaths avoided, life-years gained (LYG) and quality adjusted life years (QALY's) gained. Effectiveness, utility, local epidemiology and cost of treating pneumococcal diseases were extracted from published sources. Univariate sensitivity analysis were performed. RESULTS: Immunization dominates no-vaccination: strategy based on 13-valent vaccine prevented 16.205 deaths, gained 331.230 LY's and 332.006 QALY's and saved US$1.307/child vaccinated. Strategies based on 7 and 10-valent PCV's prevented 13.806 and 5.589 deaths, gained 282.193 and 114.251 LY's, 282.969 and 114.972 QALY's and saved US$1.084 and US$731/child vaccinated, respectively. These results were robust to variations in herd immunity and lower immunogenicity of 10-valent vaccine. CONCLUSIONS: In Mexico, immunization strategies based on 7, 10 and 13-valent PCV's would be cost-saving interventions, however, health outcomes and savings of the strategy based on 13-valent vaccine are greater than those estimated for 7 and 10-valent PCV's.

[Cost-effectiveness of universal pneumococcal vaccination in Uruguay]. / Costo-efectividad de la vacunación universal antineumocócica en Uruguay.

OBJECTIVE: Evaluate the cost-effectiveness ratio of the program for universal vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) in children under 5 years of age in Uruguay. METHODS: A Markov model was developed that simulated a cohort of 48 000 children born in 2007 and their progress to age 76. The baseline case used a regimen of three doses with estimated protection for five years. The presumption of vaccine efficacy and effectiveness was based on studies conducted in the United States with adjustment for serotype prevalence-incidence in Uruguay. The results were expressed as the incremental cost per life year gained (LYG) and quality-adjusted life year (QALY) [gained]. RESULTS: For the baseline case, the incremental cost was US $7334.60 for each LYG and US $4655.80 for each QALY. Eight deaths and 4 882 cases of otitis, 56 cases of bacteremia-sepsis, 429 cases of pneumonia, and 7 cases of meningitis were prevented. The model shows sensitivity to variations in vaccine cost, efficacy, and pneumonia-related mortality. CONCLUSIONS: The universal vaccination program with PCV7 in Uruguay is highly cost-effective. Therefore, it is recommended for other countries with burden of pneumococcal disease and serotype coverage similar to those of Uruguay.

Costo-efectividad de la vacunación universal antineumocócica en Uruguay / Cost-effectiveness of universal pneumococcal vaccination in Uruguay

OBJETIVO: Evaluar la relación costo-efectividad del programa de vacunación universal con la vacuna antineumocócica conjugada heptavalente (VCN7) en niños menores de 5 años en Uruguay. MÉTODOS: Se desarrolló un modelo Markov simulando una cohorte de 48 000 niños nacidos en 2007 y su evolución hasta los 76 años de edad. El caso base usó un esquema de tres dosis con una duración estimada de protección de cinco años. La presunción de eficacia y efectividad de la vacuna se realizó acorde con estudios realizados en Estados Unidos con ajuste a la prevalencia-incidencia de serotipos en Uruguay. Los resultados se expresaron como costo incremental por año de vida ganado (AVG) y por año de vida [ganado] ajustado por calidad (AVAC). RESULTADOS: Para el caso base, el costo incremental fue de US$ 7 334,6 por AVG y US$ 4 655,8 por AVAC, previniéndose 8 muertes y 4 882 casos de otitis, 56 bacteriemias-sepsis, 429 neumonías y 7 meningitis. El modelo muestra sensibilidad a variaciones en eficacia, costo de la vacuna y tasa de mortalidad por neumonía. CONCLUSIONES: El programa de vacunación universal con VCN7 en Uruguay es altamente costo-efectivo y, en consecuencia, recomendable para otros países con carga de enfermedad neumocócica y cobertura de serotipos similares a Uruguay.

OBJECTIVE: Evaluate the cost-effectiveness ratio of the program for universal vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) in children under 5 years of age in Uruguay. METHODS: A Markov model was developed that simulated a cohort of 48 000 children born in 2007 and their progress to age 76. The baseline case used a regimen of three doses with estimated protection for five years. The presumption of vaccine efficacy and effectiveness was based on studies conducted in the United States with adjustment for serotype prevalence-incidence in Uruguay. The results were expressed as the incremental cost per life year gained (LYG) and quality-adjusted life year (QALY) [gained]. RESULTS: For the baseline case, the incremental cost was US $7334.60 for each LYG and US $4655.80 for each QALY. Eight deaths and 4 882 cases of otitis, 56 cases of bacteremia-sepsis, 429 cases of pneumonia, and 7 cases of meningitis were prevented. The model shows sensitivity to variations in vaccine cost, efficacy, and pneumonia-related mortality. CONCLUSIONS: The universal vaccination program with PCV7 in Uruguay is highly cost-effective. Therefore, it is recommended for other countries with burden of pneumococcal disease and serotype coverage similar to those of Uruguay.

Identifying unit costs for use in regional economic evaluation: an illustrative analysis of childhood pneumococcal conjugate vaccine in Latin America and the Caribbean / Identificación de los costos unitarios para evaluaciones económicas regionales: análisis ilustrativo de la vacuna conjugada infantil antineumocócica en América Latina y el Caribe

Se analizan algunos temas relacionados con la selección y la construcción de los datos de costos unitarios para utilizar en análisis económicos regionales, con ejemplos ilustrativos de un análisis de la vacuna conjugada infantil antineumocócica realizado en 10 países de América Latina y el Caribe en 2006. El objetivo del análisis fue obtener un conjunto consistente de costos unitarios de recursos empleados en el tratamiento de la enfermedad neumocócica, según una bien ponderada combinación de datos publicados, tasas de reembolso, datos de cobro y nuevos métodos de determinación de costos detallados. Los pasos previos al análisis abarcaron la determinación del grado de detalle requerido, la definición del intervalo de costos de interés y la selección de conceptos de medición apropiados. Se determinó el costo detallado de los ítems mediante la descomposición de los componentes del tratamiento. Para el análisis se utilizaron los costos promedio ponderados por la población. En este informe se describen los diferentes métodos de determinación del costo empleados en el estudio y los problemas conceptuales y prácticos encontrados para su aplicación. También se identifican los posibles retos para generalizar este enfoque a otros escenarios de determinación de costos con otras enfermedades.

Cost-effectiveness of pneumococcal conjugate vaccination in Latin America and the Caribbean: a regional analysis / Rentabilidad médica de la vacunación antineumocócica en América Latina y el Caribe: un análisis regional

OBJECTIVE: In Latin America and the Caribbean, routine vaccination of infants against Streptococcus pneumoniae would need substantial investment by governments and donor organizations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate vaccine, demographic, epidemiologic, and cost data into an economic analysis of pneumococcal vaccination of infants in Latin America and the Caribbean. METHODS: We previously used a structured literature review to develop regional estimates of the incidence of disease. Cost data were collected from physician interviews and public fee schedules. We then constructed a decision analytic model to compare pneumococcal conjugate vaccination of infants with no vaccination across this region, examining only vaccine's direct effects on children. RESULTS: Pneumococcal vaccination at the rate of diphtheria-tetanus-pertussis vaccine coverage was projected to prevent 9 500 deaths per year in children aged 0 to 5 years in the region, or approximately one life saved per 1 100 infants vaccinated. These saved lives as well as averted cases of deafness, motor deficit, and seizure result in 321 000 disability-adjusted life years (DALYs) being averted annually. At vaccine prices between US$5 and US$53 per dose, the cost per DALY averted from a societal perspective would range from US$154 to US$5 252. CONCLUSION: Pneumococcal conjugate vaccine was highly cost-effective up to $40 per dose. Introduction of pneumococcal vaccine in the Latin American and Caribbean region is projected to reduce childhood mortality and to be highly cost-effective across a range of possible costs.

OBJETIVO: En América Latina y el Caribe, la vacunación sistemática de niños contra Streptococcus pneumoniae podría requerir inversiones considerables de los gobiernos y organizaciones donantes. Al evaluar estas inversiones se requiere información sobre los posibles beneficios sanitarios, costos y rentabilidad (relación costo-efectividad) de la vacunación. Se presenta un análisis económico de la vacunación infantil antineumocócica en América Latina y el Caribe a partir de la información de la vacuna y de datos demográficos, epidemiológicos y de costos. MÉTODOS: Se realizó una revisión bibliográfica estructurada previa para llegar a estimados regionales de la incidencia de la enfermedad. Los costos se tomaron de entrevistas a médicos y tarifas públicas. Se construyó un modelo analítico de decisión para comparar la vacunación de los niños de esta región con la vacuna antineumocócica conjugada y la no vacunación, tomando en cuenta solamente el efecto directo de la vacuna en los niños. RESULTADOS: Se proyectó la vacunación antineumocócica con las tasas de cobertura de la vacuna contra la difteria, el tétanos y la tosferina para prevenir 9 500 muertes anuales en menores de 5 años en esta región, o aproximadamente 1 vida salvada por cada 1 100 niños vacunados. Las vidas salvadas y los casos prevenidos de sordera, trastornos psicomotores y convulsiones equivalen a evitar anualmente 321 000 años de vida ajustados por incapacidad (AVAD). A un precio de la vacuna de US$ 5,00 a US$ 53,00 por dosis, el costo por AVAD evitado desde el punto de vista de la sociedad sería de US$ 154,00 a US$ 5 252,00. CONCLUSIONES: La vacuna antineumocócica conjugada fue altamente rentable hasta un precio de US$ 40,00 por dosis. La introducción de esta vacuna en América Latina y el Caribe puede reducir la mortalidad infantil con una alta rentabilidad en un amplio espectro de posibles costos.

Impacto da vacina conjugada contra Streptococcus pneumoniae em doenças invasivas / Impact of pneumococcal conjugate vaccine on the prevention of invasive pneumococcal diseases

OBJETIVOS: Rever os estudos que avaliam o impacto da vacina conjugada 7-valente na incidência de doenças invasivas por pneumococo e analisar o possível impacto dessa vacina no Brasil. FONTE DE DADOS:Foram pesquisadas as bases de dados MEDLINE, LILACS, Cochrane Database Reviews (janeiro de 2000 a janeiro de 2006), selecionando-se para análise os artigos contendo as seguintes palavras-chave: Streptococcus pneumoniae, pneumococo, vacina conjugada, resistência, antibióticos e meningite. Também foi realizada busca de informações sobre o tema nos sites do Centers for Disease Control, Ministério da Saúde e Centro de Vigilância Epidemiológica do Estado de São Paulo. SíNTESE DOS DADOS: A vacina conjugada 7-valente reduziu a incidência de doenças invasivas por pneumococo, número de consultas por doenças respiratórias de vias aéreas superiores e inferiores, consumo de antibióticos e incidência de doenças invasivas por pneumococo por cepas resistentes a antibióticos não apenas nas crianças vacinadas, como em adultos e idosos. No Brasil, os coeficientes de incidência de doenças invasivas por pneumococo em crianças menores de 5 anos são elevados, a taxa de letalidade de meningites pneumocócicas é alta e as taxas de resistência parcial e plena à penicilina aumentaram substancialmente nos últimos 5 anos. CONCLUSÕES:Devido aos benefícios diretos e indiretos do uso em larga escala da vacina conjugada 7-valente, essa vacina deve ser incluída no calendário básico de imunização do Brasil.

Impact of pneumococcal conjugate vaccine on the prevention of invasive pneumococcal diseases.

OBJECTIVES: To evaluate the impact of heptavalent pneumococcal conjugate vaccine in invasive pneumococcal diseases in the United States, and to analyze the potential impact of this vaccine in Brazil. SOURCES OF DATA: MEDLINE, LILACS, Cochrane Database Reviews, as well as the websites of the Centers for Disease Control and Prevention (CDC), Brazilian Ministry of Health and Centro de Vigilância Epidemiológica do Estado de São Paulo from January 2000 to January 2006. Articles retrieved with the keywords Streptococcus pneumoniae, pneumococcal diseases, conjugate vaccine, antimicrobial resistance and meningitis were reviewed. SUMMARY OF THE FINDINGS: The introduction of heptavalent pneumococcal conjugate vaccine caused a dramatic reduction in the incidence of invasive pneumococcal diseases in American children, reduced antibiotic use and the number of medical visits due to otitis media and pneumonia by children. The incidence of invasive pneumococcal diseases caused by resistant strains declined in immunized children, adults and elderly individuals. In Brazil, the mortality rate of pneumococcal meningitis is very high and the resistance to antibiotics has increased over the last 5 years. CONCLUSIONS: Heptavalent pneumococcal conjugate vaccine can benefit not only children, but the entire community and should be included in the Brazilian routine immunization schedule.

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

Vacinas glicoconjugadas, cujo carboidrato da superfície de um microrganismo está covalentemente ligado a uma proteína carreadora, vêm sendo consideradas como efetivas para gerar respostas imunes que previnem um grande número de doenças. A tecnologia é genérica e aplicável a vários patógenos, se os anticorpos contra os carboidratos de superfície forem capazes de proteger contra a infecção. Três vacinas contra Haemophilus influenzae tipo b, Neissseria meningitidis Grupo C e sete sorotipos de Streptococcus pneumoniae já foram licenciadas e muitas outras estão em desenvolvimento. Este artigo discute o racional para o desenvolvimento e uso de vacinas glicoconjugadas; os mecanismos pelos quais elas induzem respostas imune dependentes de célula T e suas implicações para o seu desenvolvimento; o papel dos métodos físico-químicos na caracterização e no controle de qualidade dessas vacinas; e os produtos novos que estão em desenvolvimento.

Vaccines based on the cell surface carbohydrates of pathogenic bacteria.

Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development. This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.