Modeling the cost-effectiveness of maternal acellular pertussis immunization (aP) in different socioeconomic settings: A dynamic transmission model of pertussis in three Brazilian states.

OBJECTIVES: Using dynamic transmission models we evaluated the health and cost outcomes of adding acellular pertussis (aP) vaccination of pregnant women to infant vaccination in three Brazilian states that represent different socioeconomic conditions. The primary objective was to determine whether the same model structure could be used to represent pertussis disease dynamics in differing socioeconomic conditions. METHODS: We tested three model structures (SIR, SIRS, SIRSIs) to represent population-level transmission in three socio-demographically distinct Brazilian states: São Paulo, Paraná and Bahia. Two strategies were evaluated: infant wP vaccination alone versus maternal aP immunization plus infant wP vaccination. Model projections for 2014-2029 include outpatient and inpatient pertussis cases, pertussis deaths, years of life lost, disability-adjusted life-years (DALYs) lost, and costs (in 2014 USD) of maternal aP vaccination, infant vaccination, and pertussis medical treatment. Incremental cost per DALY averted is presented from the perspective of the Brazilian National Health System. RESULTS: Based on goodness-of-fit statistics, the SIRSIs model fit best, although it had only a modest improvement in statistical quantitative assessments relative to the SIRS model. For all three Brazilian states, maternal aP immunization led to higher costs but also saved infant lives and averted DALYs. The 2014 USD cost/DALY averted was $3068 in Sao Paulo, $2962 in Parana, and $2022 in Bahia. These results were robust in sensitivity analyses with the incremental cost-effectiveness ratios exceeding per capita gross regional product only when the probability that a pertussis case is reported was assumed higher than base case implying more overt cases and deaths and therefore more medical costs. CONCLUSIONS: The same model structure fit all three states best, supporting the idea that the disease behaves similarly across different socioeconomic conditions. We also found that immunization of pregnant women with aP is cost-effective in diverse Brazilian states.

Cost-effectiveness of maternal pertussis immunization: Implications of a dynamic transmission model for low- and middle-income countries.

OBJECTIVE: This study evaluates the cost-effectiveness of maternal acellular pertussis (aP) immunization in low- and middle-income countries using a dynamic transmission model. METHODS: We developed a dynamic transmission model to simulate the impact of infant vaccination with whole-cell pertussis (wP) vaccine with and without maternal aP immunization. The model was calibrated to Brazilian surveillance data and then used to project health outcomes and costs under alternative strategies in Brazil, and, after adjusting model parameter values to reflect their conditions, in Nigeria and Bangladesh. The primary measure of cost-effectiveness is incremental cost (2014 USD) per disability-adjusted life-year (DALY). RESULTS: The dynamic model shows that maternal aP immunization would be cost-effective in Brazil, a middle-income country, under the base-case assumptions, but would be very expensive at infant vaccination coverage in and above the threshold range necessary to eliminate the disease (90-95%). At 2007 infant coverage (DTP1 90%, DTP3 61% at 1 year of age), maternal immunization would cost < $4,000 per DALY averted. At high infant coverage, such as Brazil in 1996 (DTP1 94%, DTP3 74% at 1 year), cost/DALY increases to $1.27 million. When the model's time horizon was extended from 2030 to 2100, cost/DALY increased under both infant coverage levels, but more steeply with high coverage. The results were moderately sensitive to discount rate, maternal vaccine price, and maternal aP coverage and were robust using the 100 best-fitting parameter sets. Scenarios representing low-income countries showed that maternal aP immunization could be cost-saving in countries with low infant coverage, such as Nigeria, but very expensive in countries, such as Bangladesh, with high infant coverage. CONCLUSION: A dynamic model, which captures the herd immunity benefits of pertussis vaccination, shows that, in low- and middle-income countries, maternal aP immunization is cost-effective when infant vaccination coverage is moderate, even cost-saving when it is low, but not cost-effective when coverage levels pass 90-95%.

Comparison of static and dynamic models of maternal immunization to prevent infant pertussis in Brazil.

BACKGROUND: This paper compares cost-effectiveness results from two models of maternal immunization to prevent pertussis in infants in Brazil, one static, one dynamic, to explore when static models are adequate for public health decisions and when the extra effort required by dynamic models is worthwhile. METHODS: We defined two scenarios to explore key differences between static and dynamic models, herd immunity and time horizon. Scenario 1 evaluates the incremental cost/DALY of maternal acellular pertussis (aP) immunization as routine infant vaccination coverage ranges from low/moderate up to, and above, the threshold at which herd immunity begins to eliminate pertussis. Scenario 2 compares cost-effectiveness estimates over the models' different time horizons. Maternal vaccine prices of $9.55/dose (base case) and $1/dose were evaluated. RESULTS: The dynamic model shows that maternal immunization could be cost-saving as well as life-saving at low levels of infant vaccination coverage. When infant coverage reaches the threshold range (90-95%), it is expensive: the dynamic model estimates that maternal immunization costs $2 million/DALY at infant coverage > 95% and maternal vaccine price of $9.55/dose; at $1/dose, cost/DALY is $200,000. By contrast, the static model estimates costs/DALY only modestly higher at high than at low infant coverage. When the models' estimates over their different time horizons are compared at infant coverage < 90-95%, their projections fall in the same range. CONCLUSIONS: Static models may serve to explore an intervention's cost-effectiveness against infectious disease: the direction and principal drivers of change were the same in both models. When, however, an intervention too small to have significant herd immunity effects itself, such as maternal aP immunization, takes place against a background of vaccination in the rest of the population, a dynamic model is crucial to accurate estimates of cost-effectiveness. This finding is particularly important in the context of widely varying routine infant vaccination rates globally. CLINICAL TRIAL REGISTRY: Clinical Trial registry name and registration number: Not applicable.

Combined effect of PCV10 and meningococcal C conjugate vaccination on meningitis mortality among children under five years of age in Brazil.

The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the Brazilian National Immunization Program in March 2010, scheduled at 2, 4, and 6 months, with a booster at 12-15 months of age. The meningococcal C conjugate vaccine (MCC) was introduced in November 2010, scheduled at 3 and 5 months, with a booster dose at 12-15 months of age and no catch-up for older age groups. In this interrupted time-series analysis study, we used Brazilian mortality data from 2005 to 2015 for children under five years of age (excluding data from the state of Bahia) to assess the combined impact of these vaccines on the overall burden of meningitis mortality among children aged 0-23 months and 2-4 years, as defined using meningitis and meningococcemia specific International Classification of Diseases - tenth revision codes. Secular trends and seasonality were taken into account. We found significant reductions for both age groups relative to those observed for the comparison group of diseases, with immediate effects after the transition period (2010-2011) of 29.2% and 27.5% for children aged 0-23 months and 2-4 years, respectively. These immediate effects were sustained throughout the post-vaccination period (2012-2015). In total, 337 deaths were averted by the combined effect of both vaccines, 238 (95%CI 169-319) for children aged 0-23 months and 99 (95%CI 56-144) for those aged 2-4 years. These results add strong evidence in support of investments in these vaccines by low and middle-income countries.

Direct and indirect impact of 10-valent pneumococcal conjugate vaccine introduction on pneumonia hospitalizations and economic burden in all age-groups in Brazil: A time-series analysis.

Background: Ten-valent pneumococcal conjugate vaccine (PCV10) was introduced in the National Immunization Program of Brazil in March/2010. Although there are recent reports of PCV10 impact on pneumonia hospitalizations, there is still uncertainty regarding the indirect impact in individuals non-targeted by vaccination. We assessed both direct and indirect effect of PCV10 on pneumonia hospitalizations and the impact on the economic burden of pneumonia hospitalizations. Methods: An interrupted time-series analysis was conducted considering monthly rates of pneumonia hospitalizations and comparison groups, in all age-groups, from January/2005-December/2015. We used records of the National Hospitalizations Information System. Observed pneumonia rates in the post-vaccination period (2011­2015) were compared to predicted rates, should PCV10 had not been introduced. Relative percent difference in rates and its 95% confidence interval were estimated. The number of pneumonia hospitalizations averted by vaccination was calculated as the difference between the predicted and observed cumulative number of pneumonia hospitalizations in the post-vaccination period. The impact of PCV10 on economic burden was presented as averted costs of pneumonia hospitalization. Results: Significant decrease in rates of pneumonia hospitalization was observed in both children targeted by vaccination (17.4%­26.5%; p<0.01), and in age-groups not targeted by vaccination (11.1%­27.1%, in individuals 10­49 years; p<0.01). In contrast, PCV10 introduction did not alter the increasing trends in pneumonia hospitalization among elderly ≥65 years. A total of 457,564 pneumonia hospitalizations was averted in Brazil for individuals aged <50 years, with a total averted costs of BRL 383.2 million (Int$ 225.2 million, and USD 147 million) for the 5 year period after PCV introduction. Conclusion: Vaccination with PCV10 5 years after its introduction in Brazil was associated with a relevant reduction in pneumonia hospitalization in the target age-groups, with an indirect effect in individuals aged 10­49 years, and significant reduction in associated economic burden. The increasing trends in pneumonia hospitalization rates in the elderly is a matter of concern for public health and should be further investigated.

Hospitalization costs of severe bacterial pneumonia in children: comparative analysis considering different costing methods.

OBJECTIVE: To determine and compare hospitalization costs of bacterial community-acquired pneumonia cases via different costing methods under the Brazilian Public Unified Health System perspective. METHODS: Cost-of-illness study based on primary data collected from a sample of 59 children aged between 28 days and 35 months and hospitalized due to bacterial pneumonia. Direct medical and non-medical costs were considered and three costing methods employed: micro-costing based on medical record review, micro-costing based on therapeutic guidelines and gross-costing based on the Brazilian Public Unified Health System reimbursement rates. Costs estimates obtained via different methods were compared using the Friedman test. RESULTS: Cost estimates of inpatient cases of severe pneumonia amounted to R$ 780,70/$Int. 858.7 (medical record review), R$ 641,90/$Int. 706.90 (therapeutic guidelines) and R$ 594,80/$Int. 654.28 (Brazilian Public Unified Health System reimbursement rates). Costs estimated via micro-costing (medical record review or therapeutic guidelines) did not differ significantly (p=0.405), while estimates based on reimbursement rates were significantly lower compared to estimates based on therapeutic guidelines (p<0.001) or record review (p=0.006). CONCLUSION: Brazilian Public Unified Health System costs estimated via different costing methods differ significantly, with gross-costing yielding lower cost estimates. Given costs estimated by different micro-costing methods are similar and costing methods based on therapeutic guidelines are easier to apply and less expensive, this method may be a valuable alternative for estimation of hospitalization costs of bacterial community-acquired pneumonia in children. OBJETIVO: Determinar e comparar custos hospitalares no tratamento da pneumonia bacteriana adquirida na comunidade por diferentes metodologias de custeio, na perspectiva do Sistema Único de Saúde. MÉTODOS: Estudo de custo, com coleta de dados primários de uma amostra de 59 crianças com 28 dias a 35 meses de idade hospitalizadas por pneumonia bacteriana. Foram considerados custos diretos médicos e não médicos. Três metodologias de custeio foram utilizadas: microcusteio por revisão de prontuários, microcusteio considerando diretriz terapêutica e macrocusteio por ressarcimento do Sistema Único de Saúde. Os custos estimados pelas diferentes metodologias foram comparados utilizando o teste de Friedman. RESULTADOS: Os custos hospitalares de crianças com pneumonia grave foram R$ 780,70 ($Int. 858.7) por revisão de prontuários, R$ 641,90 ($Int. 706.90) por diretriz terapêutica e R$ 594,80 ($Int. 654.28) por ressarcimento do Sistema Único de Saúde, respectivamente. A utilização de metodologias de microcusteio (revisão de prontuários e diretriz) resultou em estimativas de custos equivalentes (p=0,405), enquanto o custo estimado por ressarcimento foi significativamente menor do que aqueles estimados por diretriz (p<0,001) e por revisão de prontuário (p=0,006), sendo, assim, significativamente diferentes. CONCLUSÃO: Na perspectiva do Sistema Único de Saúde, existe diferença significativa nos custos estimados quando se utilizam diferentes metodologias, sendo a estimativa por ressarcimento a que resulta em valores menores. Considerando que não há diferença nos valores de custos estimados por diferentes metodologias de microcusteio, a metodologia de custeio por diretriz, de mais fácil e rápida execução, é uma alternativa válida para estimativa de custos de hospitalização por pneumonias bacterianas em crianças.

Hospitalization costs of severe bacterial pneumonia in children: comparative analysis considering different costing methods / Custos hospitalares de pneumonia bacteriana grave em crianças: análise comparativa por diferentes métodos de custeio

ABSTRACT Objective To determine and compare hospitalization costs of bacterial community-acquired pneumonia cases via different costing methods under the Brazilian Public Unified Health System perspective. Methods Cost-of-illness study based on primary data collected from a sample of 59 children aged between 28 days and 35 months and hospitalized due to bacterial pneumonia. Direct medical and non-medical costs were considered and three costing methods employed: micro-costing based on medical record review, micro-costing based on therapeutic guidelines and gross-costing based on the Brazilian Public Unified Health System reimbursement rates. Costs estimates obtained via different methods were compared using the Friedman test. Results Cost estimates of inpatient cases of severe pneumonia amounted to R$ 780,70/$Int. 858.7 (medical record review), R$ 641,90/$Int. 706.90 (therapeutic guidelines) and R$ 594,80/$Int. 654.28 (Brazilian Public Unified Health System reimbursement rates). Costs estimated via micro-costing (medical record review or therapeutic guidelines) did not differ significantly (p=0.405), while estimates based on reimbursement rates were significantly lower compared to estimates based on therapeutic guidelines (p<0.001) or record review (p=0.006). Conclusion Brazilian Public Unified Health System costs estimated via different costing methods differ significantly, with gross-costing yielding lower cost estimates. Given costs estimated by different micro-costing methods are similar and costing methods based on therapeutic guidelines are easier to apply and less expensive, this method may be a valuable alternative for estimation of hospitalization costs of bacterial community-acquired pneumonia in children.

RESUMO Objetivo Determinar e comparar custos hospitalares no tratamento da pneumonia bacteriana adquirida na comunidade por diferentes metodologias de custeio, na perspectiva do Sistema Único de Saúde. Métodos Estudo de custo, com coleta de dados primários de uma amostra de 59 crianças com 28 dias a 35 meses de idade hospitalizadas por pneumonia bacteriana. Foram considerados custos diretos médicos e não médicos. Três metodologias de custeio foram utilizadas: microcusteio por revisão de prontuários, microcusteio considerando diretriz terapêutica e macrocusteio por ressarcimento do Sistema Único de Saúde. Os custos estimados pelas diferentes metodologias foram comparados utilizando o teste de Friedman. Resultados Os custos hospitalares de crianças com pneumonia grave foram R$ 780,70 ($Int. 858.7) por revisão de prontuários, R$ 641,90 ($Int. 706.90) por diretriz terapêutica e R$ 594,80 ($Int. 654.28) por ressarcimento do Sistema Único de Saúde, respectivamente. A utilização de metodologias de microcusteio (revisão de prontuários e diretriz) resultou em estimativas de custos equivalentes (p=0,405), enquanto o custo estimado por ressarcimento foi significativamente menor do que aqueles estimados por diretriz (p<0,001) e por revisão de prontuário (p=0,006), sendo, assim, significativamente diferentes. Conclusão Na perspectiva do Sistema Único de Saúde, existe diferença significativa nos custos estimados quando se utilizam diferentes metodologias, sendo a estimativa por ressarcimento a que resulta em valores menores. Considerando que não há diferença nos valores de custos estimados por diferentes metodologias de microcusteio, a metodologia de custeio por diretriz, de mais fácil e rápida execução, é uma alternativa válida para estimativa de custos de hospitalização por pneumonias bacterianas em crianças.

Effect of 10-valent pneumococcal vaccine on pneumonia among children, Brazil.

Pneumonia is most problematic for children in developing countries. In 2010, Brazil introduced a 10-valent pneumococcal conjugate vaccine (PCV10) to its National Immunization Program. To assess the vaccine's effectiveness for preventing pneumonia, we analyzed rates of hospitalization among children 2-24 months of age who had pneumonia from all causes from January 2005 through August 2011. We used data from the National Hospitalization Information System to conduct an interrupted time-series analysis for 5 cities in Brazil that had good data quality and high PCV10 vaccination coverage. Of the 197,975 hospitalizations analyzed, 30% were for pneumonia. Significant declines in hospitalizations for pneumonia were noted in Belo Horizonte (28.7%), Curitiba (23.3%), and Recife (27.4%) but not in São Paulo and Porto Alegre. However, in the latter 2 cities, vaccination coverage was less than that in the former 3. Overall, 1 year after introduction of PCV10, hospitalizations of children for pneumonia were reduced.

Spatial clusters of violent deaths in a newly urbanized region of Brazil: highlighting the social disparities.

BACKGROUND: Deaths due to homicides and traffic accidents among youth are a public health issue worldwide. Studies of the complex network of cause and effect on this topic point to both poverty and health inequalities. Different investigational approaches to intentional and unintentional deaths combined with socioeconomic variables can help create a better understanding of the association between violence and socioeconomic conditions. This study analyzed the spatial distribution and potential clusters of risk for intentional and unintentional deaths among youths aged 15-24 years in Goiânia, a newly urbanized city in central Brazil. METHODS: Death data and residential addresses were extracted from the national Mortality Information System and validated by household visits. To detect all potential cases, we prospectively investigated every death classified as a transport accident, assault, legal intervention, intentional self-harm, unknown underlying cause, and undetermined intent according to the ICD-10.The Geographical Information System was used to plot residential addresses, and cases were interactively geocoded to the residential address level using a digital map of the municipality. Spatial scan statistic was applied (Poisson model) to identify clusters of census tracts with high mortality due to intentional injuries and traffic accidents. The socioeconomic variables obtained using census data were compared between the most likely cluster and other areas of the municipality. RESULTS: The most violent deaths among young people were due to intentional injuries. Between August 2005 and August 2006, 145 addresses for cases of intentional injuries and traffic accidents were located and geocoded. No significant clusters for deaths due to traffic accidents were found within the municipality. One significant cluster (RR = 4.65; p = 0.029) composed of 14 cases of intentional deaths, mostly homicides, was detected in an emergent, populated, and very poor area on the outskirts of the town. This cluster had a significantly higher proportion of people with the lowest educational status, lowest income, and poor housing conditions in comparison to the remainder of the municipality. CONCLUSION: Our findings highlight the link between social inequalities and intentional deaths, clearly showing the need for urgent social interventions to reduce violence and premature mortality.