Article

Cost-effectiveness of the CRM-based 7-valent pneumococcal conjugated vaccine (PCV7) in Argentina

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Abstract

Due to the region's own conditions, universal vaccination with pneumococcal conjugate heptavalent vaccine (PCV-7) in Latin American countries is still controversial. To compare projected economic costs and health benefits associated with pneumococcal conjugate heptavalent vaccine as a routine immunization in healthy children in Argentina. A decision analytic model of Markov simulated lifetime evolution of a birth cohort (n 696,451) was developed and compared costs and health benefits of pneumococcal disease in the presence and absence of vaccination. Cost per life year (LY) gained, reduce in diseases burden and costs of vaccination. From the society's perspective, the incremental cost per LY gained was US$ 5599.42 and the purchase of the 4 doses of vaccine for the entire cohort with a cost of US$ 26.5 dose requires an investment of US$ 73,823,806.00. The model estimated that vaccination reduce the number of death by 159 cases of meningitis, 756 cases of bacteriemias 4594 cases of pneumonias about 84,769 cases of otitis media and 20 meningitis sequelae. The value of the cost per LY gained was considerably modified by the variation in the cost of the vaccine dose, efficacy/effectiveness of the vaccine for pneumonia the mortality from pneumonia and herd immunity. Our analysis predicted that routine vaccination of healthy infants <2 years could prevent an important number of pneumococcal infectious and reduce related mortality and morbidity. This strategic could be highly cost-effective in Argentina.

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... There were four papers on Brazil [9][10][11][12], three on Argentina [13][14][15], two on Colombia [16,17], two on Mexico [18,19], one on Uruguay [20], one on Chile [21], and three that analyzed groups of LAC countries [22][23][24]. The main characteristics of these studies are described in Tables 1 and 2. In addition, two theses were initially identified from the Brazilian "Banco de Teses" database. ...
... Eight of the 16 studies assessed the economic impact of pneumococcal disease in children up to 5 years of age [9,10,12,15,[20][21][22][23][24]. Different target age groups (2, 3, and 10 years old) were used in the remaining studies [11,13,14,[16][17][18][19]21]. ...
... Cost-effectiveness studies (n = 11) were conducted considering hypothetical birth cohorts [9,10,12,14,15,[17][18][19][20]23,24], and Table 1 Main characteristics of studies on pneumococcal disease costs and productivity loss in LAC. cost-of-illness studies (n = 4) considered actual child population estimates [11,16,21,22]. ...
... Chest Xrays are considered the gold standard for diagnosing pneumonia, despite the variability in their interpretation even when standard guidelines are used [27,28]. The efficacy of PCV in protecting against RCP has been established in clinical trials and has been used in economic evaluations of PCV29303132333435. The etiology of AOM is also not usually established in clinical practice, and given that data on the efficacy of PCV against all-cause AOM are available, all-cause AOM can be used in economic evaluations of PCV30313233343536. ...
... The efficacy of PCV in protecting against RCP has been established in clinical trials and has been used in economic evaluations of PCV29303132333435. The etiology of AOM is also not usually established in clinical practice, and given that data on the efficacy of PCV against all-cause AOM are available, all-cause AOM can be used in economic evaluations of PCV30313233343536. Our assumption that all patients with IPDs are hospitalized may have led to an underestimation of the number of cases, in that some severe cases may evolve to death in emergency rooms and are not recorded by SIH/SUS. ...
... As a less severe disease, it is possible that cases of NMNS were treated in outpatient care; however, these data were not estimated because of a lack of available information. Information on invasive pneumococcal disease other than meningitis and sepsis (in this study, NMNS) has not been included in any of the economic evaluations of PCV in Latin American and Caribbean countries [3,32,343536 . Models used in costeffectiveness analyses of PCV generally include four syndromes: pneumonia, AOM, meningitis, and non-pneumonia non-meningitis disease (NPNM) [35]. ...
... The size of the externality is a nonlinear function of the proportion of the population vaccinated [33]. Ecological externalities were captured in five cost-effectiveness analyses [34][35][36][37][38] and three cost-benefit analyses [20,39,40]. ...
... One of the cost-benefit analyses was based on willingness-to-pay values from a contingent valuation study [20]. Of these, six captured the effect of ecological externalities in the base case [20,34,35,37,39,40] and two in sensitivity analyses [36,38]. All the studies found that including herd immunity resulted in more favorable cost-effectiveness or cost-benefit ratios and an increase in the predicted number of cases averted by vaccination. ...
... All the studies found that including herd immunity resulted in more favorable cost-effectiveness or cost-benefit ratios and an increase in the predicted number of cases averted by vaccination. Giglio et al. [37] opted for the simplest (and most approximate) approach, assuming that the number of indirectly prevented cases is just a multiple of the number of directly vaccinated individuals. Kim et al. [36] and Vespa et al. [38] examined the cost-effectiveness of different pneumococcal conjugate vaccines in the Gambia and Brazil respectively. ...
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Background Most health economic evaluations of childhood vaccination only capture the health and short-term economic benefits. Measuring broader, long-term effects of vaccination on productivity and externalities could provide a more complete picture of the value of vaccines. Method MEDLINE, EconLit and NHS-EED databases were searched for articles published between January 1990 and July 2011, which captured broader economic benefits of vaccines in low and middle income countries. Studies were included if they captured at least one of the following categories on broader economic impact: outcome-related productivity gains, behaviour-related productivity gains, ecological externalities, equity gains, financial sustainability gains or macroeconomic benefits. Results Twenty-six relevant studies were found, including observational studies, economic models and contingent valuation studies. Of the identified broader impacts, outcome-related productivity gains and ecological externalities were most commonly accounted for. No studies captured behaviour-related productivity gains or macroeconomic effects. There was some evidence to show that vaccinated children 8–14 years of age benefit from increased cognitive ability. Productivity loss due to morbidity and mortality was generally measured using the human capital approach. When included, herd immunity effects were functions of coverage rates or based on reduction in disease outcomes. External effects of vaccines were observed in terms of equitable health outcomes and contribution towards synergistic and financially sustainable healthcare programs. Conclusion Despite substantial variation in the methods of measurement and outcomes used, the inclusion of broader economic impact was found to improve the attractiveness of vaccination. Further research is needed on how different tools and techniques can be used in combination to capture the broader impact of vaccination in a way that is consistent with other health economic evaluations. In addition, more country level evidence is needed from low and middle income countries to justify future investments in vaccines and immunization programs. Finally, the proposed broader economic impact framework may contribute towards better communication of the economic arguments surrounding vaccine uptake, leading to investments in immunization by stakeholders outside of the traditional health care sector such as ministries of finance and national treasuries.
... During the data extraction process, 19 studies were excluded (not being about pneumococcal etiology, or no data set available). As shown in Figure 1, with the addition of 1 personal communication, 35 studies remained for analyses (26 with epidemiological data and 9 for costs and use of resources analysis [42][43][44][45][46][47][48][49][50]). Of the 26 studies used to perform meta-analyses, 7 studies carried a low risk of bias, 14 moderate risk, and 5 serious risk, as assessed through the methods described previously. ...
... Regarding use of resources, studies identified included data from Argentina [42,45], Brazil [43,47,50], Chile [43,46], Mexico [49], Uruguay [43,44], and the LAC region [48]. The mean length of stay per PP case was 10 days (95% CI 7.7-12.3) ...
Article
Background: Pneumococcal pneumonia (PP) causes almost one in five deaths in children younger than 5 years worldwide. In Latin America and the Caribbean (LAC), pneumonia causes 14% of all deaths. Although pneumococcal disease is a vaccine-preventable disease that accounts for a significant proportion of this burden, the decision-making process to introduce pneumococcal conjugate vaccines in official schedules is still complex in LAC. Confirmed PP cases and epidemiology are the basis for broader projections. Objective: To gather all the information available in the LAC region to assist decision makers. Methods: We performed a systematic review of studies of consolidating and culture-confirmed pediatric PP in LAC (2000-2016) using a generic academic Internet search and search engines without language restrictions. Pairs of reviewers independently selected and assessed the studies' methodological quality. We analyzed meta-information on pneumococcal serotypes available from the SIREVA laboratory-based surveillance system. Results: A total of 35 out of 750 initially identified studies were included. In the age group between 0 and 59 years, the incidence of culture-confirmed PP ranged from 10.2 to 43.0/100,000 children, with a pooled incidence of 20.4/100,000 children (95% confidence interval 0.0-123.2). Mortality ranged from 0.4 to 5.7/100,000 children, and the pooled mortality was 2.9/100,000 children (95% confidence interval 0.3-8.2). The pooled serotype distribution from surveillance data showed that serotypes 14, 1, and 6B were the most frequent serotypes in LAC, all included in licensed vaccines. Conclusions: Studies on confirmed pediatric PP were scarce in LAC in 2000 to 2016. Epidemiology indicators and health resource use are still poorly defined.
... Other studies explored the benefits of vaccination by looking at the indirect effects of vaccination or herd immunity that result from the reduction of disease incidence in unvaccinated individuals. Indirect effects were captured in five cost-effectiveness analyses [34][35][36][37][38] and three cost-benefit analyses [39][40][41]. Of these, six captured the effect of ecological externalities (indirect effects) in the base case [37,[39][40][41]34] and two in sensitivity analyses [36,38]. ...
... Indirect effects were captured in five cost-effectiveness analyses [34][35][36][37][38] and three cost-benefit analyses [39][40][41]. Of these, six captured the effect of ecological externalities (indirect effects) in the base case [37,[39][40][41]34] and two in sensitivity analyses [36,38]. All the studies found that including herd immunity resulted in more favourable cost-effectiveness or cost-benefit ratios and an increase in the predicted number of cases averted by vaccination. ...
Article
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Economic evaluations have routinely understated the net benefits of vaccination by not including the full range of economic benefits that accrue over the lifetime of a vaccinated person. Broader approaches for evaluating benefits of vaccination can be used to more accurately calculate the value of vaccination. This paper reflects on the methodology of one such approach - the health investment life course approach - that looks at the impact of vaccine investment on lifetime returns. The role of this approach on vaccine decision-making will be assessed using the malaria health investment life course model example. We describe a framework that measures the impact of a health policy decision on government accounts over many generations. The methodological issues emerging from this approach are illustrated with an example from a recently completed health investment life course analysis of malaria vaccination in Ghana. Beyond the results, various conceptual and practical challenges of applying this framework to Ghana are discussed in this paper. The current framework seeks to understand how disease and available technologies can impact a range of economic parameters such as labour force participation, education, healthcare consumption, productivity, wages or economic growth, and taxation following their introduction. The framework is unique amongst previous economic models in malaria because it considers future tax revenue for governments. The framework is complementary to cost-effectiveness and budget impact analysis. The intent of this paper is to stimulate discussion on how existing and new methodology can add to knowledge regarding the benefits from investing in new and underutilized vaccines. Copyright © 2015. Published by Elsevier Ltd.
... Ejemplo de ello es el estudio de Giglio y col. en el que determinan la costo efectividad de la inmunización para neumococo en Argentina (9). En este estudio se consideraron los costos de todos los subsectores. ...
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Los betabloqueantes se clasifican como de 1ra, 2da y 3ra generación según la selectividad sobre el subtipo de receptores b y la presencia de propiedades vasodilatadoras. Además, se los agrupa como bB tradicionales (1ra y 2da generación) o no tradicionales (3ra generación). A pesar de su heterogeneidad como grupo, todos los bB disminuyen la presión arterial. Sin embargo, el mecanismo antihipertensivo exacto no es del todo conocido. Los nuevos betabloqueantes no tradicionales son ampliamente utilizados en el tratamiento de la insuficiencia cardíaca. Numerosos estudios aleatorizados y controlados han demostrado su eficacia, seguridad y hasta su superioridad sobre los betabloqueantes tradicionales. Curiosamente su uso en la hipertensión arterial cuenta con menor nivel y calidad de evidencia científica que en la insuficiencia cardíaca. En la presente revisión se consideran aspectos farmacocinéticos, farmacodinámicos y hemodinámicos de los betabloqueantes no tradicionales. Asimismo, se analiza la evidencia disponible sobre los efectos de este grupo farmacológico respecto del impacto en órganos blanco y su efecto sobre la morbimortalidad cardiovascular.
... The full texts of the remaining articles were further screened for inclusion in the review. Fourteen articles were excluded for not including any cost discussion or cost figures [30][31][32][33][34][35][36][37][38][39][40][41][42][43]. A further eight were excluded for not discussing costs specific to meningitis [24,29,[44][45][46][47][48][49]. ...
Article
Meningitis infections are often associated with high mortality and risk of sequelae. The costs of treatment and care for meningitis are a great burden on health care systems, particularly in resource-limited settings. The objective of this study is to review data on the costs of care for meningitis in low- and middle-income countries, as well as to show how results could be extrapolated to countries without sound data. We conducted a systematic review of the literature from six databases to identify studies examining the cost of care in low- and middle-income countries for all age groups with suspected, probable, or confirmed meningitis. We extracted data on treatment costs and sequelae by infectious agent and/or pathogen, where possible. Using multiple regression analysis, a relationship between hospital costs and associated determinants was investigated in order to predict costs in countries with missing data. This relationship was used to predict treatment costs for all 144 low- and middle-income countries. The methodology of conducting a systematic review, extrapolating, and setting up a standard database can be used as a tool to inform cost-effectiveness analyses in situations where cost of care data are poor. Both acute and long-term costs of meningitis could be extrapolated to countries without reliable data. Although only bacterial causes of meningitis can be vaccine-preventable, a better understanding of the treatment costs for meningitis is crucial for low- and middle-income countries to assess the cost-effectiveness of proposed interventions in their country. This cost information will be important as inputs in future cost-effectiveness studies, particularly for vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.
... EEs concur [54,55]. In Argentina [56], Uruguay [57], and Brazil [58,59] PCV was shown to be more cost-effective than the nonvaccination scenario. ...
... This country has a comprehensive immunization program, in which MINSA provides vaccines to the whole population through the social security system and, in some cases, within the private sector [39,51]. There have been studies assessing cost effectiveness of PCV7 [23,27,28,52], but few studies assessing PCV10 and PCV13 [29,32,35] have been conducted in this part of the world. ...
Article
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Introduction: Pneumococcal pneumonia (PP) has a high burden of morbimortality in children. Use of pneumococcal conjugate vaccines (PCVs) is an effective preventive measure. After PCV 7-valent (PCV7) withdrawal, PCV 10-valent (PCV10) and PCV 13-valent (PCV13) are the alternatives in Peru. This study aimed to evaluate cost effectiveness of these vaccines in preventing PP in Peruvian children <5 years-old. Methodology: A cost-effectiveness analysis was developed in three phases: a systematic evidence search for calculating effectiveness; a cost analysis for vaccine strategies and outcome management; and an economic model based on decision tree analysis, including deterministic and probabilistic sensitivity analysis using acceptability curves, tornado diagram, and Monte Carlo simulation. A hypothetic 100 vaccinated children/vaccine cohort was built. An incremental cost-effectiveness ratio (ICER) was calculated. Results: The isolation probability for all serotypes in each vaccine was estimated: 38% for PCV7, 41% PCV10, and 17% PCV13. Avoided hospitalization was found to be the best effectiveness model measure. Estimated costs for PCV7, PCV10, and PCV13 cohorts were USD13,761, 11,895, and 12,499, respectively. Costs per avoided hospitalization were USD718 for PCV7, USD333 for PCV10, andUSD 162 for PCV13. At ICER, PCV7 was dominated by the other PCVs. Eliminating PCV7, PCV13 was more cost effective than PCV10 (confirmed in sensitivity analysis). Conclusions: PCV10 and PCV13 are more cost effective than PCV7 in prevention of pneumonia in children <5 years-old in Peru. PCV13 prevents more hospitalizations and is more cost-effective than PCV10. These results should be considered when making decisions about the Peruvian National Inmunizations Schedule.
... Treatment cost analyses of pneumonia and diarrheal disease among children under-5 are scarce in Latin American and Caribbean (LAC) countries. In the published literature on pneumonia treat- ment costs, data are available for only a limited number of countries [9][10][11][12][13][14][15]. In Colombia, for example, only two studies have described pneumonia costs among children [16,17]. ...
... At higher cutoffs, 34 (77%) and 38 (86%) articles reported results of less than or equal to $500/DALY averted and $1000/DALY averted, respectively. Only nine of the costeffectiveness/cost-utility articles (12%) modeled herd immunity to capture health gains by the community, including unvaccinated individuals [35,52,64,65,71,74,87,106,108]. Table 1 We also looked at cost-benefit analysis studies that reported results with a benefit cost ratio or net benefit. ...
... Several economic studies on PCV have been carried out in Latin America [37][38][39][40]. In Argentina N.D. Giglio conducted one with PCV-7 [41] and some others are in progress in different countries using the same integrated TRIVAC vaccine cost-effectiveness model [42]. So far, as our analysis, all of them have shown that vaccination against S. pneumoniae in the region is cost-effective and would represent a high-impact intervention for the national public health status due to the high disease burden related to this pathogen, and the costs of the healthcare system associated with treatment. ...
Article
Since the 10-valent pneumococcal conjugate vaccine (PCV-10) and 13-valent pneumococcal conjugate vaccine (PCV-13) were recently licensed for use in Argentina, both vaccines were evaluated to estimate the costs, health benefits and cost-effectiveness of adding a PCV to the routine child immunization schedule. The integrated TRIVAC vaccine cost-effectiveness model from Pan American Health Organization's ProVac Initiative (Version 1.0.65) was used to assess the health outcomes of 20 successive cohorts from birth to 5 years of age. PCV-10 and PCV-13 were each compared to a scenario assuming no PCV vaccination. A 3+1 (three doses+booster) schedule and a vaccination price of US$ 20.75 per dose was assumed in the base case for both vaccines. Introduction of PCV-13 rather than PCV-10 would increase the number of life years gained (LYG) by at least 10%. The number of LYG (and LYG after adjustment for DALY morbidity weights) was 56,882 (64,252) for PCV-10 compared to 65,038 (71,628) for PCV-13. From the health system perspective, the cost per DALY averted was US$ 8973 and US$ 10,948 for PCV-10 and PCV-13 respectively, and US$ 8546 and US$ 10,510 respectively, after incorporating costs saved by households. When PCV13 was compared to PCV10 directly, the additional benefits of PCV-13 was conferred at a cost of US$ 28,147 per DALY averted. Cost-effectiveness was influenced mainly by vaccine price, serotype replacement, pneumonia mortality and discount rate. Routine vaccination against S. pneumoniae in Argentina would be cost-effective with either PCV-10 or PCV-13. PCV-13, with higher coverage of local serotypes, would prevent more cases of pneumonia, invasive pneumococcal disease, sequelae and deaths with a higher number of LYG and DALYs averted, but PCV-10, due its higher impact in the prevention of AOM, would save more costs to the healthcare system.
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Background Pneumococcal diseases cause substantial mortality, morbidity, and economic burden. Evidence on data inputs for economic evaluations of interventions targeting pneumococcal disease is critical. Objectives To summarize evidence on resource use, costs, health utilities, and cost-effectiveness for pneumococcal disease and associated interventions to inform future economic analyses. Methods We searched MEDLINE, Embase, Web of Science, CINAHL, PsycINFO, EconLit, and Cochrane databases for peer-reviewed studies in English on pneumococcal disease that reported health utilities using direct or indirect valuation methods, resource use, costs, or cost-effectiveness of intervention programs, and summarized the evidence descriptively. Results We included 383 studies: 9 reporting health utilities, 131 resource use, 160 economic costs of pneumococcal disease, 95 both resource use and costs, and 178 economic evaluations of pneumococcal intervention programs. Health state utility values ranged from 0 to 1 for both meningitis and otitis media and from 0.3 to 0.7 for both pneumonia and sepsis. Hospitalization was shortest for otitis media (range: 0.1-5 days) and longest for sepsis/septicemia (6-48). The main categories of costs reported were drugs, hospitalization, and household or employer costs. Resource use was reported in hospital length of stay and number of contacts with general practitioners. Costs and resource use significantly varied among population ages, disease conditions, and settings. Current vaccination programs for both adults and children, antibiotic use and outreach programs to promote vaccination, early disease detection, and educational programs are cost-effective in most countries. Conclusion This study has generated a comprehensive repository of health economic evidence on pneumococcal disease that can be used to inform future economic evaluations of pneumococcal disease intervention programs.
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While the clinical evidence of vaccine benefits is generally well established, the argument on the broader economic benefits resulting from investments in vaccines and immunization programs is murky and oftentimes, not well articulated. This is mostly true for low and middle-income countries. In this article, we examined literature evaluating both narrow and broad economic benefits of vaccines in LMICs from January 2000 to October 2016. A total of 177 studies were reviewed. Of these, 146 (82%) focused on understanding short-term direct and indirect impact (narrow economic benefits) of vaccines and 31 (18%) examined broader economic benefits which included willingness to pay for vaccines, outcome-related productivity gains, and savings accrued from preventing vaccine preventable disease (VPD) outbreaks. Virtually all studies reviewed concluded that implementation of various vaccine strategies were cost saving, cost-effective or, both cost saving and highly cost-effective under varying assumptions. The studies were further analyzed under three broad vaccine categories which included those focusing on new and underutilized vaccines 125 (71%), vaccines at the prequalification stage 31 (17%) and the traditional vaccines deployed through the Expanded Programme on Immunization such as pentavalent diphtheria-pertussis-tetanus, and those against polio, tuberculosis and measles which accounted for 21 (12%) of the studies. There was unequal geographic distribution of these studies when analyzed by World Health Organization regions. Regions like the Eastern Mediterranean and Europe had fewest studies completed (6) and (7) respectively. The lack of a standardized methodology and assumptions made cross-study comparisons and also broad generalization of some of the conclusions difficult. Most studies indicate that investments in immunization programs are cost effective and in some cases cost saving. Studies were skewed to narrow economic benefits. Wide variations in methods and assumptions made cross-country/study and regions comparisons difficult to achieve.
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Seven-valent pneumococcal conjugate vaccines (PCV7) have been used in children for more than a decade. Given the observed increase in disease caused by pneumococcal serotypes not covered by PCV7, an increasing number of countries are switching from 7-valent to 10- and 13-valent PCVs ("PCV10" and "PCV13"). Economic evaluations are important tools to inform decisions and price negotiations to make such a switch. This review aims to provide a critical assessment of economic evaluations involving PCV10 or PCV13, published since 2006. We searched Scopus, ISI Web of Science (SCI and SSCI) and Pubmed to retrieve, select and review relevant studies, which were archived between 1st January 2006 and 31st January 2014. The review protocol involved standard extraction of assumptions, methods, results and sponsorships from the original studies. Sixty-three economic evaluations on PCVs published since January 2006 were identified. About half of these evaluated PCV10 and/or PCV13, the subject of this review. At current prices, both PCV13 and PCV10 were likely judged preferable to PCV7. However, the combined uncertainty related to price differences, burden of disease, vaccine effectiveness, herd and serotype replacement effects determine the preference base for either PCV10 or PCV13. The pivotal assumptions and results of these analyses also depended on which manufacturer sponsored the study. A more thorough exploration of uncertainty should be made in future analyses on this subject, as we lack understanding to adequately model herd and serotype replacement effects to reliably predict the population impact of PCVs. The introduction of further improved PCVs in an environment of evolving antibiotic resistance and under the continuing influence of previous PCVs implies that the complexity and data requirements for relevant analyses will further increase. Decision makers using these analyses should not just rely on an analysis from a single manufacturer. Copyright © 2015. Published by Elsevier Ltd.
Article
Pneumococcal meningitis and bacteremia pose a significant disease burden in Latin America and the Caribbean (LAC). To perform a systematic review of studies of pediatric pneumococcal meningitis and non-pneumonia, non-meningitis (NPNM) pneumococcal bacteremia in LAC, we conducted an exhaustive search from 2000 to 2010 in electronic databases and grey literature. Pairs of independently selected reviewers assessed the quality and extracted the studies' data. A STROBE-based checklist was used to assess the risk of bias in observational studies. Meta-analyses were performed. 39 out of 1218 retrieved studies were included. In children less than 5 years the pooled 95%CI percentage of pneumococcal etiology out of cases studied with cerebrospinal fluid/blood cultures was 6.0%(95%CI 3.3-9.5) for meningitis and 8.0%(95%CI 5.3-12.4) for bacteremia. The incidences per 100.000 children were 4.7(CI95%, 3.2-6.1) and 3.9(CI95% 2.0-5.9) for pneumococcal meningitis and NPNM bacteremia, respectively. The mortality was 8.3(95%CI 0.0-21.0) and 0.5(95%CI 0.3.0-0.6)/100,000 for meningitis and sepsis, respectively. The case fatality ratio was 33.2%(CI95% 21.3-46.2) for meningitis and 29.0%(CI95% 21.9-36.8) for sepsis. The pooled serotype distribution from SIREVA surveillance data showed that 14, 5, 6B (for meningitis) and 14, 6B, 19F (for bacteremia) were the most frequent serotypes, all included in licensed vaccines. Pneumococcal meningitis and bacteremia are important causes of morbidity and mortality in LAC children under 5 years old. This systematic review provided evidence about the burden of pneumococcal disease and the serotype distribution in order to assess the impact the pneumococcal vaccines and to assist decision-makers in the region.
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This is a 2011 government report that reviews the literature on pneumococcal conjugate vaccination in terms of efficacy, safety, effectiveness and cost-effectiveness. It also presents an extensive head to head comparison of the cost-effectiveness and cost-utility of 10 and 13-valent pneumococcal conjugate vaccines in Belgium. It includes an exploration of different measures for direct vaccine efficacy as well as of the indirect effects due to herd immunity and serotype replacement.
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Pneumococcal conjugate vaccines (PCVs) are in the process of implementation in Latin America. Experience in developed countries has shown that they reduce the incidence of invasive and non-invasive disease. However, there is evidence that the introduction of PCVs in universal mass vaccination programs, combined with inappropriate and extensive use of antibiotics, could be associated to changes in non-PCV serotypes, including serotype 19A. We conducted a systematic review to determine the distribution of serotype 19A, burden of pneumococcal disease and antibiotic resistance in the region. We performed a systematic review of serotype 19A data from observational and randomized clinical studies in the region, conducted between 1990 and 2010, for children under 6 years. Pooled prevalence estimates from surveillance activities with confidence intervals were calculated. We included 100 studies in 22 countries and extracted data from 63. These data reported 19733 serotyped invasive pneumococcal isolates, 3.8% of which were serotype 19A. Serotype 19A isolates were responsible for 2.4% acute otitis media episodes, and accounted for 4.1% and 4.4% of 4,380 nasopharyngeal isolates from healthy children and in hospital-based/sick children, respectively. This serotype was stable over the twenty years of surveillance in the region. A total of 53.7% Spn19A isolates from meningitis cases and only 14% from non meningitis were resistant to penicillin. Before widespread PCV implementation in this region, serotype 19A was responsible for a relatively small number of pneumococcal disease cases. With increased use of PCVs and a greater number of serotypes included, monitoring S. pneumoniae serotype distribution will be essential for understanding the epidemiology of pneumococcal disease.
Article
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.
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Background: Argentina’s population was heavily affected by the 2009 influenza pandemic, particularly children, in whom incidence of seasonal influenza is consistently high. Following the pandemic, Argentinean national recommendations for pediatric vaccination against A/H1N1 influenza were defined for all children aged up to five years, in line with programs implemented by national authorities elsewhere. Economic evaluations have found that vaccination programs for this population against seasonal influenza are cost-effective, if not cost-saving in many countries. Recently, Argentina decided to routinely vaccinate against influenza children aged 6–23 mo-old. But, the economic value of such strategies for the country has never been assessed. Methods: A model was developed to assess the value of four different vaccination strategies: (1) no pediatric vaccination; (2) vaccination of 6–23 mo-old children; (3) vaccination of 6–36 mo-old children; (4) vaccination of 6 mo−5 y-old children. We first estimated community health benefits of vaccination then we evaluated the economic and quality-of-life impact of these strategies on the population. Data used in the model come from surveillance networks, published literature, national databases and retrospective hospital-based data. Results: Pediatric influenza vaccination benefited not only children but also the overall community, due to decreased disease transmission. Our results showed that the recent decision by Argentina to vaccinate 6–23 mo-old children is cost-effective as would be the incremental vaccination of broader age groups. Conclusions: Results from this study are consistent with previous analyses in other countries confirming that implementing influenza pediatric vaccination programs can be highly cost-effective through individual- and community protection against the disease.
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There are few data with respect to pneumococcal meningitis in neonates. Epidemiological aspects, clinical features and outcomes in newborn infants diagnosed with pneumococcal meningitis were evaluated in this study. Nineteen newborn infants in a neonatal intensive care unit diagnosed with culture-proven community-acquired bacterial meningitis between January 1999 and December 2008 were reviewed, and of them, eight patients were diagnosed as pneumococcal meningitis. Overall, among 10,186 hospitalized newborn infants, 132 community-acquired sepsis/meningitis cases (1.3%) were suspected, and blood cultures were performed in all, while cerebrospinal fluid (CSF) cultures could be performed in 124 cases. Rate of blood culture positivity was 45%. Nineteen (15.3%) of 124 were diagnosed as culture-proven community-acquired bacterial meningitis, which was confirmed by CSF growth. Eight (42.1%) of 19 had pneumococcal meningitis. In pneumococcal cases, abundant Gram-positive diplococci were seen on CSF smear and Streptococcus pneumoniae was isolated from CSF cultures. All isolates were susceptible to penicillin and third-generation cephalosporins. Irritability (n: 7), poor sucking (n: 7) and fever (n: 6) were the principal findings on the initial physical examination. Of all patients with pneumococcal meningitis, four were initially given cefotaxime plus amikacin treatment, and the remaining four were initially given cefotaxime plus ampicillin plus vancomycin. Antibiotic treatment in two patients was revised during their clinical course. Additionally, in three patients, vancomycin and ampicillin was discontinued on the third day when antibiogram of CSF cultures revealed penicillin sensitivity. Overall, mortality in pneumococcal meningitis was 50%. In the surviving patients, two had epilepsy, one sensorineural hearing loss, and two mental-motor retardation. Pneumococcal meningitis was the leading cause of community-acquired neonatal meningitis in our patients. Immunization against pneumococcal disease in developing countries would be beneficial for public health and for newborn infants.
Article
While pneumococcal conjugate vaccines have shown to be highly effective against invasive pneumococcal disease, their potential effectiveness against acute otitis media (AOM) might become a major economic driver for implementing these vaccines in national immunization programmes. However, the relationship between the costs and benefits of available vaccines remains a controversial topic. Our objective is to systematically review the literature on the cost effectiveness of pneumococcal conjugate vaccination against AOM in children. We searched PubMed, Cochrane and the Centre for Reviews and Dissemination databases (Database of Abstracts of Reviews of Effects [DARE], NHS Economic Evaluation Database [NHS EED] and Health Technology Assessment database [HTA]) from inception until 18 February 2010. We used the following keywords with their synonyms: ‘otitis media’, ‘children’, ‘cost-effectiveness’, ‘costs’ and ‘vaccine’. Costs per AOM episode averted were calculated based on the information in this literature. A total of 21 studies evaluating the cost effectiveness of pneumococcal conjugate vaccines were included. The quality of the included studies was moderate to good. The cost per AOM episode averted varied from €168 to €4214, and assumed incidence rates varied from 20952 to 118000 per 100000 children aged 0–10 years. Assumptions regarding direct and indirect costs varied between studies. The assumed vaccine efficacy of the 7-valent pneumococcal CRM197-conjugate vaccine was mainly adopted from two trials, which reported 6–8% efficacy. However, some studies assumed additional effects such as herd immunity or only took into account AOM episodes caused by serotypes included in the vaccine, which resulted in efficacy rates varying from 12% to 57%. Costs per AOM episode averted were inversely related to the assumed incidence rates of AOM and to the estimated costs per AOM episode. The median costs per AOM episode averted tended to be lower in industry-sponsored studies. Key assumptions regarding the incidence and costs ofAOMepisodes have major implications for the estimated cost effectiveness of pneumococcal conjugate vaccination against AOM. Uniform methods for estimating direct and indirect costs of AOM should be agreed upon to reliably compare the cost effectiveness of available and future pneumococcal vaccines against AOM.
Article
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Las infecciones invasivas por Streptococcus pneumoniae (Spn) producen mortalidad elevada en países en desarrollo, con tasas entre 4 y 100 veces mayores que las de Estados Unidos o Canadá. Es el primer agente causal de neumonía en la infancia y de meningitis fuera de los brotes epidémicos por Neisseria meningitidis. La OPS, a través del grupo SIREVA, dedicado al desarrollo de vacunas en Latinoamérica, organizó un programa de vigilancia de infecciones invasivas por Spn en seis países: Argentina, Brasil, Chile, Colombia, México y Uruguay, iniciado en 1993 y que continúa actualmente. En Argentina participan en la actualidad más de 20 centros hospitalarios distribuidos en todas las áreas geográficas del país, actuando como Centro Nacional de referencia para la serotipificación y determinación de la resistencia a los antibióticos el Instituto ANLIS “Dr. Carlos G. Malbrán”. Objetivos. 1) Determinar los serotipos predominantes, su resistencia a los antibióticos y los cambios temporales en infecciones invasivas por Spn de niños menores de 5 años de edad. 2) Obtener información confiable para la formulación de una vacuna conjugada adecuada para la región. Metodología. Diseño prospectivo observacional. Se incluyeron todos los niños menores de 6 años de edad internados por infecciones invasivas (neumonía, meningitis, sepsis o bacteriemia), en los que se aisló Spn de un sitio previamente estéril. Se realizó control externo de confiabilidad de los resultados, inicialmente en el laboratorio de referencia de Canadá y actualmente en el Instituto Adolfo Lutz de San Pablo. El análisis estadístico se realizó con EPIINFO 6 y con el programa WHONET de OMS. Resultados. Se destacan los siguientes hallazgos: Se aisló Spn en 1.390 muestras clínicas. La edad media (N= 1.175) fue de 19,5 meses, con 74,4% - 2 años; fueron neumonías 60,5%; meningitis 26,6%, sepsis 8,2%. Se halló sensibilidad disminuida a penicilina en 32,1% (414/1.288), con resistencia alta 16,1% e intermedia 16%. La resistencia a los antibióticos betalactámicos se incrementó en el período 1993-8. Los serotipos prevalentes fueron: 14 (32,5%), 6A/6B, 9V, 23F, 19F, 18C, 4, 5, 1. Los serotipos 14 y 6AB prevalecieron en menores de 2 años mientras que el 5 y el 1 prevalecieron en mayores de 2 años (p <0,001). El serotipo 14, la neumonía y la edad menor de 2 años fueron los factores de riesgo para resistencia a penicilina. La representatividad para las vacunas conjugadas 7-valente, 9-valente y 11-valente fue de 53,3%, 77,4% y 82,6% respectivamente, mayorpara la 7-valente en los menores de 2 años (61,2%) y en los menores de 2 años con neumonía (71,2%). Más del 90% de los serotipos aislados con algún grado de resistencia estuvieron contenidos en las tres vacunas analizadas. Conclusiones. Un programa nacional de vigilancia de Spn invasivo fue desarrollado en Argentina y otros países latinoamericanos. Se identificaron por primera vez los serotipos predominantes en infecciones invasivas y se comprobó el incremento significativo de la resistencia a penicilina y otros antibióticos, similar a lo informado en casi todos los países del mundo. Se obtuvo información epidemiológica válida para evaluar estrategias de prevención con nuevas vacunas.
Article
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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. 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. 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. 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.
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The incidence by age and causative organism of bacterial meningitis are not known on a community basis. The epidemiology of bacterial meningitis in a metropolitan county was studied by identifying all cases admitted to a hospital from 1983 through 1987. The overall incidence of bacterial meningitis was 5 per 100,000 person-years, but numbers of cases ranged from 40 per 100,000 for children younger than 5 years to 1.0 per 100,000 in adults aged between 16 and 64 years. No significant excesses of cases were found in male patients or in blacks. The predominant causative organism varied with age. Overall, Haemophilus influenzae was the most common causative organism, but 32 percent of cases were due to Streptococcus pneumoniae. Case fatality rates were high for S. pneumoniae (12.5 percent) and very high for the small number of elderly patients suffering from bacterial meningitis. Significant declines have occurred in the last decade in the incidence of bacterial meningitis in children, particularly in those younger than 5 years, and in disease caused by H. influenzae and group B streptococcus.
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To determine life expectancy of children with cerebral palsy. Cohort analysis, by means of register compiled from multiple sources of ascertainment, of all children with cerebral palsy born during 1966-84 to mothers resident in Mersey region. Status of children was determined by flagging through NHS central register. 1258 subjects with idiopathic cerebral palsy, of whom 1251 were traced and included in analysis. Effect of functional ability (ambulation, manual dexterity, and mental ability), sex, birth weight, and gestational age on survival. 20 year survival for whole cohort was 89.3% for females and 86.9% for males. For subjects with no severe functional disabilities 20 year survival was 99% (95% confidence interval 98% to 100%), while subjects severely disabled in all three functional groups had 20 year survival of 50% (42% to 58%). Subjects with birth weight < or = 2500 g had 20 year survival of 92% (89% to 95%), while those with birth weight > 2500 g had survival of 87% (84% to 89%). Subjects with gestational age of > 37 weeks had 20 year survival of 93% (91% to 96%), while those with gestational age > or = 37 weeks had survival of 85% (83% to 88%). Birth weight and gestational age were less predictive of survival than functional disability. Best statistical model used gestational age and number of severe functional disabilities as predictors. Life expectancy of this cohort of children with cerebral palsy was greater than has been suggested in some previous studies. This has important implications for social, educational, and health services.
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Markov models are useful when a decision problem involves risk that is continuous over time, when the timing of events is important, and when important events may happen more than once. Representing such clinical settings with conventional decision trees is difficult and may require unrealistic simplifying assumptions. Markov models assume that a patient is always in one of a finite number of discrete health states, called Markov states. All events are represented as transitions from one state to another. A Markov model may be evaluated by matrix algebra, as a cohort simulation, or as a Monte Carlo simulation. A newer representation of Markov models, the Markov-cycle tree, uses a tree representation of clinical events and may be evaluated either as a cohort simulation or as a Monte Carlo simulation. The ability of the Markov model to represent repetitive events and the time dependence of both probabilities and utilities allows for more accurate representation of clinical settings that involve these issues.
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Laboratory-based surveillance of invasive pneumococcal infections in adults in Finland from 1983 to 1992 identified 862 episodes of pneumococcal bacteraemia and 97 episodes of meningitis. The overall incidence of invasive pneumococcal infections was 9.1 per 100,000 for all adults per year, but 27.1, 35.8, and 44.5 per 100,000 in those aged 65 years or over, 75 years or over, and 85 years or over, respectively. Most (99.7%) of the pneumococcal strains were sensitive to penicillin. Ninety-five percent of the strains belonged to serogroups/types present in the 23-valent pneumococcal polysaccharide vaccine. Group/type distribution was different in patients aged 16-64 years compared to those 65 years or over (P < 0.001), in bacteraemia compared to meningitis (P < 0.001), and in the years 1983-7 compared to 1988-92 (P < 0.05).
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Clinical decisions often have long-term implications. Analysis encounter difficulties when employing conventional decision-analytic methods to model these scenarios. This occurs because probability and utility variables often change with time and conventional decision trees do not easily capture this dynamic quality. A Markov analysis performed with current computer software programs provides a flexible and convenient means of modeling long-term scenarios. However, novices should be aware of several potential pitfalls when attempting to use these programs. When deciding how to model a given clinical problem, the analyst must weigh the simplicity and clarity of a conventional tree against the fidelity of a Markov analysis. In direct comparisons, both approaches gave the same qualitative answers.
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This paper describes how to estimate probabilities and outcome values for decision trees. Probabilities are usually derived from published studies, but occasionally are derived from existing databases, primary data collection, or expert judgment. Outcome values represent quantitative estimates of the desirability of the outcome states, and are often expressed as utility values between 0 and 1. Utility values for different health states can be derived from the published literature, from direct measurement in appropriate subjects, or from expert opinion. Methods for assigning utilities to complex outcome states are described, and the concept of quality-adjusted life years is introduced.
Chapter
Streptococcus pneumoniae (the pneumococcus) is a pathogen with significant disease implications, especially for the (very) young and the (very) old. It causes mucosal infections such as otitis media and pneumonia but also causes invasive diseases such as bacteremia and meningitis. In this book of seven chapters, international experts address the major challenges facing the current use and future development of pneumococcal conjugate vaccines - both from the scientific and the political standpoint. As such, the book comprises a comprehensive and up-to-date overview of this rapidly evolving field.
Article
Citizen participation in local redevelopment has recently been regarded as essential, since progress in democracy and diversified public interests have contributed to more importance being placed on citizen participation in the implementation of public policies. While the importance of resident participation has been increasingly emphasized in principle, in reality more effort is still required in its application. We need to develop practical strategies of collecting community opinion in order to reflect it in public policy, if we are to achieve a resident and citizen-centered society. The purpose of this study is to develop an image map construction tool that can be applied to the "Maul-Mandulgi" projects as a visualized method to facilitate the exchange of opinions and work toward agreements. The tool is intended to assist public discussion by visualizing policies and plans and reducing the possibility of misunderstanding, so that residents can properly respond to the plans. Second, this study will verify the effectiveness of the tool in the application to local community workshops. The main research method is participant observation method and field study. Major findings are as follows, First, every resident who had participated in previous workshops gathered together, used the tool and represented their opinions unusually more than once. Each resident tried to make sure that other participants appropriately understood his or her opinion. The workshop finished when all participants agreed and produced a consensus. The workshop took much less time, which is in stark contrast to previous workshops in which it took significantly more time to collect opinions. Second, it proved that residents in the redevelopment area can strike a broad agreement by themselves on a method and direction for residential improvement. In previous workshops, conflicts between residents developed over the choice between the two methods, of local improvement and total demolition prior to multi-housing construction. In this study, opinions of residents were not limited to the two methods by finding a winwin solution. Third, the use of the tool kit for image map became efficient for inactive residents to develop their own opinions in regard to the direction and orientations of the residential improvement process. In addition, for those who have either no or a slight understanding of the residential improvement projects, the tool can provide access to information and knowledge. This study concludes that the developed tool for imaging of the redevelopment projection like a design game, rather than using forms of text and speech, can be a useful tool in collecting opinions and forming an agreed opinion for forthcoming residential improvement plans.
Article
This study aimed at estimating the health and economic outcomes of universal infant vaccination with seven-valent pneumococcal conjugate vaccine (PCV-7) in Italy. A Markov model simulated lifetime evolution of a birth cohort (538,138 children): universal vaccination would avert 769 invasive infections, 18 deaths and 1323 life years. At base-case analysis, universal three-dose vaccination would cost € 26,449 (95% CI: €1975–62,075) and €38,286 (95% CI: 22,164–70,801) per life year-saved in the societal and the NHS perspective, respectively. In the hypothesis of a 5-year long protection period, vaccination would cost € 32,694 and €43,115 per life-year saved. Considering yearly incidence of invasive pneumococcal disease reported for Veneto and Sardinia regions, PCV-7 vaccination would result highly cost-effective determining a cost of €10,479 and €16,890 per life year-save in the NHS and the societal perspective, respectively.
Article
Introducción. El objetivo del trabajo fue investigar la incidencia de enfermedad invasiva por Streptococcus pneumoniae en pacientes hospitalizados y ambulatorios atendidos en centros de la ciudad de Córdoba, Argentina.Población, material y métodos. Este estudio de incidencia se realizó entre diciembre de 1999 y noviembre de 2002. Se obtuvieron hemocultivos en todos los pacientes de 2 a 23 meses de edad con sospecha de la enfermedad (temperatura axilar ≥ 39 ºC, sospecha clínica de neumonía o sospecha clínica de otra enfermedad invasiva por Streptococcus pneumoniae). A los pacientes con sintomatología respiratoria y temperatura <39 °C, se les realizó radiografía de tórax y a los que presentaban neumonías con condensación, se les realizó hemocultivo. Tanto la información demográfica y patológica como la evolución de la enfermedad se consignaron en una hoja de toma de datos.Resultados. La incidencia global de enfermedad invasiva por S. pneumoniae fue de 206,8 por 105/año, mayor en los pacientes de 6 a 17 meses. Entre las formas de presentación de la enfermedad se encontraron: 47,5% (IC 95% 40,0-55,0) de bacteriemia sin foco; 45,8% (IC 95% 38,4-53,4) de neumonía; 3,9% (IC 95% 1,7-8,2) de meningitis y 2,8% (IC 95%1,0- 6,7) de abscesos. El serotipo más frecuente fue el 14 en el 45,6% de los aislamientos, seguido del 6B y 1 con ambos en el 10,8% de los casos. Durante la vigilancia se encontró un 68% de cepas sensibles, 26% con resistencia intermedia y 6% resistentes a penicilina.Conclusiones. La tasa de incidencia de la enfermedad invasiva por S. pneumoniae en niños de Córdoba se sitúa en valores elevados en comparación con Latinoamérica y Europa, probablemente revelada por la pesquisa de la enfermedad, que en este estudio se realizó en pacientes ambulatorios que representaron más de la mitad del total de aislamientos.
Article
Objective. To determine the efficacy, safety and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine against invasive disease caused by vaccine serotypes and to determine the effectiveness of this vaccine against clinical episodes of otitis media. Methods. The Wyeth Lederle Heptavalent CRM197 (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a double blind trial; 37 868 children were randomly assigned 1:1 to receive either the pneumococcal conjugate vaccine or meningococcus type C CRM197 conjugate. The primary study outcome was invasive disease caused by vaccine serotype. Other outcomes included overall impact on invasive disease regardless of serotype, effectiveness against clinical otitis media visits and episodes, impact against frequent and severe otitis media and ventilatory tube placement. In addition the serotype-specific efficacy against otitis media was estimated in an analysis of spontaneously draining ears. Results. In the interim analysis in August, 1998, 17 of the 17 cases of invasive disease caused by vaccine serotype in fully vaccinated children and 5 of 5 of partially vaccinated cases occurred in the control group for a vaccine efficacy of 100%. Blinded case ascertainment was continued until April, 1999. As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified, all but 1 in controls for an efficacy of 97.4% (95% confidence interval, 82.7 to 99.9%), and 52 cases, all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9% (95% confidence interval, 79.6 to 98.5%). There was no evidence of any increase of disease caused by nonvaccine serotypes. Efficacy for otitis media against visits, episodes, frequent otitis and ventilatory tube placement was 8.9, 7.0, 9.3 and 20.1% with P < 0.04 for all. In the analysis of spontaneously draining ears, serotype-specific effectiveness was 66.7%. Conclusion. This heptavalent pneumococcal conjugate appears to be highly effective in preventing invasive disease in young children and to have a significant impact on otitis media.
Article
Invasive pneumococcal disease declined among children and adults after the introduction of the pediatric heptavalent pneumococcal conjugate vaccine (PCV7) in 2000, but its effect on pneumococcal meningitis is unclear. We examined trends in pneumococcal meningitis from 1998 through 2005 using active, population-based surveillance data from eight sites in the United States. Isolates were grouped into PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV7-related serotypes (6A, 9A, 9L, 9N, 18A, 18B, 18F, 19B, 19C, 23A, and 23B), and non-PCV7 serotypes (all others). Changes in the incidence of pneumococcal meningitis were assessed against baseline values from 1998-1999. We identified 1379 cases of pneumococcal meningitis. The incidence declined from 1.13 cases to 0.79 case per 100,000 persons between 1998-1999 and 2004-2005 (a 30.1% decline, P<0.001). Among persons younger than 2 years of age and those 65 years of age or older, the incidence decreased during the study period by 64.0% and 54.0%, respectively (P<0.001 for both groups). Rates of PCV7-serotype meningitis declined from 0.66 case to 0.18 case (a 73.3% decline, P<0.001) among patients of all ages. Although rates of PCV7-related-serotype disease decreased by 32.1% (P=0.08), rates of non-PCV7-serotype disease increased from 0.32 to 0.51 (an increase of 60.5%, P<0.001). The percentages of cases from non-PCV7 serotypes 19A, 22F, and 35B each increased significantly during the study period. On average, 27.8% of isolates were nonsusceptible to penicillin, but fewer isolates were nonsusceptible to chloramphenicol (5.7%), meropenem (16.6%), and cefotaxime (11.8%). The proportion of penicillin-nonsusceptible isolates decreased between 1998 and 2003 (from 32.0% to 19.4%, P=0.01) but increased between 2003 and 2005 (from 19.4% to 30.1%, P=0.03). Rates of pneumococcal meningitis have decreased among children and adults since PCV7 was introduced. Although the overall effect of the vaccine remains substantial, a recent increase in meningitis caused by non-PCV7 serotypes, including strains nonsusceptible to antibiotics, is a concern.
Article
To evaluate the economic impact of vaccination with the pneumococcal 7-valent conjugate vaccine (PCV7) in Brazil, Chile, and Uruguay. A decision analytic model was constructed to compare pneumococcal vaccination of children 0-5 years old with no vaccination in Brazil, Chile, and Uruguay. Costs and health outcomes were analyzed from the societal perspective. Vaccine, demographic, epidemiologic, and cost data were incorporated into this economic analysis. At the rate of diphtheria-tetanus-pertussis (DTP) vaccine coverage and a vaccine price of US$ 53 per dose, PCV7 was projected to prevent 23 474 deaths per year in children under 5 years old in the three countries studied, thus averting 884,841 disability-adjusted life years (DALYs) yearly. To vaccinate the entire birth cohort of the three countries, total vaccine costs would be US$ 613.9 million. At US$ 53 per dose, the cost per DALY averted from a societal perspective would range from US$ 664 (Brazil) to US$ 2019 (Chile). At a cost of US$ 10 per dose, vaccine cost is lower than the overall cost of illness averted (US$ 125,050,497 versus US$ 153,965,333), making it cost effective and cost-saving. The results of this study demonstrate that the incorporation of PCV7 vaccine at US$ 53 per dose confers health benefits at extra costs. It is unclear whether vaccinatfon at the current price is affordable to these countries.
Article
To determine the epidemiology of acute otitis media (AOM) and duration of middle ear effusion (MEE), we followed consecutively enrolled children from shortly after birth until 7 y of age. Because some children dropped out of the study, data were analyzed for 877 children observed for at least 1 y; 698 were observed for at least 3 y, and 498 were observed until 7 y of age. By 1 y of age, 62% of the children had ⩾1 episode of AOM and 17% had ⩾3 episodes; by 3 y of age, 83% had ⩾1 episode of AOM and 46% had ⩾3 episodes. The peak incidence occurred during the second 6-mo period of life. Significantly increased risk (by multivariate analysis) for AOM was associated with male gender, sibling history of recurrent AOM, early occurrence of AOM, and not being breast fed. MEE persisted after onset of AOM for weeks to months; prolonged duration of MEE was associated with male gender, sibling history of ear infection, and not being breast fed.
Article
We abstracted the results of all English language reports of the outcomes of bacterial meningitis published after 1955. We used hierarchical Bayesian meta-analysis to determine the overall and organism-specific frequencies of death and persistent neurologic sequelae in children 2 months to 19 years of age. A total of 4920 children with acute bacterial meningitis were included in 45 reports that met the inclusion criteria. Children described in the 19 reports of prospectively enrolled cohorts from developed countries had lower mortality (4.8% vs. 8.1%) and were more likely to have no sequelae (82.5% vs. 73.9%). In these 19 studies 1602 children were evaluated for at least 1 sequela after hospital discharge. The mean probabilities of these sequelae were: deafness, 10.5%; bilateral severe or profound deafness, 5.1%; mental retardation, 4.2%; spasticity and/or paresis, 3.5%; seizure disorder, 4.2%; and no detectable sequelae, 83.6%. Mean probabilities of outcomes varied significantly by etiologic bacteria, e.g. mortality: Haemophilus influenzae, 3.8%; Neisseria meningitis, 7.5%; Streptococcus pneumoniae, 15.3%.
Article
To determine the efficacy, safety and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine against invasive disease caused by vaccine serotypes and to determine the effectiveness of this vaccine against clinical episodes of otitis media. The Wyeth Lederle Heptavalent CRM197 (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a double blind trial; 37,868 children were randomly assigned 1:1 to receive either the pneumococcal conjugate vaccine or meningococcus type C CRM197 conjugate. The primary study outcome was invasive disease caused by vaccine serotype. Other outcomes included overall impact on invasive disease regardless of serotype, effectiveness against clinical otitis media visits and episodes, impact against frequent and severe otitis media and ventilatory tube placement. In addition the serotype-specific efficacy against otitis media was estimated in an analysis of spontaneously draining ears. In the interim analysis in August, 1998, 17 of the 17 cases of invasive disease caused by vaccine serotype in fully vaccinated children and 5 of 5 of partially vaccinated cases occurred in the control group for a vaccine efficacy of 100%. Blinded case ascertainment was continued until April, 1999. As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified, all but 1 in controls for an efficacy of 97.4% (95% confidence interval, 82.7 to 99.9%), and 52 cases, all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9% (95% confidence interval, 79.6 to 98.5%). There was no evidence of any increase of disease caused by nonvaccine serotypes. Efficacy for otitis media against visits, episodes, frequent otitis and ventilatory tube placement was 8.9, 7.0, 9.3 and 20.1% with P < 0.04 for all. In the analysis of spontaneously draining ears, serotype-specific effectiveness was 66.7%. This heptavalent pneumococcal conjugate appears to be highly effective in preventing invasive disease in young children and to have a significant impact on otitis media.
Article
To determine the effectiveness of the Wyeth heptavalent pneumococcal conjugate vaccine against clinical and radiograph-confirmed pneumonia in children. The heptavalent CRM(197) pneumococcal conjugate vaccine (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a randomized, double blind trial. Children were randomized to receive either the CRM(197) PCV (vaccine group) or the meningococcal type C CRM(197) conjugate vaccine (control group). The primary outcome of this trial was invasive pneumococcal disease. In addition children with the clinical diagnosis of pneumonia in the study population were identified through review of automated inpatient, emergency and outpatient databases. The subset of the cohort of these children who had chest radiographs obtained at the time of diagnosis was identified, and the original reading of their radiographs by the radiologist was obtained from automated databases. Rates of clinically diagnosed pneumonia, of pneumonia with a radiograph obtained regardless of result, of pneumonia with positive radiograph (consolidation, empyema or parenchymal infiltrate) and of pneumonia with only perihilar infiltrates were compared between vaccinated and nonvaccinated groups. In addition risk of disease pneumonia was evaluated by race and ethnicity. The incidence of a first pneumonia episode in the control group was 55.9 per 1000 person-years. A radiograph was obtained in 61% of episodes, a positive radiograph in 21% and perihilar findings in an additional 5%. In per protocol follow-up of children given PCV, first episodes of all clinically diagnosed pneumonia were reduced by 4.3% [95% confidence interval (CI), -3.5, 11.5%, = 0.27], episodes with a radiograph were reduced by 9.8% (CI 0.1, 18.5%, < 0.05) and episodes with a positive radiograph were reduced by 20.5% (CI 4.4, 34.0, = 0.02). In the intent to treat analysis including all episodes after randomization, episodes with a positive radiograph were reduced by 17.7%, =.01). The greatest impact was in the first year of life with a 32.2% reduction and a 23.4% reduction in the first 2 years, but only a 9.1% reduction in children >2 years of age. Asians, blacks and Hispanics were at higher risk of pneumonia than were whites, but there was no evidence of ethnic variation in PCV effectiveness. Ten of the 11 cases of pneumococcal pneumonia with a positive blood culture were in the control group. The pneumococcal conjugate vaccine tested was effective in reducing the risk of pneumonia in young children.
Article
Streptococcus pneumoniae is a major cause of acute otitis media (AOM) in young children. More than 90 immunologically distinct pneumococcal serotypes have been identified, but limited information is available regarding their relative importance in AOM. We analyzed nine existing datasets comprising pneumococcal isolates from middle ear fluid samples collected from 1994 through 2000 from 3,232 children with AOM from Finland, France, Greece, Israel, several East European countries, the US and Argentina. We examined the distribution of pneumococcal serotypes in relation to several demographic and epidemiologic variables, including gender, age, antibiotic resistance and source of culture material. The major serotypes identified included 19F and 23F, each comprising 13 to 25% of pneumococcal middle ear fluid isolates in most datasets; 14 and 6B, comprising 6 to 18%; whereas 6A, 19A and 9V each comprised 5 to 10%. Despite differences in location, study design and antibiotic susceptibility, each major serotype was prominent in most age groups of each dataset. Serotypes represented in the 7-valent pneumococcal conjugate vaccine (PCV-7, 4, 6B, 9V, 14, 18C, 19F, 23F) accounted for 60 to 70% of all pneumococcal isolates in the 6- to 59-month age range, but only 40 to 50% of isolates in children <6 or >/=60 months old. Serotype 3 and, in certain datasets, serotypes 1 and 5, were more important in the <6- and >/=60-month age groups. In each age group vaccine-related serotypes (mainly 6A and 19A) comprised an additional 10 to 15% of all pneumococcal isolates. Four serotypes (23F, 19F, 14 and 6B) accounted for 83% of all penicillin-resistant observations. This analysis of several geographically diverse datasets indicates that a limited number of serotypes, largely represented in PCV-7, accounted for the majority of episodes of pneumococcal AOM in children between 6 and 59 months of age. Certain serotypes appeared to be relatively more significant in children <6 months or >59 months of age.
Article
Nine- and 11-valent pneumococcal conjugate vaccines under development may control pediatric pneumococcal disease in nonindustrialized countries. Because these vaccines are expensive, population-based surveillance of pneumococcal disease in children <36 months of age was undertaken in Santiago, Chile to provide health authorities with reliable data on the burden of invasive pneumococcal disease and causative serotypes, including those in outpatients with high fever. Automated blood culture machines were introduced into 9 hospitals that admit 85% of all hospitalized children in Santiago. Acutely ill pediatric febrile ambulatory patients are attended at 8 emergency rooms (ERs) and 36 urgent primary care services. After a 12-month pilot study in 3 ERs, health authorities collected blood cultures from children <36 months of age with high fever seen in the ER as standard practice. isolates were serotyped. Blood cultures of 18 (1.2%) of 1,503 outpatients 6 to 35 months of age with high fever in the pilot study yielded S. In the ensuing 24 months 236 children <36 months old were hospitalized with invasive pneumococcal disease (incidence, 33.9 cases/10(5) children), and 188 bacteremias were detected among ambulatory ER patients with high fever (incidence, 27.0 cases/10(5) children). Although serotypes were similar among hospitalized and ambulatory cases (except 18C, which was more common in the latter), case fatality was 9.5% in hospitalized (21 of 236) 0% in ambulatory cases (0 of 188) (P = <0.0001). High level resistance to penicillin (25.8% vs 10.1%) and cefotaxime (19.5% vs 6.2%) was observed more often among pneumococcal isolates from hospitalized than among ambulatory cases (P < 0.001). ER surveillance detected approximately one case of pneumococcal bacteremia among febrile ambulatory patients for each hospitalized invasive case. Because 71% of cases were caused by vaccine serotypes (and 87% by vaccine serogroups), 9- and 11-valent pneumococcal conjugate vaccines could prevent most invasive pediatric pneumococcal disease in Chile.
Article
The heptavalent pneumococcal conjugate vaccine (PCV) is recommended for infants to protect against invasive disease, but its impact on otitis might also have public health importance. To examine the impact of PCV on the incidence of otitis media, frequent otitis media and tympanostomy tube procedures and to assess whether the effectiveness of the vaccine wanes after age 24 months and varies by race, sex or season. From 1995 to 1998, 37 868 children at Kaiser Permanente in Northern California were randomized to receive PCV or a control vaccine in a double blind trial and were followed through April 1999. Children received a primary series at 2, 4 and 6 months of age and a booster at 12 to 15 months. Visits for otitis, frequent visits for otitis and tympanostomy tube procedures. Otitis was ascertained from diagnosis checklists routinely marked by physicians. Control children averaged 1.8 otitis visits per year. Children given PCV had fewer otitis visits than control children in every age group, sex, race and season examined. Intention-to-treat analysis permitted rejection of the null hypothesis that PCV is ineffective against otitis media (P < 0.0001). In children who completed the primary series per protocol, PCV reduced otitis visits by 7.8% [95% confidence interval (CI), 5.4 to 10.2%] and antibiotic prescriptions by 5.7% (CI 4.2 to 7.2%). Frequent otitis was reduced by amounts that increased with otitis frequency, from a 10% reduction in the risk of 3 visits to a 26% reduction in the risk of 10 visits within a 6-month period. Tube placements were reduced by 24% (CI 12 to 35%). In children followed up to 3.5 years, PCV provided a moderate amount of protection against ear infections while reducing frequent otitis media and tube procedures by greater amounts.
Article
To compare projected economic costs and health benefits associated with using pneumococcal conjugate heptavalent vaccine as routine immunisation in healthy children in Switzerland. A cost-utility analysis was performed from both the societal as well as the sickness funds' perspective. Simulated birth cohorts of 80,000 children (the approximate size of a birth cohort in Switzerland) were followed from birth up to age of 5. Reduction in disease burden, costs of vaccination, cost-utility ratio (cost per quality-adjusted life year (QALY)). With a vaccine coverage of 70% vaccination of newborns only would avert 4 deaths, 8 cases of meningitis, 37 cases of other invasive pneumococcal disease, 150 cases of pneumococcal pneumonia and about 2700 cases of otitis media (OM) per year. The net cost of the vaccination program would be 22 Mio. CHF per year for society and about 19 Mio. CHF for the sickness funds. This results in a cost-utility ratio of 35,700 CHF (approximately 26,300 USD (1)) per QALY from the societal perspective and 39,300 CHF (28,900 USD) per QALY from the sickness funds' perspective. Additional catch-up vaccination of all infants <24 months in the years after vaccine introduction would result in additional benefits at a cost of 33,600 CHF per additional QALY gained. However, if the catch-up vaccination should include all children <60 months, each additional QALY would be gained at a very high cost (162,000 CHF per additional QALY). Routine vaccination of healthy infants <2 years in Switzerland can reduce mortality and long term neurologic impairment resulting from invasive pneumococcal disease at a reasonable cost-utility ratio.
Article
Streptococcus pneumoniae is one of the main causes of bacterial meningitis, bacteremia, pneumonia, and otitis media in the Netherlands. These diseases lead to substantial mortality, morbidity, and costs. The societal impact is especially severe because most cases occur in very young infants. The aim of this study was to estimate the epidemiological impact and cost-effectiveness of universal infant vaccination with a 7-valent conjugated pneumococcal vaccine in the Netherlands. Decision analysis was performed using epidemiological data and data on health care resource use from 1996 to 2001. A model was used to project the impact of pneumococcal vaccination on the incidence of pneumococcal infections in infants and children from birth to age 10 years. Costs, benefits, and health gains were estimated, and cost-effectiveness was calculated. All analyses were performed from a societal perspective. On average, 339 cases per year of invasive pneumococcal infection occurred in infants and children from birth to age 10 years in the Netherlands from 1996 to 2001. The model predicted that introduction of the 7-valent conjugated pneumococcal vaccine would prevent 48 cases of bacterial meningitis and 88 cases of pneumococcal bacteremia per year, as well as 42,695 cases of pneumococcal otitis media and 3411 cases of invasive pneumococcal pneumonia. The model also predicted that vaccination would save 13 lives per year and prevent 31 cases of lifelong sequelae, rendering 382 discounted quality-adjusted life-years (QALYs) gained or 329 discounted life-years gained per year. Considering these health gains, vaccination would prevent Euro 9,453,600 of direct and indirect medical costs of meningococcal and pneumococcal infections in the Netherlands, including acute medical care, management of sequelae, and lost time at work. With a vaccine price of Euro 40 per dose, the base-case cost-effectiveness ratio would be Euro 71,250 per QALY. The model was sensitive to changes in incidence of infections, vaccine effectiveness, and vaccine price. Our analytic model predicted that universal pneumococcal vaccination of infants in the Netherlands could prevent a large number of pneumococcal infections and considerably reduce related mortality and morbidity. However, the baseline cost-effectiveness ratio of such a vaccination program would be relatively unfavorable compared with other interventions implemented in the Netherlands.
Article
The novel pneumococcal conjugate vaccine, PncCRM, has been shown to prevent acute otitis media caused by vaccine serotypes and to reduce otitis surgery. Our aim was to assess long term efficacy of the vaccine on tympanostomy tube placements. Children with complete follow-up in the Finnish Otitis Media Vaccine Trial up to 24 months of age and still living in the study area (1490 of 1662 randomized at 2 months of age) were invited to a single visit at 4-5 years of age. The children had been vaccinated at 2, 4, 6 and 12 months of age with PncCRM or hepatitis B vaccine (control). Tympanostomy tube placements reported by parents at the visit were verified from hospital and private medical center records. Additionally, tympanostomy tube placements of all children were verified from the hospital discharge registry. Vaccine efficacy (VE) was estimated by comparing all events of tympanostomy tube placement between vaccine groups. During the vaccine trial (2-24 months of age), VE (95% confidence interval) in preventing tympanostomy tube placement was only 4% (-19-23%). Altogether 756 children were enrolled for the follow-up study. After 24 months of age, the rate of surgery was 3.5 per 100 person-years in the PncCRM and 5.7 per 100 person-years in the control children, giving VE of 39% (4-61%). In the hospital-based data of all children (N = 1490), VE of 44% was obtained (19-62%). Receipt of PncCRM vaccine at infancy was associated with a reduction in tympanostomy tube placement from 2 to 4-5 years of age.
Article
The US Food and Drug Administration approved a meningococcal conjugate A/C/Y/W-135 vaccine (MCV-4) for use in persons aged 11 to 55 years in January, 2005; licensure for use in younger age groups is expected in 2 to 4 years. To evaluate and compare the projected health and economic impact of MCV-4 vaccination of US adolescents, toddlers, and infants. Cost-effectiveness analysis from a societal perspective based on data from Active Bacterial Core Surveillance (ABCs) and other published and unpublished sources. Sensitivity analyses in which key input measures were varied over plausible ranges were performed. A hypothetical 2003 US population cohort of children 11 years of age and a 2003 US birth cohort. Hypothetical routine vaccination of adolescents (1 dose at 11 years of age), toddlers (1 dose at 1 year of age), and infants (3 doses at 2, 4, and 6 months of age). Each vaccination scenario was compared with a "no-vaccination" scenario. Meningococcal cases and deaths prevented, cost per case prevented, cost per life-year saved, and cost per quality-adjusted life-year saved. Routine MCV-4 vaccination of US adolescents (11 years of age) would prevent 270 meningococcal cases and 36 deaths in the vaccinated cohort over 22 years, a decrease of 46% in the expected burden of disease. Before program costs are counted, adolescent vaccination would reduce direct disease costs by $18 million and decrease productivity losses by $50 million. At a cost per vaccination (average public-private price per dose plus administration fees) of $82.50, adolescent vaccination would cost society $633000 per meningococcal case prevented and $121000 per life-year saved. Key variables influencing results were disease incidence, case-fatality ratio, and cost per vaccination. The cost-effectiveness of toddler vaccination is essentially equivalent to adolescent vaccination, whereas infant vaccination would be much less cost-effective. Routine MCV-4 vaccination of US children would reduce the burden of disease in vaccinated cohorts but at a relatively high net societal cost. The projected cost-effectiveness of adolescent vaccination approaches that of recently adopted childhood vaccines under conditions of above-average meningococcal disease incidence or at a lower cost per vaccination.
Article
Hepatitis A is an important public health problem in Chile. Childhood vaccination has reduced hepatitis A rates in several countries, prompting this evaluation of its cost-effectiveness in Chile. Using a Markov model, we project mass vaccination would reduce hepatitis A cases among birth cohort members and their personal contacts >80%. Vaccination costs of US dollars 5.3-6.4 million would be offset by US dollars 9.2-9.4 million reductions in disease costs. Further, approximately 70 fatal infections would be averted and >4600 quality-adjusted life years would be saved. This analysis supports the cost-effectiveness of universal childhood hepatitis A vaccination in Chile.
Article
This study aimed at estimating the health and economic outcomes of universal infant vaccination with seven-valent pneumococcal conjugate vaccine (PCV-7) in Italy. A Markov model simulated lifetime evolution of a birth cohort (538,138 children): universal vaccination would avert 769 invasive infections, 18 deaths and 1323 life years. At base-case analysis, universal three-dose vaccination would cost euro 26,449 (95% CI: 1975-62,075) and euro 38,286 (95% CI: 22,164-70,801) per life year-saved in the societal and the NHS perspective, respectively. In the hypothesis of a 5-year long protection period, vaccination would cost euro 32,694 and euro 43,115 per life-year saved. Considering yearly incidence of invasive pneumococcal disease reported for Veneto and Sardinia regions, PCV-7 vaccination would result highly cost-effective determining a cost of euro 10,479 and euro 16,890 per life year-save in the NHS and the societal perspective, respectively.
Article
The aim of this study was to evaluate cost-effectiveness of pneumococcal conjugate vaccine (PCV7) in children <5 y of age. A Markov simulation model was used to compare the cost-effectiveness of 4 doses (assumed 50.5 euros per dose) of PCV7 with no intervention. Only direct effects of the vaccine were taken into account. In Finland, vaccination of a birth cohort of 57,500 healthy infants would potentially prevent annually 60 cases of invasive PD, 1,400 cases of pneumococcal pneumonia, 15,000 episodes of acute otitis media, 3,000 otological surgery procedures and 0.9 deaths in children aged <5 y. Investing 12.0 million euros to vaccinate a birth cohort would save annually 6.3 million euros in medical, and 2.0 million euros in productivity and other, costs. Therefore, investing 1 euros in a vaccination programme would return 0.53 euros in medical costs and 0.70 euros in societal costs. In the base case, vaccination would cost society 139,986 euros per life y gained. To achieve cost savings from a health care provider (societal) perspective, without considering herd effects or replacement phenomenon, the price of PCV7 should be 50% (70%) of the price used in the base case.
Article
Active surveillance of ambulatory and hospitalized children 2-23 months old in Cordoba, Argentina for invasive pneumococcal disease and radiographically confirmed "obvious" pneumonia revealed annual incidences of 206.8 and 2422 cases, respectively, per 100,000 children. The invasive pneumococcal disease incidence was substantially higher than those previously reported from Latin America and Europe.
Article
Streptococcus pneumoniae is a frequent bacterial cause of serious infections that may cause permanent sequelae and death. A 7-valent conjugate vaccine may reduce the incidence of pneumococcal disease, but some previous studies have questioned the cost-effectiveness of the vaccine. The aim of this study was to estimate costs and health consequences of adding this pneumococcal vaccine to the Norwegian childhood vaccination programme, taking the possibility of herd immunity into account. We developed a simulation model (Markov-model) using data on the risk of pneumococcal disease in Norway, the efficacy of the vaccine as observed in clinical trials from other countries and adjusted for serotype differences, the cost of the vaccine and quality of life for patients with sequelae from pneumococcal disease. The results were expressed as incremental (additional) costs (in euros; euro1.00 approximately NOK8.37), incremental life years and incremental quality adjusted life years. Four different sets of main results are presented: costs and (quality adjusted) life years, with and without indirect costs (the value of lost production due to work absenteeism) and with and without potential herd immunity (i.e. childhood vaccination protects adults against pneumococcal disease). When indirect costs were disregarded, and four vaccine doses used, the incremental cost per life year gained was euro153,000 when herd immunity was included, and euro311,000 when it was not. When accounting for indirect costs as well, the cost per life year gained was euro58,000 and euro124,000, respectively. Assuming that three vaccine doses provide the same protection as four, the cost per life year gained with this regimen was euro90,000 with herd immunity and euro184,000 without (when indirect costs are disregarded). If indirect costs are also included, vaccination both saves costs and gains life years. In Norway, governmental guidelines indicate that only interventions with cost per life year of less than euro54,000 should be implemented. This implies that four dose vaccination is not cost-effective even if decision makers includes both herd immunity and indirect costs in their decisions. If three doses offer the same protection as four doses, however, vaccination would be cost-saving when indirect costs are included, but not with only herd immunity. In the autumn of 2005, the Norwegian Government decided to include PCV-7 in the vaccination program. This analysis was used by the Ministry of Health and Ministry of Finance during the decision process.
Article
This piece summarizes the presentations and discussions at a meeting on pneumococcal disease surveillance in the Americas that was held in Mexico City, Mexico, on 2 November 2004. This meeting was organized by the Pan American Health Organization (PAHO) and the Pneumococcal Vaccines Accelerated Development and Introduction Plan (PneumoADIP) of the Global Alliance for Vaccines and Immunization (GAVI). The meeting participants reviewed the status of pneumococcal disease surveillance in the Region of the Americas, estimates of the burden of pneumococcal disease, the distribution of Streptococcus pneumoniae serotypes that cause invasive disease, the status of pneumococcal vaccine introduction, health economic analyses, and financial issues related to vaccine introduction. The meeting participants also worked to identify the next steps for generating the critical information needed to help make decisions on pneumococcal vaccine introduction. Coordinated pneumococcal disease surveillance for the Region of the Americas dates back to the 1993 establishment by PAHO of the Regional System for Vaccines (RSV) project for surveillance of bacterial meningitis and pneumonia, including pneumococcal disease. Surveillance data from the RSV indicate that the distribution of major serotypes in the Americas has been stable over time (but that antibiotic resistance is increasing), with serotype 14 being the leading serotype isolated in most countries participating in RSV. Based on local serotype data from six of the RSV countries (Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay), the 7-valent vaccine would cover 65% of serotypes, the 9-valent vaccine would cover 77%, and the 11-valent vaccine would cover 83%.
Article
Routine infant immunisation with seven-valent pneumococcal conjugate vaccine (PCV7) began in the USA in 2000. Although invasive pneumococcal disease has declined substantially, the programme's effect on hospital admissions for pneumonia is unknown. We therefore assessed the effect of the programme on rates of all-cause and pneumococcal pneumonia admissions. Data from the Nationwide Inpatient Sample, the largest inpatient database available in the USA, were analysed with an interrupted time-series analysis that used pneumonia (all-cause and pneumococcal) admission rates as the main outcomes. Monthly admission rates estimated for years after the introduction of PCV7 vaccination (2001-2004) were compared with expected rates calculated from pre-PCV7 years (1997-1999). The year of vaccine introduction (2000) was excluded, and rates of admission for dehydration were assessed for comparison. At the end of 2004, all-cause pneumonia admission rates had declined by 39% (95% CI 22-52) for children younger than 2 years, who were the target population of the vaccination programme. This annual decline in all-cause pneumonia admissions of 506 (291-675) per 100,000 children younger than 2 years represented about 41,000 pneumonia admissions prevented in 2004. During the 8 study years, 10,659 (2%) children younger than 2 years admitted with pneumonia were coded as having pneumococcal disease; these rates declined by 65% (47-77). This decline represented about 17 fewer admissions per 100,000 children in 2004. Admission rates for dehydration for children younger than 2 years remained stable over the study period. The reduction in all-cause pneumonia admissions in children younger than 2 years provides an estimate of the proportion of childhood pneumonias attributable to Streptococcus pneumoniae in the USA that are vaccine preventable. Our results contribute to the growing body of evidence supporting the beneficial effects of the pneumococcal conjugate vaccines in children.
Article
To estimate the effect of 7-valent pneumococcal conjugate vaccine (PCV7) on rates of pneumonia-related health care utilization and costs in children younger than 2 years. Retrospective population study. Approximately 40 large employers each year, from 1997 to 2004. Enrollees in the MarketScan databases collected by Thomson Medstat. Pneumococcal conjugate vaccine immunization program. Rates of International Classification of Diseases, Ninth Revision-coded hospitalizations and ambulatory visits due to all-cause and pneumococcal pneumonia and their medical expenditures. Comparing the rates in 2004 with those in the baseline period of 1997 to 1999 among children younger than 2 years, hospitalizations due to all-cause pneumonia declined from 11.5 to 5.5 per 1000 children (52.4% decline; P < .001) and ambulatory visits due to all-cause pneumonia declined from 99.3 to 58.5 per 1000 children (41.1% decline; P < .001). Rates of hospitalizations due to pneumococcal pneumonia declined from 0.6 to 0.3 per 1000 children (57.6% decline; P < .001) and rates of ambulatory visits declined from 1.7 to 0.9 per 1000 children (46.9% decline; P < .001). Projecting from these data to the US population, the total estimated direct medical expenditures for all-cause pneumonia-related hospitalizations and ambulatory visits in young children were reduced from an annual average of $688.2 million during the period of 1997 to 1999 to $376.7 million in 2004 (45.3% decline and approximately $310 million decrease). In children younger than 2 years, the age group targeted for vaccination, pneumonia-related health care utilization in a privately insured population declined substantially following PCV7 introduction. These results suggest that PCV7 may play an important role in reducing the burden of pneumonia, resulting in major savings in medical care cost.
Article
The goal was to estimate the population effect of 7-valent pneumococcal conjugate vaccine on rates of acute otitis media-related ambulatory visits and antibiotic prescriptions for <2-year-old children enrolled in private insurance plans. We performed a retrospective analysis of a defined population by using the 1997-2004 MarketScan databases, which included an average of >500,000 person-years of observations for children <2 years of age. Trends in rates of International Classification of Diseases, Ninth Revision-coded ambulatory visits and antibiotic prescriptions attributable to acute otitis media were evaluated, and the national direct medical expenditures for these outcomes were estimated. In a comparison of 2004 with 1997-1999 (baseline period), rates of ambulatory visits and antibiotic prescriptions attributable to acute otitis media decreased from 2173 to 1244 visits per 1000 person-years (42.7% reduction) and from 1244 to 722 prescriptions per 1000 person-years (41.9% reduction), respectively. Total, estimated, national direct medical expenditures for acute otitis media-related ambulatory visits and antibiotic prescriptions for children <2 years of age decreased from an average of $1.41 billion during 1997 to 1999 to $0.95 billion in 2004 (32.3% reduction). Acute otitis media-related health care utilization and associated antibiotic prescriptions for privately insured young children decreased more than expected (on the basis of efficacy estimates in prelicensure clinical trials) after the introduction of routine 7-valent pneumococcal conjugate vaccine immunization. Although other factors, such as clinical practice guidelines to reduce antibiotic use, might have contributed to the observed trend, 7-valent pneumococcal conjugate vaccine may play an important role in reducing the burden of acute otitis media, resulting in substantial savings in medical care costs.
Morbidity and mortality of no neonatal childhood bacterial meningitis
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Critical analysis of vaccination coverage in the country
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