7-Valent pneumococcal conjugate vaccine and lower respiratory tract infections: effectiveness of a 2-dose versus 3-dose primary series.

BACKGROUND: Immunogenicity studies suggest antibody responses from a 7-valent pneumococcal conjugate vaccine (PCV7) regimen consisting of 2 doses in the primary series are less immunogenic, for at least several vaccine serotypes, compared with a regimen consisting of 3 doses; evidence of effectiveness for prevention of invasive pneumococcal disease for both regimens is available but comparative data are lacking for prevention of lower respiratory tract diseases (LRTD). METHODS: We compared rates of LRTD between children who were born in 2002 and received 2 versus 3 PCV7 doses in the primary series, both before and after receipt of the booster dose, using a retrospective matched-cohort design and health insurance claims data. Two-dose and 3-dose children were matched (1:1) using propensity scoring. Cumulative rates of hospital admissions and outpatient visits for LRTD were tallied during the post-primary/pre-booster period and the post-booster period (to age 3 years), respectively. RESULTS: During the post-primary/pre-booster period, 3-dose children (n=3293) had 7.8 (95% CI: 0.8 to 14.8) fewer LRTD-related hospital admissions (per 1000 children) and 57 (95% CI: -6 to 128) fewer LRTD-related outpatient visits (per 1000 children) than matched 2-dose subjects (n=3293). During the post-booster period, the numbers of LRTD-related hospital admissions and outpatient visits did not differ significantly between 3-dose and 2-dose children. CONCLUSIONS: Our findings suggest that a 2-dose PCV7 primary series, while conferring savings from reduced vaccine costs in comparison with a 3-dose primary series, also may confer less protection against LRTD in the first year of life, at least during the period soon after the vaccine is introduced.

Transmission-dynamic model to capture the indirect effects of infant vaccination with Prevnar (7-valent pneumococcal conjugate vaccine (PCV7)) in older populations.

We developed an age-structured, transmission-dynamic, mathematical model to quantify the direct and indirect benefits of infant PCV7 vaccination. The model simulates the acquisition of asymptomatic carriage of Streptococcus pneumoniae and the development of fatal and non-fatal invasive pneumococcal disease (IPD) among vaccinated and unvaccinated individuals aged <2, 2-4, 5-17, 18-49, 50-64, and >or=65 years old. The model was parameterized using published US surveillance data, supplemented with data from published literature. The model predicts the observed incidence of IPD with good agreement and may be used to predict the impact of various vaccination strategies in the US or other populations yet to introduce PCV7.

The impact of indirect (herd) protection on the cost-effectiveness of pneumococcal conjugate vaccine.

BACKGROUND: The heptavalent pneumococcal polysaccharide-protein conjugate vaccine (PCV7) confers protection against invasive pneumococcal disease (IPD) caused by serotypes that are responsible for substantial morbidity and mortality throughout the world. In 2000, the 7 serotypes covered by PCV7 accounted for 80% to 90% of serotypes isolated from the blood or cerebrospinal fluid of children aged <6 years in the United States. A previous review of the literature spanning the years 1998 to 2005 pertaining to the incidence of IPD among nonimmunized individuals in countries with universal PCV7 immunization suggested an indirect protective effect (herd protection, or community immunity) after widespread vaccination. Consideration of indirect protection against IPD may enhance cost-benefit evaluations of vaccination programs. OBJECTIVE: The objective of this analysis was to review the literature on cost-effectiveness analyses of PCV7 vaccination to determine whether inclusion of the indirect effect in decision-analysis models substantially affects the cost-effectiveness findings in favor of vaccination. METHODS: A literature review of cost-effectiveness analyses of PCV7 vaccination was conducted using the DIMDI (Deutschen Institut fur Medizinische Dokumentation und Information) superbase, which comprises 12 databases, to identify articles published between January 2000 and October 2006 using the search terms 7-valent pneumococcal conjugate vaccine AND herd immunity/herd effect, and 7-valent pneumococcal conjugate vaccine AND cost-effectiveness, cost-utility, or cost-benefit analyses. Monetary values were converted to euros and inflated to 2006 values, and events avoided were converted to rates per 100,000 vaccinated to allow comparison across studies. The sensitivity analyses from the models that included indirect effects were examined. RESULTS: There was wide variability in the health-economic results of the 16 studies that met the inclusion criteria. In studies that did not include indirect effects, the adjusted cost per life-year gained ranged from cost saving to euro140,723 from the societal perspective and from euro56,724 to euro324,218 from the payer perspective. In the 4 studies that included indirect effects, a significant and consistent improvement was seen in the health-economic results in favor of vaccination with PCV7. No trends in variability across time or geographic region were observed. CONCLUSIONS: Indirect effects had a significant effect on cost-effectiveness, as seen in the sensitivity analyses. Future models should include indirect effects in evaluating the cost-effectiveness of PCV7.

Indirect effects associated with widespread vaccination of infants with heptavalent pneumococcal conjugate vaccine (PCV7; Prevnar).

Prevnar (heptavalent pneumococcal conjugate vaccine; PCV7) provides protection against invasive pneumococcal disease (IPD) caused by vaccine serotypes. Indirect protection of non-immunised individuals may be the consequence of decreased transmission of vaccine serotypes, generally carried in the nasopharynx of infants and young children. This review summarises published reports of IPD incidence (1998-2005) among non-immunised individuals in countries with universal PCV7 immunisation. Findings suggest that non-immunised individuals benefit from indirect protection following widespread vaccination, enhancing cost-benefit evaluations of vaccination programs. Continued surveillance will be important, to follow future changes associated with non-vaccine type IPD, particularly among individuals with medical co-morbidities that may put them at higher risk of disease.

Cost-effectiveness of pneumococcal conjugate vaccine: evidence from the first 5 years of use in the United States incorporating herd effects.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) has been in routine use in the United States for 5 years. Prior U.S. cost-effectiveness analyses have not taken into account the effect of the vaccine on nonvaccinated persons. METHODS: We revised a previously published model to simulate the effects of PCV on children vaccinated between 2000 and 2004, and to incorporate the effect of the vaccine in reducing invasive pneumococcal disease (IPD) in nonvaccinated persons during those years. Data from the Active Bacterial Core Surveillance of the Centers for Disease Control and Prevention (2000-2004) were used to estimate changes in the burden of IPD in nonvaccinated adults since the introduction of PCV (compared with the baseline years 1997-1999). Results combined the simulated effects of the vaccine on the vaccinated and nonvaccinated populations. RESULTS: Before incorporating herd effects in the model, the PCV was estimated to have averted 38,000 cases of IPD during its first 5 years of use at a cost of dollar 112,000 per life-year saved. After incorporating the reductions in IPD for nonvaccinated individuals, the vaccine averted 109,000 cases of IPD at a cost of dollar 7500 per life-year saved. When the herd effect was assumed to be half that of the base case, the cost per life-year saved was dollar 18,000. CONCLUSIONS: IPD herd effects in the nonvaccinated population substantially reduce the cost, and substantially improve the cost-effectiveness, of PCV. The cost-effectiveness of PCV in actual use has been more favorable than predicted by estimates created before the vaccine was licensed.

Population-wide benefits of routine vaccination of children against influenza.

Using a stochastic simulation model of influenza transmission, clinical illness, and economic costs, we estimated the population-wide benefits of routinely vaccinating US children (ages 6 months to 18 years) against influenza. Disease burden was projected to decline as a result of both reduced susceptibility to infection among vaccinees and reductions in disease transmission to others in the community. Vaccination of 20% of children would reduce the total number of influenza cases in the US by 46%; 80% coverage would reduce the total number of cases by 91%. Similar reductions were estimated to occur in influenza-related mortality and economic costs.

Economic impact of respiratory syncytial virus-related illness in the US: an analysis of national databases.

OBJECTIVE: To determine the impact of respiratory syncytial virus (RSV) infection on healthcare resource use and costs in the US from the third-party payer perspective. DESIGN: The study retrospectively analysed cross-sectional medical encounter data from three federally funded databases that comprise nationally representative samples of hospital inpatient stays, physician office visits and visits to hospital outpatient departments and emergency rooms. METHODS: Identification of RSV infection-related medical encounters was based on the occurrence of RSV-specific International Classification of Diseases (9th Edition)-Clinical Modification diagnosis codes (079.6, 466.11, 480.1) as principal discharge diagnoses or the assumption that 10-15% of all otitis media visits were due to RSV infection. Outpatient drug costs were estimated based on average wholesale price, and physician fees and test/procedure costs were estimated based on prevailing national fees. Inpatient costs were estimated from total billed charges using a cost-to-charge ratio of 0.53. RESULTS: In 2000, nearly 98% of RSV infection-related hospitalisations occurred in children <5 years old. There were approximately 86,000 hospitalisations, 1.7 million office visits, 402 000 emergency room visits and 236,000 hospital outpatient visits for children <5 years old that were attributable to RSV infection. Total annual direct medical costs for all RSV infection-related hospitalisations ($US394 million) and other medical encounters ($US258 million) for children <5 years old were estimated at $US652 million in 2000. Otitis media was a major cost driver for physician visits. RSV infection-related hospitalisations increased from 1993 to 2000, but average costs per hospitalisation were relatively stable. CONCLUSION: Treatment of RSV infection-related illness represents a significant healthcare burden in the US. The economic impact of ambulatory care for RSV infection-related illness could be as important as that for RSV infection-related hospitalisation.

A pharmacoeconomic evaluation of seven-valent pneumococcal conjugate vaccine in Spain.

BACKGROUND: Streptococcus pneumoniae is a leading cause of illness in children. Seven-valent pneumococcal conjugate vaccine (PCV-7), recently approved in the United States, is the first vaccine to provide protective immunity against pneumococcal disease in children under the age of 2. PCV-7 is nearly 100% effective in preventing invasive pneumococcal infections and has been shown to significantly decrease the incidence of pneumonia and otitis media. OBJECTIVE: The objective of this study was to evaluate the health outcomes, costs, and cost-effectiveness of vaccination with PCV-7, compared with no vaccination for children in Spain. METHODS: A health state model was used to determine the health and economic outcomes in vaccinated and unvaccinated groups among children less than 5 years old. This analysis was conducted for a 10-year time horizon, beginning with initial vaccinations. Information on the burden of pneumococcal disease, in terms of data on the incidence and seroprevalence of disease, was collected from published and unpublished records, supplemented, and verified by Spanish pediatric and infectious disease experts. The efficacy of PCV-7 was based on updated findings of the Kaiser Permanente Efficacy Study. A cost-of-illness estimate for each pneumococcal disease was determined using decision tree analysis that considered direct and indirect costs. A birth cohort analysis compared the expected cost of vaccinated populations to age-matched unvaccinated populations. RESULTS: Implementing a PCV-7 vaccine program in Spain in a birth cohort of 360000 is expected to save approximately 16 lives and 132000 cases of pneumococcal disease over 10 years, resulting in total savings estimated at Euros 81 million (ESP13.5 billion), of which Euros 43.5 million (ESP7.1 billion) are direct medical savings. At a vaccine cost up to Euros 56.87 per dose (ESP9,462, the total cost of vaccinating a birth cohort of 360000 will be offset by the total savings owing to reduced morbidity. CONCLUSIONS: Implementing a universal PCV-7 vaccination program in Spain will significantly decrease the mortality and morbidity associated with pneumococcal infections in young children. At an assumed cost of Euros 48.56 (ESP8080) per dose, PCV-7 vaccination of Spanish children under the age of 5, followed over a 10-year period, is cost saving from the societal perspective and cost-effective from the payer perspective at Euros 22500 per LYG (ESP3,734713), comparing favorably with other preventive programs in Spain.

A pharmacoeconomic evaluation of 7-valent pneumococcal conjugate vaccine in Canada.

The objective of this study was to evaluate the projected health benefits, costs, and cost-effectiveness of pneumococcal conjugate vaccination for infants and children aged <5 years in Canada. A health state model incorporating incidence, vaccine efficacy, costs, and transitional probabilities for the health states (well, meningitis, bacteremia, otitis media, pneumonia, and death) was constructed for a 10-year time horizon. Implementation of a pneumococcal conjugate vaccine program in Canada for each annual birth cohort of 340,000 persons observed over 10 years would be expected to save approximately 12 lives and 100,000 cases of pneumococcal disease over 10 years, resulting in total savings of $67 million (Canadian dollars [Can$]). Vaccination of healthy infants would result in net savings for society if the vaccine costs less than Can$50 per dose. Moreover, for a vaccine purchase price of Can$67.50, infant vaccination would cost society Can$79,000 per life-year gained. Pneumococcal conjugate vaccination is a potentially cost-effective means of pneumococcal disease prevention.