Assessment of State Perinatal Hepatitis B Prevention Laws.

INTRODUCTION: Identifying pregnant women with hepatitis B virus (HBV) infection for post-exposure prophylaxis of their infants is critical to preventing mother-to-child transmission of HBV infection. HBV infection in infancy results in premature death from chronic liver disease or cancer in 25% of affected infants. Universal screening of pregnant women for HBV infection is the standard of care, and in many states is supported by laws for screening and reporting these infections to public health. No recent assessment of state screening and reporting laws for HBV infection has been published. METHODS: In 2014, the authors analyzed laws current through December 31, 2013 from U.S. jurisdictions (50 states and the District of Columbia) related to HBV infection and hepatitis B surface antigen screening and reporting requirements generally and for pregnant women specifically. RESULTS: All states require reporting of cases of HBV infection. Twenty-six states require pregnant women to be screened. Thirty-three states require public health reporting of HBV infections in pregnant women, but only 12 states require reporting pregnancy status of women with HBV infection. CONCLUSIONS: This assessment revealed significant variability in laws related to screening and reporting of HBV infection among pregnant women in the U.S. Implementing comprehensive HBV infection screening and reporting laws for pregnant women may facilitate identifying HBV-infected pregnant women and preventing HBV infection in their infants.

Progress Toward Eliminating Hepatitis A Disease in the United States.

Hepatitis A virus (HAV) disease disproportionately affects adolescents and young adults, American Indian/Alaska Native and Hispanic racial/ethnic groups, and disadvantaged populations. During 1996-2006, the Advisory Committee on Immunization Practices (ACIP) made incremental changes in hepatitis A (HepA) vaccination recommendations to increase coverage for children and persons at high risk for HAV infection. This report examines the temporal association of ACIP-recommended HepA vaccination and disparities (on the absolute scale) in cases of HAV disease and on seroprevalence of HAV-related protection (measured as antibody to HAV [anti-HAV]). ACIP-recommended childhood HepA vaccination in the United States has eliminated most absolute disparities in HAV disease by age, race/ethnicity, and geographic area with relatively modest ≥1-dose and ≥2-dose vaccine coverage. However, the increasing proportion of cases of HAV disease among adults with identified and unidentified sources of exposure underscores the importance of considering new strategies for preventing HAV infection among U.S. adults. For continued progress to be made toward elimination of HAV disease in the United States, additional strategies are needed to prevent HAV infection among an emerging population of susceptible adults. Notably, HAV infection remains endemic in much of the world, contributing to U.S. cases through international travel and the global food economy.

Cost-effectiveness of active-passive prophylaxis and antiviral prophylaxis during pregnancy to prevent perinatal hepatitis B virus infection.

UNLABELLED: In an era of antiviral treatment, reexamination of the cost-effectiveness of strategies to prevent perinatal hepatitis B virus (HBV) transmission in the United States is needed. We used a decision tree and Markov model to estimate the cost-effectiveness of the current U.S. strategy and two alternatives: (1) Universal hepatitis B vaccination (HepB) strategy: No pregnant women are screened for hepatitis B surface antigen (HBsAg). All infants receive HepB before hospital discharge; no infants receive hepatitis B immunoglobulin (HBIG). (2) Current strategy: All pregnant women are screened for HBsAg. Infants of HBsAg-positive women receive HepB and HBIG ≤12 hours of birth. All other infants receive HepB before hospital discharge. (3) Antiviral prophylaxis strategy: All pregnant women are screened for HBsAg. HBsAg-positive women have HBV-DNA load measured. Antiviral prophylaxis is offered for 4 months starting in the third trimester to women with DNA load ≥10(6) copies/mL. HepB and HBIG are administered at birth to infants of HBsAg-positive women, and HepB is administered before hospital discharge to infants of HBsAg-negative women. Effects were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER). Compared to the universal HepB strategy, the current strategy prevented 1,006 chronic HBV infections and saved 13,600 QALYs (ICER: $6,957/QALY saved). Antiviral prophylaxis dominated the current strategy, preventing an additional 489 chronic infections, and saving 800 QALYs and $2.8 million. The results remained robust over a wide range of assumptions. CONCLUSION: The current U.S. strategy for preventing perinatal HBV remains cost-effective compared to the universal HepB strategy. An antiviral prophylaxis strategy was cost saving compared to the current strategy and should be considered to continue to decrease the burden of perinatal hepatitis B in the United States.

Cost-effectiveness of ensuring hepatitis B protection for previously vaccinated healthcare personnel.

OBJECTIVE: To examine the cost-effectiveness of pre- and postexposure approaches for ensuring hepatitis B protection among previously vaccinated healthcare personnel (HCP). DESIGN: A decision-analytic model was developed for alternative strategies of ensuring hepatitis B protection under assumptions of 68% and 95% long-term protection after a primary vaccination series. Costs and quality-adjusted life years (QALYs) lost from infections were estimated, and incremental cost-effectiveness ratios (ICERs) were calculated relative to a no intervention alternative over 10 years of intervention. Separate analyses were performed for trainees and nontrainees, using the healthcare system perspective. Trainees face higher risk of exposure and likely received primary vaccination as infants. SETTING: General healthcare settings. PARTICIPANTS: Trainee and nontrainee HCP. INTERVENTIONS: Preexposure testing for antibody to hepatitis B surface antigen followed by additional vaccination for HCP without protective antibody levels; postexposure evaluation and management for HCP reporting blood or body fluid exposures RESULTS: The preexposure strategy prevents more infections and has higher costs than the postexposure strategy or no intervention. For trainees, 10-year preexposure evaluation ICERs are $832,875 and $144,457 per QALY for 95% and 68% long-term vaccine protection, respectively. Trainee 10-year postexposure evaluation ICERs are $1,146,660 and $191,579 per QALY under the 95% and 68% long-term protection assumptions, respectively. For nontrainees, 10-year ICERs are $745,739 and $1,129,286 per QALY for the preexposure and postexposure evaluation strategies, respectively. CONCLUSIONS: ICERs may inform decision makers as they decide whether the added cost of the preexposure strategy provides sufficient value in preventing infections.

Cost-effectiveness of testing hepatitis B-positive pregnant women for hepatitis B e antigen or viral load.

OBJECTIVE: To estimate the cost-effectiveness of testing pregnant women with hepatitis B (hepatitis B surface antigen [HBsAg]-positive) for hepatitis B e antigen (HBeAg) or hepatitis B virus (HBV) DNA, and administering maternal antiviral prophylaxis if indicated, to decrease breakthrough perinatal HBV transmission from the U.S. health care perspective. METHODS: A Markov decision model was constructed for a 2010 birth cohort of 4 million neonates to estimate the cost-effectiveness of two strategies: testing HBsAg-positive pregnant women for 1) HBeAg or 2) HBV load. Maternal antiviral prophylaxis is given from 28 weeks of gestation through 4 weeks postpartum when HBeAg is positive or HBV load is high (10 copies/mL or greater). These strategies were compared with the current recommendation. All neonates born to HBsAg-positive women received recommended active-passive immunoprophylaxis. Effects were measured in quality-adjusted life-years (QALYs) and all costs were in 2010 U.S. dollars. RESULTS: The HBeAg testing strategy saved $3.3 million and 3,080 QALYs and prevented 486 chronic HBV infections compared with the current recommendation. The HBV load testing strategy cost $3 million more than current recommendation, saved 2,080 QALYs, and prevented 324 chronic infections with an incremental cost-effectiveness ratio of $1,583 per QALY saved compared with the current recommendations. The results remained robust over a wide range of assumptions. CONCLUSION: Testing HBsAg-positive pregnant women for HBeAg or HBV load followed by maternal antiviral prophylaxis if HBeAg-positive or high viral load to reduce perinatal hepatitis B transmission in the United States is cost-effective.

Economic evaluation of the routine childhood immunization program in the United States, 2009.

OBJECTIVES: To evaluate the economic impact of the 2009 routine US childhood immunization schedule, including diphtheria and tetanus toxoids and acellular pertussis, Haemophilus influenzae type b conjugate, inactivated poliovirus, measles/mumps/rubella, hepatitis B, varicella, 7-valent pneumococcal conjugate, hepatitis A, and rotavirus vaccines; influenza vaccine was not included. METHODS: Decision analysis was conducted using population-based vaccination coverage, published vaccine efficacies, historical data on disease incidence before vaccination, and disease incidence reported during 2005 to 2009. Costs were estimated using the direct cost and societal (direct and indirect costs) perspectives. Program costs included vaccine, administration, vaccine-associated adverse events, and parent travel and work time lost. All costs were inflated to 2009 dollars, and all costs and benefits in the future were discounted at a 3% annual rate. A hypothetical 2009 US birth cohort of 4,261,494 infants over their lifetime was followed up from birth through death. Net present value (net savings) and benefit-cost ratios of routine childhood immunization were calculated. RESULTS: Analyses showed that routine childhood immunization among members of the 2009 US birth cohort will prevent ∼42,000 early deaths and 20 million cases of disease, with net savings of $13.5 billion in direct costs and $68.8 billion in total societal costs, respectively. The direct and societal benefit-cost ratios for routine childhood vaccination with these 9 vaccines were 3.0 and 10.1. CONCLUSIONS: From both direct cost and societal perspectives, vaccinating children as recommended with these vaccines results in substantial cost savings.

Cost-effectiveness analysis of the national Perinatal Hepatitis B Prevention Program.

OBJECTIVE: To analyze the cost-effectiveness of the national Perinatal Hepatitis B Prevention Program (PHBPP) over the lifetime of the 2009 US birth cohort and compare the costs and outcomes of the program to a scenario without PHBPP support. PHBPP's goals are to ensure all infants born to hepatitis B (HepB) surface antigen-positive women receive timely postexposure prophylaxis, complete HepB vaccine series, and obtain serologic testing after series completion. METHODS: A decision analytic tree and a long-term Markov model represented the risk of perinatal and childhood infections under different prevention alternatives, and the long-term health and economic consequences of HepB infection. Outcome measures were the number of perinatal infections and childhood infections from infants born to HepB surface antigen-positive women, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost per QALY gained. The health outcomes and total costs of each strategy were compared incrementally. Costs were evaluated from the health care system perspective and expressed in US dollars at a 2010 price base. RESULTS: In all analyses, the PHBPP increased QALYs and led to higher reductions in the number of perinatal and childhood infections than no PHBPP, with a cost-effectiveness ratio of $2602 per QALY. In sensitivity analyses, the cost-effectiveness ratio was robust to variations in model inputs, and there were instances where the program was both more effective and cost saving. CONCLUSIONS: This study indicated that the current PHBPP represents a cost-effective use of resources, and ensuring the program reaches all pregnant women could present additional public health benefits.

Cost-effectiveness of hepatitis B vaccination in adults with diagnosed diabetes.

OBJECTIVE To examine the cost-effectiveness of a hepatitis B vaccination program for unvaccinated adults with diagnosed diabetes in the U.S. RESEARCH DESIGN AND METHODS We used a cost-effectiveness simulation model to estimate the cost-effectiveness of vaccinating adults 20-59 years of age with diagnosed diabetes not previously vaccinated for or infected by hepatitis B virus (HBV). The model estimated acute and chronic HBV infections, complications, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Data sources included surveillance data, epidemiological studies, and vaccine prices. RESULTS With a 10% uptake rate, the intervention will vaccinate 528,047 people and prevent 4,271 acute and 256 chronic hepatitis B infections. Net health care costs will increase by $91.4 million, and 1,218 QALYs will be gained, producing a cost-effectiveness ratio of $75,094 per QALY gained. Results are most sensitive to age, the discount rate, the hepatitis B incidence ratio for people with diabetes, and hepatitis B infection rates. Cost-effectiveness ratios rise with age at vaccination; an alternative intervention that vaccinates adults with diabetes 60 years of age or older had a cost-effectiveness ratio of $2.7 million per QALY. CONCLUSIONS Hepatitis B vaccination for adults with diabetes 20-59 years of age is modestly cost-effective. Vaccinating older adults with diabetes is not cost-effective. The study did not consider hepatitis outbreak investigation costs, and limited information exists on hepatitis progression among older adults with diabetes. Partly based on these results, the Advisory Committee on Immunization Practices recently recommended hepatitis B vaccination for people 20-59 years of age with diagnosed diabetes.

Sociodemographic and dietary risk factors for natural infant intussusception in the United States.

BACKGROUND: In 1999, a US case-control study demonstrated a strong association between intussusception and a rotavirus vaccine (Rotashield). However, because most (87%) cases were not temporally associated with vaccination, we reanalyzed these data to assess risk factors for intussusception cases unrelated to Rotashield. PATIENTS AND METHODS: Case-patients were infants with intussusception between November 1998 and June 1999. Controls were matched by age and hospital of birth. Sociodemographic and feeding practice data were collected through parent and provider interviews. Conditional logistic regression was used to identify risk factors for intussusception, controlling for exposure to Rotashield <21 days before intussusception. RESULTS: Four hundred twenty-nine cases and 1763 controls were enrolled. Among case-patients, 372 (87%) had not received Rotashield within 21 days before intussusception. After adjusting for recent Rotashield administration, factors associated with intussusception included male sex (odds ratio [OR] 1.7; 95% confidence interval [CI] 1.3-2.2), Hispanic (OR 2.1; 95% CI 1.4-3.2) or black (OR 1.8; 95% CI 1.2-2.7) race/ethnicity, and Medicaid enrollment (OR 1.5; 95% CI 1.1-2.0). Feeding practices modified the risk of intussusception. Interaction was found between introduction of solid food (ISF) and type of formula consumption. Using breast milk as the referent group, infants with ISF for at least 5 weeks who consumed soy milk-based formula had a lower risk (OR 0.26; 95% CI 0.1-0.7) and infants without ISF who consumed cow's-milk formula had an increased risk (OR 2.33; 95% CI 1.4-3.9). CONCLUSIONS: Risk of intussusception among US infants varies based on sociodemographic characteristics and feeding patterns.

Cost effectiveness of pertussis vaccination in adults.

BACKGROUND: Prior economic analyses have reached disparate conclusions about whether vaccinating adults against pertussis would be cost effective. Newly available data on pertussis incidence were used to evaluate the cost effectiveness of one-time adult vaccination and adult vaccination with decennial boosters. METHODS: A Markov model was used to calculate the health benefits, risks, costs, and cost effectiveness of the following strategies: (1) no adult pertussis vaccination, (2) one-time adult vaccination at 20-64 years, and (3) adult vaccination with decennial boosters. The impact of the severity of pertussis illness, vaccine adverse events, and herd immunity on model outcomes were also examined. RESULTS: At a disease incidence of 360 per 100,000, the one-time adult vaccination strategy would prevent 2.8 million cases, and the decennial vaccination strategy would prevent 8.3 million cases. As disease incidence varied from 10 to 500 per 100,000, the one-time adult vaccination strategy was projected to prevent 79,000 to 3.8 million adult pertussis cases, while the decennial vaccination program would prevent 239,000 to 11.4 million cases. A one-time adult vaccination strategy would result in 106 million people vaccinated, or approximately 64% of the adult cohort, for a total program cost of $2.1 billion, while a decennial vaccination strategy would cost $6.7 billion. The one-time and decennial booster vaccination strategies result in cost-effectiveness ratios of <$50,000 per quality-adjusted life year saved if disease incidence in adults were greater than 120 cases per 100,000 population. CONCLUSIONS: Routine vaccination of adults aged 20 to 64 years with combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis is cost effective if pertussis incidence in this age group is greater than 120 per 100,000 population.

Nosocomial pertussis: costs of an outbreak and benefits of vaccinating health care workers.

BACKGROUND: In September 2003, 17 symptomatic cases of pertussis among health care workers (HCWs) resulted from a 1-day exposure to an infant who was later confirmed to have pertussis. These HCWs identified 307 close contacts. The hospital implemented extensive infection-control measures. The objective of this study was to determine direct and indirect costs incurred by the hospital and symptomatic HCWs as a result of the September 2003 outbreak and to estimate possible benefits of vaccinating HCWs from the hospital perspective. METHODS: We determined costs by interviewing infection-control and hospital personnel, reviewing billing records, and surveying symptomatic HCWs. We calculated the benefits and costs of a vaccination program for HCWs, using a probabilistic model to estimate the number of pertussis exposures that would require control measures annually. Sensitivity and threshold analyses were performed. RESULTS: The outbreak cost to the hospital was 74,870 dollars. The total measured cost of the outbreak was 81,382 dollars, including costs incurred by HCWs (6512 dollars). Our model predicted that vaccinating HCWs against pertussis would prevent >46% of exposures from HCWs with pertussis per year and would provide net savings. The benefit for the hospital was estimated to be 2.38 times the dollar amount invested in vaccinating HCWs. The number of exposures prevented and the benefit-cost ratio were sensitive to the number of exposures identified, the incidence of pertussis among HCWs, and HCW turnover. CONCLUSIONS: A single nosocomial pertussis outbreak resulted in substantial disruption and costs to the hospital and to HCWs. Our model suggests that cost savings and benefits could be accrued by vaccinating HCWs against pertussis.

Who's calling the shots? Pediatricians' adherence to the 2001-2003 pneumococcal conjugate vaccine-shortage recommendations.

BACKGROUND: A national shortage of heptavalent pneumococcal conjugate vaccine (PCV7) occurred from September 2001 through May 2003. In December 2001 and January 2002, the Advisory Committee on Immunization Practices and the American Academy of Pediatrics (AAP) issued PCV7-shortage recommendations, emphasizing that all health care providers decrease the number of doses for healthy children so that more children could receive some PCV7. OBJECTIVES: We assessed (1) how the PCV7 shortage affected pediatricians, (2) whether children in the public and private sectors were vaccinated differently during the shortage, (3) pediatricians' knowledge of and adherence to the Advisory Committee on Immunization Practices/AAP recommendations, (4) and what factors were associated with nonadherence to the recommendations. METHODS: We conducted a cross-sectional mail survey of 2500 US physician-members of the AAP from November 2002 through March 2003; physicians providing childhood immunizations were eligible. We asked about PCV7-shortage experience, assessed recommendation adherence through clinical scenarios, and modeled potential factors associated with reported nonadherence to the recommendation to defer the fourth PCV7 dose. RESULTS: Of 2478 surveys sent to valid addresses, 1412 (57%) completed surveys were received; 946 (67%) of these were from eligible pediatricians. Overall, 79% experienced a PCV7 shortage, 94% reported being aware of the recommendations, and 42% reported barriers to recommendation adherence. Ninety-four percent reported vaccinating 6-month-old infants with private or public insurance in the same manner. As recommended, 91% reported fully vaccinating high-risk patients. Contrary to recommendations, 49% reported sometimes or always administering the fourth PCV7 dose to healthy children 12 to 15 months old; their reasons included recurrent otitis media, childcare attendance, and parental desire. Controlling for other characteristics, pediatricians who had no PCV7 shortage in their practices were significantly more likely to report administering the fourth dose than pediatricians who had a shortage (odds ratio [OR]: 3.67; 95% confidence interval [CI]: 2.40-5.63). Other factors associated with nonadherence were being in solo private practice (OR: 2.18; 95% CI: 1.26-3.77) or being male (OR: 1.51; 95% CI: 1.08-2.12). Among pediatricians deferring PCV7, 36% reported having no system to track children for whom PCV7 was deferred. CONCLUSIONS: Many pediatricians, both with and without a PCV7 shortage, administered more PCV7 doses than recommended. Pediatricians without a shortage were less likely to limit use, which suggests that they might have focused on the perceived value of administering the full schedule to their patients in preference to broader public health goals. Providing more information to physicians on the effectiveness of a fewer-dose schedule and the risk of disease when vaccine is deferred and educating parents might increase adherence to recommendations and achieve more equitable coverage during vaccine shortages.

Pertussis in adolescents and adults: should we vaccinate?

BACKGROUND: The incidence of reported pertussis among adolescents, adults, and young infants has increased sharply over the past decade. Combined acellular pertussis vaccines for adolescents and adults are available in Canada, Australia, and Germany and may soon be considered for use in the United States. OBJECTIVE: To evaluate the potential health benefits, risks, and costs of a national pertussis vaccination program for adolescents and/or adults. DESIGN, SETTING, AND POPULATION: The projected health states and immunity levels associated with pertussis disease and vaccination were simulated with a Markov model. The following strategies were examined from the health care payer and societal perspectives: (1) no vaccination; (2) 1-time adolescent vaccination; (3) 1-time adult vaccination; (4) adult vaccination with boosters; (5) adolescent and adult vaccination with boosters; and (6) postpartum vaccination. Data on disease incidence, costs, outcomes, vaccine efficacy, and adverse events were based on published studies, recent unpublished clinical trials, and expert panel input. MAIN OUTCOME MEASURES: Cases prevented, adverse events, costs (in 2004 US dollars), cost per case prevented, and cost per quality-adjusted life-year (QALY) saved. RESULTS: One-time adolescent vaccination would prevent 30800 cases of pertussis (36% of projected cases) and would result in 91000 vaccine adverse events (67% local reactions). If pertussis vaccination cost $15 and vaccine coverage was 76%, then 1-time adolescent vaccination would cost $1100 per case prevented (or $1200 per case prevented) or $20000 per QALY (or $23000 per QALY) saved, from the societal (or health care payer) perspective. With a threshold of $50000 per QALY saved, the adolescent and adult vaccination with boosters strategy became potentially cost-effective from the societal perspective only if 2 conditions were met simultaneously, ie, (1) the disease incidence for adolescents and adults was > or =6 times higher than base-case assumptions and (2) the cost of vaccination was less than $10. Adult vaccination strategies were more costly and less effective than adolescent vaccination strategies. The results were sensitive to assumptions about disease incidence, vaccine efficacy, frequency of vaccine adverse events, and vaccine costs. CONCLUSIONS: Routine pertussis vaccination of adolescents results in net health benefits and may be relatively cost-effective.

Societal costs and morbidity of pertussis in adolescents and adults.

BACKGROUND: Since the 1980s, the reported incidence of pertussis among adolescents and adults has been steadily increasing. To understand whether the benefits of an acellular pertussis vaccine formulated for adolescents and adults might offset its costs, policy makers will need information about morbidity and societal (medical and nonmedical) costs of pertussis. METHODS: Adolescents (age, 10-17 years) and adults (age, >or=18 years) with confirmed pertussis illness were identified by the Massachusetts enhanced pertussis surveillance system. We evaluated medical costs in a cohort of patients who had confirmed pertussis during the period of January 1998 through December 2000; nonmedical costs, by means of prospective interviews, in a cohort of patients who had confirmed pertussis during the period of December 2001 through January 2003; and morbidity in both cohorts. Our main outcome measures were mean costs per case, in 2002 US dollars. RESULTS: In the analysis of medical costs, 1679 adolescents and 936 adults were found to have mean costs of 242 dollars and 326 dollars, respectively (P<.05). In interviews with 314 adolescents and 203 adults, adults had significantly higher nonmedical costs (447 dollars) than those of adolescents (155 dollars). A total of 83% of adolescents missed a mean of 5.5 days from school (range, 0.4-32 days), and 61% of adults missed a mean of 9.8 days from work (range, 0.1-180 days) because of pertussis. Thirty-eight percent of adolescents and 61% of adults were still coughing at the time of the interview, which occurred an average of 106 days and 94 days, respectively, after cough onset. CONCLUSIONS: Pertussis causes significant morbidity in and costs for adolescents and adults, with time losses comprising the largest proportion of the cost. Societal costs should be considered when making decisions about potential vaccine use in the future.

Impact of universal Haemophilus influenzae type b vaccination starting at 2 months of age in the United States: an economic analysis.

OBJECTIVE: To evaluate the economic impact of universal Haemophilus influenzae type b (Hib) vaccination starting at 2 months of age. METHODS: Decision-tree-based analysis was conducted of a hypothetical US birth cohort of 3 815 469 infants using population-based vaccination coverage and disease incidence data. All costs were estimated from both the direct cost (medical and nonmedical) and societal perspectives. Net present value, cost-effectiveness ratios, and benefit-cost ratios of the US Hib vaccination program were evaluated. RESULTS: The results of these analyses showed that the universal vaccination program using the Hib conjugate vaccines in the United States in 2000 was cost-saving from both the direct and societal perspectives, with the benefit of the Hib vaccination program (net present value) from the direct cost and societal perspectives of $0.95 billion and $2.09 billion, respectively. Without a Hib vaccination program, the direct and societal costs of Hib invasive cases would be $1.35 billion and $2.58 billion, respectively. The direct and societal costs of the Hib vaccination program were estimated at $0.39 billion and $0.48 billion, respectively. The direct and societal benefit-cost ratios for the Hib vaccination program were 3.4 and 5.4, respectively. Varying the proportion of vaccines purchased and administered in the public versus the private sector and the proportion of combination vaccine versus monovalent vaccine administered did not have much effect on the results. CONCLUSIONS: Regardless of the perspective (direct cost or societal) and the assumptions used, the benefit-cost ratios of the US vaccination program are >1.0. Potential changes in the program, including use of more or less Hib combination vaccines, would not significantly alter the benefit-cost ratio. The national Hib vaccination program is highly cost beneficial and results in substantial cost savings.