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Article |

Economic Evaluation of the 7-Vaccine Routine Childhood Immunization Schedule in the United States, 2001 FREE

Fangjun Zhou, PhD; Jeanne Santoli, MD, MPH; Mark L. Messonnier, PhD; Hussain R. Yusuf, MBBS, MPH; Abigail Shefer, MD; Susan Y. Chu, PhD, MSPH; Lance Rodewald, MD; Rafael Harpaz, MD, MPH
[+] Author Affiliations

Author Affiliations: National Immunization Program, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta, Ga. Dr Yusuf is now with UNICEF, New Delhi, India.


Arch Pediatr Adolesc Med. 2005;159(12):1136-1144. doi:10.1001/archpedi.159.12.1136.
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Objective  To evaluate the economic impact of the routine US childhood immunization schedule: diphtheria and tetanus toxoids and acellular pertussis; tetanus and diphtheria toxoids; Haemophilus influenzae type b conjugate; inactivated poliovirus; measles, mumps, and rubella; hepatitis B; and varicella vaccines.

Design  Decision tree–based analysis was conducted using population-based vaccination coverage, published vaccine efficacies, historical data on disease incidence before vaccination, and disease incidence reported for 1995-2001. 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 time lost. All costs were inflated to 2001 US dollars, and all costs and benefits in the future were discounted at a 3% annual rate.

Participants  A hypothetical 2001 US birth cohort of 3 803 295 infants was followed up from birth through death.

Main Outcome Measures  Net present value (net savings) and benefit-cost ratios of routine immunization.

Results  Routine childhood immunization with the 7 vaccines was cost saving from the direct cost and societal perspectives, with net savings of $9.9 billion and $43.3 billion, respectively. Without routine vaccination, direct and societal costs of diphtheria, tetanus, pertussis, H influenzae type b, poliomyelitis, measles, mumps, rubella, congenital rubella syndrome, hepatitis B, and varicella would be $12.3 billion and $46.6 billion, respectively. Direct and societal costs for the vaccination program were an estimated $2.3 billion and $2.8 billion, respectively. Direct and societal benefit-cost ratios for routine childhood vaccination were 5.3 and 16.5, respectively.

Conclusion  Regardless of the perspective, the current routine childhood immunization schedule results in substantial cost savings.

Figures in this Article

Numerous studies133 have demonstrated the cost savings of childhood vaccination in the United States. However, in most cases, studies focused on single vaccines, and widely different methods and assumptions were used, which prevents adequate comparisons. To date, we know of no study that has examined the benefits and costs of the routine childhood immunization schedule using consistent methods and assumptions.

Vaccines are one of the greatest achievements of biomedical science and public health and represent one of the most effective tools for the prevention of diseases.34 The introduction and widespread use of vaccines have resulted in dramatic declines in the United States in the morbidity, disability, and mortality caused by a variety of infectious diseases, including diphtheria, tetanus, pertussis, Haemophilus influenzae type b (Hib), poliomyelitis, measles, mumps, rubella, hepatitis B virus (HBV), and varicella.3537 The current routine immunization schedule represents nearly 8 decades of vaccine development.3845

Some of the economic studies still being cited as evidence that older vaccines result in net savings are now more than 20 years old. The prices of these vaccines, their formulations and uses, and the cost of medical care for the diseases they prevent have changed across the years; for example, 2 doses of measles, mumps, and rubella (MMR) vaccine are now recommended; inactivated poliovirus (IPV) vaccine has replaced oral poliovirus vaccine; and acellular pertussis vaccine has replaced whole-cell pertussis vaccine. Given that immunization is a cornerstone of preventive health care for children and that US vaccine financing mechanisms are still less than perfect, an updated and comprehensive economic evaluation is important and useful for making future policy decisions regarding childhood vaccination.

We applied a decision analysis model using population-based surveillance of diseases, published vaccine efficacies, historical data on disease incidence before vaccination, and disease incidence reported around 1995-2001, along with the available estimates of current costs of treating diseases and complications and administering vaccines. The objective of this study was to provide a comprehensive economic evaluation of routine childhood immunization with diphtheria and tetanus toxoids and acellular pertussis (DTaP); tetanus and diphtheria toxoids (Td); Hib conjugate; IPV; MMR; hepatitis B (HB); and varicella vaccines in the United States, addressing current costs and benefits. Although recommended for routine immunization, pneumococcal conjugate and influenza vaccines are not included in this study because they are not yet fully implemented (ie, they are relatively newly recommended by the Advisory Committee on Immunization Practices).

DECISION ANALYSIS MODEL

We developed a decision tree as the basis for our model (Figure 1) and then evaluated the effect of routine childhood vaccination with DTaP, Td, Hib, IPV, MMR, HB, and varicella vaccines on a hypothetical US birth cohort of 3 803 295 children (the estimated number of births in 2001 [http://www.census.gov/population/projections/nation/detail/p2001_10.a]) from birth through death. The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices routinely recommends 5 doses of DTaP,46 3 or 4 doses of Hib,47 4 doses of IPV,40 2 doses of MMR,48 3 doses of HB,49 and 1 dose of varicella vaccine.44 Additional booster doses of Td are required every 10 years, and the first booster dose may be given at 11 to 12 years of age.39 Our analysis is based on coverage attained in the United States as estimated by the 2000 National Immunization Survey, the 1999 National Health Interview Survey, and the 2000-2001 School and Childcare Vaccination Surveys.

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Figure 1.

Simplified decision tree.

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We calculated net present values (NPVs) and benefit-cost ratios (BCRs) for all 7 vaccines together. The analyses were performed from 2 perspectives: direct cost (direct medical and nonmedical costs) and societal (direct and indirect costs). All costs were inflated to 2001 dollars, and all costs and benefits in the future were discounted at a 3% annual rate for the base case analysis.

The data used in this analysis were compiled from a variety of sources: the published literature, including surveillance data, study data, and expert consensus; several large, computerized data sets; and CDC unpublished data. When it was necessary to make estimates about the incidence of disease and complications from multiple publications, results from existing meta-analyses were used as the estimates if possible. Otherwise, conservative assumptions were made, thereby intentionally underestimating the benefits of vaccination.

ESTIMATING THE BURDEN OF DISEASES WITHOUT VACCINATION

The age-specific annual incidence rates of diphtheria, tetanus, pertussis, Hib, poliomyelitis, measles, mumps, rubella, and varicella diseases in the United States in the prevaccine era were estimated or obtained from the National Health Interview Survey and the literature (Table 1).5,6,10,22,39,5059Table 2 lists the health care utilizations for each of these diseases as appropriate. For diphtheria and tetanus, all cases were assumed to be hospitalized, with case-fatality ratios of 10%5,39,57 and 15%,5,39,56 respectively. Age-specific probabilities of pertussis hospitalizations and case-fatality ratios were used in the analysis.5,60,61 In the base case analysis, the case-fatality ratio for Hib was estimated to be 3.78%.6,10,53 For poliomyelitis, we assumed that 40% of the cases were paralytic and that 60% were nonparalytic.59,62 We also assumed that all the paralytic cases needed acute care; that 22.4% had minor residual deficit, 41.4% had moderate residual deficit, and 24.3% had severe residual deficit without severe respiratory problems; and that 2% had severe respiratory problems.14,63,64 This analysis also included postpoliomyelitis syndrome as part of the long-term course of poliomyelitis.6567 The case-fatality ratio for paralytic cases was assumed to be 3%.68

Table Graphic Jump LocationTable 1. Diphtheria, Tetanus, Pertussis, Hib, Poliomyelitis, Measles, Mumps, Rubella, and Varicella Annual Incidence Rates Without and With Vaccination*
Table Graphic Jump LocationTable 2. Probabilities and Costs of Hospitalizations and Outpatient Visits for Selected Vaccine-Preventable Diseases*

In the base case analysis, the estimated case-fatality ratios were 0.08% for measles infection,69 5% for measles encephalitis,22 and 0.46% for thrombocytopenia after measles infection.70 We assumed that the subacute sclerosing panencephalitis rate was 10 per million measles cases.20,71,72 The incidence of congenital rubella syndrome, its complications, and its associated costs were estimated from the literature.22,73,74 For varicella, age-specific probabilities of hospitalizations and case-fatality ratios were used.75,76

In the United States, the prevalence of HB surface antigen positivity among women of childbearing age was assumed to be 0.57%, with 15% of these women being HB e antigen positive.26,77 The prevalence of anti–HB core antibody at age 5 years is 0.56%, and the lifetime risk of HBV infection is 6.1%.78 We assumed that 90% of infants born to HB surface antigen–positive/HB e antigen–positive women and 10% of infants born to HB surface antigen–positive/HB e antigen–negative women become perinatally infected. We assumed that acute HB occurs in 1% of perinatal infections, 6% of early childhood infections (after birth through 5 years old), and 30% of late infections (>5 years old through adulthood).26 We assumed that 0.1% of infants and 0.6% of young children, adolescents, and adults who develop acute HB will develop fulminant hepatitis, and the mortality of fulminant HB is assumed to be 70%.23,24,26,79,80 We assumed that 90% of infants, 30% of young children, and 6% of adolescents and adults who become infected will develop chronic HB infection.26 Long-term sequelae develop in 25% of chronic infections from perinatal or early childhood infection and in 15% of chronic infections from late infection; sequelae include chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma.26,7983

ESTIMATING THE BURDEN OF DISEASES WITH VACCINATION

For all diseases except varicella and HB, we used surveillance data from the National Notifiable Diseases Surveillance System to estimate the burden of diseases with vaccination in 2001. Incidence data were averaged for the 6 years from 1995 through 2000. For varicella, because it is not a nationally notifiable disease, we used the average incidence for the 2 sites (Antelope Valley, Calif, and West Philadelphia, Pa) in the Varicella Active Surveillance Project36 during 2000 to estimate the total number of varicella cases in the United States. We assumed that 20.9% of these cases involved persons who had previously received varicella vaccine and that these were thus much milder than cases among unvaccinated persons. For HB, because acute cases were underreported and chronic cases were not reported to the National Notifiable Diseases Surveillance System, we decided to use an established decision tree model26 and the efficacy of the vaccine84 to estimate the likelihood of HB infection and sequelae in vaccinated and unvaccinated children in the cohort.

COSTS ASSOCIATED WITH DISEASE
Direct Costs

Direct health care costs include those associated with the treatment, complications, and sequelae of diseases. Outpatient and inpatient costs were included in the analysis. The cost of outpatient visits, the average duration of hospitalization, and hospitalization costs for each condition related to these diseases or congenital rubella syndrome were obtained from HCUPnet,85 the Marketscan database,86 and published and unpublished studies (Table 2).5,6,10,13,14,20,22,26,87

We assumed that the annual cost of epilepsy and hemiplegia during a 50-year life span was $169388; the annual special education cost for severely disabled children until age 18 years was $16 75089; the average annual long-term care cost for patients with poliomyelitis and severe respiratory problems during a 30-year life span was $137 2209093; the annual cost for the long-term care of individuals with moderate and severe mental retardation during a 50-year life span was $31 059 and $78 448, respectively10; and the cost for periodic hearing aid evaluation is $243 per year and for hearing aids (binaural) is $1141 per year.94

Indirect Costs

Our model estimated the productivity losses due to premature mortality and the indirect costs from permanent disability as well as opportunity costs associated with caregivers who missed work to care for their sick children or patients themselves for missed work. To estimate the productivity losses from premature mortality, we used the human capital approach.95 Costs for work loss were determined by the number of days of missed work (for the illness, for a resulting disability, or for the provision of care to sick children) multiplied by the daily wage rate associated with the value of lost wage-earning work and the imputed value of housekeeping and home care activities. Appropriate values, taken from published studies,95 the Bureau of Labor Statistics, and the Bureau of the Census, were applied for the general working population and for parents who missed work to care for their sick children. We assumed that the days of morbidity were distributed randomly throughout the week.

COSTS AND ADVERSE EVENTS ASSOCIATED WITH VACCINATION

Routine childhood vaccines are purchased with public and private funds. The distribution of publicly purchased vs privately purchased vaccines was derived from the CDC Vaccine Management database and from voluntary manufacturer reports to the CDC. Overall, approximately 55% of all US childhood vaccines were publicly purchased in 2001. The public and private prices for all vaccines were obtained from the CDC Vaccine Price List in 2001. We assumed that the average total cost to distribute (transport from the manufacturer to the site where administered) a dose of public vaccine was $0.68 and that the overall rate of vaccine wastage (public and private sectors) was 12%.10,22 The federal excise tax that supports the National Vaccine Injury Compensation Program (http://www.hrsa.gov/osp/vicp) was included in all vaccine prices.

Most vaccines for children are administered by private sector providers. National Immunization Survey data indicate that approximately 76% of children obtained their vaccines from private providers, and 24% from public providers. The cost for administering a vaccine during a visit to a public clinic was estimated to be $5.23. In the private sector, we used an administration cost of $18.65.10,22

We used the same assumptions as previous economic studies,10,22 and we assumed that the cost of caregiver travel to the clinic was $3.50 and that 2 hours away from work was needed to take the child for vaccination. We assumed that the average cost for these caregivers was $8.50 per hour. We calculated the indirect caregiver costs using the estimate of the average number of vaccination visits for each child derived from National Immunization Survey, National Health Interview Survey, and School and Childcare Vaccination Surveys data. We assumed that there were a mean of 7.8 vaccination visits for each child by age 12 years.

Vaccination coverage rates by age and number of doses administered were estimated for children in the cohort aged 1 to 3 years using 2000 National Immunization Survey data and aged 4 to 6 years using 1999 National Health Interview Survey and 2000-2001 School and Childcare Vaccination Surveys data. By 19 to 35 months of age, 94.1% of the children had received 3 or more doses of DTaP vaccine, 93.4% had received 3 or more doses of Hib vaccine, 89.5% had received 3 or more doses of poliomyelitis vaccine, 90.5% had received 1 or more doses of MMR vaccine, 90.3% had received 3 or more doses of HB vaccine, and 67.8% had received 1 or more doses of varicella vaccine.96 By 6 years of age, 95% of the children had received 3 or more doses of DTaP vaccine, 94% had received 3 or more doses of Hib vaccine, 94% had received 3 or more doses of poliomyelitis vaccine, 95% had received 1 or more doses of MMR vaccine, and 93% had received 3 or more doses of HB vaccine. For varicella, we assumed that in a fully implemented program, 93% of the children would receive 1 or more doses of varicella vaccine.

The frequency and cost of care for adverse events associated with each of the vaccines is summarized in Table 3.

Table Graphic Jump LocationTable 3. Probabilities and Costs of Adverse Reactions*
NPV AND BCRs

The benefits of routine childhood immunization consist of the savings from reduced morbidity and mortality resulting from vaccine use, including direct medical and nonmedical and indirect costs. The costs associated with the vaccination program include the vaccines, their administration, parent travel and time lost, and adverse events associated with these vaccines. The NPV is the most widely used summary measure in economic analysis to determine the return on any investment and in this case is the sum of the discounted benefits from the routine childhood vaccination program minus the sum of the discounted costs. The NPV can be written as follows:

where Bt and Ct are the benefits and costs, respectively, in year t; T is the life expectancy; and r is the annual discount rate.

The BCRs also provide a summary measure to determine the return on any investment. In this analysis, the BCR is equal to the discounted costs averted by the vaccination program divided by the discounted vaccination program costs. The BCR can be calculated as follows:

SENSITIVITY ANALYSES

Sensitivity analyses were used to assess the robustness of the economic estimates and to estimate the impact of potential changes to the vaccination program. Univariate sensitivity analyses were performed to assess the effect of varying (1) the rates of adverse events; (2) the postvaccination disease incidence rates; (3) the total direct and indirect costs without vaccination; (4) the proportion of vaccines purchased in the public vs private sector; (5) the vaccine administration costs; (6) the vaccine wastage rate; (7) the inclusion of federal, state, and local vaccination program management expenditures; (8) the costs associated with parent travel and time lost; and (9) the discount rate. Each new variable was introduced by itself in the sensitivity analyses. We also performed the worst-case scenario analysis: the combination of the worst case of items 1 to 7.

BASE CASE ANALYSIS

Table 4 summarizes the expected diphtheria, tetanus, pertussis, Hib, poliomyelitis, measles, mumps, rubella, congenital rubella syndrome, HBV, and varicella cases and deaths, as well as the associated economic burden with and without a vaccination program. Without a routine childhood vaccination program, the model estimated that in a cohort of 3 803 295 children, approximately 14.3 million cases of these diseases would occur, resulting in 33 564 deaths. These cases would result in direct costs of $12.3 billion and societal costs of $46.6 billion. Disease-associated costs with vaccination were $0.1 billion and $0.5 billion, respectively. The direct and societal costs of the routine childhood vaccination program with DTaP, Td, Hib, IPV, MMR, HB, and varicella vaccines were estimated to be $2.3 billion and $2.8 billion, respectively (Table 5). The calculated NPVs (net savings) of the routine childhood vaccination program from the direct cost and societal perspectives were $9.9 billion and $43.3 billion, respectively. The direct and societal BCRs for the routine vaccination program were 5.3 and 16.5, respectively.

Table Graphic Jump LocationTable 4. Health and Economic Outcomes for Selected Vaccine-Preventable Diseases With and Without a Vaccination Program*
Table Graphic Jump LocationTable 5. Summary of Costs and Benefit-Cost Ratios*
SENSITIVITY ANALYSES

Table 6 gives the direct and societal BCRs after sensitivity analysis, and Figure 2 shows the related tornado graph for the societal BCRs. When we doubled the adverse events rate used in the base case analysis, the direct and societal BCRs became 5.2 and 16.3, respectively. To evaluate the extent to which underestimation of disease incidence in the postvaccination era may have affected our analysis, we ran the model using postvaccination diphtheria, tetanus, pertussis, measles, mumps, and rubella rates that were 1000% of the rates in the base case analysis. The direct and societal BCRs did not change substantially. The incidences, costs, and patterns of treatment of some diseases likely have changed across time even without vaccination. For the worse-case scenario, if the total direct and indirect costs without vaccination were reduced by 20%, the related direct and societal BCRs became 4.2 and 13.2, respectively. If 100% of these 7 vaccines were purchased at private sector prices and administered by the private sector, the total direct and societal vaccination program costs increased to $2.8 billion and $3.3 billion, and the related direct and societal BCRs became 4.3 and 13.8, respectively. If the administration costs in the public and private sectors were doubled, the related direct and societal BCRs became 3.7 and 12.3, respectively. With a lower or higher wastage rate, the BCRs changed only slightly. When federal, state, and local vaccination program management expenditures (approximately $700 million based on estimated costs for 2001 and including section 317 of the Public Health Services Act, Vaccines for Children program, state and local funds, and part of the National Vaccine Injury Compensation Fund, which covered the vaccines administered before October 1, 1988) were included, the direct and societal BCRs were 4.1 and 13.2, respectively. In the worst case, which included all the worse-case scenarios mentioned previously herein, the related direct and societal BCRs were 1.8 and 6.5, respectively.

Place holder to copy figure label and caption
Figure 2.

Sensitivity analysis: societal benefit-cost ratios (baseline = 16.5).

Graphic Jump Location
Table Graphic Jump LocationTable 6. Benefit-Cost Ratios: Univariate Sensitivity Analysis

If we assumed no costs associated with parent travel and time lost (because most routine vaccination occurs during well-child care visits at which other services are delivered), the related direct and societal BCRs were 5.5 and 20.8, respectively. Finally, with higher discount rates (ie, 8%), the direct BCR decreased slightly and the societal BCR (6.1 for 8%) decreased by two thirds from the base case.

The results of this study show that for the 2001 US birth cohort alone, routine childhood immunization with DTaP, Td, Hib, IPV, MMR, HB, and varicella resulted in substantial cost savings (~$10 billion and >$43 billion from the direct cost and societal perspectives, respectively) and has high BCRs: for every dollar spent, the vaccination program saves more than $5 in direct costs and approximately $11 in additional costs to society.

The sensitivity analysis found the results to be most sensitive to discount rate, yet even with the worst-case scenario, the BCRs were still greater than 1. Our results remained stable across a wide range of vaccine wastage rate estimates. In recent years, approximately half of the childhood vaccines have been purchased at public sector prices through programs such as the Vaccines for Children Program and the State Child Health Insurance Program.97,98 In our sensitivity analysis, increasing the proportion of vaccines purchased by private providers did not substantially change BCRs. This finding is important because costs are higher for privately purchased and administered vaccines compared with publicly purchased and administered vaccines. The role of the private sector in administering vaccines is expected to continue to increase with insurance reform to improve vaccination coverage rates in children (ie, first dollar laws) and the increasing delivery of vaccines by managed care organizations.99 The BCRs remained high when all vaccines were purchased in the private sector, so one might conclude that there is no need for public purchase. However, this 1-way sensitivity analysis did not account for changes in immunization rates that might result from higher vaccine prices. Neither does it address equity issues associated with public purchase, such as vaccine access for the underserved and the public good of preventing infectious disease with vaccines.

This study has some limitations. Some of the cost data used in the analysis may not be representative because we derived some of the cost estimates from commercial databases. Also, by not including items such as pain and suffering to the family and friends of the ill patients, our model underestimated the benefit of the immunization program. In addition, by increasing the number of physician contacts, vaccination programs introduce indirect benefits by adding new opportunities for the provision of other preventive counseling and services. Regarding varicella, the vaccination program was not mature in 2001, and 6 years after vaccine licensure, full reduction of varicella cases had not yet occurred, so our model underestimated the benefits of the fully implemented varicella program. Furthermore, regarding varicella vaccination, we made the conservative assumption that all the children received vaccine regardless of a history of chickenpox. We also did not analyze for undefined impacts of varicella vaccination on risk of herpes zoster in either vaccinees or persons with a history of chickenpox.

Data on the probability distributions of variables are unavailable, which prevents us from conducting a Monte Carlo simulation for a multivariate probabilistic sensitivity analysis and estimating confidence intervals. Also, this analysis does not include hospital infection control costs and costs to the public sector, such as surveillance officers and outbreak response, and neither does it include the indirect costs of diagnostic and confirmatory laboratory testing for persons with compatible illnesses. Whereas some diagnostic testing has long been conducted for treatment purposes, the establishment of vaccination and disease control programs generally leads to substantial increases in testing, particularly for viral illnesses, such as measles or rubella.

Finally, as in most economic analyses, caution should be exercised in interpreting and generalizing these results. For example, we did not include pneumococcal conjugate and influenza vaccines, and so this analysis should not be viewed as an analysis of the whole immunization program in the United States. In addition, we did not consider the future cost of disease if we stop vaccination now, and neither did we estimate the marginal cost of increasing vaccination coverage from current levels. Neither did we address the vaccine supply and demand issues and the benefits for vaccine producers.

This analysis will be helpful in understanding the economic effects of the immunization program under current circumstances. Administrators and policy makers may use the results to obtain sustained support for programs, make needed modifications, and guide future programs. Overall, as the burden of disease decreases owing to the use of vaccines, this type of analysis will help ensure that society remains aware of the tremendous return on the investment in vaccines, measured not only in dollars but in health. Conversely, if the current high vaccination coverage levels are not maintained, vaccine-preventable diseases will recur along with the health burden, deaths, and costs to the medical system and society.

Despite the substantial success in achieving high immunization coverage and in reducing vaccine-preventable diseases in children, challenges remain. Efforts must continue to reach 2010 goals of 90% coverage for selected vaccines and to reduce remaining socioeconomic and racial/ethnic disparities in coverage and to improve adult and adolescent immunization rates. Concerns related to the safety of vaccines can lead to declining coverage if not appropriately addressed.100 As newer and better vaccines (some of which are much more expensive) and combination vaccines become available, they will need to be incorporated into the already complex, increasingly expensive immunization system. Pertussis is the only disease for which children are routinely vaccinated that is not at historically low levels in the United States. Because the coverage among vaccine-eligible age groups remains high and the effectiveness of acellular pertussis vaccine has been demonstrated to be high in postlicensure evaluations, new strategies are needed to further reduce the incidence of pertussis.

The current immunization program with these 7 vaccines is cost saving, although newer vaccines (eg, varicella and pneumococcal conjugate) have proved to be more expensive than older ones. However, future recommendations should not be limited to vaccines that demonstrate cost savings. To do so would place them at a comparative disadvantage that few other prevention interventions could meet and would likely lead to missed opportunities to provide good value to society by prevention of diseases.

Because of the success of the current routine childhood vaccination program, diphtheria, tetanus, pertussis, Hib, poliomyelitis, measles, mumps, and rubella are no longer major health threats in the United States, and the threat of HB and varicella is substantially decreased. Although not reflected in this analysis and difficult to quantify, a dramatic decrease in the loss and suffering of patients, family, and friends is also a direct result of this achievement. Routine childhood vaccination against diphtheria, tetanus, pertussis, Hib, poliomyelitis, measles, mumps, rubella, HB, and varicella in the United States is a remarkable medical accomplishment that achieves significant public health benefit at a substantial cost savings.

Correspondence: Fangjun Zhou, PhD, National Immunization Program, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop E-52, Atlanta, GA 30333 (faz1@cdc.gov).

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention, US Department of Health and Human Services.

Accepted for Publication: June 23, 2005.

Acknowledgment: We thank Christine M. Arcari, PhD, MPH, Palmer Beasley, MD, John Bergstrom, PhD, Kristine M. Bisgard, DVM, MPH, James D. Cherry, MD, Patrick J. Coleman, PhD, Robert R. Deuson, PhD, MS, Donatus U. Ekwueme, PhD, Edith Gary, MT, Dalya Guris, MD, MPH, Neal Halsey, MD, Lauro S. Halstead, MD, Alan Hinman, MD, Sam Katz, MD, Robert Kim-Farley, MD, MPH, Tracy Lieu, MD, John Modlin, MD, Trudy V. Murphy, MD, Walter Orenstein, MD, Gary Don Overturf, MD, Mark Papania, MD, MPH, Susan Reef, MD, Jane Seward, MBBS, MPH, and Peter M. Strebel, MD, for their critical assistance and thoughtful review of this manuscript; and Mary McCauley, MTSC, for her assistance in manuscript preparation.

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Hatziandreu  EJBrown  REHalpern  MT A Cost Benefit Analysis of the Measles-Mumps-Rubella (MMR) Vaccine: Report Prepared for the Centers for Disease Control and Prevention.  Arlington, Va Battelle Inc1994;
Zhou  FReef  SMassoudi  M  et al.  An economic analysis of the current universal 2-dose measles-mumps-rubella vaccination program in the United States. J Infect Dis 2004;189S131- S145
PubMed
Mulley  AGSilverstein  MDDienstag  JL Indications for use of hepatitis B vaccine, based on cost-effectiveness analysis. N Engl J Med 1982;307644- 652
PubMed
Bloom  BSHillman  ALFendrick  AMSchwartz  JS A reappraisal of hepatitis B virus vaccination strategies using cost-effectiveness analysis. Ann Intern Med 1993;118298- 306
PubMed
Bergus  GMeis  S Hepatitis B vaccination: a cost analysis. Iowa Med 1995;85209- 211
PubMed
Margolis  HSColeman  PJBrown  REMast  EESheingold  SHArevalo  JA Prevention of hepatitis B virus transmission by immunization: an economic analysis of current recommendations. JAMA 1995;2741201- 1208
PubMed
Hadler  SC Cost benefit of combining antigens. Biologicals 1994;22415- 418
PubMed
Fendrick  AMLee  JHLaBarge  CGlick  HA Clinical and economic impact of a combination Haemophilus influenzae and hepatitis B vaccine: estimating cost-effectiveness using decision analysis. Arch Pediatr Adolesc Med 1999;153126- 136
PubMed
Preblud  SROrenstein  WAKoplan  JPBart  KJHinman  AR A benefit-cost analysis of a childhood varicella vaccination programme. Postgrad Med J 1985;61 ((suppl 4)) 17- 22
PubMed
Lieu  TACochi  SLBlack  SB  et al.  Cost-effectiveness of a routine varicella vaccination program for US children. JAMA 1994;271375- 381
PubMed
Huse  DMMeissner  HCLacey  MJOster  G Childhood vaccination against chickenpox: an analysis of benefits and costs. J Pediatr 1994;124869- 874
PubMed
Lieu  TARay  GTBlack  SB  et al.  Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children. JAMA 2000;2831460- 1468
PubMed
Miller  MAHinman  AR Cost-benefit and cost-effectiveness analysis of vaccine policy. Plotkin  SAOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;1075- 1088
Centers for Disease Control and Prevention, Ten great public health achievements—United States, 1900-1999. MMWR Morb Mortal Wkly Rep 1999;48241- 243
PubMed
Centers for Disease Control and Prevention, Impact of vaccines universally recommended for children—United States, 1990-1998. MMWR Morb Mortal Wkly Rep 1999;48243- 248
PubMed
Seward  JFWatson  BMPeterson  CL  et al.  Varicella disease after introduction of varicella vaccine in the United States, 1995-2000. JAMA 2002;287606- 611
PubMed
Nguyen  HQJumaan  AOSeward  JF Decline in mortality due to varicella after implementation of varicella vaccination in the United States. N Engl J Med 2005;352450- 458
PubMed
 Use of diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine as a five-dose series: supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2000;49 ((RR-13)) 1- 8
Atkinson  WWolfe  Seds Epidemiology and Prevention for Vaccine-Preventable Disease. 7th ed. Washington, DC Public Health Foundation2003;
 Poliomyelitis prevention in the United States: updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2000;49 ((RR-5)) 1- 22
Redd  SMarkowitz  LEKatz  SL Measles vaccine. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;409- 439
Plotkin  SWharton  M Mumps vaccine. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;267- 292
Plotkin  S Rubella vaccine. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;409- 439
 Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1996;45 ((RR-11)) 1- 36
Advisory Committee on Immunization Practices, Preventing pneumococcal disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2000;49 ((RR-9)) 1- 35
PubMed
 Pertussis vaccination: use of acellular pertussis vaccines among infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1997;46 ((RR-7)) 1- 25
 Haemophilus B conjugate vaccines for prevention of Haemophilus influenzae type B disease among infants and children two months of age and older: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep 1991;40 ((RR-1)) 1- 7
 Measles, mumps, and rubella—vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep 1998;47 ((RR-8)) 1- 57
 Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep 1991;40 ((RR-13)) 1- 25
Murata  R Immunization against diphtheria in Japan. Jpn J Med Sci Biol 1981;34329- 354
PubMed
Romanus  VJonsell  RBergquist  SO Pertussis in Sweden after the cessation of general immunization in 1979. Pediatr Infect Dis J 1987;6364- 371
PubMed
Collins  SA Age incidence of the common communicable diseases in children. Public Health Rep 1929;44763- 826
Granoff  DMBasden  M Haemophilus influenzae infections in Fresno County, California: a prospective study of the effects of age, race, and contact with a case on incidence of disease. J Infect Dis 1980;14140- 46
PubMed
Ward  JIZangwill  KM Haemophilus influenzae vaccines. In: Plotkin S, Orenstein WA, eds. Vaccines.  Philadelphia, Pa WB Saunders Co1999;183- 211
Langmuir  AD Medical importance of measles. AJDC 1962;103224- 226
PubMed
Wassilak  SGOrenstein  WASutter  RW Tetanus toxoid. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;441- 474
Mortimer  EA  JrWharton  M Diphtheria toxoid. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;140- 157
Edwards  KMDecker  MDMortimer  EA  Jr Pertussis vaccine. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;293- 344
Centers for Disease Control (CDC) and Prevention, Summary of notifiable diseases, United States: 1990. MMWR Morb Mortal Wkly Rep 1991;391- 61
PubMed
Tanaka  MVitek  CRPascual  FBBisgard  KMTate  JEMurphy  TV Trends in pertussis among infants in the United States, 1980-1999. JAMA 2003;2902968- 2975
PubMed
Lee  GMLett  SSchauer  S  et al.  Societal costs and morbidity of pertussis in adolescents and adults. Clin Infect Dis 2004;391572- 1580
PubMed
Horstmann  DM Poliomyelitis: severity and type of disease in different age groups. Ann N Y Acad Sci 1955;61956- 967
PubMed
Codd  MBMulder  DWKurland  LTBeard  CMO'Fallon  WM Poliomyelitis in Rochester, Minnesota, 1935-1955: epidemiology and long-term sequelae: a preliminary report. Halstead  LSWiechers  DOeds.Late Effects of Poliomyelitis Miami, Fla Symposia Foundation1985;121- 134
Alcock  AJHildes  JAKaufert  PAKaufert  JMBickford  J Respiratory poliomyelitis: a follow-up study. CMAJ 1984;1301305- 1310
Ramlow  JAlexander  MLaPorte  RKaufmann  CKuller  L Epidemiology of the post-polio syndrome. Am J Epidemiol 1992;136769- 786
PubMed
Halstead  LSWiechers  DORossi  CD Results of a survey of 201 polio survivors. South Med J 1985;781281- 1287
PubMed
Halstead  LSSilver  JK Nonparalytic polio and postpolio syndrome. Am J Phys Med Rehabil 2000;7913- 18
PubMed
Plotkin  SMurdin  ADVidor  E Inactivated polio vaccine. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;345- 363
Pelletier  LChung  PDuclos  PManga  PScott  J A benefit-cost analysis of two-dose measles immunization in Canada. Vaccine 1998;16989- 996
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Centers for Disease Control, Subacute sclerosing panencephalitis surveillance—United States. MMWR Morb Mortal Wkly Rep 1982;31585- 588
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Miller  ECradock-Watson  JEPollock  TM Consequences of confirmed maternal rubella at successive stages of pregnancy. Lancet 1982;2781- 784
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Meyer  PASeward  JFJumaan  AOWharton  M Varicella mortality: trends before vaccine licensure in the United States, 1970-1994. J Infect Dis 2000;182383- 390
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Margolis  HSAlter  MJHadler  SC Hepatitis B: evolving epidemiology and implications for control. Semin Liver Dis 1991;1184- 92
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Andre  FEZuckerman  AJ Review: protective efficacy of hepatitis B vaccines in neonates. J Med Virol 1994;44144- 151
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 HCUPnet Web site. Available at:http://www.ahrq.gov/data/hcup/hcupnet.htmAccessed December 27, 2001
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Boyle  CADecoufle  PYeargin-Allsopp  M Prevalence and health impact of developmental disabilities in US children. Pediatrics 1994;93399- 403
PubMed
Halpern  MRentz  AMurray  M Cost of illness of epilepsy in the US: comparison of patient-based and population-based estimates. Neuroepidemiology 2000;1987- 99
PubMed
Chambers  JGWolman  JM What Can We Learn From State Data Systems About the Cost of Special Education: A Case Study of Ohio.  Palo Alto, Calif Center for Special Education Finance, American Institutes for Research1998;
Iregui  MMalen  JTuteur  PLynch  JHoltzman  MJKollef  MH Determinants of outcome for patients admitted to a long-term ventilator unit. South Med J 2002;95310- 317
PubMed
Davis  HLefrak  SSMiller  DMalt  S Prolonged mechanically assisted ventilation: an analysis of outcome and charges. JAMA 1980;24343- 45
PubMed
 Rotary Club of Santa Monica. Payment options for senior housing and residential care Available at:http://www.helpguide.org/elder/paying_for_senior_housing_residential_care.htmAccessed August 10, 2004
Rosen  RLBone  RC Economics of mechanical ventilation. Clin Chest Med 1988;9163- 169
PubMed
Mohr  PEFeldman  JJDunbar  JL  et al.  The societal costs of severe to profound hearing loss in the United States. Int J Technol Assess Health Care 2000;161120- 1135
PubMed
Haddix  AETeutch  SMCorso  PS Prevention Effectiveness: A Guide to Decision Analysis and Economic Evaluation.  New York, NY Oxford University Press2003;
Centers for Disease Control and Prevention, National, state, and urban area vaccination coverage levels among children aged 19-35 months—United States, 2000. MMWR Morb Mortal Wkly Rep 2001;50637- 641
PubMed
Santoli  JMRodewald  LEMaes  EFBattaglia  MPCoronado  VG Vaccines for Children program, United States, 1997. Pediatrics 1999;104e15
PubMed
Rodewald  LESzilagyi  PGHoll  JShone  LRZwanziger  JRaubertas  RF Health insurance for low-income working families: effect on the provision of immunizations to preschool-age children. Arch Pediatr Adolesc Med 1997;151798- 803
PubMed
National Vaccine Advisory Committee, Strategies to sustain success in childhood immunizations. JAMA 1999;282363- 370
PubMed
Marshall  GSGellin  BG Challenges to vaccine safety. Prim Care 2001;28853- 868
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Simplified decision tree.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Sensitivity analysis: societal benefit-cost ratios (baseline = 16.5).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Diphtheria, Tetanus, Pertussis, Hib, Poliomyelitis, Measles, Mumps, Rubella, and Varicella Annual Incidence Rates Without and With Vaccination*
Table Graphic Jump LocationTable 2. Probabilities and Costs of Hospitalizations and Outpatient Visits for Selected Vaccine-Preventable Diseases*
Table Graphic Jump LocationTable 3. Probabilities and Costs of Adverse Reactions*
Table Graphic Jump LocationTable 4. Health and Economic Outcomes for Selected Vaccine-Preventable Diseases With and Without a Vaccination Program*
Table Graphic Jump LocationTable 5. Summary of Costs and Benefit-Cost Ratios*
Table Graphic Jump LocationTable 6. Benefit-Cost Ratios: Univariate Sensitivity Analysis

References

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Hatziandreu  EJBrown  REHalpern  MT A Cost Benefit Analysis of the Measles-Mumps-Rubella (MMR) Vaccine: Report Prepared for the Centers for Disease Control and Prevention.  Arlington, Va Battelle Inc1994;
Zhou  FReef  SMassoudi  M  et al.  An economic analysis of the current universal 2-dose measles-mumps-rubella vaccination program in the United States. J Infect Dis 2004;189S131- S145
PubMed
Mulley  AGSilverstein  MDDienstag  JL Indications for use of hepatitis B vaccine, based on cost-effectiveness analysis. N Engl J Med 1982;307644- 652
PubMed
Bloom  BSHillman  ALFendrick  AMSchwartz  JS A reappraisal of hepatitis B virus vaccination strategies using cost-effectiveness analysis. Ann Intern Med 1993;118298- 306
PubMed
Bergus  GMeis  S Hepatitis B vaccination: a cost analysis. Iowa Med 1995;85209- 211
PubMed
Margolis  HSColeman  PJBrown  REMast  EESheingold  SHArevalo  JA Prevention of hepatitis B virus transmission by immunization: an economic analysis of current recommendations. JAMA 1995;2741201- 1208
PubMed
Hadler  SC Cost benefit of combining antigens. Biologicals 1994;22415- 418
PubMed
Fendrick  AMLee  JHLaBarge  CGlick  HA Clinical and economic impact of a combination Haemophilus influenzae and hepatitis B vaccine: estimating cost-effectiveness using decision analysis. Arch Pediatr Adolesc Med 1999;153126- 136
PubMed
Preblud  SROrenstein  WAKoplan  JPBart  KJHinman  AR A benefit-cost analysis of a childhood varicella vaccination programme. Postgrad Med J 1985;61 ((suppl 4)) 17- 22
PubMed
Lieu  TACochi  SLBlack  SB  et al.  Cost-effectiveness of a routine varicella vaccination program for US children. JAMA 1994;271375- 381
PubMed
Huse  DMMeissner  HCLacey  MJOster  G Childhood vaccination against chickenpox: an analysis of benefits and costs. J Pediatr 1994;124869- 874
PubMed
Lieu  TARay  GTBlack  SB  et al.  Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children. JAMA 2000;2831460- 1468
PubMed
Miller  MAHinman  AR Cost-benefit and cost-effectiveness analysis of vaccine policy. Plotkin  SAOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;1075- 1088
Centers for Disease Control and Prevention, Ten great public health achievements—United States, 1900-1999. MMWR Morb Mortal Wkly Rep 1999;48241- 243
PubMed
Centers for Disease Control and Prevention, Impact of vaccines universally recommended for children—United States, 1990-1998. MMWR Morb Mortal Wkly Rep 1999;48243- 248
PubMed
Seward  JFWatson  BMPeterson  CL  et al.  Varicella disease after introduction of varicella vaccine in the United States, 1995-2000. JAMA 2002;287606- 611
PubMed
Nguyen  HQJumaan  AOSeward  JF Decline in mortality due to varicella after implementation of varicella vaccination in the United States. N Engl J Med 2005;352450- 458
PubMed
 Use of diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine as a five-dose series: supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2000;49 ((RR-13)) 1- 8
Atkinson  WWolfe  Seds Epidemiology and Prevention for Vaccine-Preventable Disease. 7th ed. Washington, DC Public Health Foundation2003;
 Poliomyelitis prevention in the United States: updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2000;49 ((RR-5)) 1- 22
Redd  SMarkowitz  LEKatz  SL Measles vaccine. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;409- 439
Plotkin  SWharton  M Mumps vaccine. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;267- 292
Plotkin  S Rubella vaccine. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;409- 439
 Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1996;45 ((RR-11)) 1- 36
Advisory Committee on Immunization Practices, Preventing pneumococcal disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2000;49 ((RR-9)) 1- 35
PubMed
 Pertussis vaccination: use of acellular pertussis vaccines among infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1997;46 ((RR-7)) 1- 25
 Haemophilus B conjugate vaccines for prevention of Haemophilus influenzae type B disease among infants and children two months of age and older: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep 1991;40 ((RR-1)) 1- 7
 Measles, mumps, and rubella—vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep 1998;47 ((RR-8)) 1- 57
 Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep 1991;40 ((RR-13)) 1- 25
Murata  R Immunization against diphtheria in Japan. Jpn J Med Sci Biol 1981;34329- 354
PubMed
Romanus  VJonsell  RBergquist  SO Pertussis in Sweden after the cessation of general immunization in 1979. Pediatr Infect Dis J 1987;6364- 371
PubMed
Collins  SA Age incidence of the common communicable diseases in children. Public Health Rep 1929;44763- 826
Granoff  DMBasden  M Haemophilus influenzae infections in Fresno County, California: a prospective study of the effects of age, race, and contact with a case on incidence of disease. J Infect Dis 1980;14140- 46
PubMed
Ward  JIZangwill  KM Haemophilus influenzae vaccines. In: Plotkin S, Orenstein WA, eds. Vaccines.  Philadelphia, Pa WB Saunders Co1999;183- 211
Langmuir  AD Medical importance of measles. AJDC 1962;103224- 226
PubMed
Wassilak  SGOrenstein  WASutter  RW Tetanus toxoid. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;441- 474
Mortimer  EA  JrWharton  M Diphtheria toxoid. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;140- 157
Edwards  KMDecker  MDMortimer  EA  Jr Pertussis vaccine. Plotkin  SOrenstein  WAeds.Vaccines Philadelphia, Pa WB Saunders Co1999;293- 344
Centers for Disease Control (CDC) and Prevention, Summary of notifiable diseases, United States: 1990. MMWR Morb Mortal Wkly Rep 1991;391- 61
PubMed
Tanaka  MVitek  CRPascual  FBBisgard  KMTate  JEMurphy  TV Trends in pertussis among infants in the United States, 1980-1999. JAMA 2003;2902968- 2975
PubMed
Lee  GMLett  SSchauer  S  et al.  Societal costs and morbidity of pertussis in adolescents and adults. Clin Infect Dis 2004;391572- 1580
PubMed
Horstmann  DM Poliomyelitis: severity and type of disease in different age groups. Ann N Y Acad Sci 1955;61956- 967
PubMed
Codd  MBMulder  DWKurland  LTBeard  CMO'Fallon  WM Poliomyelitis in Rochester, Minnesota, 1935-1955: epidemiology and long-term sequelae: a preliminary report. Halstead  LSWiechers  DOeds.Late Effects of Poliomyelitis Miami, Fla Symposia Foundation1985;121- 134
Alcock  AJHildes  JAKaufert  PAKaufert  JMBickford  J Respiratory poliomyelitis: a follow-up study. CMAJ 1984;1301305- 1310
Ramlow  JAlexander  MLaPorte  RKaufmann  CKuller  L Epidemiology of the post-polio syndrome. Am J Epidemiol 1992;136769- 786
PubMed
Halstead  LSWiechers  DORossi  CD Results of a survey of 201 polio survivors. South Med J 1985;781281- 1287
PubMed
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