Published online June 1, 2005
PEDIATRICS Vol. 115 No. 6 June 2005, pp. 1675-1684 (doi:10.1542/peds.2004-2509)
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Pertussis in Adolescents and Adults: Should We Vaccinate?

Grace M. Lee, MD, MPH*,{ddagger}, Charles LeBaron, MD§, Trudy V. Murphy, MD§, Susan Lett, MD, MPH||, Stephanie Schauer, PhD|| and Tracy A. Lieu, MD, MPH*,¶

* Center for Child Health Care Studies, Department of Ambulatory Care and Prevention, Harvard Pilgrim Health Care and Harvard Medical School, Boston, Massachusetts
{ddagger} Divisions of Infectious Diseases
General Pediatrics, Children's Hospital Boston, Boston, Massachusetts
§ National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia
|| Massachusetts Department of Public Health, Boston, Massachusetts


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
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on disease incidence, costs, outcomes, vaccine efficacy, and adverse events were based on published studies, recent unpublished clinical trials, and expert panel input.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 ≥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.

Key Words: pertussis • cost-effectiveness • adolescent • immunization • vaccine

Abbreviations: QALY, quality-adjusted life-year • CE, cost-effectiveness • Td, tetanus-diphtheria • TdaP, tetanus-diphtheria-acellular pertussis • LYS, life-year saved

The incidence of reported pertussis in the United States has been increasing steadily in the past 2 decades.1–5 This trend is occurring despite the fact that childhood vaccination rates are at all-time highs and vaccine efficacy remains good.6,7 Some of this increase in disease is attributable to improved diagnostic techniques and increased awareness of this disease.2,8–12 However, several studies have suggested that immunity after vaccination wanes over time and protection may last only 10 to 15 years, leading to a susceptible population around the time of mid-adolescence.13–15 Pertussis cases among adolescents and adults now account for the bulk of the recent increase in the United States, with more than one half of reported cases now occurring in these age groups.3 The morbidity associated with pertussis among adolescents and adults can be severe and its economic impact quite substantial, with significant time lost from school and work for these individuals.2,16–19 Concomitantly, there has been an increase in the number of cases and deaths reported among infants <4 months of age.3,20,21 Adolescents and adults are thought to serve as the reservoir of infection and source of transmission to infants too young to receive a full series of pertussis immunizations.22–29

Acellular pertussis boosters formulated specifically for adolescents and adults are now available for use in Canada, France, Germany, and Australia.30–34 Combination vaccines that include tetanus, diphtheria, and acellular pertussis were shown to be safe and immunogenic in several clinical trials and may soon be available for use in the United States.35–40 One study suggested that the booster might be efficacious against cough illness attributable to pertussis among adolescents and adults.41,42 Routine use of an effective vaccine among adolescents and adults not only might reduce morbidity rates in these age groups but also might prevent infant pertussis infection through herd protection.22,25–29,43 However, the potential benefits of vaccination need to be weighed against the possible problems. Vaccine adverse events,44–48 waning immunity after adolescent or adult vaccination,14,15,49–51 and costs may all decrease the desirability of routine pertussis vaccination in these age groups.

We conducted this study to assist policymakers in decisions about whether and how pertussis vaccination of adolescents and/or adults should be adopted in the United States. Our objective was to evaluate the health benefits, risks, costs, and cost-effectiveness (CE) of alternative strategies for pertussis vaccination among adolescents and adults.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Model
We constructed a Markov model to calculate the health benefits, risks, costs, and CE of 6 vaccination strategies for healthy adolescents and/or adults, with an analytic horizon of a lifetime (Fig 1). On the basis of input from an expert panel, we evaluated the following strategies: (1) no vaccination (or status quo, with children being vaccinated at 2, 4, 6, and 12–15 months and 4–6 years of age), (2) 1-time adolescent vaccination at 11 years of age, (3) 1-time adult vaccination at 20 years of age, (4) adult vaccination with 10-year boosters, (5) adolescent and adult vaccination with 10-year boosters, and (6) postpartum vaccination (vaccinating mothers after birth plus another adult caregiver after the firstborn child). In our computer simulation model, we analyzed the health outcomes and costs for a US cohort of 4 million 11-year-old adolescents over their lifetimes. The base-case analysis assumed that the vaccination strategies had reached steady state in their implementation. The potential impact of alternative vaccination strategies on infant disease was considered in a separate decision-analytic model, and the results were combined with results from the adolescent/adult model in a spreadsheet, for comparison of the overall costs and benefits of each strategy.


Figure 1
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  		Fig 1. Decision-analytic model.

 
Probabilities and costs used in the model were derived from a review of the literature (Medline database search of articles in the English language from 1965 to 2004), recent vaccine clinical trial data, and unpublished data provided by the Centers for Disease Control and Prevention and the Massachusetts Department of Public Health. Where estimates were unavailable or uncertain despite these sources, we relied on a pertussis expert panel convened in November 2002 in Atlanta, Georgia. We used a modified Delphi process to obtain our estimates.

Outcomes included cases of pertussis prevented, number of vaccine adverse events, costs in 2004 US dollars,52 and incremental CE ratios, expressed as dollars per case prevented and dollars per quality-adjusted life-year (QALY) saved. The health care payer and societal perspectives were adopted, and future costs and health benefits were discounted at an annual rate of 3%.53 Modeling was performed with Data Professional software (TreeAge Software, Williamstown, MA) and Microsoft Excel 2000 (Microsoft, Redmond, WA).54

Probabilities
Disease Probabilities
At the start of the simulation, all adolescents were considered to be susceptible to pertussis. Each individual was assigned an age-specific risk of developing pertussis (1-year Markov cycles). Adolescents and adults with pertussis were classified as having mild cough illness, severe cough illness, or pneumonia (Fig 1). Each year, individuals also faced age-specific risks of dying from other causes. Estimates of adolescent and adult disease were based on incidence data for Massachusetts (Table 1), for 2 reasons. First, US incidence estimates are thought to be underestimated significantly.55 Second, Massachusetts is the only state in the United States that has a single-serum enzyme-linked immunosorbent assay for IgG to pertussis toxin (specificity of 99%) available as a diagnostic test, which allows enhanced detection of adolescent and adult disease.2,12


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  		TABLE 1. Disease and Vaccine Probabilities Used in the Model

 
Infants who had pertussis developed either respiratory or neurologic complications or died as a result of the disease. Respiratory complications among infants included mild disease that was treated on an outpatient basis and severe disease that required hospitalization. We assumed that pertussis survivors experienced no long-term complications. In the baseline analysis, only the postpartum vaccination strategy was assumed to reduce the number of cases of infant disease. Adolescent or adult vaccination strategies were assumed to have no impact on transmission to infants in the baseline analysis.

Vaccine Probabilities
Because the proposed vaccines would add an acellular pertussis booster to the tetanus-diphtheria (Td) vaccine, we assumed that realistically achievable pertussis booster rates would be similar to current Td booster rates. Therefore, vaccine coverage estimates were based on Td booster immunization rates from the National Health Interview Survey56 (Centers for Disease Control and Prevention, unpublished data) and expert panel input. For the postpartum vaccination strategy, we based our estimate of vaccine delivery in this population on rates of postpartum vaccination achieved among women who were rubella nonimmune.57–60 We assumed a small incremental increase in the frequency of adverse events after vaccination with tetanus-diphtheria-acellular pertussis (TdaP) vaccine, compared with Td vaccine.37,38,40

Waning Immunity
Health states in the model incorporated waning immunity after disease or vaccination. An individual who had disease or received a vaccine was boosted up to full immunity. On the basis of expert panel input and published data, immunity was assumed to wane each year for 15 years, after which the individual was considered nonimmune.14,15,50,51 These 15 immunity classes (Table 1) were associated with time-dependent probabilities of developing pertussis disease. Although past infection or vaccination could affect the future rate of disease, we assumed it did not affect the severity of disease in our baseline analysis, although we did address this issue in sensitivity analyses.

Infant Transmission
The baseline model assumed that universal adolescent or adult vaccination would have no impact on infant disease. We made this baseline assumption for 2 reasons. First, vaccine clinical trial data regarding the efficacy of the adolescent/adult formulation of the vaccine in reducing infant disease is not yet available. Second, we wanted to examine the CE of universal vaccination strategies independent of any potential benefit attributable to reduced infant transmission, to ensure that vaccine programs were justified on the basis of the impact for those vaccinated.

In an alternative analysis, we varied the potential to reduce infant transmission for each strategy, assuming vaccine delivery rates as used in the baseline analysis. We estimated that each vaccination strategy could reduce infant disease as follows: no vaccination (0%), 1-time adolescent vaccination (17%), 1-time adult vaccination (10%), adult vaccination with 10-year boosters (17%), and adolescent and adult vaccination with 10-year boosters (35%).61 For the postpartum vaccination strategy, we estimated that infant disease would be reduced by 40% in both baseline and alternative analyses, on the basis of estimates of 66% vaccine delivery and 87% vaccine efficacy and the assumption that caregivers were responsible for 70% of infant disease.

Patient Preferences
Preferences for study-specific health states were obtained from adults and parents of adolescents with confirmed pertussis disease in a separate study (Table 2). 18 Because the major impact of an adolescent/adult pertussis booster would be to reduce morbidity rates, rather than mortality rates, we chose to use QALYs as the unit of effectiveness in this study. QALYs combine both life expectancy and health-related quality of life into one measure. The number of QALYs related to a health outcome is calculated as the value given to a particular health state multiplied by the duration of that state.62 The time–trade-off method was used to measure preferences for health states.63,64 With the time–trade-off method, respondents were asked how much longevity they would be willing to give up, if any, to avoid living with a particular health outcome. We assumed that the mean durations of vaccination health states were 2 days for anaphylaxis and 7 days for local or systemic reactions. Estimates for the mean durations of infant disease (80 days) and adolescent or adult disease (87 days) were derived from available data.18,65


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  		TABLE 2. Utilities for Disease and Vaccination for Pertussis

 
Costs
Disease Costs
Disease costs (medical and nonmedical costs) for adolescents and adults were based on a recently published study (Table 3). 18 For infants, medical costs for respiratory and neurologic complications were estimated from health service utilization data from the Massachusetts enhanced pertussis surveillance system multiplied by the unit cost per service, from sources such as the Medicare fee schedule and the American Academy of Pediatrics fee schedule.66–69 We assumed that infant pertussis deaths incurred medical costs attributable to hospitalization and ICU admission.66,70 Nonmedical costs for infants were estimated to include time costs of work missed for 1 adult while the child received medical care (2 hours per office visit and 8 hours per day for hospitalizations). The median wage rate for female workers 25 to 35 years of age was used to calculate time costs related to infant disease.71 All disease costs were adjusted for inflation to 2004 US dollars.52


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  		TABLE 3. Disease and Vaccine Costs Used in the Model, in 2004 US Dollars

 
Vaccine Costs
Because the vaccine is not yet available for use in the United States, we estimated the incremental vaccine price from prices charged in other countries. The vaccine is available in Canada and Australia, with estimated incremental costs of approximately $10 and $22 (in US dollars), respectively (G.M. Lee, verbal communication, November 11, 2003).34,72,73 Therefore, we assumed an incremental vaccine price of $15 in our base-case analysis, ie, TdaP was assumed to cost $25, which is $15 more than the current Td cost ($10) (Table 3). For adolescent and adult visits, we assumed there was no incremental cost for a vaccine visit, vaccine administration, or time costs. For the postpartum vaccination strategy, we assumed the mother would be vaccinated immediately after birth in the hospital and would not incur additional costs. However, the other adult caregiver would need to visit a primary care provider to receive the vaccine and would incur additional costs attributable to a vaccine visit and administration.

In our baseline analysis, we assumed that local and systemic reactions resulted rarely in medically attended events (2%) that required a level 2 outpatient visit ($37).67 Therefore, the average cost of medically attended events attributable to vaccination was approximately $1. We varied the rate of medically attended adverse events from 0 to 100%, or from $0 to $37, in sensitivity analyses. A rare event such as anaphylaxis was assumed to require hospitalization.

Sensitivity Analyses
To address the potential impact of herd immunity, we conducted an alternative analysis with different assumptions about reduced infant transmission, as described above. To evaluate whether the results were sensitive to other baseline assumptions, we performed 1-way sensitivity analyses with the ranges provided in Tables 1, 2, and 3. We also examined 2-way sensitivity analyses of significant parameters identified in 1-way analyses. We used $50000 per QALY as a benchmark for considering vaccination to be cost-effective, relative to other interventions.74–77


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Health Benefits and Risks
Health outcomes were modeled over the lifetime of a hypothetical cohort of 4 million adolescents. Approximately 85000 cases would occur if no vaccination program were implemented (Table 4). The adolescent and adult vaccination with boosters strategy would prevent the most pertussis cases (35000 cases, or 41%) but would potentially cause 253000 adverse events (mostly minor). The 1-time adolescent vaccination strategy would prevent almost as many cases (30800 cases, or 36%), with many fewer adverse events. The 1-time adult vaccination, adult vaccination with boosters, and postpartum vaccination strategies each would prevent only a small percentage of pertussis cases (<8%), because of the relatively low baseline incidence of disease among adults, compared with adolescents.


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  		TABLE 4. Health Benefits, Risks, and QALY Saved Because of Pertussis Vaccination of a Hypothetical Cohort of 4 Million Individuals

 
When patient preferences regarding disease and vaccination were incorporated into the analysis through QALYs, the 1-time adolescent vaccination and adolescent and adult vaccination with boosters strategies resulted in the greatest health benefits, measured as net QALYs saved (Table 4). For the postpartum vaccination strategy, the benefits of preventing pertussis were much smaller, resulting in significantly fewer net QALYs. The 1-time adult vaccination and adult vaccination with boosters strategies resulted in fewer QALYs, compared with no vaccination, because of the small number of cases prevented and the frequent occurrence of minor adverse events.

Costs and CE
The overall costs for the cohort from the health care payer and societal perspectives were estimated at $23.7 million and $37.6 million, respectively, with no immunization program. None of the vaccination strategies resulted in net savings, because the savings from pertussis cases averted did not offset the costs of vaccination (Table 5). The adolescent and adult vaccination with boosters strategy had the highest total costs at $101.1 million (health care payer) and $109.3 million (societal), whereas the 1-time adolescent vaccination strategy cost $61.5 million (health care payer) and $70.6 million (societal).


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  		TABLE 5. Costs (2004 US Dollars) and CE of Pertussis Vaccination of a Hypothetical Cohort of 4 Million Individuals, From the Health Care Payer and Societal Perspectives

 
The 1-time adolescent vaccination strategy cost $1200 per case prevented (health care payer) and $1100 per case prevented (societal), compared with no vaccination (Table 5). The adolescent and adult vaccination with boosters strategy cost $9200 or more per case prevented, compared with the next-best strategy of 1-time adolescent vaccination. When we examined the incremental cost per QALY saved, the baseline analysis demonstrated a CE ratio of $23000 per QALY saved (health care payer) and $20000 per QALY saved (societal) for the 1-time adolescent vaccination strategy. All other strategies were dominated, meaning that they were more costly and less effective than other available interventions.

Sensitivity Analyses
When the probability and cost estimates in the model were varied over plausible ranges, 1-time adolescent vaccination usually remained the most effective and cost-effective strategy, with a criterion of less than $50000 per QALY saved. However, the adolescent and adult vaccination with boosters strategy potentially became cost-effective if 2 conditions were met simultaneously, ie, (1) the disease incidence for adolescents and adults was ≥6 times higher than base-case assumptions and (2) the cost of vaccination was less than $10. Similar results from sensitivity analyses were obtained for the health care payer and societal perspectives; therefore, results from the societal perspective are reported below, for simplicity.

Disease Incidence, Costs, and Outcomes
Because pertussis is thought to be underdiagnosed and underreported, we varied disease incidence over a very wide range (Fig 2). The CE ratio of the 1-time adolescent vaccination strategy ranged from $227000 per QALY saved (at 0.2 times the base-case estimate) to cost saving (at ≥4 times the base-case estimate). When medical costs of pertussis for adolescents and adults were varied from 0.1 to 5 times base-case estimates, the CE ratio for the 1-time adolescent vaccination strategy ranged from $24000 to $4000 per QALY saved. When nonmedical costs of pertussis were varied over the same range, the incremental CE ratio ranged from $23000 to $8000 per QALY saved. The probabilities of disease outcomes associated with pertussis among adolescents, adults, or infants did not affect the results significantly when varied over plausible ranges.


Figure 2
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  		Fig 2. Cost per case prevented (gray bars) and cost per QALY saved (black bars) for the 1-time adolescent vaccination strategy from the societal perspective when significant model parameters were varied. The dotted line indicates the baseline analysis estimate of $1100 per case prevented or $20000 per QALY saved. {dagger} One-time adolescent vaccination becomes cost-saving if the disease incidence is ≥4 times the base-case estimates.

 
Vaccine Efficacy, Costs, and Outcomes
Assumptions about vaccine-associated costs (price, visit, and administration), vaccine efficacy, and frequency of vaccine adverse events all affected significantly the CE of the 1-time adolescent vaccination strategy (Fig 2). If the incremental vaccine cost was $5, then the CE ratio dropped to $2200 per QALY saved. However, the CE ratio increased to $84500 per QALY saved at a vaccine cost of $50. The incremental CE ratio for 1-time adolescent vaccination exceeded $50000 per QALY if vaccine efficacy fell below 50% or if the frequencies of adverse events were higher than base-case assumptions (>12% systemic reactions or >0.7% anaphylaxis).

Even if we assumed there were no incremental adverse events attributable to vaccination, the 1-time adolescent vaccination strategy was not cost saving, with a CE ratio of $18000 per QALY and 1800 QALYs saved, whereas the adolescent and adult vaccination with boosters strategy saved 1880 QALYs and had an incremental CE ratio of $500000 per QALY. The 1-time adult vaccination, adult vaccination with boosters, and postpartum vaccination strategies could potentially save up to 40, 80, and 285 QALYs, respectively, if no vaccine adverse events occurred; however, these strategies were far more costly than adolescent vaccination strategies, because of the large number needed for immunization to prevent 1 case of pertussis.

Infant Transmission
To determine whether the potential to reduce infant transmission through vaccination of adolescents or adults would affect our results, we reanalyzed the model with herd immunity assumptions based on the dynamic model described by van Rie and Hethcote.61 The alternative assumptions did not change the results of our analysis significantly. From the health care payer perspective, the incremental CE ratio of the 1-time adolescent vaccination strategy decreased from $23000 to $22000 per QALY saved and the incremental CE ratio of the adolescent and adult vaccination with boosters strategy went from dominated to $1.5 million per QALY saved. From the societal perspective, the incremental CE ratio of the 1-time adolescent vaccination strategy went from $20000 to $19000 per QALY saved and the adolescent and adult vaccination with boosters strategy went from dominated to $1.4 million per QALY saved. All other strategies remained dominated (more costly and less effective), despite the reduction in infant disease.

For the alternative analysis, we also evaluated the outcome measure of cost per life-year saved (LYS), because infant deaths were prevented. Compared with no vaccination, the postpartum vaccination strategy resulted in a CE ratio of $275000 per LYS and $268000 per LYS from the health care payer and societal perspectives, respectively. The adult vaccination with boosters strategy and the adolescent and adult vaccination with boosters strategy were dominated, because they were more costly and less effective than other options. The 1-time adolescent vaccination and 1-time adult vaccination strategies were eliminated by extended dominance, because they had higher incremental CE ratios than the postpartum vaccination strategy.

Utilities
If utilities for disease outcomes approached 1, or near perfect health, then the CE ratio for the 1-time adolescent vaccination strategy would increase to $36000 per QALY saved. However, if utilities for disease outcomes were 0.5 times our base-case assumptions, then the CE ratio would decrease to $8000 per QALY saved. If we varied the utilities for vaccine adverse events from 0.5 to 1.05 times base-case estimates, then the CE ratio for the 1-time adolescent vaccination strategy ranged from $20000 to $39000 per QALY saved.

Two-Way Sensitivity Analysis
On the basis of the results of 1-way sensitivity analyses, we conducted a 2-way sensitivity analysis by varying disease incidence and vaccine efficacy simultaneously. If disease incidence was greater than estimated, then the 1-time adolescent vaccination strategy remained effective and cost-effective. If vaccine efficacy was >90% and disease incidence was 8 times higher than base-case estimates, then the adolescent and adult vaccination with boosters strategy became reasonably cost-effective. As vaccine efficacy fell below 50%, the CE ratio of the 1-time adolescent vaccination strategy exceeded $50000 per QALY and no vaccination was preferred unless disease incidence was ≥2 times base-case estimates.

We also examined disease incidence versus vaccine cost in a 2-way sensitivity analysis. The 1-time adolescent vaccination strategy remained a cost-effective strategy when both parameters were varied simultaneously. As disease incidence increased to ≥6 times base-case estimates and vaccine cost fell below $10, the adolescent and adult vaccination with boosters strategy became reasonably cost-effective, with CE ratios of less than $50000 per QALY. Adult vaccination strategies were less desirable than adolescent vaccination strategies under all sets of plausible assumptions for both analyses.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Our study found that 1-time vaccination of adolescents would result in significant net health benefits and might be reasonably cost-effective if the vaccine price in the United States is comparable to that in other countries where it is being used currently. With an incremental vaccine price of $15, the 1-time adolescent vaccination strategy cost $1100 per case prevented or $20000 per QALY saved, from the societal perspective. Compared with older, well-established immunization programs that are cost-saving, such as Haemophilus influenzae type b or measles vaccination programs, pertussis vaccination of adolescents would cost considerably more per health benefit gained.78,79 However, this intervention does fall within the range of CE ratios for newer, currently recommended immunizations, such as the conjugate pneumococcal vaccine for children in the United States.80,81

Our study is the first to consider patient preferences associated with pertussis and with vaccine adverse events to evaluate the cost per QALY saved, which allows this vaccine to be compared with other preventive interventions. In addition, our study is strengthened by the inclusion of medical and nonmedical costs of pertussis estimated in a recently published study.18 Furthermore, we chose the analytic horizon of a lifetime and incorporated waning immunity in our analysis, so that the long-term benefits of the vaccine could be fairly assessed. A recently published cost-benefit analysis also suggested that using an acellular pertussis vaccine for adolescents would be economically desirable.82 However, the previous study did not incorporate information regarding patient preferences or recent estimates of medical and nonmedical costs of pertussis at the time. In addition, the time horizon was only 10 years, which might have resulted in some bias, because vaccine-mediated immunity is estimated to last 10 to 15 years.

The results of our analysis were sensitive to several key assumptions, ie, disease incidence, vaccine efficacy, vaccine-associated costs, and frequency of vaccine adverse events. Although the baseline incidence rates used in the model (155 and 11 cases per 100000 for adolescents and adults) were significantly higher than current US surveillance estimates (7 and 1 cases per 100000 in adolescents and adults), prospective studies suggested that the incidence of pertussis might be as high as 507 cases per 100000 among adolescents and adults.9,41,55 Therefore, we might have underestimated the true impact of the vaccine in the population, although we used Massachusetts incidence rates. At extremely high disease rates, the CE ratio for vaccination appears more favorable and vaccination may even be cost saving. These findings underscore the need for additional research and surveillance efforts to assess accurately the true burden of pertussis in the population.

High vaccine cost, low vaccine efficacy, and high adverse-event rates would affect the CE of this vaccine significantly. We chose to vary these parameters over wide ranges because of their uncertainty. For example, the true effectiveness of a vaccine may be somewhat lower when a vaccine is implemented at the population level, instead of in a clinical trial setting. In addition, although clinical trials suggest that incremental adverse events are minimal, it will be critical to monitor these rates as a vaccine is deployed in the population, particularly given the concern over entire-limb swelling with booster doses of TdaP administered among children.44,45,83

The goal of preventing infant deaths attributable to pertussis has been discussed as a potentially important rationale for vaccination of adolescents and adults. However, limited information exists about how frequently pertussis is transmitted from one age group to another and how effective adolescent or adult vaccination would be in interrupting transmission to infants. In a dynamic model described by van Rie and Hethcote,61 vaccination of adolescents was found to increase the number of susceptible adults of childbearing age, presumably because of waning immunity, although the number of infant cases declined. The overall impact of an adolescent vaccination program on infant disease will depend on whether adults or adolescents are primarily responsible for transmitting infection to young infants. Because such uncertainty exists about infant transmission, we chose to focus our model on evaluating the risks and benefits for those who would receive vaccination, ie, adolescents and adults. We did attempt to address the potential impact of herd immunity in an alternative analysis that projected additional reductions in disease among infant age groups. Although we found no significant change in the overall CE of these preventive interventions, the decision to vaccinate will depend on multiple factors, of which CE is only one. Another limitation of our model includes the uncertainty with respect to the duration of vaccine- and disease-mediated immunity, particularly because there is limited experience with currently available adolescent/adult boosters on the market.

We conclude that routine pertussis vaccination is likely to be beneficial and may be reasonably cost-effective for adolescents, but not for adults, under our base-case assumptions. Additional information about disease incidence, vaccine efficacy, and vaccine adverse events would contribute to policy decisions about vaccine use.


   ACKNOWLEDGMENTS
 
This study was funded by the National Immunization Program, Centers for Disease Control and Prevention, through cooperative agreement with the Association of Teachers of Preventive Medicine (task order TS-0675), by National Vaccine Program Office funds, and by Agency for Healthcare Research and Quality grants T32 HS00063 and K08 HS13908-01A1 (to G.M.L.).

We gratefully acknowledge the colleagues who contributed invaluable input through our expert panel (which also included S.L.): Kris Bisgard, Kathy Edwards, Scott Halperin, Colin Marchant, Margaret Rennels, Joel Ward, and Melinda Wharton. We also thank our collaborators at the National Immunization Program at the Centers for Disease Control and Prevention, including Melinda Wharton, Lance Rodewald, Susan Chu, Donna Rickert, Ismael Ortega, John Glasser, Kris Bisgard, Karen Broder, Margaret Cortese, Elizabeth Fair, F. Brian Pascual, Martha Roper, Pamela Srivastava, Tejpratap Tiwari, and Gregory Wallace. Finally, we acknowledge the contribution to this work by our study coordinator in the Department of Ambulatory Care and Prevention, Donna Rusinak, and the pertussis epidemiologists at the Massachusetts Department of Public Health, including Kirsten Buckley, Nancy Harrington, Elissa Laitin, Marija Popstefanija, James Ransom, Kurt Seetoo, Jill Sheets, and Kristin Sullivan.


   FOOTNOTES
 
Accepted Feb 28, 2005.

Address correspondence to Grace M. Lee, MD, MPH, Department of Ambulatory Care and Prevention, Harvard Pilgrim Health Care and Harvard Medical School, 133 Brookline Ave, 6th Floor, Boston, MA 02215. E-mail: grace_lee{at}hphc.org

No conflict of interest declared.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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