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Societal Costs and Morbidity of Pertussis in Adolescents and Adults

  1. Grace M. Lee1,2,
  2. Susan Lett4,
  3. Stephanie Schauer4,
  4. Charles LeBaron5,
  5. Trudy V. Murphy5,
  6. Donna Rusinak1,
  7. Tracy A. Lieu1,3, and
  8. for the Massachusetts Pertussis Study Group4,a
  1. 1Center for Child Health Care Studies, Department of Ambulatory Care and Prevention, Harvard Pilgrim Health Care and Harvard Medical School, Boston, Massachusetts
  2. 2Division of Infectious Diseases, Boston, Massachusetts
  3. 3Division of General Pediatrics, Children's Hospital Boston, Boston, Massachusetts
  4. 4Massachusetts Department of Public Health, Boston, Massachusetts
  5. 5National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia
  1. Reprints or correspondence: Dr. Grace M. Lee, Dept. of Ambulatory Care and Prevention, Harvard Pilgrim Health Care and Harvard Medical School, 133 Brookline Ave., 6th Fl., Boston, MA 02215 (grace_lee{at}hphc.org).
 
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Abstract

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, ⩾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$.

Results. In the analysis of medical costs, 1679 adolescents and 936 adults were found to have mean costs of $242 and $326, respectively (P < .05). In interviews with 314 adolescents and 203 adults, adults had significantly higher nonmedical costs ($447) than those of adolescents ($155). 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.

Although childhood immunization levels are at all-time highs [1] and vaccine efficacy remains good [2], the numbers of reported cases, hospitalizations, and deaths due to pertussis have been relentlessly increasing over the past decade in the United States [3, 4]. A leading hypothesis posits that high pertussis vaccination levels have reduced childhood disease but that vaccine-induced immunity wanes as vaccinees reach adolescence and young adulthood, allowing for increased circulation of pertussis among these groups [5]. During 1990–1996, the reported incidence of pertussis doubled in the United States for persons >10 years of age, whereas the incidence for children aged 4 months to 10 years changed little [6]. Although it is unclear what proportion of the increase in reported cases among adolescents and adults results from greater recognition of the disease, a number of studies describe Bordetella pertussis as an important pathogen in these age groups, accounting for 10%–26% of respiratory illnesses [7–11] and producing symptoms that are severe and prolonged [9, 12–14]. Furthermore, adults and, possibly, adolescents may contribute to the transmission of the pathogen to infants who are too young to benefit from being fully vaccinated [15–17], resulting in increasing disease and mortality rates among patients <4 months of age [3].

Acellular pertussis vaccines for adolescents and adults have recently become available for use in Canada, France, Germany, and Australia [18]. Vaccine trials have demonstrated that pertussis booster doses are safe and immunogenic in these age groups [19, 20] and may be effective at preventing disease [21]. Some recent editorials have been for and some have been against consideration of similar policies in the United States [5, 22–25]. Before a vaccination policy for adolescents and adults can be considered, however, the programmatic costs need to be weighed against the burden of pertussis morbidity. Current information on disease costs in these age groups is needed to enable policy makers to make informed decisions about whether pertussis vaccination should be recommended. Our aim was to describe the morbidity, medical costs, and nonmedical costs associated with pertussis in adolescents and adults with confirmed disease.

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Methods

Study populations. We used 2 study populations identified through the enhanced pertussis surveillance system of the Massachusetts Department of Public Health (MDPH). For more than a decade, the MDPH has been engaged in rigorous pertussis surveillance and the Massachusetts State Laboratory Institute (MA SLI) has offered free diagnostic testing (culture and serologic analysis) to patients and health care professionals. The MA SLI performs single-serum ELISAs for IgG to pertussis toxin in individuals aged ⩾11 years, which is not available in other states [12, 26]. A confirmed case of pertussis is defined as an acute cough illness of any duration with laboratory confirmation by culture or as a cough illness lasting ⩾2 weeks with ⩾1 of the following symptoms: paroxysm, whoop, or posttussive vomiting in an individual with a laboratory-confirmed (i.e., by PCR or serologic analysis) infection or with epidemiologic-linkage to a laboratory-confirmed case.

To evaluate medical costs, we analyzed data, obtained from the MDPH, for individuals who had confirmed pertussis with onset of cough during the period of 1 January 1998 through 31 December 2000. To evaluate nonmedical costs, we conducted telephone interviews during the period of 1 December 2001 through 31 January 2003 in English or Spanish with individuals who were prospectively identified by the MDPH as having confirmed pertussis. The morbidity of pertussis disease was assessed in both cohorts. Cases were classified as mild cough illness, severe cough illness (cough associated with apnea, cyanosis, vomiting, or urinary incontinence), or pneumonia. The study was reviewed and approved by the institutional review boards of Children's Hospital Boston (Boston), Harvard Pilgrim Health Care (Boston), the MDPH (Jamaica Plain), and the Centers for Disease Control and Prevention (Atlanta).

Medical costs. Our analysis of medical costs included all confirmed cases of pertussis in adolescents (age, 10–17 years) and adults (age, ⩾18 years) during 1998–2000. Data were routinely collected as part of the enhanced pertussis surveillance system and included information about outpatient and hospital-based medical services. The major variables of interest were age, sex, race/ethnicity, dates of symptom onset and diagnosis, vaccination status, associated symptoms, types and results of laboratory tests, hospitalization, number of ambulatory visits, use of chest radiography, and antibiotic(s). The number of contacts recommended to receive prophylaxis with antibiotics to prevent the spread of pertussis was also recorded.

Estimates of medical costs were obtained by linking health service utilization data with national estimates of the costs of services. For example, the medical costs of a pertussis case were calculated by multiplying the number of units of each service (e.g., outpatient visits, hospital days, and laboratory tests) by the unit cost of the service. Unit costs for services were based on reimbursement rates from the Medicare Fee Schedule [27, 28] and the Physician Fee Schedule [29]. The 2002 Drug Topics Red Book was used to estimate average wholesale prices of prescription and nonprescription medications [30].

Nonmedical costs. To obtain information about morbidity and nonmedical costs, we conducted structured telephone interviews with adults or parents of adolescents with pertussis after resolution of symptoms or 12 weeks after symptom onset, whichever came first. Individuals were considered to be eligible if they had confirmed pertussis identified by surveillance activities and lived in Massachusetts. The interview, which took an average of 20–30 min to complete, included questions about the type and duration of symptoms, time missed from work or school, personal time missed, and other out-of-pocket costs, such as those for transportation to doctor visits, for babysitting, and for over-the-counter medications.

Nonmedical costs were estimated in accordance with the guidelines of the National Panel on Cost-Effectiveness in Health and Medicine [31]. Work-loss costs for adults were based on time missed from work multiplied by the national median wage rate for the age and sex of the individual affected [32]. Adolescent work-loss costs were not included in this analysis. However, we did calculate work-loss costs for parents of adolescents and other caregivers. Personal time for adults and parents (i.e., time lost from non-work-related activities) was valued at the same rate as time lost from work [31]. Although data on personal time costs were collected to understand the extent to which pertussis illness disrupts the lives of patients, we did not include such data in our primary analysis, to provide a conservative estimate of the total nonmedical costs.

Data analysis. Medical and nonmedical costs were adjusted to 2002 US$. Descriptive analyses were performed for medical and nonmedical costs associated with pertussis for adolescents and adults and included means and ranges. Mean values were chosen for comparison rather than median values because the latter do not reflect high costs that may occur with rare events. For comparisons of demographic and clinical characteristics, χ2 tests were used. A P value <.05 was considered to be significant in our analyses.

We compared mean arithmetic costs in 2 separate models. For medical costs, we compared costs by age group, sex, race/ethnicity, severity of symptoms, and vaccination status. For nonmedical costs, we compared costs by age group, sex, race/ethnicity of respondent, household income, educational level of respondent (or parent), and severity of symptoms. Because costs were not normally distributed, we used a nonparametric bootstrap approach using 1000 resamples to compare mean costs and calculate 95% bias-corrected CIs, which enabled us to avoid distributional assumptions [33]. When the 95% CIs excluded 0, mean differences were judged to be significant at P < .05.

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Results

Study population. For the medical-cost analysis, the MDPH enhanced surveillance system identified a total of 2793 cases of pertussis confirmed by culture (15%), serologic analysis (83%), or epidemiologic linkage (2%) during 1998–2000. A total of 1679 adolescents and 936 adults accounted for 94% of all reported cases in Massachusetts. Serologic testing and enhanced surveillance activities for pertussis are unique to Massachusetts. As a result, although Massachusetts has only 2% of the entire US population, 23% of all reported cases in the United States during this period were reported from this state.

For the nonmedical-cost analysis, there were 800 cases of pertussis among adolescents and adults in Massachusetts from December 2001 through January 2003. Of these cases, 314 adolescents (64%) and 203 adults (66%) completed telephone interviews. There were no significant differences with respect to age group, sex, or race/ethnicity between enrolled patients and all patients with confirmed cases during the enrollment period (data not shown). We also did not find significant differences with respect to age group, sex, or method of diagnosis between the medical- and nonmedical-cost cohorts (table 1). No significant differences in race/ethnicity were found when unknown cases were excluded.

Table 1
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Table 1

Demographic and clinical characteristics of patients in the medical-cost or nonmedical-cost cohorts.

Morbidity. The reported frequency of symptoms among adolescents and adults in the medical-cost cohort is described in table 2. When classified by severity of illness, disease in adults was worse than that in adolescents (P < .001). At the final interview, which occurred an average of 41 and 48 days after cough onset for adolescents and adults, respectively, 79% of adolescents and 83% of adults were still coughing.

Table 2
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Table 2

Morbidity of pertussis in adolescents and adults in the medical- and nonmedical-cost cohorts.

In the nonmedical-cost cohort, adolescents and adults described frequent symptoms and complications due to pertussis (table 2). Other symptoms described by participants that were not included in the survey included neck or back pain, bruised ribs or pulled rib muscles, fatigue or decreased energy, headaches, sore throat, nausea, gagging, fever, depression, worsened underlying disease (e.g., asthma, gastroesophageal reflux, and multiple sclerosis), irritability, suffocation, cyanosis, and seizures or convulsions. A total of 38% of adolescents and 61% of adults were still coughing at the time of the interview, which took place an average of 106 and 94 days after cough onset for adolescents and adults, respectively. Similar to the medical cost cohort described above, adults in the nonmedical-cost cohort had increased severity of illness, compared with adolescents (P = .029).

In the nonmedical-cost cohort, 261 adolescents (83%) missed a mean of 5.5 days of school (range, 0.4–32 days) because of pertussis. A total of 136 parents (43%) missed a mean of 2.4 days of work (range, 0.1–25 days) because of their child's illness. A second parent or caregiver also missed a mean of 1.8 days of work (range, 0.1–11 days) in 53 families. Among adolescents, 78 (25%) had jobs, and 46 (15%) missed a mean of 4.5 days of work (range, 0.6–35 days). Respondents were also asked about personal time missed from non-work-related activities during their child's illness. A total of 40% of parents reported missing a mean of 1.9 days of personal time (range, 0.02–58.3 days). Among adults with pertussis, 158 (78%) were employed at the time of illness, and 123 (61%) missed a mean of 9.8 days of work (range, 0.1–180 days). In 22 families, 27 additional adults also missed a mean of 4.0 days of work (range, 0.1–30 days) to care for family members with pertussis. A total of 76% of adults reported missing a mean of 5.7 days of personal time (range, 0.1–77.1 days) because of their illness.

Medical costs. Health service utilization for adolescents and adults is described in table 3. The mean medical cost per case in adolescent and adult patients was $242 and $326, respectively (table 4). Physician visits and antibiotics were responsible for a major proportion of the total medical costs. Medical costs were significantly higher in adults, in patients who had not received vaccination during childhood or had an unknown vaccination status, and in patients with severe cough illness or pneumonia (table 5). The mean cost of antibiotics to treat contacts was $242 (range, $0–$5614) for adolescent cases and $225 (range, $0–$11,766) for adult cases. If these costs were included in our analysis, the medical cost per case nearly doubled to $484 for adolescents and $551 for adults.

Table 3
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Table 3

Utilization of health services by 2615 adolescents and adults with pertussis in Massachusetts during 1998–2000.

Table 4
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Table 4

Mean medical, nonmedical, and societal costs among adolescent and adult patients with pertussis.

Table 5
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Table 5

Comparison of mean medical and nonmedical costs due to pertussis.

Nonmedical costs. The average nonmedical costs per case for adolescents and adults were $155 and $447, respectively (table 4). The majority of costs were due to time missed from work for adults and parents of adolescents. Adults were found to have nonmedical costs that were significantly higher than those of adolescents (table 5). There were no significant differences with respect to sex, race/ethnicity, income level, education level, or severity of illness. If we also considered the cost of personal time missed in our analysis, the total nonmedical cost per case would increase to $320 and $1400 for adolescents and adults, respectively.

Societal costs. The total costs of pertussis illness in adolescents and adults were $397 and $773 per case, respectively. Nonmedical costs represented 39% of the total cost in adolescents and 58% of the total cost in adults. If we included the costs of antibiotics to treat contacts and of personal time in our estimates, the societal cost could be as high as $804 and $1952 per case in adolescents and adults, respectively.

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Discussion

This is the first large-scale study to focus on the societal costs of pertussis illness in adolescents ($397) and adults ($773), for whom candidate vaccines now exist. The societal costs per case of pertussis appear to exceed the societal costs estimated for other common infections in adults and children, such as viral respiratory tract infections (∼$80) and varicella (∼$255) [34, 35]. On the basis of incidence data from Massachusetts and prospective studies of cough illness [9, 13], the extrapolated societal cost of pertussis illness in these age groups in the United States may be as high as $150–$980 million annually.

Previous studies have estimated the societal costs of pertussis to be $2115–$3561 per case, although disease occurred predominantly in young children rather than in adolescents or adults [36, 37]. Estimates from these studies may be higher because younger children are more likely to have severe complications due to pertussis [3]. Additionally, charges, rather than costs, were used for medical services, which may result in higher estimates that do not accurately reflect the true cost to society. Our study focused solely on adolescents and adults and estimated costs, rather than charges.

Adolescents and adults in our study were found to have significant morbidity due to pertussis. Yih et al. [12] reported a cough duration of ⩾4 weeks for 41% of adolescents and 52% of adults. Birkbaek et al. [8] estimated a cough duration of 46 days for adults at the time of their study. We found that 38% of adolescents and 62% of adults were still coughing at the time of our interview, which occurred an average of 106 days and 93 days, respectively, after cough onset. Although, classically, childhood pertussis is also known as the 100-day cough, the prolonged duration of disease in adolescents and adults has not, to our knowledge, previously been documented. Additionally, the time costs of pertussis illness are significant, compared with those of other common illnesses, such as influenza-like illnesses or chickenpox, for which the average number of workdays missed are 1.3 and 2.5 days, respectively [38, 39].

In our estimates of medical costs, we did not incorporate the cost of treating contacts with antibiotics, although we found these costs to be substantial in separate analyses. We also did not consider the costs of surveillance and outbreak control by the public health system in our analysis. The public health costs of infectious diseases has not been traditionally included in economic analyses, although one could argue that the cost of public health efforts to limit the spread of disease in the community is unique to infectious diseases and should be considered for inclusion in future analyses.

Nonmedical costs were responsible for more than one-third of the societal costs among adolescents and adults. These findings underscore the importance of collecting data on time costs and other out-of-pocket expenses, because these results may significantly affect the potential cost-effectiveness of vaccination programs from the societal perspective. Time costs due to missed work for adults and parents were responsible for a significant proportion of nonmedical costs, even though we did not incorporate dollar estimates of personal time missed or, for adolescents, time missed from school or work.

We also sought to understand which groups incurred higher medical and nonmedical costs due to pertussis. In the medical-cost cohort, adults, patients with severe disease, and patients who had not received vaccination during childhood or had an unknown vaccination status were more likely to have higher medical costs. It is not surprising that adults who were vaccinated long ago or patients who had never been vaccinated should have increased severity of disease resulting in higher costs [40, 41]. Or, perhaps there is greater selection bias among adults, insofar as only the most-severe cases are recognized. It may also be possible that adults are more likely to undergo additional testing (e.g., chest radiography) and to receive additional treatment (e.g., prescription cough medicine and inhalers) than are adolescents because of comorbidities that we could not account for in our analysis. For nonmedical costs, age group was the only significant predictor of higher cost. It is clear that adults incurred more nonmedical costs (because of more time lost from work due to their own illness) than did parents of adolescents.

Limitations of our study include the potential for selection bias in both the medical- and nonmedical-cost cohorts. Our study cohorts in Massachusetts may be different from the general US population, and, thus, these costs may not be a true reflection of the national costs of pertussis. For example, our respondents were predominantly white and had high education and income levels, compared with the general US population. Also, severe cases of pertussis are more likely to be identified by surveillance. Conversely, Massachusetts is a unique setting for the study of adolescent and adult disease because it is the only state in the United States that uses serologic analysis to diagnose cases. Improved diagnostic capabilities have resulted in better recognition and reporting of disease in Massachusetts, compared with other states, which may have resulted in somewhat reduced selection bias in our population. Nonetheless, current surveillance activities may still only be identifying the “tip of the iceberg” when it comes to pertussis. Although the cost per case may be overestimated because of selection bias, we are also likely underestimating the true costs of disease to society because of underdiagnosis.

Another potential limitation in our study is recall bias. Because the duration of illness was quite long for these patients, we performed interviews as soon as possible after symptoms had resolved or after the twelfth week of symptoms, whichever came first. We attempted to link the timing of the interview to the time of symptom resolution, because interviewing too early may miss some of the costs associated with the loss of work or other time-related factors due to the disease. If symptoms lasted for >12 weeks, the interview was done despite the persistence of symptoms, to try and minimize recall bias.

In conclusion, the morbidity and economic impact of pertussis illness in adolescents and adults is substantial. This fact, in conjunction with the concern about the increasing number of reported pertussis cases in this population, puts the question about vaccine use at the forefront. The societal costs and morbidity of pertussis in adolescents and adults need to be weighed against the vaccine's cost, efficacy, and frequency of adverse events. We believe these data will provide policy makers with additional information needed for weighing the potential risks and benefits of vaccination.

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Massachusetts Pertussis Study Group

Kirsten Buckley, Nancy Harrington, Elissa Laitin, Marija Popstefanija, James Ransom, Kurt Seetoo, Jill Sheets, and Kristin Sullivan.

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Acknowledgments

We gratefully acknowledge the assistance of our collaborators at the National Immunization Program at the Centers for Disease Control and Prevention (Atlanta), including Melinda Wharton, Lance Rodewald, Susan Chu, Donna Rickert, and particularly the following members of the pertussis unit, without whom this study would not have been possible: Kris Bisgard, Karen Broder, Margaret Cortese, Elizabeth Fair, F. Brian Pascual, Martha Roper, Pamela Srivastava, Tejpratap Tiwari, and Gregory Wallace. We also wish to thank our study interviewers, Laura Laguna and Erika Nakamoto.

Financial support. National Immunization Program, Centers for Disease Control and Prevention, via a cooperative agreement with the Association of Teachers of Preventive Medicine (task order TS-0675); National Vaccine Program Office funds; and the Agency for Healthcare Research and Quality, US Department of Health and Human Services (grant T32 HS00063; to G.M.L.).

Potential conflicts of interest. All authors: no conflicts.

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Footnotes

  • ↵a Members of the study group are listed at the end of the text.

  • Received April 14, 2004.
  • Accepted May 24, 2004.
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  1. Clin Infect Dis. (2004) 39 (11): 1572-1580. doi: 10.1086/425006
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