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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Am J Manag Care. Author manuscript; available in PMC Sep 1, 2010.
Published in final edited form as:
PMCID: PMC2918289

Cost-Effectiveness of Healthcare Worker Pneumococcal Polysaccharide Vaccination During Pandemic Influenza



In prior influenza pandemics, pneumococcal complications of influenza have caused substantial morbidity and mortality. The usefulness and cost-effectiveness of pneumococcal vaccination for healthcare workers during an influenza pandemic is unknown.

Study Design

Markov modeling was used to estimate the cost-effectiveness of pneumococcal polysaccharide vaccination (PPV) in previously unvaccinated healthcare workers during an influenza pandemic.


Invasive pneumococcal disease (IPD) incidence rates were incorporated into the model, assuming that IPD events occurred at twice the usual rate during the year of pandemic influenza. Both societal and hospital perspectives were examined. Assumptions were that: pneumococcal disease transmission from healthcare worker to patient did not occur, heightened IPD risk occurred for only 1 year, and PPV did not prevent noninvasive pneumonia, all of which potentially bias against vaccination.


From a societal standpoint, pneumococcal vaccination of healthcare workers during an influenza pandemic is economically reasonable, costing $2,935 per quality adjusted life year gained; results were robust to variation in multiple sensitivity analyses. However, from the hospital perspective vaccinating healthcare workers was expensive, costing $1,676 per employee absence day avoided, given an IPD risk that, though increased, would still remain <1%.


Vaccinating all healthcare workers to protect against pneumococcal disease during a pandemic influenza outbreak is likely to be economically reasonable from the societal standpoint. However, pneumococcal vaccination is expensive from the hospital perspective, which might prevent implementation of a PPV program unless it is externally subsidized.

Keywords: pneumococcal polysaccharide vaccine, healthcare workers, pandemic influenza, cost-effectiveness, secondary pneumococcal pneumonia


As governmental, scientific, medical and public health communities respond to the 2009 influenza pandemic, many strategies are being considered to reduce the possibility of widespread morbidity and mortality. Primary, secondary and tertiary prevention measures have been devised, including the development of priority groups for pandemic influenza immunization.1 In a pandemic, where demand for health care would inevitably increase, the stability of health care systems would be threatened if healthcare workers became ill in sufficient numbers, a possible scenario, given their heightened exposure to a highly infectious illness. Thus, the Centers for Disease Control and Prevention (CDC) have listed healthcare workers among Tier 1 groups for priority influenza vaccination.1

Secondary pneumococcal infections caused as much as 20% of mortality during the 1918–19 pandemic as demonstrated in a review of autopsy series which found that 27% of blood cultures were positive for Streptococcus pneumoniae.2 This has led to recommendations that pandemic preparedness plans comprise more than just influenza vaccination and include, for example, vaccination against pneumococcal disease.2;3

Vaccinating healthcare workers against pneumococcal disease is a strategy with significant potential, but it is not without countervailing arguments. For example, based on what is known about the efficacy of pneumococcal polysaccharide vaccine (PPV) against invasive pneumococcal disease, is this a cost-effective solution? Given the worldwide nature of a pandemic, potential costs associated with prevention measures must be considered. Secondly, concerns about hypo-responsiveness, i.e., immunologic interference from the first dose limiting gains from a subsequent dose,4 raise the question about whether vaccination of healthy healthcare workers during a pandemic merely shifts the burden of pneumococcal disease to later years, without changing the cumulative incidence of disease. The purpose of this study is to use Markov modeling to estimate the cost-effectiveness of PPV in healthcare workers compared to nonuse during an influenza pandemic. The results of these analyses will help health systems to anticipate needs and costs in their pandemic preparedness planning.


The cost-effectiveness of 23-valent PPV use among healthcare workers was compared to nonuse of PPV during an influenza pandemic using a Markov decision model, shown schematically in eAppendix A. The model was programmed using TreeAge Pro Suite (TreeAge Software, Williamstown, MA). In the model, identical hypothetical cohorts of previously unvaccinated healthcare workers can remain well or develop invasive pneumococcal disease (IPD). Those developing IPD can recover completely, become disabled, or die due to IPD. Risks of death from other causes for individuals in any health state can be determined from U.S. life table data.5 Patients with disabilities due to IPD will die at higher rates. It should be noted that we model increases in IPD rates that might occur as a result of influenza, but do not model influenza itself.

eAppendix A
Markov model. IPD indicates invasive pneumococcal disease

Three model assumptions were made that potentially bias it against PPV use in healthcare workers. The first is that pneumococcal disease transmission from healthcare worker to patient does not occur. This assumption is based on pneumococcal disease resulting as an influenza complication in an individual already colonized with pneumococci and the unlikely possibility of simultaneous transmission of influenza and pneumococcus.6 The second assumption is that heightened IPD risk due to pandemic influenza occurs for only one year, because the duration of any influenza pandemic is unknown. The third assumption is that PPV does not prevent noninvasive pneumonia because PPV protection against noninvasive pneumonia is unclear and controversial6

Analyses were performed from both societal and hospital perspectives. In the societal perspective analysis, the time horizon was 15 years with costs and benefits discounted at 3% per year, following the recommendations of the US Panel on Cost-Effectiveness in Health and Medicine.7 Effectiveness was valued in quality adjusted life years (QALY) to account for changes in life span and quality of life due to PPV. QALYs are the product of the time spent in a health state and the quality of life utility associated with that state summed over time; utilities are a measure of preference for a health state, ranging from 0 (death) to 1 (perfect health). In all analyses, costs were estimated in 2006 U.S. dollars. In the hospital perspective analysis, the effectiveness term was employee absence day avoided over a five-year time horizon and three additional assumptions were made: 1) all direct medical costs are covered by insurance; 2) all healthcare workers with IPD miss work for 10 days; 3) two months are required to replace healthcare workers who are disabled or die due to IPD.

Age-specific IPD incidence data shown in eAppendix B were incorporated into the model.8 In the base case analysis, we assumed that IPD cases and deaths occurred at twice the usual rate during the year of pandemic influenza in healthcare workers with an average age of 45 years. This age was derived using U.S. Bureau of Health Professions data for registered nurses and licensed practical nurses, who comprise the bulk of healthcare workers.9;10 We averaged the published age distributions of these workers to calculate the usual IPD rate for this cohort, 13.7 cases per 100,000, using CDC Active Bacterial Core Surveillance (ABCs) data (eAppendix B). Using similar methods, we aged the cohort 15 years and calculated an IPD risk of 24.4/100,000, then used linear interpolation to estimate IPD risk between years 1 and 15. We used the general population risk because there are no specific data on IPD risk in healthcare workers. Thus, IPD rates were varied from 50%–150% of their base case levels in a separate sensitivity analysis.

eAppendix B
Invasive Pneumococcal Disease (IPD) Rates

The concept of increased pneumococcal disease rates is based on autopsy studies demonstrating pneumococcal bacteremia and empyema in the 1918–19 pandemic and bacterial lung infection in the current pandemic2;11 Because the specific impact of influenza on IPD is unknown, we arbitrarily set IPD rates at twice the usual rate and varied the relative risk of IPD from 1 (no change in IPD rates) to 6 (six times the usual IPD rates) in sensitivity analyses. The probability that IPD was caused by a pneumococcal serotype contained in the PPV was derived from CDC ABCs data,12 shown in eAppendix C. Costs related to vaccination and vaccination adverse events were also obtained from the literature;1316 and age-specific IPD costs were obtained from the 2006 National Inpatient Sample (Table 1). A panel of pneumococcal disease experts estimated duration-specific protection from PPV for susceptible pneumococcal serotypes, basing their estimates on data from Shapiro et al. (Table 2).17 IPD-related meningitis incidence was used as a proxy for the probability of IPD-related disability.12

Table 1
Base Case Values and Ranges Examined in Sensitivity Analyses for Both Societal and Hospital Perspectives.
Table 2
Estimates* of Pneumococcal Polysaccharide Vaccine Efficacy for Susceptible Serotypes Over Time (%)
eAppendix C
Probability that Invasive Pneumococcal Disease is Due to a Pneumococcal Serotype Contained in the Pneumococcal Polysaccharide Vaccine (PPV)

For all parameters, the base case value and range of values examined in one-way sensitivity analyses are shown in Table 1. Two-way sensitivity analyses were conducted to examine combined impact of age and IPD rate variation on model results. To test the robustness of model results, parameter values were varied simultaneously in a probabilistic sensitivity analysis, where parameters were assigned distributions and values were chosen from each distribution 5000 times. Uniform distributions were used for utility values, triangular distributions were used for hospital perspective costs, and clinical trial data and CDC data were assigned distributions based on data characteristics and skewness. Triangular distributions were also used to model estimates of PPV efficacy, using the time-specific base case estimates shown in Table 2 as the most common value and the low and high range efficacy estimates as the lower and upper bounds of these distributions.


Societal perspective

Base case results are summarized in Table 3. For healthcare workers with an average age of 45 years and twice the usual IPD incidence and mortality rates during the pandemic influenza year, the per patient total cost (including vaccination and IPD costs) for the PPV strategy was $3.14 greater than no vaccination while gaining 0.00107 QALY (about 0.4 days). Thus, the incremental cost effectiveness ratio of vaccination compared to no vaccination was $2,935 per QALY gained (Table 3, top).

Table 3
Cost Effectiveness of PPV Vaccination of Healthcare Workers - Base Case

We estimated that 284 cases and 32 deaths per 100,000 healthcare workers would occur without PPV and 171 cases and 19 deaths per 100,000 healthcare workers would occur with PPV. Therefore, a PPV strategy prevented about 40% of IPD cases and deaths in healthcare workers.

In one-way sensitivity analyses, where parameter values were individually varied, results were most sensitive to healthcare worker age, with incremental cost-effectiveness ratios >$100,000 per QALY for healthcare workers age 29 or less (Figure 1). Conversely, pandemic-based PPV was cost saving in healthcare workers aged ≥49 years under base case assumptions. Results were less sensitive to variation of IPD relative risk (eAppendix D). In a 2-way sensitivity analysis, we varied both the healthcare worker age and the relative risk of IPD during an influenza pandemic year (Figure 2). Using a $100,000 per QALY gained acceptability threshold, we found that PPV would be favored for workers aged 29 or more when the relative IPD risk is 1 or more, or for all workers, regardless of age, when the relative risk is ≥3.4.

Figure 1
One-way sensitivity analysis, showing the effects of age variation on cost-effectiveness results
Figure 2
Two-way sensitivity analysis, using a $100,000 per quality adjusted life year gained acceptability threshold, showing the effects of simultaneous variation of age and the invasive pneumococcal disease (IPD) multiplier, the relative risk of IPD during ...
eAppendix D
One-way sensitivity analysis, showing the effects of varying IPD relative risk on cost-effectiveness results. IPD indicates invasive pneumococcal disease

When the base case parameters were used with a heightened IPD risk related to pandemic influenza lasting two years instead of one, PPV cost $398 per QALY gained. If no increase in IPD rates occur with an influenza pandemic or if a pandemic occurs after PPV loses effectiveness (i.e., after 15 years), PPV vaccination costs $6199/QALY. While there is no standard criterion for cost-effectiveness, interventions that cost <$100,000 per QALY gained are generally acceptable and are comparable to other commonly used interventions.18 Interventions that cost <$20,000 per QALY are typically felt to be a “good buy” and to represent strong evidence for adoption.19 Studies suggest higher acceptability thresholds for interventions related to occupational health, making our results even more favorable from that standpoint.20 The ABCs IPD risk data are risks for the general population; it is unclear if this risk applies to healthcare workers. Using 50%–150% of the general public’s risk as a way to assess varying risk for healthcare workers, PPV in healthcare workers cost $31,600/QALY if their IPD risk is 50% of the general population risk and PPV is cost saving if healthcare worker risk is 150% of the population risk.

In the probabilistic sensitivity analysis, where all parameter values listed in Table 1 were simultaneously varied, vaccinating all healthcare workers was favored >91% of the time using an acceptability threshold of $20,000/QALY and in >99% of the time if the threshold was $100,000.

Hospital perspective

From a hospital perspective, the PPV strategy had a total cost per vaccinated worker that was $20.70 greater than no vaccination while avoiding 0.0124 absence days per worker, for a cost-effectiveness ratio of $1,676 per employee absence day avoided (Table 3, bottom). This figure could be an overestimate, given the assumption of no vaccine efficacy for noninvasive pneumonia, and that does not account for lost revenue due to reduced hospital manpower and capacity, as well as the intangible costs of negative public perception if hospital services were to be curtailed. PPV in healthcare workers cost $4,103 per absence day avoided if their IPD risk is 50% of the general population risk and cost $867 per absence day if healthcare worker risk is 150% of the population risk. In a probabilistic sensitivity analysis, the 95% probability range for vaccination compared to no vaccination was $20–$10,800 per employee absence day avoided.


In this analysis we found that PPV is an economically reasonable strategy to be considered for healthcare workers during an influenza pandemic from a societal perspective, with robust results in one-way sensitivity analyses and a high likelihood of cost-effectiveness in a probabilistic sensitivity analysis. Our results are comparable to a recent analysis by the CDC, examining PPV use in critical infrastructure personnel (e.g., healthcare workers, utility workers).21;22 The investigators estimated 35,000 invasive and noninvasive pneumococcal disease cases in a population of 20 million, or an attack rate of 175 per 100,000. Using their age-specific hospitalization rates and assuming that 25% of workers are aged 50 or older, the pneumococcal disease hospitalization rate was about 25.8 per 100,000. If half of those hospitalized had IPD, then the IPD rate was 12.9 per 100,000, slightly less than our calculated IPD rate from healthcare workers, 13.7 per 100,000. Using 0.942 (i.e., 12.9/13.7), the IPD relative risk derived from their study, in our analysis produces an incremental cost effectiveness ratio of $6,419 per QALY gained. This value falls within the range of their discounted life years saved result of $37,320 (95%CI $5,865 – 80,359). It should be noted that, unlike our analysis, the CDC study did not use utilities, or account for disability or PPV effects beyond the pandemic year.21

On the other hand, from the hospital perspective, PPV of healthcare workers costs almost $1,700 per employee absence day avoided, which most hospitals would consider a relatively steep premium to pay for a small expected return. Our analysis highlights the dilemma many hospital systems face: trying to do the right thing from a societal standpoint while at the same time attempting to remain fiscally sound. Managed care faces this tension of the hospital versus societal perspectives as it seeks to maximize health in a cost-effective way. Even with a heightened risk of pneumococcal disease during an influenza pandemic, the risk of IPD would probably remain less than 1% for healthcare workers and this fact might lead hospital systems to defer PPV for their workers unless some subsidy to defray vaccination costs were available. We did not include the possibility that healthcare workers would infect other workers or patients or that hospitals would be unable to meet staffing needs due to absenteeism; thus, our estimates are conservative. Maintenance of appropriate staffing levels is a priority in managed care. Although expensive from the hospital perspective, vaccination may lead workers to feel better protected and more willing to work in the face of a pandemic. Given that PPV is less expensive than many other occupationally indicated vaccines, it may be reasonable to consider PPV as a means to allay worker concerns about complications of pandemic influenza.

From a societal standpoint, PPV administration to healthy healthcare workers at the pandemic’s onset has pros and cons. Vaccination is likely to reduce IPD2326 and, in healthy workers, may reduce pneumococcal pneumonia.27 However, concerns exist about vaccine efficacy against noninvasive pneumonia and about hypo-responsiveness to subsequent vaccination, also known as tolerance.4 If hypo-responsiveness occurs following PPV, it might simply shift the burden of pneumococcal disease from the time of the pandemic to a time later in the life of the healthcare worker, without changing the cumulative incidence. Repeat doses of PPV later in life are generally safe;28 thus the concern is not safety at the time of vaccination or of repeat vaccination years later, but of potential hypo-responsiveness. Another potential limitation of our analysis is that recent PPV recommendations29 have added smoking and asthma to the list of comorbid conditions for which vaccination before the age of 65 is recommended and could further lessen the impact of healthcare worker vaccination, given the considerable proportion of workers falling into these categories.

Due to the absence of clinical trial data both now and for the foreseeable future, we used a Markov decision model to synthesize available data. We also used a series of conservative estimates and assumptions, including PPV effectiveness against IPD, not pneumococcal pneumonia, even though some data suggest that PPV may have some effectiveness against pneumonia in healthy adults.27 Despite these assumptions, vaccination of healthcare workers with PPV was cost-effective from the societal perspective. Limitations include the unknown increased IPD risk in a pandemic and the inability to address PPV vaccination impact on hypo-responsiveness to future pneumococcal vaccines, either polysaccharide or conjugate, the latter of which may be licensed for adults in the future. We used longer time horizons than prior analyses; this has the advantage not being limited to pandemic effects but the disadvantage of not accounting for future new vaccines and changes in epidemiology. Because we used a 15 year time frame and a single PPV in those who were previously unvaccinated and because current CDC recommendations only call for PPV revaccination at age 65 for those vaccinated prior to 65, we did not include revaccination as part of our analyses of current workers. If a longer time horizon were examined or if hypo-responsiveness occurred, greater costs per QALY gained would result.


Vaccinating all healthcare workers to protect against pneumococcal disease during a pandemic influenza outbreak is likely to be economically reasonable from a societal perspective in an analysis biased against vaccination. However, when analyzed from a hospital perspective, PPV is expensive and the relatively small risk of illness might prevent hospital implementation unless vaccination is externally subsidized.

Take away points

  • One of the causes of extended morbidity and mortality in previous influenza pandemics has been invasive pneumococcal disease (IPD).
  • In an influenza pandemic, healthcare resources will be strained as increased numbers of patients seek care and healthcare workers themselves fall ill and cannot work.
  • One potential means of preventing healthcare worker illness and absence from work is to vaccinate them with pneumococcal polysaccharide vaccine.
  • From a societal perspective, this strategy is cost-effective, with an additional cost of $3.14/healthcare worker and $2,935 per quality adjusted life year gained.
  • From the hospital perspective vaccinating healthcare workers was expensive, costing $1,676 per employee absence day avoided.


This is the pre-publication version of a manuscript that has been accepted for publication in The American Journal of Managed Care (AJMC). This version does not include post-acceptance editing and formatting. The editors and publisher of AJMC are not responsible for the content or presentation of the prepublication version of the manuscript or any version that a third party derives from it. Readers who wish to access the definitive published version of this manuscript and any ancillary material related to it (eg, correspondence, corrections, editorials, etc) should go to www.ajmc.com or to the print issue in which the article appears. Those who cite this manuscript should cite the published version, as it is the official version of record.

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