Published online May 1, 2006
PEDIATRICS
Vol. 117
No. 5
May 2006, pp.
1650-1655
(doi:10.1542/peds.2005-0822)
Economic Analysis of Prevaccination Serotesting Compared With Presumptive Immunization for Polio, Diphtheria, and Tetanus in Internationally Adopted and Immigrant Infants
Adam L. Cohen, MD, MPHa and
David Veenstra, PharmD, PhDb
a Child Health Institute, Department of Pediatrics
b Department of Pharmacy, University of Washington, Seattle, Washington
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ABSTRACT
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BACKGROUND. No consensus exists about whether to conduct prevaccination serotesting or to presumptively vaccinate internationally adopted and immigrant infants with inactivated polio (IPV) and diphtheria-tetanus-acellular pertussis (DTaP) immunizations.
OBJECTIVE. To study the clinical and economic outcomes from a societal perspective of prevaccination serotesting in a hypothetical 12-month-old internationally adopted or immigrant infant.
DESIGN AND METHODS. A decision analysis model was developed comparing presumptive vaccination with IPV versus serotesting for poliovirus type 1, 2, and 3 antibodies followed by vaccination in unprotected patients. A similar decision analysis model was developed comparing presumptive vaccination with DTaP versus serotesting for diphtheria and tetanus toxoid antibodies. The main outcome measures were cost per patient protected from polio, diphtheria, and tetanus.
RESULTS. Compared with presumptive immunization, prevaccination serotesting for polio increases the cost per patient from $57 to $62 and decreases the percentage of patients protected against polio from 95.3% to 94.0%. Serotesting for diphtheria and tetanus increases the cost per patient from $62 to $119 and increases the percentage of patients protected against both diphtheria and tetanus from 91.5% to 92.3%. Presumptive immunization with DTaP costs less and is more clinically effective than serotesting if >80% of patients do not complete the full vaccine series or if antibody seroprevalence to both diphtheria and tetanus is <51%.
CONCLUSIONS. Presumptive immunization for polio improves outcomes and saves costs compared with prevaccination serotesting in internationally adopted and immigrant infants. The results for DTaP are less definitive, although immunization is the preferred strategy in populations with poor vaccine compliance or low seroprevalence of antibodies to diphtheria and tetanus.
Key Words: international adoption • immunizations • cost-effectiveness • cost analysis • immigration issues
Abbreviations: Hib—Haemophilus influenzae type b • IPV—inactivated polio • DTaP—diphtheria-tetanus-acellular pertussis
In 2003, >36000 immigrant children and 18000 international adoptees under the age of 5 years immigrated to the United States.1 Many internationally adopted and immigrant infants receive immunizations before coming to the United States. For international adoptees, providers cannot always rely on previous vaccination records because of concerns about vaccine administration, storage, and potency in other parts of the world.2, 3 In contrast, providers are encouraged to accept written immunization records for immigrant and refugee infants.3 Records may be missing or incomplete, but international adoptees with documentation of immunizations have high levels (>85%) of protection for diphtheria, tetanus, and polio.4 Providers, thus, choose between either presumptively vaccinating these children or first serotesting them for adequate immunity to identify patients requiring immunization. Compared with presumptive immunization, serotesting could save money and unnecessary vaccine administration by identifying children who are protected in this population.
All 12-month-old immigrant infants to the United States need proven immunization against hepatitis B, diphtheria, tetanus, pertussis, polio, measles, mumps, and rubella,5 and the Advisory Committee on Immunization Practices also recommends varicella, Haemophilus influenzae type b (Hib), and pneumococcus vaccination for all 12-month-old infants.3 Of all the recommended vaccines for 12-month-old internationally adopted and immigrant infants, only 2 vaccines have reliable and available serologic tests: inactivated polio (IPV) and diphtheria-tetanus-acellular pertussis (DTaP). Although some debate exists over which tests to use and how to interpret results for diphtheria and tetanus, most providers have access to serologic tests for polio, diphtheria, and tetanus. Most experts agree that all new immigrants should be serotested for hepatitis B regardless of immunization records to evaluate carrier status.3 No widely available serologic tests currently exist for pertussis, Hib, or pneumococcus. Serologic tests for measles, mumps, rubella, and varicella may be widely available, but these vaccines must be given after 12 months of age, so a 12-month-old new immigrant who has already received these vaccines will need them repeated to be considered up to date.3
Few cost-effectiveness analyses have evaluated prevaccination serotesting compared with presumptive immunization. Prevaccination serotesting for varicella in refugees is cost-effective in children 
5 years of age.6 Presumptive immunization for hepatitis B was found to be more cost-effective than prevaccination serotesting in preadolescents unless the seroprevalence was >40%.7 Similarly, prevaccination serotesting for hepatitis A was not found to be cost-effective unless children were >15 years of age, and the seroprevalence of natural immunity was >22%.8 No consensus exists about whether to conduct prevaccination serotesting or to presumptively vaccinate for polio, diphtheria, and tetanus.9, 10 The main objective of this analysis was to study the cost-effectiveness from a societal perspective of prevaccination serotesting versus presumptive immunization for polio, diphtheria, and tetanus in internationally adopted or immigrant infants.
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METHODS
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Study Design
We chose to evaluate costs and outcomes in a hypothetical 12-month-old internationally adopted or immigrant infant for 3 reasons. First, infants both in the United States and abroad receive many essential immunizations in their first year.3 Second, maternal antibodies have diminished enough by the first birthday to allow accurate serotesting for these diseases.3 Third, the most common age of arrival in the United States for international adoptees at the University of Washington Medical Center is 12 months of age (Jeffrey Wright, MD, written communication, 2004). Parents of international adoptees can legally choose to not have their child immunized in the birth country11 and then may choose to decline immunizations once they are in the United States; however; for the purpose of this study, we assumed that the children's parents would choose to fully immunize.
Two decision analysis models were developed for this study. The IPV decision analysis model compared the following: (1) serotesting for poliovirus types 1, 2, and 3 antibodies; and (2) vaccination with IPV (Fig 1). Serotesting could reveal either full or incomplete antibody protection. If the subject had full antibody protection, then the subject was considered fully immunized. We assumed that if a child was found to have incomplete antibody protection on serotesting, then that child would need to return to clinic 3 times to complete the full catch-up series. If a provider chose to presumptively immunize, then the infant would receive the first vaccine at the first visit and then would need to return for 2 more follow-up visits to complete the series. Whether an infant completed 0, 1, 2, or all 3 immunizations in the series depended on the estimated vaccination compliance rate.
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FIGURE 1 IPV decision tree comparing the strategy of prevaccination testing versus presumptive immunization with no testing.
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The DTaP decision analysis model compared the following: (1) serotesting for diphtheria antibody and tetanus toxoid, and (2) vaccination with DTaP. The DTaP model was identical to the IPV model except that the prevaccination choice had 4 branches: (1) complete immunization against diphtheria and tetanus, (2) immunization against diphtheria but not tetanus, (3) immunization against tetanus but not diphtheria, and (4) immunization against neither diphtheria nor tetanus. Because there is no widely available test for antibodies to pertussis, we did not include this in our decision tree.
The main outcome measures were the separate costs per patient protected from polio, diphtheria, and tetanus. We considered a child to be fully protected if serotesting showed complete immunity or if the full vaccination series was completed. We did not assume partial immunity if some but not all of the DTaP vaccine series was given, because vaccine-induced immunity to tetanus and diphtheria is not long lasting in infants. Because completing 2 of the 3 immunizations for polio may confer long-lasting protection in up to 95% of infants,3 we conducted the polio analysis with and without the assumption of long-lasting protection after partial completion of the series to evaluate whether that changed our conclusions.
We conducted one-way sensitivity analyses for every estimated probability and cost in the study. In addition, we conducted two-way sensitivity analyses of seroprevalence and vaccination compliance. No human subjects were used in the study.
Probabilities
Seroprevalence of antibody protection to polio (62%), diphtheria (70%), and tetanus (65%) were derived from peer-reviewed studies of antibody prevalence in internationally adopted children (Table 1). 2, 12 We did not find any published studies of antibody prevalence in immigrant children, but we assumed the seroprevalence to be similar to that of internationally adopted children and varied this estimate over a wide range in the sensitivity analyses.
Vaccine antibody response (99% for polio and tetanus, 95% for diphtheria) were obtained from nationally published data of the Centers for Disease Control and Prevention (Atlanta, GA).13 Because the vaccine antibody response of the diphtheria vaccine is less than the vaccine antibody response of the polio vaccine, we used the lower vaccine antibody response of diphtheria (95%) in our calculations for the DTaP decision analysis.
Vaccination compliance rates (85% completion rate) were obtained from estimates by experts in international adoption and pediatric immigrant health at the University of Washington Medical Center (Seattle, WA). For ease of model design, we assumed that an equal percentage of children would not return with each additional catch-up immunization. In other words, we assumed that 85% of children would complete the full catch-up series, so we estimated that 5% would not return for each of the 3 catch-up visits. Because internationally adopted infants may have a higher compliance rate than immigrant children, we varied the compliance rate widely from 55% to 100% for a sensitivity analysis.
Costs
Charges for serotesting and vaccine administration were obtained from the University of Washington Medical Center (Table 2). All of the University of Washington charges from 2004 were converted to costs using the hospital-specific Medicare charge/cost ratio (0.632). Nearly all new immigrants receive an initial blood draw for screening tests such as human immunodeficiency virus, syphilis, anemia, or hepatitis B,3 so we did not include the cost of an initial blood draw in the cost of serotesting. Follow-up visits for vaccination were assumed to be either nurse visits with no physician charges or scheduled physician visits for pneumococcus and Hib vaccine administration. Newly internationally adopted and immigrant infants return to clinic for 2 visits to catch up on pneumococcus and Hib vaccinations. Because of the 2 visits for catch-up vaccination of pneumococcus and Hib, the additional cost of parent's wages lost was not included until the third visit.
We assumed that most children would be brought to clinic by their mother and that a working mother would lose 
2 hours of wages for each visit.7 Using data from the US Bureau of Labor Statistics, wages lost per immunization visit were calculated based on median weekly earnings of working mothers ($571)14 and percentage of mothers of infants who are working (53.7%).15
We used the Centers for Disease Control and Prevention contract price of vaccine for vaccine costs (Table 2).16 Although a combination IPV-DTaP-hepatitis B vaccine is available, we considered only the separate DTaP and IPV vaccines in this analysis.16
Exceedingly rare serious adverse reactions have been reported for IPV.13 For DTaP, severe systemic reactions do occur, but we assumed that adverse events were rare enough not to factor into the analysis. An exaggerated local reaction can occur in patients who have received previous doses of diphtheria or tetanus toxoid,13 which may alert a provider that the patients had been immunized previously. We did not include this rare outcome in the analysis, because it is not a reliable indicator of previous immunization.
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RESULTS
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Compared with presumptive immunization, prevaccination serotesting for polio increases the cost per patient from $57 to $61 and decreases the percentage of patients protected against polio from 95.3% to 94.0% (Table 3). Presumptive vaccination is more effective and less costly when the seroprevalence is <69%. The cost per patient protected against polio increases when the seroprevalence rises >69%, and at seroprevalence >86%, presumptive serotesting both costs less and is more effective. Presumptive immunization was the preferred method unless the compliance was extremely high (>96% follow-up). A two-way sensitivity analysis of seroprevalence and vaccine compliance found little change based on compliance rates (Fig 2). The results were not sensitive to increasing the protection conferred by completing 2 of the 3 immunizations to 95%, increasing the vaccine antibody response to 100%, or varying the amount of lost wages per visit.
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FIGURE 2 Two-way sensitivity analysis of IPV antibody seroprevalence and vaccination compli-ance. IPV 2-way sensitivity analysis.
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Prevaccination serotesting becomes less costly and more effective if the cost of serotesting decreases or the cost of immunizing increases. We estimated the cost of serotesting to be $36.48. It becomes less costly to serotest than presumptively vaccinate when serotesting costs less than $31.50 (Table 4). At a cost for serotesting of $27 (base cost $36.48 – 25%), the cost per protected patient was $342. Similarly, when the cost of immunization was greater than $22.70, serotesting was less costly. At a cost of $25 (base cost $20 + 25%), the cost per protected patient was $318.
Serotesting for diphtheria and tetanus both increases the cost per patient from $61.60 to $118.80 and increases the percentage of patients protected against both diphtheria and tetanus from 91.5% to 92.3% (Table 3). The cost per patient protected against both diphtheria and tetanus is $7148. Presumptive immunization with DTaP costs less and is more clinically effective than serotesting when >80% of patients do not complete the full catch-up vaccine series in follow-up and when the seroprevalence of antibodies to both diphtheria and tetanus is <51%. At very high rates of vaccine compliance (>96% completion), the cost per patient protected was $2176. Presumptive immunization was the preferred strategy if we assumed 100% vaccine effectiveness. A two-way sensitivity analysis found presumptive immunization to be the preferred method over a wide range of likely probabilities (Fig 3). When we varied the cost of immunization from $16 to $27 (base cost of $21.60 ± 25%), the cost per patient protected ranged from $5955 to $8389. When we varied the cost of serotesting from $67 to $113 (base cost of $90.22 ± 25%), the cost per patient protected ranged from $4245 to $9995 (Table 4).
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FIGURE 3 Two-way sensitivity analysis of DTaP antibody seroprevalence and vaccination compliance. DTaP, 2-way sensitivity analysis.
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DISCUSSION
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Presumptive immunization for polio improves outcomes and saves costs compared with prevaccination serotesting in internationally adopted and immigrant infants. The results for DTaP are less definitive, although immunization was the preferred strategy in populations with poor vaccine compliance or low seroprevalence of antibodies to diphtheria and tetanus. These results are applicable to the large and growing number of internationally adopted and immigrant infants that come to the United States each year.
There are no standard criteria for cost-effectiveness in vaccination strategies. Public health campaigns are effective in increasing vaccinations and may cost between $250 and $450 per completed series.17 Prevaccination serotesting for diphtheria or tetanus was not cost-saving in our analysis, and the cost per patient protected against both diphtheria and tetanus is $7148, much higher than the cost in public health campaigns. The results for the DTaP analysis were not sensitive to a range of cost and probability estimates. The IPV analysis was most sensitive to changes in the cost of immunization and serotesting. The cost per patient protected with prevaccination serotesting was similar to the cost of public health campaigns when serotesting was less expensive or immunization was more expensive.
Prevaccination serotesting increases the percentage of patients protected against both diphtheria and tetanus but decreases the percentage of patients protected against polio. In the DTaP analysis, the increase in protection is explained by increased identification of unprotected children. The differences in efficiency between IPV and DTaP were not sensitive to a wide range of baseline seroprevalances.
This analysis has several potential limitations. First, the costs in our study are derived from the University of Washington Medical Center and may not reflect costs at other institutions; however, we standardized costs with the institution-specific cost/charge ratio of Medicare. Second, no studies have examined compliance rates for catch-up immunization in internationally adopted and immigrant infants, so we relied on experts in the field to estimate these rates. Third, we did not have data on seroprevalence of polio, diphtheria, and tetanus for refugee or immigrant infant populations and extrapolated seroprevalence data from international adoptees. Similarly, we had a limited number of studies of seroprevalence data for international adoptees, so we used a wide sensitivity analysis to account for the uncertainty in our data. The seroprevalence may also vary with documentation of immunization status. Fourth, the literature does not accurately report seroprevalence for those with immunity to diphtheria and not tetanus and vice versa, so we estimated these values based on existing data. Lastly, cost-analysis studies of vaccination often evaluate the cost of vaccine compared with the cost of disease prevented.18, 19 We did not calculate the cost per life-year saved, because there are no accurate estimates of the acute disease or lifetime costs for tetanus, polio, or diphtheria.
There are some implications of our assumptions. In the rare case where an exaggerated local reaction occurs in patients who have received previous doses of diphtheria or tetanus toxoid, stopping the vaccination series early would save costs for presumptive immunization and bias against serotesting. However, we felt that this was a rare enough event that it would not affect the results. Testing solely for polio is not the currently recommended method of testing for immunity to DTaP, so we did not explore the option of testing for only polio as a marker for completion of the DTaP vaccine series. Using the increased vaccine antibody response of polio compared with diphtheria (99% vs 95%) would bias the results toward serotesting. Similarly, if we had given partial protection to those patients who did not complete the vaccine series, then presumptive vaccination would have been more effective than serotesting.
We recognize that parents and providers may choose to serotest simply to avoid unnecessary needle sticks, rather than to increase effectiveness or decrease societal cost. This analysis also would not apply to infants who were known to have had no previous immunizations. In addition, combination vaccines exist for IPV, DTaP, and hepatitis B, and this vaccine may be the most cost-effective choice in patients that need hepatitis B vaccination. Based on our analyses, we conclude that, in most cases, presumptive immunization is the preferred option for DTaP and IPV in internationally adopted and immigrant infants.
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FOOTNOTES
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Accepted Oct 31, 2005.
Address correspondence to Adam L. Cohen, MD, MPH, Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, MS A-35, Atlanta, GA 30333. E-mail: alcohen{at}u.washington.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
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ABSTRACT
METHODS
