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Adult Vaccination Strategies for the Control of Pertussis in the United States: An Economic Evaluation Including the Dynamic Population Effects

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Authors:
Laurent Coudeville at Sanofi
Laurent Coudeville
Annelies Van Rie at University of Antwerp
Annelies Van Rie
Denis Getsios at United BioSource Corporation
Denis Getsios
J Jaime Caro
J Jaime Caro
J Jaime Caro
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Prior economic evaluations of adult and adolescent vaccination strategies against pertussis have reached disparate conclusions. Using static approaches only, previous studies failed to analytically include the indirect benefits derived from herd immunity as well as the impact of vaccination on the evolution of disease incidence over time. We assessed the impact of different pertussis vaccination strategies using a dynamic compartmental model able to consider pertussis transmission. We then combined the results with economic data to estimate the relative cost-effectiveness of pertussis immunization strategies for adolescents and adults in the US. The analysis compares combinations of programs targeting adolescents, parents of newborns (i.e. cocoon strategy), or adults of various ages. In the absence of adolescent or adult vaccination, pertussis incidence among adults is predicted to more than double in 20 years. Implementing an adult program in addition to childhood and adolescent vaccination either based on 1) a cocoon strategy and a single booster dose or 2) a decennial routine vaccination would maintain a low level of pertussis incidence in the long run for all age groups (respectively 30 and 20 cases per 100,000 person years). These strategies would also result in significant reductions of pertussis costs (between -77% and -80% including additional vaccination costs). The cocoon strategy complemented by a single booster dose is the most cost-effective one, whereas the decennial adult vaccination is slightly more effective in the long run. By providing a high level of disease control, the implementation of an adult vaccination program against pertussis appears to be highly cost-effective and often cost-saving.
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... Household adults are the main source of infection for infants [13][14][15][16]. Adults' immunization with a vaccine that provides herd protection could be an additional strategy to reduce pertussis among infants [17][18][19][20][21][22]. A significant increase in pertussis incidence rates was observed in Brazil from 2011 to 2014, in spite of high coverage of childhood immunization with whole-cell pertussis containing vaccines (from 93.8 to 99.6% in these years). ...
... Most previous studies that evaluated vaccination of adolescents or adults used dynamic model and included herd protection [17,18,[20][21][22][44][45][46][47][48][49]. Considering that severe cases and deaths happen mostly among infants and adults are the main source of infection for infants [3,[13][14][15][16]50,51], vaccinating adults would have better performance if this strategy results in herd protection and prevent cases in infants under one year of age [52]. ...
... In our dynamic model, even asymptomatic or mild cases contribute to disease transmission. Other Tdap economic evaluations using dynamic models also considered the contribution of asymptomatic cases in disease transmission [20][21][22]45,55]. However, most of previous studies considered costs with health services or products for all infected adolescents and adults [17][18][19]46,47,56]. ...
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... Few studies considered asymptomatic cases and recognized their importance in the transmission of the disease. 24,26,28,34,35 Eleven studies that evaluated adolescents or adults vaccination considered herd protection. 14,17,19,20,22,24,26,28,29,35,38 Eight of them used dynamic models and three studies used static models and included herd protection as a correction factor. ...
... 24,26,28,34,35 Eleven studies that evaluated adolescents or adults vaccination considered herd protection. 14,17,19,20,22,24,26,28,29,35,38 Eight of them used dynamic models and three studies used static models and included herd protection as a correction factor. Herd protection refers to protection of susceptible individuals due to decreased transmission of the pathogen, i.e., reduction in the force of infection, when a high proportion of the population is immunized. ...
A systematic review of adult tetanus-diphtheria-acellular (Tdap) coverage among healthcare workers
Article
  • Feb 2019
During the last decades pertussis incidence raised globally. Several vaccination strategies targeting adults to reduce pertussis among young infants have been proposed, including vaccination of healthcare workers (HCWs). The aim of this study was to analyse, by performing a systematic review of literature, published papers that evaluated Tdap coverage among HCWs, variables associated with vaccine uptake and efforts implemented to raise vaccination rates. We searched the MedLine, Embase, SCOPUS, LILACS, Web of Science and Cochrane for full-text studies that evaluated Tdap coverage in HCW. Two independent reviewers screened the articles and extracted the data. Twenty-eight studies published from 2009 to 2018 were reviewed. Most studies were conducted in the USA. Initial Tdap coverage varied from 6.1% to 63.9%. USA and France are the only two countries with studies evaluating Tdap coverage within HCWs using national data. In the USA, Tdap coverage in HCWs raised from 6.1% to 45.1% from 2007 to 2015. In the analysis of French national data, a Tdap coverage of 63.9% was observed. Five studies used interventions to raise Tdap coverage in HCWs. Two intervention studies implemented mandatory vaccination and three used educational strategies. All of them achieved coverages over 86%. Only eleven studies analysed the association of Tdap vaccination with variables of interest. Previous immunization with other vaccines recommended for HCWs (like influenza, hepatitis B and MMR) was positively associated with Tdap uptake in four studies. In conclusion, overall Tdap coverage among HCWs is low, but seems to increase over the years after the vaccine introduction and with implementation of interventions to increase coverage.
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... Few studies considered asymptomatic cases and recognized their importance in the transmission of the disease. 24,26,28,34,35 Eleven studies that evaluated adolescents or adults vaccination considered herd protection. 14,17,19,20,22,24,26,28,29,35,38 Eight of them used dynamic models and three studies used static models and included herd protection as a correction factor. ...
... 24,26,28,34,35 Eleven studies that evaluated adolescents or adults vaccination considered herd protection. 14,17,19,20,22,24,26,28,29,35,38 Eight of them used dynamic models and three studies used static models and included herd protection as a correction factor. Herd protection refers to protection of susceptible individuals due to decreased transmission of the pathogen, i.e., reduction in the force of infection, when a high proportion of the population is immunized. ...
Economic evaluation of adolescents and adults’ pertussis vaccination: A systematic review of current strategies
Article
Full-text available
  • Aug 2018
The reemergence of pertussis in the last two decades led to the introduction of adolescents and adults immunization strategies of tetanus–diphtheria–acellular pertussis vaccines (Tdap) in several countries. The health authorities must consider economic aspects when deciding to recommend and fund new programs. Here we present a systematic review of worldwide full economic evaluations of pertussis vaccination targeting adolescents or adults published from 2000. Studies were identified by searching MEDLINE, Excerpta Medica, CRD, and Lilacs databases. Twenty-seven economic evaluations of different strategies with Tdap were identified. Booster vaccination for adolescents and adults were the most frequent, followed by cocooning and pregnant women vaccination. Strategies performance varied considerably among different studies. Assumptions regarding underreporting correction, herd protection and vaccine coverage were crucial to cost-effectiveness results. Understanding the model and the parameters used is essential to understand the results, and identify the major issues important to public health decisions.
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... Как показывает международный опыт, о котором говорилось выше, проведение возрастных ревакцинаций против коклюшной инфекции детей в возрасте 6-7 и 14 лет и взрослых приводит к снижению заболеваемости как в данных возрастных группах, так и в популяции в целом, препятствуя передаче коклюша наиболее уязвимому контингенту -детям до 1 года жизни, снижая при этом показатели младенческой заболеваемости и существенно уменьшая риск их заражения [42,43]. Ревакцинация АакдС может быть легко интегрирована в национальные программы иммунизации в дошкольном и подростковом возрасте (5-6 и 14 лет) путем замены АДС-М на АакдС, что обеспечит защиту от трех заболеваний вместо двух, не требуя серьезных изменений программ вакцинации [43][44][45]. ...
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... Maternal vaccination, however, can also prevent pertussis in mothers, and studies have demonstrated that pertussis vaccination can be cost-effective in adults. [25][26][27][28] It is important, therefore, to include all direct benefits of maternal vaccination. A similar approach was also undertaken in a UK cost-effectiveness analysis of maternal vaccination. ...
Is adding maternal vaccination to prevent whooping cough cost-effective in Australia?
Article
Full-text available
  • May 2018
Pertussis or whooping cough, a highly infectious respiratory infection, causes significant morbidity and mortality in infants. In adolescents and adults, pertussis presents with atypical symptoms often resulting in under-diagnosis and under-reporting, increasing the risk of transmission to more vulnerable groups. Maternal vaccination against pertussis protects mothers and newborns. This evaluation assessed the cost-effectiveness of adding maternal dTpa (reduced antigen diphtheria, Tetanus, acellular pertussis) vaccination to the 2016 nationally-funded pertussis program (DTPa [Diphtheria, Tetanus, acellular Pertussis] at 2, 4, 6, 18 months, 4 years and dTpa at 12–13 years) in Australia. A static cross-sectional population model was developed using a one-year period at steady-state. The model considered the total Australian population, stratified by age. Vaccine effectiveness against pertussis infection was assumed to be 92% in mothers and 91% in newborns, based on observational and case-control studies. The model included conservative assumptions around unreported cases. With 70% coverage, adding maternal vaccination to the existing pertussis program would prevent 8,847 pertussis cases, 422 outpatient cases, 146 hospitalizations and 0.54 deaths per year at the population level. With a 5% discount rate, 138.5 quality-adjusted-life-years (QALYs) would be gained at an extra cost of AUS$ 4.44 million and an incremental cost-effectiveness ratio of AUS$ 32,065 per QALY gained. Sensitivity and scenario analyses demonstrated that outcomes were most sensitive to assumptions around vaccine effectiveness, duration of protection in mothers, and disutility of unreported cases. In conclusion, dTpa vaccination in the third trimester of pregnancy is likely to be cost-effective from a healthcare payer perspective in Australia.
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Cost-Effectiveness Analysis of Revaccination Against Pertussis in Preschool Children
Article
  • Feb 2020
Foreign practices of cost-effectiveness analysis of revaccination against pertussis in preschool children, teenagers and adults are presented. The economic viability of the second revaccination against pertussis at preschool/early-school age is shown: it can reduce both direct and indirect expenses associated with pertussis not only in revaccinated groups but also in infants due to increasing of population immunity. International guidelines on the implementation of revaccination against pertussis through replacing of exhausted diphtheria tetanus modified vaccine on DTaP within the framework of the national vaccination schedule.
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Cost-effectiveness of adult vaccinations: A systematic review
Article
  • Dec 2018
Background: Coverage levels for many recommended adult vaccinations are low. The cost-effectiveness research literature on adult vaccinations has not been synthesized in recent years, which may contribute to low awareness of the value of adult vaccinations and to their under-utilization. We assessed research literature since 1980 to summarize economic evidence for adult vaccinations included on the adult immunization schedule. Methods: We searched PubMed, EMBASE, EconLit, and Cochrane Library from 1980 to 2016 and identified economic evaluation or cost-effectiveness analysis for vaccinations targeting persons aged ≥18 years in the U.S. or Canada. After excluding records based on title and abstract reviews, the remaining publications had a full-text review from two independent reviewers, who extracted economic values that compared vaccination to "no vaccination" scenarios. Results: The systematic searches yielded 1688 publications. After removing duplicates, off-topic publications, and publications without a "no vaccination" comparison, 78 publications were included in the final analysis (influenza = 25, pneumococcal = 18, human papillomavirus = 9, herpes zoster = 7, tetanus-diphtheria-pertussis = 9, hepatitis B = 9, and multiple vaccines = 1). Among outcomes assessing age-based vaccinations, the percent indicating cost-savings was 56% for influenza, 31% for pneumococcal, and 23% for tetanus-diphtheria-pertussis vaccinations. Among age-based vaccination outcomes reporting $/QALY, the percent of outcomes indicating a cost per QALY of ≤$100,000 was 100% for influenza, 100% for pneumococcal, 69% for human papillomavirus, 71% for herpes zoster, and 50% for tetanus-diphtheria-pertussis vaccinations. Conclusions: The majority of published studies report favorable cost-effectiveness profiles for adult vaccinations, which supports efforts to improve the implementation of adult vaccination recommendations.
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First Mexican Consensus of Vaccination in Adults
Article
Full-text available
  • Mar 2017
  • GAC MED MEX
For years our efforts have been focused on vaccination during childhood. Today we know that this is not enough to ensure health in the rest of the life. Childhood is as important as any other stage and, therefore, vaccination must be permanent and differentiated, according to our age, throughout life. Introducing a life course perspective in vaccination programs, with emphasis on adult vaccination, particularly in older adults, offers us the opportunity to review the performance of health programs, actions, and services in the field of immunization, as well as strengthening health promotion actions. In this context, the first Mexican Consensus on Adult Vaccination was carried out in a joint effort of the National Institute of Geriatrics, bringing together a group of specialists who worked on three central objectives: establishing vaccination guidelines throughout the life course, with emphasis on new vaccines; defining priority groups according to their risk factors; and contributing to the effort to promote healthy aging.
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Estimation épidémiologique de l’efficacité de la vaccination anticoquelucheuse au cours d’épidémies en collectivité
Article
  • Aug 1997
  • Arch Pediatr
Contexte et objectifs. — Grâce aux récents essais cliniques, l’efficacité des vaccins coquelucheux acelluiaires est connue, de l’ordre de 85 % pour les vaccins multicomposés. Les vaccins à germes entiers ont en revanche une efficacité variable, de 36 à 98 % selon les vaccins. L’efficacité du vaccin à germes entiers utilisé en France (EV) a pu être estimée en situation épidémique.
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Pertussis Hospitalizations and Mortality in the United States, 1985-1988
Article
  • Jan 1992
Objective. —To determine the magnitude of hospitalizations for pertussis and pertussis mortality and to estimate the total burden of clinically significant pertussis in the United States.
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Pertussis hospitalizations and mortality in the United States, 1985-1988. Evaluation of the completeness of national reporting
Article
  • Feb 1992
--To determine the magnitude of hospitalizations for pertussis and pertussis mortality and to estimate the total burden of clinically significant pertussis in the United States. --Capture-recapture methods for estimating population size from independent surveillance systems were used to analyze morbidity and mortality data from case report forms received at the Centers for Disease Control (CDC) from the states, and compared these data with pertussis hospitalizations compiled from a database of US hospitals participating in the Commission on Professional and Hospital Activities-Professional Activities Survey (CPHA-PAS) and death certificate reports compiled by the National Center for Health Statistics (NCHS). --All pertussis hospitalizations and pertussis-related deaths in the United States, 1985 through 1988. --We estimated that 13,557 pertussis hospitalizations (95% confidence interval [CI], 12,953 to 14,162) and 98 pertussis deaths had occurred during the 4-year study period (an average of more than 3300 hospitalizations and 25 deaths per year). The completeness of reporting hospitalizations to the CDC was 32% and to the CPHA-PAS, 23%, while the completeness of reporting pertussis deaths to the CDC was 33% and to NCHS, 23%. Patients who were hospitalized with pertussis and reported to CDC were at a higher risk for developing pneumonia (31.0% vs 20.0%, relative risk [RR], 1.6; 95% CI, 1.4 to 1.7), seizures (3.7% vs 2.1%; RR, 1.9; 95% CI, 1.4 to 2.5) and encephalitis (1.2% vs 0.2%; RR, 5.3; 95% CI, 2.4 to 11.6) compared with patients recorded in the CPHA-PAS system. --Our study suggests that there is substantial underreporting of pertussis, that severe complications of pertussis (including hospitalizations) are reported preferentially to the CDC, and that the national health impact of pertussis based on these indicators is considerably higher than previously published reports have suggested.
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Household Contact Study of Bordetella pertussis Infections
Article
  • Nov 1995
Household contacts of primary pertussis cases were evaluated. Infection was determined by culture, direct fluorescent antibody assay, and serological criteria. Agglutinin titers and values of ELISA IgG and IgA antibodies to lymphocytosis-promoting factor, filamentous hemagglutinin, and pertactin were determined. In 39 households 255 subjects were exposed; 114 remained well (group 1), 53 had mild illness (group 2), and 88 had pertussis (group 3). The infection rates were 46% (group 1), 43% (group 2), and 80% (group 3). In a subgroup of subjects seen within 14–28 days of exposure, it was found that none with clinical pertussis had a value of IgG antibody to pertactin in acute-phase sera of ⩾50 ELISA units (EU) per mL or an agglutinin titer of >256. Of the primary cases, 53% were ⩾13 years of age. These data point out the importance of Bordetella pertussis infections in adolescents and adults as a source of infection in young children. Our subgroup data suggest that high values of antibody to pertactin and high agglutinin titers may be predictive of protection against clinical pertussis.
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An age-structured model for pertussis transmission
Article
  • Nov 1997
  • MATH BIOSCI
The vaccination program for pertussis (whooping cough) in the United States consists of giving multiple doses of pertussis vaccine to young children. A demographic model with a steady-state age distribution is used as a basis for building an epidemiologic model for the transmission of pertussis. This age-structured model includes vaccination of infants and children for pertussis with waning of both infection-acquired and vaccine-induced immunity. Computer simulations of the mathematical model between 1940 and 2040 show the changes that took place during the implementation phase of the U.S. program and predict only minor future changes in the age distribution and incidence of pertussis if the vaccination program is maintained at the 1995 level. The sensitivities of these results to changes in demographic and epidemiologic parameters, vaccine efficacy, duration of protection, and levels of vaccination coverage are investigated.
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[Epidemiological estimation of the effectiveness of the pertussis vaccination during outbreaks in a community. Les pédiatres et bactériologistes du réseau RENACOQ]
Article
  • Sep 1997
  • Arch Pediatr
With the recent pertussis vaccine trials, the efficacy of acellular vaccines is now well known, estimated at 85% for multicomponent vaccines. On the other hand, the estimates of whole cell vaccines efficacy varies from 36% to 98% with the different vaccines used. We evaluated the field effectiveness of the French whole cell pertussis vaccine during outbreaks in schools and centers for disabled children. Four limited outbreaks between 1993 and 1995 were investigated using a retrospective cohort study design. Vaccine effectiveness (VE) was assessed for the following case definition: clinical pertussis, laboratory-confirmed pertussis, epidemiologically confirmed pertussis (documented contact with a laboratory confirmed case). Immunization history was obtained by reviewing the child health record book. Effectiveness of a whole vaccination (four injections) and of a partial vaccination (one to three injections) were estimated as 1-(attack rate among vaccinated/attack rate among non-vaccinated). A whole immunization conferred good protection against pertussis with an estimated VE higher than 92% in three surveys, lower in the fourth survey (84%) in which antibiotic prophylaxis was set up very rapidly. A partial immunization conferred a mild protection (median: 60%). These results are consistent with a previous report about the effectiveness of this whole cell vaccine using the screening method in a hospital network survey in France. In the same way, a large efficacy trial in Senegal comparing it with an acellular bivalent vaccine estimated its efficacy at 96%. This high efficacy together with a satisfactory vaccine coverage leads to the current epidemiological profile of pertussis in childhood in France: majority of cases occurring before 6 months of age, limited outbreaks in school children, many of whom being unvaccinated or partially vaccinated.
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Simulations of pertussis epidemiology in the United States: Effects of adult booster vaccinations
Article
  • May 1999
  • MATH BIOSCI
An expanded pertussis (whooping cough) vaccination program which includes adult boosters every 10 yr is studied using computer simulations of two models. These age-structured pertussis transmission models include waning of both infection-acquired and vaccine-induced immunity, and vaccination of children corresponding to the vaccination coverage since 1940. Adult vaccinations cause a larger boost in the immunity level in the second model than in the first model. In the simulations the addition of adult pertussis booster vaccinations every 10 yr is beneficial in reducing adult incidence, but causes only modest reductions in the incidence in infants and young children. These simulations suggest that a careful cost effectiveness analysis is needed before implementation of an adult pertussis vaccination program.
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