Attributes influencing parental decision-making to receive the Tdap vaccine to reduce the risk of pertussis transmission to their newborn - outcome of a cross-sectional conjoint experiment in Spain and Italy.

Pertussis vaccination of parents and household contacts ('cocooning') to protect newborn infants is an established strategy in many countries, although uptake may be low. Many aspects may influence such decision-making. We conducted a cross-sectional survey (NCT01890447) of households and other close contacts of newborns aged ≤6 months (or of expectant mothers in their last trimester) in Spain and Italy, using an adaptive discrete-choice experiment questionnaire. Aims were to assess the relative importance of attributes influencing vaccine adoption, and to estimate variation in vaccine adoption rates and the impact of cost on vaccination rates. Six hundred and fifteen participants (Spain, n = 313; Italy, n = 302) completed the survey. Of 144 available questionnaire scenarios, the most frequently selected (14% of respondents in both countries) were infant protection by household vaccination at vaccination center, recommendation by family physician and health authorities, with information available on leaflets and websites. The attribute with highest median relative importance was 'reduction in source of infection' in Spain (23.1%) and 'vaccination location' in Italy (18.8%). Differences between other attributes were low in both countries, with media attributes showing low importance. Over 80% of respondents indicated a definite or probable response to vaccine adoption (at no-cost) with estimated probability of adoption of 89-98%; applying vaccine costs (25€ per person) would reduce the probability of uptake by 7-20% in definite/probable respondents. Awareness of these determinants is helpful in informing Health Authorities and healthcare practitioners implementing a cocooning strategy for those populations where maternal immunization is not a preferred option.

Assessment of clinical symptoms in household contacts of confirmed pertussis cases.

OBJECTIVES: We assessed the value of the clinical symptoms included in the case definition of pertussis in household contacts of laboratory-confirmed cases. METHODS: A prospective epidemiological study was made in two Spanish regions. Household contacts were identified for each confirmed case reported during 2012 and 2013. Two clinical samples were taken to determine the presence or absence of Bordetella pertussis by culture or real-time PCR. Clinical variables, age and vaccination status were recorded. Positive and negative likelihood ratios (PLR, NLR) were estimated for each symptom. RESULTS: 2852 household contacts of 688 confirmed cases were reported. 178 household contacts with clinical symptoms were analyzed: 150 were laboratory confirmed and 28 were not. The clinical symptom with the highest PLR in comparison with the NLR was paroxysmal cough(PLR 4.76; 95% CI 1.91-11.87 and NLR 0.37; 95% CI 0.28-0.49). The contrast between the PLR and NLR was especially important for persons aged <18 years (PLR 7.08; 95% CI 1.10-45.74 and NLR 0.32; 95% CI 0.21-0.49). CONCLUSIONS: The clinical symptoms of pertussis are poor predictors of pertussis disease, independently of the vaccination status. Differences were observed between persons aged <18 years and adults. To adopt the appropriate treatment and control measures, rapid laboratory confirmation by PCR of all household contacts of confirmed cases who present any clinical symptoms compatible with pertussis should be recommended.

Intention to Accept Pertussis Vaccination for Cocooning: A Qualitative Study of the Determinants.

CONTEXT: Several countries have reported a resurgence of pertussis in the last decades. This puts infants (especially <6 months) at risk of severe complications, because they are too young to be fully protected by vaccination. The global pertussis initiative has proposed pertussis vaccination of young infants' close contacts, in order to reduce pertussis transmission and the burden of the disease on infants. Our aim is to explore the perceived determinants (barriers and facilitators) of intention to accept vaccination among the possible target groups of pertussis vaccination for cocooning. Consideration of these determinants is necessary to optimise the uptake of the vaccination. METHODS: We conducted 13 focus groups and six individual semi-structured interviews with members of possible target groups for pertussis cocooning (i.e. parents, maternity assistants, midwives, and paediatric nurses) in the Netherlands. Here, both maternal pertussis vaccination as well as pertussis cocooning has not been implemented. The topic list was based on a literature review and a barrier framework. All interviews were transcribed verbatim and two researchers performed thematic content analysis. FINDINGS: The participants' risk perception, outcome expectations, general vaccination beliefs, moral norms, opinion of others, perceived autonomy, anticipated regret, decisional uncertainty, and perceived organisational barriers were all factors that influenced the intention to accept pertussis vaccination for cocooning. DISCUSSION: This study has identified nine perceived determinants that influence the intention to accept pertussis cocooning vaccination. We add the following determinants to the literature: perceived cost-effectiveness (as a concept of outcome expectations), justice (as a concept of moral norms), anticipated regret, and decisional uncertainty. We recommend considering these determinants in vaccination programmes for pertussis cocooning vaccination. Experience, information and trust emerged as predominant themes within these determinants. These themes require particular attention in future research on vaccination acceptance, especially with regard to their role in use and implementation in policy and practice.

Suffer the Infants: A Severe Case of Pertussis in Oregon, 2012.

Pertussis remains a public health concern in Oregon, especially among young infants. The disease can be severe in this age group and is associated with a high inpatient cost. This report describes an Oregon infant who was hospitalized with pertussis for 90 days, required extracorporeal oxygenation for 43 days, suffered complications including stroke, and had hospital charges totaling $1.5 million. Pertussis morbidity among young infants argues for vaccination of women during each pregnancy and of infants beginning promptly at two months of age.

Estimation of the serial interval of pertussis in Dutch households.

Increasing incidence has led to the re-appearance of pertussis as a public health problem in developed countries. Pertussis infection is usually mild in vaccinated children and adults, but it can be fatal in infants who are too young for effective vaccination (≤3 months). Tailoring of control strategies to prevent infection of the infant hinges on the availability of estimates of key epidemiological quantities. Here we estimate the serial interval of pertussis, i.e., the time between symptoms onset in a case and its infector, using data from a household-based study carried out in the Netherlands in 2007-2009. We use statistical methodology to tie infected persons to probable infector persons, and obtain statistically supported stratifications of the data by person-type (infant, mother, father, sibling). The analyses show that the mean serial interval is 20 days (95% CI: 16-23 days) when the mother is the infector of the infant, and 28 days (95% CI: 23-33 days) when the infector is the father or a sibling. These time frames offer opportunities for early mitigation of the consequences of infection of an infant once a case has been detected in a household. If preventive measures such as social distancing or antimicrobial treatment are taken promptly they could decrease the probability of infection of the infant.

Cost-effectiveness of Tdap vaccination of adults aged ≥65 years in the prevention of pertussis in the US: a dynamic model of disease transmission.

OBJECTIVES: In February 2012, the Advisory Committee on Immunization Practices (ACIP) advised that all adults aged ≥65 years receive a single dose of reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap), expanding on a 2010 recommendation for adults >65 that was limited to those with close contact with infants. We evaluated clinical and economic outcomes of adding Tdap booster of adults aged ≥65 to "baseline" practice [full-strength DTaP administered from 2 months to 4-6 years, and one dose of Tdap at 11-64 years replacing decennial Td booster], using a dynamic model. METHODS: We constructed a population-level disease transmission model to evaluate the cost-effectiveness of supplementing baseline practice by vaccinating 10% of eligible adults aged ≥65 with Tdap replacing the decennial Td booster. US population effects, including indirect benefits accrued by unvaccinated persons, were estimated during a 1-year period after disease incidence reached a new steady state, with consequences of deaths and long-term pertussis sequelae projected over remaining lifetimes. Model outputs include: cases by severity, encephalopathy, deaths, costs (of vaccination and pertussis care) and quality-adjusted life-years (QALYs) associated with each strategy. Results in terms of incremental cost/QALY gained are presented from payer and societal perspectives. Sensitivity analyses vary key parameters within plausible ranges. RESULTS: For the US population, the intervention is expected to prevent >97,000 cases (>4,000 severe and >5,000 among infants) of pertussis annually at steady state. Additional vaccination costs are $4.7 million. Net cost savings, including vaccination costs, are $47.7 million (societal perspective) and $44.8 million (payer perspective). From both perspectives, the intervention strategy is dominant (less costly, and more effective by >3,000 QALYs) versus baseline. Results are robust to sensitivity analyses and alternative scenarios. CONCLUSIONS: Immunization of eligible adults aged ≥65, consistent with the current ACIP recommendation, is cost saving from both payer and societal perspectives.

Assessment of pertussis vaccination strategies using a mathematical model of disease transmission.

Pertussis or whooping cough is a vaccine-preventable respiratory disease that has reemerged in the past decades. A higher morbidity and mortality has been recorded in infants, although cases have also been reported in adolescents and adults. The epidemiological scenario for this condition has urged to review and implement new strategies aimed at improving its control. However, many of these strategies have not been investigated in depth so as to be established as universal. In this context, mathematical models of disease transmission are useful decision-making tools. Using a mathematical model of pertussis, this study assessed the possible impact of the different control measures on the most vulnerable population (0-1 year old infants). In particular, the analysis focused on the impact of including a booster vaccination at 11 years old, the effect of improving the coverage provided by primary doses, and the reduction of any delay in their administration. The assessment also estimated the effect of immunizing pregnant women. Results show that including a booster dose at 11 years reduces the incidence of pertussis by 3% in infants younger than 1 year old. In addition, administering primary doses in compliance with the schedule (with no delays) reduces pertussis incidence by 16%. Increasing coverage from 80% to 95% results in a signifcantly decreased incidence in the vulnerable population (38%). If the percentage of immunized pregnant women reaches 50%, the reduction of the most severe infant cases could be more than 43% (0-2 month-old infants).

Assessment of pertussis vaccination strategies using a mathematical model of disease transmission / Evaluación de las estrategias de vacunación contra la tos convulsa mediante un modelo matemático de transmisión de la enfermedad

Pertussis or whooping cough is a vaccine-preventable respiratory disease that has reemerged in the past decades. A higher morbidity and mortality has been recorded in infants, although cases have also been reported in adolescents and adults. The epidemiological scenario for this condition has urged to review and implement new strategies aimed at improving its control. However, many of these strategies have not been investigated in depth so as to be established as universal. In this context, mathematical models of disease transmission are useful decision-making tools. Using a mathematical model of pertussis, this study assessed the possible impact of the different control measures on the most vulnerable population (0-1 year old infants). In particular, the analysis focused on the impact of including a booster vaccination at 11 years old, the effect of improving the coverage provided by primary doses, and the reduction of any delay in their administration. The assessment also estimated the effect of immunizing pregnant women. Results show that including a booster dose at 11 years reduces the incidence of pertussis by 3% in infants younger than 1 year old. In addition, administering primary doses in compliance with the schedule (with no delays) reduces pertussis incidence by 16%. Increasing coverage from 80% to 95% results in a signifcantly decreased incidence in the vulnerable population (38%). If the percentage of immunized pregnant women reaches 50%, the reduction of the most severe infant cases could be more than 43% (0-2 month-old infants).

La tos convulsa o coqueluche es una enfermedad respiratoria inmunoprevenible que ha resurgido en las últimas décadas. La mayor morbimortalidad se registra en los lactantes, aunque también se detectan casos en adolescentes y adultos. La situación epidemiológica de la enfermedad ha obligado a revisar e implementar nuevas estrategias para mejorar su control. Sin embargo, muchas de estas estrategias aún no cuentan con un sustento experimental que permita su universalización. En este contexto, los modelos matemáticos de transmisión de enfermedades resultan herramientas útiles en la toma de decisiones. En este trabajo se evaluó, mediante un modelo matemático para coqueluche, el impacto que tendrían distintas medidas de control en la población más vulnerable (0 a 1 año). En particular, se analizó el impacto de la inclusión de un refuerzo a los 11 años, el efecto de la mejora en las coberturas de las dosis primarias y la disminución del retraso en la aplicación de estas. También se estimó el efecto de la vacunación a embarazadas. Los resultados muestran que la inclusión de un refuerzo a los 11 años disminuye un 3% la incidencia en los menores de 1 año. Por su parte, la aplicación de las dosis primarias a tiempo calendario (sin retrasos) la reduce un 16%. Al aumentar la cobertura del 80% al 95%, la incidencia en la población vulnerable se reduce signifcativamente (38%). Cuando el porcentaje de las embarazadas inmunizadas alcanza el 50%, la reducción de los casos más graves en los infantes superaría el 43% (0 - 2 meses).

Cost-effectiveness analysis of a pertussis vaccination programme for Japan considering intergenerational infection.

OBJECTIVE: The incidence of pertussis in adolescence and adulthood has been increasing, and pertussis outbreaks have occurred sporadically in Japan. The risk of intergenerational infection of pertussis is of concern. The aim of this study is to assess the cost-effectiveness of alternative vaccination programmes for replacing the conventional diphtheria-tetanus (DT) vaccine programme administered in adolescence, considering the risk of intergenerational infection. METHODS: We examined the cost-effectiveness of 4 pertussis vaccination programmes: (1) one-time adolescent DT vaccination (DT); (2) one-time adolescent DT-acellular pertussis (DTaP) vaccination; (3) one-time adolescent DTaP with decennial booster (DTaP+booster); and (4) one-time adolescent DTaP with additional vaccination targeted at parents with infants (additional DTaP for parents). We adapted a state-transition Markov model to estimate the costs and effectiveness of vaccination in the adolescent and adult cohorts and then considered intergenerational infection from adolescents/adults to infants. We assumed a societal perspective to estimate results and expressed these in terms of cost, life expectancy, quality-adjusted life expectancy, benefit-cost ratio (BCR), and incremental cost-effectiveness ratio (ICER). RESULTS: At an incidence of 25 per 100,000, the ICERs of the DTaP and additional DTaP for parents strategies were 3,576,072 JPY and 240,055,273 JPY, respectively, when intergenerational transmission of infection was considered. The ICER for the DTaP+booster strategy was dominated. MAJOR CONCLUSION: Alternative vaccination programmes are not currently cost-effective. If intergenerational infection considered, one-time adolescent DTaP vaccination is cost-effective. More accurate reports of pertussis incidence are required as the results of cost-effectiveness analyses of vaccination vary greatly depending on incidence.

Inference for ecological dynamical systems: a case study of two endemic diseases.

A Bayesian Markov chain Monte Carlo method is used to infer parameters for an open stochastic epidemiological modEL: the Markovian susceptible-infected-recovered (SIR) model, which is suitable for modeling and simulating recurrent epidemics. This allows exploring two major problems of inference appearing in many mechanistic population models. First, trajectories of these processes are often only partly observed. For example, during an epidemic the transmission process is only partly observable: one cannot record infection times. Therefore, one only records cases (infections) as the observations. As a result some means of imputing or reconstructing individuals in the susceptible cases class must be accomplished. Second, the official reporting of observations (cases in epidemiology) is typically done not as they are actually recorded but at some temporal interval over which they have been aggregated. To address these issues, this paper investigates the following problems. Parameter inference for a perfectly sampled open Markovian SIR is first considered. Next inference for an imperfectly observed sample path of the system is studied. Although this second problem has been solved for the case of closed epidemics, it has proven quite difficult for the case of open recurrent epidemics. Lastly, application of the statistical theory is made to measles and pertussis epidemic time series data from 60 UK cities.

[Immunization of adolescents and adults as the strategy of improvement of epidemiology of pertussis]. / Szczepienia mlodzieizy i osób doroslych jako strategia poprawy sytuacji epidemiologicznej zachorowan na krztusiec.

Increase of pertussis incidence has been recognised mainly among adolescents and adults since 90. As adolescents and adults sustain the reservoir of infection for non immunized and not completely immunized newborns and neonates, increased rates of pertussis are dangerous. The improvement of pertussis epidemiology might have been obtained through routine immunization of adolescents and adults able to interrupt of B. pertussis circulation in the population. The improvement of surveillance and diagnostics might have result in better detection of the disease in children at the age up to first year and in older age groups.

Cost-effectiveness of adolescent pertussis vaccination for the Netherlands: using an individual-based dynamic model.

BACKGROUND: Despite widespread immunization programs, a clear increase in pertussis incidence is apparent in many developed countries during the last decades. Consequently, additional immunization strategies are considered to reduce the burden of disease. The aim of this study is to design an individual-based stochastic dynamic framework to model pertussis transmission in the population in order to predict the epidemiologic and economic consequences of the implementation of universal booster vaccination programs. Using this framework, we estimate the cost-effectiveness of universal adolescent pertussis booster vaccination at the age of 12 years in the Netherlands. METHODS/PRINCIPAL FINDINGS: We designed a discrete event simulation (DES) model to predict the epidemiological and economic consequences of implementing universal adolescent booster vaccination. We used national age-specific notification data over the period 1996-2000--corrected for underreporting--to calibrate the model assuming a steady state situation. Subsequently, booster vaccination was introduced. Input parameters of the model were derived from literature, national data sources (e.g. costing data, incidence and hospitalization data) and expert opinions. As there is no consensus on the duration of immunity acquired by natural infection, we considered two scenarios for this duration of protection (i.e. 8 and 15 years). In both scenarios, total pertussis incidence decreased as a result of adolescent vaccination. From a societal perspective, the cost-effectiveness was estimated at €4418/QALY (range: 3205-6364 € per QALY) and €6371/QALY (range: 4139-9549 € per QALY) for the 8- and 15-year protection scenarios, respectively. Sensitivity analyses revealed that the outcomes are most sensitive to the quality of life weights used for pertussis disease. CONCLUSIONS/SIGNIFICANCE: To our knowledge we designed the first individual-based dynamic framework to model pertussis transmission in the population. This study indicates that adolescent pertussis vaccination is likely to be a cost-effective intervention for The Netherlands. The model is suited to investigate further pertussis booster vaccination strategies.

Boostrix: a reduced-dose acellular pertussis vaccine for use in adolescents and adults.

Pertussis remains a serious problem in many countries. Even in countries with high vaccine coverage and a long vaccination history, pertussis outbreaks occur periodically. Rather than being a disease of young children, pertussis has shifted to affect adolescents and adults. Increased pertussis burden in adolescents and adults is the major source of severe infection for young infants. An effective vaccine is needed to control the spread of pertussis beyond preschool children. Boostrix is a reduced-dose acellular pertussis vaccine with diphtheria and tetanus toxoids, and is designed for use in adolescents and adults. Current evidence suggests that Boostrix is immunogenic and well tolerated. The pertussis component of Boostrix has been shown to be efficacious in a large-scale Phase III trial. More than 50 countries have given permit to the use of Boostrix, and many of them formally recommend the use of Boostrix in adolescents and adults. Designed as a vaccine for adolescence and adults, Boostrix has a long way to go to achieve large-scale use in those target groups. Nevertheless, we expect that the advent of Boostrix will lead to a much better control of pertussis in the general population.

Using computer simulations to compare pertussis vaccination strategies in Australia.

High levels of notified pertussis in adolescents and adults, persisting severe disease (hospitalization and deaths) in infants despite high childhood immunization coverage, together with the availability of adult-formulated pertussis vaccines, have made alternate strategies for vaccine control of pertussis an important issue in Australia. An age-structured computer simulation model was used to compare the likely effects of adopting different vaccination strategies in Australia on pertussis transmission by age group over a 50 year time period. Epidemiological parameters and vaccination coverage in Australia were estimated from previous pertussis modeling studies and existing data. In the simulations, replacing the pertussis booster at 18 months with a booster dose for adolescents at an age between 12 and 17 years, assuming 80% coverage, led to decreases in pertussis cases of 30% in children of ages 0-23 months (who have the highest complication rates) and of 25% in adolescents, but an increase of 15% in cases in 2-4-year-old children. The simulations did not suggest any shift of pertussis cases into the adult child-bearing years. Varying parameter values in the simulations in a series of sensitivity analyses showed the model predictions to be robust over a plausible range. The results of these simulations suggest that the recent change in the Australian pertussis vaccination schedule, replacing the 18 month dose with a pertussis booster in 15-17-year-old adolescents, is very likely to reduce overall pertussis incidence in Australia without increasing the cost of the current vaccine program.

Estimating heterogeneous transmission with multiple infectives using MCMC methods.

We developed a general procedure for estimating the transmission probability adjusting for covariates when susceptibles are exposed to several infectives concurrently and taking correlation within transmission units into account. The procedure is motivated by a study estimating efficacy of pertussis vaccination based on the secondary attack rate in a rural sub-Saharan community (Niakhar, Senegal) and illustrated with simulations. The procedure is also appropriate to estimate the pairwise transmission probability in transmission studies of live vaccine virus in a collection of transmission units, such as day-care centres or retirement centres. Previously, analyses either excluded transmission units with multiple infectives or ignored co-infectives. Excluding transmission units with multiple infectives is statistically less efficient and ignoring co-infectives can lead to biased estimation. Modelling is carried out by regressing the latent pairwise transmission probability from each infective to a susceptible on covariates and specifying a transmission linkage function linking the latent pairwise transmission probability to the overall transmission probability. Parameters are estimated using Markov chain Monte Carlo methods.

Estimating the potential health gain and cost consequences of introducing a pre-school DTPa pertussis booster into the UK child vaccination schedule.

This work estimates the health and cost impacts of a pre-school booster vaccination for Bordetella pertussis, when added to existing UK primary vaccination. A transition state simulation model of pertussis infection in a closed population was constructed comprising of susceptible, infected and immune population sub-groups, across eight age bands. Epidemiological, service use and cost data were sourced from routine statistics, published literature and clinician estimates. The introduction of a pre-school booster is predicted to reduce the number of hospitalisations by approximately 1400 and pertussis cases suffered by up to 28,000 at a net investment of under 13 million pounds over a 5-year period.

Recommendations are needed for adolescent and adult pertussis immunisation: rationale and strategies for consideration.

Pertussis vaccination of infants has dramatically reduced disease, complications and deaths in infancy and early childhood. But there is still a major public health challenge--to deal with the morbidity and economic burden of illness in older children, adolescents and adults. Furthermore, it is these groups that form a major source of infection for non-immunised and partially immunised infants who are at high risk of severe complications. Adult-type acellular pertussis vaccine confers safe and effective protection against pertussis. There are several strategies to consider for immunising older individuals. Universal vaccination of all age groups would be the best available strategy for protecting individuals. It would also reduce the potential for transmitting the disease to other susceptibles, particularly infants. However, such a policy may be difficult both logistically and economically at this time. More easily achievable as a first step would be a strategy of universal adolescent booster vaccination combined with a programme targeted at adults most likely to have contact with very young babies including healthcare and childcare workers, parents and close family contacts. There is also potential for offering vaccination to adults (and their carers and close contacts) whose medical conditions or advanced age may place them at increased risk of more severe pertussis disease. Specific details of immunisation programmes must be made on a country by country basis depending on local circumstances.

Simulations of pertussis epidemiology in the United States: effects of adult booster vaccinations.

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.