Durchimpfung und Determinanten des Impfstatus in Deutschland

The level of childhood immunisation is an acknowledged indicator for health prevention. In Germany, vaccination is not compulsive. Continuous representative data derive only from school health examinations. From May 2003 until May 2006 the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) was conducted and vaccination information on 16,460 participants was obtained. Using data on the vaccination cards, it was possible to make detailed analyses of vaccination coverage in children up to the age of 17. Different vaccine types were taken into consideration in defining the term 'immunisation coverage'. The average prevalence of full immunisation for tetanus, diphtheria und polio as well as the coverage for the first dose of measles, mumps and rubella (MMR) vaccination was above 90% in children aged 2-17 years. Vaccination coverage for pertussis, Hib and hepatitis B is higher in younger than in older age groups. Compliance with the recommendation to have a second MMR dose and to make up of hepatitis B and pertussis immunisation is still low, especially in adolescents. In 7- to 17-year-old children the additional booster (recommended for 5- to 6-year-old children) is frequently missing.     

The cost of epidemiological transition: a study of a decrease in pertussis vaccination coverage

Based on a transfer function intervention model applied to epidemiological data of pertussis incidence and pertussis vaccination in England and Wales, the consequences of pertussis vaccination strategies were estimated in terms of health effects and economic direct costs. It was established that sixth dose pertussis vaccination programs at 90% coverage were the most cost saving for short-term and for long-term vaccination prevention strategies. We considered two alternative strategies with whole-cell or acellular vaccines for primary course and acellular vaccine for two booster doses in children and one booster in adolescents. As a rule, programs based on exclusive use of acellular vaccines for all the doses were more expensive. Direct costs of programs with the vaccination rate at 90% remained systematically lower than the expected cost of pertussis disease in the case of non prevention. The stability over time of the vaccination coverage at a constant level of 90% made it possible to ensure the largest cost saving strategy during the period of 14 years of analysis. Transitions to programs with a lower proportion of vaccinated children systematically incurred an incremental direct cost for society. The amount of that cost rose with the size of the drop in the new vaccination coverage and diminished, due to the J-curve optimistic effect, when the fall in vaccination rate generated a delayed increase in notification cases of pertussis.     

The cost of epidemiological transition: A study of a decrease in pertussis vaccination coverage

Based on a transfer function intervention model applied to epidemiological data of pertussis incidence and pertussis vaccination in England and Wales, the consequences of pertussis vaccination strategies were estimated in terms of health effects and economic direct costs. It was established that sixth dose pertussis vaccination programs at 90% coverage were the most cost saving for short-term and for long-term vaccination prevention strategies. We considered two alternative strategies with whole-cell or acellular vaccines for primary course and acellular vaccine for two booster doses in children and one booster in adolescents. As a rule, programs based on exclusive use of acellular vaccines for all the doses were more expensive.Direct costs of programs with the vaccination rate at 90% remained systematically lower than the expected cost of pertussis disease in the case of non prevention. The stability over time of the vaccination coverage at a constant level of 90% made it possible to ensure the largest cost saving strategy during the period of 14 years of analysis. Transitions to programs with a lower proportion of vaccinated children systematically incurred an incremental direct cost for society. The amount of that cost rose with the size of the drop in the new vaccination coverage and diminished, due to the J-curve optimistic effect, when the fall in vaccination rate generated a delayed increase in notification cases of pertussis.     

Accelerating control of pertussis in England and Wales

Results of an accelerated pertussis vaccination schedule for infants introduced in 1990 in England and Wales were examined. Earlier scheduling and sustained high vaccine coverage resulted in fewer reported cases of pertussis among infants, reinforcing the World Health Organization drive for on-time completion of the infant vaccination schedule. As determined by using the screening method, the first dose of vaccine was 61.7% effective in infants <6 months of age, and effectiveness increased with subsequent doses. Three doses of a good whole-cell pertussis vaccine were 83.7% effective in children 10-16 years of age; a preschool booster vaccination further reduced pertussis incidence in children <10 years of age. As in other industrialized countries, surveillance data during 1998-2009 showed that pertussis in England and Wales mainly persists in young infants (i.e., <3 months of age), teenagers, and adults. Future vaccine program changes may be beneficial, but additional detail is required to inform such decisions.     

Declining pertussis incidence in Sweden following the introduction of acellular pertussis vaccine

Acellular pertussis vaccines were introduced nation-wide in Sweden in 1996, 17 years after the withdrawal of whole-cell pertussis vaccine from the childhood immunisation schedule. We report national data on age specific incidence of culture-confirmed Bordetella pertussis for 1986-2000, and clinical follow-up for 3 years (October 1997-September 2000) in children born in 1996-2000 and from children born in 1993-1994 who had participated in a trial of pertussis vaccines. The annual incidence of culture-confirmed B. pertussis was 89-150 per 100,000 before introduction of acellular pertussis vaccines and has dropped to 17-26 per 100,000. The data suggest that unimmunised infants and children who have received only one dose of pertussis vaccine were provided some protection. The decline is most obvious from the second dose onwards and remained stable for 4-5 years after the third dose in the absence of any booster dose. The first signs of waning immunity were observed at 6-7 years of age in the trial cohort. The short-term benefits reflect high vaccination coverage and high initial efficacy. The full impact of the acellular pertussis vaccination programme in infants remains to be established.     

Adult pertussis vaccination strategies and their impact on pertussis in the United States: evaluation of routine and targeted (cocoon) strategies

A compartmental, age-structured mathematical model was developed and recent US pertussis epidemiology data were used to evaluate the impact on pertussis infection rates of routine and targeted adult immunization strategies. Model simulations predict that the implementation of adolescent immunization only could reverse the current rise in pertussis infection rates but may lead to a resurgence of pertussis in subsequent decades. In contrast, inclusion of a routine adult strategy is likely to lead to sustained control of pertussis. Routine adult vaccination could control the disease even with relatively low coverage rates of 40% for routine vaccination of all adults every 10 years, or 65% for a targeted vaccination of close contacts of newborns completed by one booster dose for all adults. The model also predicts that the optimal age for this booster dose is 40 years. These results support the 2006 American Academy of Immunization Practices' recommendations for adolescent and adult vaccination against pertussis.     

Use of mass Tdap vaccination to control an outbreak of pertussis in a high school--Cook County, Illinois, September 2006-January 2007

On September 6, 2006, the Cook County Department of Public Health (CCDPH) was notified that a local high school student aged 17 years had pertussis. During September 2006-January 2007, 36 pertussis cases directly linked to the high school were identified. Because Bordetella pertussis immunity from childhood vaccinations wanes over time, outbreaks of pertussis can periodically occur among students and staff at middle and high schools. School settings facilitate transmission of pertussis, disrupting school and community activities and putting vulnerable populations, such as unvaccinated infants, at risk. A pertussis booster vaccine suitable for adolescents and adults became available in the United States in 2005, when two new tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines were licensed for persons aged 10-18 years and 11-64 years, respectively. In 2006, the Advisory Committee on Immunization Practices (ACIP) recommended that all adolescents and adults receive a one-time Tdap booster vaccination. This report summarizes strategies used to control the pertussis outbreak in Cook County, Illinois, including efforts to increase Tdap vaccination coverage. Despite multiple communications recommending Tdap vaccination and implementation of a cough exclusion policy during the pertussis outbreak, student vaccination rates did not increase substantially until a school-based Tdap vaccination clinic was implemented. Because persons at risk for pertussis might not seek vaccination from their usual health-care provider, even during an outbreak, local health departments might consider early implementation of a cough exclusion policy and on-site Tdap vaccination clinic as control measures.     

Cost-effectiveness of pertussis booster vaccination for preschool children in Japan

Introduction: Japan currently recommends four doses of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine in its routine vaccination program, but the introduction of a fifth dose is currently under consideration. An objective of the booster vaccination is to prevent severe cases of pertussis in infants through herd immunity. Thus, the aim of this analysis was to demonstrate the cost-effectiveness of a fifth-dose of the DTaP vaccine for 6-year-old children, taking herd immunity for unvaccinated infants into account.MethodAn economic model analysis was conducted comparing the cost and effectiveness of the two strategies based on quality-adjusted life years (QALYs). We evaluated the incremental cost-effectiveness ratio (ICER) of the booster strategy to the no booster strategy. This model contained two sub-models: one for children aged 6 years or older and one for infants under 3 months old. Herd immunity for infants is modeled as when siblings in the same family are infected.ResultsThe ICER was JPY 71,605,491 (USD 656,931) per QALY gained from the societal perspective, and 7.10% of incremental QALYs (0.0000934) were from a reduction in infant infection. In the sensitivity analysis, no variables moved the ICER under the threshold (JPY 5,000,000 per QALY gained), and the duration of pertussis disease and the incidence rate of pertussis had a significant impact on the ICER. When the disease burden of pertussis decreased, the booster strategy resulted in fewer QALYs gained and greater costs compared with the no booster strategy.ConclusionThe introduction of a DTaP booster vaccination to the routine immunization schedule can be expected to reduce the number of pertussis cases in the target population. However, our study showed that adding a booster vaccination for 6-year-old children to the schedule in Japan would not be cost-effective in terms of achieving herd immunity among unvaccinated infants.     

COVID-19 vaccinations in Bhutan – Mix-and-Match to Boosters: An experience

Bhutan – a landlocked least developed country in the Himalayas – vaccinated 94% of its adults with the first dose of COVID-19 vaccine in March-April 2021, 90.2% with second dose in July 2021, and 89.1% with booster (third) dose by March 2022.The country used COVISHIELD (Oxford-Astrazeneca) vaccine for the first dose but decided to pursue a heterologous prime-boost strategy (“mix-and-match”) for the second dose using Moderna’s mRNA vaccine for adults.Bhutan rapidly rolled out Pfizer and Moderna vaccines for 12 to 17-year-olds through a school-based vaccination strategy followed by booster doses: 78.6% of adolescents aged 12–17 years were vaccinated with the first dose by August 2021, 92.8% with second dose by November 2021, and 79.7% with booster (third) dose by March 2022. More than 97% of children aged 5 to 11 years have received Pfizer’s Comirnaty vaccine for their first dose.Bhutan is steadily vaccinating its population and might soon become one of the few least developed countries to achieve herd immunity-level vaccination coverage with more than 80% of its population fully vaccinated.     

Community awareness and predictors of uptake of pertussis booster vaccine in South Australian adults

ObjectivePertussis is a highly virulent vaccine preventable disease that remains a global challenge. This study aimed to assess community knowledge of pertussis infection as well as awareness and uptake of adult pertussis booster vaccine.MethodsA cross-sectional survey was conducted of randomly selected households in South Australia by Computer Assisted Telephone Interviews in 2011. Survey data were weighted to the age, gender and geographical area profile of the population.ResultsFrom 3124 randomly sampled contactable households, 1967 interviews were conducted (participation rate 63%) with individuals aged 18–93 years, including 608 parents of children aged <18 years. The majority of respondents (97%) had heard of pertussis (whooping cough) and 18% reported that a household member had previously contracted whooping cough infection. Most respondents considered whooping cough to be highly contagious (73%) and severe for infants (89%). Over half (51%) of those surveyed were aware that family members commonly transmit pertussis to infants. Despite high knowledge, pertussis vaccine uptake was low, with only 10% of respondents reporting pertussis vaccination in the previous five years. Whilst 61% of respondents were aware of the availability of an adult pertussis booster vaccine, only 8% (n = 154) reported their Family Physician had discussed it with them. If provided free, 77% agreed that they would be more likely to accept a booster pertussis vaccination. Independent predictors of recent pertussis vaccination included higher education, larger household size, perception of greater disease severity for infants and discussion with a Family Physician about pertussis vaccination.ConclusionsWhilst knowledge regarding transmission and severity of Bordetella pertussis was high, uptake of pertussis vaccination for adults is remarkably low amongst the South Australian community. Improved awareness regarding the availability of a booster pertussis vaccine through Family Physicians and/or provision of funded pertussis vaccination for adults has the potential to improve pertussis vaccine coverage.     

Differences of humoral and cellular immune response to an acellular pertussis booster in adolescents with a whole cell or acellular primary vaccination

To study the pertussis-specific immune response of adolescents with different prevaccination schedules, we measured the humoral and cell-mediated immunity (CMI) to pertussis antigens before and after a five-component Tdap booster vaccination in 78 adolescents, who had previously received either five doses of a two-component acellular pertussis vaccine (aP; last dose age 4-6 years), four doses of aP (last dose age 18-24 months), or four doses of whole cell pertussis vaccine (wcP; last dose age 18-24 months). The proportion of participants with a twofold rise in titre was 79% against pertussis toxin (PT), 94% against filamentous hemagglutinin (FHA), and 99% against pertactin (PRN) without significant differences between the three groups. However, participants with primary wcP vaccination showed higher postvaccination titres to pertussis toxin (geometric mean titre, GMT 50.3EU/ml) than those with either four (GMT 17.1EU/ml) or five (GMT 16.4EU/ml) previous aP doses. CMI indices to PT, FHA, PRN and fimbriae (FIM) increased after vaccination and were similar between groups. The current adolescent Tdap booster immunization induced good humoral and cellular immune response to pertussis. The higher antibody titres to pertussis toxin may indicate a more effective priming of B cell memory after primary whole-cell vaccination.     

Persistence of antibodies at 5-6 years of age for children who had received a primary series vaccination with a pentavalent whole-cell pertussis vaccine and a first booster with a pentavalent acellular pertussis vaccine: immunogenicity and tolerance of second booster with a tetravalent acellular vaccine at 5-6 years of age

The main objective of this study was to assess in 5-6-year-old French children (n=162) the persistence of antibodies induced by a primary series vaccination (at 2-4 months of age) with a pentavalent whole-cell pertussis combined vaccine (DTwcP-IPV-Hib; Pentacoq) and a first booster (at 12-16 months of age) with a pentavalent two-component acellular pertussis combined vaccine (DTacP-IPV-Hib; Pentavac). The second objective was to evaluate in these 5-6-year-old French children the safety and the immunogenicity of a tetravalent pertussis combined vaccine (DTacP-IPV, Tetravac) given as a second booster. RESULTS: before the 2nd booster, more than 90% of children had antibody titers above the defined threshold for polyribosyl ribitol phosphate (PRP), tetanus, diphtheria and poliomyelitis; antibody titers were very low for pertussis. One month after the second booster, all children had sero-protective post-booster titers for tetanus, diphtheria and poliomyelitis types 1-3; over 90% of children had a four-fold rise in titers against DTacP-IPV antigens. Adverse events were mostly solicited reactions, with no serious adverse event. A strong anamnestic response was also observed after the second booster injection with Tetravac, with a satisfactory safety profile. CONCLUSION: Pentavac and Tetravac (acellular pertussis containing vaccines) may thus be administered as first and second boosters respectively, in children primed with Pentacoq (whole-cell pertussis containing vaccine).     

The impact of pre-school booster vaccination of 4--6-year-old children on pertussis in 0--1-year-old children

Pertussis in young children is severe and relatively prevalent in vaccinated populations. We estimated the impact of pre-school booster vaccination of 4-6-year-old children on pertussis in 0-1-year-old children. We conducted a population-based historical cohort study of all children born in Denmark, 1977-2001 (N=1,536,717) using information on place of residence to identify household members and vaccination history from nationwide registers. We estimated rate ratios (RRs) of pertussis hospitalisation among children in the cohort according to number, age, and vaccination status of their household members. This enabled, through population attributable risks, the estimation of the preventable proportion of hospitalisations among 0-1-year-old children according to age at booster vaccination (4-6 years), booster uptake, and the efficacy of the booster against transmission. The preventable proportion of pertussis hospitalisations among 0-1-year-old children ranged from 7% to 33% (most realistic scenario=18%), varying according to age at booster vaccination, uptake, and efficacy of booster against transmission. This relatively limited impact of a pre-school booster was partly a consequence of the actual number of 0-1-year-old children living with children of pre-school age or older and partly the result of significant exposure from children younger than pre-school age in the household. According to our model the effectiveness of pre-school booster vaccination as an intervention to prevent pertussis hospitalisation of 0-1-year-old children is modest.     

Acellular pertussis vaccine use in risk groups (adolescents, pregnant women, newborns and health care workers): a review of evidences and recommendations

Background

Pertussis is an acute infectious illness, caused by the bacteria Bordetella pertussis and commonly known as “whooping cough”. Waning immunity after vaccination or after natural infection contributes significantly to the increasing incidence rates in adolescents and adults. Prevention of pertussis in industrialized countries is mainly based on immunization with acellular vaccines in combination with other antigens. A booster dose with an adult-formulation tetanus-diphtheria toxoid and acellular pertussis vaccine (Tdap) is now recommended for all adolescents by several countries, and replacement of the decennial Td dose with a single or more doses of Tdap is recommended for adults.

Objective

Our review aims at describing the current knowledge on the impact of acellular pertussis vaccination in adolescents and adults, with particular focus on specific risk groups: adolescents, pregnant women and their newborns, and health care workers (HCWs), and secondly at suggesting possible immunization strategies.

Methods

Data were retrieved by searches of Pubmed, references, from relevant articles and open-access websites.

Results

In countries where an adolescent booster dose was adopted, a certain decrease of incidence rates was observed. No serologic correlate of protection after immunization exists, but subjects with high antibody levels against pertussis antigens are less likely to develop the disease. Tdap vaccine was demonstrated to induce antibodies to pertussis antigens exceeding those associated with efficacy in infants, in both adolescents and adults. Tdap use in pregnant women seems to be safe and might represent a useful tool in order to prevent pertussis cases in the first months of life. Neonatal immunization with monovalent acellular pertussis vaccine can efficiently prime T and B cells and act as a basis for future immune responses. Cocooning strategies involving all those surrounding newborns have started to be implemented. Their impact on infant pertussis cases will be evaluated in the coming years. Coverage in HCWs should be increased, given their important role in pertussis transmission in health care settings.

Conclusions

Despite the more recent position paper of WHO gives priority to infant and childhood vaccination against pertussis and leaves adolescent, adult and risk group immunization as an option for the future, data are quickly accumulating to support the need to consider pertussis vaccination as a crucial preventative intervention even in adolescents and special risk groups.     

Antibody persistence against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b (Hib) in 5-6-year-old children after primary vaccination and first booster with a pentavalent combined acellular pertussis vaccine: immunogenicity and tolerance of a tetravalent combined acellular pertussis vaccine given as a second booster

The main objective of this study was to assess in 5-6-year-old French children (n=234) the persistence of antibodies induced by a primary series vaccination (at 2-4 months of age) and a first booster (at 12-16 months of age) with a pentavalent two-component acellular pertussis combined vaccine (DTacP-IPV-Hib; Pentavac). The second objective was to evaluate in these 5-6-year-old French children the safety and the immunogenicity of a tetravalent acellular pertussis combined vaccine (DTacP-IPV; Tetravac) given as second booster. RESULTS: Seroprotective antibody levels against diphtheria, tetanus, types 1-3 poliomyelitis and PRP were maintained 4-5 years after primary-vaccination and first booster with Pentavac. As expected, anti-PT antibodies levels were low, suggesting that children were not colonised by Bordetella pertussis. The second booster with Tetravac was well tolerated and elicited a strong booster response for all antigens. CONCLUSION: acellular pertussis combined vaccine, used in primary-vaccination, could be considered as having the same priming effect and the same efficacy as whole cell pertussis vaccine.     

Pertussis after end of a mass vaccination project--end of the "vaccination honey-moon"

After 16 years of no vaccination against pertussis in Sweden, mass vaccination of infants and catch-up vaccination of children up to 10 years with a monocomponent pertussis toxoid vaccine was performed in the Greater Gothenburg area of Sweden between 1995 and 1999. At the end of the project in February 1999, 56% of all 10 year old children born in the Greater Gothenburg area had received 3 doses of the pertussis toxoid. No booster doses were given. This led to a temporary almost complete elimination of the disease. The aim of the present study was to follow the incidence of pertussis after end of the mass vaccination project (1999-2009) as it is reflected by laboratory verified cases (cultures and/or PCR) and pertussis hospitalizations. A reemergence of pertussis was seen from the end of 1999 with a peak in 2004 followed by a decrease when booster doses to both 6 and 10 year old children were introduced in 2005-2006. From July 1, 1999 through December 31, 2009 a total of 1973 cases were diagnosed with culture or PCR. The disease was prevalent in all age groups. The highest documented incidence was seen in infants younger than 12 months. 450 patients with verified pertussis had received 3 doses of the pertussis toxoid vaccine in the mass vaccination project and some other trials (comprising a total of 69,423 children). The mean time from the last dose to the laboratory verification of pertussis was 5 years in these 450 cases. There were 128 hospitalizations, 106 of which were in infants. In conclusion, pertussis is still not eliminated from the area. Booster doses are needed but the numbers and optimal timing are not known.     

Vaccination coverage among foreign-born and U.S.-born adolescents in the United States: Successes and gaps – National Immunization Survey-Teen, 2012–2014

BackgroundAn overall increase has been reported in vaccination rates among adolescents during the past decade. Studies of vaccination coverage have shown disparities when comparing foreign-born and U.S.-born populations among children and adults; however, limited information is available concerning potential disparities in adolescents.MethodsThe National Immunization Survey-Teen is a random-digit–dialed telephone survey of caregivers of adolescents aged 13–17 years, followed by a mail survey to vaccination providers that is used to estimate vaccination coverage among the U.S. population of adolescents. Using the National Immunization Survey-Teen data, we assessed vaccination coverage during 2012–2014 among adolescents for routinely recommended vaccines for this age group (≥1 dose tetanus and diphtheria toxoids and acellular pertussis [Tdap] vaccine, ≥1 dose quadrivalent meningococcal conjugate [MenACWY] vaccine, ≥3 doses human papillomavirus [HPV] vaccine) and for routine childhood vaccination catch-up doses (≥2 doses measles, mumps, and rubella [MMR] vaccine, ≥2 doses varicella vaccine, and ≥3 doses hepatitis B [HepB] vaccine). Vaccination coverage prevalence and vaccination prevalence ratios were estimated.ResultsOf the 58,090 respondents included, 3.3% were foreign-born adolescents. Significant differences were observed between foreign-born and U.S.-born adolescents for insurance status, income-to-poverty ratio, education, interview language, and household size. Foreign-born adolescents had significantly lower unadjusted vaccination coverage for HepB (89% vs. 93%), and higher coverage for the recommended ≥3 doses of HPV vaccine among males, compared with U.S.-born adolescents (22% vs. 14%). Adjustment for demographic and socioeconomic factors accounted for the disparity in HPV but not HepB vaccination coverage.ConclusionsWe report comparable unadjusted vaccination coverage among foreign-born and U.S.-born adolescents for Tdap, MenACWY, MMR, ≥2 varicella. Although coverage was high for HepB vaccine, it was significantly lower among foreign-born adolescents, compared with U.S.-born adolescents. HPV and ≥2-dose varicella vaccination coverage were low among both groups.     

全球百日咳现状以及免疫策略进展

即使在疫苗覆盖率高的发达国家,百日咳仍然是一个全球公共卫生的难题。百日咳发病率的上升伴随着流行病学的改变,特别是青少年和成人的报告病例显著增多。事实上,被报告的病例只是冰山一角。因此,许多国家已采取青少年加强免疫的策略。现从全球百日咳的流行现状入手,详细分析百日咳再现的玄机,并介绍各国免疫策略的演变,从而为我国免疫决策提供依据。     

Seroepidemiology of diphtheria and pertussis in Luxembourg in 2000

A large serosurvey was carried out in Luxembourg in 2000-2001, to determine the population immunity against a number of vaccine-preventable infections including diphtheria and pertussis. Immunity to diphtheria and pertussis was assessed using an in-house neutralization assay and a commercial ELISA test respectively. Mean pertussis antibody activity decreased from 4 to 8 years of age, reflecting the effects of waning of vaccine-induced immunity. Mean pertussis antibody activity increased during adolescence due to infection in previously vaccinated individuals and levelled out after approximately 20 years of age. For adults>25 years age, a statistically significant 30% difference in mean antibody activity between men and women was observed. The proportion of seronegatives for diphtheria among children and adolescents aged<20 years was 2.5% reflecting the high vaccination coverage. The proportion seronegative for diphtheria tended to increase with age such that 42% of individuals aged>40 years were seronegative. Our study supports the recently introduced acellular pertussis vaccine booster at 6 years to reduce pertussis transmission in school-aged children and adolescents.