Effectiveness of quadrivalent influenza vaccination in the first year of a funded childhood program in Queensland,Australia, 2018

BackgroundFollowing high influenza activity in 2017, the state of Queensland, Australia, funded a quadrivalent inactivated influenza vaccination program for children aged 6 months to <5 years in 2018. We calculated influenza vaccine effectiveness (VE) among children eligible for this program.MethodsA matched case-control study was conducted. Cases were identified using Queensland 2018 influenza notification data among children age-eligible for funded vaccination. Controls were drawn from Australian Immunisation Register records of Queensland resident children age-eligible for funded influenza vaccine. Up to 10 controls per case were matched for location and birthdate. First dose vaccination was valid if received ≥14 days prior to specimen collection; a second dose was valid if received ≥28 days after first dose receipt. VE was calculated for vaccine doses and adherence to national recommendations for two doses in the first season (schedule completeness) and adjusted (VE_adj) for sex and First Nations status.ResultsThere were 1,125 cases and 10,645 matched controls analysed. Overall VE_adj against laboratory-confirmed influenza was 51% (95% confidence interval (CI) 41–60). VE_adj was 60% (95% CI 46–70) for children who received two doses in 2018, and 60% (95% CI 48–69) for children vaccinated appropriately according to schedule completeness. VE increased with age.ConclusionsModerate vaccine effectiveness was observed for children eligible for the funded program in Queensland in 2018, adding to the sparse evidence for influenza vaccine use in Australian children. Adhering to the national first season two dose schedule for influenza vaccine receipt in children ensures maximum protection.     

Differences of IgG antibody avidity after an acellular pertussis (aP) booster in adolescents after a whole cell (wcP) or aP primary vaccination

Compared to whole cell pertussis (wcP) vaccines, acellular pertussis vaccines (aP) have a better safety profile with lower reactogenicity, although their short and long-term efficacy was found to be slightly lower. Up to now, no established serological parameter to predict long-term protection exists. IgG-anti-pertussis avidity possibly determines the effect of different pertussis vaccines and boosting intervals on long-term immunity. Thus, the avidity of a tetanus-diphtheria-aP booster at 10–14 years was tested in three groups of adolescents who had been previously immunized with either five doses of aP (5aP) at 2, 4, 6, 15–18 months and 5–6 years of age, four doses of aP (4aP) or four doses of wcP (4wcP) at 2, 4, 6 and 15–18 months of age.     

Pertussis vaccine effectiveness and duration of protection – A systematic review and meta-analysis

A comprehensive review of observational pertussis vaccine effectiveness (VE) studies is needed to update gaps from previous reviews. We conducted a systematic review of VE and duration of protection studies for the whole-cell (wP) and acellular (aP) pertussis vaccines and conducted a formal meta-analysis using random effects models. Evidence continues to suggest that receipt of any pertussis vaccine confers protection in the short-term against disease although this protection wanes rapidly for aP vaccine. We detected significant heterogeneity in pooled estimates due, in part, to factors such as bias and confounding which may be mitigated by study design. Our review of possible sources of heterogeneity may help interpretation of other VE studies and aid design decisions in future pertussis VE research.     

Effectiveness of a vaccination programme for an epidemic of meningococcal B in New Zealand

New Zealand has experienced a prolonged epidemic of meningococcal B disease since 1991. The epidemic has waned significantly since its most recent peak in 2001. A strain-specific vaccine, MeNZB, was introduced to control the epidemic in 2004, achieving 81% coverage of people under the age of 20. The vaccine was rolled out in a staged manner allowing the comparison of disease rates in vaccinated and unvaccinated individuals in each year.Vaccine effectiveness in people aged under 20 years is estimated using a Poisson regression model in the years 2001-2008, including adjustments for year, season, age, ethnicity, region and socioeconomic status. Further analyses investigate the dose response relationship, waning of the vaccine effect after one year, and cross-protection against other strains of meningococcal disease.The primary analysis estimates MeNZB vaccine effectiveness to be 77% (95% CI 62-85) after 3 doses and a mean follow-up time of 3.2 years. There is evidence for a protective effect after 2 doses 47% (95% CI 16-67), and no evidence for a waning of effectiveness after one year. Simultaneous modelling of invasive pneumococcal disease and epidemic strain meningococcal B suggests a degree of residual confounding that reduces the effectiveness estimate to 68%. There is evidence for some cross-protection of MeNZB against non-epidemic strains.The MeNZB vaccine was effective against the New Zealand epidemic strain of meningococcal B disease. Between July 2004 and December 2008 an estimated 210 epidemic strain cases (95% CI 100-380), six deaths and 15-30 cases of severe sequelae were avoided in New Zealand due to the introduction of the MeNZB vaccine.     

Reciprocal interference of maternal and infant immunization in protection against pertussis

BackgroundBecause of the current re-emergence of pertussis, vaccination during the 3rd trimester of pregnancy is recommended in several countries in order to protect neonates by placental transfer of maternal antibodies. Here, we examined the potential reciprocal interference of mother and infant vaccination in protection against pertussis in mice.MethodsFemale mice were vaccinated with acellular pertussis vaccines and protection against Bordetella pertussis challenge, as well as functional antibodies were measured in their offspring with or without re-vaccination.ResultsMaternal immunization protected the offspring against B. pertussis challenge, but protection waned quickly and was lost after vaccination of the infant mice with the same vaccine. Without affecting antibody titers, infant vaccination reduced the protective functions of maternally-derived antibodies, evidenced both in vitro and in vivo. Protection induced by infant vaccination was also affected by maternal antibodies. However, when mothers and infants were immunized with two different vaccines, no interference of infant vaccination on the protective effects of maternal antibodies was noted.ConclusionIt may be important to determine the functionality of antibodies to evaluate potential interference of maternal and infant vaccination in protection against pertussis.     

Effectiveness of two pertussis vaccines in preterm Danish children

Reduced immunogenicity in preterm children has been observed for pertussis vaccines. How immunogenicity relates to clinical protection is not well-established for pertussis, and the corresponding reduction, if any, in post-licensure vaccination effectiveness among preterm children has not been determined. We conducted a nationwide cohort study of 879,424 Danish children including 1553 cases of pertussis hospitalisation. The effectiveness of pertussis vaccination, both whole-cell and acellular, was evaluated in preterm and full-term children. The effectiveness of a completed primary series of pertussis vaccination, whole-cell or acellular, was similar in preterm and full-term children.     

Persistence of antibodies 3 years after booster vaccination of adults with combined acellular pertussis, diphtheria and tetanus toxoids vaccine

The duration of protection after vaccination with reduced antigen content diphtheria, tetanus and acellular pertussis vaccines (Tdap) is not known. Long-term post-vaccination serological data will help to improve understanding of the duration of humoral immunity and guide vaccination policy for the timing of repeat dose administration. The persistence of antibodies to Tdap antigens was measured 3 years after vaccination of adults 19-64 years of age with one of 2 Tdap vaccines (Boostrix^®, GlaxoSmithKline Biologicals; Tdap-B: or Adacel^®, Sanofi Pasteur; Tdap-A). In both groups, geometric mean concentrations for antibodies to diphtheria, tetanus, and pertussis vaccine antigens were decreased at year 3 relative to levels observed 1 month and 1 year following vaccination, but remained higher than pre-vaccination levels. Seroprotection rates for diphtheria and tetanus remained high for both Tdap vaccines (for diphtheria, 96.9% and 97.8% for the Tdap-B and Tdap-A groups, respectively; for tetanus, 98.1% and 99.6%, respectively).     

Universal tetanus,diphtheria, acellular pertussis (Tdap) vaccination of adults: What the Canadian public knows and wants to know

Tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is recommended for all adults in Canada but uptake is low. This study measured the knowledge, attitudes, beliefs, and behaviors of Canadian adults to identify potential barriers and facilitators to Tdap uptake. A survey was undertaken on a geographically representative sample of Canadian adults (n = 4023) and 8 focus groups (62 participants) were conducted nationwide. The survey revealed that knowledge about pertussis and Tdap was low (38.3% correct answers). Only 36.0% of respondents reported being aware that all adults were recommended to receive Tdap and only 10.7% reported being immunized; 36.7% did not know whether they had received Tdap. Respondents who were aware of the immunization recommendations were twice as likely to be immunized (16.6% vs. 8.3%; p < 0.001). Only 9.3% believed that their health care provider thought that Tdap was important for adults. The focus group data supported the survey results. Participants wanted information about pertussis and Tdap communicated through multiple modalities, but a recommendation by their family physician was most important to their decision to be immunized or not. This study demonstrates that current recommendations for universal adult vaccination with Tdap are not reaching the general public in Canada and an alternative strategy will be required to improve Tdap vaccine uptake.     

Hospital admissions for pertussis in Spain, 1995-1998

This epidemiological survey was undertaken to estimate the annual burden of hospitalizations for pertussis in Spain during a four-year period 1995–1998. Data were obtained from the national surveillance system for hospital data. All hospital discharges for pertussis (ICD-9- CM 033) were analyzed. The annual incidence of hospitalization for pertussis was 1.7 per 100,000 population. Eighty-nine percent of the cases were <1 year of age (incidence of 78 per 100,000) and 95% were ≤5 years of age (incidence of 28 per 100,000). During the study period, 14 deaths were reported among patients hospitalized by pertussis. Despite of the high inmunization rates, many pertussis cases occur each year, mostly of them among very young children.     

Durability of protection after 5 doses of acellular pertussis vaccine among 5–9 year old children in King County,Washington

PurposeWaning of immunity after vaccination with the acellular Pertussis (aP) vaccine has been proposed as one of the main reasons for pertussis resurgence in the US. In this study, we estimated time-varying vaccine effectiveness after 5 doses of aP vaccine.MethodsWe conducted a retrospective cohort study among children 5–9 years old (born between 2008 and 2012) living in King County, Washington, USA, who participated in the Washington State Immunization Information System. We estimated time-varying vaccine effectiveness after 5 doses of aP using smoothed scaled Schoenfeld residuals obtained from fitting Cox proportional hazards models to the data as well as piecewise constant Poisson regression.ResultsThere were 55 pertussis cases in this cohort, of whom 22 (40%) were fully-vaccinated and 33 (60%) were under-vaccinated. Vaccine effectiveness (VE) remained high for up to 42 months after the fifth dose (VE(t) = 89%; 95% CI: 64%, 97%) as estimated using survival analysis methods and up to 4 years (VE(t) = 93%; 95% CI: 67%, 98%) as estimated using Poisson regression.ConclusionWe did not find evidence for waning of vaccine effectiveness for up to four years after 5 doses of aP among 5 –9 years old children in King County, WA.     

Announcing the publication of the WHO immunological basis for immunization series module on pertussis vaccines

In 2017, the World Health Organization (WHO) published an updated document aimed at facilitating the understanding of the immunological basis of pertussis vaccines and their use. The document “The Immunological Basis for Immunization Series: Pertussis Vaccines” is freely available on the WHO website. The main purpose of the module is to provide national immunization managers and vaccination professionals with an overview of the scientific basis of vaccination against pertussis and the immunological basis for the WHO position on pertussis vaccines.The Immunological Basis for Immunization Series was initially developed in 1993. Since then the series was regularly updated and extended. They reflect the biological differences in immune responses to the individual pathogens and the differing strategies employed to create the best possible level of protection that can be provided by vaccination.We invite the immunization community to use these references, and we hope the updated pertussis vaccine module will be a valuable resource.     

Inequalities in the transition of cerebrovascular disease mortality in New South Wales, Australia 1969-1996

With reference to epidemiological transition theory, this paper examines change in cerebrovascular disease mortality in Australia's most populous state in the 28 year period, 1969-1996. The hypotheses were that in the context of overall stroke mortality decline over the period, marital status, occupational status and spatial differences decreased. However, while overall mortality declined, differentials increased. The reasons for this are considered, with particular implications for epidemiological transition theory and for the targeting of populations at risk in policy terms.     

Reporter cell lines for detection of pertussis toxin in acellular pertussis vaccines as a functional animal-free alternative to the in vivo histamine sensitization test

Detoxified pertussis toxin (pertussis toxoid) is a major antigen in acellular pertussis vaccines. Testing these vaccines on the presence of residual pertussis toxin (PTx) and reversion to toxicity is performed by the regulatory required in vivo Histamine Sensitization test (HIST). Lack of mechanistic understanding of the HIST, technical handicaps and animal welfare concerns, have promoted the development of alternative methods. As the majority of the cellular effects of PTx depend on its ability to activate intracellular pathways involving cAMP, the in vitro cAMP-PTx assay was developed. Although this assay could be used to detect PTx activity, it lacked sensitivity and robustness for use in a quality control setting. In the present study, novel reporter cell lines (CHO-CRE and A10-CRE) were generated that stably express a reporter construct responsive to changes in intracellular cAMP levels. These reporter cell lines were able to detect PTx in a concentration-dependent manner when combined with fixed amounts of forskolin. The CHO-CRE cell line enabled detection of PTx in the context of a multivalent vaccine containing aP, with a sensitivity equal to the HIST. However, the sensitivity of the A10-CRE cells was insufficient for this purpose. The experiments also suggest that the CHO-CRE reporter cell line might be suitable for assessment of cellular effects of PTd reverted to PTx. The CHO-CRE reporter cell line provides a platform that meets the criteria for specificity and sensitivity and is a promising in vitro model with potential to replace the HIST.     

Age-related differences in antibody avidities to pertussis toxin and filamentous hemagglutinin in a healthy Japanese population

To gain insights into the current Japanese pertussis immunization schedule, we examined the distributions of antibody titers and avidities to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in 460 Japanese healthy subjects (aged 1–60?years) based on age category. Our avidity enzyme-linked immunosorbent assays revealed that young children aged 1–2?years, which corresponded to ages after receiving primary and/or booster pertussis vaccinations, had relatively high-avidity anti-PT IgG (mean avidity index [AI], 40.5%) compared with other age groups (AI, 26.5–31.9%); however, they had relatively low-avidity anti-FHA IgG (AI, 41.8%). In contrast, children aged 3–6?years had both low-avidity anti-PT IgG (AI, 26.5%) and low-avidity anti-FHA IgG (AI, 40.4%). A significant age-related difference in anti-PT IgG avidity was observed between children aged 1–2?years and 3–6?years (P?<?0.05); however, the difference in anti-FHA IgG avidity was not significant. The anti-PT IgG avidity was positively correlated with the antibody titer, especially among children aged 1–15?years (r_s?=?0.508–0.685; P?<?0.01), indicating that the avidity of vaccine-induced anti-PT IgG decreases with decreasing IgG antibody titer to PT. Our findings strongly suggest that vaccine-induced anti-PT IgG avidity rapidly wanes after vaccination, but this is not observed for anti-FHA IgG avidity. Because children aged 3–6?years have both low-quantity and low-quality antibodies against PT, an additional booster vaccination with acellular pertussis vaccines is required for such children in Japan.     

Effectiveness of the whole-cell pertussis vaccine produced in Poland against different Bordetella parapertussis isolates in the mouse intranasal challenge model

The aim of the study was to evaluate the effectiveness of the whole-cell pertussis vaccine produced locally and routinely used in Poland in the elimination of Bordetella parapertussis strains from the lungs and trachea of a mouse model. We found that the average protective effect against B. parapertussis in the lungs of mice immunized with the whole-cell pertussis vaccine (DTwP) was significantly higher than in animals immunized with the acellular pertussis vaccine (DTaP). The effectiveness of B. parapertussis elimination rates from the lungs of DTwP-immunized mice, depending on the strain used as a challenge, was found to be 1.2-3.0 times or 3.1-7.0 times lower than against Bordetella. pertussis Tohama I or vaccine B. pertussis 606/67 isolates, respectively. Our results show that the locally produced DTwP vaccine is able to protect against B. parapertussis isolates; however, the level of protection and course of B. parapertussis infection in the lungs and trachea seems to be strain specific.     

Cost-effectiveness of pertussis booster vaccination in the Netherlands

The aim of the current study is to estimate the epidemiological and economical consequences of several extended pertussis booster vaccination strategies and to explore the impact of parameters surrounded by large uncertainty on the cost-effectiveness.