The impact of childhood varicella vaccination on the incidence of herpes zoster in the general population: modelling the effect of exogenous and endogenous varicella-zoster virus immunity boosting.

BACKGROUND: A controversy exists about the potential effect of childhood varicella vaccination on Herpes Zoster (HZ) incidence. Mathematical models projected temporary HZ incidence increase after vaccine introduction that was not confirmed by real-world evidence. These models assume that absence of contacts with infected children would prevent exogenous boosting of Varicella-Zoster-Virus (VZV) immunity and they do not include an endogenous VZV immunity-boosting mechanism following asymptomatic VZV reactivation. This study aims to explore the effect of various assumptions on exogenous and endogenous VZV immunity-boosting on HZ incidence in the general population after introduction of routine childhood varicella vaccination. METHODS: An age-structured dynamic transmission model was adapted and fitted to the seroprevalence of varicella in France in absence of vaccination using the empirical contact matrix. A two-dose childhood varicella vaccination schedule was introduced at 12 and 18 months. Vaccine efficacy was assumed at 65%/95% (dose 1/dose 2), and coverage at 90%/80% (dose 1/dose 2). Exogenous boosting intensity was based on assumptions regarding HZ-immunity duration, age-dependent boosting effect, and HZ reactivation rates fitted to observed HZ incidence. Endogenous boosting was the same as pre-vaccination exogenous boosting but constant over time, whilst exogenous boosting depended on the force of infection. Five scenarios were tested with different weightings of exogenous (Exo) - endogenous (Endo) boosting: 100%Exo-0%Endo, 75%Exo-25%Endo, 50%Exo-50%Endo, 25%Exo-75%Endo, 0%Exo-100%Endo. RESULTS: HZ incidence before varicella vaccination, all ages combined, was estimated at 3.96 per 1000 person-years; it decreased by 64% by year 80 post vaccine introduction, for all boosting assumptions. The 100%Exo-0%Endo boosting scenario, predicted an increase in HZ incidence for the first 21 years post vaccine introduction with a maximum increase of 3.7% (4.1/1000) at year 9. However, with 0%Exo-100%Endo boosting scenario an immediate HZ decline was projected. The maximum HZ incidence increases at 10, 3, and 2 years post vaccination were 1.8% (75%Exo-25%Endo), 0.8% (50%Exo-50%Endo) and 0.2% (25%Exo-75%Endo), respectively. CONCLUSIONS: Assuming modest levels of endogenous boosting, the increase in HZ incidence following childhood varicella vaccination was smaller and lasted for a shorter period compared with 100%Exo-0%Endo boosting assumption. Endogenous boosting mechanism could partly explain the divergence between previous HZ-incidence projections and real-world evidence.

Women and vaccinations: From smallpox to the future, a tribute to a partnership benefiting humanity for over 200 years.

Vaccines were first developed in England over 200 years ago and have made a significant positive impact on human society since. Not often realized is the intimate relationship shared between vaccines and women. Women were key to the initial development of vaccines; some were even advocating the concept of protection against infectious disease through prior asymptomatic infection (by variolation) before the publication of the report of the first successful smallpox vaccination in 1798. Since that milestone, women have been important partners in the development of vaccines and advocates for their widespread introduction. Modern vaccine development would not be possible without the altruistic informed consent granted by many women for the participation of themselves or their children in vaccine clinical trials all over the world. Vaccines have rewarded women handsomely in return. Individual women benefit in many ways ranging from safer pregnancies to preventing cancers to attractive, unblemished skin. Some vaccines are even specifically designed to prevent diseases primarily affecting women such as cervical cancer. Vaccines also have offered societal benefits to women. These include better maternal health and fostering an environment more amenable to effective family planning. With these advances, women become more empowered and have access to better economic opportunities. The challenge of meeting the millennium development goals specifically targeted for women will be facilitated by vaccines. A better realization by women of the benefits of this partnership secured over the past 200 years will enable them to reap fully the rewards of the future.

Anaphylaxis following quadrivalent human papillomavirus vaccination.

BACKGROUND: In 2007, Australia implemented the National human papillomavirus (HPV) Vaccination Program, which provides quadrivalent HPV vaccine free to all women aged 12-26 years. Following notification of 7 presumptive cases of anaphylaxis in the state of New South Wales, Australia, we verified cases and compared the incidence of anaphylaxis following HPV vaccination to other vaccines in comparable settings. METHODS: We contacted all patients with suspected anaphylaxis and obtained detailed histories from telephone interviews and a review of medical records. A multidisciplinary team determined whether each suspected case met the standardized Brighton definition. Some participants also received skin-prick allergy testing for common antigens and components of the HPV vaccine. RESULTS: Of 12 suspected cases, 8 were classified as anaphylaxis. Of these, 4 participants had negative skin-prick test results for intradermal Gardasil. From the 269 680 HPV vaccine doses administered in schools, 7 cases of anaphylaxis were identified, which represents an incidence rate of 2.6 per 100 000 doses (95% CI 1.0-5.3 per 100 000). In comparison, the rate of identified anaphylaxis was 0.1 per 100 000 doses (95% CI 0.003-0.7) for conjugated meningococcal C vaccination in a 2003 school-based program. INTERPRETATION: Based on the number of confirmed cases, the estimated rate of anaphylaxis following quadrivalent HPV vaccine was significantly higher than identified in comparable school-based delivery of other vaccines. However, overall rates were very low and managed appropriately with no serious sequelae.

Compulsory vaccination and conscientious or philosophical exemptions: past, present, and future.

Compulsory vaccination has contributed to the success of immunisation programmes in the USA and Australia, yet the benefits from compulsory vaccination are not universally recognised. Some people--experts and the public alike--believe that the benefits of compulsory vaccination are outweighed by the associated ethical problems. A review of vaccination legislation in the UK, Australia, and the USA raises four main points. First, compulsory vaccination may be effective in preventing disease outbreaks, reaching and sustaining high immunisation coverage rates, and expediting the introduction of new vaccines. Second, to be effective, compulsory programmes must have a reliable supply of safe and effective vaccines and most people must be willing to be vaccinated. Third, allowance of exemptions to compulsory vaccination may limit public backlash. Finally, compulsory vaccination may increase the burden on governments to ensure the safety of vaccines. Nevertheless, although compulsory immunisation can be very effective, it might not be acceptable in some countries where high coverage has been achieved through other approaches or efforts, such as in Sweden, Norway, Denmark, the Netherlands, and the UK. These factors should be considered when compulsory vaccinations are being introduced or immunisation laws refined. Lessons learned from compulsory vaccination could be useful to other public-health programmes.

Modelling the impact of vaccination on the epidemiology of varicella zoster virus in Australia.

OBJECTIVE: To model the impact of universal varicella vaccination in Australia. METHODS: The results of an Australia-wide serosurvey for varicella zoster virus (VZV) immunity were used to parameterise realistic, age-structured deterministic models (RAS) developed by Brisson and colleagues. We examined the impact of a vaccination program for one-year-olds alone, and with a catch-up campaign for 11-year-olds, on the incidence of varicella and zoster, using Australia's population structure. Morbidity was then determined by calculating the number of hospital in-patient days. RESULTS: Infant vaccination is predicted to reduce the incidence of varicella. However, zoster incidence is expected to increase initially, assuming exposure to varicella boosts immunity to zoster. Accumulated morbidity from both varicella and zoster is predicted to remain above that expected without vaccination for the first 70 years of an infant program (assuming 90% coverage with boosting for 20 years). However, after 70 years the net health savings from vaccination are predicted to increase substantially. CONCLUSIONS AND IMPLICATIONS: Infant vaccination is expected to be a successful long-term commitment to reducing morbidity associated with VZV infection in Australia.

Prevalence and determinants of influenza vaccination in Australians aged 40 years and over--a national survey.

OBJECTIVES: To determine influenza vaccination coverage in 2001 in Australian adults aged > or = 40 years, assess awareness of and attitudes to influenza vaccine, factors associated with vaccination, and estimate uptake of free vaccine provided to those aged > or = 65 years. METHODS: National computer-assisted telephone interview (CATI) survey in October/November 2001. RESULTS: Interviews were completed with 5,266 people aged > or = 65 and 2,415 aged 40-64 years. Thirty per cent of selected households participated. Overall, 67% of respondents believed that the vaccine was somewhat to very effective in preventing influenza. Seventy-eight per cent of those aged > or = 65 years reported influenza vaccination; 89% had received it free. Independent predictors of vaccination were: belief that influenza vaccine is effective in preventing influenza (OR=13.5, 95% CI 10.6-17.2); and the presence of chronic disease (OR=1.6, 95% CI 1.3-2.0). Overall, 24% of those aged 40-64 years were vaccinated; only 34% of those who met any of the criteria for vaccination (medical risk factor, at-risk occupation, or being Aboriginal or Torres Strait Islander) reported vaccination. CONCLUSIONS: Influenza vaccine coverage was high in those aged > or = 65 years, but coverage of those at-risk aged 40-64 years remained suboptimal. Immunisation against influenza was influenced more by beliefs about the vaccine's effectiveness and existing medical risk factors, rather than socio-demographic factors such as gender and income.

National serosurvey of poliovirus immunity in Australia, 1996-99.

OBJECTIVE: To measure immunity to poliovirus types 1, 2 and 3 in the Australian population. METHODS: Sera were collected opportunistically from laboratories around Australia between 1996 and 1999. A representative sample by age and gender was tested for neutralising antibodies to poliovirus types 1, 2 and 3. A titre of > or = 8 was considered antibody positive and indicative of immunity. RESULTS: Of the 1,813 sera tested, 82% were antibody positive for poliovirus type 1 and 88% were positive for type 2. Immunity to type 3 poliovirus was lower overall (74%) and especially in school-aged children and young adults. For all three poliovirus types, there were more females immune than males and immunity peaked in the 2-4 years age group. The proportion of the population immune to all three types was 59%, and 3% were negative for all three types. CONCLUSIONS AND IMPLICATIONS: This is the first national serosurvey for immunity to poliovirus in Australia. Herd immunity is probably sufficient to prevent generalised outbreaks due to type 1 and 2 poliovirus, but this may not be the case for type 3. However, localised outbreaks of any poliovirus type could still occur following reintroduction unless uniformly high levels of vaccination coverage are maintained. Ongoing serosurveillance is required following the recent change back to inactivated polio vaccine.

Models of strategies for control of rubella and congenital rubella syndrome-a 40 year experience from Australia.

We investigated the impact of vaccination on rubella epidemiology in Australia, using a mathematical model fitted to Australian serosurvey data and incorporating pre-vaccination European estimates of rubella transmissibility. Mass infant measles-mumps-rubella (MMR) vaccination produced a 99% reduction in both rubella and congenital rubella syndrome (CRS) incidence by 2010 compared to the pre-vaccination era (1960-70). The model is consistent with reductions in CRS based on surveillance of congenital hearing impairment. Model simulations suggest that selective schoolgirl vaccination (1971-88) was associated with a 90% reduction in CRS incidence, but only a 1-4% reduction in rubella incidence. Our model predicted that these reductions in rubella were much less vulnerable to reductions in MMR vaccine coverage than for measles. In the future, a less than 15% decrease in MMR vaccine coverage is estimated to have minimal impact before 2060, but a 20% reduction may result in a 7-fold increase in rubella incidence, with the effective reproductive number R rising from 0.28 to 0.78 by 2060. The 99% reduction in both rubella and CRS incidence and low effective reproductive number (R≤0.28) we documented after 2010 are consistent with Australia having achieved rubella elimination.

Antibody persistence six years after two doses of combined hepatitis A and B vaccine.

Persistent immunity to hepatitis A and hepatitis B antibodies six years after vaccination of adolescents (aged 12-15 years) with a combined hepatitis A and B (HAB) vaccine following a 0, 6 month or a 0, 12 month schedule was assessed. Yearly (Year-2-6) serum samples were tested for anti-HAV and anti-HBs using EIA. Subjects with anti-HBs concentrations <10 mIU/mL (14/23) at Year-5 or Year-6, received an additional HBV vaccine dose approximately 12 months after Year-6. Blood samples were collected pre-booster and 1 month post-booster to assess booster response. 240 subjects were vaccinated in the study; at Year-6, data were available from 88 subjects. At that time 84.8% (39/46; 0, 6 month) and 92.9% (39/42; 0, 12 month) of subjects had anti-HBs concentrations > or = 10 mIU/mL. All but one of the 14 boosted subjects responded to the additional HBV vaccine dose with anti-HBs concentrations > or = 100 mIU/mL. All seroconverted subjects who returned at Year-6 were seropositive for anti-HAV. Simplification, reduced number of doses and similar long-term persistence of immunity make the 0, 6 month and 0, 12 month schedule preferable for immunization against HAV/HBV in this population.

Rapid impact of rotavirus vaccination in the United States: implications for Australia.

Australia is in a unique position to assess the impact of two different rotavirus vaccines.

Booster vaccination of adults with reduced-antigen-content diphtheria, Tetanus and pertussis vaccine: immunogenicity 5 years post-vaccination.

At 60 months post-vaccination, adults (mean age 45.6 years) randomised to receive combined reduced-antigen-content diphtheria-tetanus and acellular pertussis vaccine (dTpa) versus tetanus-diphtheria (Td)+monovalent acellular pertussis (pa) were seroprotected against diphtheria (> or =0.016IU/mL Vero cell assay) and tetanus (> or =0.1IU/mL ELISA assay) in 94.4% and 96.2%, respectively (dTpa), compared with 93.7% and 90.6% (Td+pa). Anti-FHA, anti-PT and anti-PRN antibodies (> or =5EL.U/mL) were maintained in 100%, 89.5% and 95.0% of dTpa versus 100%, 85.5% and 90.6% of pa vaccine recipients. At 5 years post boosting, antibody levels to diphtheria and tetanus are similar amongst adults receiving a dTpa or dT, and pertussis antibodies remain above pre-booster levels in at least 85%.

Varicella vaccination in Australia and New Zealand.

Varicella-zoster virus has been responsible for a significant disease burden, including hospitalizations and deaths in Australia and New Zealand. Varicella vaccine has been available in Australia since 1999 and, since November 2005, has been funded under the National Immunisation Program for use in all children as a single dose at 18 months of age and in a school-based catch-up program at 10-13 years of age. Recent hospitalization data from Australia show a decline in varicella hospitalizations in children 1-4 years of age, most likely related to vaccination. In New Zealand, varicella vaccine has been available since 1999 but is currently not recommended or funded on the New Zealand national immunization schedule. The anticipated licensure of combination measles-mumps-rubella-varicella vaccines in both countries may lead to future schedule changes.

The MMR vaccination and autism controversy in United Kingdom 1998-2005: inevitable community outrage or a failure of risk communication?

BACKGROUND: The report of an hypothesised link between measles-mumps-rubella (MMR) vaccination and autism in 1998 became a major public health issue in the United Kingdom (UK), leaving most experts surprised by the overwhelming influence it had on public opinion about MMR vaccination. Coverage rates fell dramatically, and did not start to recover until 2004. Could this public reaction have been predicted? METHODS: We used Sandman's model of components predicting community outrage to assess the MMR controversy. RESULTS: The controversy fulfilled all of Sandman's 12 primary components and six of the eight additional components. CONCLUSIONS: The Sandman model provided a useful framework to analyse this controversy and explained a significant portion of the community reaction and subsequent fall in vaccination coverage rates.

Probability of coincident vaccination in the 24 or 48 hours preceding sudden infant death syndrome death in Australia.

OBJECTIVE: Vaccination does not cause sudden infant death syndrome (SIDS). However, SIDS peaks at 2 months of age, when vaccination encounters are frequent. There are no published estimates using population data on age of death and immunization coverage to indicate to practitioners how often coincident vaccination may occur by chance. This study aimed to determine the probability that an Australian infant who has died of SIDS was vaccinated in the days before death. METHODS: An analytical study of population death data and immunization coverage was conducted for Australian children who were born between April 1, 2002, and March 31, 2003. Also evaluated were Australian children who were registered as dying of SIDS between 1997 and 2001. The main outcomes measured were distribution of SIDS deaths by age and distribution of immunization coverage by age. RESULTS: The probability of recent vaccination and SIDS coinciding varied by age and day of the week of death. The overall estimated probability of vaccination within the last 24 hours for a child who has died of SIDS in Australia is estimated as 1.3%. In the last 48 hours, it is 2.6%. With the average number of SIDS deaths for the period 1997-2001 equal to 130 cases per year, we estimated that a case of SIDS will occur when vaccination was given in the last 24 hours in 1.7 cases per year and within 48 hours in 3.5 cases. CONCLUSIONS: Although coincident vaccination and SIDS should not be a frequent problem, it can be expected to occur at least annually in Australia by chance alone. The probabilities of vaccination by age estimated in this study can also be applied to estimate the probability of a vaccination encounter for children who have experienced any unusual medical condition or death, when these occurrences are known to be unrelated to vaccination.

Immunity to diphtheria and tetanus in Australia: a national serosurvey.

OBJECTIVE: To determine immunity to tetanus and diphtheria in the Australian population. DESIGN AND SETTING: Analysis, using double antigen enzyme immunoassays, of a representative sample of sera (1950 samples tested for diphtheria and 2884 for tetanus) collected opportunistically from Australian laboratories between July 1996 and May 1999. MAIN OUTCOME MEASURE: Immunity to diphtheria and tetanus, defined as negative (susceptible) when the antitoxin level was < 0.01 IU/mL, positive (immune) when it was > or = 0.1 IU/mL, and low positive (partially immune) when it was in the range 0.01-< 0.1 IU/mL. RESULTS: About 99% of children aged 5-9 years had diphtheria and tetanus antitoxin levels > or = 0.01 IU/mL (immune or partially immune). Antitoxin levels declined with age and generally more markedly for diphtheria than tetanus. For subjects aged 50 years and over, less than 60% were immune or partially immune to diphtheria and less than 75% to tetanus. Men and women had similar diphtheria antitoxin levels, while women had lower levels of tetanus antitoxin compared with men of the same age, with the difference being most marked in the age group > or = 70 years (37% v 60%; P < 0.001). CONCLUSIONS: Immunity in children appears to be good, but adults, especially older people, may not be adequately protected. Recent changes to the Australian Standard Vaccination Schedule should improve immunity in cohorts now aged < 50 years. However, additional efforts are required to protect those over 50 years (especially travellers), who are most susceptible.

Age-related risk of adverse events following yellow fever vaccination in Australia.

Reports of six deaths internationally, including one from Australia, plus other cases of severe systemic adverse events following yellow fever (YF) vaccination have raised concern about the safety of YF vaccine, particularly among older vaccinees. We investigated the age-related reporting rates of adverse events following YF vaccination reported to the Australian Adverse Drug Reactions Advisory Committee for the period 1993 to 2002. The reporting rate of systemic adverse events leading to hospitalisation or death was significantly higher among vaccinees aged > or = 65 years [reporting rate ratio (RRR) 8.95, 95% confidence interval (CI) 1.49-53.5] or > or = 45 years (RRR 5.30, 95% CI 1.33-21.2) compared with younger YF vaccinees. The higher reporting rates among older vaccinees are similar to those identified in the United States of America. The data highlight the importance of assessing the destination-specific risk, especially for older travellers to yellow fever endemic areas, and careful monitoring of those who are vaccinated.

High levels of antibody in adults three years after vaccination with a reduced antigen content diphtheria-tetanus-acellular pertussis vaccine.

There is increasing interest in prevention of pertussis in adults by vaccination, but little is known about the duration of the antibody response to pertussis, diphtheria or tetanus in reduced antigen content vaccines formulated for adult use. Follow-up of a clinical trial including 550 adults comparing responses to reduced antigen content diphtheria-tetanus-acellular pertussis (dTpa) vaccine, or a licensed Td vaccine, provided the opportunity to evaluate this. Blood samples were collected at 0, 1, 12, 24 and 36 months following vaccination; of the original cohort of 550, 387 subjects (dTpa group N=310, Td+pa group N=77) were tested at month 36. Following a decrease in antibody levels against all vaccine antigens between one and 24 months following vaccination, levels stabilized during the third year, remaining higher at 36 months than pre-vaccination for all vaccine antigens. In particular, more than 90% of subjects remained seropositive for pertussis toxin and pertactin antibodies at 36 months after vaccination, suggesting ongoing protection against pertussis. Adult-formulated dTpa vaccines could replace Td for routine booster vaccination of older individuals.

Influenza A associated morbidity and mortality in a Paediatric Intensive Care Unit.

This paper reports the clinical features and outcome of all children with a laboratory proven diagnosis of influenza A virus infection admitted to a major Paediatric Intensive Care Unit (PICU) in 2003. Eight of the 22 patients with influenza A virus infection (A/Fujian/411/2002-like type) presented with encephalopathy and three of the 22 patients died. This can be compared with 44 admissions and seven (16%) deaths of patients with influenza virus admitted in the same PICU in the preceding 15 years. In the present cohort, four (18%) of the 22 patients, including one child who died, should have received influenza vaccine according to the current Australian immunisation recommendations. We have no documented evidence that any of the 22 children received influenza vaccination. During the 2003 influenza season there was an increased number of children admitted to our PICU with influenza A infection and an increased number of deaths compared with previous years. Influenza infection causes significant morbidity and mortality in young children, most of whom are not currently recommended for annual influenza vaccination.