[Show abstract][Hide abstract] ABSTRACT: Introduction: Vaccines in pregnancy can minimise diseases with associated high morbidity and mortality in pregnant women, their unborn and newly born infants. Immunisations against influenza and pertussis are routinely offered in pregnancy in a number of countries including the UK, US, Australia and Belgium, but vaccine uptake could be improved. Methods: In January 2013, an online survey of pregnant women and women with children under 2 years of age was undertaken. The survey focused on vaccination in pregnancy. Results and conclusions: Of 1892 respondents, the majority indicated they definitely, or probably, would accept a nationally-approved vaccine offered by their midwife or GP during pregnancy for their own protection (94%) and/or to protect their baby when it was born (96%). Vaccine safety for the baby and for the woman, vaccine effectiveness and perceived seriousness of the disease remain key considerations for women. Health professionals, midwives in particular, are pivotal in informing women, promoting the vaccine and discussing concerns.
British Journal of Midwifery 08/2015; 23(8):566-573. DOI:10.12968/bjom.2015.23.8.566
[Show abstract][Hide abstract] ABSTRACT: Stefan Flasche and colleagues consider whether the number of PCV doses in the infant schedule could be reduced without compromising its public health benefit in high-income settings.
PLoS Medicine 06/2015; 12(6):e1001839. DOI:10.1371/journal.pmed.1001839 · 14.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In 2011-2012 a large pertussis outbreak occurred in England. This provided an opportunity to estimate the disease burden in those aged 5 years and over. As pertussis is likely to be under reported both laboratory-confirmed and non-confirmed cases were included.
Laboratory-confirmed cases of pertussis, as well as their coughing but non-confirmed household members, were sent a questionnaire that collected information on clinical features and quality of life for the most severe day of disease and the day the patient filled in the questionnaire. The EuroQol-5 dimension questionnaire (EQ-5D) was used to evaluate quality of life. The duration of symptoms was obtained by contacting the patient every two weeks until symptoms stopped.
Data for 535 (out of 1262) laboratory confirmed pertussis patients and 44 (out of 140) coughing household contacts was available for analysis. On the most severe day, 56% of laboratory-confirmed cases reported they had 20+ more paroxysms, 58% reported they had a severe cough and 46% reported disruption of sleep for more than 4 hours. For non-confirmed coughing household contacts there were a similar number of coughing spells per day at the height, though the cough was reported to be less severe and to cause less sleep disruption. The main clinical symptoms on the worst day for both were shortness of breath, tiredness, sore ribs and vomiting. The duration of symptoms for both patient groups was around 160 days (162 and 168 days). Under base case assumptions the overall loss of quality of life was 0.097 QALY (0.089-0.106) for confirmed pertussis cases and 0.0365 QALY (0.023-0.054) for coughing household contacts.
Pertussis is a serious disease in those aged 5 years and over, causing disruption of sleep and daily activities over long period of time. The burden of illness due to undiagnosed pertussis is also considerable.
PLoS ONE 11/2014; 9(11):e111807. DOI:10.1371/journal.pone.0111807 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Measles is a highly contagious and potentially fatal illness preventable through vaccination. Outbreaks in the UK and many other European countries have been increasing over recent years, with over 3,207 laboratory-confirmed cases reported by Public Health England from January 2012 to the end of June 2013. To aid rational decision making regarding measles control versus other use of healthcare resources, it is important to measure the severity of measles in units that are comparable to other diseases. The standard metric for this in the UK is the quality-adjust life year (QALY). To our knowledge, the impact of measles on health-related quality of life (HRQoL) in terms of QALYs has not been quantified.
Methods and Findings
Individuals with confirmed measles were sent questionnaires requesting information on the short-term impact of the illness on their HRQoL using the EuroQol EQ-5D-3L questionnaire. HRQoL was reported for the day the questionnaire was received, the worst day of infection and at follow-up three weeks later. 507 questionnaires were sent to individuals with confirmed measles with 203 returned (40%). The majority of respondents were not vaccinated. The mean time off work or school was 9.6 days. The mean duration of perceived illness was 13.8 days. The mean number of QALYs lost was 0.019 (equivalent to 6.9 days). The overall burden of disease in terms of QALYs lost in England based on the total number of confirmed cases in the twelve month period from 1st June 2012 was estimated to be 44.2 QALYs.
The short-term impact of measles infection on HRQoL is substantial, both at the level of the individual patient and in terms of the overall disease burden. This is the first attempt to quantify QALY-loss due to measles at a population level, and provides important parameters to guide future intervention and control measures.
PLoS ONE 09/2014; 9(9):e105153. DOI:10.1371/journal.pone.0105153 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In April 2010 the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 13-valent PCV. We investigated pneumococcal carriage in children eligible for PCV7 or PCV13 and their household contacts.
Eligible families in Hertfordshire and Gloucester were identified and a nasopharyngeal swab obtained from consenting household members between July 2012 and March 2013. Samples were cultured for Streptococcus pneumoniae and serotyped by standard methods. For each serotype the ratio of its prevalence in invasive pneumococcal disease (IPD) to its carriage prevalence (case:carrier ratio, CCR) was calculated. Results were compared with previous carriage studies in 2001/2002 and 2008/2009, before and after PCV7 introduction.
217 households were included. Among <5-year olds 47.7% (95% confidence interval 41.8-53.5) were carrying a pneumococcus compared with 51.0% (95% CI: 44.0-58.0) in 2008/2009 and 48.4% (95% CI: 44.1-52.7) in 2001/2002. The odds of carrying a PCV7 serotype was significantly reduced in 2008/2009 (0.07, 95% CI: 0.03-0.16) and 2012/2013 (0.01 95% CI: 0.00-0.07) relative to 2001/2002, while the odds of carrying any of the extra six PCV13 serotypes increased after PCV7 introduction (1.38, 95%CI: 0.73-2.59) but declined significantly after PCV13 introduction (0.05, 95%CI: 0.01-0.37). The CCRs for the frequently carried serotypes were relatively low, with the highest CCR observed for serotypes 7F, 19A, 3, 8, and 33F. Across the three carriage studies, CCR estimates were stable for nearly all serotypes.
Carriage of additional PCV13 serotypes has rapidly reduced post-PCV13 introduction in both vaccinated and unvaccinated individuals with a continued decline in transmission of PCV7 serotypes. Carriage rates in children remain unchanged, but the low CCRs of replacing serotypes would be expected to further reduce overall IPD across all age groups.
[Show abstract][Hide abstract] ABSTRACT: To assess the burden of influenza by age and clinical status and use this to inform evaluations of the age and risk-based influenza vaccination policy in the United Kingdom.
Weekly laboratory reports for influenza and 7 other respiratory pathogens were extracted from the national database and used in a regression model to estimate the proportion of acute respiratory illness outcomes attributable to each pathogen.
Influenza accounted for ∼10% of the attributed respiratory admissions and deaths in hospital. Healthy children under five had the highest influenza admission rate (1.9/1,000). The presence of co-morbidities increased the admission rate by 5.7 fold for 5-14 year olds (from 0.1 to 0.56/1000), the relative risk declining to 1.8 fold in 65+ year olds (from .46 to .84/1000). The majority (72%) of influenza-attributable deaths in hospital occurred in 65+ year olds with co-morbidities. Mortality in children under 15 years was low with around 12 influenza-attributable deaths in hospital per year in England; the case fatality rate was substantially higher in risk than non-risk children. Infants under 6 months had the highest consultation and admission rates, around 70/1000 and 3/1000 respectively.
Additional strategies are needed to reduce the remaining morbidity and mortality in the high-risk and elderly populations, and to protect healthy children currently not offered the benefits of vaccination.
The Journal of infection 11/2013; 68(4). DOI:10.1016/j.jinf.2013.11.013 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Insight into how humans interact helps further understanding of the transmission of infectious diseases. For diseases such as pertussis, infants are at particular risk for severe outcomes. To understand the contact pattern of infants, especially those too young to be vaccinated, we sent contact diaries to a representative sample of 1000 mothers in the United Kingdom. We received 115 responses with a total of 758 recorded contacts. The average number of daily contacts for an infant was 6.68 overall and 5.7 for those aged ≤10 weeks. Of the latter, 2.1 (37%) contacts were with non-household members and were >15 minutes duration, suggesting that a cocooning programme may miss a substantial proportion of exposures leading to disease transmission. The least contact was between adolescents and infants. Thus the impact of adolescent (pertussis) vaccination on infants would likely be limited, unless it reduces transmission to other age groups whose contact with infants is greater.
PLoS ONE 10/2013; 8(10):e76180. DOI:10.1371/journal.pone.0076180 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the UK, primary varicella is usually a mild infection in children, but can cause serious illness in susceptible pregnant women and adults. The UK Joint Committee on Vaccination and Immunisation is considering an adolescent varicella vaccination programme. Cost-effectiveness depends upon identifying susceptibles and minimising vaccine wastage, and chickenpox history is one method to screen for eligibility. To inform this approach, we estimated the proportion of adolescents with varicella antibodies by reported chickenpox history.
[Show abstract][Hide abstract] ABSTRACT: Aim:
To assess the effectiveness and cost-effectiveness of a universal childhood varicella-zoster vaccination programme in Belgium (1) using the most recent Belgian data on varicella-zoster burden, (2) exploring different options for the timing of the second dose, (3) obtaining results with and without exogenous natural boosting, and (4) investigating the possible additional benefit of zoster booster vaccination for adults at age 50 or 60 y.
An extensively studied and improved dynamic model is used to estimate primary and breakthrough chickenpox and zoster cases over time. For a range of vaccination options, we compared the direct costs (health care payer perspective) and health outcomes (including Quality-Adjusted Life-Years (QALYs) lost) associated with chickenpox and herpes zoster. Estimates of social contact patterns, health care use, costs and QALY losses are almost exclusively based on Belgian databases and surveys.
Results and conclusions:
If exogenous natural boosting exists, a net loss in QALYs is expected for several decades after implementing a universal chickenpox vaccination programme, due to an increase in zoster mainly in persons aged 50-80 y. This result holds also for scenarios that minimise or counteract the expected increase in zoster incidence (e.g. additional booster vaccinations in adults). However, if the boosting hypothesis is not true or if costs and QALYs are cumulated over at least 33 to more than 100 y after vaccination (depending on the assumptions made), different options for universal 2-dose vaccination against chickenpox in Belgium would be cost-effective at a vaccine price of €43/dose or lower.
[Show abstract][Hide abstract] ABSTRACT: Objective To estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine.
Design Economic evaluation using a cohort model from the perspective of healthcare providers.
Participants People aged 2 years and older at increased risk of invasive pneumococcal disease due to chronic kidney disease; splenic dysfunction; HIV infection; a compromised immune system; chronic heart, liver, or respiratory disease; or diabetes.
Main outcome measures Costs, gains in life years and quality adjusted life years (QALYs), and incremental cost effectiveness ratios.
Results Increasing indirect protection resulting from the vaccination programme of infants using the 13 valent pneumococcal conjugate vaccine means that the burden of disease preventable by targeting high risk groups will diminish in time. Under base case assumptions—that is, no overall impact on non bacteraemic pneumonia in high risk groups and assuming the high risk vaccination programme would be launched two to three years after the infant programme—the incremental cost effectiveness ratio was estimated to be more than £30 000 (€37 216; $48 210) per QALY gained for most risk groups. If, however, the vaccine does not offer protection against non-bacteraemic pneumococcal pneumonia or the vaccine was introduced concomitantly with the infant 13 valent pneumococcal conjugate vaccination programme then vaccinating high risk people would (more) likely be cost effective. Sensitivity analyses showed that the cost effectiveness was particularly sensitive to assumed herd benefits and vaccine efficacy estimates.
Conclusion Under base case assumptions it is unlikely that a pneumococcal vaccination programme aimed at risk groups could be considered cost effective. Uncertainty could be substantially reduced by establishing the effectiveness of the 13 valent pneumococcal conjugate vaccine against non-bacteraemic pneumococcal pneumonia, particularly in at risk groups.
[Show abstract][Hide abstract] ABSTRACT: Diarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination.
Cost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain.
The median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix.
Vaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability.
PLoS ONE 10/2012; 7(10):e47511. DOI:10.1371/journal.pone.0047511 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: In the immunisation schedule in England and Wales, the 7-valent pneumococcal conjugate vaccine (PCV-7) was replaced by the 13-valent vaccine (PCV-13) in April 2010 after having been used since September 2006. The introduction of PCV-7 was informed by a cost effectiveness analysis using an infectious disease model which projected herd immunity and serotype replacement effects based on the post-vaccine experience in the United States at that time. AIM: To investigate the cost effectiveness of the introduction of PCV-13. METHOD: Invasive disease incidence following vaccination was projected from a dynamic infectious disease model, and combined with serotype specific disease outcomes obtained from a large hospital dataset linked to laboratory confirmation of invasive pneumococcal disease. The economic impact of replacing PCV-7 with PCV-13 was compared to stopping the use of pneumococcal conjugate vaccination altogether. RESULTS: Discontinuing PCV-7 would lead to a projected increase in invasive pneumococcal disease, costs and loss of quality of life compared to the introduction of PCV-13. However under base case assumptions (assuming no impact on non-invasive disease, maximal competition between vaccine and non-vaccine types, time horizon of 30years, vaccine price of £49.60 a dose+£7.50 administration costs and discounting of costs and benefits at 3.5%) the introduction of PCV-13 is only borderline cost effective compared to a scenario of discontinuing of PCV-7. The intervention becomes more cost-effective when projected impact of non-invasive disease is included or the discount factor for benefits is reduced to 1.5%. CONCLUSION: To our knowledge this is the first evaluation of a transition from PCV-7 to PCV-13 based on a dynamic model. The cost-effectiveness of such a policy change depends on a number of crucial assumptions for which evidence is limited, particularly the impact of PCV-13 on non-invasive disease.
[Show abstract][Hide abstract] ABSTRACT: Differences in pathogenicity between pneumococcal serotypes are important when assessing the potential benefit of different valency vaccines. We investigated the effect of serotype on clinical presentation, outcome, and quality of life lost from invasive pneumococcal disease (IPD) in the context of the 7, 10, and 13 valent pneumococcal conjugate vaccines (PCV7, PCV10, PCV13).
Serotyped IPD cases in England were linked to the national dataset of hospital admissions for April 2002 to March 2011. Based on patients' diagnostic codes and vital status at the end of the admission, disease focus (meningitis, empyema, sepsis, or respiratory disease) and case fatality rates by serotype and age group (5, 5-64, and 65 years and over) were obtained. Using these data the quality adjusted life years (QALY) lost from the IPD remaining when use of PCV7 stopped in 2010 was estimated for the serotypes covered by higher valency vaccines.
The linked dataset contained 23,688 cases with information on diagnosis, mortality, and serotype. There were significant differences between serotypes in the propensity to cause meningitis, death, and QALY loss in each of the investigated age groups. As a result, vaccines' coverage of disease burden differed by endpoint. For example, in children under 5 years in 2009/10, PCV10 covered 39% of meningitis, 19% of deaths and 28% of the QALY loss of attributable to IPD, whereas the respective percentages for PCV13 were 65%, 67%, and 66%. The highest QALY loss per serotype in this age group was for 6A. Non-PCV serotypes causing the highest QALY loss were 22F and 33F in <5 year olds and 31 in older individuals.
Marked differences exist between serotypes in clinical presentation and outcome, and these should be considered when evaluating the potential impact of higher valency vaccines on overall disease burden and associated QALY loss.
PLoS ONE 07/2012; 7(7):e39150. DOI:10.1371/journal.pone.0039150 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To inform national policy making on the use of the 13-valent pneumococcal vaccine among risk groups we estimated the increased risk of invasive pneumococcal disease (IPD) outcomes among clinical risk groups. Three years of post 7-valent pneumococcal conjugate vaccine (PCV7) data was included to investigate the herd protection effects.
Over 22,000 IPD patients in England (March 2002-March 2009 - aged 2 and over) were linked to their hospitalisation records. The prevalence of risk factors in these patients was compared to the prevalence of risk factors in the general population.
There was an increased odds ratio (OR) for hospitalisation (OR 11.7 2-15 years; 7.6 16-64; 2.7 65+) and death (OR 2.4 2-15 years, 3.9 16-64, 1.2 65+) from IPD among risk group. The most important risk factors that predict IPD are chronic liver disease, immunosuppression, and chronic respiratory diseases. Herd protection effects due to introduction of the 7-valent vaccine were identical in both patient groups as shown by the similar decline in the proportion of IPD caused by PCV7 serotypes in risk and non-risk groups.
There is a marked increased risk of IPD among those with certain clinical conditions, suggesting potential benefit from a targeted vaccination approach. However, the indirect protection from conjugate vaccination of children suggests PCV vaccination of high-risk groups may not provide substantial additional benefit once herd immunity takes effect.
The Journal of infection 03/2012; 65(1):17-24. DOI:10.1016/j.jinf.2012.02.017 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite the existence of varicella vaccine, many developed countries have not introduced it into their national schedules, partly because of concerns about whether herpes zoster (HZ, shingles) will increase due to a lack of exogenous boosting. The magnitude of any increase in zoster that might occur is dependent on rates at which adults and children mix - something that has only recently been quantified - and could be reduced by simultaneously vaccinating older individuals against shingles. This study is the first to assess the cost-effectiveness of combined varicella and zoster vaccination options and compare this to alternative programmes.
[Show abstract][Hide abstract] ABSTRACT: Following the emergence of a novel strain of influenza A(H1N1) in Mexico and the United States in April 2009, its epidemiology in Europe during the summer was limited to sporadic and localised outbreaks. Only the United Kingdom experienced widespread transmission declining with school holidays in late July. Using statistical modelling where applicable we explored the following causes that could explain this surprising difference in transmission dynamics: extinction by chance, differences in the susceptibility profile, age distribution of the imported cases, differences in contact patterns, mitigation strategies, school holidays and weather patterns. No single factor was able to explain the differences sufficiently. Hence an additive mixed model was used to model the country-specific weekly estimates of the effective reproductive number using the extinction probability, school holidays and weather patterns as explanatory variables. The average extinction probability, its trend and the trend in absolute humidity were found to be significantly negatively correlated with the effective reproduction number - although they could only explain about 3% of the variability in the model. By comparing the initial epidemiology of influenza A (H1N1) across different European countries, our analysis was able to uncover a possible role for the timing of importations (extinction probability), mixing patterns and the absolute humidity as underlying factors. However, much uncertainty remains. With better information on the role of these epidemiological factors, the control of influenza could be improved.
[Show abstract][Hide abstract] ABSTRACT: We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7) programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines.
Nasopharyngeal swabs were taken from children <5 y old and family members (n=400) 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case carrier ratios (CCRs) were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT) carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76-1.49). The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence.
Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors' Summary.
PLoS Medicine 04/2011; 8(4):e1001017. DOI:10.1371/journal.pmed.1001017 · 14.43 Impact Factor