-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Meningococcal disease remains an important cause of morbidity and mortality worldwide. The first broadly effective vaccine against group B disease (which causes considerable meningococcal disease in Europe, the Americas and Australasia) was licensed in the EU in January 2013; our objective was to estimate the potential impact of introducing such a vaccine in England. METHODS: We developed two models to estimate the impact of introducing a new 'MenB' vaccine. The cohort model assumes the vaccine protects against disease only; the transmission dynamic model also allows the vaccine to protect against carriage (accounting for herd effects). We used these, and economic models, to estimate the case reduction and cost-effectiveness of a number of different vaccine strategies. RESULTS: We estimate 27% of meningococcal disease cases could be prevented over the lifetime of an English birth cohort by vaccinating infants at 2,3,4 and 12 months of age with a vaccine that prevents disease only; this strategy could be cost-effective at £9 per vaccine dose. Substantial reductions in disease (71%) can be produced after 10 years by routinely vaccinating infants in combination with a large-scale catch-up campaign, using a vaccine which protects against carriage as well as disease; this could be cost-effective at £17 per vaccine dose. CONCLUSIONS: New 'MenB' vaccines could substantially reduce disease in England and be cost-effective if competitively priced, particularly if the vaccines can prevent carriage as well as disease. These results are relevant to other countries, with a similar epidemiology to England, considering the introduction of a new 'MenB' vaccine.
Vaccine 04/2013; · 3.77 Impact Factor
-
-
Mark Jit,
Niel Hens,
Marco Massari,
Philippe Beutels,
Magdalena Rosinska,
Stefania Salmaso,
Jacco Wallinga,
W John Edmunds,
Janneke Heijne,
Kari Auranen,
Joël Mossong,
Rafael Mikolajczyk,
Malgorzata Sadkowska-Todys, Gianpaolo Scalia Tomba
-
[show abstract]
[hide abstract]
ABSTRACT: Patterns of social mixing are key determinants of epidemic spread. Here we present the results of an internet-based social contact survey completed by a cohort of participants over 9,000 times between July 2009 and March 2010, during the 2009 H1N1v influenza epidemic. We quantify the changes in social contact patterns over time, finding that school children make 40% fewer contacts during holiday periods than during term time. We use these dynamically varying contact patterns to parameterise an age-structured model of influenza spread, capturing well the observed patterns of incidence; the changing contact patterns resulted in a fall of approximately 35% in the reproduction number of influenza during the holidays. This work illustrates the importance of including changing mixing patterns in epidemic models. We conclude that changes in contact patterns explain changes in disease incidence, and that the timing of school terms drove the 2009 H1N1v epidemic in the UK. Changes in social mixing patterns can be usefully measured through simple internet-based surveys.
PLoS Computational Biology 03/2012; 8(3):e1002425. · 5.22 Impact Factor
-
[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. SETTING: England. 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.
BMJ (Clinical research ed.). 01/2012; 345:e6879.
-
[show abstract]
[hide abstract]
ABSTRACT: Knowledge of the determinants of infectious disease transmission is a public health priority as it allows the design of optimal control strategies for endemic or emerging infections. We analyse a detailed dataset on contact patterns across five European countries and use available serological profiles for varicella and parvovirus B19 infections to identify the types of contact that may be most relevant for transmission. We show that models informed by contact data fit well the observed serological profiles of both infections. We find that intimate types of contacts explain the pattern of acquisition of serological markers by age better than other types of social contacts. We observe similar patterns in each of the countries analysed, suggesting that there are consistent biological mechanisms at work.
Epidemics. 09/2011; 3(3-4):143-51.
-
[show abstract]
[hide abstract]
ABSTRACT: School holidays are recognised to be of great epidemiological importance for a wide range of infectious diseases; this is postulated to be because the social mixing patterns of school children - a key population group - change significantly during the holiday period. However, there is little direct quantitative evidence to confirm this belief. Here, we present the results of a prospective survey designed to provide a detailed comparison of social mixing patterns of school children during school terms and during the school holidays. Paired data were collected, with participants recording their social contacts once during term time and once during the holiday period. We found that the daily number of recorded encounters approximately halved during the holidays, and that the number of close contact encounters fell by approximately one third. The holiday period also saw a change in the age structure of children's social contacts, with far fewer contacts of their own age, but an increase in the number of encounters with adults, particularly older adults. A greater amount of mixing between children at different schools was recorded during the holiday. We suggest, therefore, that whilst infections may spread rapidly within schools during term time, in the holiday period there are increased opportunities for transmission to other schools and other age groups.
Epidemics. 06/2011; 3(2):103-8.
-
Stefan Flasche,
Niel Hens,
Pierre-Yves Boëlle,
Joël Mossong,
W Marijn van Ballegooijen,
Baltazar Nunes,
Caterina Rizzo,
Florin Popovici,
Patricia Santa-Olalla,
Frantiska Hrubá,
Kremena Parmakova,
Marc Baguelin,
Albert Jan van Hoek,
Jean-Claude Desenclos,
Pascale Bernillon,
Amparro Larrauri Cámara,
Jacco Wallinga,
Tommi Asikainen,
Peter J White, W John Edmunds
[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.
Epidemics. 06/2011; 3(2):125-33.
-
Vaccine 03/2011; · 3.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: During the 2009 H1N1v influenza epidemic, the total number of symptomatic cases was estimated by combining influenza-like illness (ILI) consultations, virological surveillance and assumptions about healthcare-seeking behaviour. Changes in healthcare-seeking behaviour due to changing scientific information, media coverage and public anxiety, were not included in case estimates. The purpose of the study was to improve estimates of the number of symptomatic H1N1v cases and the case fatality rate (CFR) in England by quantifying healthcare-seeking behaviour using an internet-based survey carried out during the course of the 2009 H1N1v influenza epidemic.
We used an online survey that ran continuously from July 2009 to March 2010 to estimate the proportion of ILI cases that sought healthcare during the 2009 H1N1v influenza epidemic. We used dynamic age- and gender-dependent measures of healthcare-seeking behaviour to re-interpret consultation numbers and estimate the true number of cases of symptomatic ILI in 2009 and the case fatality rate (CFR).
There were significant differences between age groups in healthcare usage. From the start to the end of the epidemic, the percentage of individuals with influenza-like symptoms who sought medical attention decreased from 43% to 32% (p < 0.0001). Adjusting official numbers accordingly, we estimate that there were 1.1 million symptomatic cases in England, over 320,000 (40%) more cases than previously estimated and that the autumn epidemic wave was 45% bigger than previously thought. Combining symptomatic case numbers with reported deaths leads to a reduced overall CFR estimate of 17 deaths per 100,000 cases, with the largest reduction in adults.
Active surveillance of healthcare-seeking behaviour, which can be achieved using novel data collection methods, is vital for providing accurate real-time estimates of epidemic size and disease severity. The differences in healthcare-seeking between different population groups and changes over time have significant implications for estimates of total case numbers and the case fatality rate.
BMC Infectious Diseases 03/2011; 11:68. · 3.12 Impact Factor
-
Thomas House,
Marc Baguelin,
Albert Jan Van Hoek,
Peter J White,
Zia Sadique,
Ken Eames,
Jonathan M Read,
Niel Hens,
Alessia Melegaro, W John Edmunds,
Matt J Keeling
[show abstract]
[hide abstract]
ABSTRACT: Despite the fact that the 2009 H1N1 pandemic influenza strain was less severe than had been feared, both seasonal epidemics of influenza-like-illness and future influenza pandemics have the potential to place a serious burden on health services. The closure of schools has been postulated as a means of reducing transmission between children and hence reducing the number of cases at the peak of an epidemic; this is supported by the marked reduction in cases during school holidays observed across the world during the 2009 pandemic. However, a national policy of long-duration school closures could have severe economic costs. Reactive short-duration closure of schools in regions where health services are close to capacity offers a potential compromise, but it is unclear over what spatial scale and time frame closures would need to be made to be effective. Here, using detailed geographical information for England, we assess how localized school closures could alleviate the burden on hospital intensive care units (ICUs) that are reaching capacity. We show that, for a range of epidemiologically plausible assumptions, considerable local coordination of school closures is needed to achieve a substantial reduction in the number of hospitals where capacity is exceeded at the peak of the epidemic. The heterogeneity in demand per hospital ICU bed means that even widespread school closures are unlikely to have an impact on whether demand will exceed capacity for many hospitals. These results support the UK decision not to use localized school closures as a control mechanism, but have far wider international public-health implications. The spatial heterogeneities in both population density and hospital capacity that give rise to our results exist in many developed countries, while our model assumptions are sufficiently general to cover a wide range of pathogens. This leads us to believe that when a pandemic has severe implications for ICU capacity, only widespread school closures (with their associated costs and organizational challenges) are sufficient to mitigate the burden on the worst-affected hospitals.
Proceedings of the Royal Society B: Biological Sciences 02/2011; 278(1719):2753-60. · 5.41 Impact Factor
-
Peter Horby,
Quang Thai Pham,
Niel Hens,
Thi Thu Yen Nguyen,
Quynh Mai Le,
Dinh Thoang Dang,
Manh Linh Nguyen,
Thu Huong Nguyen,
Neal Alexander, W John Edmunds,
Nhu Duong Tran,
Annette Fox,
Tran Hien Nguyen
[show abstract]
[hide abstract]
ABSTRACT: The spread of infectious diseases from person to person is determined by the frequency and nature of contacts between infected and susceptible members of the population. Although there is a long history of using mathematical models to understand these transmission dynamics, there are still remarkably little empirical data on contact behaviors with which to parameterize these models. Even starker is the almost complete absence of data from developing countries. We sought to address this knowledge gap by conducting a household based social contact diary in rural Vietnam.
A diary based survey of social contact patterns was conducted in a household-structured community cohort in North Vietnam in 2007. We used generalized estimating equations to model the number of contacts while taking into account the household sampling design, and used weighting to balance the household size and age distribution towards the Vietnamese population. We recorded 6675 contacts from 865 participants in 264 different households and found that mixing patterns were assortative by age but were more homogenous than observed in a recent European study. We also observed that physical contacts were more concentrated in the home setting in Vietnam than in Europe but the overall level of physical contact was lower. A model of individual versus household vaccination strategies revealed no difference between strategies in the impact on R(0).
This work is the first to estimate contact patterns relevant to the spread of infections transmitted from person to person by non-sexual routes in a developing country setting. The results show interesting similarities and differences from European data and demonstrate the importance of context specific data.
PLoS ONE 01/2011; 6(2):e16965. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study updates previous work on modelling the incidence of varicella and Herpes Zoster (HZ) following the introduction of childhood vaccination. The updated model includes new data on age-specific contact patterns, as well as data on the efficacy of zoster vaccination in the elderly and allows for HZ among vaccinees. The current study also looks at two-dose varicella childhood programmes, and assesses the combined impact of varicella vaccination in childhood and zoster vaccination of the elderly. The results suggest that a two-dose schedule is likely to reduce the incidence of varicella to very low levels, provided first dose coverage is around 90% and second dose coverage is in excess of 70%. Single dose varicella vaccination programmes are expected to result in large numbers of breakthrough cases. Childhood vaccination is expected to increase the incidence of zoster for more than 40 years after introduction of the programme, the magnitude of this increase being influenced primarily by the duration of boosting following exposure to the varicella zoster virus. Though this increase in zoster incidence can be partly offset by vaccination of the elderly, the effectiveness of this combined strategy is limited, as much of the increase occurs in those adults too young to be vaccinated. Childhood vaccination at intermediate levels of coverage (70% and 60% for first and second dose coverage respectively) is expected to lead to an increase in adult varicella. At high coverage (90% and 80% coverage) this is unlikely to be the case. These results will be used to inform a cost-effectiveness analysis of combined varicella and zoster vaccination programmes.
Vaccine 01/2011; 29(13):2411-20. · 3.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: While the H1N1v influenza pandemic in 2009 was clinically mild, with a low case-fatality rate, the overall disease burden measured in quality-adjusted life years (QALY) lost has not been estimated. Such a measure would allow comparison with other diseases and assessment of the cost-effectiveness of pandemic control measures.
Cases of H1N1v confirmed by polymerase chain reaction (PCR) and PCR negative cases with similar influenza-like illness (ILI controls) in 7 regions of England were sent two questionnaires, one within a week of symptom onset and one two weeks later, requesting information on duration of illness, work loss and antiviral use together with EQ-5D questionnaires. Results were compared with those for seasonal influenza from a systematic literature review. A total QALY loss for the 2009 pandemic in England was calculated based on the estimated total clinical cases and reported deaths. A total of 655 questionnaires were sent and 296 (45%) returned. Symptoms and average illness duration were similar between confirmed cases and ILI controls (8.8 days and 8.7 days respectively). Days off work were greater for cases than ILI controls (7.3 and 4.9 days respectively, p = 0.003). The quality-adjusted life days lost was 2.92 for confirmed cases and 2.74 for ILI controls, with a reduction in QALY loss after prompt use of antivirals in confirmed cases. The overall QALY loss in the pandemic was estimated at 28,126 QALYs (22,267 discounted) of which 40% was due to deaths (24% with discounting).
Given the global public health significance of influenza, it is remarkable that no previous prospective study of the QALY loss of influenza using standardised and well validated methods has been performed. Although the QALY loss was minor for individual patients, the estimated total burden of influenza over the pandemic was substantial when compared to other infectious diseases.
PLoS ONE 01/2011; 6(3):e17030. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A cost-effectiveness analysis of rotavirus vaccination in Belgium, England and Wales, Finland, France and the Netherlands published in 2009 was updated based on recent studies on rotavirus burden of disease and vaccine efficacy. All the qualitative conclusions in the previous study were found to remain valid. Vaccination remains cost-effective in Finland only when using plausible tender prices.
Vaccine 11/2010; 28(47):7457-9. · 3.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A Markov model of hepatitis B virus (HBV) disease progression in the UK estimated that 81% of predicted HBV-associated morbidity and mortality could be prevented by universal infant vaccination at a cost of approximately £ 260,000 per QALY gained. Universal adolescent vaccination would be less effective (45% prevented) and less cost-effective (£ 493,000 per QALY gained). Higher HBV incidence rates in males and intermediate/high risk ethnic populations meant it was approximately 3 times more cost-effective to vaccinate these groups. At current vaccine costs a selective infant vaccination programme, based on vaccinating intermediate/high risk ethnic populations would not be considered cost effective. The threshold cost per vaccinated child at which the programme would be considered cost-effective was investigated. Universal infant vaccination would be cost-effective if the average cost of vaccinating each child against HBV, including vaccine and administration costs of all doses, was less than £ 4.09. Given the low cost of vaccination required to make a universal programme cost-effective the most feasible policy in the UK would be to use a suitably priced combined vaccine that included the other antigens in the current infant vaccination schedule.
Vaccine 11/2010; 29(3):466-75. · 3.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Internet-based surveillance systems to monitor influenza-like illness (ILI) have advantages over traditional (physician-based) reporting systems, as they can potentially monitor a wider range of cases (i.e. including those that do not seek care). However, the requirement for participants to have internet access and to actively participate calls into question the representativeness of the data. Such systems have been in place in a number of European countries over the last few years, and in July 2009 this was extended to the UK. Here we present results of this survey with the aim of assessing the reliability of the data, and to evaluate methods to correct for possible biases.
Internet-based monitoring of ILI was launched near the peak of the first wave of the UK H1N1v influenza pandemic. We compared the recorded ILI incidence with physician-recorded incidence and an estimate of the true number of cases over the course of the epidemic. We also compared overall attack rates. The effect of using different ILI definitions and alternative denominator assumptions on incidence estimates was explored.
The crude incidence measured by the internet-based system appears to be influenced by individuals who participated only once in the survey and who appeared more likely to be ill. This distorted the overall incidence trend. Concentrating on individuals who reported more than once results in a time series of ILI incidence that matches the trend of case estimates reasonably closely, with a correlation of 0.713 (P-value: 0.0001, 95% CI: 0.435, 0.867). Indeed, the internet-based system appears to give a better estimate of the relative height of the two waves of the UK pandemic than the physician-recorded incidence. The overall attack rate is, however, higher than other estimates, at about 16% when compared with a model-based estimate of 6%.
Internet-based monitoring of ILI can capture the trends in case numbers if appropriate weighting is used to correct for differential response. The overall level of incidence is, however, difficult to measure. Internet-based systems may be a useful adjunct to existing ILI surveillance systems as they capture cases that do not necessarily contact health care. However, further research is required before they can be used to accurately assess the absolute level of incidence in the community.
BMC Public Health 10/2010; 10:650. · 2.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The 7-valent pneumococcal conjugate vaccine has been introduced in national immunisation programmes of most industrialised countries and recently in two African GAVI eligible countries (Rwanda and The Gambia). However the long term effects of PCV are still unclear, as beneficial direct and herd immunity effects might be countered by serotype replacement.
A dynamic, age-structured, compartmental model of Streptococcus pneumoniae transmission was developed to predict the potential impact of PCV7 on the incidence of invasive disease accounting for both herd immunity and serotype replacement effects. The model was parameterised using epidemiological data from England and Wales and pre and post-vaccination surveillance data from the US.
Model projections showed that serotype replacement plays a crucial role in determining the overall effect of a PCV7 vaccination programme and could reduce, negate or outweigh its beneficial impact. However, using the estimate of the competition parameter derived from the US post-vaccination experience, an infant vaccination programme would prevent 39,000 IPD cases in the 20 years after PCV7 introduction in the UK. Adding a catch-up campaign for under 2 or under 5 year olds would provide a further reduction of 1,200 or 3,300 IPD cases respectively, mostly in the first few years of the programme.
This analysis suggests that a PCV vaccination programme would eradicate vaccine serotypes from circulation. However, the increase in carriage of non-vaccine serotypes, and the consequent increase in invasive disease, could reduce, negate or outweigh the benefit. These results are sensitive to changes in the protective effect of the vaccine, and, most importantly, to the level of competition between vaccine and non-vaccine types. The techniques developed here can be used to assess the introduction of vaccination programmes in developing countries and provide the basis for cost-effectiveness analyses.
BMC Infectious Diseases 04/2010; 10:90. · 3.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Decisions on how to mitigate an evolving pandemic are technically challenging. We present a real-time assessment of the effectiveness and cost-effectiveness of alternative influenza A/H1N1v vaccination strategies. A transmission dynamic model was fitted to the estimated number of cases in real-time, and used to generate plausible autumn scenarios under different vaccination options. The proportion of these cases by age and risk group leading to primary care consultations, National Pandemic Flu Service consultations, emergency attendances, hospitalisations, intensive care and death was then estimated using existing data from the pandemic. The real-time model suggests that the epidemic will peak in early November, with the peak height being similar in magnitude to the summer wave. Vaccination of the high-risk groups is estimated to prevent about 45 deaths (80% credibility interval 26-67), and save around 2900 QALYs (80% credibility interval 1600-4500). Such a programme is very likely to be cost-effective if the cost of vaccine purchase itself is treated as a sunk cost. Extending vaccination to low-risk individuals is expected to result in more modest gains in deaths and QALYs averted. Extending vaccination to school-age children would be the most cost-effective extension. The early availability of vaccines is crucial in determining the impact of such extensions. There have been a considerable number of cases of H1N1v in England, and so the benefits of vaccination to mitigate the ongoing autumn wave are limited. However, certain groups appear to be at significantly higher risk of complications and deaths, and so it appears both effective and cost-effective to vaccinate them. The United Kingdom was the first country to have a major epidemic in Europe. In countries where the epidemic is not so far advanced vaccination of children may be cost-effective. Similar, detailed, real-time modelling and economic studies could help to clarify the situation.
Vaccine 03/2010; 28(12):2370-84. · 3.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Little is known about the possible impact of an influenza pandemic on a nation's economy. We applied the UK macroeconomic model 'COMPACT' to epidemiological data on previous UK influenza pandemics, and extrapolated a sensitivity analysis to cover more extreme disease scenarios. Analysis suggests that the economic impact of a repeat of the 1957 or 1968 pandemics, allowing for school closures, would be short-lived, constituting a loss of 3.35 and 0.58% of GDP in the first pandemic quarter and year, respectively. A more severe scenario (with more than 1% of the population dying) could yield impacts of 21 and 4.5%, respectively. The economic shockwave would be gravest when absenteeism (through school closures) increases beyond a few weeks, creating policy repercussions for influenza pandemic planning as the most severe economic impact is due to policies to contain the pandemic rather than the pandemic itself.Accounting for changes in consumption patterns made in an attempt to avoid infection worsens the potential impact. Our mild disease scenario then shows first quarter/first year reductions in GDP of 9.5/2.5%, compared with our severe scenario reductions of 29.5/6%. These results clearly indicate the significance of behavioural change over disease parameters.
Health Economics 10/2009; 19(11):1345-60. · 2.12 Impact Factor
