Mark Jit

Social Contacts and Mixing Patterns Relevant to the Spread of Infectious Diseases

Background Mathematical modelling of infectious diseases transmitted by the respiratory or close-contact route (e.g., pandemic influenza) is increasingly being used to determine the impact of possible interventions. Although mixing patterns are known to be crucial determinants for model outcome, researchers often rely on a priori contact assumptions with little or no empirical basis. We conducted a population-based prospective survey of mixing patterns in eight European countries using a common paper-diary methodology. Methods and Findings 7,290 participants recorded characteristics of 97,904 contacts with different individuals during one day, including age, sex, location, duration, frequency, and occurrence of physical contact. We found that mixing patterns and contact characteristics were remarkably similar across different European countries. Contact patterns were highly assortative with age: schoolchildren and young adults in particular tended to mix with people of the same age. Contacts lasting at least one hour or occurring on a daily basis mostly involved physical contact, while short duration and infrequent contacts tended to be nonphysical. Contacts at home, school, or leisure were more likely to be physical than contacts at the workplace or while travelling. Preliminary modelling indicates that 5- to 19-year-olds are expected to suffer the highest incidence during the initial epidemic phase of an emerging infection transmitted through social contacts measured here when the population is completely susceptible. Conclusions To our knowledge, our study provides the first large-scale quantitative approach to contact patterns relevant for infections transmitted by the respiratory or close-contact route, and the results should lead to improved parameterisation of mathematical models used to design control strategies.

Economic evaluation of human papillomavirus vaccination in the United Kingdom

Objective To assess the cost effectiveness of routine vaccination of 12 year old schoolgirls against human papillomavirus infection in the United Kingdom. Design Economic evaluation. Setting UK. Population Schoolgirls aged 12 or older. Main outcome measures Costs, quality adjusted life years (QALYs), and incremental cost effectiveness ratios for a range of vaccination options. Results Vaccinating 12 year old schoolgirls with a quadrivalent vaccine at 80% coverage is likely to be cost effective at a willingness to pay threshold of £30 000 (€37 700;

Vaccination against pandemic influenza A/H1N1v in England: a real-time economic evaluation.

59 163) per QALY gained, if the average duration of protection from the vaccine is more than 10 years. Implementing a catch-up campaign of girls up to age 18 is likely to be cost effective. Vaccination of boys is unlikely to be cost effective. A bivalent vaccine with the same efficacy against human papillomavirus types 16 and 18 costing £13-£21 less per dose (depending on the duration of vaccine protection) may be as cost effective as the quadrivalent vaccine although less effective as it does not prevent anogenital warts. Conclusions Routine vaccination of 12 year old schoolgirls combined with an initial catch-up campaign up to age 18 is likely to be cost effective in the UK. The results are robust to uncertainty in many parameters and processes. A key influential variable is the duration of vaccine protection.

An update to "the cost-effectiveness of rotavirus vaccination: comparative analyses for five European countries and transferability in Europe".

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.

Cost-effectiveness of female human papillomavirus vaccination in 179 countries: a PRIME modelling study

Cost-effectiveness analyses are usually not directly comparable between countries because of differences in analytical and modelling assumptions. We investigated the cost-effectiveness of rotavirus vaccination in five European Union countries (Belgium, England and Wales, Finland, France and the Netherlands) using a single model, burden of disease estimates supplied by national public health agencies and a subset of common assumptions. Under base case assumptions (vaccination with Rotarix, 3% discount rate, health care provider perspective, no herd immunity and quality of life of one caregiver affected by a rotavirus episode) and a cost-effectiveness threshold of euro30,000, vaccination is likely to be cost effective in Finland only. However, single changes to assumptions may make it cost effective in Belgium and the Netherlands. The estimated threshold price per dose for Rotarix (excluding administration costs) to be cost effective was euro41 in Belgium, euro28 in England and Wales, euro51 in Finland, euro36 in France and euro46 in the Netherlands.

Estimation of the impact of genital warts on health-related quality of life

BACKGROUND Introduction of human papillomavirus (HPV) vaccination in settings with the highest burden of HPV is not universal, partly because of the absence of quantitative estimates of country-specific effects on health and economic costs. We aimed to develop and validate a simple generic model of such effects that could be used and understood in a range of settings with little external support. METHODS We developed the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess cost-effectiveness and health effects of vaccination of girls against HPV before sexual debut in terms of burden of cervical cancer and mortality. PRIME models incidence according to proposed vaccine efficacy against HPV 16/18, vaccine coverage, cervical cancer incidence and mortality, and HPV type distribution. It assumes lifelong vaccine protection and no changes to other screening programmes or vaccine uptake. We validated PRIME against existing reports of HPV vaccination cost-effectiveness, projected outcomes for 179 countries (assuming full vaccination of 12-year-old girls), and outcomes for 71 phase 2 GAVI-eligible countries (using vaccine uptake data from the GAVI Alliance). We assessed differences between countries in terms of cost-effectiveness and health effects. FINDINGS In validation, PRIME reproduced cost-effectiveness conclusions for 24 of 26 countries from 17 published studies, and for all 72 countries in a published study of GAVI-eligible countries. Vaccination of a cohort of 58 million 12-year-old girls in 179 countries prevented 690,000 cases of cervical cancer and 420,000 deaths during their lifetime (mostly in low-income or middle-income countries), at a net cost of US

Comparing bivalent and quadrivalent human papillomavirus vaccines: economic evaluation based on transmission model

4 billion. HPV vaccination was very cost effective (with every disability-adjusted life-year averted costing less than the gross domestic product per head) in 156 (87%) of 179 countries. Introduction of the vaccine in countries without national HPV vaccination at present would prevent substantially more cases of cervical cancer than in countries with such programmes, although the disparity has narrowed since 2012. If 71 phase 2 GAVI-eligible countries adopt vaccination according to forecasts, then in 2070 GAVI Alliance-funded vaccination could prevent 200,000 cases of cervical cancer and 100,000 deaths in some of the highest-burden countries. INTERPRETATION Large between-country disparities exist for HPV vaccination, with countries with the most to gain yet to introduce national HPV vaccination. Support from the GAVI Alliance could help to reduce such disparities, but a substantial burden will remain even after presently projected vaccine introductions. FUNDING WHO.

Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England.

Objectives: One of the two new human papillomavirus (HPV) vaccines protects against HPV types 6 and 11, which cause over 95% of genital warts, in addition to protecting against HPV types 16 and 18. In anticipation of HPV vaccine implementation, the impact of genital warts on health-related quality of life (HRQoL) was measured to assess the potential benefits of the quadrivalent over the bivalent vaccine. Methods: Genitourinary medicine clinic patients aged 18 years and older with a current diagnosis of genital warts were eligible; 81 consented and were interviewed by a member of the research team. A generic HRQoL questionnaire, the EQ-5D (comprising EQ-5D index and EQ visual analogue scale (VAS) scores) and a disease-specific HRQoL instrument, the CECA10, were administered. Previously established UK population norms were used as a control group for EQ-5D comparisons. Results: Cases (with genital warts) had lower EQ VAS and EQ-5D index scores than controls. After adjusting for age a mean difference between cases and controls 30 years of age and under (n  =  70) of 13.9 points (95% CI 9.9 to 17.6, p<0.001) for the EQ VAS and 0.039 points (95% CI 0.005 to 0.068, p = 0.02) on the EQ-5D index (also adjusted for sex) was observed. The difference between cases and controls for the EQ VAS was especially notable in young women. Conclusions: Genital warts are associated with a significant detriment to HRQoL. The potential added benefit of preventing most cases of genital warts by HPV vaccination should be considered in decisions about which HPV vaccine to implement in the United Kingdom.

Accounting for methodological, structural, and parameter uncertainty in decision-analytic models: a practical guide.

Objectives To compare the effect and cost effectiveness of bivalent and quadrivalent human papillomavirus (HPV) vaccination, taking into account differences in licensure indications, protection against non-vaccine type disease, protection against disease related to HPV types 6 and 11, and reported long term immunogenicity. Design A model of HPV transmission and disease previously used to inform UK vaccination policy, updated with recent evidence and expanded to include scenarios where the two vaccines differ in duration of protection, cross protection, and end points prevented. Setting United Kingdom. Population Males and females aged 12–75 years. Main outcome measure Incremental cost effectiveness ratios for both vaccines and additional cost per dose for the quadrivalent vaccine to be equally cost effective as the bivalent vaccine. Results The bivalent vaccine needs to be cheaper than the quadrivalent vaccine to be equally cost effective, mainly because of its lack of protection against anogenital warts. The price difference per dose ranges from a median of £19 (interquartile range £12–£27) to £35 (£27–£44) across scenarios about vaccine duration, cross protection, and end points prevented (assuming one quality adjusted life year (QALY) is valued at £30 000 and both vaccines can prevent all types of HPV related cancers). Conclusions The quadrivalent vaccine may have an advantage over the bivalent vaccine in reducing healthcare costs and QALYs lost. The bivalent vaccine may have an advantage in preventing death due to cancer. However, considerable uncertainty remains about the differential benefit of the two vaccines.

Transmission dynamic modelling of the impact of human papillomavirus vaccination in the United Kingdom.

Highlights • We monitor HPV infection in sexually active young women in England.• The prevalence of HPV 16/18 has reduced within 3 years of HPV immunisation.• Reductions in HPV 16/18 were greatest at ages with highest immunisation coverage.• The data suggest reductions in HPV 16/18 amongst unvaccinated young women and men.