William John Edmunds

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

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.

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

Many countries are considering vaccination against human papillomavirus (HPV). However, the long-term impact of vaccination is difficult to predict due to uncertainty about the prevalence of HPV infection, pattern of sexual partnerships, progression of cervical neoplasias, accuracy of screening as well as the duration of infectiousness and immunity. Dynamic models of human papillomavirus (HPV) transmission were developed to describe the infection spread and development of cervical neoplasia, cervical cancer (squamous cell and adenocarcinoma) and anogenital warts. Using different combinations of assumptions, 9900 scenarios were created. Each scenario was then fitted to epidemiological data and the best-fitting scenarios used to predict the impact of vaccination. Results suggest that vaccinating 12-year-old girls at 80% coverage will result in a 38-82% reduction in cervical cancer incidence and 44-100% reduction in anogenital warts incidence after 60 years of an ongoing vaccination programme if vaccine protection lasts 20 years on average. The marginal benefit of vaccinating boys depends on the degree of protection achieved by vaccinating girls.

Modelling the transmission of healthcare associated infections: a systematic review.

BackgroundDynamic transmission models are increasingly being used to improve our understanding of the epidemiology of healthcare-associated infections (HCAI). However, there has been no recent comprehensive review of this emerging field. This paper summarises how mathematical models have informed the field of HCAI and how methods have developed over time.MethodsMEDLINE, EMBASE, Scopus, CINAHL plus and Global Health databases were systematically searched for dynamic mathematical models of HCAI transmission and/or the dynamics of antimicrobial resistance in healthcare settings.ResultsIn total, 96 papers met the eligibility criteria. The main research themes considered were evaluation of infection control effectiveness (64%), variability in transmission routes (7%), the impact of movement patterns between healthcare institutes (5%), the development of antimicrobial resistance (3%), and strain competitiveness or co-colonisation with different strains (3%). Methicillin-resistant Staphylococcus aureus was the most commonly modelled HCAI (34%), followed by vancomycin resistant enterococci (16%). Other common HCAIs, e.g. Clostridum difficile, were rarely investigated (3%). Very few models have been published on HCAI from low or middle-income countries.The first HCAI model has looked at antimicrobial resistance in hospital settings using compartmental deterministic approaches. Stochastic models (which include the role of chance in the transmission process) are becoming increasingly common. Model calibration (inference of unknown parameters by fitting models to data) and sensitivity analysis are comparatively uncommon, occurring in 35% and 36% of studies respectively, but their application is increasing. Only 5% of models compared their predictions to external data.ConclusionsTransmission models have been used to understand complex systems and to predict the impact of control policies. Methods have generally improved, with an increased use of stochastic models, and more advanced methods for formal model fitting and sensitivity analyses. Insights gained from these models could be broadened to a wider range of pathogens and settings. Improvements in the availability of data and statistical methods could enhance the predictive ability of models.

Health and economic impact of the seasonal influenza vaccination programme in England

BACKGROUND The seasonal influenza vaccination programme in England targets individuals over 65 years old and in clinical risk groups. METHODS A model of influenza transmission and disease was fitted to weekly primary care consultations due to influenza in a typical pre-pandemic season (2006/2007). Different scenarios were constructed about influenza severity and how well vaccines match circulating strains to assess the impact and cost-effectiveness of the current vaccination programme. RESULTS A well-matched vaccine may reduce the incidence of laboratory-confirmed influenza illness from 8.2% (95% range 4.3-13%) to 5.9% (95% range 2.9-9.7%), with 56-73% of this due to indirect protection. The programme is likely to be cost-effective unless both low severity and poor matching is assumed. CONCLUSION The current seasonal influenza vaccination programme appears to substantially reduce disease burden and provides good value for money.

Modelling the seasonality of rotavirus disease and the impact of vaccination in England and Wales

Two rotavirus vaccines are currently recommended for inclusion in routine childhood immunization programmes. We developed a deterministic age-structured model of rotavirus transmission and disease to investigate the population-level effects of vaccination in England and Wales. The model explicitly captures the natural history of infection and uses realistic population mixing patterns. The model accurately reproduces the strong seasonal pattern and age distribution of rotavirus disease observed in England and Wales. We predict vaccination will provide both direct and indirect protection within the population. If coverage levels comparable to other childhood vaccines are achieved, we predict that vaccination will reduce rotavirus disease incidence by 61% resulting in a potential fall in burden on health-care services.

Effect of pre-exposure prophylaxis and combination HIV prevention for men who have sex with men in the UK: a mathematical modelling study

BACKGROUND HIV transmission in men who have sex with men (MSM) in the UK has shown no sign of decreasing in the past decade. Additional prevention measures are needed. We aimed to estimate the effect of various potential interventions implemented individually and in combination on prevention of HIV infection. METHODS We extended a deterministic partnership-based mathematical model for HIV transmission, informed by detailed behavioural and surveillance data, to assess the effect of seven different HIV interventions implemented in MSM (aged 15-64 years) in the UK during 2014-20, including increasing rates of HIV testing, test-and-treat programmes, pre-exposure prophylaxis (PrEP), and sexual behavioural changes. We did sensitivity analyses on risk compensation. FINDINGS We predicted a baseline of 16 955 new infections (IQR 13 156-21 669) in MSM in the UK during 2014-20. At a coverage of ≤50%, testing twice a year outperformed all other interventions. Of all intervention combinations, only the combined effect of test and treat and annual HIV testing (61·8%, IQR 47·2-81·8, of total incidence) was greater than the sum of effects of the two interventions individually (32·6%, 23·7-46·0, and 23·9%, 16·5-33·3, respectively). Simultaneous PrEP, expansion of HIV testing, and initiation of test-and-treat programme in 25% of high-activity MSM could save 7399 (IQR 5587-9813) UK MSM from HIV infection (43·6%, IQR 32·9-57·9, of total incidence). An increase in unsafe sex or sexual partners to 50% or more could substantially reduce the effect of interventions, but is unlikely to negate the prevention benefit completely. INTERPRETATION PrEP could prevent a large number of new HIV infections if other key strategies including HIV testing and treatment are simultaneously expanded and improved. Without PrEP, HIV incidence in MSM in the UK is unlikely to decrease substantially by the end of this decade. FUNDING Health Protection Agency (now Public Health England).

Estimating the number of deaths with rotavirus as a cause in England and wales.

The precise number of deaths due to rotavirus infection in England and Wales is difficult to determine because mortality is usually low and reported simply as death due to gastrointestinal disease. We have used two independent methods to estimate this figure. Firstly, we obtained records from the Office for National Statistics of deaths in children with any mention of gastroenteritis. For deaths with uncertain aetiology, we estimated the proportion attributable to rotavirus using a linear model with monthly laboratory reports of gastrointestinal micro-organisms as predictors. Secondly, we calculated the case-fatality ratio of records in Hospital Episode Statistics with rotavirus indicated, and applied this ratio to an estimate of the actual number of rotavirus hospital admissions. The two methods gave estimates of 3.8 and 3.2 rotavirus deaths a year respectively.

Estimating progression rates for human papillomavirus infection from epidemiological data.

A Markov model was constructed in order to estimate typespecific rates of cervical lesion progression and regression in women with high-risk human papillomavirus (HPV). The model was fitted to age- and type-specific data regarding the HPV DNA and cytological status of women undergoing cervical screening in a recent screening trial, as well as cervical cancer incidence. It incorporates different assumptions about the way lesions regress, the accuracy of cytological screening, the specificity of HPV DNA testing, and the age-specific prevalence of HPV infection. Combinations of assumptions generate 162 scenarios for squamous cell carcinomas and 54 scenarios for adenocarcinomas. Simulating an unscreened cohort of women infected with high-risk HPV indicates that the probability of an infection continuing to persist and to develop into invasive cancer depends on the length of time it has already persisted. The scenarios and parameter sets that produce the best fit to available epidemiological data provide a basis for modeling the natural history of HPV infection and disease.

Cost of treatment and QALYs lost due to genital warts: data for the economic evaluation of HPV vaccines in the United Kingdom.

Background: Data on the burden of genital warts in terms of treatment costs and detriment to quality of life (QoL) are required to assess cost-effectiveness of quadrivalent human papillomavirus vaccination. We investigated the cost of treatment and period of time for which QoL is affected to obtain estimates of quality-adjusted life year (QALY) loss associated with an episode of genital warts. Methods: Adults diagnosed with genital warts attending the York sexually transmitted disease clinic during two 3-month periods in 2006 and 2007 were enrolled (n = 189). Data on cost of treatment and duration of episode of care were collected from a retrospective case note review. QALY loss was calculated by applying estimates of the duration of time for which QoL was affected to the previously reported detriment to QoL associated with genital warts. Results: The average cost per episode of care was

Effectiveness of Ring Vaccination as Control Strategy for Ebola Virus Disease.

286 (£139, 95% CI: