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Background: In response to the COVID-19 pandemic, the UK first adopted physical distancing measures in March, 2020. Vaccines against SARS-CoV-2 became available in December, 2020. We explored the health and economic value of introducing SARS-CoV-2 immunisation alongside physical distancing in the UK to gain insights about possible future scenarios in a post-vaccination era., Methods: We used an age-structured dynamic transmission and economic model to explore different scenarios of UK mass immunisation programmes over 10 years. We compared vaccinating 75% of individuals aged 15 years or older (and annually revaccinating 50% of individuals aged 15-64 years and 75% of individuals aged 65 years or older) to no vaccination. We assumed either 50% vaccine efficacy against disease and 45-week protection (worst-case scenario) or 95% vaccine efficacy against infection and 3-year protection (best-case scenario). Natural immunity was assumed to wane within 45 weeks. We also explored the additional impact of physical distancing on vaccination by assuming either an initial lockdown followed by voluntary physical distancing, or an initial lockdown followed by increased physical distancing mandated above a certain threshold of incident daily infections. We considered benefits in terms of quality-adjusted life-years (QALYs) and costs, both to the health-care payer and the national economy. We discounted future costs and QALYs at 3·5% annually and assumed a monetary value per QALY of £20 000 and a conservative long-run cost per vaccine dose of £15. We explored and varied these parameters in sensitivity analyses. We expressed the health and economic benefits of each scenario with the net monetary value: QALYs × (monetary value per QALY) - costs., Findings: Without the initial lockdown, vaccination, and increased physical distancing, we estimated 148·0 million (95% uncertainty interval 48·5-198·8) COVID-19 cases and 3·1 million (0·84-4·5) deaths would occur in the UK over 10 years. In the best-case scenario, vaccination minimises community transmission without future periods of increased physical distancing, whereas SARS-CoV-2 becomes endemic with biannual epidemics in the worst-case scenario. Ongoing transmission is also expected in intermediate scenarios with vaccine efficacy similar to published clinical trial data. From a health-care perspective, introducing vaccination leads to incremental net monetary values ranging from £12·0 billion to £334·7 billion in the best-case scenario and from -£1·1 billion to £56·9 billion in the worst-case scenario. Incremental net monetary values of increased physical distancing might be negative from a societal perspective if national economy losses are persistent and large., Interpretation: Our model findings highlight the substantial health and economic value of introducing SARS-CoV-2 vaccination. Smaller outbreaks could continue even with vaccines, but population-wide implementation of increased physical distancing might no longer be justifiable. Our study provides early insights about possible future post-vaccination scenarios from an economic and epidemiological perspective., Funding: National Institute for Health Research, European Commission, Bill & Melinda Gates Foundation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The eradication of wild and vaccine-derived poliovirus requires the global withdrawal of oral poliovirus vaccines (OPVs) and replacement with inactivated poliovirus vaccines (IPVs). The first phase of this effort was the withdrawal of the serotype 2 vaccine in April 2016, with a switch from trivalent OPVs to bivalent OPVs. The aim of our study was to produce comparative estimates of humoral and intestinal mucosal immunity associated with different routine immunisation schedules., Methods: We did a random-effect meta-analysis with single proportions and a network meta-analysis in a Bayesian framework to synthesise direct and indirect data. We searched MEDLINE and the Cochrane Library Central Register of Controlled Trials for randomised controlled trials published from Jan 1, 1980, to Nov 1, 2018, comparing poliovirus immunisation schedules in a primary series. Only trials done outside western Europe or North America and without variation in age schedules (ie, age at administration of the vaccine) between study groups were included in the analyses, because trials in high-income settings differ in vaccine immunogenicity and schedules from other settings and to ensure consistency within the network of trials. Data were extracted directly from the published reports. We assessed seroconversion against poliovirus serotypes 1, 2, and 3, and intestinal immunity against serotype 2, measured by absence of shedding poliovirus after a challenge OPV dose., Findings: We identified 437 unique studies; of them, 17 studies with a maximum of 8279 evaluable infants were eligible for assessment of humoral immunity, and eight studies with 4254 infants were eligible for intestinal immunity. For serotype 2, there was low between-trial heterogeneity in the data (τ=0·05, 95% credible interval [CrI] 0·009-0·15) and the risk ratio (RR) of seroconversion after three doses of bivalent OPVs was 0·14 (95% CrI 0·11-0·17) compared with three doses of trivalent OPVs. The addition of one or two full doses of an IPV after a bivalent OPV schedule increased the RR to 0·85 (0·75-1·0) and 1·1 (0·98-1·4). However, the addition of an IPV to bivalent OPV schedules did not significantly increase intestinal immunity (0·33, 0·18-0·61), compared with trivalent OPVs alone. For serotypes 1 and 3, there was susbstantial inconsistency and between-trial heterogeneity between direct and indirect effects, so we only present pooled estmates on seroconversion, which were at least 80% for serotype 1 and at least 88% for serotype 3 for all vaccine schedules., Interpretation: For WHO's polio eradication programme, the addition of one IPV dose for all birth cohorts should be prioritised to protect against paralysis caused by type 2 poliovirus; however, this inclusion will not prevent transmission or circulation in areas with faecal-oral transmission., Funding: UK Medical Research Council., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Health care workers (HCW) are at risk of infection during Ebola virus disease outbreaks and therefore may be targeted for vaccination before or during outbreaks. The effect of these strategies depends on the role of HCW in transmission which is understudied., Methods: To evaluate the effect of HCW-targeted or community vaccination strategies, we used a transmission model to explore the relative contribution of HCW and the community to transmission. We calibrated the model to data from multiple Ebola outbreaks. We quantified the impact of ahead-of-time HCW-targeted strategies, and reactive HCW and community vaccination., Results: We found that for some outbreaks (we call "type 1″) HCW amplified transmission both to other HCW and the community, and in these outbreaks prophylactic vaccination of HCW decreased outbreak size. Reactive vaccination strategies had little effect because type 1 outbreaks ended quickly. However, in outbreaks with longer time courses ("type 2 outbreaks"), reactive community vaccination decreased the number of cases, with or without prophylactic HCW-targeted vaccination. For both outbreak types, we found that ahead-of-time HCW-targeted strategies had an impact at coverage of 30%., Conclusions: The vaccine strategies tested had a different impact depending on the transmission dynamics and previous control measures. Although we will not know the characteristics of a new outbreak, ahead-of-time HCW-targeted vaccination can decrease the total outbreak size, even at low vaccine coverage., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Health care workers (HCW) are at high risk of Ebola virus disease (EVD) infection during epidemics and may contribute to onward transmission, and therefore HCW-targeted prophylactic vaccination strategies are being considered as interventions. To assess the feasibility of preventive HCW vaccination, we conducted a pilot survey on staff turnover and vaccine acceptance amongst 305 HCW in Freetown and Kambia districts of Sierra Leone. Multivariable logistic regression demonstrated which demographic and behavioural factors were associated with acceptance of a hypothetical new vaccine. We quantified the duration of employment of HCW, and used multivariable gamma regression to detect associations with duration of employment in current or any health care position. Finally, we simulated populations of HCW, to determine the likely future immunisation coverage amongst HCW based on our estimates of vaccine acceptance and employment duration. Most HCW we surveyed had a positive opinion of EVD vaccination (76.3%). We found that being a volunteer HCW (vs being on the government payroll) was associated with increased vaccine acceptance. We found that HCW have stable employment, with a mean duration of employment in the health sector of 10.9 years (median 8.0 years). Older age and being on the government payroll (vs volunteer HCW) were associated with a longer duration of employment in the health sector. Assuming a single vaccine campaign, with 76.3% vaccine acceptance, 100% vaccine efficacy and no waning of vaccine-induced protection, immunisation coverage was sustained over 50% until 6 years after a vaccination campaign. If vaccine-induced immunity wanes at 10% per year, then the immunisation coverage among HCW would fall below 50% after 3 years. Vaccinating HCW against EVD could be feasible as employment appeared stable and vaccine acceptance high. However, even with high vaccine efficacy and long-lasting immunity, repeated campaigns or vaccination at employment start may be necessary to maintain high coverage., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Social and cultural disparities in infectious disease burden are caused by systematic differences between communities. Some differences have a direct and proportional impact on disease burden, such as health-seeking behaviour and severity of infection. Other differences-such as contact rates and susceptibility-affect the risk of transmission, where the impact on disease burden is indirect and remains unclear. Furthermore, the concomitant impact of vaccination on such inequalities is not well understood., Methods: To quantify the role of differences in transmission on inequalities and the subsequent impact of vaccination, we developed a novel mathematical framework that integrates a mechanistic model of disease transmission with a demographic model of social structure, calibrated to epidemiologic and empirical social contact data., Results: Our model suggests realistic differences in two key factors contributing to the rates of transmission-contact rate and susceptibility-between two social groups can lead to twice the risk of infection in the high-risk population group relative to the low-risk population group. The more isolated the high-risk group, the greater this disease inequality. Vaccination amplified this inequality further: equal vaccine uptake across the two population groups led to up to seven times the risk of infection in the high-risk group. To mitigate these inequalities, the high-risk population group would require disproportionately high vaccination uptake., Conclusion: Our results suggest that differences in contact rate and susceptibility can play an important role in explaining observed inequalities in infectious diseases. Importantly, we demonstrate that, contrary to social policy intentions, promoting an equal vaccine uptake across population groups may magnify inequalities in infectious disease risk.

Background: In March, 2016, a flare-up of Ebola virus disease was reported in Guinea, and in response ring vaccination with the unlicensed rVSV-ZEBOV vaccine was introduced under expanded access, the first time that an Ebola vaccine has been used in an outbreak setting outside a clinical trial. Here we describe the safety of rVSV-ZEBOV candidate vaccine and operational feasibility of ring vaccination as a reactive strategy in a resource-limited rural setting., Methods: Approval for expanded access and compassionate use was rapidly sought and obtained from relevant authorities. Vaccination teams and frozen vaccine were flown to the outbreak settings. Rings of contacts and contacts of contacts were defined and eligible individuals, who had given informed consent, were vaccinated and followed up for 21 days under good clinical practice conditions., Findings: Between March 17 and April 21, 2016, 1510 individuals were vaccinated in four rings in Guinea, including 303 individuals aged between 6 years and 17 years and 307 front-line workers. It took 10 days to vaccinate the first participant following the confirmation of the first case of Ebola virus disease. No secondary cases of Ebola virus disease occurred among the vaccinees. Adverse events following vaccination were reported in 47 (17%) 6-17 year olds (all mild) and 412 (36%) adults (individuals older than 18 years; 98% were mild). Children reported fewer arthralgia events than adults (one [<1%] of 303 children vs 81 [7%] of 1207 adults). No severe vaccine-related adverse events were reported., Interpretation: The results show that a ring vaccination strategy can be rapidly and safely implemented at scale in response to Ebola virus disease outbreaks in rural settings., Funding: WHO, Gavi, and the World Food Programme., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Fiji, an upper-middle income state in the Pacific Ocean, has experienced an increase in confirmed case notifications of enteric fever caused by Salmonella enterica serovar Typhi (S. Typhi). To characterize the epidemiology of typhoid exposure, we conducted a cross-sectional sero-epidemiological survey measuring IgG against the Vi antigen of S. Typhi to estimate the effect of age, ethnicity, and other variables on seroprevalence. Epidemiologically relevant cut-off titres were established using a mixed model analysis of data from recovering culture-confirmed typhoid cases. We enrolled and assayed plasma of 1787 participants for anti-Vi IgG; 1,531 of these were resident in mainland areas that had not been previously vaccinated against S. Typhi (seropositivity 32.3% (95%CI 28.2 to 36.3%)), 256 were resident on Taveuni island, which had been previously vaccinated (seropositivity 71.5% (95%CI 62.1 to 80.9%)). The seroprevalence on the Fijian mainland is one to two orders of magnitude higher than expected from confirmed case surveillance incidence, suggesting substantial subclinical or otherwise unreported typhoid. We found no significant differences in seropositivity prevalences by ethnicity, which is in contrast to disease surveillance data in which the indigenous iTaukei Fijian population are disproportionately affected. Using multivariable logistic regression, seropositivity was associated with increased age (odds ratio 1.3 (95% CI 1.2 to 1.4) per 10 years), the presence of a pit latrine (OR 1.6, 95%CI 1.1 to 2.3) as opposed to a septic tank or piped sewer, and residence in settlements rather than residential housing or villages (OR 1.6, 95% CI 1.0 to 2.7). Increasing seropositivity with age is suggestive of low-level endemic transmission in Fiji. Improved sanitation where pit latrines are used and addressing potential transmission routes in settlements may reduce exposure to S. Typhi. Widespread unreported infection suggests there may be a role for typhoid vaccination in Fiji, in addition to public health management of cases and outbreaks.

Background: Men who have sex with men (MSM) have a high lifetime risk of anogenital warts and cancers related to infection with human papillomavirus (HPV). They also benefit less from herd protection than heterosexual males in settings with female-only HPV vaccination., Methods: We evaluated the potential health impact and cost-effectiveness of offering vaccination to MSM who visit genitourinary medicine (GUM) clinics. We used a mathematical model of HPV 6/11/16/18 sexual transmission within an MSM population in England, parameterized with sexual behaviour, GUM attendance, HPV prevalence, HIV prevalence, warts, and cancer incidence data. Interventions considered were offering HPV vaccination to either HIV-positive MSM or MSM regardless of HIV status, for age bands 16-25, 16-30, 16-35, and 16-40 years., Results: Substantial declines in anogenital warts and male HPV-related cancer incidence are projected to occur following an offer of vaccination to MSM. MSM not attending GUM clinics will partially benefit from herd protection. Offering vaccination to HIV-positive MSM up to age 40 is likely to be cost-effective if vaccine procurement and administration costs are below £96.50 a dose. At £48 a dose, offering vaccination to all MSM up to age 40 is likely to be cost-effective., Conclusions: Quadrivalent HPV vaccination of MSM via GUM clinics is likely to be an effective and cost-effective way of reducing the burden of HPV-related disease in MSM., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The present study aims to evaluate the cost-effectiveness of extending the pre-2013 influenza immunisation programme for high-risk and elderly individuals to those at low risk of developing complications following infection with seasonal influenza., Methods: We performed an economic evaluation comparing different extensions of the pre-2013 influenza programme to seven possible age groups of low-risk individuals (aged 2-4 years, 50-64 years, 5-16 years, 2-4 and 50-64 years, 2-16 years, 2-16 and 50-64 years, and 2-64 years). These extensions are evaluated incrementally on four base scenarios (no vaccination, risk group only with coverage as observed between 1995 and 2009, risk group and 65+, and risk group with 75% coverage and 65+). Impact of vaccination is assessed using a transmission model built and parameterised from a previously published study. The study population is all individuals of all ages in England and Wales representing an average total of 52.6 million people over 14 influenza seasons (1995-2009)., Results: The influenza programme (risk group and elderly) prior to 2013 is likely to be cost effective (incremental cost effectiveness ratio: 7,475 £/QALY, net benefit: 253 M£ [15-829]). Extension to any one of the low-risk target groups defined earlier is likely to be cost-effective. However, strategies that do not include vaccination of school-aged children are less likely to be cost-effective. The most efficient strategy is extension to the 5-16 year age group while universal vaccination (extension to all low-risk individuals over 2 years) will achieve the highest net benefit. While extension to the 2-16 year age group is likely to be very cost effective, the cost-effectiveness of extensions beyond 2-16 years is very uncertain. Extension to the 5-16 year age group would likely remain cost-effective even without herd immunity effects to other age groups. As our study includes a strong historical component, our results depend on the efficacy of the influenza vaccine remaining at levels similar to the ones achieved in the past over a long-period of time (assumed to vary between 28% and 70% depending of the circulating strains and age groups)., Conclusions: Making use of surveillance data from over a decade in conjunction with a dynamic model, we find that vaccination of children in the United Kingdom is likely to be highly cost-effective, not only for their own benefit but also to reduce the disease burden in the rest of the community.

Despite a recommendation by the World Health Organization (WHO) that typhoid vaccines be considered for the control of endemic disease and outbreaks, programmatic use remains limited. Transmission models and economic evaluation may be informative in decision making about vaccine programme introductions and their role alongside other control measures. A literature search found few typhoid transmission models or economic evaluations relative to analyses of other infectious diseases of similar or lower health burden. Modelling suggests vaccines alone are unlikely to eliminate endemic disease in the short to medium term without measures to reduce transmission from asymptomatic carriage. The single identified data-fitted transmission model of typhoid vaccination suggests vaccines can reduce disease burden substantially when introduced programmatically but that indirect protection depends on the relative contribution of carriage to transmission in a given setting. This is an important source of epidemiological uncertainty, alongside the extent and nature of natural immunity. Economic evaluations suggest that typhoid vaccination can be cost-saving to health services if incidence is extremely high and cost-effective in other high-incidence situations, when compared to WHO norms. Targeting vaccination to the highest incidence age-groups is likely to improve cost-effectiveness substantially. Economic perspective and vaccine costs substantially affect estimates, with disease incidence, case-fatality rates, and vaccine efficacy over time also important determinants of cost-effectiveness and sources of uncertainty. Static economic models may under-estimate benefits of typhoid vaccination by omitting indirect protection. Typhoid fever transmission models currently require per-setting epidemiological parameterisation to inform their use in economic evaluation, which may limit their generalisability. We found no economic evaluation based on transmission dynamic modelling, and no economic evaluation of typhoid vaccination against interventions such as improvements in sanitation or hygiene., (Copyright © 2015. Published by Elsevier Ltd.)

Background: Human papillomavirus (HPV) vaccination of girls will have relatively little effect on HPV-related disease in men who have sex with men (MSM). We determined HPV prevalence and risk factors in MSM to inform the potential effectiveness of vaccinating MSM., Methods: Cross-sectional study of 522 MSM aged 18-40 attending a London sexual health clinic who completed a computer-assisted self-interview. Urine and two swabs (anal and penile/scrotal/perianal) were collected and tested using an in-house Luminex-based HPV genotyping system., Results: Prevalence of DNA of the vaccine-preventable HPV types in ano-genital specimens of men was 87/511 (17.0%), 166/511 (32.5%) and 232/511 (45.4%) for the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18) and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccine types, respectively. A total of 25.1% had one of the quadrivalent types, and 7.4% had 2+ types. Median age at first anal sex was 19 (IQR 17-23) and at first clinic attendance was 24 (IQR 20-27). The increase in the odds of any HPV infection per year of age was 4.7% (95% CI 1.2-8.4)., Conclusions: On the basis of the current infection status, most MSM, even among a high-risk population attending a sexual health clinic, are not currently infected with the vaccine-type HPV. A targeted vaccination strategy for MSM in the UK could have substantial benefits.

Pneumococcal conjugate vaccines (PCVs) have substantially reduced morbidity and mortality of pneumococcal disease. The impact of the 7-valent PCV on all-serotype invasive pneumococcal disease (IPD) among children was reported to vary between high-income countries. We investigate the ability to predict this heterogeneity from pre-vaccination data. We propose a parsimonious model that predicts the impact of PCVs from the odds of vaccine serotype (VT) among carriers and IPD cases in the pre-PCV period, assuming that VT are eliminated in a mature PCV programme, that full serotype replacement occurs in carriage and that invasiveness of the NVT group is unchanged. We test model performance against the reported impact of PCV7 on childhood IPD in high-income countries from a recent meta-analysis. The odds of pre-PCV7 VT IPD, PCV schedule, PCV coverage and whether a catch up campaign was used for introduction was gathered from the same analysis. We conducted a literature review and meta-analysis to obtain the odds of pre-PCV7 VT carriage in the respective settings. The model predicted the reported impact on childhood IPD of mature PCV programmes; the ratio of predicted and observed incidence risk ratios was close to 1 in all settings. In the high income settings studied differences in schedule, coverage, and catch up campaigns were not associated with the observed heterogeneity in impact of PCV7 on childhood all-serotype IPD. The pre-PCV7 proportion of VT IPD alone also had limited predictive value. The pre-PCV7 proportion of VT carriage and IPD are the main determinants for the impact of PCV7 on childhood IPD and can be combined in a simple model to provide predictions of the vaccine preventable burden of IPD.

Introduction: Despite the global success of Hib vaccination in reducing disease and mortality, uncertainty about the disease burden and the potential impact of Hib vaccination in Southeast Asia has delayed the introduction of vaccination in some countries in the region. Hib vaccination was introduced throughout Vietnam in July 2010 without catch-up. In an observational, population based surveillance study we estimated the impact of routine Hib vaccination on all cause radiologically confirmed childhood pneumonia in Nha Trang, Vietnam., Materials and Methods: In 2007 active hospital based surveillance was established in Khanh Hoa General Hospital, the only hospital in Nha Trang, Khanh Hoa province. Nasopharyngeal samples and chest radiographs are taken routinely from all children diagnosed with acute respiratory illness on admission. For admissions between 02/2007 and 03/2012 chest radiographs were interpreted for the presence of WHO primary endpoint pneumonia and nasopharyngeal swabs were analysed by PCR for the presence of Influenza A or B, RSV and rhinovirus. We employed Poisson regression to estimate the impact of Hib vaccination on radiologically confirmed pneumonia (RCP) while statistically accounting for potential differences in viral circulation in the post vaccination era which could have biased the estimate., Results: Of 3151 cases admitted during the study period, 166 had RCP and major viruses were detected in 1601. The adjusted annual incidence of RCP in children younger than 5 years declined by 39% (12-58%) after introduction of Hib vaccination. This decline was most pronounced in children less than 2 years old, adjusted IRR: 0.52 (0.33-0.81), and no significant impact was observed in the 2-4 years old who were not eligible for vaccination, adjusted IRR: 0.96 (0.52-1.72)., Discussion: We present early evidence that the burden of Hib associated RCP in Nha Trang before vaccination was substantial and that shortly after introduction to the routine childhood immunisation scheme vaccination has substantially reduced that burden., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Data on the prevalence of nasopharyngeal carriage of S.pneumoniae in all age groups are important to help predict the impact of introducing pneumococcal conjugate vaccines (PCV) into routine infant immunization, given the important indirect effect of the vaccine. Yet most carriage studies are limited to children under five years of age. We here explore the association between carriage prevalence and serotype distribution in children aged ≥5 years and in adults compared to children., Methods: We conducted a systematic review of studies providing carriage estimates across age groups in healthy populations not previously exposed to PCV, using MEDLINE and Embase. We used Bayesian linear meta-regression models to predict the overall carriage prevalence as well as the prevalence and distribution of vaccine and nonvaccine type (VT and NVT) serotypes in older age groups as a function of that in <5 y olds., Results: Twenty-nine studies compromising of 20,391 individuals were included in the analysis. In all studies nasopharyngeal carriage decreased with increasing age. We found a strong positive linear association between the carriage prevalence in pre-school childen (<5 y) and both that in school aged children (5-17 y olds) and in adults. The proportion of VT serotypes isolated from carriers was consistently lower in older age groups and on average about 73% that of children <5 y among 5-17 y olds and adults respectively. We provide a prediction model to infer the carriage prevalence and serotype distribution in 5-17 y olds and adults as a function of that in children <5 years of age., Conclusion: Such predictions are helpful for assessing the potential population-wide effects of vaccination programmes, e.g. via transmission models, and thus assist in the design of future pneumococcal conjugate vaccination strategies.

More than 90 capsular serotypes of Streptococcus pneumoniae coexist despite competing for nasopharyngeal carriage and a gradient in fitness. The underlying mechanisms for this are poorly understood and make assessment of the likely population impact of vaccination challenging. We use an individual-based simulation model to generalize widely used deterministic models for pneumococcal competition and show that in these models short-term serotype-specific and serotype non-specific immunity could constitute the mechanism governing between-host competition and coexistence. We find that non-specific immunity induces between-host competition and that serotype-specific immunity limits a type's competitive advantage and allows stable coexistence of multiple serotypes. Serotypes carried at low prevalence show high variance in carriage levels, which would result in apparent outbreaks if they were highly pathogenic. Vaccination against few serotypes can lead to elimination of the vaccine types and induces replacement by others. However, in simulations where the elimination of the targeted types is achieved only by a combination of vaccine effects and the competitive pressure of the non-vaccine types, a universal vaccine with similar-type-specific effectiveness can fail to eliminate pneumococcal carriage and offers limited herd immunity. Hence, if vaccine effects are insufficient to control the majority of serotypes at the same time, then exploiting the competitive pressure by selective vaccination can help control the most pathogenic serotypes.

The demand for vaccination against infectious diseases involves a choice between vaccinating and not vaccinating, in which there is a trade-off between the benefits and costs of each option. The aim of this paper is to investigate these trade-offs and to estimate how the perceived prevalence and severity of both the disease against which the vaccine is given and any vaccine associated adverse events (VAAE) might affect demand. A discrete choice experiment (DCE) was used to elicit stated preferences from a representative sample of 369 U.K. mothers of children below 5 years of age, for three hypothetical vaccines. Cost was included as an attribute, which enabled estimation of the willingness to pay for different vaccines having differing levels of the probability of occurrence and severity of both the infection and VAAE. The results suggest that the severity of the health effects associated with both the diseases and VAAEs exert an important influence on the demand for vaccination, whereas the probability of these events occurring was not a significant predictor. This has important implications for public health policy, which has tended to focus on the probability of these health effects as the main influence on decision making. Our results also suggest that anticipated regrets about the consequences of making the wrong decision also exert an influence on demand.

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.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Early observations from countries that have introduced rotavirus vaccination suggest that there may be indirect protection for unvaccinated individuals, but it is unclear whether these benefits will extend to the long term. Transmission dynamic models have attempted to quantify the indirect protection that might be expected from rotavirus vaccination in developed countries, but results have varied. To better understand the magnitude and sources of variability in model projections, we undertook a comparative analysis of transmission dynamic models for rotavirus. We fit five models to reported rotavirus gastroenteritis (RVGE) data from England and Wales, and evaluated outcomes for short- and long-term vaccination effects. All of our models reproduced the important features of rotavirus epidemics in England and Wales. Models predicted that during the initial year after vaccine introduction, incidence of severe RVGE would be reduced 1.8-2.9 times more than expected from the direct effects of the vaccine alone (28-50% at 90% coverage), but over a 5-year period following vaccine introduction severe RVGE would be reduced only by 1.1-1.7 times more than expected from the direct effects (54-90% at 90% coverage). Projections for the long-term reduction of severe RVGE ranged from a 55% reduction at full coverage to elimination with at least 80% coverage. Our models predicted short-term reductions in the incidence of RVGE that exceeded estimates of the direct effects, consistent with observations from the United States and other countries. Some of the models predicted that the short-term indirect benefits may be offset by a partial shifting of the burden of RVGE to older unvaccinated individuals. Nonetheless, even when such a shift occurs, the overall reduction in severe RVGE is considerable. Discrepancies among model predictions reflect uncertainties about age variation in the risk and reporting of RVGE, and the duration of natural and vaccine-induced immunity, highlighting important questions for future research.

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., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

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., (Copyright 2010 Elsevier Ltd. All rights reserved.)

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.

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 pound30,000 (euro37,700; $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 pound13- pound21 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.

Aim: Rotavirus is the leading cause of acute gastroenteritis in children. Two rotavirus vaccines (RotaTeq and Rotarix) have recently completed clinical trials. We investigated whether routine infant immunisation with either vaccine can be cost effective., Methods: We compared costs and outcomes of vaccination using a cohort model, following children over the first 5 years of life. We estimated health provider costs, economic costs and quality adjusted life years (QALYs) lost due to rotavirus-related deaths, hospital admissions, nosocomial infections, accident and emergency attendances, general practice consultations and calls to NHS Direct., Results: Under base case assumptions, a programme using RotaTeq (priced at pound 25 a dose) would cost the health provider pound 79,900 per QALY gained. Using Rotarix (priced at pound 35 a dose) would cost pound 61,000 per QALY gained. Univariate and multivariate sensitivity analysis indicate that at these prices an immunisation programme would be unlikely to be cost-effective for any realistic value of the key parameters., Conclusions: Rotavirus immunisation could reduce the substantial short-term morbidity burden due to rotavirus, but is unlikely to be deemed cost effective unless the vaccine is competitively priced.

With a human papillomavirus (HPV) vaccine soon to become available for widespread use, several studies have modelled the cost-effectiveness of vaccination. These pioneer studies are likely to be influential on the design of further analyses, and we have therefore summarised and critically reviewed the strengths and limitations of their methods and assumptions. Despite a lack of transparency in some key elements, the most influential assumptions were identified as relating to vaccine effectiveness, cervical screening, and model design. Although the studies suggest that the introduction of an HPV vaccine could be cost effective compared with current practice in the USA, there is still substantial uncertainty around key variables, and model validation seems insufficient. The desirability of vaccinating boys in addition to girls has been explored in only one study. Further refinements to model design and epidemiological variables of (type-specific) HPV disease progression, and expansions on the options for vaccine use, are required for policy making.

Background: The recent emergence of hypervirulent subtypes of avian influenza has underlined the potentially devastating effects of pandemic influenza. Were such a virus to acquire the ability to spread efficiently between humans, control would almost certainly be hampered by limited vaccine supplies unless global spread could be substantially delayed. Moreover, the large increases that have occurred in international air travel might be expected to lead to more rapid global dissemination than in previous pandemics., Methods and Findings: To evaluate the potential of local control measures and travel restrictions to impede global dissemination, we developed stochastic models of the international spread of influenza based on extensions of coupled epidemic transmission models. These models have been shown to be capable of accurately forecasting local and global spread of epidemic and pandemic influenza. We show that under most scenarios restrictions on air travel are likely to be of surprisingly little value in delaying epidemics, unless almost all travel ceases very soon after epidemics are detected., Conclusions: Interventions to reduce local transmission of influenza are likely to be more effective at reducing the rate of global spread and less vulnerable to implementation delays than air travel restrictions. Nevertheless, under the most plausible scenarios, achievable delays are small compared with the time needed to accumulate substantial vaccine stocks.

A vaccination programme offering hepatitis B (HBV) vaccine at reception into prison has been introduced into selected prisons in England and Wales. The work here considers the impact of prison vaccination on the incidence and prevalence of hepatitis B virus (HBV) in the injecting drug user (IDU) population of England and Wales. A dynamic model of the transmission of HBV in IDUs is developed with key model assumptions and parameters being subject to sensitivity analyses. The base case model (that assumes that the vaccination coverage on prison reception is 5% in 2002, 10% in 2003 and then increases linearly up to 50% of prison receptions being vaccinated by 2006) predicts that the incidence of HBV in IDUs might be reduced by almost 80% in 12 years, and the HBV prevalence (IDUs ever infected by HBV) may be reduced from approximately 18% in 2002 to 7% in 2015. The model presented here demonstrates that HBV vaccination on prison reception can have a significant impact on the prevalence and incidence of HBV in the IDU population over time.

In recent years, several countries have experienced increases in the incidence of serogroup C meningococcal disease. It can be controlled with older polysaccharide vaccines and particularly the recently developed conjugate vaccines. For 21 developed countries, we investigated the role that economic evaluation played in the decision to introduce the conjugate vaccine into either the routine childhood vaccination schedule, as a mass vaccination 'catch-up' campaign or not at all. A literature review was performed and experts from these countries were contacted. For six countries, we identified published economic evaluations for meningococcal C conjugate vaccination. In four of them (Australia, Canada [Quebec], The Netherlands and the UK) the analyses were performed before a decision about the use of the conjugate vaccine was made. In all of these countries, the economic evaluation offered guidance as to the most efficient way to add the conjugate vaccine to the routine infant immunisation schedule and, in three countries, this advice was adopted by decision makers. In Portugal and Switzerland, initial vaccination decisions were made without the economic evaluations that are influencing current decision making. Of the countries without economic evaluations, six implemented vaccination programmes. Overall, there was a positive correlation between the reported incidence of meningococcal C disease and (a) the decision to vaccinate and (b) performing an economic evaluation. All economic evaluations were modelling studies. The reported cost-effectiveness ratios were sensitive to the age of vaccination, the future meningococcal incidence, vaccine price and some methodological characteristics that varied widely between studies making direct comparisons difficult. In conclusion, in almost all countries where economic evaluations for meningococcal C conjugate vaccinations have been conducted, their results had an important role in the decision-making process. However, in most countries with strongly increasing meningococcal incidence, public health considerations took precedence. In order to improve the international comparability of such studies, firmer national and international modelling guidelines and better adherence to such guidelines seem necessary.

A deterministic realistic age-structured model was used to predict the impact of vaccination on the incidence of varicella and zoster. Unit costs, estimated from literature, were applied to the predicted health outcomes. Various vaccination programs were investigated and a sensitivity analysis was performed. Assuming no impact of vaccination on zoster, varicella vaccination is estimated to cost 45,000 dollars, 51,000 dollars and 18,000 dollars per life-year gained from the health payer's perspective for infant, infant with catch-up campaign, and preteen programs, respectively. From the societal perspective, mass infant varicella vaccination was estimated to be highly cost saving in Canada. Importantly, infant varicella vaccination could result in a short- to medium-term increase of zoster incidence and thus cause vaccination to be highly cost-ineffective (118,000 dollars per life-year gained) under the health payer's perspective. From a health payer's perspective the preteen vaccination is the only strategy that is deemed cost-effective. The cost-effectiveness of infant vaccination rests heavily on the unknown relationship between varicella and zoster.

Assuming that the level of Bacille Calmette Guerin (BCG) coverage gives a measure of access to immunisation services, it is possible to derive what fraction of infants are not immunised against measles due to under-utilisation of existing services (rather than unavailability of services). According to the most recent official statistics, the overall coverage for measles vaccine is 53% in Africa (10% lower than for BCG). This difference amounts to 3 million African children who will not be vaccinated against measles this year even though they probably have access to immunisation services.

Although there are many models which are used to calculate the health benefits (and thus the cost-effectiveness) of vaccination programmes, they can be divided into two groups: those which assume a constant force of infection, that is a constant per-susceptible rate of infection; and those which assume that the force of infection (at time t) is a function of the number of infectious individuals in the population at that time (dynamic models). In constant force of infection models the per-susceptible rate of infection is not altered, whereas in dynamic models mass immunization results in fewer infectious individuals in the community and thus a lower force of infection acting on those who were not immunized. We take an example of each of these types of model, examine their underlying assumptions and compare their predictions of the cost-effectiveness of a mass immunization programme against a hypothetical close contact infection, such as measles. We show that if cases of infection are the outcome of interest then the constant force of infection model will always underestimate the cost-effectiveness of the immunization programme except at the extremes when no one or everyone is immunized. However, unlike the constant force of infection model, the dynamic model predicts an increase in the average age at infection after immunization which could impact on the estimate of the cost-effectiveness of the programme if the risk of developing serious disease is a function of the age at infection (as, for instance, is the case for congenital rubella syndrome). Taking cases of infection as the outcome measure and using the dynamic model, the undiscounted cost-effectiveness ratio will tend to decline over time and approach a constant value, as the system moves from pre- to post-immunization equilibrium. We go on to show how the cost-effectiveness of a fixed-term immunization programme might change over time, and discuss why, under most circumstances, decision makers should not assume that elimination (permitting termination of mass immunization) will occur., (Copyright 1999 John Wiley & Sons, Ltd.)

There is still no consensus on which hepatitis B virus (HBV) immunisation option should be adopted in the United Kingdom (UK). This review considers why three recent UK studies on the subject reached different conclusions, and whether they provide sufficient information to base an informed decision on cost-effectiveness grounds. The studies differed in methodology, particularly in the models used to estimate the effectiveness of the competing programmes. This led the authors to draw very different conclusions as to the relative cost-effectiveness of universal infant and selective immunisation, probably because the study that favoured infant immunisation omitted an allowance for the indirect protection afforded to others by immunisation of a proportion of the population. This would lead to the underestimation of the relative effectiveness of a programme targeted at high-risk individuals. Selective vaccination is probably more cost-effective than mass immunisation, but universal immunisation may still be considered a cost-effective option (in addition to selective immunisation) if future health benefits are not discounted (i.e., given a lower value than present ones). If future health benefits are discounted then mass infant immunisation is almost certainly not cost-effective. If selective immunisation is to be adopted, then the current (selective) strategy should be properly implemented, as it appears to have had little impact on HBV infection and disease.

A dynamic model of the transmission of hepatitis B virus (HBV) was used to investigate some of the possible implications of the loss of vaccine-induced immunity on the effectiveness of mass HBV vaccination in high endemicity countries. The model, which describes the processes of horizontal and vertical transmission of HBV in a rapidly growing population, was based on one previously published, modified to allow for waning vaccine-induced immunity. All model parameters were empirically based. Summaries of published data provided estimates of the mean duration of immunity in vaccine responders and age-dependence in the risk of developing acute HBV disease. Simulations of the temporal and long-term impact of mass infant immunization on the prevalence of HBV chronic carriage and acute disease suggested that booster doses are of little benefit in coping with waning vaccine protection. The key factor is that vaccine-induced protection should be long enough to prevent infection in the first few years of life, when the risk of developing chronic carriage is highest.