In 2024 England, in common with many other countries, experienced a pertussis resurgence the cause of which is unclear. We used a pertussis transmission model, previously developed to investigate the cause of the pertussis resurgence in England in 2012, to explore potential factors contributing to the increase in pertussis cases observed in England in 2024. An age-stratified dynamic transmission model fitted to pertussis notification data from England between 1953 and 2013 was run until 2034 with and without changes in social mixing as estimated from Google mobility and school attendance data during the COVID-19 pandemic. The model assumes vaccination protects better against disease than pertussis infection, and that infected vaccinees can transmit if asymptomatic or with only mild/atypical symptoms. Infection is assumed to result in protection against clinical symptoms and infection, and provide more durable immunity than vaccination. Counterfactual scenarios were run to explore the effect of reductions in vaccine coverage during the pandemic and of the addition in 2014 of boosters in the 2nd year of life and in adolescence. A resurgence was only generated with reduced social mixing and could not be explained by short-term reductions in vaccine coverage. Additional boosters from 2014 would not have prevented a resurgence. Peaks of increased pertussis incidence are predicted over the next decade. The parameter sets that generated a resurgence in 2024 had the shortest duration of acellular vaccine protection, median 5 years with 90

Three separate transmission models were developed to investigate the drivers of pertussis resurgence in the United States (US), United Kingdom (UK) and Australia. While these models were all able to reproduce pertussis trends in the setting for which they were developed, they include different assumptions about infection, immunity and vaccination, reflecting the uncertainties of pertussis epidemiology. A key question is whether, despite these differences, these models produce consistent results across settings with diverse vaccination schedules, epidemiologic histories and surveillance systems. A pilot study was conducted in 2016 for the World Health Organization to examine whether findings from the US, UK and Australian models were generalisable to other country contexts. In Stage I of the study, each of the UK, US and Australian models was applied to the other two settings, using the previously identified best fitting parameter sets. The major aim of this phase was to determine whether there is overall evidence that the models may be applied to high-income countries with long histories of pertussis vaccination. In Stage II of the study, each of the UK, US and Australian models was fitted to the other two settings using the same model selection techniques originally applied, to evaluate consistency of model results and identify broadly congruent characteristics of pertussis transmission and immunity. A major aim of this phase was to determine whether, for a given country, the different models provided similar reasons for pertussis resurgence. Each of the models worked well in the setting for which they were designed, but were not able to capture all of the epidemiologic features in different countries. Limited availability of historical data on vaccination, age-specific burden of disease and the relationship between infection and disease is likely to make fitting of the models to other settings without adaptation challenging. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the World Health Organization. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The source data used to develop the models compared in this project were publicly available within the published modelling papers: 1) UK: Choi, Y.H., Campbell, H., Amirthalingam, G. et al. Investigating the pertussis resurgence in England and Wales, and options for future control. BMC Med 14, 121 (2016). https://doi.org/10.1186/s12916-016-0665-8 2) US: Gambhir M., Clark T.A., Cauchemez S., Tartof S.Y., Swerdlow D.L., Ferguson N.M. (2015) A Change in Vaccine Efficacy and Duration of Protection Explains Recent Rises in Pertussis Incidence in the United States. PLoS Comput Biol 11(4): e1004138. doi:10.1371/journal.pcbi.1004138 3) Australia: Campbell P.T., McCaw J.M., McIntyre P., McVernon J. (2015) Defining long-term drivers of pertussis resurgence, and optimal vaccine control strategies. Vaccine. 33(43):5794-5800. doi: 10.1016/j.vaccine.2015.09.025. Epub 2015 Sep 19. PMID: 26392008. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Measles outbreaks have occurred across England since mid-2023. We estimated measles and rubella antibody seroprevalence among individuals in 2018 in English regions outside London, and estimated the effective reproduction number (Re) for measles to predict the potential for outbreaks. Using validated enzyme-linked immunosorbent assays, anti-Measles and anti-Rubella IgG antibodies were measured in residual sera from 3758 1-30-year-olds born after introduction of measles-mumps-rubella vaccination who submitted samples to clinical laboratories outside London. The measles Re was calculated using seronegatives defined by the manufacturer’s cutoff, mixture modelling, and vaccination coverage data. Using the manufacturer’s cutoffs, the overall proportion seronegative to measles was 9.2

Background. In 2024 England, in common with many other countries, experienced a pertussis resurgence the cause of which is unclear. We used a pertussis transmission model, previously developed to investigate the cause of the pertussis resurgence in England in 2012, to explore potential factors contributing to the increase in pertussis cases observed in England in 2024. Methods An age-stratified dynamic transmission model fitted to pertussis notification data from England between 1953 and 2013 was run until 2054 with and without changes in social mixing as estimated from Google mobility and school attendance data during the COVID-19 pandemic. The model assumes vaccination protects better against disease than pertussis infection, and that an infection results in more durable immunity than vaccination. Counterfactual scenarios were also run to explore the effect of reductions in vaccine coverage during the pandemic and of the addition in 2014 of boosters in the 2nd year of life and in adolescence. Results A resurgence was only generated with reduced social mixing and could not be explained by short-term reductions in vaccine coverage. Additional boosters at 18 months and 14 years from 2014 would not have prevented a resurgence though would have reduced its magnitude. Peaks of increased pertussis incidence are predicted over the next decade. The parameter sets that generated a resurgence in 2024 had the shortest duration of acellular vaccine protection, median 5 years with 90% protection against infection. Conclusion This modelling study implicates reduced mixing in England during the COVID-19 pandemic as the cause of the pertussis resurgence in 2024 together with the short duration of protection from acellular vaccine. Interruption of the background rate of natural boosting during the pandemic increased the pool of susceptible individuals resulting in increased transmission post-pandemic with clinical cases in those with waned vaccine–induced protection and the unvaccinated, including infants of unvaccinated mothers. In countries using acellular pertussis vaccines, infection continues to play an important role in maintaining population immunity around an endemic equilibrium. Improved pertussis vaccines that provide more complete and more durable protection against infection are needed to improve pertussis control.

Background:Vaccination of infants with pneumococcal conjugate vaccines is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. Objectives:The primary objective was to compare the immunogenicity of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13. The main secondary objective was to compare the seroefficacy of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13. Methods:We searched the Cochrane Library, EMBASE, Global Health, MEDLINE, ClinicalTrials.gov and trialsearch.who.int up to July 2022. Studies were eligible if they directly compared either pneumococcal conjugate vaccine-7, pneumococcal conjugate vaccine-10 or pneumococcal conjugate vaccine-13 in randomised trials of children under 2 years of age, and provided immunogenicity data for at least one time point. Individual participant data were requested and aggregate data used otherwise. Outcomes included the geometric mean ratio of serotype-specific immunoglobulin G and the relative risk of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Each trial was analysed to obtain the log of the ratio of geometric means and its standard error. The relative risk of seroinfection ('seroefficacy') was estimated by comparing the proportion of participants with seroinfection between vaccine groups. The log-geometric mean ratios, log-relative risks and their standard errors constituted the input data for evidence synthesis. For serotypes contained in all three vaccines, evidence could be synthesised using a network meta-analysis. For other serotypes, meta-analysis was used. Results from seroefficacy analyses were incorporated into a mathematical model of pneumococcal transmission dynamics to compare the differential impact of pneumococcal conjugate vaccine-10 and pneumococcal conjugate vaccine-13 introduction on invasive pneumococcal disease cases. The model estimated the impact of vaccine introduction over a 25-year time period and an economic evaluation was conducted. Results:In total, 47 studies were eligible from 38 countries. Twenty-eight and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. Geometric mean ratios comparing pneumococcal conjugate vaccine-13 versus pneumococcal conjugate vaccine-10 favoured pneumococcal conjugate vaccine-13 for serotypes 4, 9V and 23F at 1 month after primary vaccination series, with 1.14- to 1.54-fold significantly higher immunoglobulin G responses with pneumococcal conjugate vaccine-13. Risk of seroinfection prior to the time of booster dose was lower for pneumococcal conjugate vaccine-13 for serotype 4, 6B, 9V, 18C and 23F than for pneumococcal conjugate vaccine-10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Twofold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (relative risk 0.46, 95% confidence interval 0.23 to 0.96). In modelled scenarios, pneumococcal conjugate vaccine-13 or pneumococcal conjugate vaccine-10 introduction in 2006 resulted in a reduction in cases that was less rapid for pneumococcal conjugate vaccine-10 than for pneumococcal conjugate vaccine-13. The pneumococcal conjugate vaccine-13 programme was predicted to avoid an additional 2808 (95% confidence interval 2690 to 2925) cases of invasive pneumococcal disease compared with pneumococcal conjugate vaccine-10 introduction between 2006 and 2030. Limitations:Analyses used data from infant vaccine studies with blood samples taken prior to a booster dose. The impact of extrapolating pre-booster efficacy to post-booster time points is unknown. Network meta-analysis models contained significant heterogeneity which may lead to bias. Conclusions:Serotype-specific differences were found in immunogenicity and seroefficacy between pneumococcal conjugate vaccine-13 and pneumococcal conjugate vaccine-10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These methods can be used to compare the pneumococcal conjugate vaccines and optimise vaccination strategies. For future work, seroefficacy estimates can be determined for other pneumococcal vaccines, which could contribute to licensing or policy decisions for new pneumococcal vaccines. Study registration:This study is registered as PROSPERO CRD42019124580. Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/03) and is published in full in Health Technology Assessment; Vol. 28, No. 34. See the NIHR Funding and Awards website for further award information.

Background Paediatric pneumococcal conjugate vaccine (PCV) programmes in England using seven-valent PCV (PCV7) in 2006 and 13-valent PCV (PCV13) in 2010 have reduced vaccine-type invasive pneumococcal disease, but the overall effect has been reduced by an increase in invasive pneumococcal disease due to non-vaccine serotypes and serotype 3. We developed pneumococcal transmission models to investigate the potential effect on invasive pneumococcal disease of higher valency PCVs covering an additional two (ie, 15-valent PCV [PCV15]) or seven serotypes (ie, 20-valent PCV [PCV20]) in England. Methods We conducted a modelling study using realistic, age-structured, and compartmental deterministic models fitted to carriage data from before the introduction of PCVs and invasive pneumococcal disease data from before and after the introduction of PCV7 and PCV13 in England from the UK Heath Security Agency invasive pneumococcal disease surveillance system. We estimated key parameters, including PCV7 and PCV13 efficacy against vaccine-type carriage and invasiveness of PCV7 serotypes; the additional serotypes in PCV13, PCV15 and PCV20; and non-vaccine serotypes. We simulated the effect of transitioning from PCV13 to PCV15 or PCV20 in infants under the current 1 + 1 vaccination schedule and investigated the effect of reduced carriage protection against PCV13 serotypes due to attenuation of immunogenicity in higher valency vaccines. Findings Our results suggest that PCV15 might increase overall invasive pneumococcal disease as the reduction in vaccine-type invasive pneumococcal disease would be counterbalanced by an increase in non-PCV15 invasive pneumococcal disease. By contrast, PCV20 is projected to have a substantial impact on overall invasive pneumococcal disease due to higher invasiveness of the additional serotypes covered by PCV20 than the replacing non-vaccine serotypes. Reduced carriage protection against PCV13 serotypes with higher valency vaccines would amplify these effects. Interpretation Replacing PCV13 with PCV20 is likely to have a substantial public health benefit, but PCV15 could potentially increase the overall burden of disease. Funding UK Health Security Agency and National Institute of Health Research.

Background Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. Methods In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global Health, Medline, clinicaltrials.gov and trialsearch.who.int up to February 17, 2023 with no language restrictions. Studies were eligible if they presented data comparing the immunogenicity of either PCV7, PCV10 or PCV13 in head-to-head randomised trials of young children under 2 years of age, and provided immunogenicity data for at least one time point after the primary vaccination series or the booster dose. Publication bias was assessed via Cochrane's Risk Of Bias due to Missing Evidence tool and comparison-adjusted funnel plots with Egger's test. Individual participant level data were requested from publication authors and/or relevant vaccine manufacturers. Outcomes included the geometric mean ratio (GMR) of serotype-specific IgG and the relative risk (RR) of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Seroefficacy was defined as the RR of seroinfection. We also estimated the relationship between the GMR of IgG one month after priming and the RR of seroinfection by the time of the booster dose. The protocol is registered with PROSPERO, ID CRD42019124580. Findings 47 studies were eligible from 38 countries across six continents. 28 and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. GMRs comparing PCV13 vs PCV10 favoured PCV13 for serotypes 4, 9V, and 23F at 1 month after primary vaccination series, with 1.14-to 1.54-fold significantly higher IgG responses with PCV13. Risk of seroinfection prior to the time of booster dose was lower for PCV13 for serotype 4, 6B, 9V, 18C and 23F than for PCV10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Two-fold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (RR 0.46, 95% CI 0.23-0.96). Interpretation Serotype-specific differences were found in immunogenicity and seroefficacy between PCV13 and PCV10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These findings could be used to compare PCVs and optimise vaccination strategies. 2023;61:

To eliminate cervical cancer as a public health problem, the World Health Organization had recommended routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual initiation. However, many countries have yet to implement HPV vaccination because of financial or logistical barriers to delivering two doses outside the infant immunisation programme. Using three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 188 countries, under scenarios in which one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g. 80

OBJECTIVES:Incremental cost-effectiveness analyses may inform the optimal choice of healthcare interventions. Nevertheless, for many vaccines, benefits fluctuate with incidence levels over time. Reevaluating a vaccine after it has successfully decreased incidences may eventually cause a disease resurgence if switching to a vaccine with lower indirect benefits. Decisions may successively alternate between vaccines alongside repeated rises and falls in incidence and when indirect effects from historic use are ignored. Our suggested proposal aims to prevent suboptimal decision making.METHODS:We used a conceptual model of demand to illustrate alternating decisions between vaccines because of time-varying levels of indirect effects. Similar to the concept of subsidies, we propose internalizing the indirect effects achievable with vaccines. In a case study over 60 years, we simulated a hypothetical 10-year reevaluation of 2 oncogenic human papillomavirus vaccines, of which only 1 protects additionally against anogenital warts.RESULTS:Our case study showed that the vaccine with additional warts protection is initially valued higher than the vaccine without additional warts protection. After 10 years, this differential decreases because of declines in warts incidence, which supports switching to the nonwarts vaccine that causes a warts resurgence eventually. Instead, pricing the indirect effects separately supports continuing with the warts vaccine.CONCLUSIONS:Ignoring how the observed incidences depend on the indirect effects achieved with a particular vaccine may lead to repeated changes in vaccines at successive reevaluations, with unintended resurgences, economic inefficiencies, and eroding vaccine confidence. We propose internalizing indirect effects to prevent vaccines falling victim to their own success.

ObjectivesIn January 2020, the UK moved to a 1+1 schedule for the 13-valent pneumococcal conjugate vaccine (PCV13) with a single priming dose at 3-month and a 12-month booster. We modelled the impact on invasive pneumococcal disease (IPD) out to 2030/2031 of reductions in PCV13 coverage and population mixing associated with restrictions on non-essential healthcare visits and social distancing measures introduced in 2020/2021 to reduce SARS-CoV-2 transmission.DesignUsing an existing model of pneumococcal transmission in England and Wales, we simulated the impact of a 40% reduction in coverage and a 40% reduction in mixing between and within age groups during two lockdowns in spring 2020 and autumn/winter 2020/2021. More and less extreme reductions in coverage and mixing were explored in a sensitivity analysis.Main outcome measuresPredicted annual numbers of IPD cases under different coverage and mixing reduction scenarios with uncertainty intervals (UIs) generated from minimum and maximum values of the model predictions using 500 parameter sets.ResultsThe model predicted that any increase in IPD cases resulting from a reduction in PCV13 coverage would be more than offset by a reduction in pneumococcal transmission due to social distancing measures and that overall reductions in IPD cases will persist for a few years after resumption of normal mixing. The net reduction in cumulative IPD cases over the five epidemiological years from July 2019 was predicted to be 13 494 (UI 12 211, 14 676) all ages. Similar results were obtained in the sensitivity analysis.ConclusionCOVID-19 lockdowns are predicted to have had a profound effect on pneumococcal transmission resulting in a reduction in pneumococcal carriage prevalence and IPD incidence for up to 5 years after the end of the lockdown period. Carriage studies will be informative in confirming the predicted impact of the lockdown measures after they have been lifted.

Introduction: An unexpected resurgence of pertussis cases and infant deaths was observed in some countries that had switched to acellular pertussis vaccines in the primary immunisation schedule. In response to the outbreaks, maternal pertussis vaccination programmes in pregnant women have been adopted worldwide, including the USA in 2011 and the UK in 2012. Following the success of the programme in England, we evaluated the health and economic impact of stopping versus continuing the maternal pertussis immunisation to inform public health policy making. Methods: We used a mathematical model to estimate the number of infant hospitalisations and deaths related to pertussis in England over 2019-2038. Losses in quality-adjusted life years, QALYs, were considered for infants (aged 0-2 months) who survived or died from pertussis, bereaved parents (of infants who died from pertussis), and women with pertussis (aged 20-44 years). Direct medical costs to the National Health Service included infant hospitalisations, maternal vaccinations, and disease in women. Costs and QALYs were discounted at 3.5%. Changes in the incremental cost-effectiveness ratio, ICER, were explored in sensitivity analyses. Results: The model supports continuing the maternal pertussis immunisation programme as a costeffective intervention at an ICER of 14,500 pound/QALY (2.5% and 97.5%-quantile: 7,300 pound/QALY to 32,400 pound/ QALY). Stopping versus continuing the maternal programme results in an estimated mean of 972 (range 582 to 1489) versus 308 (184 to 471) infant hospitalisations annually. Results were most sensitive to the number of hospitalisations and deaths when stopping the maternal programme. At a cost-effectiveness threshold of 30,000 pound/QALY, the probability of the maternal programme being cost-effective was 96.2%. Conclusion: Our findings support continuing the maternal pertussis vaccination programme as otherwise higher levels of disease activity and infant mortality are expected to return. These results have led policy makers to decide to continue the maternal programme in the UK routine immunisation schedule. (c) 2021 Published by Elsevier Ltd.

In October 2012, a maternal pertussis vaccination program was implemented in England following an increased incidence and mortality in infants. We evaluated the cost-effectiveness of the program by comparing pertussis-related infant hospitalizations and deaths in 2012-2017 with nonvaccination scenarios. Despite considerable uncertainties, findings support the cost-effectiveness of the program.

In January 2020, the United Kingdom (UK) removed one of the two infant doses of the 13-valent pneumococcal conjugate vaccine (PCV13), leaving a single priming dose at 3 months and a 12 month booster. We modelled the potential impact on invasive pneumococcal disease (IPD) of a drop in PCV13 coverage associated with the restrictions on non-essential health care visits introduced to combat COVID-19 in the UK on 23 March 2020. Using a previously published model of pneumococcal transmission in England and Wales we simulated the impact of reducing PCV13 coverage by 50% for 3 months from 23 March without subsequent catch-up vaccination. To implement social distancing, we reduced mixing between and within age-groups by either 10% or 50%. In a sensitivity analysis we explored the effect of complete cessation of PCV13 vaccination during the lockdown and of extending its duration to 6 months. Annual numbers of IPD cases predicted by the model under different vaccination and lockdown scenarios with uncertainty intervals (UI) generated from the minimum and maximum values of the model predictions using 500 parameter sets with values within a pre-specified range of the maximum likelihood set. The model predicted that any increase in IPD cases from a reduction in PCV13 coverage would be more than offset by a reduction in pneumococcal transmission due to social distancing, with a net reduction in cumulative IPD cases (UI -1,479, -1,061, all ages) over the next five years. Similar results were obtained in the sensitivity analysis, though with a greater reduction with a 6 month lockdown. COVID-19 social distancing measures are predicted to have had a profound effect on pneumococcal transmission resulting in a reduction in pneumococcal carriage prevalence and IPD incidence over the first two years after the lockdown. Carriage studies will be informative in confirming the predicted impact of the social distancing measures after they have been lifted.

Objectives In England, human papillomavirus (HPV) testing is to replace cytological screening by 2019–2020. We conducted a model-based economic evaluation to project the long-term clinical impact and cost-effectiveness of routine cytology versus HPV testing. Methods An individual-based model of HPV acquisition, natural history, and cervical cancer screening was used to compare cytological screening and HPV testing with cytology triage for women aged 25–64 years (with either 3- or 5-year screening intervals for women aged under 50 years). The model was fitted to data from England's National Health Service Cervical Screening Programme. Both clinical and economic outcomes were projected to inform cost-effectiveness analyses. Results HPV testing is likely to decrease annual cytology testing (by 2.76 million), cervical cancer incidence (by 290 cases), and health system costs (by £13 million). It may increase the number of colposcopies, although this could be reduced without leading to more cancers compared with primary cytology by increasing the interval between screens to 5 years. The impact in terms of quality-adjusted life-years (QALYs) depends on the quality of life weight given to colposcopies versus cancer. Conclusions England's move from cytology to HPV screening may potentially be life-saving and cost-effective. Cost-effectiveness can be improved further by extending the interval between screens or using alternative triage methods such as partial or full genotyping.

Background In October 2017, the United Kingdom Joint Committee on Vaccination and Immunisation (JCVI) recommended removal of one primary dose of the 13-valent pneumococcal conjugate vaccine (PCV13) from the existing 2+1 schedule (2, 4, 12 months). We conducted a mathematical modelling study to investigate the potential impact of a 1+1 (3, 12 month) schedule on invasive pneumococcal disease (IPD) and pneumococcal community-acquired pneumonia (CAP). Our results and those from a 1+1 immunogenicity study formed the key evidence reviewed by JCVI. Methods and findings We developed age-structured, dynamic, deterministic models of pneumococcal transmission in England and Wales to describe the impact on IPD of 7-valent PCV (PCV7; introduced in 2006) and PCV13 (introduced in 2010). Key transmission and vaccine parameters were estimated by fitting to carriage data from 2001/2002 and post-PCV IPD data to 2015, using vaccine coverage, mixing patterns between ages, and population data. We considered various models to investigate potential reasons for the rapid increase in non-PCV13 (non-vaccine serotype [NVT]) IPD cases since 2014. After searching a large parameter space, 500 parameter sets were identified with a likelihood statistically close to the maximum and these used to predict future cases (median, prediction range from 500 parameter sets). Our findings indicated that the emergence of individual NVTs with higher virulence resulting from ongoing replacement was likely responsible; the NVT increase was predicted to plateau from 2020. Long-term simulation results suggest that changing to a 1+1 schedule would have little overall impact, as the small increase in vaccine-type IPD would be offset by a reduction in NVT IPD. Our results were robust to changes in vaccine assumptions in a sensitivity analysis. Under the base case scenario, a change to a 1+1 schedule in 2018 was predicted to produce 31 (6, 76) additional IPD cases over five years and 83 (-10, 242) additional pneumococcal-CAP cases, with together 8 (-2, 24) additional deaths, none in children under 15 years. Long-term continuation with the 2+1 schedule, or changing to a 1+1, was predicted to sustain current reductions in IPD cases in under-64-year-olds, but cases in 65+-year-olds would continue to increase because of the effects of an aging population. Limitations of our model include difficulty in fitting to past trends in NVT IPD in some age groups and inherent uncertainty about future NVT behaviour, sparse data for defining the mixing matrix in 65+-year-olds, and the methodological challenge of defining uncertainty on predictions. Conclusions Our findings suggest that, with the current mature status of the PCV programme in England and Wales, removing one primary dose in the first year of life would have little impact on IPD or pneumococcal CAP cases or associated deaths at any age. A reduction in the number of priming doses would improve programmatic efficiency and facilitate the introduction of new vaccines by reducing the number of coadministered vaccines given at 2 and 4 months of age in the current UK schedule. Our findings should not be applied to other settings with different pneumococcal epidemiology or with immature programmes and poor herd immunity.

ABSTRACTBackgroundCatch-up campaigns (CCs) at the introduction of the pneumococcal conjugate vaccines (PCVs) may accelerate the impact of PCVs. However, limited vaccine supplies may delay vaccine introduction if additional doses are needed for such campaigns. We studied the relative impact of introducing PCV13 with and without catch-up campaign, and the implications of potential introduction delays.MethodsWe used a dynamic transmission model applied to the population of Nha Trang in Sout central Vietnam. Four strategies were considered: routine vaccination (RV) only, and RV alongside catch-up campaigns among <1y olds (CC1), <2y olds (CC2) and <5y olds (CC5). The model was parameterised with local data on human social contact rates, and was fitted to local carriage data. Post-PCV predictions were based on best estimates of parameters governing post-PCV dynamics, including serotype competition, vaccine efficacy and duration of protection.ResultsOur model predicts elimination of vaccine-type (VT) carriage across all age groups within 10 years of introduction in all scenarios with near-complete replacement by non-VT. Most of the benefit of CCs is predicted to occur within the first 3 years after introduction, with the highest impact in the first year, when IPD incidence is predicted to be 11% (95%CrI 9 – 14%) lower than RV with CC1, 25% (21 – 30 %) lower with CC2 and 38% (32 – 46%) lower with CC5.However, CCs would only prevent more cases of IPD insofar such campaigns do not delay introduction by more than 31 (95%CrI 30 – 32) weeks with CC1, 58 (53 – 63) weeks with CC2 and 89 (78 – 101) weeks for CC5.ConclusionCCs are predicted to offer a substantial additional reduction in pneumococcal disease burden over RV alone, if their implementation does not result in much introduction delay. Those findings are important to help guide vaccine introduction in countries that have not yet introduced PCV, particularly in Asia.

The recent resurgence of pertussis in England and Wales has been marked by infant deaths and rising cases in teens and adults. To understand which age cohorts are most responsible for these trends, we employed three separate statistical methods to analyze high-resolution pertussis reports from 1982 to 2012. The fine-grained nature of the time-series allowed us to describe the changes in age-specific incidence and contrast the transmission dynamics in the 1980s and during the resurgence era. Our results identified infants and school children younger than 10 years of age as a core group, prior to 2002: pertussis incidence in these populations was predictive of incidence in other age groups. After 2002, no core groups were identifiable. This conclusion is independent of methodology used. Because it is unlikely that the underlying contact patterns substantially changed over the study period, changes in predictability likely result from the introduction of more stringent diagnostics tests that may have inadvertently played a role in masking the relative contributions of core transmission groups.

Background:The national human papillomavirus (HPV) immunization program was introduced in England in September 2008 using the bivalent vaccine.Methods:We collected residual vulva-vaginal swab specimens from 16 to 24-year-old women attending for chlamydia screening between 2010 and 2016 and tested for HPV DNA. We compared changes in type-specific (vaccine and nonvaccine) HPV prevalence over time and association with vaccination coverage. For women with known vaccination status, vaccine effectiveness was estimated.Results:HPV DNA testing was completed for 15459 specimens. Prevalence of HPV16/18 decreased between 2010/2011 and 2016 from 8.2% to 1.6% in 16-18 year olds and from 14.0% to 1.6% in 19-21 year olds. Declines were also seen for HPV31/33/45 (6.5% to 0.6% for 16-18 year olds and 8.6% to 2.6% for 19-21 year olds). Vaccine effectiveness for HPV16/18 was 82.0% (95% confidence interval [CI], 60.6%-91.8%) and for HPV31/33/45 was 48.7% (95% CI, 20.8%-66.8%). Prevalence of HPV16/18 was compared to findings in 2007-2008 (prevaccination) and to predictions from Public Health England's mathematical model.Discussion:Eight years after the introduction of a national HPV vaccination program, substantial declines have occurred in HPV16/18 and HPV31/33/45. The prevalence of other high-risk HPV types has not changed.

To inform mathematical modelling of the impact of chlamydia screening in England since 2000, a complete picture of chlamydia testing is needed. Monitoring and surveillance systems evolved between 2000 and 2012. Since 2012, data on publicly funded chlamydia tests and diagnoses have been collected nationally. However, gaps exist for earlier years. We collated available data on chlamydia testing and diagnosis rates among 15-44-year-olds by sex and age group for 2000-2012. Where data were unavailable, we applied data- and evidence-based assumptions to construct plausible minimum and maximum estimates and set bounds on uncertainty. There was a large range between estimates in years when datasets were less comprehensive (2000-2008); smaller ranges were seen hereafter. In 15-19-year-old women in 2000, the estimated diagnosis rate ranged between 891 and 2,489 diagnoses per 100,000 persons. Testing and diagnosis rates increased between 2000 and 2012 in women and men across all age groups using minimum or maximum estimates, with greatest increases seen among 15-24-year-olds. Our dataset can be used to parameterise and validate mathematical models and serve as a reference dataset to which trends in chlamydia-related complications can be compared. Our analysis highlights the complexities of combining monitoring and surveillance datasets.

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 pound a dose. At 48 pound 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.