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Pneumonia is an important cause of illness and death in England. To describe trends in pneumonia hospitalizations, we extracted information on all episodes of pneumonia that occurred from April 1997 through March 2005 recorded in the Hospital Episode Statistics (HES) database by searching for International Classification of Diseases 10th revision codes J12-J18 in any diagnostic field. The age-standardized incidence of hospitalization with a primary diagnosis of pneumonia increased by 34% from 1.48 to 1.98 per 1,000 population between 1997-98 and 2004-05. The increase was more marked in older adults, in whom the mortality rate was also highest. The proportion of patients with recorded coexisting conditions (defined by using the Charlson Comorbidity Index score) increased over the study period. The rise in pneumonia hospital admissions was not fully explained by demographic change or increasing coexisting conditions. It may be attributable to other population factors, changes in HES coding, changes to health service organization, other biologic phenomenon, or a combination of these effects. [ABSTRACT FROM AUTHOR]

BACKGROUND: The meningococcal serogroup C conjugate (MCC) vaccination program has successfully reduced morbidity and mortality from serogroup C disease in England and Wales, owing to high short-term vaccine effectiveness and substantial herd immunity. The latter effect was not accounted for in the previous economic analysis of the MCC program. METHODS: The authors applied a transmission dynamic model, which accounts for herd immunity, to reevaluate the cost-effectiveness of MCC vaccination. The direct and indirect benefits of the MCC vaccine strategy implemented in England and Wales were compared. The cost-effectiveness of alternative MCC vaccine strategies, including future changes to the current schedule, were evaluated. RESULTS: The authors found that including herd immunity improved the average cost-effectiveness ratio in all cases, although the extent depended on the vaccine strategy considered. Incremental analysis showed that those strategies that offered 1 dose early in the 2nd year of life dominated strategies that offered 3 doses of vaccine in infancy and that catch-up vaccination up to the age of 18 years was also highly attractive. Furthermore, the authors analyzed the effect of future changes to the routine vaccine schedule and predicted that shifting the age at routine vaccination from 2, 3, and 4 months (3 doses) to 12 months (1 dose) resulted in a net gain in the total number of cases prevented with only a few extra cases occurring in children under 1 year of age. This program dominated the current strategy. CONCLUSIONS: Models that do not include the indirect effects of vaccination will underestimate the impact of MCC vaccination and may lead to distorted decision making. [ABSTRACT FROM AUTHOR]

Estimates of the global health impact of immunisation are important for quantifying historical benefits as well as planning future investments and strategy. The Vaccine Impact Modelling Consortium (VIMC) was established in 2016 to provide reliable estimates of the health impact of immunisation. In this article we examine the consortium in its first five-year phase. We detail how vaccine impact was defined and the methods used to estimate it as well as the technical infrastructure required to underpin robust reproducibility of the outputs. We highlight some of the applications of estimates to date, how these were communicated and what their effect were. Finally, we explore some of the lessons learnt and remaining challenges for estimating the impact of vaccines and forming effective modelling consortia then discuss how this may be addressed in the second phase of VIMC. Modelled estimates are not a replacement for surveillance; however, they can examine theoretical counterfactuals and highlight data gaps to complement other activities. VIMC has implemented strategies to produce robust, standardised estimates of immunisation impact. But through the first phase of the consortium, critical lessons have been learnt both on the technical infrastructure and the effective engagement with modellers and stakeholders. To be successful, a productive dialogue with estimate consumers, producers and stakeholders needs to be underpinned by a rigorous and transparent analytical framework as well as an approach for building expertise in the short and long term., Competing Interests: Competing interests: KAMG, XL, HC, ED, RF, WH, DH, MJ, TM, TAP, AP, EV, KW, NMF, CLT, received funding from Gavi, BMGF and/or the Wellcome Trust via VIMC during the course of the study. The authors declare no other competing interests., (Copyright: © 2024 Gaythorpe KAM et al.)

Background: WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception., Methods: In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period., Findings: Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood., Interpretation: Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality., Funding: WHO., Competing Interests: Declaration of interests CLT and KAMG assert that their employer, Imperial College, receives funding for the Vaccine Impact Modelling Consortium from the Bill & Melinda Gates Foundation; Gavi, the Vaccine Alliance; and the Wellcome Trust. CLT has received consulting fees from GSK for attending an advisory board meeting on CMV vaccines in May, 2022 and is pro bono Chair of the Scientific Advisory Panel of the Meningitis Research Foundation. HF asserts that her employer, London School of Hygiene & Tropical Medicine, receives funding for the Vaccine Impact Modelling Consortium from the Gates Foundation. JFM asserts that his employer, University of Washington, receives grant funding from Gavi and from the Gates Foundation. KB and KMT assert that their organisation Kid Risk holds a cooperative agreement with the US Centers for Disease Control and Prevention and holds grants from the Gates Foundation. MJF asserts that his employer, Penn State University, is a subrecipient of funds from Imperial College London for a grant from Gavi and that he holds grants from the Gates Foundation and the US National Science Foundation. MJ asserts that his employer, London School of Hygiene & Tropical Medicine, receives funding from the UK National Institute of Health Research, RCUK; the Gates Foundation; Gavi; the Wellcome Trust; WHO; the European Commission; the US Centers for Disease Control and Prevention; the Hong Kong Special Administrative Region Government; and the Task Force for Global Health. RAH and SPS assert that their employer, University of Cape Town, receives grant funding from the African Field Epidemiology Network and the US Centers for Disease Control and Prevention. RGW asserts that he receives funding from the Wellcome Trust (grant numbers 218261/Z/19/Z), National Institutes of Health (1R01AI147321-01, G-202303-69963, and R-202309-71190), European and Developing Countries Clinical Trials Partnership (RIA208D-2505B), UK Medical Research Council (CCF17-7779 via SET Bloomsbury), UK Economic and Social Research Council (ES/P008011/1), Bill & Melinda Gates Foundation (INV-004737 and INV-035506), and WHO (2020/985800-0). AL, KLO-B, NB-Z, PL, RCWH, and SYS work for WHO. All other authors declare no competing interests., (Copyright © 2024 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: There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered., Methods: For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up., Findings: We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073])., Interpretation: Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption., Funding: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation., Translations: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests A-MH, XL, SE-L, JR, KA, MA, MJdV, MJF, KF, HF, TH, MJ, AK, SMM, SN, TP, TAP, AP, QTM, EV, AKW, HB, CC, HEC, AD, SH, JH, KJ, CK, J-HK, JK, BAL, VEP, YT, KW, NMF, CLT, and KAMG received funding from Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation via the Vaccine Impact Modelling Consortium (VIMC) during the study. A-MH, JR, SE-L, XL, SN, MJdV, TH, WH, KW, NMF, CLT, and KAMG receive funding from the Medical Research Council Centre for Global Infectious Disease Analysis (reference MR/R015600/1), which is jointly funded by the UK Medical Research Council and the UK Foreign, Commonwealth, and Development Office under a concordant agreement, and is also part of the European and Developing Countries Clinical Trials Partnership programme supported by the EU. A-MH, JR, SE-L, XL, SN, MJdV, TH, WH, KW, NMF, CLT, and KAMG receive funding from Community Jameel. A-MH is supported by the German Federal Ministry of Education and Research (grant 01LN2210A) and declares stock options in BIONTECH. CLT received payment for advice from GlaxoSmithKline. KA is supported by the Japan Agency for Medical Research and Development (JP223fa627004). KAMG received a speaker fee from Sanofi Pasteur. SN receives consulting fees from WHO. VEP is a member of the WHO Immunization and Implementation Research Advisory Committee. BAL receives personal fees from Epidemiologic Research and Methods and Hillevax. SMM receives consultant fees from Emergent Biosolutions. NMF receives grant funding from Janssen Pharmaceuticals, UK Research and Innovation, and the UK National Institute for Health and Care Research; declares consulting fees from the World Bank, WHO, and Gavi; receives travel expenses for WHO meetings; was on an advisory board for Takeda; and is a senior editor for eLife. All other authors declare no competing interests., (Copyright © 2024 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.)

Group B streptococcus (GBS) is a major global cause of neonatal meningitis, sepsis and pneumonia, with an estimated 91,000 infant deaths per year and an additional 46,000 stillbirths. GBS infection in pregnancy is also associated with adverse maternal outcomes and preterm births. As such, the World Health Organization (WHO) prioritised the development of a GBS vaccine suitable for use in pregnant women and use in LMICs, where the burden of disease is highest. Several GBS vaccines are in clinical development. The WHO Defeating Meningitis by 2030 has set a target of 2026 for vaccine licensure. This 'Vaccine Value Profile' (VVP) for GBS is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO regions of AFR, AMR, EUR, WPR. All contributors have extensive expertise on various elements of the GBS VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Brucella spp., Toxoplasma gondii, and Chlamydia abortus have long been recognized as zoonoses and significant causes of reproductive failure in small ruminants globally. A cross-sectional study was conducted in August 2020 to determine the seroprevalences of Brucella spp., Toxoplasma gondii and Chlamydia abortus in 398 small ruminants from four districts of Zimbabwe (Chivi, Makoni, Zvimba, and Goromonzi) using Indirect-ELISAs. A structured questionnaire was used to assess the knowledge, attitudes, and practices of 103 smallholder farmers towards small ruminant abortions, Brucella spp., T. gondii and C. abortus, and to obtain a general overview of the significance of small ruminant reproductive failure(s) on their livelihoods. The overall seroprevalences were: 9.1% (95% CI: 6.4-12.3) for Brucella spp., 6.8% (95% CI: 4.5-9.7) for T. gondii and 2.0% (95% CI: 0.9-3.9) for C. abortus. Location, age, parity, and abortion history were associated with Brucella spp. seropositivity. Location was also associated with both T. gondii and C. abortus seropositivity. The questionnaire survey established that 44% of respondents had recently faced reproductive disease challenges within their flocks, with 34% correctly identifying abortion causes and only 10%, 6% and 4% having specific knowledge of Brucella spp., C. abortus and T. gondii, respectively. This study provides the first serological evidence of Brucella spp. in small ruminants since 1996 and builds the evidence on small ruminant toxoplasmosis and chlamydiosis in Zimbabwe. Evidence of these zoonoses in small ruminants and the paucity of knowledge shows the need for a coordinated One Health approach to increase public awareness of these diseases, and to establish effective surveillance and control measures. Further studies are required to establish the role these diseases play in small ruminant reproductive failure(s), to identify the Brucella spp. detected here to species/subspecies level, and to assess the socio-economic impact of reproductive failure in livestock among marginalised rural communities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tarusikirwa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Over the past decade, numerous approaches have been taken to replace unsustainable chemical syntheses with green biosynthetic alternatives. In a landmark paper, Yim et al. utilised an in silico-to-in vivo workflow to enable the high-level bioproduction of the unnatural small molecule 1,4-butanediol in the bacterium Escherichia coli., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Over the past two decades, vaccination programmes for vaccine-preventable diseases (VPDs) have expanded across low- and middle-income countries (LMICs). However, the rise of COVID-19 resulted in global disruption to routine immunisation activities. Such disruptions could have a detrimental effect on public health, leading to more deaths from VPDs, particularly without mitigation efforts. Hence, as routine immunisation activities resume, it is important to estimate the effectiveness of different approaches for recovery. We apply an impact extrapolation method developed by the Vaccine Impact Modelling Consortium to estimate the impact of COVID-19-related disruptions with different recovery scenarios for ten VPDs across 112 LMICs. We focus on deaths averted due to routine immunisations occurring in the years 2020-2030 and investigate two recovery scenarios relative to a no-COVID-19 scenario. In the recovery scenarios, we assume a 10% COVID-19-related drop in routine immunisation coverage in the year 2020. We then linearly interpolate coverage to the year 2030 to investigate two routes to recovery, whereby the immunization agenda (IA2030) targets are reached by 2030 or fall short by 10%. We estimate that falling short of the IA2030 targets by 10% leads to 11.26% fewer fully vaccinated persons (FVPs) and 11.34% more deaths over the years 2020-2030 relative to the no-COVID-19 scenario, whereas, reaching the IA2030 targets reduces these proportions to 5% fewer FVPs and 5.22% more deaths. The impact of the disruption varies across the VPDs with diseases where coverage expands drastically in future years facing a smaller detrimental effect. Overall, our results show that drops in routine immunisation coverage could result in more deaths due to VPDs. As the impact of COVID-19-related disruptions is dependent on the vaccination coverage that is achieved over the coming years, the continued efforts of building up coverage and addressing gaps in immunity are vital in the road to recovery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diagnostics for COVID-19 detection are limited in many settings. Syndromic surveillance is often the only means to identify cases but lacks specificity. Rapid antigen testing is inexpensive and easy-to-deploy but can lack sensitivity. We examine how combining these approaches can improve surveillance for guiding interventions in low-income communities in Dhaka, Bangladesh. Rapid-antigen-testing with PCR validation was performed on 1172 symptomatically-identified individuals in their homes. Statistical models were fitted to predict PCR-status using rapid-antigen-test results, syndromic data, and their combination. Under contrasting epidemiological scenarios, the models' predictive and classification performance was evaluated. Models combining rapid-antigen-testing and syndromic data yielded equal-to-better performance to rapid-antigen-test-only models across all scenarios with their best performance in the epidemic growth scenario. These results show that drawing on complementary strengths across rapid diagnostics, improves COVID-19 detection, and reduces false-positive and -negative diagnoses to match local requirements; improvements achievable without additional expense, or changes for patients or practitioners., (© 2022. The Author(s).)

Background: To adapt communications concerning vaccine prevention, we studied knowledge, beliefs and practices around meningitis risk and prevention in a young adult population in Burkina Faso in 2016, 5 years after the MenAfriVac® mass campaign and one year before the vaccine's inclusion in the infant immunization schedule., Methods: In a representative sample of the population aged 15 to 33 years (N = 220) in Bobo-Dioulasso, Burkina Faso, study nurses administered a standardized paper questionnaire consisting of predominantly open questions, collecting information on meningitis risk factors and prevention, and on exposure to dry air and kitchen fire smoke. We identified themes and analyzed their frequency. We created a meningitis knowledge score (range 0 to 4) based on pre-defined best responses and analyzed the determinants of knowledge score levels ≥2 (basic score) and ≥3 (high score) using multivariate logistic regression., Results: Biomedically supported facts and good practices were known by the majority of participants (eg vaccine prevention, 84.5%). Younger women aged 15-20 years had a higher frequency of low scores <2 (17.0%) compared to older women aged 21-33 years (6.3%) and men of both age groups (3.8%). Junior secondary School attendance explained the differences between the two groups of women, the gender gap for the older, but not the young women, and explained score differences among young women. Local understandings and practices for risk and prevention were commonly reported and used (risk from unripe mango consumption and prevention through nasal application of shea nut butter)., Discussion: This study shows a gender gap in knowledge of meningitis risk and prevention, largely due to education-level inequalities. Women below 21 years had particularly low levels of knowledge and may need interventions outside schools and perinatal care. Our study suggests a strong adherence to local understandings of and practices around meningitis risk and prevention, which should be taken into account by vaccination promotion., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RB performs contract research on behalf of Public Health England for GSK, Pfizer and Sanofi Pasteur. JEM, JS, CLT and TGV declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae , and yellow fever over the years 2000-2030 across 112 countries., Methods: Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios., Results: We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases., Conclusions: This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future., Funding: VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication., Competing Interests: JT, SE, XL, KA, EC, HC, AC, Md, KE, MF, IG, TH, WH, DH, JH, KJ, AK, PK, AK, JL, XL, TM, CM, SM, SN, TP, AP, DR, SR, CS, SS, YT, HT, QT, ST, EV, NW, AW, KW, NF, KG No competing interests declared, MJ MLJ has received research funding from Sanofi Pasteur unrelated to the present work, MJ Reviewing editor, eLife, BL BAL reports grants and personal fees from Takeda Pharmaceuticals, personal fees from World Health Organization, outside the submitted work, TP TAP receives support from Emergent Biosolutions for work unrelated to his contribution to this study, HR HR is an employee of Center for Disease Analysis Foundation which has received grants from Gilead Sciences, AbbVie, Zeshan Foundation and EndHep2030 fund for projects unrelated to this work; HBV epidemiology data was funded by a grant from John Martin Foundation (Grant number 24), CT CLT received a consulting payment from GSK in 2018 (outside the submitted work), (© 2021, Toor et al.)

Background and Objectives: Group B Streptococcus (GBS) is the leading cause of sepsis and meningitis in infants <90 days. In this study, the burden of GBS disease and mortality in young infants in England was assessed., Methods: Using linked hospitalization records from every National Health Service (NHS) hospital from April 1, 1998 to March 31, 2017, we calculated annual GBS incidence in infants aged <90 days and, using regression models, compared their perinatal factors, rates of hospital-recorded disease outcomes, and all-cause infant mortality rates with those of the general infant population., Results: 15 429 infants aged <90 days had a hospital-recorded diagnosis of GBS, giving an average annual incidence of 1.28 per 1000 live births (95% CI 1.26-1.30) with no significant trend over time. GBS-attributable mortality declined significantly from 0.044 (95% CI .029-.065) per 1000 live births in 2001 to 0.014 (95% CI .010-.026) in 2017 (annual percentage change -6.6, 95% CI -9.1 to -4.0). Infants with GBS had higher relative rates of visual impairment (HR 7.0 95% CI 4.1-12.1), cerebral palsy (HR 9.3 95% CI 6.6-13.3), hydrocephalus (HR 17.3 95% CI 13.8-21.6), and necrotizing enterocolitis (HR 18.8 95% CI 16.7-21.2) compared with those without GBS., Conclusions: Annual rates of GBS disease in infants have not changed over 19 years. The reduction in mortality is likely multifactorial and due to widespread implementation of antibiotics in at-risk mothers and babies, as well as advances in managing acutely unwell infants. New methods for prevention, such as maternal vaccination, must be prioritized., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

We previously developed a transmission dynamic model of Neisseria meningitidis serogroup A (NmA) with the aim of forecasting the relative benefits of different immunisation strategies with MenAfriVac. Our findings suggested that the most effective strategy in maintaining disease control was the introduction of MenAfriVac into the Expanded Programme on Immunisation (EPI). This strategy is currently being followed by the countries of the meningitis belt. Since then, the persistence of vaccine-induced antibodies has been further studied and new data suggest that immune response is influenced by the age at vaccination. Here, we aim to investigate the influence of both the duration and age-specificity of vaccine-induced protection on our model predictions and explore how the optimal vaccination strategy may change in the long-term. We adapted our previous model and considered plausible alternative immunization strategies, including the addition of a booster dose to the current schedule, as well as the routine vaccination of school-aged children for a range of different assumptions regarding the duration of protection. To allow for a comparison between the different strategies, we use several metrics, including the median age of infection, the number of people needed to vaccinate (NNV) to prevent one case, the age distribution of cases for each strategy, as well as the time it takes for the number of cases to start increasing after the honeymoon period (resurgence). None of the strategies explored in this work is superior in all respects. This is especially true when vaccine-induced protection is the same regardless of the age at vaccination. Uncertainty in the duration of protection is important. For duration of protection lasting for an average of 18 years or longer, the model predicts elimination of NmA cases. Assuming that vaccine protection is more durable for individuals vaccinated after the age of 5 years, routine immunization of older children would be more efficient in reducing disease incidence and would also result in a fewer number of doses necessary to prevent one case. Assuming that elimination does not occur, adding a booster dose is likely to prevent most cases but the caveat will be a more costly intervention. These results can be used to understand important sources of uncertainty around MenAfriVac and support decisions by policymakers.

Background: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030., Methods: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort., Findings: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort., Interpretation: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained., Funding: Gavi, the Vaccine Alliance and the 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: Recent debates on the introduction of new childhood vaccines in the UK have suggested that 'peace of mind' (PoM) might influence decision making. The aim of this study is to ascertain the importance of 'PoM' in individuals' decision making., Methods: Four focus groups were conducted in the UK. Participants were 22 females and 2 males, aged 18-74 years, with a selection of non-parents, parents, guardians and foster carers. Data were analysed using an inductive thematic framework approach and conceptualised using the Health Belief Model, which provided an overview of participants' perceptions and behaviours about childhood vaccinations., Results: Vaccine associated PoM was associated with individuals' perceptions of disease severity, with individuals feeling more reassurance after obtaining vaccinations against diseases that they considered to be severe compared to relatively mild diseases. Conversely, concerns about vaccination side-effects reduced participants PoM, but the duration of this effect varied between individuals. Other factors, such as social pressure and the emotional anxiety related to children's feelings, or physical reactions, to vaccinations also negatively impacted on participants' vaccine associated PoM., Conclusion: Vaccine associated PoM was a consideration for some participants seeking vaccinations but was only a minor motivating factor for these individuals. These differences stemmed from whether participants received PoM from the uptake of a vaccination because they perceived some intrinsic benefit from it or, conversely, they considered vaccinations as a routine health intervention. Overall, vaccine related PoM varied between participants in magnitude and fluctuated over time, even in the same individuals., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HC reports receiving honoraria from Sanofi Pasteur, and consultancy fees from IMS Health, AstraZeneca and GSK all paid to her employer. HA reports receiving personal fees to attend a workshop organised by GSK. CT reports receiving personal fees from GSK and Sanofi Pasteur. This does not alter our adherence to Vaccine policies on sharing data and materials. Funding This work was supported by the Meningitis Research Foundation (grant number 1506.1) via a charitable donation from Pfizer Limited. GL, HC and CT are supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Evaluation of Interventions at the University of Bristol in partnership with Public Health England. HA is supported by a NIHR Career Development Fellowship (CDF-15-08-025). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: After the re-emergence of serogroup C meningococcal meningitis (MM) in Nigeria and Niger, we aimed to re-evaluate the vaccination policy used to respond to outbreaks of MM in the African meningitis belt by investigating alternative strategies using a lower incidence threshold and information about neighboring districts., Methods: We used data on suspected and laboratory-confirmed cases in Niger and Nigeria from 2013 to 2017. We calculated global and local Moran's I-statistics to identify spatial clustering of districts with high MM incidence. We used a Pinner model to estimate the impact of vaccination campaigns occurring between 2015 and 2017 and to evaluate the impact of 3 alternative district-level vaccination strategies, compared with that currently used., Results: We found significant clustering of high incidence districts in every year, with local clusters around Tambuwal, Nigeria in 2013 and 2014, Niamey, Niger in 2016, and in Sokoto and Zamfara States in Nigeria in 2017.We estimate that the vaccination campaigns implemented in 2015, 2016, and 2017 prevented 6% of MM cases. Using the current strategy but with high coverage (85%) and timely distribution (4 weeks), these campaigns could have prevented 10% of cases. This strategy required the fewest doses of vaccine to prevent a case. None of the alternative strategies we evaluated were more efficient, but they would have prevented the occurrence of more cases overall., Conclusions: Although we observed significant spatial clustering in MM in Nigeria and Niger between 2013 and 2017, there is no strong evidence to support a change in methods for epidemic response in terms of lowering the intervention threshold or targeting neighboring districts for reactive vaccination., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Invasive meningococcal disease (IMD) is associated with a high mortality and severe sequelae. The aim of the present study was to evaluate the potential cost-effectiveness of the Bexsero vaccine in Brazil. We used a cohort model to compare routine vaccination against MenB disease with no vaccination. Epidemiological and cost estimates were obtained from the Brazilian Health Information System. The cost per disability-adjusted life year (DALY) averted and incremental cost-effectiveness ratio (ICER) was estimated assuming a 3-dose vaccination schedule, at R$90 (£ 20.50) per vaccine dose, 82.0% vaccine efficacy against MenB disease and a vaccine uptake of 90.0%. We estimated that 1,527 MenB cases would be prevented and 78 deaths averted. This strategy would cost R$ 762,381, 000 (£ 174,059,503) with a R$ 4,364,280 (£ 996,410) reduction in disease treatment costs. However, at an ICER of 372,256 (£ 84,990) per DALY averted, a vaccination programme is unlikely to be cost-effective., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Streptococcus pneumoniae is increasingly recognised as an important cause of bacterial meningitis in the African meningitis belt. The World Health Organization sets guidelines for response to outbreaks of meningococcal meningitis, but there are no current guidelines for outbreaks where S. pneumoniae is implicated. We aimed to evaluate the impact of using a similar response to target outbreaks of vaccine-preventable pneumococcal meningitis in the meningitis belt. Here, we adapt a previous model of reactive vaccination for meningococcal outbreaks to estimate the potential impact of reactive vaccination in a recent pneumococcal meningitis outbreak in the Brong-Ahafo region of central Ghana using weekly line list data on all suspected cases over a period of five months. We determine the sensitivity and specificity of various epidemic thresholds and model the cases and deaths averted by reactive vaccination. An epidemic threshold of 10 suspected cases per 100,000 population per week performed the best, predicting large outbreaks with 100% sensitivity and more than 85% specificity. In this outbreak, reactive vaccination would have prevented a lower number of cases per individual vaccinated (approximately 15,300 doses per case averted) than previously estimated for meningococcal outbreaks. Since the burden of death and disability from pneumococcal meningitis is higher than that from meningococcal meningitis, there may still be merit in considering reactive vaccination for outbreaks of pneumococcal meningitis. More outbreak data are needed to refine our model estimates. Whatever policy is followed, we emphasize the importance of timely laboratory confirmation of suspected cases to enable appropriate decisions about outbreak response., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To investigate potential risk factors for acquisition in seven countries of the meningitis belt., Methods: Households were followed up every 2 weeks for 2 months, then monthly for a further 4 months. Pharyngeal swabs were collected from all available household members at each visit and questionnaires completed. Risks of acquisition over the whole study period and for each visit were analysed by a series of logistic regressions., Results: Over the course of the study, acquisition was higher in: (i) 5-to 14-year olds, as compared with those 30 years or older (OR 3.6, 95% CI 1.4-9.9); (ii) smokers (OR 3.6, 95% CI 0.98-13); and (iii) those exposed to wood smoke at home (OR 2.6 95% CI 1.3-5.6). The risk of acquisition from one visit to the next was higher in those reporting a sore throat during the dry season (OR 3.7, 95% CI 2.0-6.7) and lower in those reporting antibiotic use (OR 0.17, 95% CI 0.03-0.56)., Conclusions: Acquisition of meningococcal carriage peaked in school age children. Recent symptoms of sore throat during the dry season, but not during the rainy season, were associated with a higher risk of acquisition. Upper respiratory tract infections may be an important driver of epidemics in the meningitis belt., (© 2019 John Wiley & Sons Ltd.)

Objective: To review the findings of studies of pharyngeal carriage of Neisseria meningitidis and related species conducted in the African meningitis belt since a previous review published in 2007., Methods: PubMed and Web of Science were searched in July 2018 using the terms 'meningococcal OR Neisseria meningitidis OR lactamica AND carriage AND Africa', with the search limited to papers published on or after 1st January 2007. We conducted a narrative review of these publications., Results: One hundred and thirteen papers were identified using the search terms described above, 20 of which reported new data from surveys conducted in an African meningitis belt country. These papers described 40 surveys conducted before the introduction of the group A meningococcal conjugate vaccine (MenAfriVac R ) during which 66 707 pharyngeal swabs were obtained. Carriage prevalence of N. meningitidis varied substantially by time and place, ranging from <1% to 24%. The mean pharyngeal carriage prevalence of N. meningitidis across all surveys was 4.5% [95% CI: 3.4%, 6.8%] and that of capsulated N. meningitidis was 2.8% [95% CI: 1.9%; 5.2%]. A study of households provided strong evidence for meningococcal transmission within and outside households. The introduction of MenAfriVac ® led to marked reductions in carriage of the serogroup A meningococcus in Burkina Faso and Chad., Conclusions: Recent studies employing standardised methods confirm the findings of older studies that carriage of N. meningitidis in the African meningitis belt is highly variable over time and place, but generally occurs with a lower prevalence and shorter duration than reported from industrialised countries., (© 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Meningococcal carriage dynamics drive patterns of invasive disease. The distribution of carriage by age has been well described in Europe, but not in the African meningitis belt, a region characterised by frequent epidemics of meningitis. We aimed to estimate the age-specific prevalence of meningococcal carriage by season in the African meningitis belt. We searched PubMed, Web of Science, the Cochrane Library and grey literature for papers reporting carriage of Neisseria meningitidis in defined age groups in the African meningitis belt. We used a mixed-effects logistic regression to model meningococcal carriage prevalence as a function of age, adjusting for season, location and year. Carriage prevalence increased from low prevalence in infants (0.595% in the rainy season, 95% CI 0.482-0.852%) to a broad peak at age 10 (1.94%, 95% CI 1.87-2.47%), then decreased in adolescence. The odds of carriage were significantly increased during the dry season (OR 1.5 95% CI 1.4-1.7) and during outbreaks (OR 6.7 95% CI 1.6-29). Meningococcal carriage in the African meningitis belt peaks at a younger age compared to Europe. This is consistent with contact studies in Africa, which show that children 10-14 years have the highest frequency of contacts. Targeting older children in Africa for conjugate vaccination may be effective in reducing meningococcal transmission.

Posttraumatic stress disorder (PTSD) can be a very debilitating condition. Effective approaches to prevent and treat PTSD are important areas of basic science research. Pregabalin (PGB), a gabapentinoid derivative of γ-aminobutyric acid, possesses the potential to positively affect neurobehavioral changes associated with PTSD. Using a rodent model of PTSD, the aims of this study were to determine the effects of PGB as a possible prevention for the development of PTSD-like symptoms and its use as a possible treatment. A prospective, experimental, between groups design was used in conjunction with a three-day restraint/shock PTSD stress model. Sixty rats were randomly assigned between two groups, non-stressed and stressed (PTSD). Each of the main two groups was then randomly assigned into six experimental groups: control vehicle, control PGB, control naïve, PTSD vehicle, PTSD Pre-PGB (prophylactic), PTSD Post-PGB (non-prophylactic). The neurobehavioral components of PTSD were evaluated using the elevated plus maze (EPM), Morris water maze (MWM), and forced swim test (FST). Pregabalin administered 24 hours before the initial PTSD event or for 10 days following the last PTSD stress event did not statistically improve mean open arm exploration on the EPM, spatial memory, and learning in the MWM or behavioral despair measured by the FST (p > 0.05)., Competing Interests: The authors have declared that no competing interests exist.

Background: Norovirus is thought to be responsible for a fifth of all acute gastroenteritis cases globally each year. The population level transmission dynamics of this very common virus are still poorly understood, in part because illness is under-reported. With vaccines undergoing clinical trials, there is a growing need for appropriate, empirically grounded models, to predict the likely impact of vaccination., Methods: We developed a dynamic age-specific mathematical model of norovirus transmission and vaccination, informed by available data, particularly age-stratified time series case notification data. We introduce the use of a self-reporting Markov model to account for variation by age and over time in the statutory reporting of norovirus in Germany. We estimated the model using a sequential Monte Carlo particle filter. We then extended and applied our estimated model to investigate the potential impact of a range of immunisation strategies. We performed sensitivity analyses on the mode of vaccine action and other vaccine-related parameters., Results: We find that routine immunisation could reduce the incidence of norovirus by up to 70.5% even when those vaccines do not provide complete protection from disease. Furthermore, we find that the relative efficiency of alternative strategies targeting different age groups are dependant on the outcome we consider and are sensitive to assumptions on the mode of vaccine action. Strategies that target infants and toddler are more efficient in preventing infection but targeting older adults is preferable for preventing severe outcomes., Conclusions: Our model provides a robust estimate of a dynamic transmission model for norovirus at the population level. Vaccination may be an effective strategy in preventing disease but further work is required to ascertain norovirus vaccine efficacy, its mode of action and to estimate the cost-effectiveness of immunisation against norovirus., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Decisions regarding which vaccines are funded in the United Kingdom (UK) are increasingly informed by cost-effectiveness analyses. Such analyses use Quality Adjusted Life Years (QALYs) as a measure of effectiveness and assume that QALYs are equal regardless of where and in whom they occur in the population. However, there is increasing debate about whether this QALY approach is appropriate and whether societal preferences for childhood vaccinations should be used to help inform childhood immunisation policy., Objective: To gauge the general public's preferences for prioritising certain characteristics of childhood vaccination, to help inform future policy making decisions in the UK., Design: Qualitative design using individual face-to-face interviews, with data analysed using an inductive thematic framework approach., Setting: Two counties in England, UK., Population: Adult members of the general public were recruited using the Bristol and South Gloucestershire open electoral registers, using gender and deprivation quotas for each area., Participants: 21 members of the public participated in qualitative interviews., Results: The qualitative research identified three major themes and several key attributes that influences participant's opinions about priority setting for childhood vaccinations: (1) population segment (i.e. age group, carer impact and social group), (2) vaccine preventable diseases preferences (i.e. disease severity, disease incidence and declining infection) and (3) risks and benefits associated with childhood vaccinations (i.e. vaccine associated side-effects, herd protection and peace of mind)., Conclusion: Evidence from this qualitative study suggests that some members of the UK general public have more nuanced views than the health-maximisation approach when considering how childhood vaccines should be prioritised. This is not necessarily captured by the current economic approaches for assessing the benefits from childhood vaccinations in the UK, but is an important area for future research to ensure appropriate decision making., Competing Interests: HC reports receiving honoraria from Sanofi Pasteur, and consultancy fees from IMS Health, AstraZeneca and GSK all paid to her employer. HA reports receiving personal fees to attend a workshop organised by GSK. CT reports receiving personal fees from GSK and Sanofi Pasteur. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Norovirus is one of the leading causes of viral gastroenteritis worldwide and responsible for substantial morbidity, mortality and healthcare costs. To further understanding of the epidemiology and control of norovirus, there has been much recent interest in describing the transmission dynamics of norovirus through mathematical models. In this study, we review the current modelling approaches for norovirus transmission. We examine the data and methods used to estimate these models that vary structurally and parametrically between different epidemiological contexts. Many of the existing studies at population level have focused on the same case notification dataset, whereas models from outbreak settings are highly specific and difficult to generalise. In this review, we explore the consistency in the description of norovirus transmission dynamics and the robustness of parameter estimates between studies. In particular, we find that there is considerable variability in estimates of key parameters such as the basic reproduction number, which may mean that the effort required to control norovirus at the population level may currently be underestimated.

Background: Serum bactericidal antibody titres that correlate with protection against invasive meningococcal disease have been characterised. However, titres that are associated with protection against acquisition of pharyngeal carriage of Neisseria meningitidis are not known., Methods: Sera were obtained from the members of a household in seven countries of the African meningitis belt in which a pharyngeal carrier of N. meningitidis had been identified during a cross-sectional survey. Serum bactericidal antibody titres at baseline were compared between individuals in the household of the carrier who became a carrier of a meningococcus of the same genogroup during six months of subsequent follow-up and household members who did not become a carrier of a meningococcus of this genogroup during this period., Results: Serum bacterial antibody titres were significantly higher in carriers of a serogroup W or Y meningococcus at the time of recruitment than in those who were not a carrier of N. meningitidis of the same genogroup. Serum bactericidal antibody titres to a strain of N. meningitis of the same genogroup as the index cases were no different in individuals who acquired carriage with a meningococcus of the same genogroup as the index case than in those who did not become a carrier during six months of follow-up., Conclusion: Serum bacterial antibody titres to N. meningitidis of genogroup W or Y in the range of those acquired by natural exposure to meningococci of these genogroups, or with cross-reactive bacteria, are not associated with protection against acquisition of carriage with meningococci of either of these genogroups.

Background: In preparation for the introduction of MenAfriVac, a meningococcal group A conjugate vaccine developed for the African meningitis belt, an enhanced meningitis surveillance network was established. We analysed surveillance data on suspected and confirmed cases of meningitis to quantify vaccine impact., Methods: We compiled and analysed surveillance data for nine countries in the meningitis belt (Benin, Burkina Faso, Chad, Côte d'Ivoire, Ghana, Mali, Niger, Nigeria, and Togo) collected and curated by the WHO Inter-country Support Team between 2005 and 2015. The incidence rate ratios (IRRs) of suspected and confirmed cases in vaccinated and unvaccinated populations were estimated with negative binomial regression models. The relative risk of districts reaching the epidemic threshold of ten per 100 000 per week was estimated according to district vaccination status., Findings: The incidence of suspected meningitis cases declined by 57% (95% CI 55-59) in vaccinated compared with unvaccinated populations, with some heterogeneity observed by country. We observed a similar 59% decline in the risk of a district reaching the epidemic threshold. In fully vaccinated populations, the incidence of confirmed group A disease was reduced by more than 99%. The IRR for non-A serogroups was higher after completion of MenAfriVac campaigns (IRR 2·76, 95% CI 1·21-6·30)., Interpretation: MenAfriVac introduction has led to substantial reductions in the incidence of suspected meningitis and epidemic risk, and a substantial effect on confirmed group A meningococcal meningitis. It is important to continue strengthening surveillance to monitor vaccine performance and remain vigilant against threats from other meningococcal serogroups and other pathogens., Funding: World Health Organization., (Copyright © 2017 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Background: Serogroup A Neisseria meningitidis (NmA) was the cause of the 2011 meningitis epidemics in Chad. This bacterium, often carried asymptomatically, is considered to be an "accidental pathogen"; however, the transition from carriage to disease phenotype remains poorly understood. This study examined the role genetic diversity might play in this transition by comparing genomes from geographically and temporally matched invasive and carried NmA isolates., Results: All 23 NmA isolates belonged to the ST-5 clonal complex (cc5). Ribosomal MLST comparison with other publically available NmA:cc5 showed that isolates were closely related, although those from Chad formed two distinct branches and did not cluster with other NmA, based on their MLST profile, geographical and temporal location. Whole genome MLST (wgMLST) comparison identified 242 variable genes among all Chadian isolates and clustered them into three distinct phylogenetic groups (Clusters 1, 2, and 3): no systematic clustering by disease or carriage source was observed. There was a significant difference (p = 0.0070) between the mean age of the individuals from which isolates from Cluster 1 and Cluster 2 were obtained, irrespective of whether the person was a case or a carrier., Conclusions: Whole genome sequencing provided high-resolution characterization of the genetic diversity of these closely related NmA isolates. The invasive meningococcal isolates obtained during the epidemic were not homogeneous; rather, a variety of closely related but distinct clones were circulating in the human population with some clones preferentially colonizing specific age groups, reflecting a potential age-related niche adaptation. Systematic genetic differences were not identified between carriage and disease isolates consistent with invasive meningococcal disease being a multi-factorial event resulting from changes in host-pathogen interactions along with the bacterium.

We assessed the cost-effectiveness of offering catch-up vaccination with Bexsero against meningococcal disease to children too old to receive the vaccine under the recently introduced infant programme. Offering catch-up vaccination to increasingly older children is less economically attractive because of declining disease burden. We estimate catch-up vaccination of 1year old children could be cost-effective, incremental on the infant programme with a vaccine price of ⩽£8 per dose. Extending vaccination to 2year olds could only be cost-effective (incremental on infant and 1year old catch-up) with a vaccine price of ⩽£3 per dose and was not cost-effective in sensitivity analyses with more conservative vaccine assumptions. Extending catch-up further to 3-4year olds was not cost-effective. Employing the current criteria for assessing vaccines, our models suggest that even with low vaccine prices only catch-up vaccination in 1year old children could be cost-effective, when considered incrementally on the infant programme., (Copyright © 2016. Published by Elsevier Ltd.)

Conventional methods for detecting pharyngeal carriage of Neisseria meningitidis are complex. There is a need for simpler methods with improved performance. We have investigated two alternative approaches. Three pharyngeal swabs were collected from 999 pupils aged 10 to 18 years in The Gambia. Carriage of N. meningitidis was investigated by using three different methods: (i) plating on Thayer-Martin selective medium and testing by conventional microbiological methods followed by PCR testing; (ii) seeding in Todd-Hewitt broth (THB) and, after culture overnight, testing by PCR; and (iii) compression of the swab on filter paper and, after DNA concentration, testing by PCR. PCR after culture in THB was more than twice as sensitive as conventional methods in detecting N. meningitidis (13.2% versus 5.7%; P < 0.0001). PCR after DNA extraction from filter paper had a sensitivity similar to that of conventional methods (4.9% versus 5.7%; P = 0.33). Capsular genogroups detected by broth culture were genogroups W (21 isolates), B (12 isolates), Y (8 isolates), E (3 isolates), and X (2 isolates), and 68 meningococci had the capsule-null intergenic region. The distributions of genogroups and of capsule-null organisms were similar with each of the three methods. The carriage density in samples extracted from filter paper ranged from 1 to 25,000 DNA copies. PCR of broth cultures grown overnight doubled the yield of N. meningitidis carriage isolates compared with conventional methods. This approach could improve the efficiency of carriage studies. Collection on filter paper followed by quantitative PCR could be useful for density measurement and for carriage studies in areas with limited resources., (Copyright © 2016 Manigart et al.)

Background: To identify the barriers and facilitators to uptake of the HPV vaccine in an ethnically diverse group of young women in the south west of England., Methods: Three school-based vaccination sessions were observed. Twenty-three young women aged 12 to 13 years, and six key informants, were interviewed between October 2012 and July 2013. Data were analysed using thematic analysis and the Framework method for data management., Results: The priority given to preventing cervical cancer in this age group influenced whether young women received the HPV vaccine. Access could be affected by differing levels of commitment by school staff, school nurses, parents and young women to ensure parental consent forms were returned. Beliefs and values, particularly relevant to minority ethnic groups, in relation to adolescent sexual activity may affect uptake. Literacy and language difficulties undermine informed consent and may prevent vaccination., Conclusions: The school-based HPV vaccination programme successfully reaches the majority of young women. However, responsibility for key aspects remain unresolved which can affect delivery and prevent uptake for some groups. A multi-faceted approach, targeting appropriate levels of the socio-ecological model, is required to address procedures for consent and cultural and literacy barriers faced by minority ethnic groups, increase uptake and reduce inequalities., (© The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health.)

Bexsero, a new vaccine against serogroup B meningococcal disease (MenB), was licensed in Europe in January 2013. In Germany, Bexsero is recommended for persons at increased risk of invasive meningococcal disease, but not for universal childhood vaccination. To support decision making we adapted the independently developed model for England to the German setting to predict the potential health impact and cost-effectiveness of universal vaccination with Bexsero(®) against MenB disease. We used both cohort and transmission dynamic mathematical models, the latter allowing for herd effects, to consider the impact of vaccination on individuals aged 0-99 years. Vaccination strategies included infant and adolescent vaccination, alone or in combination, and with one-off catch-up programmes. German specific data were used where possible from routine surveillance data and the literature. We assessed the impact of vaccination through cases averted and quality adjusted life years (QALY) gained and calculated costs per QALY gained. Assuming 65% vaccine uptake and 82% strain coverage, infant vaccination was estimated to prevent 15% (34) of MenB cases over the lifetime of one birth cohort. Including herd effects from vaccination increased the cases averted by infant vaccination to 22%, with an estimated 8461 infants requiring vaccination to prevent one case. In the short term the greatest health benefit is achieved through routine infant vaccination with large-scale catch-up, which could reduce cases by 24.9% after 5 years and 27.9% after 10 years. In the long term (20+ years) policies including routine adolescent vaccination are most favourable if herd effects are assumed. Under base case assumptions with a vaccine list price of €96.96 the incremental cost-effectiveness ratio (ICER) was >€500,000 per QALY for all considered strategies. Given the current very low incidence of MenB disease in Germany, universal vaccination with Bexsero(®) would prevent only a small absolute number of cases, at a high overall cost., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Since 2010, countries in the African meningitis belt have been introducing a new serogroup A meningococcal conjugate vaccine (MenAfriVac(®)) through mass campaigns. With the subsequent decline in meningitis due to Neisseria meningitidis serogroup A (NmA) and relative increase in meningitis due to other serogroups, mainly N. meningitidis serogroup W (NmW), the World Health Organisation (WHO) initiated a review of the incidence thresholds that guide response to meningitis epidemics in the African meningitis belt., Methods: Meningitis surveillance data from African meningitis belt countries from 2002 to 2013 were used to construct a single NmW dataset. The performance of different weekly attack rates, used as thresholds to initiate vaccination response, on preventing further cases was estimated. The cumulative seasonal attack rate used to define an epidemic was also varied., Results: Considerable variation in effect at different thresholds was observed. In predicting epidemics defined as a seasonal cumulative incidence of 100/10(5) population, an epidemic threshold of 10 cases/10(5) population/week performed well. Based on this same epidemic threshold, with a 6 week interval between crossing the epidemic threshold and population protection from a meningococcal vaccination campaign, an estimated 17 cases per event would be prevented by vaccination. Lowering the threshold increased the number of cases per event potentially prevented, as did shortening the response interval. If the interval was shortened to 4 weeks at the threshold of 10/10(5), the number of cases prevented would increase to 54 per event., Conclusions: Accelerating time to vaccination could prevent more cases per event than lowering the threshold. Once the meningitis epidemic threshold is crossed, it is of critical importance that vaccination campaigns, where appropriate, are initiated rapidly., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: In 2010, mass vaccination with a then-new meningococcal A polysaccharide-tetanus toxoid protein conjugate vaccine (PsA-TT, or MenAfriVac) was undertaken in 1- to 29-year-olds in Bamako, Mali. Whether vaccination with PsA-TT effectively boosts tetanus immunity in a population with heterogeneous baseline tetanus immunity is not known. We assessed the impact of PsA-TT on tetanus toxoid (TT) immunity by quantifying age- and sex-specific immunity prior to and 2 years after introduction., Methods: Using a household-based, age-stratified design, we randomly selected participants for a prevaccination serological survey in 2010 and a postvaccination survey in 2012. TT immunoglobulin G (IgG) antibodies were quantified and geometric mean concentrations (GMCs) pre- and postvaccination among all age groups targeted for vaccination were compared. The probability of TT IgG levels ≥0.1 IU/mL (indicating short-term protection) and ≥1.0 IU/mL (indicating long-term protection) by age and sex was determined using logistic regression models., Results: Analysis of 793 prevaccination and 800 postvaccination sera indicated that while GMCs were low pre-PsA-TT, significantly higher GMCs in all age-sex strata were observed 2 years after PsA-TT introduction. The percentage with short-term immunity increased from 57.1% to 88.4% (31.3-point increase; 95% confidence interval [CI], 26.6-36.0;, P < .0001) and with long-term immunity increased from 20.0% to 58.5% (38.5-point increase; 95% CI, 33.7-43.3; P < .0001) pre- and postvaccination., Conclusions: Significantly higher TT immunity was observed among vaccine-targeted age groups up to 2 years after Mali's PsA-TT mass vaccination campaign. Our results, combined with evidence from clinical trials, strongly suggest that conjugate vaccines containing TT such as PsA-TT should be considered bivalent vaccines because of their ability to boost tetanus immunity., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: The introduction of MenAfriVac in campaigns targeting people aged 1-29 years across the African meningitis belt has successfully reduced meningitis incidence and carriage due to Neisseria meningitidis group A (MenA). It is important to consider how best to sustain population protection in the long term., Methods: We created a mathematical model of MenA transmission and disease to investigate the potential impact of a range of immunization strategies. The model is age structured; includes classes of susceptible, carrier, ill, and immune people (who may be vaccinated or unvaccinated); and incorporates seasonal transmission and a stochastic forcing term that models between year variation in rates of transmission. Model parameters were primarily derived from African sources. The model can describe the typical annual incidence of meningitis in the prevaccine era, with irregular epidemics of varying size. Parameter and structural uncertainty were explored in sensitivity analyses., Results: Following MenAfriVac introduction at high uptake, the model predicts excellent short-term disease control. With no subsequent immunization, strong resurgences in disease incidence were predicted after approximately 15 years (assuming 10 years' average vaccine protection). Routine immunization at 9 months of age resulted in lower average annual incidence than regular mass campaigns of 1- to 4-year-olds, provided coverage was above approximately 60%. The strategy with the lowest overall average annual incidence and longest time to resurgence was achieved using a combination strategy of introduction into the Expanded Programme on Immunization at 9 months, 5 years after the initial mass campaigns, with a catch-up targeting unvaccinated 1- to 4-year-olds., Conclusions: These results can be used to inform policy recommendations for long-term vaccination strategies with MenAfriVac., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: A group A meningococcal (MenA) conjugate vaccine, PsA-TT (MenAfriVac), was introduced in Burkina Faso via mass campaigns between September and December 2010, targeting the 1- to 29-year-old population. This study describes specific antibody titers in the general population 11 months later and compares them to preintroduction data obtained during 2008 using the same protocol., Methods: During October-November 2011, we recruited a representative sample of the population of urban Bobo-Dioulasso aged 6 months to 29 years, who underwent standardized interviews and blood draws. We assessed anti-MenA immunoglobulin G (IgG) concentrations (n = 200) and, using rabbit complement, serum bactericidal antibody (SBA) titers against 2 group A strains: reference strain F8238 (SBAref) (n = 562) and strain 3125 (SBA3125) (n = 200)., Results: Among the 562 participants, 481 (86%) were aged ≥23 months and had been eligible for the PsA-TT campaign. Among them, vaccine coverage was 86.3% (95% confidence interval [CI], 82.7%-89.9%). Prevalence of putatively protective antibodies among vaccine-eligible age groups was 97.3% (95% CI, 95.9%-98.7%) for SBAref titers ≥128, 83.6% (95% CI, 77.6%-89.7%) for SBA3125 ≥128, and 84.2% (95% CI, 78.7%-89.7%) for anti-MenA IgG ≥2 µg/mL. Compared to the population aged 23 months to 29 years during 2008, geometric mean titers of SBAref were 7.59-fold higher during 2011, 51.88-fold for SBA3125, and 10.56-fold for IgG., Conclusions: This study shows high seroprevalence against group A meningococci in Burkina Faso following MenAfriVac introduction. Follow-up surveys will provide evidence on the persistence of population-level immunity and the optimal vaccination strategy for long-term control of MenA meningitis in the African meningitis belt., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Pertussis, or whooping cough, is an important respiratory infection causing considerable infant mortality worldwide. Recently, incidence has risen in countries with strong vaccine programmes and there are concerns about antigenic shift resulting in vaccine evasion. Interactions between pertussis and non-vaccine-preventable strains will play an important role in the evolution and population dynamics of pertussis. In particular, if we are to understand the role strain replacement plays in vaccinated settings, it will be essential to understand how strains or variants of pertussis interact. Here we explore under what conditions we would expect strain replacement to be of concern in pertussis. We develop a dynamic transmission model that allows for coinfection between Bordetella pertussis (the main causative agent of pertussis) and a strain or variant unaffected by the vaccine. We incorporate both neutrality (in the sense of ecological/population genetic neutrality) and immunity into the model, leaving the specificity of the immune response flexible. We find that strain replacement may be considerable when immunity is non-specific. This is in contrast to previous findings where neutrality was not considered. We conclude that the extent to which models reflect ecological neutrality can have a large impact on conclusions regarding strain replacement. This will likely have onward consequences for estimates of vaccine efficacy and cost-effectiveness., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Infant 13-valent pneumococcal conjugate vaccination (PCV13) was introduced to the UK in 2010. Its impact on serotypes implicated in adult non-bacteraemic pneumococcal pneumonia is not known. Beginning in 2008, a 5-year prospective cohort study of adults admitted to hospital with community-acquired pneumonia (CAP) was conducted. Pneumococcal serotype was established using a validated multiplex immunoassay (Bio-Plex; Bio-Rad, Hercules, CA, USA). The overall incidence for hospitalised CAP and pneumococcal CAP was 79.9 (95% CI 76.6-83.3) and 23.4 (95% CI 21.6-25.3) per 100,000 population, respectively. A decline in CAP (incidence rate ratio (IRR) per year 0.96, 95% CI 0.94-0.99; p=0.016) and pneumococcal CAP (IRR per year 0.84, 95% CI 0.80-0.89; p<0.001) was observed over the 5-year period of the study. Between the pre- and post-PCV13 periods of the study, the incidence of CAP due to serotypes included in the PCV7 declined by 88% (IRR 0.12, 95% CI 0.08-0.20; p<0.001), and CAP due to the additional 6 serotypes in PCV13 declined by 30% (IRR 0.70, 95% CI 0.51-0.96; p=0.024). Incidence of adult pneumococcal pneumonia declined over the last 5 years, with serotypes included in PCV13 declining post-PCV13 introduction, indicating early herd protection effects from PCV13 infant vaccination on adult non-bacteraemic disease. These effects may accrue over the coming years with implications for national pneumococcal vaccination policies in adults., (Copyright ©ERS 2015.)

In 2011, vaccination with a serogroup A meningococcal polysaccharide conjugate vaccine was implemented in 3 of 23 regions in Chad. Cases of meningitis declined dramatically in vaccinated areas, but an epidemic continued in the rest of Chad. In 2012, the remaining Chad population was vaccinated, and the epidemic was halted.