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Background: A concern in high-income countries is that switching to 1-dose human papillomavirus (HPV) vaccination could cause a rebound in HPV infection and cervical cancer if 1-dose efficacy or duration were inferior to 2 doses. Using mathematical modeling and up-to-date trial-based data, we projected the population-level effectiveness of switching from 2-dose to 1-dose vaccination under different vaccine efficacy and duration assumptions in high-income countries., Methods: We used HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation), a transmission-dynamic model of HPV infection and cervical cancer, varying key model assumptions to identify those with the greatest impact on projections of HPV-16 and cervical cancer incidence over time: 1) 1-dose vaccine efficacy and vaccine duration, 2) mechanisms of vaccine efficacy and duration over time, 3) midadult (>30 years of age) sexual behavior, 4) progression to cervical cancer among midadults, and 5) vaccination coverage and programs., Results: In high-income countries, 1-dose vaccination would cause no appreciable rebound in HPV-16 infection, except for a limited rebound under the most pessimistic assumptions of vaccine duration (average, 25 years), because 1) the switch would occur when HPV prevalence is low because of high 2-dose vaccination coverage and 2) individuals would be protected during their peak ages of sexual activity (<35 to 40 years of age). Our model projects a more limited rebound in cervical cancer because of a shift to older age at infection, resulting in fewer life-years left to potentially develop cancer. Projections were robust when varying key model assumptions., Conclusions: High protection during peak ages of sexual activity in high-income countries would likely mitigate any potential rebounds in HPV infection and cervical cancer under the most pessimistic assumptions of 1-dose efficacy and duration., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Recommendations around the use of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13) seldom focus on potential benefits of vaccine on comorbidities. We aimed to investigate whether sequential vaccination with PCV13 and PPSV23 among older adults would provide protection against cardiovascular diseases (CVD) compared with using a single pneumococcal vaccine., Methods: We conducted a Hong Kong-wide retrospective cohort study between 2012 and 2020. Adults aged ≥65 years were identified as receiving either a single or sequential dual vaccination and followed up until the earliest CVD occurrence, death or study end. To minimize confounding, we matched each person receiving a single vaccination to a person receiving sequential vaccination according to their propensity scores. We estimated the hazard ratio (HR) of CVD risk using Cox regression and applied structural equation modelling to test whether the effect of sequential dual vaccination on CVD was mediated via the reduction in pneumonia., Results: After matching, 69 390 people remained in each group and the median (interquartile range) follow-up time was 1.89 (1.55) years. Compared with those receiving a single vaccine, those receiving sequential dual vaccination had a lower risk of CVD [HR (95% CI): 0.75 (0.71, 0.80), P < 0.001]. Post-hoc mediation analysis showed strong evidence that the decreased CVD risk was mediated by the reduction in all-cause pneumonia., Conclusions: Sequential dual pneumococcal vaccination was associated with lower risk of CVD compared with single-dose PCV13 or PPSV23 in older adults. Such additional CVD benefits should be considered when making decisions about pneumococcal vaccination., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings., Methods: After screening 16 822 citations, we identified 9 articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria., Results: Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], -212.4 to -31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, -95.3 to -12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, -62.6 to -3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, -51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection., Conclusions: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination., Competing Interests: Potential conflict of interests. M. J. received research grant funding for measles from the Bill & Melinda Gates Foundation and Gavi, The Vaccine Alliance, and was also a member on the WHO SAGE Working Group on measles and rubella. S. F. received research funding from Wellcome Trust. W. A. O. worked as unpaid consultant to Merck on revising measles vaccine production process. W. J. M. is a former member of the World Health Organization SAGE Working Group on Measles and Rubella. J. M. H. received grant funding Natural Science and Engineering Research Council of Canada. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Her Majesty the Queen in Right of Canada, as represented by the Public Health Ontario, 2022.)

Background: We aimed to quantify the unknown losses in health-related quality of life of coronavirus disease 2019 (COVID-19) cases using quality-adjusted lifedays (QALDs) and the recommended EQ-5D instrument in England., Methods: Prospective cohort study of nonhospitalized, polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2-positive (SARS-CoV-2-positive) cases aged 12-85 years and followed up for 6 months from 1 December 2020, with cross-sectional comparison to SARS-CoV-2-negative controls. Main outcomes were QALD losses; physical symptoms; and COVID-19-related private expenditures. We analyzed results using multivariable regressions with post hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls., Results: Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on nonprescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95% confidence interval [CI]: 9.7, 17.7) QALDs, whereas those reporting symptoms at month 6 lost 32.9 (95% CI: 24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in the England., Conclusions: One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms., (© Crown copyright 2022.)

Background: Every winter, respiratory syncytial virus (RSV) disease results in thousands of cases in Norwegian children under 5 years of age. We aim to assess the RSV-related economic burden and the cost-effectiveness of upcoming RSV disease prevention strategies including year-round maternal immunization and year-round and seasonal monoclonal antibody (mAb) programs., Methods: Epidemiological and cost data were obtained from Norwegian national registries, while quality-adjusted life-years (QALYs) lost and intervention characteristics were extracted from literature and phase 3 clinical trials. A static model was used and uncertainty was accounted for probabilistically. Value of information was used to assess decision uncertainty. Extensive scenario analyses were conducted, including accounting for long-term consequences of RSV disease., Results: We estimate an annual average of 13 517 RSV cases and 1572 hospitalizations in children under 5, resulting in 79.6 million Norwegian kroner (~€8 million) treatment costs. At €51 per dose for all programs, a 4-month mAb program for neonates born in November to February is the cost-effective strategy for willingness to pay (WTP) values up to €40 000 per QALY gained. For higher WTP values, the longer 6-month mAb program that immunizes neonates from October to March becomes cost-effective. Sensitivity analyses show that year-round maternal immunization can become a cost-effective strategy if priced lower than mAb., Conclusions: Assuming the same pricing, seasonal mAb programs are cost-effective over year-round programs in Norway. The timing and duration of the cost-effective seasonal program are sensitive to the pattern of the RSV season in a country, so continued RSV surveillance data are essential., Competing Interests: Potential conflicts of interest. T. W. received funding for working on vaccines related to other diseases, varicella, and herpes zoster from MSD Norway, outside the submitted work. P. B. declared consultancy fees paid to the University of Antwerp from GSK and Pfizer on 2 occasions for discussions on economic evaluation (<€3000 in total), outside the submitted work. L. B. declares regular interaction with pharmaceutical and other industrial partners, but has not received personal fees or other personal benefits. University Medical Center Utrecht (UCMU) has received major funding (>€100,000 per industrial partner) for investigator-initiated studies from AbbVie, MedImmune, Janssen, Pfizer, the Bill and Melinda Gates Foundation, and MeMed Diagnostics. UMCU has received major cash or in-kind funding as part of the public-private partnership Innovative Medicines Initiative–funded RESCEU project from GSK, Novavax, Janssen, AstraZeneca, Pfizer, and Sanofi. UMCU has received major funding by Julius Clinical for participating in the INFORM study. M. J. is an affiliate member of RESCEU, but neither M. J. nor his research group has received any forms of pecuniary or other support from the pharmaceutical industry. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Sepsis and meningitis are among the leading causes of neonatal deaths in sub-Saharan Africa (SSA). Neonatal sepsis caused ~400 000 deaths globally in 2015, half occurring in Africa. Despite this, there are few published data on the acute costs of neonatal sepsis or meningitis, with none in SSA., Methods: We enrolled neonates admitted to 2 hospitals in South Africa and Mozambique between 16 April 2020 and 1 April 2021. In South Africa all cases were microbiologically confirmed, but in Mozambique both clinically suspected and microbiologically confirmed cases were included. Data were collected on healthcare resource use and length of stay, along with information on household expenditure and caregiving. We used unit costs of healthcare resources in local currencies to estimate healthcare provider costs per patient and costs per household. Results were converted to 2019 international dollars (I$)., Results: We enrolled 11 neonates in Mozambique and 18 neonates in South Africa. Mean length of stay was 10 days (median, 9 [interquartile range {IQR}, 4-14) and 16 days (median, 15 [IQR, 13-18]), respectively. In Mozambique we estimated mean household costs of I$49.62 (median, 10.19 [IQR, 5.10-95.12]) and hospitalization costs of I$307.58 (median, 275.12 [IQR, 149.43-386.12]). In South Africa these costs were I$52.31 (median, 30.82 [IQR, 19.25-73.08]) and I$684.06 (median, 653.62 [IQR, 543.33-827.53]), respectively., Conclusions: We found substantial costs associated with acute neonatal bacterial (all-cause) sepsis and meningitis in SSA. Our estimates will inform economic evaluations of interventions to prevent neonatal invasive bacterial infections., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

The global burden of Group B Streptococcus (GBS) was estimated for 2015 prompting inclusion of GBS as a priority in the Global Meningitis Roadmap. New estimates for the year 2020 and a WHO report analysing the full value of GBS maternal vaccines has been launched to advance evidence based decision making for multiple stakeholders. In this first of a 10-article supplement, we discuss the following (1) gaps in evidence and action, (2) new evidence in this supplement, and (3) what actions can be taken now and key research gaps ahead. We call for investment in the research pipeline, notably description, development, and delivery, in order to accelerate progress and address the large burden of GBS for every family in every country., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Internationally, key workers such as healthcare staff are advised to stay at home if they or household members experience coronavirus disease 2019 (COVID-19)-like symptoms. This potentially isolates/quarantines many staff without SARS-CoV-2, while not preventing transmission from staff with asymptomatic infection. We explored the impact of testing staff on absence durations from work and transmission risks to others., Methods: We used a decision-analytic model for 1000 key workers to compare the baseline strategy of (S0) no RT-PCR testing of workers to testing workers (S1) with COVID-19-like symptoms in isolation, (S2) without COVID-19-like symptoms but in household quarantine, and (S3) all staff. We explored confirmatory re-testing scenarios of repeating all initial tests, initially positive tests, initially negative tests, or no re-testing. We varied all parameters, including the infection rate (0.1-20%), proportion asymptomatic (10-80%), sensitivity (60-95%), and specificity (90-100%)., Results: Testing all staff (S3) changes the risk of workplace transmission by -56.9 to +1.0 workers/1000 tests (with reductions throughout at RT-PCR sensitivity ≥65%), and absences by -0.5 to +3.6 days/test but at heightened testing needs of 989.6-1995.9 tests/1000 workers. Testing workers in household quarantine (S2) reduces absences the most by 3.0-6.9 days/test (at 47.0-210.4 tests/1000 workers), while increasing risk of workplace transmission by 0.02-49.5 infected workers/1000 tests (which can be minimized when re-testing initially negative tests)., Conclusions: Based on optimizing absence durations or transmission risk, our modeling suggests testing staff in household quarantine or all staff, depending on infection levels and testing capacities., (© Crown copyright 2020.)

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., (© Crown copyright 2020.)

Background: Norovirus places a substantial burden on healthcare systems, arising from infected patients, disease outbreaks, beds kept unoccupied for infection control, and staff absences due to infection. In settings with high rates of bed occupancy, opportunity costs arise from patients who cannot be admitted due to beds being unavailable. With several treatments and vaccines against norovirus in development, quantifying the expected economic burden is timely., Methods: The number of inpatients with norovirus-associated gastroenteritis in England was modeled using infectious and noninfectious gastrointestinal Hospital Episode Statistics codes and laboratory reports of gastrointestinal pathogens collected at Public Health England. The excess length of stay from norovirus was estimated with a multistate model and local outbreak data. Unoccupied bed-days and staff absences were estimated from national outbreak surveillance. The burden was valued conventionally using accounting expenditures and wages, which we contrasted to the opportunity costs from forgone patients using a novel methodology., Results: Between July 2013 and June 2016, 17.7% (95% confidence interval [CI], 15.6%‒21.6%) of primary and 23.8% (95% CI, 20.6%‒29.9%) of secondary gastrointestinal diagnoses were norovirus attributable. Annually, the estimated median 290000 (interquartile range, 282000‒297000) occupied and unoccupied bed-days used for norovirus displaced 57800 patients. Conventional costs for the National Health Service reached £107.6 million; the economic burden approximated to £297.7 million and a loss of 6300 quality-adjusted life-years annually., Conclusions: In England, norovirus is now the second-largest contributor of the gastrointestinal hospital burden. With the projected impact being greater than previously estimated, improved capture of relevant opportunity costs seems imperative for diseases such as norovirus.

Background: Cervical cancer incidence has decreased over time in England particularly after the introduction of organized screening. In Portugal, where opportunistic screening has been widely available with only slightly lower coverage than that of the organized programme in England, rates of cervical cancer have been higher than in England. We compared the burden of cervical cancer, risk factors and preventive interventions over time in both countries, to identify elements hindering the further decline in incidence and mortality in Portugal., Methods: We used joinpoint regression to identify significant changes in rate time-trends. We also analyzed individual-level Portuguese data on sexual behaviour and human papillomavirus prevalence, and recent aggregate data on organized and opportunistic screening coverage. We compared published estimates of survival, risk factors and historical screening coverage for both countries., Results: Despite stable incidence, cervical cancer mortality has declined in both countries in the last decade. The burden has been 4 cases and 1 death per 100 000 women annually higher in Portugal than in England. Differences in human papillomavirus prevalence and risk factors for infection and disease progression do not explain the difference found in cervical cancer incidence. Significant mortality declines in both countries followed the introduction of different screening policies, although England showed a greater decline than Portugal over nearly 2 decades after centralizing organized screening., Conclusion: The higher rates of cervical cancer in Portugal compared to England can be explained by differences in screening quality and coverage.

Dengue viral infections are endemic or epidemic in virtually all tropical countries. Among individuals infected with the dengue virus, severe dengue syndromes (i.e., dengue haemorrhagic fever and dengue shock syndromes) tend to affect only some and this may be due to a combination of host genetic susceptibility and viral factors. In this review article we analyse and discuss the present knowledge of non-human leucocyte antigen host genetic susceptibility to severe dengue syndromes. The relevance of genetic polymorphisms in the pathways of antigen recognition, uptake, processing and presentation, activation of interferon α responses, mast cell and complement activation and T cell activation and dengue disease severity has been reviewed and analysed., (© The Author(s) 2018. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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

Objectives: Neutralization of TNF-alpha with either monoclonal antibodies or soluble receptors, although not curative, has significant clinical benefit in patients with rheumatoid arthritis (RA). In contrast, blockade of TNF-alpha has little clinical benefit in the majority of patients with systemic inflammatory response syndrome (SIRS) in spite of the identification of TNF-alpha as a key factor in its pathology. It is not clear why there is such a significant difference in the responses to TNF-alpha neutralization in these two conditions. Here we use mathematical modelling to investigate this discrepancy., Methods: Using the known pharmacokinetic and pharmacodynamic properties of TNF-alpha-blocking biological agents, we constructed a mathematical model of the biological actions of soluble(s) TNFR2, Etanercept and Infliximab., Results: Our model predicts that all three inhibitors, but especially Etanercept, are effective at controlling TNF-alpha levels in RA, which we propose is a condition in which TNF-alpha production and inhibition are in equilibrium. However, when free TNF-alpha drops to a low level, as can occur in SIRS, which we propose is a non-equilibrium condition, the sequestered TNF-alpha can act as a slow-release reservoir, thereby sabotaging its effectiveness., Conclusions: These results may explain the effectiveness of TNF-alpha blockade in the equilibrium condition RA and the ineffectiveness in the non-equilibrium condition SIRS.