Estimating the health effects of COVID-19-related immunisation disruptions in 112 countries during 2020-30: a modelling study.

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.

Preventing iatrogenic HCV infection: A quantitative risk assessment based on observational data in an Egyptian hospital.

When compliance with infection control recommendations is non-optimal, hospitals may play an important role in hepatitis C (HCV) transmission. However, few studies have analyzed the nosocomial HCV acquisition risk based on detailed empirical data. Here, we used data from a prospective cohort study conducted on 500 patients in the Ain Shams hospital (Cairo, Egypt) in 2017 with the objective of identifying (i) high-risk patient profiles and (ii) transmission hotspots within the hospital. Data included information on patient HCV status upon admission, their trajectories between wards and the invasive procedures they underwent. We first performed a sequence analysis to identify different hospitalization profiles. Second, we estimated each patient's individual risk of HCV acquisition based on ward-specific prevalence and procedures undergone, and risk hotspots by computing ward-level risks. Then, using a beta regression model, we evaluated upon-admission factors linked to HCV acquisition risk and built a score estimating the risk of HCV infection during hospitalization based on these factors. Finally, we assessed and compared ward-focused and patient-focused HCV control strategies. The sequence analysis based on patient trajectories allowed us to identify four distinct patient trajectory profiles. The risk of HCV infection was greater in the internal medicine department, compared to the surgery department (0·188% [0·142%-0·235%] vs. 0·043%, CI 95%: [0·036%-0·050%]), with risk hotspots in the geriatric, tropical medicine and intensive-care wards. Upon-admission risk predictors included source of admission, age, reason for hospitalization, and medical history. Interventions focused on the most at-risk patients were most effective to reduce HCV infection risk. Our results might help reduce the risk of HCV acquisition during hospitalization in Egypt by targeting enhanced control measures to ward-level transmission hotspots and to at-risk patients identified upon admission.

Investigating inequalities in HIV testing in sub-Saharan Africa: spatial analysis of cross-sectional population-based surveys in 25 countries.

OBJECTIVES: We aim to explore spatial variations in socioeconomic inequalities in HIV testing uptake in sub-Saharan Africa (SSA) at different geographical scales to identify potential geographical hotspots of inequalities. Additionally, to evaluate the potential benefits of HIV testing programmes, we assess whether local levels of HIV testing match the local levels of HIV prevalence. DESIGN: A multi-country analysis of population-based cross-sectional surveys in SSA. SETTING: We analysed data from 25 SSA countries with Demographic and Health Surveys between 2011 and 2019. PARTICIPANTS: Country-level analysis included 473 775 participants (312 104 women and 161 671 men) and cluster-level analysis included 328 283 individuals (241 084 women and 87 199 men). Women aged 15-49 years and men aged 15-54/59 years in selected households who were tested for HIV in the last 12 months were eligible. We quantified inequalities in self-reported recent HIV testing with the Slope Index of Inequality (SII) and the Relative Index of Inequality (RII) across geographical scales to capture sex-specific within-country spatial variations. We also conducted local Getis-Ord Gi* statistics to consider the autocorrelation in fine-scale SII and RII across countries. To assess the efficiency of HIV testing programmes, we measured the correlation between recent HIV testing and HIV prevalence through Spearman correlation across geographical scales. RESULTS: We observed varying inequalities in recent HIV testing in magnitude and spatial distribution on both absolute and relative scales in many countries for both sexes at national and subnational levels. Hotspots of absolute and relative inequalities were mostly observed in Western and Central Africa with a few regions in Eastern and Southern Africa. Despite significant sex-specific correlations between testing and prevalence in all countries when assessed at the national level, we report an absence of such a correlation at fine scale in 17 of 50 sex-country combinations. CONCLUSIONS: We highlight the importance of investigating the spatial variability of various HIV indicators and related inequalities across different geographical levels. Results may help inform an equitable distribution of HIV testing services.

Sick leave due to COVID-19 during the first pandemic wave in France, 2020.

OBJECTIVES: To quantify the burden of COVID-19-related sick leave during the first pandemic wave in France, accounting for sick leaves due to symptomatic COVID-19 ('symptomatic sick leaves') and those due to close contact with COVID-19 cases ('contact sick leaves'). METHODS: We combined data from a national demographic database, an occupational health survey, a social behaviour survey and a dynamic SARS-CoV-2 transmission model. Sick leave incidence from 1 March 2020 to 31 May 2020 was estimated by summing daily probabilities of symptomatic and contact sick leaves, stratified by age and administrative region. RESULTS: There were an estimated 1.70M COVID-19-related sick leaves among France's 40M working-age adults during the first pandemic wave, including 0.42M due to COVID-19 symptoms and 1.28M due to COVID-19 contacts. There was great geographical variation, with peak daily sick leave incidence ranging from 230 in Corse (Corsica) to 33 000 in Île-de-France (the greater Paris region), and greatest overall burden in regions of north-eastern France. Regional sick leave burden was generally proportional to local COVID-19 prevalence, but age-adjusted employment rates and contact behaviours also contributed. For instance, 37% of symptomatic infections occurred in Île-de-France, but 45% of sick leaves. Middle-aged workers bore disproportionately high sick leave burden, owing predominantly to greater incidence of contact sick leaves. CONCLUSIONS: France was heavily impacted by sick leave during the first pandemic wave, with COVID-19 contacts accounting for approximately three-quarters of COVID-19-related sick leaves. In the absence of representative sick leave registry data, local demography, employment patterns, epidemiological trends and contact behaviours can be synthesised to quantify sick leave burden and, in turn, predict economic consequences of infectious disease epidemics.

Changes in Presentation, Treatment, and Survival of Patients with Hepatocellular Carcinoma in Damietta, Egypt, 2007-2019: A Retrospective Monocentric Cohort Study.

Introduction: We aimed to assess temporal changes in the presentation and survival of patients with hepatocellular carcinoma (HCC) in the northern Egypt region, one of the regions reporting the highest incidence of the disease globally. Methods: We conducted a monocentric retrospective study. Patients presenting at the Damietta Oncology referral center between 2007 and 2019 with a diagnosed HCC were eligible. Individual, clinical and tumor characteristics at HCC diagnosis, including the Barcelona Clinic Liver Cancer (BCLC) staging, were retrieved from medical files and patients' final vital status was ascertained by combining various data sources. Patients were divided into 2 groups based on diagnosis period: pre- and post-2014. Survival was analysed based on Kaplan-Meier curves and differences in restricted mean survival time (RMST). Results: Data from 5097 patients (among 5210 eligible, 97.8%) were analyzed. We observed a significant trend toward HCC diagnosed at earlier stage in the post- vs pre-2014 period (BCLC stage 0/A or B: 37.2% vs 27.1%, p<10-3). Overall patient's survival after the HCC diagnosis was poor, with a median of 8.1 months. The BCLC staging system performed well in predicting survival. Despite a trend toward HCC diagnosed at earlier stages, we did not observe a significant improvement in survival over time. Overall, treatments offered in this medical center were in line with international guidelines, and 16.1% of the patients who received a curative treatment had an improved survival (30.7 months in median). However, HCC recurrence was frequent among patients cured for HCC, with a median time to recurrence of 22 months. Discussion: Overall survival after HCC diagnosis in Egypt remains poor but is significantly improved by curative therapy. Despite a trend toward earlier diagnosis of HCC, we did not observe a general improvement in survival over time, which remains to be clearly understood.

Maladies non transmissibles et comorbidités chez les séniors dans le service de medécine interne du CHU de Bouaké / Non-Communicable Diseases and Comorbidities in Seniors in the Internal Medicine Department of the University Hospital of Bouake

. Les maladies non transmissibles chez le sujet âgé sont négligées en Afrique car l'espérance de vie n'était aussi élevée qu'aujourd'hui. Quel en était donc le panorama, il y a 10 ans ? Objectif : Améliorer les connaissances des maladies non transmissibles et des comorbidités chez les sujets âgés. Méthodes. Il s'agissait d'une étude transversale, rétrospective à visée descriptive du 1er janvier 2009 au 31 décembre 2013 dans le service de Médecine Interne du Centre Hospitalier Universitaire de Bouaké (CHU). Elle portait sur 151 patients hypertendus âgés de 65 ans et plus. Résultats. L'âge moyen était de 75 ans avec des extrêmes de 65 ans et 93 ans. Le sex-ratio était de 1,07. Les comorbidités étaient marquées principalement par le diabète (47%). Les motifs d'hospitalisation étaient dominés par les signes neurologiques (70%). L'hypertension artérielle (HTA) systolique isolée représentait 48% et l'HTA de grade III 23%. Ses principales complications étaient les accidents vasculaires cérébraux (AVC) (62%) et les cardiopathies (32%). Ces AVC étaient surtout ischémiques (78%). L'HTA était associée à d'autres facteurs de risque cardiovasculaire (78%) notamment la pression pulsée (52%) et le diabète (47%). Les Inhibiteurs de l'enzyme de conversion (IEC) étaient les plus prescrits (64%). La mortalité était de 23%. Conclusion. Les facteurs de risque cardiovasculaire constituent depuis plus de 10 ans à Bouaké, la morbidité mais surtout la mortalité des séniors, du fait de la gravité de leurs complications.

Estimating the risk of incident SARS-CoV-2 infection among healthcare workers in quarantine hospitals: the Egyptian example.

In response to the COVID-19 epidemic, Egypt established a unique care model based on quarantine hospitals where only externally-referred confirmed COVID-19 patients were admitted, and healthcare workers resided continuously over 1- to 2-week working shifts. Using a mathematical model accounting for the false-negative rates of RT-PCR tests, we computed the incidence rate of SARS-CoV-2 infection among HCWs, while unveiling the proportion of infections remaining undiagnosed despite routine testing. We relied on longitudinal data, including results of routine RT-PCR tests, collected within three Egyptian quarantine hospitals. We estimated an incidence rate (per 100 person-day, PD) of 1.05 (95% CrI 0.58-1.65) at Hospital 1, 1.92 (95% CrI 0.93-3.28) at Hospital 2 and 7.62 (95% CrI 3.47-13.70) at Hospital 3. We found that the risk for an HCW to be infected during a working shift lay within the range of risk levels previously documented in standard healthcare settings for Hospitals 1-2, whereas it was > threefold higher for Hospital 3. This large variation suggests that HCWs from quarantine hospitals may face a high occupational risk of infection, but that, with sufficient infection control measures, this risk can be brought down to levels similar to those observed in standard healthcare settings.

Association between Conflict and Cholera in Nigeria and the Democratic Republic of the Congo.

Cholera outbreaks contribute substantially to illness and death in low- and middle-income countries. Cholera outbreaks are associated with several social and environmental risk factors, and extreme conditions can act as catalysts. A social extreme known to be associated with infectious disease outbreaks is conflict, causing disruption to services, loss of income, and displacement. To determine the extent of this association, we used the self-controlled case-series method and found that conflict increased the risk for cholera in Nigeria by 3.6 times and in the Democratic Republic of the Congo by 2.6 times. We also found that 19.7% of cholera outbreaks in Nigeria and 12.3% of outbreaks in the Democratic Republic of the Congo were attributable to conflict. Our results highlight the value of providing rapid and sufficient assistance during conflict-associated cholera outbreaks and working toward conflict resolution and addressing preexisting vulnerabilities, such as poverty and access to healthcare.

Understanding the pathways leading to socioeconomic inequalities in HIV testing uptake in 18 sub-Saharan African countries.

OBJECTIVE: To better understand the different pathways linking socioeconomic position and HIV testing uptake in 18 sub-Saharan African countries. DESIGN: We used cross-sectional population-based surveys between 2010 and 2018. METHODS: Using a potential outcomes framework and the product method, we decomposed the total effect linking wealth and recent (<12 months) HIV testing into direct effects, and indirect effects, via internal (related to individual's ability to perceive need for and to seek care) or external (ability to reach, pay for and engage in healthcare) mediators to calculate the proportion mediated (PM) by each mediator. RESULTS: High levels of inequalities were observed in nine and 15 countries among women and men, respectively. The mediator indirect effect varied greatly across countries. The PM tended to be higher for internal than for external mediators. For instance, among women, HIV-related knowledge was estimated to mediate up to 12.1% of inequalities in Côte d'Ivoire; and up to 31.5% for positive attitudes towards people with HIV (PWH) in Senegal. For the four external mediators, the PM was systematically below 7%. Similar findings were found when repeating analyses on men for the internal mediators, with higher PM by attitudes towards PWH (up to 39.9% in Senegal). CONCLUSIONS: Our findings suggest that wealth-related inequalities in HIV testing may be mediated by internal more than external characteristics, with important variability across countries. Overall, the important heterogeneities in the pathways of wealth-related inequalities in HIV testing illustrate that addressing inequalities requires tailored efforts and upstream interventions.

Assessing the Health Benefits of Physical Activity Due to Active Commuting in a French Energy Transition Scenario.

Objectives: Energy transition scenarios are prospective outlooks describing combinations of changes in socio-economic systems that are compatible with climate targets. These changes could have important health co-benefits. We aimed to quantify the health benefits of physical activity caused by active transportation on all-cause mortality in the French negaWatt scenario over the 2021-2050 period. Methods; Relying on a health impact assessment framework, we quantified the health benefits of increased walking, cycling and E-biking projected in the negaWatt scenario. The negaWatt scenario assumes increases of walking and cycling volumes of +11% and +612%, respectively, over the study period. Results: As compared to a scenario with no increase in volume of active travel, we quantified that the negaWatt scenario would prevent 9,797 annual premature deaths in 2045 and translate into a 3-month increase in life expectancy in the general population. These health gains would generate €34 billion of economic benefits from 2045 onwards. Conclusion: Increased physical activity implied in the negaWatt transition scenario would generate substantial public health benefits, which are comparable to the gain expected by large scale health prevention interventions.

Meta-analysis: risk of hepatitis C virus infection associated with hospital-based invasive procedures.

BACKGROUND: Healthcare settings, where invasive procedures are frequently performed, may play an important role in the transmission dynamics of blood-borne pathogens when compliance with infection control precautions is suboptimal. AIMS: To understand and quantify the role of hospital-based invasive procedures on hepatitis C virus (HCV) transmission. METHODS: We conducted a systematic review and meta-analysis to identify recent studies reporting association measures of HCV infection risk that are linked to iatrogenic procedures. Based on expert opinion, invasive procedures were categorised into 10 groups for which pooled measures were calculated. Finally, the relationship between pooled measures and the country-level HCV prevalence or the Healthcare Access and Quality (HAQ) index was assessed by meta-regression. RESULTS: We included 71 studies in the analysis. The most frequently evaluated procedures were blood transfusion (66 measures) and surgery (43 measures). The pooled odds ratio (OR) of HCV infection varied widely, ranging from 1.46 (95% confidence interval: 1.14-1.88) for dental procedures to 3.22 (1.7-6.11) for transplantation. The OR for blood transfusion was higher for transfusions performed before 1998 (3.77, 2.42-5.88) than for those without a specified/recent date (2.20, 1.77-2.75). In procedure-specific analyses, the HCV infection risk was significantly negatively associated with the HAQ for endoscopy and positively associated with HCV prevalence for endoscopy and surgery. CONCLUSIONS: Various invasive procedures were significantly associated with HCV infection. Our results provide a ranking of procedures in terms of HCV risk that may be used for prioritisation of infection control interventions, especially in high HCV prevalence settings.

[Dual-use research on modified pathogens in the laboratory: What framework for what issue?] / Recherche à usage dual sur les pathogènes modifiés en laboratoire - Quel encadrement pour quels enjeux ?

Technological advances in synthetic biology have made in vitro modification, or even creation, of viruses easier and more affordable. Several research studies using synthesis of potential pandemic pathogens led to controversies in the 2010's. More recently, the hypothesis that Covid-19 pandemics could originate from a lab escape is still under debate. In France, a legislative vacuum remains concerning the synthesis of modified pathogens. Initiating a collective reflection process towards setting of a legal framework on this type of work is timely so that research continues to provide profit to society rather than hazard.

Title: Recherche à usage dual sur les pathogènes modifiés en laboratoire - Quel encadrement pour quels enjeux ? Abstract: Les avancées techniques en biologie de synthèse rendent de plus en plus accessibles la modification ou même la fabrication de virus en laboratoire. Plusieurs travaux de recherche fondés sur la synthèse de pathogènes à potentiel pandémique ont créé la polémique au cours des années 2010 et, aujourd'hui encore, l'éventualité qu'une fuite de laboratoire soit à l'origine de la pandémie de Covid-19 fait débat. En France, un vide juridique subsiste concernant la synthèse de pathogènes modifiés. Une réflexion concertée vers un encadrement légal de ce type de recherche apparaît donc nécessaire et urgent pour que la recherche continue de représenter un bénéfice, plutôt qu'un risque, pour la société.

Can we distinguish the roles of demographic and temporal changes in the incidence and prevalence of musculoskeletal disorders? A systematic review.

OBJECTIVES: Musculoskeletal disorders (MSD) represent a major public health issue, affecting more then 40 million European workers in 2017. The overall aging of the working population is expected to increase the burden of disease, but temporal changes in exposures or diagnosis may also drive the global trends in MSD. We therefore conducted a systematic review to summarize the evidence on the role of demographic and temporal changes in the occurrence of MSD. METHODS: We conducted a systematic review of articles reporting temporal trends in MSD in the general working-age population. Only articles controlling for age in the analysis were included. The risk of bias was assessed. The main indicators extracted were age-controlled time trends in MSD incidence or prevalence. RESULTS: Among 966 articles, 16 fulfilled the inclusion criteria, representing 23 results according to the indicators extracted. No study was found with a high risk of bias. Results presenting time trends in prevalence were found in 12 studies and incidence in 11. After controlling for age, the reported temporal trends varied, mostly between non-monotonic changes (N=12/23) and increases (N=10/23). One article also highlighted an increase among women and non-monotonic changes among men (N=1/23). Several factors other than aging were suggested to explain temporal trends in MSD, mainly trends in obesity, changing occupational exposures, and cultural factors regarding pain tolerance. CONCLUSION: This review shows that different kind of factors in addition to aging may contribute to varying or increasing trends in MSD. This review also highlighted the scarcity of evidence regarding time trends in the burden of MSD and their underlying causes.

Monitoring socioeconomic inequalities across HIV knowledge, attitudes, behaviours and prevention in 18 sub-Saharan African countries.

OBJECTIVES: Socioeconomic inequalities in HIV prevention services coverage constitute important barriers to global prevention targets, especially in sub-Saharan Africa (SSA). We aimed at monitoring these inequalities from population-based survey data in 18 SSA countries between 2010 and 2018. METHODS: We defined eight HIV indicators aimed at capturing uptake of HIV prevention services among adult participants. Country-specific wealth-related inequalities were measured using the Relative and Slope Index of Inequalities (RII and SII, respectively) and then pooled using random-effects meta-analyses. We compared inequalities between African regions using the Wilcoxon rank-sum test. RESULTS: The sample consisted of 358 591 participants (66% women). Despite variability between countries and indicators, the meta-analysis revealed significant levels of relative and absolute inequalities in six out of eight indicators: HIV-related knowledge, positive attitudes toward people with HIV (PWH), condom use at last sexual intercourse, participation to prevention of mother-to-child transmission programs, medical male circumcision and recent HIV testing. The largest inequalities were reported in condom use, with condom use reported five times more among the richest versus the poorest [RII = 5.02, 95% confidence interval (CI) 2.79-9.05] and in positive attitudes toward PWH, with a 32-percentage point difference between the richest and poorest (SII = 0.32, 95% CI 0.26-0.39). Conversely, no significant inequalities were observed in multipartnership and HIV seropositivity among youth. Overall, inequalities tended to be larger in West and Central vs. East and Southern African countries. CONCLUSION: Despite efforts to scale-up HIV-prevention programs, socioeconomic inequalities remain substantial over the continuum of HIV primary and secondary prevention in several SSA countries.

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis.

OBJECTIVE: The benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration. DESIGN: We pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson. RESULTS: Recurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1). CONCLUSION: Effects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.

How can the public health impact of vaccination be estimated?

BACKGROUND: Deaths due to vaccine preventable diseases cause a notable proportion of mortality worldwide. To quantify the importance of vaccination, it is necessary to estimate the burden averted through vaccination. The Vaccine Impact Modelling Consortium (VIMC) was established to estimate the health impact of vaccination. METHODS: We describe the methods implemented by the VIMC to estimate impact by calendar year, birth year and year of vaccination (YoV). The calendar and birth year methods estimate impact in a particular year and over the lifetime of a particular birth cohort, respectively. The YoV method estimates the impact of a particular year's vaccination activities through the use of impact ratios which have no stratification and stratification by activity type and/or birth cohort. Furthermore, we detail an impact extrapolation (IE) method for use between coverage scenarios. We compare the methods, focusing on YoV for hepatitis B, measles and yellow fever. RESULTS: We find that the YoV methods estimate similar impact with routine vaccinations but have greater yearly variation when campaigns occur with the birth cohort stratification. The IE performs well for the YoV methods, providing a time-efficient mechanism for updates to impact estimates. CONCLUSIONS: These methods provide a robust set of approaches to quantify vaccination impact; however it is vital that the area of impact estimation continues to develop in order to capture the full effect of immunisation.

Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world.

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.

The global burden of yellow fever.

Yellow fever (YF) is a viral, vector-borne, haemorrhagic fever endemic in tropical regions of Africa and South America. The vaccine for YF is considered safe and effective, but intervention strategies need to be optimised; one of the tools for this is mathematical modelling. We refine and expand an existing modelling framework for Africa to account for transmission in South America. We fit to YF occurrence and serology data. We then estimate the subnational forces of infection for the entire endemic region. Finally, using demographic and vaccination data, we examine the impact of vaccination activities. We estimate that there were 109,000 (95% credible interval [CrI] [67,000-173,000]) severe infections and 51,000 (95% CrI [31,000-82,000]) deaths due to YF in Africa and South America in 2018. We find that mass vaccination activities in Africa reduced deaths by 47% (95% CrI [10%-77%]). This methodology allows us to evaluate the effectiveness of vaccination and illustrates the need for continued vigilance and surveillance of YF.

Assessing the impact of preventive mass vaccination campaigns on yellow fever outbreaks in Africa: A population-level self-controlled case series study.

BACKGROUND: The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, to what extent PMVCs are associated with a decreased risk of outbreak has not yet been quantified. METHODS AND FINDINGS: We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for in the SCCS method, this method is an alternative to classical cohort or case-control study designs when the risk of residual confounding is high, in particular confounding by indication. The locations and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, the first outbreak occurred during the pre-PMVC period in 26 (79%) provinces, and during the post-PMVC period in 7 (21%) provinces. At the province level, the post-PMVC period was associated with an 86% reduction (95% CI 66% to 94%, p < 0.001) in the risk of outbreak as compared to the pre-PMVC period. This negative association between exposure to PMVCs and outbreak was robustly observed across a range of sensitivity analyses, especially when using quantitative estimates of vaccination coverage as an alternative exposure measure, or when varying the observation period. In contrast, the results of the cohort-style analyses were highly sensitive to the choice of covariates included in the model. Based on the SCCS results, we estimated that PMVCs were associated with a 34% (95% CI 22% to 45%) reduction in the number of outbreaks in Africa from 2005 to 2018. A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever and possibly improved disease surveillance. CONCLUSIONS: In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention.

Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study.

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.