Effect of evidence updates on key determinants of measles vaccination impact: a DynaMICE modelling study in ten high-burden countries.

BACKGROUND: Model-based estimates of measles burden and the impact of measles-containing vaccine (MCV) are crucial for global health priority setting. Recently, evidence from systematic reviews and database analyses have improved our understanding of key determinants of MCV impact. We explore how representations of these determinants affect model-based estimation of vaccination impact in ten countries with the highest measles burden. METHODS: Using Dynamic Measles Immunisation Calculation Engine (DynaMICE), we modelled the effect of evidence updates for five determinants of MCV impact: case-fatality risk, contact patterns, age-dependent vaccine efficacy, the delivery of supplementary immunisation activities (SIAs) to zero-dose children, and the basic reproduction number. We assessed the incremental vaccination impact of the first (MCV1) and second (MCV2) doses of routine immunisation and SIAs, using metrics of total vaccine-averted cases, deaths, and disability-adjusted life years (DALYs) over 2000-2050. We also conducted a scenario capturing the effect of COVID-19 related disruptions on measles burden and vaccination impact. RESULTS: Incorporated with the updated data sources, DynaMICE projected 253 million measles cases, 3.8 million deaths and 233 million DALYs incurred over 2000-2050 in the ten high-burden countries when MCV1, MCV2, and SIA doses were implemented. Compared to no vaccination, MCV1 contributed to 66% reduction in cumulative measles cases, while MCV2 and SIAs reduced this further to 90%. Among the updated determinants, shifting from fixed to linearly-varying vaccine efficacy by age and from static to time-varying case-fatality risks had the biggest effect on MCV impact. While varying the basic reproduction number showed a limited effect, updates on the other four determinants together resulted in an overall reduction of vaccination impact by 0.58%, 26.2%, and 26.7% for cases, deaths, and DALYs averted, respectively. COVID-19 related disruptions to measles vaccination are not likely to change the influence of these determinants on MCV impact, but may lead to a 3% increase in cases over 2000-2050. CONCLUSIONS: Incorporating updated evidence particularly on vaccine efficacy and case-fatality risk reduces estimates of vaccination impact moderately, but its overall impact remains considerable. High MCV coverage through both routine immunisation and SIAs remains essential for achieving and maintaining low incidence in high measles burden settings

Strengthening national vaccine decision-making: Assessing the impact of SIVAC Initiative support on national immunisation technical advisory group (NITAG) functionality in 77 low and middle-income countries.

BACKGROUND: National Immunisation Technical Advisory Groups (NITAGs) are multi-disciplinary expert groups that provide policy-makers with independent, evidence-based advice on vaccination. Between 2008 and 2017, the SIVAC Initiative supported establishment and strengthening of NITAGs in low and lower-middle income countries though its impact was never assessed quantitatively. AIM: To quantitatively assess whether SIVAC support is associated with a faster rate at which NITAGs became functional based on six performance indicators. METHODS: Data from the World Health Organization/Unicef Joint Reporting Form (JRF) from 77 low and lower-middle-income countries were used to examine the time delay between the start of SIVAC support and NITAG functionality using a Cox proportional hazards model. RESULTS: Countries receiving SIVAC support took a mean of 2.00 (95% CI 1.40-2.60) years to reported functionality compared to 2.82 (95% CI 2.05-3.59) years for countries without SIVAC support. We found evidence that SIVAC support is associated with reduced time until NITAG functionality, and this association cannot fully be explained by GDP per capita, percentage of GDP spent on healthcare, or NITAG functionality score at the start of the study period. However, quality of JRF data for the questions used to calculate NITAG functionality were poor, particularly for countries not receiving SIVAC support. CONCLUSION: SIVAC support is likely to have enabled many countries to more rapidly achieve NITAG functionality

At the heart of the problem - A person-centred, developmental perspective on the link between alcohol consumption and cardio-vascular events.

INTRODUCTION: The cardio-protective effect of alcohol has been the subject of a long-standing scientific controversy. Emerging evidence remains equivocal, as the validity of the dose-dependent J-shape association is tainted by conceptual, theoretical and methodological problems. A major impediment for a resolution on the matter is the lack of a life-long developmental approach to pinpoint alcohol's specific impact on the risk for cardio-vascular events (CVE). OBJECTIVE: Using retrospective and prospective individual-level data of alcohol consumption (AC) we applied a model-based clustering technique to uncover life-course trajectories of AC and explored their links to CVE. METHODS: Data stemmed from a random sub-cohort of a large-scale, longitudinal study conducted in the Netherlands (N=2288). Group Based Trajectory Model (GBTM) was applied to extract distinct progressions of AC over time. Stratified by sex, the association between the developmental trajectories and CVE was examined with multiple logistic regression models, with adjustment for traditional risk factors. RESULTS: GBTM analysis laid bare the heterogeneity of AC dynamics over the life-course, reiterating sex differences in drinking habits and CVE risk. AC temporal behaviors during adolescence and adulthood were diverse, but showed relative stability in in middle-age and elderly years. For males, adjusted odds for CVE differed among the uncovered developmental classes. CONCLUSIONS: The findings elicited supportive evidence for a J-shape, but with a new twist. Besides moderation the results indicate that onset, timing, duration and stability of AC over the life-course are major aspects to be accounted for when attempting to elucidate alcohol's cardio-vascular role

COVID-19 control in low-income settings and displaced populations: what can realistically be done?

COVID-19 prevention strategies in resource limited settings, modelled on the earlier response in high income countries, have thus far focused on draconian containment strategies, which impose movement restrictions on a wide scale. These restrictions are unlikely to prevent cases from surging well beyond existing hospitalisation capacity; not withstanding their likely severe social and economic costs in the long term. We suggest that in low-income countries, time limited movement restrictions should be considered primarily as an opportunity to develop sustainable and resource appropriate mitigation strategies. These mitigation strategies, if focused on reducing COVID-19 transmission through a triad of prevention activities, have the potential to mitigate bed demand and mortality by a considerable extent. This triade is based on a combination of high-uptake of community led shielding of high-risk individuals, self-isolation of mild to moderately symptomatic cases, and moderate physical distancing in the community. We outline a set of principles for communities to consider how to support the protection of the most vulnerable, by shielding them from infection within and outside their homes. We further suggest three potential shielding options, with their likely applicability to different settings, for communities to consider and that would enable them to provide access to transmission-shielded arrangements for the highest risk community members. Importantly, any shielding strategy would need to be predicated on sound, locally informed behavioural science and monitored for effectiveness and evaluating its potential under realistic modelling assumptions. Perhaps, most importantly, it is essential that these strategies not be perceived as oppressive measures and be community led in their design and implementation. This is in order that they can be sustained for an extended period of time, until COVID-19 can be controlled or vaccine and treatment options become available

Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK.

BACKGROUND: To mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number (R0, the average number of secondary cases generated per case). METHODS: We asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire was conducted online via email recruitment and documents the age and location of contacts and a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday, 24 March, 1 day after a "lockdown" was implemented across the UK. We compared measured contact patterns during the "lockdown" to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. RESULTS: We found a 74% reduction in the average daily number of contacts observed per participant (from 10.8 to 2.8). This would be sufficient to reduce R0 from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37-0.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22-0.53) for physical (skin to skin) contacts only. CONCLUSIONS: The physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease, and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance

Efficacy of live oral rotavirus vaccines by duration of follow-up: a meta-regression of randomised controlled trials.

BACKGROUND: The duration of protection offered by rotavirus vaccines varies across the world, and this variation is important to understanding and predicting the effects of the vaccines. There is now a large body of evidence on the efficacy of live oral rotavirus vaccines in different settings, but these data have never been synthesised to obtain robust estimates of efficacy by duration of follow-up. Our aim is to estimate the efficacy of live oral rotavirus vaccines at each point during follow-up and by mortality stratum. METHODS: In our meta-regression study, we identified all randomised controlled trials of rotavirus vaccines published until April 4, 2018, using the results of a Cochrane systematic review, and cross checked these studies against those identified by another systematic review. We excluded trials that were based on special populations, trials without an infant schedule, and trials without clear reporting of numbers of enrolled infants and events in different periods of follow-up. For all reported periods of follow-up, we extracted the mean duration of follow-up (time since administration of the final dose of rotavirus vaccination), the number of enrolled infants, and case counts for rotavirus-positive severe gastroenteritis in both non-vaccinated and vaccinated groups. We used a Bayesian hierarchical Poisson meta-regression model to estimate the pooled cumulative vaccine efficacy (VE) and its waning with time for three mortality strata. We then converted these VE estimates into instantaneous VE (iVE). FINDINGS: In settings with low mortality (15 observations), iVE pooled for infant schedules of Rotarix and RotaTeq was 98% (95% credibility interval 93-100) 2 weeks following the final dose of vaccination and 94% (87-98) after 12 months. In medium-mortality settings (11 observations), equivalent estimates were 82% (74-92) after 2 weeks and 77% (67-84) after 12 months. In settings with high mortality (24 observations), there were five different vaccines with observation points for infant schedules. The pooled iVE was 66% (48-81) after 2 weeks of follow-up and 44% (27-59) after 12 months. INTERPRETATION: Rotavirus vaccine efficacy is lower and wanes more rapidly in high-mortality settings than in low-mortality settings, but the earlier peak age of disease in high-mortality settings means that live oral rotavirus vaccines are still likely to provide substantial benefit. FUNDING: Bill & Melinda Gates Foundation

Routine childhood immunisation during the COVID-19 pandemic in Africa: a benefit-risk analysis of health benefits versus excess risk of SARS-CoV-2 infection.

BACKGROUND: National immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing COVID-19 pandemic. We aimed to compare the health benefits of sustaining routine childhood immunisation in Africa with the risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through visiting routine vaccination service delivery points. METHODS: We considered a high-impact scenario and a low-impact scenario to approximate the child deaths that could be caused by immunisation coverage reductions during COVID-19 outbreaks. In the high-impact scenario, we used previously reported country-specific child mortality impact estimates of childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, Streptococcus pneumoniae, rotavirus, measles, meningitis A, rubella, and yellow fever to approximate the future deaths averted before 5 years of age by routine childhood vaccination during a 6-month COVID-19 risk period without catch-up campaigns. In the low-impact scenario, we approximated the health benefits of sustaining routine childhood immunisation on only the child deaths averted from measles outbreaks during the COVID-19 risk period. We assumed that contact-reducing interventions flattened the outbreak curve during the COVID-19 risk period, that 60% of the population will have been infected by the end of that period, that children can be infected by either vaccinators or during transport, and that upon child infection the whole household will be infected. Country-specific household age structure estimates and age-dependent infection-fatality rates were applied to calculate the number of deaths attributable to the vaccination clinic visits. We present benefit-risk ratios for routine childhood immunisation, with 95% uncertainty intervals (UIs) from a probabilistic sensitivity analysis. FINDINGS: In the high-impact scenario, for every one excess COVID-19 death attributable to SARS-CoV-2 infections acquired during routine vaccination clinic visits, 84 (95% UI 14-267) deaths in children could be prevented by sustaining routine childhood immunisation in Africa. The benefit-risk ratio for the vaccinated children is 85 000 (4900-546 000), for their siblings (60 years) is 96 (14-307). In the low-impact scenario that approximates the health benefits to only the child deaths averted from measles outbreaks, the benefit-risk ratio to the households of vaccinated children is 3 (0-10); if the risk to only the vaccinated children is considered, the benefit-risk ratio is 3000 (182-21 000). INTERPRETATION: The deaths prevented by sustaining routine childhood immunisation in Africa outweigh the excess risk of COVID-19 deaths associated with vaccination clinic visits, especially for the vaccinated children. Routine childhood immunisation should be sustained in Africa as much as possible, while considering other factors such as logistical constraints, staff shortages, and reallocation of resources during the COVID-19 pandemic. FUNDING: Gavi, the Vaccine Alliance; Bill & Melinda Gates Foundation

Characterising social contacts under COVID-19 control measures in Africa.

BACKGROUND: Early in the COVID-19 pandemic, countries adopted non-pharmaceutical interventions (NPIs) such as lockdowns to limit SARS-CoV-2 transmission. Social contact studies help measure the effectiveness of NPIs and estimate parameters for modelling SARS-CoV-2 transmission. However, few contact studies have been conducted in Africa. METHODS: We analysed nationally representative cross-sectional survey data from 19 African Union Member States, collected by the Partnership for Evidence-based Responses to COVID-19 (PERC) via telephone interviews at two time points (August 2020 and February 2021). Adult respondents reported contacts made in the previous day by age group, demographic characteristics, and their attitudes towards COVID-19. We described mean and median contacts across these characteristics and related contacts to Google Mobility reports and the Oxford Government Response Stringency Index for each country at the two time points. RESULTS: Mean reported contacts varied across countries with the lowest reported in Ethiopia (9, SD=16, median = 4, IQR = 8) in August 2020 and the highest in Sudan (50, SD=53, median = 33, IQR = 40) in February 2021. Contacts of people aged 18-55 represented 50% of total contacts, with most contacts in household and work or study settings for both surveys. Mean contacts increased for Ethiopia, Ghana, Liberia, Nigeria, Sudan, and Uganda and decreased for Cameroon, the Democratic Republic of Congo (DRC), and Tunisia between the two time points. Men had more contacts than women and contacts were consistent across urban or rural settings (except in Cameroon and Kenya, where urban respondents had more contacts than rural ones, and in Senegal and Zambia, where the opposite was the case). There were no strong and consistent variations in the number of mean or median contacts by education level, self-reported health, perceived self-reported risk of infection, vaccine acceptance, mask ownership, and perceived risk of COVID-19 to health. Mean contacts were correlated with Google mobility (coefficient 0.57, p=0.051 and coefficient 0.28, p=0.291 in August 2020 and February 2021, respectively) and Stringency Index (coefficient -0.12, p = 0.304 and coefficient -0.33, p=0.005 in August 2020 and February 2021, respectively). CONCLUSIONS: These are the first COVID-19 social contact data collected for 16 of the 19 countries surveyed. We find a high reported number of daily contacts in all countries and substantial variations in mean contacts across countries and by gender. Increased stringency and decreased mobility were associated with a reduction in the number of contacts. These data may be useful to understand transmission patterns, model infection transmission, and for pandemic planning

Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020.

Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89-6.7) and 1.3% (95% CI: 0.38-3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3-2.7) and 0.6% (95% CI: 0.2-1.3), respectively

The impact of local and national restrictions in response to COVID-19 on social contacts in England: a longitudinal natural experiment.

BACKGROUND: England's COVID-19 response transitioned from a national lockdown to localised interventions. In response to rising cases, these were supplemented by national restrictions on contacts (the Rule of Six), then 10 pm closing for bars and restaurants, and encouragement to work from home. These were quickly followed by a 3-tier system applying different restrictions in different localities. As cases continued to rise, a second national lockdown was declared. We used a national survey to quantify the impact of these restrictions on epidemiologically relevant contacts. METHODS: We compared paired measures on setting-specific contacts before and after each restriction started and tested for differences using paired permutation tests on the mean change in contacts and the proportion of individuals decreasing their contacts. RESULTS: Following the imposition of each measure, individuals tended to report fewer contacts than they had before. However, the magnitude of the changes was relatively small and variable. For instance, although early closure of bars and restaurants appeared to have no measurable effect on contacts, the work from home directive reduced mean daily work contacts by 0.99 (95% confidence interval CI] 0.03-1.94), and the Rule of Six reduced non-work and school contacts by a mean of 0.25 (0.01-0.5) per day. Whilst Tier 3 appeared to also reduce non-work and school contacts, the evidence for an effect of the lesser restrictions (Tiers 1 and 2) was much weaker. There may also have been some evidence of saturation of effects, with those who were in Tier 1 (least restrictive) reducing their contacts markedly when they entered lockdown, which was not reflected in similar changes in those who were already under tighter restrictions (Tiers 2 and 3). CONCLUSIONS: The imposition of various local and national measures in England during the summer and autumn of 2020 has gradually reduced contacts. However, these changes are smaller than the initial lockdown in March. This may partly be because many individuals were already starting from a lower number of contacts