Impact assessment of mobility restriction, testing, and vaccination on the COVID-19 pandemic in India (preprint)

Background: Before the availability of vaccines, countries largely relied on mobility restriction and testing to mitigate the COVID-19 pandemic. Our aim is to assess the combined impact of mobility restriction, testing, and vaccination on the COVID-19 pandemic in India. Methods: We conducted a multiple regression analysis to assess the impact of mobility, testing, and vaccination on COVID-19 incidence between April 28, 2021 to November 24, 2021 using data from Our World in Data and Google Mobility Report. The 7-day moving average was applied to offset the daily fluctuations in the mobility and testing. Each independent variable was lagged to construct a temporal relationship, and waning vaccination efficacy was taken into consideration. We performed additional analysis for three time periods between March 28, 2020 to November 24, 2021 (1st: March 28, 2020 ~ October 7, 2020, 2nd: October 8, 2020 ~ April 27, 2021, 3rd: April 28, 2021 ~ November 24, 2021) to examine potential heterogeneity over time. Results: Mobility (0.041, 95% CI: 0.033 to 0.048), testing (-0.008, 95% CI: -0.015 to -0.001), and vaccination (quadratic term: 0.004, 95% CI: 0.003 to 0.005, linear term: -0.130, 95% CI: -0.161 to -0.099) were all associated with COVID-19 incidence. For vaccination rate, the decrease of number of cases demonstrated a U-shaped curve, while mobility showed a positive association and testing showed an inverse association with COVID-19 incidence. Mobility restriction was effective during all three periods - March 28, 2020 to November 24, 2021 (0.009, 0.048, and 0.026 respectively). Testing was effective during the second and third period - October 8, 2020 to November 24, 2021 (-0.036, and -0.006 respectively). Conclusion: Mobility restriction and testing were effective even in the presence of vaccination. This shows the positive value of mobility restrictions, testing, and vaccination from the health system perspective on COVID-19 prevention and control, especially with continual emergence of variants in India and globally. At the same time, this health system gain must be balanced with the challenges in the delivery of non-COVID health services and broader socio-economic impact in deciding the prolonged continuance of mobility restriction.

Vaccine Equity in Low and Middle Income Countries: A Systematic Review and Meta-analysis (preprint)

Background Evidence to date has shown that inequality in health, and vaccine coverage in particular, can have ramifications to wider society. However, whilst individual studies have sought to characterise these heterogeneities in immunisation coverage at national level, few have taken a broad and quantitative view of the contributing factors to heterogeneity in vaccine coverage and impact. This systematic review aims to highlight these geographic, demographic, and sociodemographic characteristics through a qualitative and quantitative approach, vital to prioritise and optimise vaccination policies. Methods A systematic review of two databases (PubMed and Web of Science) was undertaken using Medical Subject Headings (MeSH) and keywords to identify studies examining factors on vaccine inequality and heterogeneity in vaccine coverage. Inclusion criteria were applied independently by two researchers. Studies including data on key characteristics of interest were further analysed through a meta-analysis to produce a pooled estimate of the risk ratio using a random effects model for that characteristic. Results One hundred and eight studies were included in this review. We found that inequalities in wealth, education, and geographic access can affect vaccine impact and vaccine dropout. We estimated those living in rural areas were not significantly different in terms of full vaccination status compared to urban areas but noted considerable heterogeneity between countries. We found that females were 3% (95%CI[1%, 5%]) less likely to be fully vaccinated than males. Additionally, we estimated that children whose mothers had no formal education were 28% (95%CI[18%,47%]) less likely to be fully vaccinated than those whose mother had primary level, or above, education. Finally, we found that individuals in the poorest wealth quintile were 27% (95%CI [16%,37%]) less likely to be fully vaccinated than those in the richest. Conclusions We found a nuanced picture of inequality in vaccine coverage and access with wealth disparity dominating, and likely driving, other disparities. This review highlights the complex landscape of inequity and further need to design vaccination strategies targeting missed subgroups to improve and recover vaccination coverage following the COVID-19 pandemic. Registration Prospero CRD42021261927

COVID-19 impact on routine immunisations for vaccine-preventable diseases: Projecting the effect of different routes to recovery (preprint)

Introduction: 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 (RI) activities. Such disruptions could have a detrimental effect on public health, leading to more deaths from VPDs, particularly without mitigation efforts. Hence, as RIs resume, it is important to estimate the effectiveness of different approaches for recovery. Methods: 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 RIs 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 RI 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%. Results: 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 noCOVID-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. Conclusion: Overall, our results show that drops in RI 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.

Public Health and Social Measures to Mitigate the Health and Economic Impact of the COVID-19 Pandemic in Turkey, Egypt, Ukraine, Kazakhstan, and Poland During 2020-2021: Situational Analysis (preprint)

Background: The COVID-19 pandemic had enormous impacts on human society. There were similarities and differences in the public health and social measures taken by countries, and comparative analysis facilitates cross-country learning of contextual practices and sharing lessons to mitigate the COVID-19 pandemic impact. We aim to conduct a situational analysis of the public health and social measures to mitigate the health and economic impact of the COVID-19 pandemic in Turkey, Egypt, Ukraine, Kazakhstan, and Poland during 2020-2021. Methods We conducted a situational analysis of the COVID-19 pandemic response in Turkey, Egypt, Ukraine, Kazakhstan, and Poland from the perspectives of the health system and health finance, national coordination, surveillance, testing capacity, health infrastructure, healthcare workforce, medical supply, physical distancing and non-pharmaceutical interventions, health communication, impact on non-COVID-19 health services, impact on the economy, education, gender and civil liberties, and COVID-19 vaccination. Results Since the onset of the COVID-19 pandemic, Turkey, Egypt, Ukraine, Kazakhstan, and Poland have expanded COVID-19 testing and treatment capacity over time. However, they faced a shortage of healthcare workforce and medical supplies. They took population-based quarantine measures rather than individual-based isolation measures, which significantly burdened their economies and disrupted education. The unemployment rate increased, and economic growth stagnated. Economic stimulus policy was accompanied by high inflation. Despite the effort to sustain essential health services, healthcare access declined. Schools were closed for 5-11 months. Gender inequality was aggravated in Turkey and Ukraine, and an issue was raised for balancing public health measures and civil liberties in Egypt and Poland. Digital technologies played an important role in maintaining routine healthcare, education, and public health communication. Conclusions The COVID-19 pandemic has exposed weaknesses in healthcare systems in emerging countries of Turkey, Egypt, Ukraine, Kazakhstan, and Poland, and highlighted the intricate link between health and economy. Individual-level testing, isolation, and contact tracing are effective public health interventions in mitigating the health and economic impact of the COVID-19 pandemic in comparison to population-level measures of lockdowns. Investment in health, including digital health and communication, is essential to minimize the impact of the pandemic and for more equitable and sustainable development beyond the pandemic.

Dosing interval strategies for two-dose COVID-19 vaccination in 13 low- and middle-income countries of Europe: health impact modelling and benefit-risk analysis (preprint)

Background: In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine could let more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals for low- and middle-income countries of Europe. Methods: We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 low- and middle-income countries in the World Health Organization European Region (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies related to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern into the model, and also conducted a benefit-risk assessment to quantify the trade-off between health benefits versus adverse events following immunisation. Findings: In 12 of the 13 countries, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20-59 years). These strategies lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.2% [range: 4.0% - 22.5%; n = 13 (countries)] more deaths. There is generally a negative association between dosing interval and COVID-19 mortality within the range we investigated. Assuming a shorter first dose waning duration of 120 days, as opposed to 360 days in the base case, led to shorter optimal dosing intervals of 8-12 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks. Interpretation: We infer that longer dosing intervals of over six months, which are substantially longer than the current label recommendation for most vaccine products, could reduce COVID-19 mortality in low- and middle-income countries of WHO/Europe. Certain vaccine features, such as fast waning of first doses, significantly shorten the optimal dosing intervals.

SARS-CoV-2 infection risk during delivery of childhood vaccination campaigns: a modelling study (preprint)

BackgroundThe COVID-19 pandemic has disrupted delivery of immunisation services globally. Many countries have postponed vaccination campaigns out of concern about infection risks to staff delivering vaccination, the children being vaccinated and their families. The World Health Organization recommends considering both the benefit of preventive campaigns and the risk of SARS-CoV-2 transmission when making decisions about campaigns during COVID-19 outbreaks, but there has been little quantification of the risks. MethodsWe modelled excess SARS-CoV-2 infection risk to vaccinators, vaccinees and their caregivers resulting from vaccination campaigns delivered during a COVID-19 epidemic. Our model used population age-structure and contact patterns from three exemplar countries (Burkina Faso, Ethiopia, and Brazil). It combined an existing compartmental transmission model of an underlying COVID-19 epidemic with a Reed-Frost model of SARS-CoV-2 infection risk to vaccinators and vaccinees. We explored how excess risk depends on key parameters governing SARS-CoV-2 transmissibility, and aspects of campaign delivery such as campaign duration, number of vaccinations, and effectiveness of personal protective equipment (PPE) and symptomatic screening. ResultsInfection risks differ considerably depending on the circumstances in which vaccination campaigns are conducted. A campaign conducted at the peak of a SARS-CoV-2 epidemic with high prevalence and without special infection mitigation measures could increase absolute infection risk by 32% to 45% for vaccinators, and 0.3% to 0.5% for vaccinees and caregivers. However, these risks could be reduced to 3.6% to 5.3% and 0.1% to 0.2% respectively by use of PPE that reduces transmission by 90% (as might be achieved with N95 respirators or high-quality surgical masks) and symptomatic screening. ConclusionsSARS-CoV-2 infection risks to vaccinators, vaccinees and caregivers during vaccination campaigns can be greatly reduced by adequate PPE, symptomatic screening, and appropriate campaign timing. Our results support the use of adequate risk mitigation measures for vaccination campaigns held during SARS-CoV-2 epidemics, rather than cancelling them entirely.

Inequities in childhood immunisation coverage associated with socioeconomic, geographic, maternal, child, and place of birth characteristics in Kenya (preprint)

Background The global Immunisation Agenda 2030 highlights coverage and equity as a strategic priority goal to reach high equitable immunisation coverage at national levels and in all districts. We estimated inequities in full immunisation coverage associated with socioeconomic, geographic, maternal, child, and place of birth characteristics among children aged 12-23 months in Kenya. Methods We analysed full immunisation coverage (1-dose BCG, 3-dose DTP-HepB-Hib (diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type B), 3-dose polio, 1-dose measles, and 3-dose pneumococcal vaccines) of 3,943 children aged 12–23 months from the 2014 Kenya Demographic and Health Survey. We disaggregated mean coverage by socioeconomic (household wealth, religion, ethnicity), geographic (place of residence, province), maternal (maternal age at birth, maternal education, maternal marital status, maternal household head status), child (sex of child, birth order), and place of birth characteristics, and estimated inequities in full immunisation coverage using bivariate and multivariate logistic regression. Results Immunisation coverage ranged from 82% [81–84] for the third dose of polio to 97.4% [96.7–98.2] for the first dose of DTP-HepB-Hib, while full immunisation coverage was 68% [66–71] in 2014. After controlling for other background characteristics through multivariate logistic regression, children of mothers with primary school education or higher have at least 54% higher odds of being fully immunised compared to children of mothers with no education. Children born in clinical settings had 41% higher odds of being fully immunised compared to children born in home settings. Children in the Coast, Western, Central, and Eastern regions had at least 74% higher odds of being fully immunised compared to children in the North Eastern region, while children in urban areas had 26% lower odds of full immunisation compared to children in rural areas. Children in the middle and richer wealth quintile households were 43–57% more likely to have full immunisation coverage compared to children in the poorest wealth quintile households. Children who were sixth born or higher had 37% lower odds of full immunisation compared to first-born children. Conclusions Children of mothers with no education, born in home settings, in regions with limited health infrastructure, living in poorer households, and of higher birth order are associated with lower rates of full immunisation. Targeted programmes to reach under-immunised children in these subpopulations will lower the inequities in childhood immunisation coverage in Kenya.

Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis (preprint)

Background To eliminate cervical cancer as a public health problem, the World Health Organization currently recommends routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual initiation. However, many countries have yet to implement HPV vaccination because of financial or logistical barriers to delivering two doses outside the infant immunisation programme. Methods Using three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 188 countries, assuming that one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g., 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021–2120, with a one-year catch-up campaign of 11–14-year-old girls at 80% coverage in the first year of the programme. Results Over the years 2021–2120, one-dose vaccination at 80% coverage was projected to avert 112.9 million (range of medians: 75.8–176.2) and 148.0 million (111.6–187.6) cervical cancer cases assuming one dose of the vaccine confers 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 155.2 million (143.7–170.3) cervical cancer cases could be prevented. Around 65 to 889 additional girls would need to be vaccinated with the second dose to prevent one cervical cancer case, depending on the epidemiological profiles of the country. Across all income groups, the threshold cost for the second dose was low: from 0.85 (0.07–3.82) USD in low-income countries to 18.08 (−3.62–85.64) USD in high-income countries, assuming one-dose confers 30-year protection. Conclusions Results: were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs, and alleviating vaccine supply constraints. The second dose may be cost-effective if there is a shorter duration of protection from one dose, cheaper vaccine and vaccination delivery strategies, and high burden of cervical cancer.

Health impact of routine immunisation service disruptions and mass vaccination campaign suspensions caused by the COVID-19 pandemic: Multimodel comparative analysis of disruption scenarios for measles, meningococcal A, and yellow fever vaccination in 10 low- and lower middle-income countries (preprint)

Background: Childhood immunisation services have been disrupted by the COVID-19 pandemic. WHO recommends considering outbreak risk using epidemiological criteria when deciding whether to conduct preventive vaccination campaigns during the pandemic. Methods: We used 2-3 models per infection to estimate the health impact of 50% reduced routine vaccination coverage in 2020 and delay of campaign vaccination from 2020 to 2021 for measles vaccination in Bangladesh, Chad, Ethiopia, Kenya, Nigeria, and South Sudan, for meningococcal A vaccination in Burkina Faso, Chad, Niger, and Nigeria, and for yellow fever vaccination in the Democratic Republic of Congo, Ghana, and Nigeria. Our counterfactual comparative scenario was sustaining immunisation services at coverage projections made prior to COVID-19 (i.e. without any disruption). Findings: Reduced routine vaccination coverage in 2020 without catch-up vaccination may lead to an increase in measles and yellow fever disease burden in the modelled countries. Delaying planned campaigns in Ethiopia and Nigeria by a year may significantly increased the risk of measles outbreaks (both countries did complete their SIAS planned for 2020). For yellow fever vaccination, delay in campaigns leads to a potential disease burden rise of >1 death per 100,000 people until the campaigns are implemented. For meningococcal A vaccination, short term disruptions in 2020 are unlikely to have a significant impact due to the persistence of direct and indirect benefits from past introductory campaigns of the 1 to 29-year-old population, bolstered by inclusion of the vaccine into the routine immunisation schedule accompanied by further catch-up campaigns. Interpretation: The impact of COVID-19-related disruption to vaccination programs varies between infections and countries. Planning and implementation of campaigns should consider country and infection-specific epidemiological factors and local immunity gaps worsened by the COVID-19 pandemic when prioritising vaccines and strategies for catch-up vaccination.

The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya (preprint)

BackgroundThe COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region. MethodsCombining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020. FindingsIn February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 22% (0-46). As the COVID-19 restrictions to physical contact are lifted, from December 2020, the probability of a large measles outbreak increased to 31% (8-51), 35% (16-52) and 43% (31-56) assuming a 15%, 50% and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 37% (17-54), 44% (29-57) and 57% (48-65) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of restrictions on contact can be overcome by conducting an SIA with [≥] 95% coverage in under-fives. InterpretationWhile contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once physical distancing is relaxed. Implementing delayed SIAs will be critical for prevention of measles outbreaks once contact restrictions are fully lifted in Kenya. FundingThe United Kingdoms Medical Research Council and the Department for International Development

Benefit-risk analysis of health benefits of routine childhood immunisation against the excess risk of SARS-CoV-2 infections during the Covid-19 pandemic in Africa (preprint)

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. Our aim is to compare the health benefits of sustaining routine childhood immunisation in Africa against the risk of acquiring SARS-CoV-2 infections through visiting routine vaccination service delivery points. Methods: We used two scenarios to approximate the child deaths that may be caused by immunisation coverage reductions during COVID-19 outbreaks. First, we used previously reported country-specific child mortality impact estimates of childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, pneumococcal, rotavirus, measles, meningitis A, rubella, and yellow fever (DTP3, HepB3, Hib3, PCV3, RotaC, MCV1, MCV2, MenA, RCV, YFV) to approximate the future deaths averted before completing five years of age by routine childhood vaccination during a 6-month COVID-19 risk period without catch-up campaigns. Second, we analysed an alternative scenario that approximates the health benefits of sustaining routine childhood immunisation to only the child deaths averted from measles outbreaks during the COVID-19 risk period. The excess number of infections due to additional SARS-CoV-2 exposure during immunisation visits assumes that contact reducing interventions flatten 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 would be infected. Country specific household age structure estimates and age dependent infection fatality rates are then applied to calculate the number of deaths attributable to the vaccination clinic visits. We present benefit-risk ratios for routine childhood immunisation alongside 95% uncertainty range estimates from probabilistic sensitivity analysis. Findings: For every one excess COVID-19 death attributable to SARS-CoV-2 infections acquired during routine vaccination clinic visits, there could be 84 (14-267) deaths in children prevented by sustaining routine childhood immunisation in Africa. The benefit-risk ratio for the vaccinated children, siblings, parents or adult care-givers, and older adults in the households of vaccinated children are 85,000 (4,900 - 546,000), 75,000 (4,400 - 483,000), 769 (148 - 2,700), and 96 (14 - 307) respectively. In the alternative 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) under these highly conservative assumptions and if the risk to only the vaccinated children is considered, the benefit-risk ratio is 3,000 (182 - 21,000). Interpretation: Our analysis suggests that the health benefits of deaths prevented by sustaining routine childhood immunisation in Africa far outweighs the excess risk of COVID-19 deaths associated with vaccination clinic visits, especially for the vaccinated children. However, there are other factors that must be considered for strategic decision making to sustain routine childhood immunisation in African countries during the COVID-19 pandemic. These include logistical constraints of vaccine supply chain problems caused by the COVID-19 pandemic, reallocation of immunisation providers to other prioritised health services, healthcare staff shortages caused by SARS-CoV-2 infections among the staff, decreased demand for vaccination arising from community reluctance to visit vaccination clinics for fear of contracting SARS-CoV-2 infections, and infection risk to healthcare staff providing immunisation services as well as to their households and onward SARS-CoV-2 transmission into the wider community.