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1.
Preprint En | PREPRINT-MEDRXIV | ID: ppmedrxiv-22272864

BackgroundBefore 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. MethodsWe 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. ResultsMobility (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). ConclusionMobility 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.

2.
Preprint En | PREPRINT-MEDRXIV | ID: ppmedrxiv-22268891

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSIntroductionC_ST_ABSOver 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. MethodsWe 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%. ResultsWe estimate that falling short of the IA2030 targets by 10% leads to 11.26% fewer fully vaccinated persons (FVPs) and 11.34% more deaths over the years 2020-2030 relative to the no-COVID-19 scenario, whereas, reaching the IA2030 targets reduces these proportions to 5% fewer FVPs and 5.22% more deaths. The impact of the disruption varies across the VPDs with diseases where coverage expands drastically in future years facing a smaller detrimental effect. ConclusionOverall, 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. SUMMARYO_ST_ABSWhat is already known?C_ST_ABSO_LIThe impact of vaccination programmes without COVID-19-related disruption has been assessed by the Vaccine Impact Modelling Consortium. C_LIO_LIThe COVID-19 pandemic has disrupted vaccination programmes resulting in a decline in coverage in the year 2020, the ramifications of this is unclear. C_LI What are the new findings?O_LIWe estimate the impact of disruptions to routine immunisation coverage and different routes to recovery. We compare to a scenario without COVID-19-related disruptions (assuming no drops in immunisation coverage). C_LIO_LIWe estimate that reaching the Immunization Agenda (IA2030) targets leads to 5% fewer FVPs and 5.22% more deaths over the years 2020 to 2030 relative to the scenario with no COVID-19-related disruptions, whereas falling short of the IA2030 targets by 10% leads to 11.26% fewer fully vaccinated persons (FVPs) and 11.34% more deaths. C_LIO_LIThe impact of the disruption varies across the vaccine-preventable diseases with those forecasted to have vast expansions in coverage post-2020 able to recover more. C_LI What do the new findings imply?O_LIA drop in vaccination coverage results in fewer vaccinated individuals and thus more deaths due to vaccine-preventable diseases. To mitigate this, building up coverage of routine immunisations and addressing immunity gaps with activities such as catch-up campaigns are vital in the road to recovery. C_LI

3.
Preprint En | PREPRINT-MEDRXIV | ID: ppmedrxiv-21266930

BackgroundIn 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. MethodsWe 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. FindingsIn 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. InterpretationWe 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. FundingWorld Health Organization

4.
Preprint En | PREPRINT-MEDRXIV | ID: ppmedrxiv-21257215

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.

5.
Preprint En | PREPRINT-MEDRXIV | ID: ppmedrxiv-21250489

BackgroundChildhood immunisation services have been disrupted by COVID-19. WHO recommends considering outbreak risk using epidemiological criteria when deciding whether to conduct preventive vaccination campaigns during the pandemic. MethodsWe used 2-3 models per infection to estimate the health impact of 50% reduced routine vaccination coverage and delaying campaign vaccination for measles, meningococcal A and yellow fever vaccination in 3-6 high burden countries per infection. ResultsReduced routine coverage in 2020 without catch-up vaccination may increase measles and yellow fever disease burden in the modelled countries. Delaying planned campaigns may lead to measles outbreaks and increases in yellow fever burden in some countries. For meningococcal A vaccination, short term disruptions in 2020 are unlikely to have a significant impact. ConclusionThe impact of COVID-19-related disruption to vaccination programs varies between infections and countries. FundingBill & Melinda Gates Foundation and Gavi, the Vaccine Alliance Impact statementRoutine and campaign vaccination disruption in 2020 may lead to measles outbreaks and yellow fever burden increases in some countries, but is unlikely to greatly increase meningococcal A burden. SummaryO_ST_ABSBackgroundC_ST_ABSChildhood 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. MethodsWe 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). FindingsReduced 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 increase the risk of measles outbreaks (both countries did complete their supplementary immunisation activities (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 per year 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. InterpretationThe 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. FundingBill & Melinda Gates Foundation and Gavi, the Vaccine Alliance

6.
Preprint En | PREPRINT-MEDRXIV | ID: ppmedrxiv-20181198

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

7.
Preprint En | PREPRINT-MEDRXIV | ID: ppmedrxiv-20106278

BackgroundNational 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. MethodsWe 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. FindingsFor 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). InterpretationOur 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. FundingGavi, the Vaccine Alliance and Bill & Melinda Gates Foundation (OPP1157270) Research in contextO_ST_ABSEvidence before the studyC_ST_ABSNational immunisation programmes globally are at risk of disruption due to the severe health system constraints caused by the ongoing COVID-19 pandemic and the physical distancing measures to mitigate the outbreak. The decrease in vaccination coverage increases the proportion of susceptible children at risk of increased morbidity and mortality from vaccine-preventable disease outbreaks. Outbreaks of vaccine preventable disease have been observed during previous interruptions to routine immunisation services during an ongoing infectious disease epidemic, such as during the 2013-2016 Ebola outbreak in West Africa, when most health resources were shifted towards the Ebola response which led to decreasing vaccination coverage and consequently outbreaks of measles and other vaccine-preventable diseases. Added value of this studyWe estimated the benefit-risk ratio by comparing the deaths prevented by sustaining routine childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, pneumococcal, rotavirus, measles, meningitis A, rubella, and yellow fever vaccines with the excess COVID-19 deaths associated with vaccination clinic visits. The benefit of routine childhood immunization programmes in all the 54 countries of Africa is higher than the COVID-19 risk associated with these vaccination clinic visits. Implications of all the available evidenceRoutine childhood immunisation programmes should be safeguarded for continued service delivery and prioritised for the prevention of infectious diseases, as logistically possible, as part of delivering essential health services during the COVID-19 pandemic in Africa. The current immunisation service models will require adaptation, including physical distancing measures, personal protective equipment, and good hygiene practices for infection control at the vaccination clinics, and have to be complemented by new immunisation service models for sustaining routine childhood immunisation in the African countries during the COVID-19 risk period.

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