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Early life experiences have carry-over effects that manifest in later life stages. Challenging rearing environments result in more energy invested in immediate survival and less energy on growth and maturation, which can decrease survival in both the short- and long-term. One way to measure differences in energy allocation to growth between individuals is through physiological indices, such as concentrations of the metabolic hormone corticosterone, and body condition. Corticosterone increases in response to challenges to homeostasis and mobilizes stored fat and muscle to meet energetic demands. Maintaining elevated corticosterone can result in poor body condition and decreased survival. Juvenile or pre-breeding age classes are typically a substantial portion of the total population and serve key functions in population dynamics in many long-lived species. Thus, understanding how the rearing environment may influence demographics across life-history stages is crucial to understanding larger population dynamics. Yet, demographic models and conservation planning often lack vital rate estimates for early life stages because, prior to breeding, animals cannot be effectively sampled (i.e., they are unobservable). We used corticosterone concentrations in feathers and body mass of fledged juvenile Northern Spotted Owls (Strix occidentalis caurina) as indicators of potential energetic limitations early in life and used a multi-state modeling framework to quantify the effect of these indicators on apparent annual survival prior to claiming a territory (pre-territorial birds) and the probability of recruiting into the territorial population. Apparent annual survival for pre-territorial birds was higher for birds with greater mass, earlier banding dates, and intermediate levels of corticosterone. Birds with greater mass at banding were also more likely to recruit into the territorial population. Our results demonstrate the importance of early development and traditionally excluded life-history stages on long-term demographics. Although early life stages are difficult to observe, monitoring and conservation efforts may be improved by increasing studies on pre-territorial animals, control of Barred Owls, and conservation of forest structures important for Spotted Owls. This may contribute to increased juvenile survival and recruitment.

Background To reduce the coronavirus disease burden in England, along with many other countries, the government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions. Methods Here we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020–2021. Results We report that susceptibility to norovirus infection has likely increased between March 2020 and mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels, the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels, there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages. Conclusions Continued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.

Background: Circulating vaccine derived poliovirus (cVDPV) outbreaks remain a threat to polio eradication. To reduce cases of polio from cVDPV of serotype 2, the serotype 2 component of the vaccine has been removed from the global vaccine supply, but outbreaks of cVDPV2 have continued. The objective of this work is to understand the factors associated with later detection in order to improve detection of these unwanted events. Methods: The number of nucleotide differences between each cVDPV outbreak and the oral polio vaccine (OPV) strain was used to approximate the time from emergence to detection. Only independent emergences were included in the analysis. Variables such as serotype, surveillance quality, and World Health Organization (WHO) region were tested in a negative binomial regression model to ascertain whether these variables were associated with higher nucleotide differences upon detection. Results: In total, 74 outbreaks were analysed from 24 countries between 2004-2019. For serotype 1 (n=10), the median time from seeding until outbreak detection was 284 (95% uncertainty interval (UI) 284-2008) days, for serotype 2 (n=59), 276 (95% UI 172-765) days, and for serotype 3 (n=5), 472 (95% UI 392-603) days. Significant improvement in the time to detection was found with increasing surveillance of non-polio acute flaccid paralysis (AFP) and adequate stool collection. Conclusions: cVDPVs remain a risk; all WHO regions have reported at least one VDPV outbreak since the first outbreak in 2000 and outbreak response campaigns using monovalent OPV type 2 risk seeding future outbreaks. Maintaining surveillance for poliomyelitis after local elimination is essential to quickly respond to both emergence of VDPVs and potential importations as low-quality AFP surveillance causes outbreaks to continue undetected. Considerable variation in the time between emergence and detection of VDPVs were apparent, and other than surveillance quality and inclusion of environmental surveillance, the reasons for this remain unclear.

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.

Background and aim The associations between COVID-19 transmission and meteorological factors are scientifically debated. Several studies have been conducted worldwide, with inconsistent findings. However, often these studies had methodological issues, e.g., did not exclude important confounding factors, or had limited geographic or temporal resolution. Our aim was to quantify associations between temporal variations in COVID-19 incidence and meteorological variables globally. Methods We analysed data from 455 cities across 20 countries from 3 February to 31 October 2020. We used a time-series analysis that assumes a quasi-Poisson distribution of the cases and incorporates distributed lag non-linear modelling for the exposure associations at the city-level while considering effects of autocorrelation, long-term trends, and day of the week. The confounding by governmental measures was accounted for by incorporating the Oxford Governmental Stringency Index. The effects of daily mean air temperature, relative and absolute humidity, and UV radiation were estimated by applying a meta-regression of local estimates with multi-level random effects for location, country, and climatic zone. Results We found that air temperature and absolute humidity influenced the spread of COVID-19 over a lag period of 15 days. Pooling the estimates globally showed that overall low temperatures (7.5 °C compared to 17.0 °C) and low absolute humidity (6.0 g/m3 compared to 11.0 g/m3) were associated with higher COVID-19 incidence (RR temp =1.33 with 95%CI: 1.08; 1.64 and RR AH =1.33 with 95%CI: 1.12; 1.57). RH revealed no significant trend and for UV some evidence of a positive association was found. These results were robust to sensitivity analysis. However, the study results also emphasise the heterogeneity of these associations in different countries. Conclusion Globally, our results suggest that comparatively low temperatures and low absolute humidity were associated with increased risks of COVID-19 incidence. However, this study underlines regional heterogeneity of weather-related effects on COVID-19 transmission., This paper used Copernicus Climate Change Service (C3S) and Copernicus Atmosphere Monitoring Service (CAMS) information. Hence, the authors would like to thank the European Centre for Medium-Range Weather Forecasts (ECMWF) for its data generation on behalf of the European Union.

Summary Many infection prevention and control (IPC) interventions have been adopted by hospitals to limit nosocomial transmission of SARS-CoV-2. The aim of this systematic review is to identify evidence on the effectiveness of these interventions. We conducted a literature search of five databases (OVID MEDLINE, Embase, CENTRAL, COVID-19 Portfolio(pre-print), Web of Science). SWIFT ActiveScreener software was used to screen English titles and abstracts published between 1st January 2020 and 6th April 2021. Intervention studies, defined by Cochrane Effective Practice and Organisation of Care, that evaluated IPC interventions with an outcome of SARS-CoV-2 infection in either patients or healthcare workers were included. Personal protective equipment (PPE) was excluded as this intervention had been previously reviewed. Risks of bias were assessed using the Cochrane tool for randomised trials (RoB2) and non-randomized studies of interventions (ROBINS-I). From 23,156 screened articles, we identified seven articles that met the inclusion criteria, all of which evaluated interventions to prevent infections in healthcare workers and the majority of which were focused on effectiveness of prophylaxes. Due to heterogeneity in interventions, we did not conduct a meta-analysis. All agents used for prophylaxes have little to no evidence of effectiveness against SARS-CoV-2 infections. We did not find any studies evaluating the effectiveness of interventions including but not limited to screening, isolation and improved ventilation. There is limited evidence from interventional studies, excluding PPE, evaluating IPC measures for SARS-CoV-2. This review calls for urgent action to implement such studies to inform policies to protect our most vulnerable populations and healthcare workers.

The number and geographic breadth of circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks detected after the withdrawal of type 2 containing oral polio vaccine (April 2016) have exceeded fore- casts. Using Acute Flaccid Paralysis (AFP) investigations and environmental surveillance (ES) data from the Global Polio Laboratory Network, we summarize the epidemiology of cVDPV2 outbreaks. Between 01 January 2016 to 31 December 2020, a total of 68 unique cVDPV2 genetic emergences were detected across 34 countries. The cVDPV2 outbreaks have been associated with 1596 acute flaccid paralysis cases across four World Health Organization regions: 962/1596 (60.3%) cases occurred in African Region; 619/1596 (38.8%) in the Eastern Mediterranean Region; 14/1596 (0.9%) in Western-Pacific Region; and 1/1596 (0.1%) in the European Region. As the majority of the cVDPV2 outbreaks have been seeded through monovalent type 2 oral poliovirus vaccine (mOPV2) use in outbreak responses, the introduction of the more stable novel oral poliovirus vaccine will be instrumental in stopping emergence of new cVDPV2 lineages

BACKGROUND: Circulating vaccine-derived poliovirus outbreaks are spreading more widely than anticipated, which has generated a crisis for the global polio eradication initiative. Effectively responding with vaccination activities requires a rapid risk assessment. This assessment is made difficult by the low case-to-infection ratio of type 2 poliovirus, variable transmissibility, changing population immunity, surveillance delays, and limited vaccine supply from the global stockpile. The geographical extent of responses have been highly variable between countries. METHODS: We develop a statistical spatio-temporal model of short-term, district-level poliovirus spread that incorporates known risk factors, including historical wild poliovirus transmission risk, routine immunization coverage, population immunity, and exposure to the outbreak virus. RESULTS: We find that proximity to recent cVDPV2 cases is the strongest risk factor for spread of an outbreak, and find significant associations between population immunity, historical risk, routine immunization, and environmental surveillance (p

BackgroundTo reduce the coronavirus disease burden in England, along with many other countries, the Government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions.MethodsHere we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020-2021.ResultsWe report that susceptibility to norovirus infection has likely increased between March 2020 to mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages.ConclusionsContinued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.

Summary Background Temperature and rainfall patterns are known to influence seasonal patterns of dengue transmission. However, the effect of severe drought and extremely wet conditions on the timing and intensity of dengue epidemics is poorly understood. In this study, we aimed to quantify the non-linear and delayed effects of extreme hydrometeorological hazards on dengue risk by level of urbanisation in Brazil using a spatiotemporal model. Methods We combined distributed lag non-linear models with a spatiotemporal Bayesian hierarchical model framework to determine the exposure-lag-response association between the relative risk (RR) of dengue and a drought severity index. We fit the model to monthly dengue case data for the 558 microregions of Brazil between January, 2001, and January, 2019, accounting for unobserved confounding factors, spatial autocorrelation, seasonality, and interannual variability. We assessed the variation in RR by level of urbanisation through an interaction between the drought severity index and urbanisation. We also assessed the effect of hydrometeorological hazards on dengue risk in areas with a high frequency of water supply shortages. Findings The dataset included 12 895 293 dengue cases reported between 2001 and 2019 in Brazil. Overall, the risk of dengue increased between 0–3 months after extremely wet conditions (maximum RR at 1 month lag 1·56 [95% CI 1·41–1·73]) and 3–5 months after drought conditions (maximum RR at 4 months lag 1·43 [1·22–1·67]). Including a linear interaction between the drought severity index and level of urbanisation improved the model fit and showed the risk of dengue was higher in more rural areas than highly urbanised areas during extremely wet conditions (maximum RR 1·77 [1·32–2·37] at 0 months lag vs maximum RR 1·58 [1·39–1·81] at 2 months lag), but higher in highly urbanised areas than rural areas after extreme drought (maximum RR 1·60 [1·33–1·92] vs 1·15 [1·08–1·22], both at 4 months lag). We also found the dengue risk following extreme drought was higher in areas that had a higher frequency of water supply shortages. Interpretation Wet conditions and extreme drought can increase the risk of dengue with different delays. The risk associated with extremely wet conditions was higher in more rural areas and the risk associated with extreme drought was exacerbated in highly urbanised areas, which have water shortages and intermittent water supply during droughts. These findings have implications for targeting mosquito control activities in poorly serviced urban areas, not only during the wet and warm season, but also during drought periods. Funding Royal Society, Medical Research Council, Wellcome Trust, National Institutes of Health, Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro, and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico. Translation For the Portuguese translation of the abstract see Supplementary Materials section.

There is increasing interest in wastewater-based epidemiology (WBE) of SARS-CoV-2 RNA to serve as an early warning system for a community. Despite successful detection of SARS-CoV-2 RNA in wastewaters sampled from multiple locations, there is still no clear idea on the minimal number of cases in a community that are associated with a positive detection of the virus in wastewater. To address this knowledge gap, we sampled wastewaters from a septic tank (n = 57) and biological activated sludge tank (n = 52) located on-site of a hospital. The hospital is providing treatment for SARS-CoV-2 infected patients, with the number of hospitalized patients per day known. It was observed that depending on which nucleocapsid gene is targeted by means of RT-qPCR, a range of 253–409 positive cases out of 10,000 persons are required prior to detecting RNA SARS-CoV-2 in wastewater. There was a weak correlation between N1 and N2 gene abundances in wastewater with the number of hospitalized cases. This correlation was however not observed for N3 gene. The frequency of detecting N1 and N2 gene in wastewater was also higher than that for N3 gene. Furthermore, nucleocapsid genes of SARS-CoV-2 were detected at lower frequency in the partially treated wastewater than in the septic tank. In particular, N1 gene abundance was associated with water quality parameters such as total organic carbon and pH. In instances of positive detection, the average abundance of N1 and N3 genes in the activated sludge tank were reduced by 50 and 70% of the levels detected in septic tank, suggesting degradation of the SARS-CoV-2 gene fragments already occurring in the early stages of the wastewater treatment process., Graphical abstract Image 1, Highlights • 253 to 409 positive cases out of 10,000 persons are required prior to detecting SARS-CoV-2 RNA in wastewater. • N1 and N2 gene abundance exhibit weak positive correlation with number of patients. • N1 gene provides better sensitivity and correlation for use as monitoring marker. • Abundance of N1 gene associated with total organic carbon and pH. • N1 and N3 genes were reduced by > 50% in partially treated wastewater but N2 genes abundance increased.

More than a year since its emergence, there is conflicting evidence on the potential influence of weather conditions on SARS-CoV-2 transmission dynamics. We used a two-stage ecological modelling approach to estimate weather-dependent signatures in SARS-CoV-2 transmission in the early phase of the pandemic, using a dataset of 3 million COVID-19 cases reported until 31 May 2020, spanning 409 locations in 26 countries. We calculated the effective reproduction number (Re) over a location-specific early-phase time-window of 10-20 days, for which local transmission had been established but before non-pharmaceutical interventions had become established as measured by the OxCGRT Government Response Index. We calculated mean levels of meteorological factors, including temperature and humidity observed in the same time window used to calculate Re. Using a multilevel meta-regression approach, we modelled nonlinear effects of meteorological factors, while accounting for government interventions and socio-demographic factors. A weak non-monotonic association between temperature, absolute humidity and Re was identified, with a decrease in Re of 0.087 (95% CI: 0.025; 0.148) between mean temperature of 10.2°C (maximum) and 20°C (minimum) and a decrease in Re of 0.061 (95% CI: 0.011; 0.111) between absolute humidity of 6.6 g/m3 (maximum) and 11 g/m3 (minimum). However, government interventions explained twice as much of the variation in Re compared meteorological factors. We find little evidence of meteorological conditions having influenced the early stages of local epidemics, and conclude that population behaviour and governmental intervention are more important drivers of transmission.

Background: The isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures—including novel digital tracing approaches and less intensive physical distancing—might be required to reduce transmission. We aimed to estimate the reduction in transmission under different control measures across settings and how many contacts would be quarantined per day in different strategies for a given level of symptomatic case incidence. Methods: For this mathematical modelling study, we used a model of individual-level transmission stratified by setting (household, work, school, or other) based on BBC Pandemic data from 40 162 UK participants. We simulated the effect of a range of different testing, isolation, tracing, and physical distancing scenarios. Under optimistic but plausible assumptions, we estimated reduction in the effective reproduction number and the number of contacts that would be newly quarantined each day under different strategies. Results: We estimated that combined isolation and tracing strategies would reduce transmission more than mass testing or self-isolation alone: mean transmission reduction of 2% for mass random testing of 5% of the population each week, 29% for self-isolation alone of symptomatic cases within the household, 35% for self-isolation alone outside the household, 37% for self-isolation plus household quarantine, 64% for self-isolation and household quarantine with the addition of manual contact tracing of all contacts, 57% with the addition of manual tracing of acquaintances only, and 47% with the addition of app-based tracing only. If limits were placed on gatherings outside of home, school, or work, then manual contact tracing of acquaintances alone could have an effect on transmission reduction similar to that of detailed contact tracing. In a scenario where 1000 new symptomatic cases that met the definition to trigger contact tracing occurred per day, we estimated that, in most contact tracing strategies, 15 000–41 000 contacts would be newly quarantined each day. Interpretation: Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimated that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number lower than 1 in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control of severe acute respiratory syndrome coronavirus 2 transmission. Funding: Wellcome Trust, UK Engineering and Physical Sciences Research Council, European Commission, Royal Society, Medical Research Council.

Background Release of virus-blocking Wolbachia-infected mosquitoes is an emerging disease control strategy that aims to control dengue and other arboviral infections. Early entomological data and modelling analyses have suggested promising outcomes, and wMel Wolbachia releases are now ongoing or planned in 12 countries. To help inform government, donor, or philanthropist decisions on scale-up beyond single city releases, we assessed this technology’s cost-effectiveness under alternative programmatic options. Methods Using costing data from existing Wolbachia releases, previous dynamic model-based estimates of Wolbachia effectiveness, and a spatially explicit model of release and surveillance requirements, we predicted the costs and effectiveness of the ongoing programme in Yogyakarta City and three new hypothetical programmes in Yogyakarta Special Autonomous Region, Jakarta, and Bali. Results We predicted Wolbachia to be a highly cost-effective intervention when deployed in high-density urban areas with gross cost-effectiveness below $1500 per DALY averted. When offsets from the health system and societal perspective were included, such programmes even became cost saving over 10-year time horizons with favourable benefit-cost ratios of 1.35 to 3.40. Sequencing Wolbachia releases over 10 years could reduce programme costs by approximately 38% compared to simultaneous releases everywhere, but also delays the benefits. Even if unexpected challenges occurred during deployment, such as emergence of resistance in the medium-term or low effective coverage, Wolbachia would remain a cost-saving intervention. Conclusions Wolbachia releases in high-density urban areas are expected to be highly cost-effective and could potentially be the first cost-saving intervention for dengue. Sites with strong public health infrastructure, fiscal capacity, and community support should be prioritised.

Background: \ud The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk.\ud \ud Methods: \ud We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies.\ud \ud Findings: \ud We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from 66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% [3–9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from

Summary Background Non-pharmaceutical interventions have been implemented to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the UK. Projecting the size of an unmitigated epidemic and the potential effect of different control measures has been crucial to support evidence-based policy making during the early stages of the epidemic. This study assesses the potential impact of different control measures for mitigating the burden of COVID-19 in the UK. Methods We used a stochastic age-structured transmission model to explore a range of intervention scenarios, tracking 66·4 million people aggregated to 186 county-level administrative units in England, Wales, Scotland, and Northern Ireland. The four base interventions modelled were school closures, physical distancing, shielding of people aged 70 years or older, and self-isolation of symptomatic cases. We also modelled the combination of these interventions, as well as a programme of intensive interventions with phased lockdown-type restrictions that substantially limited contacts outside of the home for repeated periods. We simulated different triggers for the introduction of interventions, and estimated the impact of varying adherence to interventions across counties. For each scenario, we projected estimated new cases over time, patients requiring inpatient and critical care (ie, admission to the intensive care units [ICU]) treatment, and deaths, and compared the effect of each intervention on the basic reproduction number, R0. Findings We projected a median unmitigated burden of 23 million (95% prediction interval 13–30) clinical cases and 350 000 deaths (170 000–480 000) due to COVID-19 in the UK by December, 2021. We found that the four base interventions were each likely to decrease R0, but not sufficiently to prevent ICU demand from exceeding health service capacity. The combined intervention was more effective at reducing R0, but only lockdown periods were sufficient to bring R0 near or below 1; the most stringent lockdown scenario resulted in a projected 120 000 cases (46 000–700 000) and 50 000 deaths (9300–160 000). Intensive interventions with lockdown periods would need to be in place for a large proportion of the coming year to prevent health-care demand exceeding availability. Interpretation The characteristics of SARS-CoV-2 mean that extreme measures are probably required to bring the epidemic under control and to prevent very large numbers of deaths and an excess of demand on hospital beds, especially those in ICUs. Funding Medical Research Council.

Surveillance for acute flaccid paralysis (AFP) cases are essential for polio eradication. However, as most poliovirus infections are asymptomatic and some regions of the world are inaccessible, additional surveillance tools require development. Within England and Wales, we demonstrate how inclusion of environmental sampling (ENV) improves the sensitivity of detecting both wild and vaccine-derived polioviruses (VDPVs) when compared to current surveillance. Statistical modelling was used to estimate the spatial risk of wild and VDPV importation and circulation in England and Wales. We estimate the sensitivity of each surveillance mode to detect poliovirus and the probability of being free from poliovirus, defined as being below a pre-specified prevalence of infection. Poliovirus risk was higher within local authorities in Manchester, Birmingham, Bradford and London. The sensitivity of detecting wild poliovirus within a given month using AFP and enterovirus surveillance was estimated to be 0.096 (95% CI 0.055–0.134). Inclusion of ENV in the three highest risk local authorities and a site in London increased surveillance sensitivity to 0.192 (95% CI 0.191–0.193). The sensitivity of ENV strategies can be compared using the framework by varying sites and the frequency of sampling. The probability of being free from poliovirus slowly increased from the date of the last case in 1993. ENV within areas thought to have the highest risk improves detection of poliovirus, and has the potential to improve confidence in the polio-free status of England and Wales and detect VDPVs.

For 45 African countries/territories already reporting COVID-19 cases before 23 March 2020, we estimate the dates of reporting 1,000 and 10,000 cases. Assuming early epidemic trends without interventions, all 45 were likely to exceed 1,000 confirmed cases by the end of April 2020, with most exceeding 10,000 a few weeks later.

For African countries currently reporting COVID-19 cases, we estimate when they will report more than 1 000 and 10 000 cases. Assuming current trends, more than 80% are likely to exceed 1 000 cases by the end of April 2020, with most exceeding 10 000 a few weeks later.

In this introduction to the Special Issue on methods for modelling of infectious disease epidemiology we provide a commentary and overview of the field. We suggest that the field has been through three revolutions that have focussed on specific methodological developments; disease dynamics and heterogeneity, advanced computing and inference, and complexity and application to the real-world. Infectious disease dynamics and heterogeneity dominated until the 1980s where the use of analytical models illustrated fundamental concepts such as herd immunity. The second revolution embraced the integration of data with models and the increased use of computing. From the turn of the century an emergence of novel datasets enabled improved modelling of real-world complexity. The emergence of more complex data that reflect the real-world heterogeneities in transmission resulted in the development of improved inference methods such as particle filtering. Each of these three revolutions have always kept the understanding of infectious disease spread as its motivation but have been developed through the use of new techniques, tools and the availability of data. We conclude by providing a commentary on what the next revoluition in infectious disease modelling may be.

BackgroundRelease of virus-blocking Wolbachia infected mosquitoes is an emerging disease control strategy that aims to control dengue and other arboviral infections. Early entomological data and modelling analyses have suggested promising outcomes and wMel Wolbachia releases are now ongoing or planned in 12 countries. To help inform potential scale-up beyond single city releases, we assessed this technology’s cost-effectiveness under different programmatic options.MethodsUsing costing data from existing Wolbachia releases, previous estimates of Wolbachia effectiveness, and a spatially-explicit model of release and surveillance requirements, we predicted the costs and effectiveness of the on-going programme in Yogyakarta City and three new hypothetical programmes in Yogyakarta Special Autonomous Region, Jakarta and Bali.ResultsWe predicted Wolbachia to be a highly cost-effective intervention when deployed in high density urban areas with gross cost-effectiveness ratios below $1,500 per DALY averted. When offsets from the health system and societal perspective were included, such programmes even became cost saving over 10-year time horizons with favourable benefit-cost ratios of 1.35 to 3.40. Sequencing Wolbachia releases over ten years could reduce programme costs by approximately 38% compared to simultaneous releases everywhere, but also delays the benefits. Even if unexpected challenges occurred during deployment, such as emergence of resistance in the medium-term or low effective coverage, Wolbachia would remain a cost saving intervention.ConclusionsWolbachia releases in high density urban areas is expected to be highly cost-effective and could potentially be the first cost saving intervention for dengue. Sites with strong public health infrastructure, fiscal capacity, and community support should be prioritized.

A public health catch-22 In 2016, the serotype 2 component of the oral poliovirus vaccine given to children was withdrawn. This measure was taken to prevent vaccine-associated disease outbreaks caused by mutation in the live attenuated vaccine. Children around the world now have poor immunity to serotype 2 poliovirus because the inactivated vaccine is far less effective and a new oral vaccine is not yet ready. Using a statistical model, Macklin et al. discovered that most current outbreaks of polio in several countries across Asia and sub-Saharan Africa are likely associated with the serotype 2 vaccine strain (see the Perspective by Donlan and Petri). To block transmission when poliovirus outbreaks occur requires deployment of the only tool in the box: the existing live attenuated serotype 2 oral vaccine, which increases the risk of vaccine-derived disease. Science , this issue p. 401 ; see also p. 362

Free-living ground squirrel species are sexually dimorphic in hibernation phenology. The underlying causes of these differences are not yet known. Androgens, testosterone (T) in particular, inhibit hibernation. To determine the influence of endogenous androgens on annual timing of hibernation we first measured circulating levels of T and dehydroepiandrosterone (DHEA), an adrenal androgen implicated in non-mating season aggression in other species, in free-living male arctic ground squirrels (Urocitellus parryii, AGS). We also manipulated endogenous androgen levels by surgical castration, and consequently compared body temperature records from intact (n = 24) and castrated (n = 9) males to elucidate the influence of endogenous androgens on annual body temperature cycles. The highest T levels (0.53 ± 0.10 ng/mL) were in reproductively mature male AGS in spring; whereas, both immature males in spring and all males in late summer had T levels an order of magnitude lower (0.07 ± 0.01 and 0.06 ± 0.00 ng/mL, respectively). DHEA levels were higher in males during the late summer compared to reproductively mature males in spring (120.6 ± 18.9 and 35.9 ± 2.3 pg/mL, respectively). Eliminating gonadal androgens via castration resulted in males delaying euthermy by extending heterothermy significantly in spring (Apr 22 ± 2.9) than reproductive males (Mar 28 ± 3.9) but did not change the timing of hibernation onset (castrate: Oct 12 ± 1.0 vs. intact: Oct 3 ± 3.1). We conclude that while androgens play a significant role in spring hibernation phenology of males, their role in fall hibernation onset is unclear.

Summary Background Substantial outbreaks of yellow fever in Angola and Brazil in the past 2 years, combined with global shortages in vaccine stockpiles, highlight a pressing need to assess present control strategies. The aims of this study were to estimate global yellow fever vaccination coverage from 1970 through to 2016 at high spatial resolution and to calculate the number of individuals still requiring vaccination to reach population coverage thresholds for outbreak prevention. Methods For this adjusted retrospective analysis, we compiled data from a range of sources (eg, WHO reports and health-service-provider registeries) reporting on yellow fever vaccination activities between May 1, 1939, and Oct 29, 2016. To account for uncertainty in how vaccine campaigns were targeted, we calculated three population coverage values to encompass alternative scenarios. We combined these data with demographic information and tracked vaccination coverage through time to estimate the proportion of the population who had ever received a yellow fever vaccine for each second level administrative division across countries at risk of yellow fever virus transmission from 1970 to 2016. Findings Overall, substantial increases in vaccine coverage have occurred since 1970, but notable gaps still exist in contemporary coverage within yellow fever risk zones. We estimate that between 393·7 million and 472·9 million people still require vaccination in areas at risk of yellow fever virus transmission to achieve the 80% population coverage threshold recommended by WHO; this represents between 43% and 52% of the population within yellow fever risk zones, compared with between 66% and 76% of the population who would have required vaccination in 1970. Interpretation Our results highlight important gaps in yellow fever vaccination coverage, can contribute to improved quantification of outbreak risk, and help to guide planning of future vaccination efforts and emergency stockpiling. Funding The Rhodes Trust, Bill & Melinda Gates Foundation, the Wellcome Trust, the National Library of Medicine of the National Institutes of Health, the European Union's Horizon 2020 research and innovation programme.

BackgroundWolbachia-infected mosquitoes reduce dengue virus transmission, and city-wide releases in Yogyakarta city, Indonesia, are showing promising entomological results. Accurate estimates of the burden of dengue, its spatial distribution and the potential impact ofWolbachiaare critical in guiding funder and government decisions on its future wider use.MethodsHere, we combine multiple modelling methods for burden estimation to predict national case burden disaggregated by severity and map the distribution of burden across the country using three separate data sources. An ensemble of transmission models then predicts the estimated reduction in dengue transmission following a nationwide roll-out of wMelWolbachia.ResultsWe estimate that 7.8 million (95% uncertainty interval [UI] 1.8–17.7 million) symptomatic dengue cases occurred in Indonesia in 2015 and were associated with 332,865 (UI 94,175–754,203) lost disability-adjusted life years (DALYs). The majority of dengue’s burden was due to non-severe cases that did not seek treatment or were challenging to diagnose in outpatient settings leading to substantial underreporting. Estimated burden was highly concentrated in a small number of large cities with 90% of dengue cases occurring in 15.3% of land area. Implementing a nationwideWolbachiapopulation replacement programme was estimated to avert 86.2% (UI 36.2–99.9%) of cases over a long-term average.ConclusionsThese results suggest interventions targeted to the highest burden cities can have a disproportionate impact on dengue burden. Area-wide interventions, such asWolbachia, that are deployed based on the area covered could protect people more efficiently than individual-based interventions, such as vaccines, in such dense environments.

Background: Circulating vaccine derived poliovirus (cVDPV) outbreaks remain a threat to polio eradication. To reduce cases of polio from cVDPV of serotype 2, the serotype 2 component of the vaccine has been removed from the global vaccine supply, but outbreaks of cVDPV2 have continued. The objective of this work is to understand the factors associated with later detection in order to improve detection of these unwanted events. Methods: The number of nucleotide differences between each cVDPV outbreak and the oral polio vaccine (OPV) strain was used to approximate the time from emergence to detection. Only independent emergences were included in the analysis. Variables such as serotype, surveillance quality, and World Health Organization (WHO) region were tested in a negative binomial regression model to ascertain whether these variables were associated with higher nucleotide differences upon detection. Results: In total, 74 outbreaks were analysed from 24 countries between 2004 and 2019. For serotype 1 (n=10), the median time from seeding until outbreak detection was 284 (95% uncertainty interval (UI) 284-2008) days, for serotype 2 (n=59), 276 (95% UI 172-765) days, and for serotype 3 (n=5), 472 (95% UI 392-603) days. Significant improvement in the time to detection was found with increasing surveillance of non-polio acute flaccid paralysis (AFP) and adequate stool collection. Conclusions: cVDPVs remain a risk globally; all WHO regions have reported at least one VDPV outbreak since the first outbreak in 2001. Maintaining surveillance for poliomyelitis after local elimination is essential to quickly respond to both emergence of VDPVs and potential importations. Considerable variation in the time between emergence and detection of VDPVs were apparent, and other than surveillance quality and inclusion of environmental surveillance, the reasons for this remain unclear.

Background Zika virus (ZIKV) emerged in Latin America & the Caribbean (LAC) region in 2013, and has had serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and a lack of a comprehensive collation of data from affected countries.Methods Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 91 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vector capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories.Results There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (pConclusions The findings suggest that the ZIKV epidemic is by and large over, with incidence projected to be low in most cities in LAC in 2018. Local low levels of transmission are probable but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.

Background The proportion of mosquito blood-meals that are of human origin, referred to as the ‘human blood index’ or HBI, is a key determinant of malaria transmission. Methods A systematic review was conducted followed by meta-regression of the HBI for the major African malaria vectors. Results Evidence is presented for higher HBI among Anopheles gambiae (M/S forms and Anopheles coluzzii/An. gambiae sensu stricto are not distinguished for most studies and, therefore, combined) as well as Anopheles funestus when compared with Anopheles arabiensis (prevalence odds ratio adjusted for collection location [i.e. indoor or outdoor]: 1.62; 95% CI 1.09–2.42; 1.84; 95% CI 1.35–2.52, respectively). This finding is in keeping with the entomological literature which describes An. arabiensis to be more zoophagic than the other major African vectors. However, analysis also revealed that HBI was more associated with location of mosquito captures (R2 = 0.29) than with mosquito (sibling) species (R2 = 0.11). Conclusions These findings call into question the appropriateness of current methods of assessing host preferences among disease vectors and have important implications for strategizing vector control. Electronic supplementary material The online version of this article (10.1186/s12936-018-2632-7) contains supplementary material, which is available to authorized users.

Summary Background The eradication of wild and vaccine-derived poliovirus requires the global withdrawal of oral poliovirus vaccines (OPVs) and replacement with inactivated poliovirus vaccines (IPVs). The first phase of this effort was the withdrawal of the serotype 2 vaccine in April 2016, with a switch from trivalent OPVs to bivalent OPVs. The aim of our study was to produce comparative estimates of humoral and intestinal mucosal immunity associated with different routine immunisation schedules. Methods We did a random-effect meta-analysis with single proportions and a network meta-analysis in a Bayesian framework to synthesise direct and indirect data. We searched MEDLINE and the Cochrane Library Central Register of Controlled Trials for randomised controlled trials published from Jan 1, 1980, to Nov 1, 2018, comparing poliovirus immunisation schedules in a primary series. Only trials done outside western Europe or North America and without variation in age schedules (ie, age at administration of the vaccine) between study groups were included in the analyses, because trials in high-income settings differ in vaccine immunogenicity and schedules from other settings and to ensure consistency within the network of trials. Data were extracted directly from the published reports. We assessed seroconversion against poliovirus serotypes 1, 2, and 3, and intestinal immunity against serotype 2, measured by absence of shedding poliovirus after a challenge OPV dose. Findings We identified 437 unique studies; of them, 17 studies with a maximum of 8279 evaluable infants were eligible for assessment of humoral immunity, and eight studies with 4254 infants were eligible for intestinal immunity. For serotype 2, there was low between-trial heterogeneity in the data (τ=0·05, 95% credible interval [CrI] 0·009–0·15) and the risk ratio (RR) of seroconversion after three doses of bivalent OPVs was 0·14 (95% CrI 0·11–0·17) compared with three doses of trivalent OPVs. The addition of one or two full doses of an IPV after a bivalent OPV schedule increased the RR to 0·85 (0·75–1·0) and 1·1 (0·98–1·4). However, the addition of an IPV to bivalent OPV schedules did not significantly increase intestinal immunity (0·33, 0·18–0·61), compared with trivalent OPVs alone. For serotypes 1 and 3, there was susbstantial inconsistency and between-trial heterogeneity between direct and indirect effects, so we only present pooled estmates on seroconversion, which were at least 80% for serotype 1 and at least 88% for serotype 3 for all vaccine schedules. Interpretation For WHO's polio eradication programme, the addition of one IPV dose for all birth cohorts should be prioritised to protect against paralysis caused by type 2 poliovirus; however, this inclusion will not prevent transmission or circulation in areas with faecal–oral transmission. Funding UK Medical Research Council.

Difficulties with observing the dispersal of insect vectors in the field have hampered understanding of several aspects of their behaviour linked to disease transmission. Here, a novel method based on detection of blood-meal sources is introduced to inform two critical and understudied mosquito behaviours: plasticity in the malaria vector’s blood-host choice and vector dispersal. Strategically located collections of Anopheles coluzzii from a malaria-endemic village of southern Ghana showed statistically significant variation in host species composition of mosquito blood-meals. Trialling a new sampling approach gave the first estimates for the remarkably local spatial scale across which host choice is plastic. Using quantitative PCR, the blood-meal digestion was then quantified for field-caught mosquitoes and calibrated according to timed blood digestion in colony mosquitoes. We demonstrate how this new ‘molecular Sella score’ approach can be used to estimate the dispersal rate of blood-feeding vectors caught in the field.

BACKGROUNDThe proportion of mosquito blood-meals that are of human origin, referred to as the ‘human blood index’ or HBI, is a key determinant of malaria transmission. We conducted a systematic review of the HBI for the major African malaria vectors.RESULTSEvidence is presented for higher HBI among Anopheles gambiae (M/S forms and An. coluzzii/An. gambiae s.s. are not distinguished for most studies and therefore combined) as well as An. funestus when compared with An. arabiensis (prevalence odds ratio adjusted for collection location [i.e. indoor or outdoor]: 1.62; 95%CI 1.09-2.42; 1.84; 95%CI 1.35-2.52, respectively). This finding is keeping with the entomological literature which describes An. arabiensis to be more zoophagic than the other major African vectors. However, analysis also revealed that HBI was more associated with location of mosquito captures (R2=0.29) than with mosquito (sibling) species (R2=0.11).CONCLUSIONSOur findings call into question the appropriateness of current methods of assessing host preferences among disease vectors and have important implications for strategizing vector control.

Background: The eradication of wild and vaccine-derived poliovirus requires the withdrawal of oral poliovirus vaccine (OPV) and replacement with inactivated poliovirus vaccine (IPV). We aim to produce comparative estimates of humoral and intestinal mucosal immunity associated with alternative immunization schedules. Methods: We performed a random-effect network meta-analysis in a Bayesian framework. We searched MEDLINE for randomised trials published up to 01 November 2018, comparing poliovirus immunisation schedules in primary series. The first endpoint was seroconversion against poliovirus serotypes 1, 2 and 3 and the second endpoint was intestinal immunity against serotype 2, measured by absence of shedding poliovirus after challenge. Findings: We identified 17 studies and eight studies, with 8256 and 4254 infants, eligible for humoral and intestinal immunity outcomes, respectively. The relative risk (RR) of seroconversion to serotype 2 after three doses of bivalent OPV was 0.12 [95% CrI: 0·09, 0·15] compared with three doses of trivalent OPV. The addition of one or two doses of IPV after bOPV increased RR to 0·85 [95% CrI: 0·75, 1·0] and 1·1 [95% CrI: 0·97, 1·4], respectively. However, IPV did not significantly increase intestinal immunity. Interpretation: The immunogenicity of vaccination schedules can be assessed using network meta-analysis. Equitable distribution of one full or two fractional IPV doses should be prioritised, with equivalent immunogenicity between low-cost IPV options (fractional, monovalent type 2, adjuvanted and Sabin-strain). However, addition of IPV will not prevent circulation of type 2 poliovirus in areas with faecal-oral transmission. Funding Statement: UK Medical Research Council studentship Declaration of Interests: The authors declare: "no competing interests."

The polio eradication endgame aims to bring transmission of all polioviruses to a halt. To achieve this aim, it is essential to block viral replication in individuals via induction of a robust mucosal immune response. Although it has long been recognized that inactivated poliovirus vaccine (IPV) is incapable of inducing a strong mucosal response on its own, it has recently become clear that IPV may boost immunity in the intestinal mucosa among individuals previously immunized with oral poliovirus vaccine. Indeed, mucosal protection appears to be stronger following a booster dose of IPV than oral poliovirus vaccine, especially in older children. Here, we review the available evidence regarding the impact of IPV on mucosal immunity, and consider the implications of this evidence for the polio eradication endgame. We conclude that the implementation of IPV in both routine and supplementary immunization activities has the potential to play a key role in halting poliovirus transmission, and thereby hasten the eradication of polio.