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Summary: Background: Bhutan has achieved a substantial reduction in both malaria morbidity and mortality over the last two decades and is aiming for malaria elimination certification in 2025. However, a significant percentage of malaria cases in Bhutan are imported (acquired in another country). The aim of the study was to understand how importation drives local malaria transmission in Bhutan. Methods: Information on geo-located individual-level laboratory-confirmed malaria cases between 2016 and 2020 was obtained from the Bhutan Vector-borne Disease Control Program. Records included the date of diagnosis and treatment, type of cases classified as indigenous or imported, and malaria species. Hawkes Processes were used to study the role of imported malaria in local transmission in Bhutan. We imposed 15 days delay for a mosquito to become infectious in the model. Findings: There were 285 cases during the study period and 58.6% (159) were imported malaria. 71.1% (113) of these imported cases were Plasmodium vivax and 73.6% (117) were from India. The model suggested that a person remains infectious for 8 days for Plasmodium falciparum malaria but over 19 days for P. vivax. The background intensity from imported malaria cases was much greater for P. vivax cases (maximum 0.17) resulting in more importations than P. falciparum cases (maximum 0.06). However, model fitting suggested that local P. falciparum transmission was mainly driven by importations but additional factors such as relapse played a role for P. vivax. Interpretation: Imported malaria cases are key drivers of transmission within Bhutan, with most cases since 2016 being P. vivax. Control programmes should be devised to target interventions towards the P. vivax strain and test those who are more likely to bring in imported malaria cases or acquire it from returning travellers. Funding: None.

Abstract Vast amounts of pathogen genomic, demographic and spatial data are transforming our understanding of SARS-CoV-2 emergence and spread. We examined the drivers of molecular evolution and spread of 291,791 SARS-CoV-2 genomes from Denmark in 2021. With a sequencing rate consistently exceeding 60%, and up to 80% of PCR-positive samples between March and November, the viral genome set is broadly whole-epidemic representative. We identify a consistent rise in viral diversity over time, with notable spikes upon the importation of novel variants (e.g., Delta and Omicron). By linking genomic data with rich individual-level demographic data from national registers, we find that individuals aged 75 years had a lower contribution to molecular change (i.e., branch lengths) compared to other age groups, but similar molecular evolutionary rates, suggesting a lower likelihood of introducing novel variants. Similarly, we find greater molecular change among vaccinated individuals, suggestive of immune evasion. We also observe evidence of transmission in rural areas to follow predictable diffusion processes. Conversely, urban areas are expectedly more complex due to their high mobility, emphasising the role of population structure in driving virus spread. Our analyses highlight the added value of integrating genomic data with detailed demographic and spatial information, particularly in the absence of structured infection surveys.

Abstract The implementation of new antimicrobial resistance stewardship programs is crucial in optimizing antibiotic use. However, prescription choices can be difficult during empiric therapy; clinicians must balance the survival benefits of broader spectrum antibiotics with associated increases in resistance. The aim of this study was to evaluate the overall feasibility of switching to narrow spectrum antibiotics during the empiric treatment of E. coli bacteraemia by quantifying changes in resistance rates, antibiotic usage, and mortality using a deterministic state-transition model. Three unique model scenarios (A, B, and C), each representing a progressively broader spectrum empiric treatment regimen, were used to compare outcomes at 5 years. We show that the empiric use of the narrowest spectrum (first-line) antibiotics can lead to reductions in resistance to second-line antibiotics and the use of third-line antibiotics, but they also lead to increases in resistance to first-line therapy and higher mortality. Crucially, we find that shortening the duration of empiric and overall treatment, as well as reducing the baseline mortality rate, are important for increasing the feasibility of switching to narrow spectrum antibiotics in the empiric treatment of E. coli bacteraemia. We provide a flexible model design to investigate optimal treatment approaches for other bacterial infections.

Abstract Understanding and facilitating healthy aging has become a major goal in medical research and it is becoming increasingly acknowledged that there is a need for understanding the aging phenotype as a whole rather than focusing on individual factors. Here, we provide a universal explanation for the emergence of Gompertzian mortality patterns using a systems approach to describe aging in complex organisms that consist of many inter-dependent subsystems. Our model relates to the Sufficient-Component Cause Model, widely used within the field of epidemiology, and we show that including inter-dependencies between subsystems and modeling the temporal evolution of subsystem failure results in Gompertizan mortality on the population level. Our model also provides temporal trajectories of mortality-risk for the individual. These results may give insight into understanding how biological age evolves stochastically within the individual, and how this in turn leads to a natural heterogeneity of biological age in a population.

Compartmental models that describe infectious disease transmission across subpopulations are central for assessing the impact of non-pharmaceutical interventions, behavioral changes and seasonal effects on the spread of respiratory infections. We present a Bayesian workflow for such models, including four features: (1) an adjustment for incomplete case ascertainment, (2) an adequate sampling distribution of laboratory-confirmed cases, (3) a flexible, time-varying transmission rate, and (4) a stratification by age group. Within the workflow, we benchmarked the performance of various implementations of two of these features (2 and 3). For the second feature, we used SARS-CoV-2 data from the canton of Geneva (Switzerland) and found that a quasi-Poisson distribution is the most suitable sampling distribution for describing the overdispersion in the observed laboratory-confirmed cases. For the third feature, we implemented three methods: Brownian motion, B-splines, and approximate Gaussian processes (aGP). We compared their performance in terms of the number of effective samples per second, and the error and sharpness in estimating the time-varying transmission rate over a selection of ordinary differential equation solvers and tuning parameters, using simulated seroprevalence and laboratory-confirmed case data. Even though all methods could recover the time-varying dynamics in the transmission rate accurately, we found that B-splines perform up to four and ten times faster than Brownian motion and aGPs, respectively. We validated the B-spline model with simulated age-stratified data. We applied this model to 2020 laboratory-confirmed SARS-CoV-2 cases and two seroprevalence studies from the canton of Geneva. This resulted in detailed estimates of the transmission rate over time and the case ascertainment. Our results illustrate the potential of the presented workflow including stratified transmission to estimate age-specific epidemiological parameters. The workflow is freely available in the R package HETTMO, and can be easily adapted and applied to other infectious diseases.

Abstract Reported incidence of the zoonotic malaria Plasmodium knowlesi has markedly increased across Southeast Asia and threatens malaria elimination. Nonzoonotic transmission of P. knowlesi has been experimentally demonstrated, but it remains unknown whether nonzoonotic transmission is contributing to increases in P. knowlesi cases. Here, we adapt model-based inference methods to estimate R C , individual case reproductive numbers, for P. knowlesi, P. falciparum and P. vivax human cases in Malaysia from 2012–2020 (n = 32,635). Best fitting models for P. knowlesi showed subcritical transmission (R C 1) was estimated historically for P. falciparum and P. vivax, with declines in R C estimates observed over time consistent with local elimination. Together, this suggests sustained nonzoonotic P. knowlesi transmission is highly unlikely and that new approaches are urgently needed to control spillover risks.

Abstract Uncertainty can be classified as either aleatoric (intrinsic randomness) or epistemic (imperfect knowledge of parameters). The majority of frameworks assessing infectious disease risk consider only epistemic uncertainty. We only ever observe a single epidemic, and therefore cannot empirically determine aleatoric uncertainty. Here, we characterise both epistemic and aleatoric uncertainty using a time-varying general branching process. Our framework explicitly decomposes aleatoric variance into mechanistic components, quantifying the contribution to uncertainty produced by each factor in the epidemic process, and how these contributions vary over time. The aleatoric variance of an outbreak is itself a renewal equation where past variance affects future variance. We find that, superspreading is not necessary for substantial uncertainty, and profound variation in outbreak size can occur even without overdispersion in the offspring distribution (i.e. the distribution of the number of secondary infections an infected person produces). Aleatoric forecasting uncertainty grows dynamically and rapidly, and so forecasting using only epistemic uncertainty is a significant underestimate. Therefore, failure to account for aleatoric uncertainty will ensure that policymakers are misled about the substantially higher true extent of potential risk. We demonstrate our method, and the extent to which potential risk is underestimated, using two historical examples.

Abstract Background As both mechanistic and geospatial malaria modeling methods become more integrated into malaria policy decisions, there is increasing demand for strategies that combine these two methods. This paper introduces a novel archetypes-based methodology for generating high-resolution intervention impact maps based on mechanistic model simulations. An example configuration of the framework is described and explored. Methods First, dimensionality reduction and clustering techniques were applied to rasterized geospatial environmental and mosquito covariates to find archetypal malaria transmission patterns. Next, mechanistic models were run on a representative site from each archetype to assess intervention impact. Finally, these mechanistic results were reprojected onto each pixel to generate full maps of intervention impact. The example configuration used ERA5 and Malaria Atlas Project covariates, singular value decomposition, k-means clustering, and the Institute for Disease Modeling’s EMOD model to explore a range of three-year malaria interventions primarily focused on vector control and case management. Results Rainfall, temperature, and mosquito abundance layers were clustered into ten transmission archetypes with distinct properties. Example intervention impact curves and maps highlighted archetype-specific variation in efficacy of vector control interventions. A sensitivity analysis showed that the procedure for selecting representative sites to simulate worked well in all but one archetype. Conclusion This paper introduces a novel methodology which combines the richness of spatiotemporal mapping with the rigor of mechanistic modeling to create a multi-purpose infrastructure for answering a broad range of important questions in the malaria policy space. It is flexible and adaptable to a range of input covariates, mechanistic models, and mapping strategies and can be adapted to the modelers’ setting of choice.

In this study, the authors provide a global overview of SARS-CoV-2 genome sequencing, and estimate the proportion of cases sequenced and time to genome upload. They identify disparities and highlight the need to strengthen surveillance in lower and middle income countries.

The time-varying reproduction number (Rt) is an important measure of epidemic transmissibility that directly informs policy decisions and the optimisation of control measures. EpiEstim is a widely used opensource software tool that uses case incidence and the serial interval (SI, time between symptoms in a case and their infector) to estimate Rt in real-time. The incidence and the SI distribution must be provided at the same temporal resolution, which can limit the applicability of EpiEstim and other similar methods, e.g. for contexts where the time window of incidence reporting is longer than the mean SI. In the EpiEstim R package, we implement an expectation-maximisation algorithm to reconstruct daily incidence from temporally aggregated data, from which Rt can then be estimated. We assess the validity of our method using an extensive simulation study and apply it to COVID-19 and influenza data. For all datasets, the influence of intra-weekly variability in reported data was mitigated by using aggregated weekly data. Rt estimated on weekly sliding windows using incidence reconstructed from weekly data was strongly correlated with estimates from the original daily data. The simulation study revealed that Rt was well estimated in all scenarios and regardless of the temporal aggregation of the data. In the presence of weekend effects, Rt estimates from reconstructed data were more successful at recovering the true value of Rt than those obtained from reported daily data. These results show that this novel method allows Rt to be successfully recovered from aggregated data using a simple approach with very few data requirements. Additionally, by removing administrative noise when daily incidence data are reconstructed, the accuracy of Rt estimates can be improved.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), large-scale social contact surveys are now longitudinally measuring the fundamental changes in human interactions in the face of the pandemic and non-pharmaceutical interventions. Here, we present a model-based Bayesian approach that can reconstruct contact patterns at 1-year resolution even when the age of the contacts is reported coarsely by 5 or 10-year age bands. This innovation is rooted in population-level consistency constraints in how contacts between groups must add up, which prompts us to call the approach presented here the Bayesian rate consistency model. The model can also quantify time trends and adjust for reporting fatigue emerging in longitudinal surveys through the use of computationally efficient Hilbert Space Gaussian process priors. We illustrate estimation accuracy on simulated data as well as social contact data from Europe and Africa for which the exact age of contacts is reported, and then apply the model to social contact data with coarse information on the age of contacts that were collected in Germany during the COVID-19 pandemic from April to June 2020 across five longitudinal survey waves. We estimate the fine age structure in social contacts during the early stages of the pandemic and demonstrate that social contact intensities rebounded in an age-structured, non-homogeneous manner. The Bayesian rate consistency model provides a model-based, non-parametric, computationally tractable approach for estimating the fine structure and longitudinal trends in social contacts and is applicable to contemporary survey data with coarsely reported age of contacts as long as the exact age of survey participants is reported.

Brazeau et al. use a statistical modelling approach to estimate COVID-19 infection fatality ratios from seroprevalence data. The authors’ model accounts for seroreversion over the course of the pandemic, as well as other important uncertainties such as serologic test characteristics.

Measurement(s) Government non-pharmaceutical interventions against Covid-19 Technology Type(s) Interpretation by researchers Sample Characteristic - Organism Homo sapiens

Introduction Maps of malaria risk are important tools for allocating resources and tracking progress. Most maps rely on cross-sectional surveys of parasite prevalence, but health facilities represent an underused and powerful data source. We aimed to model and map malaria incidence using health facility data in Uganda.Methods Using 24 months (2019–2020) of individual-level outpatient data collected from 74 surveillance health facilities located in 41 districts across Uganda (n=445 648 laboratory-confirmed cases), we estimated monthly malaria incidence for parishes within facility catchment areas (n=310) by estimating care-seeking population denominators. We fit spatio-temporal models to the incidence estimates to predict incidence rates for the rest of Uganda, informed by environmental, sociodemographic and intervention variables. We mapped estimated malaria incidence and its uncertainty at the parish level and compared estimates to other metrics of malaria. To quantify the impact that indoor residual spraying (IRS) may have had, we modelled counterfactual scenarios of malaria incidence in the absence of IRS.Results Over 4567 parish-months, malaria incidence averaged 705 cases per 1000 person-years. Maps indicated high burden in the north and northeast of Uganda, with lower incidence in the districts receiving IRS. District-level estimates of cases correlated with cases reported by the Ministry of Health (Spearman’s r=0.68, p

Summary: Background: Childhood adversity such as poverty, loss of a parent, and dysfunctional family dynamics may be associated with exposure to environmental and behavioral hazards, interfere with normal biological functions, and affect cancer care and outcomes. To explore this hypothesis, we assessed the cancer burden among young men and women exposed to adversity during childhood. Methods: We undertook a population-based study using Danish nationwide register data on childhood adversity and cancer outcomes. Children who were alive and resident in Denmark until their 16th birthday were followed into young adulthood (16–38 years). Group-based multi-trajectory modelling was used to categorize individuals into five distinct groups: low adversity, early material deprivation, persistent material deprivation, loss/threat of loss, and high adversity. We assessed the association with overall cancer incidence, mortality, and five-year case fatality; and cancer specific outcomes for the four most common cancers in this age group in sex-stratified survival analyses. Findings: 1,281,334 individuals born between Jan 1, 1980, and Dec 31, 2001, were followed up until Dec 31, 2018, capturing 8229 incident cancer cases and 662 cancer deaths. Compared to low adversity, women who experienced persistent material deprivation carried a slightly lower risk of overall cancer (hazard ratio (HR) 0.90; 95% CI 0.82; 0.99), particularly due to malignant melanoma and brain and central nervous system cancers, while women who experienced high adversity carried a higher risk of breast cancer (HR 1.71; 95% CI 1.09; 2.70) and cervical cancer incidence (HR 1.82; 95% CI 1.18; 2.83). While there was no clear association between childhood adversity and cancer incidence in men, those men who had experienced persistent material deprivation (HR 1.72; 95% CI 1.29; 2.31) or high adversity (HR 2.27; 95% CI 1.38; 3.72) carried a disproportionate burden of cancer mortality during adolescence or young adulthood compared to men in the low adversity group. Interpretation: Childhood adversity is associated with a lower risk of some subtypes of cancer and a higher risk of others, particular in women. Persistent deprivation and adversity are also associated with a higher risk of adverse cancer outcomes for men. These findings may relate to a combination of biological susceptibility, health behaviors and treatment-related factors. Funding: None.

BackgroundChina is the most populous country globally and has made significant achievements in the control of infectious diseases over the last decades. The 2003 SARS epidemic triggered the initiation of the China Information System for Disease Control and Prevention (CISDCP). Since then, numerous studies have investigated the epidemiological features and trends of individual infectious diseases in China; however, few considered the changing spatiotemporal trends and seasonality of these infectious diseases over time. ObjectiveThis study aims to systematically review the spatiotemporal trends and seasonal characteristics of class A and class B notifiable infectious diseases in China during 2005-2020. MethodsWe extracted the incidence and mortality data of 8 types (27 diseases) of notifiable infectious diseases from the CISDCP. We used the Mann-Kendall and Sen’s methods to investigate the diseases’ temporal trends, Moran I statistic for their geographical distribution, and circular distribution analysis for their seasonality. ResultsBetween January 2005 and December 2020, 51,028,733 incident cases and 261,851 attributable deaths were recorded. Pertussis (P=.03), dengue fever (P=.01), brucellosis (P=.001), scarlet fever (P=.02), AIDS (P

Purpose The Danish Pathology Life Course (PATHOLIFE) cohort was established to facilitate epidemiological research relating histological and cytological features extracted from patient tissue specimens to the rich life course histories, including both prior and future register data, of the entire Danish population. Research results may increase quality of diagnosis, prognosis and stratification of patient subtypes, possibly identifying novel routes of treatment.Participants All Danish residents from 1 January 1986 to 31 December 2019, totalling 8 593 421 individuals.Findings to date We provide an overview of the subpopulation of Danish residents who have had a tissue specimen investigated within the Danish healthcare system, including both the primary sector and hospitals. We demonstrate heterogeneity in sociodemographic and prognostic factors between the general Danish population and the above mentioned subpopulation, and also between the general Danish population and subpopulations of patients with tissue specimens from selected anatomical sites. Results demonstrate the potential of the PATHOLIFE cohort for integrating many different factors into identification and selection of the most valuable tissue blocks for studies of specific diseases and their progression. Broadly, we find that living with a partner, having higher education and income associates with having a biopsy overall. However, this association varies across different tissue and patient types, which also display differences in time-to-death and causes of death.Future plans The PATHOLIFE cohort may be used to study specified patient groups and link health related events from several national health registries, and to sample patient groups, for which stored tissue specimens are available for further research investigations. The PATHOLIFE cohort thereby provides a unique opportunity to prospectively follow people that were characterised and sampled in the past.

Access to medical treatment for fever is essential to prevent morbidity and mortality in individuals and to prevent transmission of communicable febrile illness in communities. Quantification of the rates at which treatment is accessed is critical for health system planning and a prerequisite for disease burden estimates. In this study, national data on the proportion of children under five years old with fever who were taken for medical treatment were collected from all available countries in Africa, Latin America, and Asia (n = 91). We used generalised additive mixed models to estimate 30-year trends in the treatment-seeking rates across the majority of countries in these regions (n = 151). Our results show that the proportions of febrile children brought for medical treatment increased steadily over the last 30 years, with the greatest increases occurring in areas where rates had originally been lowest, which includes Latin America and Caribbean, North Africa and the Middle East (51 and 50% increase, respectively), and Sub-Saharan Africa (23% increase). Overall, the aggregated and population-weighted estimate of children with fever taken for treatment at any type of facility rose from 61% (59-64 95% CI) in 1990 to 71% (69-72 95% CI) in 2020. The overall population-weighted average for fraction of treatment in the public sector was largely unchanged during the study period: 49% (42-58 95% CI) sought care at public facilities in 1990 and 47% (44-52 95% CI) in 2020. Overall, the findings indicate that improvements in access to care have been made where they were most needed, but that despite rapid initial gains, progress can plateau without substantial investment. In 2020 there remained significant gaps in care utilisation that must be factored in when developing control strategies and deriving disease burden estimates.

Background Spousal bereavement is a life event that affects older people differently. We investigated the impact of spousal bereavement on medical expenditures and mortality in the general population, emphasizing on age and sex. Methods Data are from a population-based, retrospective cohort study following 924,958 Danish citizens over the age of 65 years, within 2011–2016. Changes in health care expenditures in those who suffer bereavement were compared with time matched changes among those who did not. Mortality hazards were analysed with time to event analysis. Results A total of 77,722 (~8.4%) individuals experienced bereavement, 65.8% being females. Among males, bereavement was associated with increase of expenditures the year after, that was 42 Euros per week (95% CI, 36 to 48) larger than the non-bereaved group. The corresponding increase for females was 35 Euros per week (95% CI, 30 to 40). The increase of mortality hazards was highest in the first year after bereavement, higher in males than females, in young old and almost absent in the oldest old. Compared with the reference, mortality the year after spousal loss was 70% higher (HR 1.70 [95% CI 1.40 to 2.08]) for males aged 65–69 years and remained elevated for a period of six years. Mortality for females aged 65–69 years was 27% higher in the first year (HR 1.27, [1.07 to 1.52]), normalizing thereafter. Conclusion Bereavement affects older people differently with younger males being most frail with limited recovery potential.

Evaluating normalising constants is important across a range of topics in statistical learning, notably Bayesian model selection. However, in many realistic problems this involves the integration of analytically intractable, high-dimensional distributions, and therefore requires the use of stochastic methods such as thermodynamic integration (TI). In this paper we apply a simple but under-appreciated variation of the TI method, here referred to as referenced TI, which computes a single model's normalising constant in an efficient way by using a judiciously chosen reference density. The advantages of the approach and theoretical considerations are set out, along with pedagogical 1 and 2D examples. The approach is shown to be useful in practice when applied to a real problem -to perform model selection for a semi-mechanistic hierarchical Bayesian model of COVID-19 transmission in South Korea involving the integration of a 200D density.

European governments control resurging waves of COVID-19 using nonpharmaceutical interventions. Here, the authors estimate the effectiveness of 17 interventions in Europe’s second wave, and analyse differences to the first wave as well as implications for the future of the pandemic.

Abstract Background Hospitals in England have undergone considerable change to address the surge in demand imposed by the COVID-19 pandemic. The impact of this on emergency department (ED) attendances is unknown, especially for non-COVID-19 related emergencies. Methods This analysis is an observational study of ED attendances at the Imperial College Healthcare NHS Trust (ICHNT). We calibrated auto-regressive integrated moving average time-series models of ED attendances using historic (2015–2019) data. Forecasted trends were compared to present year ICHNT data for the period between March 12, 2020 (when England implemented the first COVID-19 public health measure) and May 31, 2020. We compared ICHTN trends with publicly available regional and national data. Lastly, we compared hospital admissions made via the ED and in-hospital mortality at ICHNT during the present year to the historic 5-year average. Results ED attendances at ICHNT decreased by 35% during the period after the first lockdown was imposed on March 12, 2020 and before May 31, 2020, reflecting broader trends seen for ED attendances across all England regions, which fell by approximately 50% for the same time frame. For ICHNT, the decrease in attendances was mainly amongst those aged

BackgroundAchieving herd immunity through vaccination depends upon the public’s acceptance, which in turn relies on their understanding of its risks and benefits. The fundamental objective of public health messaging on vaccines is therefore the clear communication of often complex information and, increasingly, the countering of misinformation. The primary outlet shaping public understanding is mainstream online news media, where coverage of COVID-19 vaccines was widespread. ObjectiveWe used text-mining analysis on the front pages of mainstream online news to quantify the volume and sentiment polarization of vaccine coverage. MethodsWe analyzed 28 million articles from 172 major news sources across 11 countries between July 2015 and April 2021. We employed keyword-based frequency analysis to estimate the proportion of overall articles devoted to vaccines. We performed topic detection using BERTopic and named entity recognition to identify the leading subjects and actors mentioned in the context of vaccines. We used the Vader Python module to perform sentiment polarization quantification of all collated English-language articles. ResultsThe proportion of front-page articles mentioning vaccines increased from 0.1% to 4% with the outbreak of COVID-19. The number of negatively polarized articles increased from 6698 in 2015-2019 to 28,552 in 2020-2021. However, overall vaccine coverage before the COVID-19 pandemic was slightly negatively polarized (57% negative), whereas coverage during the pandemic was positively polarized (38% negative). ConclusionsThroughout the pandemic, vaccines have risen from a marginal to a widely discussed topic on the front pages of major news outlets. Mainstream online media has been positively polarized toward vaccines, compared with mainly negative prepandemic vaccine news. However, the pandemic was accompanied by an order-of-magnitude increase in vaccine news that, due to low prepandemic frequency, may contribute to a perceived negative sentiment. These results highlight important interactions between the volume of news and overall polarization. To the best of our knowledge, our work is the first systematic text mining study of front-page vaccine news headlines in the context of COVID-19.

Abstract The UK and Sweden have among the worst per-capita COVID-19 mortality in Europe. Sweden stands out for its greater reliance on voluntary, rather than mandatory, control measures. We explore how the timing and effectiveness of control measures in the UK, Sweden and Denmark shaped COVID-19 mortality in each country, using a counterfactual assessment: what would the impact have been, had each country adopted the others’ policies? Using a Bayesian semi-mechanistic model without prior assumptions on the mechanism or effectiveness of interventions, we estimate the time-varying reproduction number for the UK, Sweden and Denmark from daily mortality data. We use two approaches to evaluate counterfactuals which transpose the transmission profile from one country onto another, in each country’s first wave from 13th March (when stringent interventions began) until 1st July 2020. UK mortality would have approximately doubled had Swedish policy been adopted, while Swedish mortality would have more than halved had Sweden adopted UK or Danish strategies. Danish policies were most effective, although differences between the UK and Denmark were significant for one counterfactual approach only. Our analysis shows that small changes in the timing or effectiveness of interventions have disproportionately large effects on total mortality within a rapidly growing epidemic.

Abstract Background The literature paints a complex picture of the association between mortality risk and ICU strain. In this study, we sought to determine if there is an association between mortality risk in intensive care units (ICU) and occupancy of beds compatible with mechanical ventilation, as a proxy for strain. Methods A national retrospective observational cohort study of 89 English hospital trusts (i.e. groups of hospitals functioning as single operational units). Seven thousand one hundred thirty-three adults admitted to an ICU in England between 2 April and 1 December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria. A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible), bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, deprivation index, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease). Results One hundred thirty-five thousand six hundred patient days were observed, with a mortality rate of 19.4 per 1000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (> 85% occupancy versus the baseline of 45 to 85%) [OR 1.23 (95% posterior credible interval (PCI): 1.08 to 1.39)]. In contrast, mortality was decreased for admissions during periods of low occupancy (

Abstract Individual-level geographic information about malaria cases, such as the GPS coordinates of residence or health facility, is often collected as part of surveillance in near-elimination settings, but could be more effectively utilised to infer transmission dynamics, in conjunction with additional information such as symptom onset time and genetic distance. However, in the absence of data about the flow of parasites between populations, the spatial scale of malaria transmission is often not clear. As a result, it is important to understand the impact of varying assumptions about the spatial scale of transmission on key metrics of malaria transmission, such as reproduction numbers. We developed a method which allows the flexible integration of distance metrics (such as Euclidian distance, genetic distance or accessibility matrices) with temporal information into a single inference framework to infer malaria reproduction numbers. Twelve scenarios were defined, representing different assumptions about the likelihood of transmission occurring over different geographic distances and likelihood of missing infections (as well as high and low amounts of uncertainty in this estimate). These scenarios were applied to four individual level datasets from malaria eliminating contexts to estimate individual reproduction numbers and how they varied over space and time. Model comparison suggested that including spatial information improved models as measured by second order AIC (ΔAICc), compared to time only results. Across scenarios and across datasets, including spatial information tended to increase the seasonality of temporal patterns in reproduction numbers and reduced noise in the temporal distribution of reproduction numbers. The best performing parameterisations assumed long-range transmission (> 200 km) was possible. Our approach is flexible and provides the potential to incorporate other sources of information which can be converted into distance or adjacency matrices such as travel times or molecular markers.

Insecticide treated nets (ITNs) are an important part of malaria control in Africa and WHO targets aim for 80% coverage. This study estimates the spatio-temporal access and use of ITNs in Africa from 2000-2020, and shows that both metrics have improved over time but access remains below WHO targets.

Although seasonal variation has a known influence on the transmission of several respiratory viral infections, its role in SARS-CoV-2 transmission remains unclear. While there is a sizable and growing literature on environmental drivers of COVID-19 transmission, recent reviews have highlighted conflicting and inconclusive findings. This indeterminacy partly owes to the fact that seasonal variation relates to viral transmission by a complicated web of causal pathways, including many interacting biological and behavioural factors. Since analyses of specific factors cannot determine the aggregate strength of seasonal forcing, we sidestep the challenge of disentangling various possible causal paths in favor of a holistic approach. We model seasonality as a sinusoidal variation in transmission and infer a single Bayesian estimate of the overall seasonal effect. By extending two state-of-the-art models of non-pharmaceutical intervention (NPI) effects and their datasets covering 143 regions in temperate Europe, we are able to adjust our estimates for the role of both NPIs and mobility patterns in reducing transmission. We find strong seasonal patterns, consistent with a reduction in the time-varying reproduction number R(t) (the expected number of new infections generated by an infectious individual at time t) of 42.1% (95% CI: 24.7%-53.4%) from the peak of winter to the peak of summer. These results imply that the seasonality of SARS-CoV-2 transmission is comparable in magnitude to the most effective individual NPIs but less than the combined effect of multiple interventions.

Social distancing policies aiming to reduce COVID-19 transmission have been reflected in reductions in human mobility. Here, the authors show that reduced mobility is correlated with decreased transmission, but that this relationship weakened over time as social distancing measures were relaxed.

Objectives: In this data collation study, we aimed to provide a comprehensive database describing the epidemic trends and responses during the first wave of coronavirus disease 2019 (COVID-19) throughout the main provinces in China. Methods: From mid-January to March 2020, we extracted publicly available data regarding the spread and control of COVID-19 from 31 provincial health authorities and major media outlets in mainland China. Based on these data, we conducted descriptive analyses of the epidemic in the six most-affected provinces. Results: School closures, travel restrictions, community-level lockdown, and contact tracing were introduced concurrently around late January but subsequent epidemic trends differed among provinces. Compared with Hubei, the other five most-affected provinces reported a lower crude case fatality ratio and proportion of critical and severe hospitalised cases. From March 2020, as the local transmission of COVID-19 declined, switching the focus of measures to the testing and quarantine of inbound travellers may have helped to sustain the control of the epidemic. Conclusions: Aggregated indicators of case notifications and severity distributions are essential for monitoring an epidemic. A publicly available database containing these indicators and information regarding control measures is a useful resource for further research and policy planning in response to the COVID-19 epidemic.

Abstract Background There were 25.6 million attendances at Emergency Departments (EDs) in England in 2019 corresponding to an increase of 12 million attendances over the past ten years. The steadily rising demand at EDs creates a constant challenge to provide adequate quality of care while maintaining standards and productivity. Managing hospital demand effectively requires an adequate knowledge of the future rate of admission. We develop a novel predictive framework to understand the temporal dynamics of hospital demand. Methods We compare and combine state-of-the-art forecasting methods to predict hospital demand 1, 3 or 7 days into the future. In particular, our analysis compares machine learning algorithms to more traditional linear models as measured in a mean absolute error (MAE) and we consider two different hyperparameter tuning methods, enabling a faster deployment of our models without compromising performance. We believe our framework can readily be used to forecast a wide range of policy relevant indicators. Results We find that linear models often outperform machine learning methods and that the quality of our predictions for any of the forecasting horizons of 1, 3 or 7 days are comparable as measured in MAE. Our approach is able to predict attendances at these emergency departments one day in advance up to a mean absolute error of ±14 and ±10 patients corresponding to a mean absolute percentage error of 6.8% and 8.6% respectively. Conclusions Simple linear methods like generalized linear models are often better or at least as good as ensemble learning methods like the gradient boosting or random forest algorithm. However, though sophisticated machine learning methods are not necessarily better than linear models, they improve the diversity of model predictions so that stacked predictions can be more robust than any single model including the best performing one.

Abstract Background Accurate measures of malaria incidence are essential to track progress and target high-risk populations. While health management information system (HMIS) data provide counts of malaria cases, quantifying the denominator for incidence using these data is challenging because catchment areas and care-seeking behaviours are not well defined. This study’s aim was to estimate malaria incidence using HMIS data by adjusting the population denominator accounting for travel time to the health facility. Methods Outpatient data from two public health facilities in Uganda (Kihihi and Nagongera) over a 3-year period (2011–2014) were used to model the relationship between travel time from patient village of residence (available for each individual) to the facility and the relative probability of attendance using Poisson generalized additive models. Outputs from the model were used to generate a weighted population denominator for each health facility and estimate malaria incidence. Among children aged 6 months to 11 years, monthly HMIS-derived incidence estimates, with and without population denominators weighted by probability of attendance, were compared with gold standard measures of malaria incidence measured in prospective cohorts. Results A total of 48,898 outpatient visits were recorded across the two sites over the study period. HMIS incidence correlated with cohort incidence over time at both study sites (correlation in Kihihi = 0.64, p

High numbers of COVID-19-related deaths have been reported in the United States, but estimation of the true numbers of infections is challenging. Here, the authors estimate that on 1 June 2020, 3.7% of the US population was infected with SARS-CoV-2, and 0.01% was infectious, with wide variation by state.

Abstract Background After experiencing a sharp growth in COVID-19 cases early in the pandemic, South Korea rapidly controlled transmission while implementing less stringent national social distancing measures than countries in Europe and the USA. This has led to substantial interest in their “test, trace, isolate” strategy. However, it is important to understand the epidemiological peculiarities of South Korea’s outbreak and characterise their response before attempting to emulate these measures elsewhere. Methods We systematically extracted numbers of suspected cases tested, PCR-confirmed cases, deaths, isolated confirmed cases, and numbers of confirmed cases with an identified epidemiological link from publicly available data. We estimated the time-varying reproduction number, R t , using an established Bayesian framework, and reviewed the package of interventions implemented by South Korea using our extracted data, plus published literature and government sources. Results We estimated that after the initial rapid growth in cases, R t dropped below one in early April before increasing to a maximum of 1.94 (95%CrI, 1.64–2.27) in May following outbreaks in Seoul Metropolitan Region. By mid-June, R t was back below one where it remained until the end of our study (July 13th). Despite less stringent “lockdown” measures, strong social distancing measures were implemented in high-incidence areas and studies measured a considerable national decrease in movement in late February. Testing the capacity was swiftly increased, and protocols were in place to isolate suspected and confirmed cases quickly; however, we could not estimate the delay to isolation using our data. Accounting for just 10% of cases, individual case-based contact tracing picked up a relatively minor proportion of total cases, with cluster investigations accounting for 66%. Conclusions Whilst early adoption of testing and contact tracing is likely to be important for South Korea’s successful outbreak control, other factors including regional implementation of strong social distancing measures likely also contributed. The high volume of testing and the low number of deaths suggest that South Korea experienced a small epidemic relative to other countries. Caution is needed in attempting to replicate the South Korean response in populations with larger more geographically widespread epidemics where finding, testing, and isolating cases that are linked to clusters may be more difficult.

Abstract Background Anti-malarial drugs play a critical role in reducing malaria morbidity and mortality, but their role is mediated by their effectiveness. Effectiveness is defined as the probability that an anti-malarial drug will successfully treat an individual infected with malaria parasites under routine health care delivery system. Anti-malarial drug effectiveness (AmE) is influenced by drug resistance, drug quality, health system quality, and patient adherence to drug use; its influence on malaria burden varies through space and time. Methods This study uses data from 232 efficacy trials comprised of 86,776 infected individuals to estimate the artemisinin-based and non-artemisinin-based AmE for treating falciparum malaria between 1991 and 2019. Bayesian spatiotemporal models were fitted and used to predict effectiveness at the pixel-level (5 km × 5 km). The median and interquartile ranges (IQR) of AmE are presented for all malaria-endemic countries. Results The global effectiveness of artemisinin-based drugs was 67.4% (IQR: 33.3–75.8), 70.1% (43.6–76.0) and 71.8% (46.9–76.4) for the 1991–2000, 2006–2010, and 2016–2019 periods, respectively. Countries in central Africa, a few in South America, and in the Asian region faced the challenge of lower effectiveness of artemisinin-based anti-malarials. However, improvements were seen after 2016, leaving only a few hotspots in Southeast Asia where resistance to artemisinin and partner drugs is currently problematic and in the central Africa where socio-demographic challenges limit effectiveness. The use of artemisinin-based combination therapy (ACT) with a competent partner drug and having multiple ACT as first-line treatment choice sustained high levels of effectiveness. High levels of access to healthcare, human resource capacity, education, and proximity to cities were associated with increased effectiveness. Effectiveness of non-artemisinin-based drugs was much lower than that of artemisinin-based with no improvement over time: 52.3% (17.9–74.9) for 1991–2000 and 55.5% (27.1–73.4) for 2011–2015. Overall, AmE for artemisinin-based and non-artemisinin-based drugs were, respectively, 29.6 and 36% below clinical efficacy as measured in anti-malarial drug trials. Conclusions This study provides evidence that health system performance, drug quality and patient adherence influence the effectiveness of anti-malarials used in treating uncomplicated falciparum malaria. These results provide guidance to countries’ treatment practises and are critical inputs for malaria prevalence and incidence models used to estimate national level malaria burden.