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Forecasts and alternative scenarios of COVID-19 mortality have been critical inputs for pandemic response efforts, and decision-makers need information about predictive performance. We screen n  = 386 public COVID-19 forecasting models, identifying n  = 7 that are global in scope and provide public, date-versioned forecasts. We examine their predictive performance for mortality by weeks of extrapolation, world region, and estimation month. We additionally assess prediction of the timing of peak daily mortality. Globally, models released in October show a median absolute percent error (MAPE) of 7 to 13% at six weeks, reflecting surprisingly good performance despite the complexities of modelling human behavioural responses and government interventions. Median absolute error for peak timing increased from 8 days at one week of forecasting to 29 days at eight weeks and is similar for first and subsequent peaks. The framework and public codebase ( https://github.com/pyliu47/covidcompare ) can be used to compare predictions and evaluate predictive performance going forward. Forecasts of COVID-19 mortality have been critical inputs into a range of policies, and decision-makers need information about their predictive performance. Here, the authors gather a panel of global epidemiological models and assess their predictive performance across time and space.

Assessments of disease burden are important to inform national, regional, and global strategies and to guide investment. We aimed to estimate the drinking water, sanitation, and hygiene (WASH)-attributable burden of disease for diarrhoea, acute respiratory infections, undernutrition, and soil-transmitted helminthiasis, using the WASH service levels used to monitor the UN Sustainable Development Goals (SDGs) as counterfactual minimum risk-exposure levels. We assessed the WASH-attributable disease burden of the four health outcomes overall and disaggregated by region, age, and sex for the year 2019. We calculated WASH-attributable fractions of diarrhoea and acute respiratory infections by country using modelled WASH exposures and exposure–response relationships from two updated meta-analyses. We used the WHO and UNICEF Joint Monitoring Programme for Water Supply, Sanitation and Hygiene public database to estimate population exposure to different WASH service levels. WASH-attributable undernutrition was estimated by combining the population attributable fractions (PAF) of diarrhoea caused by unsafe WASH and the PAF of undernutrition caused by diarrhoea. Soil-transmitted helminthiasis was fully attributed to unsafe WASH. We estimate that 1·4 (95% CI 1·3–1·5) million deaths and 74 (68–80) million disability-adjusted life-years (DALYs) could have been prevented by safe WASH in 2019 across the four designated outcomes, representing 2·5% of global deaths and 2·9% of global DALYs from all causes. The proportion of diarrhoea that is attributable to unsafe WASH is 0·69 (0·65–0·72), 0·14 (0·13–0·17) for acute respiratory infections, and 0·10 (0·09–0·10) for undernutrition, and we assume that the entire disease burden from soil-transmitted helminthiasis was attributable to unsafe WASH. WASH-attributable burden of disease estimates based on the levels of service established under the SDG framework show that progress towards the internationally agreed goal of safely managed WASH services for all would yield major public-health returns. WHO and Foreign, Commonwealth & Development Office.

The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2015 provides an up-to-date analysis of the burden of lower respiratory tract infections (LRIs) in 195 countries. This study assesses cases, deaths, and aetiologies spanning the past 25 years and shows how the burden of LRI has changed in people of all ages. We estimated LRI mortality by age, sex, geography, and year using a modelling platform shared across most causes of death in the GBD 2015 study called the Cause of Death Ensemble model. We modelled LRI morbidity, including incidence and prevalence, using a meta-regression platform called DisMod-MR. We estimated aetiologies for LRI using two different counterfactual approaches, the first for viral pathogens, which incorporates the aetiology-specific risk of LRI and the prevalence of the aetiology in LRI episodes, and the second for bacterial pathogens, which uses a vaccine-probe approach. We used the Socio-demographic Index, which is a summary indicator derived from measures of income per capita, educational attainment, and fertility, to assess trends in LRI-related mortality. The two leading risk factors for LRI disability-adjusted life-years (DALYs), childhood undernutrition and air pollution, were used in a decomposition analysis to establish the relative contribution of changes in LRI DALYs. In 2015, we estimated that LRIs caused 2·74 million deaths (95% uncertainty interval [UI] 2·50 million to 2·86 million) and 103·0 million DALYs (95% UI 96·1 million to 109·1 million). LRIs have a disproportionate effect on children younger than 5 years, responsible for 704 000 deaths (95% UI 651 000–763 000) and 60.6 million DALYs (95ÙI 56·0–65·6). Between 2005 and 2015, the number of deaths due to LRI decreased by 36·9% (95% UI 31·6 to 42·0) in children younger than 5 years, and by 3·2% (95% UI −0·4 to 6·9) in all ages. Pneumococcal pneumonia caused 55·4% of LRI deaths in all ages, totalling 1 517 388 deaths (95% UI 857 940–2 183 791). Between 2005 and 2015, improvements in air pollution exposure were responsible for a 4·3% reduction in LRI DALYs and improvements in childhood undernutrition were responsible for an 8·9% reduction. LRIs are the leading infectious cause of death and the fifth-leading cause of death overall; they are the second-leading cause of DALYs. At the global level, the burden of LRIs has decreased dramatically in the last 10 years in children younger than 5 years, although the burden in people older than 70 years has increased in many regions. LRI remains a largely preventable disease and cause of death, and continued efforts to decrease indoor and ambient air pollution, improve childhood nutrition, and scale up the use of the pneumococcal conjugate vaccine in children and adults will be essential in reducing the global burden of LRI. Bill & Melinda Gates Foundation.

Rotavirus is a leading cause of diarrhoeal mortality in children but there is considerable disagreement about how many deaths occur each year. We compared CHERG, GBD and WHO/CDC estimates of age under 5 years (U5) rotavirus deaths at the global, regional and national level using a standard year (2013) and standard list of 186 countries. The global estimates were 157,398 (CHERG), 122,322 (GBD) and 215,757 (WHO/CDC). The three groups used different methods: (i) to select data points for rotavirus-positive proportions; (ii) to extrapolate data points to individual countries; (iii) to account for rotavirus vaccine coverage; (iv) to convert rotavirus-positive proportions to rotavirus attributable fractions; and (v) to calculate uncertainty ranges. We conducted new analyses to inform future estimates. We found that acute watery diarrhoea was associated with 87% (95% CI 83-90%) of U5 diarrhoea hospitalisations based on data from 84 hospital sites in 9 countries, and 65% (95% CI 57-74%) of U5 diarrhoea deaths based on verbal autopsy reports from 9 country sites. We reanalysed data from the Global Enteric Multicenter Study (GEMS) and found 44% (55% in Asia, and 32% in Africa) rotavirus-positivity among U5 acute watery diarrhoea hospitalisations, and 28% rotavirus-positivity among U5 acute watery diarrhoea deaths. 97% (95% CI 95-98%) of the U5 diarrhoea hospitalisations that tested positive for rotavirus were entirely attributable to rotavirus. For all clinical syndromes combined the rotavirus attributable fraction was 34% (95% CI 31-36%). This increased by a factor of 1.08 (95% CI 1.02-1.14) when the GEMS results were reanalysed using a more sensitive molecular test. We developed consensus on seven proposals for improving the quality and transparency of future rotavirus mortality estimates.

The mortality and morbidity burden estimation of diarrheal diseases (DD), and Shigella and Enterotoxigenic E. Coli (ETEC) varies among different studies and by the models used for producing these estimates. Understanding the real burden of these important pathogens will guide public health and policy makers to prioritize resources for accelerating interventions against these enteric infections. In addition, long term effects, in the form of growth faltering, cognitive impairment and decreased school performance are important aspects of burden that has not been well captured. Efforts to incorporate these effects and refine their estimation, in the form of Disability Adjusted Life years (DALYs) are very important to inform the burden of diarrheal diseases and Shigella and ETEC specifically. The Institute for Health Metrics and Evaluation (IHME) at the University of Washington conducted a workshop at the VASE 2018 meeting to discuss IHME Global Burden of Diseases (GBD) modelling methods for diarrheal diseases, with a focus on ETEC and Shigella estimates in relation to other pathogens, including limitations, areas of improvements, and IHME plans for future GBD iterations.

Malnutrition among women of childbearing age is especially prevalent in Asia and sub-Saharan Africa and can be harmful to the fetus during pregnancy. In the most recently available Demographic and Health Survey (DHS), approximately 10% to 20% of pregnant women in India, Pakistan, Mali, and Tanzania were undernourished (body mass index [BMI] <18.5 kg/m2), and according to the Global Burden of Disease (GBD) 2017 study, approximately 20% of babies were born with low birth weight (LBW; <2,500 g) in India, Pakistan, and Mali and 8% in Tanzania. Supplementing pregnant women with micro and macronutrients during the antenatal period can improve birth outcomes. Recently, the World Health Organization (WHO) recommended antenatal multiple micronutrient supplementation (MMS) that includes iron and folic acid (IFA) in the context of rigorous research. Additionally, WHO recommends balanced energy protein (BEP) for undernourished populations. However, few studies have compared the cost-effectiveness of different supplementation regimens. We compared the cost-effectiveness of MMS and BEP with IFA to quantify their benefits in 4 countries with considerable prevalence of maternal undernutrition. Using nationally representative estimates from the 2017 GBD study, we conducted an individual-based dynamic microsimulation of population cohorts from birth to 2 years of age in India, Pakistan, Mali, and Tanzania. We modeled the effect of maternal nutritional supplementation on infant birth weight, stunting and wasting using effect sizes from Cochrane systematic reviews and published literature. We used a payer's perspective and obtained costs of supplementation per pregnancy from the published literature. We compared disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (ICERs) in a baseline scenario with existing antenatal IFA coverage with scenarios where 90% of antenatal care (ANC) attendees receive either universal MMS, universal BEP, or MMS + targeted BEP (women with prepregnancy BMI <18.5 kg/m2 receive BEP containing MMS while women with BMI ≥18.5 kg/m2 receive MMS). We obtained 95% uncertainty intervals (UIs) for all outputs to represent parameter and stochastic uncertainty across 100 iterations of model runs. ICERs for all scenarios were lowest in Pakistan and greatest in Tanzania, in line with the baseline trend in prevalence of and attributable burden to LBW. MMS + targeted BEP averts more DALYs than universal MMS alone while remaining cost-effective. ICERs for universal MMS compared to baseline IFA were $52 (95% UI: $28 to $78) for Pakistan, $72 (95% UI: $37 to $118) for Mali, $70 (95% UI: $43 to $104) for India, and $253 (95% UI: $112 to $481) for Tanzania. ICERs for MMS + targeted BEP compared to baseline IFA were $54 (95% UI: $32 to $77) for Pakistan, $73 (95% UI: $40 to $104) for Mali, $83 (95% UI: $58 to $111) for India, and $245 (95% UI: $127 to $405) for Tanzania. Study limitations include generalizing experimental findings from the literature to our populations of interest and using population-level input parameters that may not reflect the heterogeneity of subpopulations. Additionally, our microsimulation fuses multiple sources of data and may be limited by data quality and availability. In this study, we observed that MMS + targeted BEP averts more DALYs and remains cost-effective compared to universal MMS. As countries consider using MMS in alignment with recent WHO guidelines, offering targeted BEP is a cost-effective strategy that can be considered concurrently to maximize benefits and synergize program implementation.

Oral cholera vaccination could be deployed in a diverse range of situations from cholera-endemic areas and locations of humanitarian crises, but no clear consensus exists. The supply of licensed, WHO-prequalified cholera vaccines is not sufficient to meet endemic and epidemic needs worldwide and so prioritisation is needed. We have developed a scenario approach to systematically classify situations in which oral cholera vaccination might be useful. Our scenario approach distinguishes between five types of cholera epidemiology based on experiences from around the world and provides evidence that we hope will spur the development of detailed guidelines on how and where oral cholera vaccines could, and should, be most rationally deployed.

Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies. We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1-14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies. We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions.

Background Oral rehydration solution (ORS) is a simple intervention that can prevent childhood deaths from severe diarrhea and dehydration. In a previous study, we mapped the use of ORS treatment subnationally and found that ORS coverage increased over time, while the use of home-made alternatives or recommended home fluids (RHF) decreased, in many countries. These patterns were particularly striking within Senegal, Mali, and Sierra Leone. It was unclear, however, whether ORS replaced RHF in these locations or if children were left untreated, and if these patterns were associated with health policy changes. Methods We used a Bayesian geostatistical model and data from household surveys to map the percentage of children with diarrhea that received (1) any ORS, (2) only RHF, or (3) no oral rehydration treatment between 2000 and 2018. This approach allowed examination of whether RHF was replaced with ORS before and after interventions, policies, and external events that may have impacted healthcare access. Results We found that RHF was replaced with ORS in most Sierra Leone districts, except those most impacted by the Ebola outbreak. In addition, RHF was replaced in northern but not in southern Mali, and RHF was not replaced anywhere in Senegal. In Senegal, there was no statistical evidence that a national policy promoting ORS use was associated with increases in coverage. In Sierra Leone, ORS coverage increased following a national policy change that abolished health costs for children. Conclusions Children in parts of Mali and Senegal have been left behind during ORS scale-up. Improved messaging on effective diarrhea treatment and/or increased ORS access such as through reducing treatment costs may be needed to prevent child deaths in these areas.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 provides an up-to-date analysis of the burden of diarrhoea in 195 countries. This study assesses cases, deaths, and aetiologies in 1990–2016 and assesses how the burden of diarrhoea has changed in people of all ages. We modelled diarrhoea mortality with a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We modelled diarrhoea incidence with a compartmental meta-regression tool that enforces an association between incidence and prevalence, and relies on scientific literature, population representative surveys, and health-care data. Diarrhoea deaths and episodes were attributed to 13 pathogens by use of a counterfactual population attributable fraction approach. Diarrhoea risk factors are also based on counterfactual estimates of risk exposure and the association between the risk and diarrhoea. Each modelled estimate accounted for uncertainty. In 2016, diarrhoea was the eighth leading cause of death among all ages (1 655 944 deaths, 95% uncertainty interval [UI] 1 244 073–2 366 552) and the fifth leading cause of death among children younger than 5 years (446 000 deaths, 390 894–504 613). Rotavirus was the leading aetiology for diarrhoea mortality among children younger than 5 years (128 515 deaths, 105 138–155 133) and among all ages (228 047 deaths, 183 526–292 737). Childhood wasting (low weight-for-height score), unsafe water, and unsafe sanitation were the leading risk factors for diarrhoea, responsible for 80·4% (95% UI 68·2–85·0), 72·1% (34·0–91·4), and 56·4% (49·3–62·7) of diarrhoea deaths in children younger than 5 years, respectively. Prevention of wasting in 1762 children (95% UI 1521–2170) could avert one death from diarrhoea. Substantial progress has been made globally in reducing the burden of diarrhoeal diseases, driven by decreases in several primary risk factors. However, this reduction has not been equal across locations, and burden among adults older than 70 years requires attention. Bill & Melinda Gates Foundation.