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      Estimating national-level measles case–fatality ratios in low-income and middle-income countries: an updated systematic review and modelling study

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          Summary

          Background

          To understand the current measles mortality burden, and to mitigate the future burden, it is crucial to have robust estimates of measles case fatalities. Estimates of measles case–fatality ratios (CFRs) that are specific to age, location, and time are essential to capture variations in underlying population-level factors, such as vaccination coverage and measles incidence, which contribute to increases or decreases in CFRs. In this study, we updated estimates of measles CFRs by expanding upon previous systematic reviews and implementing a meta-regression model. Our objective was to use all information available to estimate measles CFRs in low-income and middle-income countries (LMICs) by country, age, and year.

          Methods

          For this systematic review and meta-regression modelling study, we searched PubMed on Dec 31, 2020 for all available primary data published from Jan 1, 1980 to Dec 31, 2020, on measles cases and fatalities occurring up to Dec 31, 2019 in LMICs. We included studies that previous systematic reviews had included or which contained primary data on measles cases and deaths from hospital-based, community-based, or surveillance-based reports, including outbreak investigations. We excluded studies that were not in humans, or reported only data that were only non-primary, or on restricted populations (eg, people living with HIV), or on long-term measles mortality (eg, death from subacute sclerosing panencephalitis), and studies that did not include country-level data or relevant information on measles cases and deaths, or were for a high-income country. We extracted summary data on measles cases and measles deaths from studies that fitted our inclusion and exclusion criteria. Using these data and a suite of covariates related to measles CFRs, we implemented a Bayesian meta-regression model to produce estimates of measles CFRs from 1990 to 2019 by location and age group. This study was not registered with PROSPERO or otherwise.

          Findings

          We identified 2705 records, of which 208 sources contained information on both measles cases and measles deaths in LMICS and were included in the review. Between 1990 and 2019, CFRs substantially decreased in both community-based and hospital-based settings, with consistent patterns across age groups. For people aged 0–34 years, we estimated a mean CFR for 2019 of 1·32% (95% uncertainty interval [UI] 1·28–1·36) among community-based settings and 5·35% (5·08–5·64) among hospital-based settings. We estimated the 2019 CFR in community-based settings to be 3·03% (UI 2·89–3·16) for those younger than 1 year, 1·63% (1·58–1·68) for age 1–4 years, 0·84% (0·80–0·87) for age 5–9 years, and 0·67% (0·64–0·70) for age 10–14 years.

          Interpretation

          Although CFRs have declined between 1990 and 2019, there are still large heterogeneities across locations and ages. One limitation of this systematic review is that we were unable to assess measles CFR among particular populations, such as refugees and internally displaced people. Our updated methodological framework and estimates could be used to evaluate the effect of measles control and vaccination programmes on reducing the preventable measles mortality burden.

          Funding

          Bill & Melinda Gates Foundation; Gavi, the Vaccine Alliance; and the US National Institutes of Health.

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          Most cited references20

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          Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

          Summary Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding Bill & Melinda Gates Foundation.
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            Guidelines for Accurate and Transparent Health Estimates Reporting: the GATHER statement

            Measurements of health indicators are rarely available for every population and period of interest, and available data may not be comparable. The Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) define best reporting practices for studies that calculate health estimates for multiple populations (in time or space) using multiple information sources. Health estimates that fall within the scope of GATHER include all quantitative population-level estimates (including global, regional, national, or subnational estimates) of health indicators, including indicators of health status, incidence and prevalence of diseases, injuries, and disability and functioning; and indicators of health determinants, including health behaviours and health exposures. GATHER comprises a checklist of 18 items that are essential for best reporting practice. A more detailed explanation and elaboration document, describing the interpretation and rationale of each reporting item along with examples of good reporting, is available on the GATHER website.
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              Impacts of COVID-19 on childhood malnutrition and nutrition-related mortality

              The unprecedented global social and economic crisis triggered by the COVID-19 pandemic poses grave risks to the nutritional status and survival of young children in low-income and middle-income countries (LMICs). Of particular concern is an expected increase in child malnutrition, including wasting, due to steep declines in household incomes, changes in the availability and affordability of nutritious foods, and interruptions to health, nutrition, and social protection services. 1 One in ten deaths among children younger than 5 years in LMICs is attributable to severe wasting because wasted children are at increased risk of mortality from infectious diseases. 2 Before the COVID-19 pandemic, an estimated 47 million children younger than 5 years were moderately or severely wasted, most living in sub-Saharan Africa and south Asia. 3 The economic, food, and health systems disruptions resulting from the COVID-19 pandemic are expected to continue to exacerbate all forms of malnutrition. Estimates from the International Food Policy Research Institute suggest that because of the pandemic an additional 140 million people will be thrown into living in extreme poverty on less than US$1·90 per day in 2020. 4 According to the World Food Programme, the number of people in LMICs facing acute food insecurity will nearly double to 265 million by the end of 2020. 5 Sharp declines are expected in access to child health and nutrition services, similar to those seen during the 2014–16 outbreak of Ebola virus disease in sub-Saharan Africa. 6 Early in the COVID-19 pandemic, UNICEF estimated a 30% overall reduction in essential nutrition services coverage, reaching 75–100% in lockdown contexts, including in fragile countries where there are humanitarian crises. 7 The accompanying call to action on child malnutrition and COVID-19 from leaders of four UN agencies 8 in The Lancet is an important first step for the international community. Alongside these efforts, the Standing Together for Nutrition consortium, a multidisciplinary consortium of nutrition, economics, food, and health systems researchers, is working to estimate the scale and reach of nutrition challenges related to COVID-19. These efforts link three approaches to model the combined economic and health systems impacts from COVID-19 on malnutrition and mortality: MIRAGRODEP's macroeconomic projections of impacts on per capita gross national income (GNI); 4 microeconomic estimates of how predicted GNI shocks impact child wasting using data on 1·26 million children from 177 Demographic Health Surveys (DHS) conducted in 52 LMICs between 1990–2018; 9 and the Lives Saved Tool (LiST), which links country-specific health services disruptions and predicted increases in wasting to child mortality. 10 What do our initial analyses and estimates suggest? First, the MIRAGRODEP projections suggest that even fairly short lockdown measures, combined with severe mobility disruptions and comparatively moderate food systems disruptions, result in most LMICs having an estimated average 7·9% (SD 2·4%) decrease in GNI per capita relative to pre-COVID-19 projections. 4 Second, the microeconomic model projections indicate that decreases in GNI per capita are associated with large increases in child wasting. 9 Our own analyses, based on these estimates applied to 118 LMICs, suggest there could be a 14·3% increase in the prevalence of moderate or severe wasting among children younger than 5 years due to COVID-19-related predicted country-specific losses in GNI per capita. We estimate this would translate to an additional estimated 6·7 million children with wasting in 2020 compared with projections for 2020 without COVID-19; an estimated 57·6% of these children are in south Asia and an estimated 21·8% in sub-Saharan Africa. © 2020 Reuters/Jorge Cabrera 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Third, when the projected increase in wasting in each country is combined with a projected year average of 25% reduction in coverage of nutrition and health services, we estimate there would be 128 605 (ranging from 111 193 to 178 510 for best and worst case scenarios) additional deaths in children younger than 5 years during 2020, with an estimated 52% of these deaths in sub-Saharan Africa. The range reflects coverage scenarios, as previously described by Roberton and colleagues, 10 using a low of 15% and high of 50% disruption in vitamin A supplementation, treatment of severe wasting, promotion of improved young child feeding, and provision of micronutrient supplements to pregnant women. Our projections emphasise the crucial need for the actions to protect child nutrition that are urged by the UN leaders in the accompanying Comment. 8 These actions require rapid mobilisation of domestic and donor resources at a time when most national economies are reeling from COVID-19-related losses. In 2017, the Word Bank estimated that $7 billion per year over 10 years is needed to reach the global Sustainable Development Goal nutrition targets. 11 These estimates need to be revised upwards to overcome COVID-19-related setbacks. The COVID-19 pandemic is expected to increase the risk of all forms of malnutrition. The wasting-focused estimates we present here are likely to be conservative, given that the duration of this crisis is unknown, and its full impacts on food, health, and social protection systems are yet to be realised. The disruption of other health services during lockdowns will further compromise maternal and child health and mortality, 10 and with the deepening of economic and food systems crises, other forms of malnutrition, including child stunting, micronutrient malnutrition, and maternal nutrition, are expected to increase. 1 Without adequate action, the profound impact of the COVID-19 pandemic on early life nutrition could have intergenerational consequences for child growth and development and life-long impacts on education, chronic disease risks, and overall human capital formation. 12 Forthcoming analyses by this consortium will examine a range of diet and nutrition outcomes in women and young children and provide consensus advice on multisectoral actions and resources needed to recover and support optimal nutrition now and into the future.
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                Author and article information

                Contributors
                Journal
                Lancet Glob Health
                Lancet Glob Health
                The Lancet. Global Health
                Elsevier Ltd
                2214-109X
                14 March 2023
                April 2023
                14 March 2023
                : 11
                : 4
                : e516-e524
                Affiliations
                [a ]Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
                [b ]Institute of Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
                [c ]Department of Health Metrics Sciences, University of Washington, Seattle, WA, USA
                [d ]Department of Biology, The Pennsylvania State University, University Park, PA, USA
                [e ]Department of Immunization, Vaccines, and Biologicals, WHO, Geneva, Switzerland
                [f ]Global Development Division, Bill & Melinda Gates Foundation, Seattle, WA, USA
                [g ]Center for Health Decision Science, Harvard T H Chan School of Public Health, Boston, MA, USA
                Author notes
                [* ]Correspondence to: Ms Alyssa N Sbarra, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK alyssa.sbarra@ 123456lshtm.ac.uk
                Article
                S2214-109X(23)00043-8
                10.1016/S2214-109X(23)00043-8
                10030458
                36925172
                9249c903-1ac5-4a7b-ba29-3429766d4e80
                © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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