United Nations Children's Fund

An estimated 2.6 million third trimester stillbirths occurred in 2015 (uncertainty range 2.4-3.0 million). The number of stillbirths has reduced more slowly than has maternal mortality or mortality in children younger than 5 years, which were explicitly targeted in the Millennium Development Goals. The Every Newborn Action Plan has the target of 12 or fewer stillbirths per 1000 births in every country by 2030. 94 mainly high-income countries and upper middle-income countries have already met this target, although with noticeable disparities. At least 56 countries, particularly in Africa and in areas affected by conflict, will have to more than double present progress to reach this target. Most (98%) stillbirths are in low-income and middle-income countries. Improved care at birth is essential to prevent 1.3 million (uncertainty range 1.2-1.6 million) intrapartum stillbirths, end preventable maternal and neonatal deaths, and improve child development. Estimates for stillbirth causation are impeded by various classification systems, but for 18 countries with reliable data, congenital abnormalities account for a median of only 7.4% of stillbirths. Many disorders associated with stillbirths are potentially modifiable and often coexist, such as maternal infections (population attributable fraction: malaria 8.0% and syphilis 7.7%), non-communicable diseases, nutrition and lifestyle factors (each about 10%), and maternal age older than 35 years (6.7%). Prolonged pregnancies contribute to 14.0% of stillbirths. Causal pathways for stillbirth frequently involve impaired placental function, either with fetal growth restriction or preterm labour, or both. Two-thirds of newborns have their births registered. However, less than 5% of neonatal deaths and even fewer stillbirths have death registration. Records and registrations of all births, stillbirths, neonatal, and maternal deaths in a health facility would substantially increase data availability. Improved data alone will not save lives but provide a way to target interventions to reach more than 7000 women every day worldwide who experience the reality of stillbirth.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality and is associated with long-term physical, neurodevelopmental, and socioeconomic effects. This study updated national preterm birth rates and trends, plus novel estimates by gestational age subgroups, to inform progress towards global health goals and targets, and aimed to update country, regional, and global estimates of preterm birth for 2020 in addition to trends between 2010 and 2020. METHODS: We systematically searched population-based, nationally representative data on preterm birth from Jan 1, 2010, to Dec 31, 2020 and study data (26 March-14 April, 2021) for countries and areas with no national-level data. The analysis included 679 data points (86% nationally representative administrative data [582 of 679 data points]) from 103 countries and areas (62% of countries and areas having nationally representative administrative data [64 of 103 data points]). A Bayesian hierarchical regression was used for estimating country-level preterm rates, which incoporated country-specific intercepts, low birthweight as a covariate, non-linear time trends, and bias adjustments based on a data quality categorisation, and other indicators such as method of gestational age estimation. FINDINGS: An estimated 13·4 million (95% credible interval [CrI] 12·3-15·2 million) newborn babies were born preterm (<37 weeks) in 2020 (9·9% of all births [95% CrI 9·1-11·2]) compared with 13·8 million (12·7-15·5 million) in 2010 (9·8% of all births [9·0-11·0]) worldwide. The global annual rate of reduction was estimated at -0·14% from 2010 to 2020. In total, 55·6% of total livebirths are in southern Asia (26·8% [36 099 000 of 134 767 000]) and sub-Saharan Africa (28·7% [38 819 300 of 134 767 000]), yet these two regions accounted for approximately 65% (8 692 000 of 13 376 200) of all preterm births globally in 2020. Of the 33 countries and areas in the highest data quality category, none were in southern Asia or sub-Saharan Africa compared with 94% (30 of 32 countries) in high-income countries and areas. Worldwide from 2010 to 2020, approximately 15% of all preterm births occurred at less than 32 weeks of gestation, requiring more neonatal care (<28 weeks: 4·2%, 95% CI 3·1-5·0, 567 800 [410 200-663 200 newborn babies]); 28-32 weeks: 10·4% [9·5-10·6], 1 392 500 [1 274 800-1 422 600 newborn babies]). INTERPRETATION: There has been no measurable change in preterm birth rates over the last decade at global level. Despite increasing facility birth rates and substantial focus on routine health data systems, there remain many missed opportunities to improve preterm birth data. Gaps in national routine data for preterm birth are most marked in regions of southern Asia and sub-Saharan Africa, which also have the highest estimated burden of preterm births. Countries need to prioritise programmatic investments to prevent preterm birth and to ensure evidence-based quality care when preterm birth occurs. Investments in improving data quality are crucial so that preterm birth data can be improved and used for action and accountability processes. FUNDING: The Children's Investment Fund Foundation and the UNDP, United Nations Population Fund-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

BACKGROUND: Low birthweight (LBW) of less than 2500 g is an important marker of maternal and fetal health, predicting mortality, stunting, and adult-onset chronic conditions. Global nutrition targets set at the World Health Assembly in 2012 include an ambitious 30% reduction in LBW prevalence between 2012 and 2025. Estimates to track progress towards this target are lacking; with this analysis, we aim to assist in setting a baseline against which to assess progress towards the achievement of the World Health Assembly targets. METHODS: We sought to identify all available LBW input data for livebirths for the years 2000-16. We considered population-based national or nationally representative datasets for inclusion if they contained information on birthweight or LBW prevalence for livebirths. A new method for survey adjustment was developed and used. For 57 countries with higher quality time-series data, we smoothed country-reported trends in birthweight data by use of B-spline regression. For all other countries, we estimated LBW prevalence and trends by use of a restricted maximum likelihood approach with country-level random effects. Uncertainty ranges were obtained through bootstrapping. Results were summed at the regional and worldwide level. FINDINGS: We collated 1447 country-years of birthweight data (281 million births) for 148 countries of 195 UN member states (47 countries had no data meeting inclusion criteria). The estimated worldwide LBW prevalence in 2015 was 14·6% (uncertainty range [UR] 12·4-17·1) compared with 17·5% (14·1-21·3) in 2000 (average annual reduction rate [AARR] 1·23%). In 2015, an estimated 20·5 million (UR 17·4-24·0 million) livebirths were LBW, 91% from low-and-middle income countries, mainly southern Asia (48%) and sub-Saharan Africa (24%). INTERPRETATION: Although these estimates suggest some progress in reducing LBW between 2000 and 2015, achieving the 2·74% AARR required between 2012 and 2025 to meet the global nutrition target will require more than doubling progress, involving both improved measurement and programme investments to address the causes of LBW throughout the lifecycle. FUNDING: Bill & Melinda Gates Foundation, The Children's Investment Fund Foundation, United Nations Children's Fund (UNICEF), and WHO.

BACKGROUND: Previous estimates have highlighted a large global burden of stillbirths, with an absence of reliable data from regions where most stillbirths occur. The Every Newborn Action Plan (ENAP) targets national stillbirth rates (SBRs) of 12 or fewer stillbirths per 1000 births by 2030. We estimate SBRs and numbers for 195 countries, including trends from 2000 to 2015. METHODS: We collated SBR data meeting prespecified inclusion criteria from national routine or registration systems, nationally representative surveys, and other data sources identified through a systematic review, web-based searches, and consultation with stillbirth experts. We modelled SBR (≥28 weeks' gestation) for 195 countries with restricted maximum likelihood estimation with country-level random effects. Uncertainty ranges were obtained through a bootstrap approach. FINDINGS: Data from 157 countries (2207 datapoints) met the inclusion criteria, a 90% increase from 2009 estimates. The estimated average global SBR in 2015 was 18·4 per 1000 births, down from 24·7 in 2000 (25·5% reduction). In 2015, an estimated 2·6 million (uncertainty range 2·4-3·0 million) babies were stillborn, giving a 19% decline in numbers since 2000 with the slowest progress in sub-Saharan Africa. 98% of all stillbirths occur in low-income and middle-income countries; 77% in south Asia and sub-Saharan Africa. INTERPRETATION: Progress in reducing the large worldwide stillbirth burden remains slow and insufficient to meet national targets such as for ENAP. Stillbirths are increasingly being counted at a local level, but countries and the global community must further improve the quality and comparability of data, and ensure that this is more clearly linked to accountability processes including the Sustainable Development Goals. FUNDING: Save the Children's Saving Newborn Lives programme to The London School of Hygiene & Tropical Medicine.

Despite dramatic improvements in survival, nutrition, and education over recent decades, today's children face an uncertain future. Climate change, ecological degradation, migrating populations, conflict, pervasive inequalities, and predatory commercial practices threaten the health and future of children in every country. In 2015, the world's countries agreed on the Sustainable Development Goals (SDGs), yet nearly 5 years later, few countries have recorded much progress towards achieving them. This Commission presents the case for placing children, aged 0-18 years, at the centre of the SDGs: at the heart of the concept of sustainability and our shared human endeavour. Governments must harness coalitions across sectors to overcome ecological and commercial pressures to ensure children receive their rights and entitlements now and a liveable planet in the years to come.

BACKGROUND: Reducing neonatal mortality is an essential part of the third Sustainable Development Goal (SDG), to end preventable child deaths. To achieve this aim will require an understanding of the levels of and trends in neonatal mortality. We therefore aimed to estimate the levels of and trends in neonatal mortality by use of a statistical model that can be used to assess progress in the SDG era. With these estimates of neonatal mortality between 1990 and 2017, we then aimed to assess how different targets for neonatal mortality could affect the burden of neonatal mortality from 2018 to 2030. METHODS: In this systematic analysis, we used nationally-representative empirical data related to neonatal mortality, including data from vital registration systems, sample registration systems, and household surveys, to estimate country-specific neonatal mortality rates (NMR; the probability of dying during the first 28 days of life) for all countries between 1990 (or the earliest year of available data) and 2017. For our analysis, we used all publicly available data on neonatal mortality from databases compiled annually by the UN Inter-agency Group for Child Mortality Estimation, which were extracted on or before July 31, 2018, for data relating to the period between 1950 and 2017. All nationally representative data were assessed. We used a Bayesian hierarchical penalised B-splines regression model, which allowed for data from different sources to be weighted differently, to account for variable biases and for the uncertainty in NMR to be assessed. The model simultaneously estimated a global association between NMR and under-5 mortality rate and country-specific and time-specific effects, which enabled us to identify countries with an NMR that was higher or lower than expected. Scenario-based projections were made at the county level by use of current levels of and trends in neonatal mortality and historic or annual rates of reduction that would be required to achieve national targets. The main outcome that we assessed was the levels of and trends in neonatal mortality and the global and regional NMRs from 1990 to 2017. FINDINGS: Between 1990 and 2017, the global NMR decreased by 51% (90% uncertainty interval [UI] 46-54), from 36·6 deaths per 1000 livebirths (35·5-37·8) in 1990, to 18·0 deaths per 1000 livebirths (17·0-19·9) in 2017. The estimated number of neonatal deaths during the same period decreased from 5·0 million (4·9 million-5·2 million) to 2·5 million (2·4 million-2·8 million). Annual NMRs vary widely across the world, but west and central Africa and south Asia had the highest NMRs in 2017. All regions have reported reductions in NMRs since 1990, and most regions accelerated progress in reducing neonatal mortality in 2000-17 versus 1990-2000. Between 2018 and 2030, we project that 27·8 million children will die in their first month of life if each country maintains its current rate of reduction in NMR. If each country achieves the SDG neonatal mortality target of 12 deaths per 1000 livebirths or fewer by 2030, we project 22·7 million cumulative neonatal deaths by 2030. More than 60 countries need to accelerate their progress to reach the neonatal mortality SDG target by 2030. INTERPRETATION: Although substantial progress has been made in reducing neonatal mortality since 1990, increased efforts to improve progress are still needed to achieve the SDG target by 2030. Accelerated improvements are most needed in the regions and countries with high NMR, particularly in sub-Saharan Africa and south Asia. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development.

BACKGROUND: National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010. METHODS: Small for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses. FINDINGS: In 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of term-SGA babies ranged from 5·3% of livebirths in east Asia to 41·5% in south Asia, and the prevalence of preterm-SGA infants ranged from 1·2% in north Africa to 3·0% in southeast Asia. Of 18 million low-birthweight babies, 59% were term-SGA and 41% were preterm-SGA. Two-thirds of small-for-gestational-age infants were born in Asia (17·4 million in south Asia). Preterm-SGA babies totalled 2·8 million births in low-income and middle-income countries. Most small-for-gestational-age infants were born in India, Pakistan, Nigeria, and Bangladesh. INTERPRETATION: The burden of small-for-gestational-age births is very high in countries of low and middle income and is concentrated in south Asia. Implementation of effective interventions for babies born too small or too soon is an urgent priority to increase survival and reduce disability, stunting, and non-communicable diseases. FUNDING: Bill & Melinda Gates Foundation by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group (CHERG).

WHO/UNICEF estimates for HPV vaccination coverage from 2010 to 2019 are analyzed against the backdrop of the 90% coverage target for HPV vaccination by 2030 set in the recently approved global strategy for cervical cancer elimination as a public health problem. As of June 2020, 107 (55%) of the 194 WHO Member States have introduced HPV vaccination. The Americas and Europe are by far the WHO regions with the most introductions, 85% and 77% of their countries having already introduced respectively. A record number of introductions was observed in 2019, most of which in low- and middle- income countries (LMIC) where access has been limited. Programs had an average performance coverage of around 67% for the first dose and 53% for the final dose of HPV. LMICs performed on average better than high- income countries for the first dose, but worse for the last dose due to higher dropout. Only 5 (6%) countries achieved coverages with the final dose of more than 90%, 22 countries (21%) achieved coverages of 75% or higher while 35 (40%) had a final dose coverage of 50% or less. When expressed as world population coverage (i.e., weighted by population size), global coverage of the final HPV dose for 2019 is estimated at 15%. There is a long way to go to meet the 2030 elimination target of 90%. In the post-COVID era attention should be paid to maintain the pace of introductions, specially ensuring the most populous countries introduce, and further improving program performance globally.

OBJECTIVE: It is widely assumed that growth faltering starts at around 3 months of age, but there has been no systematic assessment of its timing using representative national datasets from a variety of countries. METHODOLOGY: The World Health Organization Global Database on Child Growth and Malnutrition includes the results of 39 nationally representative datasets from recent surveys in developing countries. Based on these data, mean z scores of weight for age, length/height for age, and weight for length/height were compared with the National Center for Health Statistics and Cambridge growth references, for children younger than 60 months. RESULTS: Mean weights start to falter at about 3 months of age and decline rapidly until about 12 months, with a markedly slower decline until about 18 to 19 months and a catch-up pattern after that. Growth faltering in weight for length/height is restricted to the first 15 months of life, followed by rapid improvement. For length/height for age, the global mean is surprisingly close to National Center for Health Statistics and Cambridge references at birth, but faltering starts immediately afterward, lasting well into the third year. CONCLUSIONS: These findings highlight the need for prenatal and early life interventions to prevent growth failure.

The property of 109 CD4+ T cell clones (TCC) to induce IgE synthesis in vitro in human B cells was compared with their ability to produce IL-2, IL-4, and IFN-gamma in their supernatants (SUP) after 24-h stimulation with PHA. A significant positive correlation was found between the property of TCC to induce or enhance spontaneous IgE synthesis and their ability to release IL-4. In contrast, there was an inverse relationship between the IgE helper activity of TCC and their ability to release IFN-gamma, whereas no statistical correlation between the property to induce IgE synthesis and to produce IL-2 was observed. The ability of PHA-SUP from 71 CD4+ TCC to induce IgE synthesis in B cells was also investigated. Twenty-nine SUP (all derived from TCC active on IgE synthesis) induced production of substantial amounts of IgE in target B cells. There was a correlation between the amount of IgE synthesized by B cells in response to these SUP and their IL-4 content. An even higher correlation was found between the IgE synthesis induced by these SUP and the ratio between the amount of IL-4 and IFN-gamma present in the same SUP. Like IL-4-containing SUP, rIL-4 also showed the ability to induce IgE production in B cells from both atopic and nonatopic donors. The addition to B cell cultures of anti-IL-4 antibody virtually abolished not only the IgE synthesis induced by rIL-4, but also that stimulated by TCC and their SUP. In contrast, the IgG synthesis induced by TCC SUP was not or only slightly inhibited by the anti-IL-4 antibody. These data indicate that IL-4 is an essential mediator for the IgE synthesis induced in vitro by human TCC and their SUP in the absence of a polyclonal activator, whereas IFN-gamma seems to exert a negative regulatory effect on the production of IgE.

ABSTRACT Household investment mistakes are an important concern for researchers and policymakers alike. Portfolio underdiversification ranks among those mistakes that are potentially most costly. However, its roots and empirical importance are poorly understood. I estimate quantitatively meaningful diversification statistics and investigate their relationship with key variables. Nearly all households that score high on financial literacy or rely on professionals or private contacts for advice achieve reasonable investment outcomes. Compared to these groups, households with below‐median financial literacy that trust their own decision‐making capabilities lose an expected 50 bps on average. All group differences stem from the top of the loss distribution.

BACKGROUND: The evidence on the economic burden of cardiovascular disease (CVD) in low- and middle- income countries (LMICs) remains scarce. We conducted a comprehensive systematic review to establish the magnitude and knowledge gaps in relation to the economic burden of CVD and hypertension on households, health systems and the society. METHODS: We included studies using primary or secondary data to produce original economic estimates of the impact of CVD. We searched sixteen electronic databases from 1990 onwards without language restrictions. We appraised the quality of included studies using a seven-question assessment tool. RESULTS: Eighty-three studies met the inclusion criteria, most of which were single centre retrospective cost studies conducted in secondary care settings. Studies in China, Brazil, India and Mexico contributed together 50% of the total number of economic estimates identified. The quality of the included studies was generally low. Reporting transparency, particularly for cost data sources and results, was poor. The costs per episode for hypertension and generic CVD were fairly homogeneous across studies; ranging between $500 and $1500. In contrast, for coronary heart disease (CHD) and stroke cost estimates were generally higher and more heterogeneous, with several estimates in excess of $5000 per episode. The economic perspective and scope of the study appeared to impact cost estimates for hypertension and generic CVD considerably less than estimates for stroke and CHD. Most studies reported monthly costs for hypertension treatment around $22. Average monthly treatment costs for stroke and CHD ranged between $300 and $1000, however variability across estimates was high. In most LMICs both the annual cost of care and the cost of an acute episode exceed many times the total health expenditure per capita. CONCLUSIONS: The existing evidence on the economic burden of CVD in LMICs does not appear aligned with policy priorities in terms of research volume, pathologies studied and methodological quality. Not only is more economic research needed to fill the existing gaps, but research quality needs to be drastically improved. More broadly, national-level studies with appropriate sample sizes and adequate incorporation of indirect costs need to replace small-scale, institutional, retrospective cost studies.

BACKGROUND: Stillbirths are a major public health issue and a sensitive marker of the quality of care around pregnancy and birth. The UN Global Strategy for Women's, Children's and Adolescents' Health (2016-30) and the Every Newborn Action Plan (led by UNICEF and WHO) call for an end to preventable stillbirths. A first step to prevent stillbirths is obtaining standardised measurement of stillbirth rates across countries. We estimated stillbirth rates and their trends for 195 countries from 2000 to 2019 and assessed progress over time. METHODS: For a systematic assessment, we created a dataset of 2833 country-year datapoints from 171 countries relevant to stillbirth rates, including data from registration and health information systems, household-based surveys, and population-based studies. After data quality assessment and exclusions, we used 1531 datapoints to estimate country-specific stillbirth rates for 195 countries from 2000 to 2019 using a Bayesian hierarchical temporal sparse regression model, according to a definition of stillbirth of at least 28 weeks' gestational age. Our model combined covariates with a temporal smoothing process such that estimates were informed by data for country-periods with high quality data, while being based on covariates for country-periods with little or no data on stillbirth rates. Bias and additional uncertainty associated with observations based on alternative stillbirth definitions and source types, and observations that were subject to non-sampling errors, were included in the model. We compared the estimated stillbirth rates and trends to previously reported mortality estimates in children younger than 5 years. FINDINGS: Globally in 2019, an estimated 2·0 million babies (90% uncertainty interval [UI] 1·9-2·2) were stillborn at 28 weeks or more of gestation, with a global stillbirth rate of 13·9 stillbirths (90% UI 13·5-15·4) per 1000 total births. Stillbirth rates in 2019 varied widely across regions, from 22·8 stillbirths (19·8-27·7) per 1000 total births in west and central Africa to 2·9 (2·7-3·0) in western Europe. After west and central Africa, eastern and southern Africa and south Asia had the second and third highest stillbirth rates in 2019. The global annual rate of reduction in stillbirth rate was estimated at 2·3% (90% UI 1·7-2·7) from 2000 to 2019, which was lower than the 2·9% (2·5-3·2) annual rate of reduction in neonatal mortality rate (for neonates aged <28 days) and the 4·3% (3·8-4·7) annual rate of reduction in mortality rate among children aged 1-59 months during the same period. Based on the lower bound of the 90% UIs, 114 countries had an estimated decrease in stillbirth rate since 2000, with four countries having a decrease of at least 50·0%, 28 having a decrease of 25·0-49·9%, 50 having a decrease of 10·0-24·9%, and 32 having a decrease of less than 10·0%. For the remaining 81 countries, we found no decrease in stillbirth rate since 2000. Of these countries, 34 were in sub-Saharan Africa, 16 were in east Asia and the Pacific, and 15 were in Latin America and the Caribbean. INTERPRETATION: Progress in reducing the rate of stillbirths has been slow compared with decreases in the mortality rate of children younger than 5 years. Accelerated improvements are most needed in the regions and countries with high stillbirth rates, particularly in sub-Saharan Africa. Future prevention of stillbirths needs increased efforts to raise public awareness, improve data collection, assess progress, and understand public health priorities locally, all of which require investment. FUNDING: Bill & Melinda Gates Foundation and the UK Foreign, Commonwealth and Development Office.

In the present study, we have investigated the ability of human T cells to secrete IL-2, IL-4, and IFN-gamma. IL-4 and IFN-gamma were quantified with enzymatic immunoassays and IL-2 with a biologic assay by using the murine IL-2-dependent cell line CTLL-2. PBL, stimulated with Con A or with a combination of the phorbol ester 13-O-tetradecanoylphorbol-12-acetate and the Ca2+ ionophore A23187 secreted IL-2, IL-4, and IFN-gamma. The kinetics of the secretion of the three lymphokines was investigated with two CD4+ clones; one (GEO-2) that produced IL-2, IL-4, and IFN-gamma and another (HY640), that produced only IL-2 and IFN-gamma. Significant IL-2, IL-4, and IFN-gamma production was observed after only 8 h of activation. Maximal levels of IL-2 and IL-4 were found 20 h after the onset of the stimulation which subsequently decreased. In contrast, IFN-gamma levels continued to increase in a period up to 40 h and then leveled off. In spite of these differences in secretion, the kinetics of accumulation of mRNA did not differ. The IL-2, IL-4, and IFN-gamma mRNA were detectable 2 h after stimulation and continued to accumulate for a period up to 20 h. In a series of 22 CD4+ clones, 21 were able to secrete all three lymphokines upon stimulation. Almost all CD8+ clones were able to produce IL-2 and IFN-gamma, but only six of the 23 CD8+ T cell clones secreted IL-4. In addition, five CD4+ (allo)antigen-specific T cell clones were tested for IL-2, IL-4, and IFN-gamma secretion upon specific stimulation. Two alloantigen-specific and two tetanus toxoid-specific T cell clones secreted IL-2, IL-4, and IFN-gamma simultaneously, whereas one alloantigen-specific T cell clone secreted IL-2 and IFN-gamma, but not IL-4. A supernatant of the CD4+ T cell clone GEO-2, that contained high levels of IFN-gamma and IL-4, was unable to induce the low affinity receptor for IgE, CD23, on a Burkitt lymphoma cell line. However, after separation of IL-4 from IFN-gamma by using HPLC, the IL-4-containing fraction-induced CD23, which could be blocked by the fraction that contained IFN-gamma and by a polyclonal rabbit anti-IL-4 antiserum. Finally, the partly purified IL-4, that was devoid of IL-2, promoted the growth of the clone GEO-2.

The ongoing pandemic caused by SARS-CoV-2, the causal agent of the acute respiratory distress syndrome COVID-19, is placing unprecedented stress on healthcare systems and societies as a whole. The rapid spread of the virus in the absence of targeted therapies or a vaccine, is forcing countries to respond with strong preventative measures ranging from mitigation to containment. In extreme cases, quarantines are being imposed, limiting mobility to varying degrees. While quarantines are an effective measure of infection control, they can lead to significant social, economic and psychological consequences. Social distancing fosters isolation; exposes personal and collective vulnerabilities while limiting accessible and familiar support options. The inability to work has immediate economic repercussions and deprives many individuals of essential livelihoods and health care benefits. Psychological consequences may range from stress, frustration and anger to severe depression and post-traumatic stress disorder (PTSD). A recent review drawing on lessons from past pandemics shows the length of quarantine increases the risk for serious psychological consequences [1Brooks S.K. Webster R.K. Smith L.E. Woodland L. Wessely S. Greenberg N. et al.The psychological impact of quarantine and how to reduce it: rapid review of the evidence.Lancet. 2020; 395: 912-920Summary Full Text Full Text PDF PubMed Scopus (10176) Google Scholar]. A relevant, yet frequently ignored risk during a pandemic and its socially disrupting response, is the potential increase of intimate partner violence (IPV) [2Peterman A. Potts A. O'Donnell M. Thompson K. Shah N. Oertelt-Prigione S. et al.Pandemics and violence against women and children.Center Global Dev Work Paper 528. 2020; Google Scholar]. IPV is defined as physical, sexual, psychological, or economic violence that occurs between former or current intimate partners. While men can also be affected, IPV is a gendered phenomenon largely perpetrated against women by male partners [3Fulu E. Jewkes R. Roselli T. Garcia-Moreno G. on on behalf of the UN Multi-country Cross-sectional Study on Men and Violence research teamPrevalence of and factors associated with male perpetration of intimate partner violence: findings from the UN multi-country cross-sectional study on men and violence in Asia and the Pacific.Lancet Glob Health. 2013; 1: e187-e207Summary Full Text Full Text PDF PubMed Scopus (372) Google Scholar] and approximately one in three women worldwide will experience physical and/or sexual IPV in her lifetime [4Devries K.M. Mak J.Y. Garcia-Moreno C. Petzold M. Child J.C. Falder G. et al.Global health. The global prevalence of intimate partner violence against women.Science. 2013; 340: 1527-1528Crossref PubMed Scopus (1036) Google Scholar]. Many of the strategies employed in abusive relations overlap with the social measures imposed during quarantine. Next to physical and geographical isolation, IPV survivors describe social isolation (i.e., from family and friends), functional isolation (e.g., when peers or support systems appear to exist but are unreliable or have alliances with the perpetrator), surveillance, and control of daily activities [5Hagan Raghavan Doychak Functional isolation: understanding isolation in trafficking survivors.Sex Abuse. 2019; https://doi.org/10.1177/1079063219889059Crossref PubMed Scopus (16) Google Scholar]. During quarantine, measures intentionally imposed in an abusive partnership, may be enforced on a massive scale in the attempt to save lives. Isolation paired with greater exposure, psychological and economic stressors, as well as potential increases in negative coping mechanisms (i.e., excessive alcohol consumption) can trigger an unprecedented wave of IPV. Recent anecdotal reports from Australia, Brazil, China, and the United States already indicate increases in IPV due to quarantines [2Peterman A. Potts A. O'Donnell M. Thompson K. Shah N. Oertelt-Prigione S. et al.Pandemics and violence against women and children.Center Global Dev Work Paper 528. 2020; Google Scholar]. The global community should prepare for similar effects in other countries. While quarantines will protect people from SARS-CoV2 infection, immediate action is needed to mitigate against increases in IPV. Increase physicians’ and other frontline healthcare worker's awareness of the heightened risk of IPV during quarantine and support their ability to safely offer information and referral. Physicians and other frontline healthcare workers need to be trained to recognize signs of violence and individuals at risk and communicate with them following best practice to protect the safety, privacy and choice of the survivor [6World Health OrganizationHealth care for women subjected to intimate partner violence or sexual violence: a clinical handbook. WHO, 2014https://www.who.int/reproductivehealth/publications/violence/vaw-clinical-handbook/en/Google Scholar,7World Health OrganizationStrengthening health systems to respond to women subjected to intimate partner violence or sexual violence: a manual for health managers. WHO, 2017https://www.who.int/reproductivehealth/publications/violence/vaw-health-systems-manual/en/Google Scholar]. Standard intake forms for the assessment of women subjected to IPV or sexual assault should be made available to staff in units, clinics and community screening dedicated to the COVID-19 response. First responders need to be informed about increased risk and options for intervention. Responders at the frontlines should be offered adequate support in coping with their own traumatic experiences caring for severely ill patients during an outbreak and a rising number of patients exposed to IPV. Increase public awareness and understanding for the increased risk of IPV during quarantine and how to safely access support services. Although limited by quarantine, individuals will maintain contacts with their families, friends, coworkers and acquaintances. Non healthcare-related contacts represent the primary and most capillary detection system for IPV. Public media needs to raise awareness for the topic to sensitize the general population and share best practices. These include bystander approaches, offering supportive statements, and, accessing help on the behalf of a survivor, if consented to do so. Media should provide links to IPV services including hotlines and online/SMS channels for those who cannot speak safely by phone, especially while at home with abusers. Social networks, both formal and informal, can help decrease isolation and provide support in case of IPV [8Zapor H. Wolford-Clevenger C. Johnson D.M. The association between social support and stages of change in survivors of intimate partner violence.J Interpers Violence. 2015; 33: 1051-1070Crossref PubMed Scopus (33) Google Scholar]. Social media can aid in upholding a buddy system and emergency contacts. In times of social distancing, internet-based help platforms can effectively replace some conventional in-person support. All should have safety mechanisms to quickly exit the page and clear browsing history, as abusers may monitor phone and internet use. - Increase funding and service availability for protection needs during quarantine, including social protection, shelters and trauma-centered support for family members. Social and economic insecurity represent crucial barriers for vulnerable individuals when seeking help. Lack of social safety nets, due to e.g., school closures may increase the exposure of children to IPV, with harmful outcomes in the immediate term and later adulthood. Maintenance of social safety nets (e.g., paid sick leave, access to healthcare insurance) is of utmost importance in guaranteeing the independence needed to leave an abusive relationship. Support structures such as organizations supporting survivors, as well as shelters, need to remain available while quarantines are in place, and need to be prepared to respond more fully after containment measures end [9Selvaratnam T. Where can domestic violence victims turn during Covid-19?. New York Times, 2020, March 23https://www.nytimes.com/2020/03/23/opinion/covid-domestic-violence.htmlGoogle Scholar]. Quarantine, isolation and associated social, emotional and economic stressors increase the risk of IPV. Partner violence is a taboo topic, often considered a ‘private’ matter, with low political priority in many societies, even in times of relative stability. If we do not campaign aggressively to raise awareness and take swift action for IPV and other forms of interpersonal violence, detrimental effects on individuals, families and society will reverberate for decades. None.

INTRODUCTION: Community engagement has been considered a fundamental component of past outbreaks, such as Ebola. However, there is concern over the lack of involvement of communities and 'bottom-up' approaches used within COVID-19 responses thus far. Identifying how community engagement approaches have been used in past epidemics may support more robust implementation within the COVID-19 response. METHODOLOGY: A rapid evidence review was conducted to identify how community engagement is used for infectious disease prevention and control during epidemics. Three databases were searched in addition to extensive snowballing for grey literature. Previous epidemics were limited to Ebola, Zika, SARS, Middle East respiratory syndromeand H1N1 since 2000. No restrictions were applied to study design or language. RESULTS: From 1112 references identified, 32 articles met our inclusion criteria, which detail 37 initiatives. Six main community engagement actors were identified: local leaders, community and faith-based organisations, community groups, health facility committees, individuals and key stakeholders. These worked on different functions: designing and planning, community entry and trust building, social and behaviour change communication, risk communication, surveillance and tracing, and logistics and administration. CONCLUSION: COVID-19's global presence and social transmission pathways require social and community responses. This may be particularly important to reach marginalised populations and to support equity-informed responses. Aligning previous community engagement experience with current COVID-19 community-based strategy recommendations highlights how communities can play important and active roles in prevention and control. Countries worldwide are encouraged to assess existing community engagement structures and use community engagement approaches to support contextually specific, acceptable and appropriate COVID-19 prevention and control measures.

BACKGROUND: The Sustainable Development Goals (SDGs), set in 2015 by the UN General Assembly, call for all countries to reach an under-5 mortality rate (U5MR) of at least as low as 25 deaths per 1000 livebirths and a neonatal mortality rate (NMR) of at least as low as 12 deaths per 1000 livebirths by 2030. We estimated levels and trends in under-5 mortality for 195 countries from 1990 to 2019, and conducted scenario-based projections of the U5MR and NMR from 2020 to 2030 to assess country progress in, and potential for, reaching SDG targets on child survival and the potential under-5 and neonatal deaths over the next decade. METHODS: Levels and trends in under-5 mortality are based on the UN Inter-agency Group for Child Mortality Estimation (UN IGME) database on under-5 mortality, which contains around 18 000 country-year datapoints for 195 countries-nearly 10 000 of those datapoints since 1990. The database includes nationally representative mortality data from vital registration systems, sample registration systems, population censuses, and household surveys. As with previous sets of national UN IGME estimates, a Bayesian B-spline bias-reduction model (B3) that considers the systematic biases associated with the different data source types was fitted to these data to generate estimates of under-5 (age 0-4 years) mortality with uncertainty intervals for 1990-2019 for all countries. Levels and trends in the neonatal mortality rate (0-27 days) are modelled separately as the log ratio of the neonatal mortality rate to the under-5 mortality rate using a Bayesian model. Estimated mortality rates are combined with livebirths data to calculate the number of under-5 and neonatal deaths. To assess the regional and global burden of under-5 deaths in the present decade and progress towards SDG targets, we constructed several scenario-based projections of under-5 mortality from 2020 to 2030 and estimated national, regional, and global under-5 mortality trends up to 2030 for each scenario. FINDINGS: The global U5MR decreased by 59% (90% uncertainty interval [UI] 56-61) from 93·0 (91·7-94·5) deaths per 1000 livebirths in 1990 to 37·7 (36·1-40·8) in 2019, while the annual number of global under-5 deaths declined from 12·5 (12·3-12·7) million in 1990 to 5·2 (5·0-5·6) million in 2019-a 58% (55-60) reduction. The global NMR decreased by 52% (90% UI 48-55) from 36·6 (35·6-37·8) deaths per 1000 livebirths in 1990, to 17·5 (16·6-19·0) in 2019, and the annual number of global neonatal deaths declined from 5·0 (4·9-5·2) million in 1990, to 2·4 (2·3-2·7) million in 2019, a 51% (47-54) reduction. As of 2019, 122 of 195 countries have achieved the SDG U5MR target, and 20 countries are on track to achieve the target by 2030, while 53 will need to accelerate progress to meet the target by 2030. 116 countries have reached the SDG NMR target with 16 on track, leaving 63 at risk of missing the target. If current trends continue, 48·1 million under-5 deaths are projected to occur between 2020 and 2030, almost half of them projected to occur during the neonatal period. If all countries met the SDG target on under-5 mortality, 11 million under-5 deaths could be averted between 2020 and 2030. INTERPRETATION: As a result of effective global health initiatives, millions of child deaths have been prevented since 1990. However, the task of ending all preventable child deaths is not done and millions more deaths could be averted by meeting international targets. Geographical and economic variation demonstrate the possibility of even lower mortality rates for children under age 5 years and point to the regions and countries with highest mortality rates and in greatest need of resources and action. FUNDING: Bill & Melinda Gates Foundation, US Agency for International Development.

OBJECTIVE: Prevalence ranges to classify levels of wasting and stunting have been used since the 1990s for global monitoring of malnutrition. Recent developments prompted a re-examination of existing ranges and development of new ones for childhood overweight. The present paper reports from the WHO-UNICEF Technical Expert Advisory Group on Nutrition Monitoring. DESIGN: Thresholds were developed in relation to sd of the normative WHO Child Growth Standards. The international definition of 'normal' (2 sd below/above the WHO standards median) defines the first threshold, which includes 2·3 % of the area under the normalized distribution. Multipliers of this 'very low' level (rounded to 2·5 %) set the basis to establish subsequent thresholds. Country groupings using the thresholds were produced using the most recent set of national surveys. SETTING: One hundred and thirty-four countries. SUBJECTS: Children under 5 years. RESULTS: For wasting and overweight, thresholds are: 'very low' (≈6 times 2·5 %). For stunting, thresholds are: 'very low' (≈12 times 2·5 %). CONCLUSIONS: The proposed thresholds minimize changes and keep coherence across anthropometric indicators. They can be used for descriptive purposes to map countries according to severity levels; by donors and global actors to identify priority countries for action; and by governments to trigger action and target programmes aimed at achieving 'low' or 'very low' levels. Harmonized terminology will help avoid confusion and promote appropriate interventions.

There is an absence of guidance, facilities, and materials for schoolgirls to manage their menstruation in low-and middle-income countries (LMICs).

OBJECTIVES: To examine levels and patterns of HIV prevalence, knowledge, sexual behavior, and coverage of selected HIV services among adolescents aged 10-19 years and highlight data gaps and challenges. METHODS: Data were reviewed from Joint United Nations Programme on HIV/AIDS HIV estimates, nationally representative household surveys, behavioral surveillance surveys, and published literature. RESULTS: A number of gaps exist for adolescent-specific HIV-related data; however, important implications for programming can be drawn. Eighty-two percent of the estimated 2.1 million adolescents aged 10-19 years living with HIV in 2012 were in sub-Saharan Africa, and the majority of these (58%) were females. Comprehensive accurate knowledge about HIV, condom use, HIV testing, and antiretroviral treatment coverage remain low in most countries. Early sexual debut (sex before 15 years of age) is more common among adolescent girls than boys in low- and middle-income countries, consistent with early marriage and early childbirth in these countries. In low and concentrated epidemic countries, HIV prevalence is highest among key populations. CONCLUSIONS: Although the available HIV-related data on adolescents are limited, increased HIV vulnerability in the second decade of life is evident in the data. Improving data gathering, analysis, and reporting systems specific to adolescents is essential to monitoring progress and improving health outcomes for adolescents. More systematic and better quality disaggregated data are needed to understand differences by sex, age, geography, and socioeconomic factors and to address equity and human rights obligations, especially for key populations.