Old vaccines for new infections: Exploiting innate immunity to control COVID-19 and prevent future pandemics.

The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed "trained immunity." An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to "bend the pandemic curve," averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease.

Routine Pediatric Surgical Emergencies: Incidence, Morbidity, and Mortality During the 1st 8000 Days of Life-A Narrative Review.

BACKGROUND: Many potentially treatable non-congenital and non-traumatic surgical conditions can occur during the first 8000 days of life and an estimated 85% of children in low- and middle-income countries (LMICs) will develop one before 15 years old. This review summarizes the common routine surgical emergencies in children from LMICs and their effects on morbidity and mortality. METHODS: A narrative review was undertaken to assess the epidemiology, treatment, and outcomes of common surgical emergencies that present within the first 8000 days (or 21.9 years) of life in LMICs. Available data on pediatric surgical emergency care in LMICs were aggregated. RESULTS: Outside of trauma, acute appendicitis, ileal perforation secondary to typhoid fever, and intestinal obstruction from intussusception and hernias continue to be the most common abdominal emergencies among children in LMICs. Musculoskeletal infections also contribute significantly to the surgical burden in children. These "neglected" conditions disproportionally affect children in LMICs and are due to delays in seeking care leading to late presentation and preventable complications. Pediatric surgical emergencies also necessitate heavy resource utilization in LMICs, where healthcare systems are already under strain. CONCLUSIONS: Delays in care and resource limitations in LMIC healthcare systems are key contributors to the complicated and emergent presentation of pediatric surgical disease. Timely access to surgery can not only prevent long-term impairments but also preserve the impact of public health interventions and decrease costs in the overall healthcare system.

Surgically Correctable Congenital Anomalies: Reducing Morbidity and Mortality in the First 8000 Days of Life.

BACKGROUND: Congenital anomalies are a leading cause of morbidity and mortality worldwide. We aimed to review the common surgically correctable congenital anomalies with recent updates on the global disease burden and identify the factors affecting morbidity and mortality. METHOD: A literature review was done to assess the burden of surgical congenital anomalies with emphasis on those that present within the first 8000 days of life. The various patterns of diseases were analyzed in both low- and middle-income countries (LMIC) and high-income countries (HIC). RESULTS: Surgical problems such as digestive congenital anomalies, congenital heart disease and neural tube defects are now seen more frequently. The burden of disease weighs more heavily on LMIC. Cleft lip and palate has gained attention and appropriate treatment within many countries, and its care has been strengthened by global surgical partnerships. Antenatal scans and timely diagnosis are important factors affecting morbidity and mortality. The frequency of pregnancy termination following prenatal diagnosis of a congenital anomaly is lower in many LMIC than in HIC. CONCLUSION: Congenital heart disease and neural tube defects are the most common congenital surgical diseases; however, easily treatable gastrointestinal anomalies are underdiagnosed due to the invisible nature of the condition. Current healthcare systems in most LMICs are still unprepared to tackle the burden of disease caused by congenital anomalies. Increased investment in surgical services is needed.

Estimates of Treatable Deaths Within the First 20 Years of Life from Scaling Up Surgical Care at First-Level Hospitals in Low- and Middle-Income Countries.

BACKGROUND: Surgical care is an important, yet often neglected component of child health in low- and middle-income countries (LMICs). This study examines the potential impact of scaling up surgical care at first-level hospitals in LMICs within the first 20 years of life. METHODS: Epidemiological data from the global burden of disease 2019 Study and a counterfactual method developed for the disease control priorities; 3rd Edition were used to estimate the number of treatable deaths in the under 20 year age group if surgical care could be scaled up at first-level hospitals. Our model included three digestive diseases, four maternal and neonatal conditions, and seven common traumatic injuries. RESULTS: An estimated 314,609 (95% UI, 239,619-402,005) deaths per year in the under 20 year age group could be averted if surgical care were scaled up at first-level hospitals in LMICs. Most of the treatable deaths are in the under-5 year age group (80.9%) and relates to improved obstetrical care and its effect on reducing neonatal encephalopathy due to birth asphyxia and trauma. Injuries are the leading cause of treatable deaths after age 5 years. Sixty-one percent of the treatable deaths occur in lower middle-income countries. Overall, scaling up surgical care at first-level hospitals could avert 5·1% of the total deaths in children and adolescents under 20 years of age in LMICs per year. CONCLUSIONS: Improving the capacity of surgical services at first-level hospitals in LMICs has the potential to avert many deaths within the first 20 years of life.

Achieving global mortality reduction targets and universal health coverage: The impact of COVID-19.

Wenhui Mao and coauthors discuss possible implications of the COVID-19 pandemic for health aspirations in low- and middle-income countries.

Health-care investments for the urban populations, Bangladesh and India.

OBJECTIVE: To estimate the costs and mortality reductions of a package of essential health interventions for urban populations in Bangladesh and India. METHODS: We used population data from the countries' censuses and United Nations Population Division. For causes of mortality in India, we used the Indian Million Death Study. We obtained cost estimates of each intervention from the third edition of Disease control priorities. For estimating the mortality reductions expected with the package, we used the Disease control priorities model. We calculated the benefit-cost ratio for investing in the package, using an analysis based on the Copenhagen Consensus method. FINDINGS: Per urban inhabitant, total costs for the package would be 75.1 United States dollars (US$) in Bangladesh and US$ 105.0 in India. Of this, prevention and treatment of noncommunicable diseases account for US$ 36.5 in Bangladesh and U$ 51.7 in India. The incremental cost per urban inhabitant for all interventions would be US$ 50 in Bangladesh and US$ 75 in India. In 2030, the averted deaths among people younger than 70 years would constitute 30.5% (1027/3362) and 21.2% (828/3913) of the estimated baseline deaths in Bangladesh and India, respectively. The health benefits of investing in the package would return US$ 1.2 per dollar spent in Bangladesh and US$ 1.8 per dollar spent in India. CONCLUSION: Investing in the package of essential health interventions, which address health-care needs of the growing urban population in Bangladesh and India, seems beneficial and could help the countries to achieve their 2030 sustainable development goals.

Investment in child and adolescent health and development: key messages from Disease Control Priorities, 3rd Edition.

The realisation of human potential for development requires age-specific investment throughout the 8000 days of childhood and adolescence. Focus on the first 1000 days is an essential but insufficient investment. Intervention is also required in three later phases: the middle childhood growth and consolidation phase (5-9 years), when infection and malnutrition constrain growth, and mortality is higher than previously recognised; the adolescent growth spurt (10-14 years), when substantial changes place commensurate demands on good diet and health; and the adolescent phase of growth and consolidation (15-19 years), when new responses are needed to support brain maturation, intense social engagement, and emotional control. Two cost-efficient packages, one delivered through schools and one focusing on later adolescence, would provide phase-specific support across the life cycle, securing the gains of investment in the first 1000 days, enabling substantial catch-up from early growth failure, and leveraging improved learning from concomitant education investments.

Investing in non-communicable disease prevention and management to advance the Sustainable Development Goals.

Reduction of the non-communicable disease (NCD) burden is a global development imperative. Sustainable Development Goal (SDG) 3 includes target 3·4 to reduce premature NCD mortality by a third by 2030. Progress on SDG target 3·4 will have a central role in determining the success of at least nine SDGs. A strengthened effort across multiple sectors with effective economic tools, such as price policies and insurance, is necessary. NCDs are heavily clustered in people with low socioeconomic status and are an important cause of medical impoverishment. They thereby exacerbate economic inequities within societies. As such, NCDs are a barrier to achieving SDG 1, SDG 2, SDG 4, SDG 5, and SDG 10. Productivity gains from preventing and managing NCDs will contribute to SDG 8. SDG 11 and SDG 12 offer clear opportunities to reduce the NCD burden and to create sustainable and healthy cities.

Universal health coverage and intersectoral action for health: key messages from Disease Control Priorities, 3rd edition.

The World Bank is publishing nine volumes of Disease Control Priorities, 3rd edition (DCP3) between 2015 and 2018. Volume 9, Improving Health and Reducing Poverty, summarises the main messages from all the volumes and contains cross-cutting analyses. This Review draws on all nine volumes to convey conclusions. The analysis in DCP3 is built around 21 essential packages that were developed in the nine volumes. Each essential package addresses the concerns of a major professional community (eg, child health or surgery) and contains a mix of intersectoral policies and health-sector interventions. 71 intersectoral prevention policies were identified in total, 29 of which are priorities for early introduction. Interventions within the health sector were grouped onto five platforms (population based, community level, health centre, first-level hospital, and referral hospital). DCP3 defines a model concept of essential universal health coverage (EUHC) with 218 interventions that provides a starting point for country-specific analysis of priorities. Assuming steady-state implementation by 2030, EUHC in lower-middle-income countries would reduce premature deaths by an estimated 4·2 million per year. Estimated total costs prove substantial: about 9·1% of (current) gross national income (GNI) in low-income countries and 5·2% of GNI in lower-middle-income countries. Financing provision of continuing intervention against chronic conditions accounts for about half of estimated incremental costs. For lower-middle-income countries, the mortality reduction from implementing the EUHC can only reach about half the mortality reduction in non-communicable diseases called for by the Sustainable Development Goals. Full achievement will require increased investment or sustained intersectoral action, and actions by finance ministries to tax smoking and polluting emissions and to reduce or eliminate (often large) subsidies on fossil fuels appear of central importance. DCP3 is intended to be a model starting point for analyses at the country level, but country-specific cost structures, epidemiological needs, and national priorities will generally lead to definitions of EUHC that differ from country to country and from the model in this Review. DCP3 is particularly relevant as achievement of EUHC relies increasingly on greater domestic finance, with global developmental assistance in health focusing more on global public goods. In addition to assessing effects on mortality, DCP3 looked at outcomes of EUHC not encompassed by the disability-adjusted life-year metric and related cost-effectiveness analyses. The other objectives included financial protection (potentially better provided upstream by keeping people out of the hospital rather than downstream by paying their hospital bills for them), stillbirths averted, palliative care, contraception, and child physical and intellectual growth. The first 1000 days after conception are highly important for child development, but the next 7000 days are likewise important and often neglected.

Pandemic risk: how large are the expected losses?

There is an unmet need for greater investment in preparedness against major epidemics and pandemics. The arguments in favour of such investment have been largely based on estimates of the losses in national incomes that might occur as the result of a major epidemic or pandemic. Recently, we extended the estimate to include the valuation of the lives lost as a result of pandemic-related increases in mortality. This produced markedly higher estimates of the full value of loss that might occur as the result of a future pandemic. We parametrized an exceedance probability function for a global influenza pandemic and estimated that the expected number of influenza-pandemic-related deaths is about 720 000 per year. We calculated that the expected annual losses from pandemic risk to be about 500 billion United States dollars - or 0.6% of global income - per year. This estimate falls within - but towards the lower end of - the Intergovernmental Panel on Climate Change's estimates of the value of the losses from global warming, which range from 0.2% to 2% of global income. The estimated percentage of annual national income represented by the expected value of losses varied by country income grouping: from a little over 0.3% in high-income countries to 1.6% in lower-middle-income countries. Most of the losses from influenza pandemics come from rare, severe events.

Il est nécessaire d'investir davantage dans la préparation contre les grandes épidémies et les pandémies. Les arguments en faveur de cet investissement s'appuient en grande partie sur les estimations des pertes au niveau du revenu national que pourrait entraîner une grande épidémie ou une pandémie. Récemment, nous avons élargi ces estimations pour y inclure la valeur des pertes faisant suite à des hausses de mortalité dues à des pandémies. Cela a donné des estimations nettement plus élevées de la valeur totale de la perte que pourrait occasionner une future pandémie. Nous avons paramétré une fonction de probabilité de dépassement pour une pandémie mondiale de grippe et avons estimé que le nombre escompté de décès dus à cette pandémie de grippe était d'environ 720 000 par an. Nous avons calculé que les pertes annuelles découlant du risque de pandémie représentaient environ 500 milliards de dollars des États-Unis, soit 0,6% du revenu mondial par an. Cette estimation rejoint (dans la fourchette inférieure) celles du Groupe d'experts intergouvernemental sur l'évolution du climat quant à la valeur des pertes dues au réchauffement de la planète, qui vont de 0,2% à 2% du revenu mondial. Le pourcentage estimé du revenu national annuel représenté par la valeur escomptée des pertes variait selon la catégorie de revenu des pays: d'un peu plus de 0,3% dans les pays à revenu élevé à 1,6% dans les pays à revenu intermédiaire-tranche inférieure. La plupart des pertes découlant de pandémies de grippe sont dues à des événements rares et graves.

Hay una necesidad no satisfecha de invertir más en la preparación para grandes epidemias y pandemias. Los argumentos a favor de dicha inversión se basan, en gran parte, en las estimaciones de las pérdidas en los ingresos nacionales que podrían darse como resultado de una gran epidemia o pandemia. Recientemente, ampliamos el cálculo para incluir la valoración de las vidas perdidas como resultado del aumento de la mortalidad relacionado con la pandemia. Esto dio como resultado unas estimaciones notablemente más altas del valor de la pérdida que podría resultar de una futura pandemia. Hemos parametrizado una función de probabilidad de excedencia para una pandemia de gripe mundial y estimado que el número esperado de muertes causadas por una pandemia de gripe es de aproximadamente 720 000 por año. Calculamos que las pérdidas anuales esperadas del riesgo de pandemia son de unos 500 000 millones de dólares estadounidenses, o el 0,6 % de los ingresos mundiales, por año. Esta estimación se encuentra dentro, pero cerca del mínimo, de las estimaciones del Panel Intergubernamental del Cambio Climático sobre el valor de las pérdidas por el calentamiento global, que oscilan entre el 0,2 % y el 2 % de los ingresos globales. El porcentaje estimado de los ingresos nacionales anuales representado por el valor esperado de las pérdidas varió según la agrupación de ingresos del país: de poco más del 0,3 % en los países con ingresos altos al 1,6 % en los países con ingresos medios o bajos. La mayoría de las pérdidas por pandemias de gripe provienen de casos raros y severos.

How much donor financing for health is channelled to global versus country-specific aid functions?

The slow global response to the Ebola crisis in west Africa suggests that important gaps exist in donor financing for key global functions, such as support for health research and development for diseases of poverty and strengthening of outbreak preparedness. In this Health Policy, we use the International Development Statistics databases to quantify donor support for such functions. We classify donor funding for health into aid for global functions (provision of global public goods, management of cross-border externalities, and fostering of leadership and stewardship) versus country-specific aid. We use a new measure of donor funding that combines official development assistance (ODA) for health with additional donor spending on research and development (R&D) for diseases of poverty. Much R&D spending falls outside ODA--ie, the assistance that is conventionally reported through ODA databases of the Organisation for Economic Co-operation and Development. This expanded definition, which we term health ODA plus, provides a more comprehensive picture of donor support for health that could reshape how policy makers will approach their support for global health.

Essential surgery: key messages from Disease Control Priorities, 3rd edition.

The World Bank will publish the nine volumes of Disease Control Priorities, 3rd edition, in 2015-16. Volume 1--Essential Surgery--identifies 44 surgical procedures as essential on the basis that they address substantial needs, are cost effective, and are feasible to implement. This report summarises and critically assesses the volume's five key findings. First, provision of essential surgical procedures would avert about 1·5 million deaths a year, or 6-7% of all avertable deaths in low-income and middle-income countries. Second, essential surgical procedures rank among the most cost effective of all health interventions. The surgical platform of the first-level hospital delivers 28 of the 44 essential procedures, making investment in this platform also highly cost effective. Third, measures to expand access to surgery, such as task sharing, have been shown to be safe and effective while countries make long-term investments in building surgical and anaesthesia workforces. Because emergency procedures constitute 23 of the 28 procedures provided at first-level hospitals, expansion of access requires that such facilities be widely geographically diffused. Fourth, substantial disparities remain in the safety of surgical care, driven by high perioperative mortality rates including anaesthesia-related deaths in low-income and middle-income countries. Feasible measures, such as WHO's Surgical Safety Checklist, have led to improvements in safety and quality. Fifth, the large burden of surgical disorders, cost-effectiveness of essential surgery, and strong public demand for surgical services suggest that universal coverage of essential surgery should be financed early on the path to universal health coverage. We point to estimates that full coverage of the component of universal coverage of essential surgery applicable to first-level hospitals would require just over US$3 billion annually of additional spending and yield a benefit-cost ratio of more than 10:1. It would efficiently and equitably provide health benefits, financial protection, and contributions to stronger health systems.

Avoiding 40% of the premature deaths in each country, 2010-30: review of national mortality trends to help quantify the UN sustainable development goal for health.

BACKGROUND: The UN will formulate ambitious Sustainable Development Goals for 2030, including one for health. Feasible goals with some quantifiable, measurable targets can influence governments. We propose, as a quatitative health target, "Avoid in each country 40% of premature deaths (under-70 deaths that would be seen in the 2030 population at 2010 death rates), and improve health care at all ages". Targeting overall mortality and improved health care ignores no modifiable cause of death, nor any cause of disability that is treatable (or also causes many deaths). 40% fewer premature deaths would be important in all countries, but implies very different priorities in different populations. Reinforcing this target for overall mortality in each country are four global subtargets for 2030: avoid two-thirds of child and maternal deaths; two-thirds of tuberculosis, HIV, and malaria deaths; a third of premature deaths from non-communicable diseases (NCDs); and a third of those from other causes (other communicable diseases, undernutrition, and injuries). These challenging subtargets would halve under-50 deaths, avoid a third of the (mainly NCD) deaths at ages 50-69 years, and so avoid 40% of under-70 deaths. To help assess feasibility, we review mortality rates and trends in the 25 most populous countries, in four country income groupings, and worldwide. METHODS: UN sources yielded overall 1970-2010 mortality trends. WHO sources yielded cause-specific 2000-10 trends, standardised to country-specific 2030 populations; decreases per decade of 42% or 18% would yield 20-year reductions of two-thirds or a third. RESULTS: Throughout the world, except in countries where the effects of HIV or political disturbances predominated, mortality decreased substantially from 1970-2010, particularly in childhood. From 2000-10, under-70 age-standardised mortality rates decreased 19% (with the low-income and lower-middle-income countries having the greatest absolute gains). The proportional decreases per decade (2000-10) were: 34% at ages 0-4 years; 17% at ages 5-49 years; 15% at ages 50-69 years; 30% for communicable, perinatal, maternal, or nutritional causes; 14% for NCDs; and 13% for injuries (accident, suicide, or homicide). INTERPRETATION: Moderate acceleration of the 2000-10 proportional decreases in mortality could be feasible, achieving the targeted 2030 disease-specific reductions of two-thirds or a third. If achieved, these reductions avoid about 10 million of the 20 million deaths at ages 0-49 years that would be seen in 2030 at 2010 death rates, and about 17 million of the 41 million such deaths at ages 0-69 years. Such changes could be achievable by 2030, or soon afterwards, at least in areas free of war, other major effects of political disruption, or a major new epidemic. FUNDING: UK Medical Research Council, Norwegian Agency for Development Cooperation, Centre for Global Health Research, and Bill & Melinda Gates Foundation.

Universal public finance of tuberculosis treatment in India: an extended cost-effectiveness analysis.

Universal public finance (UPF)-government financing of an intervention irrespective of who is receiving it-for a health intervention entails consequences in multiple domains. First, UPF increases intervention uptake and hence the extent of consequent health gains. Second, UPF generates financial consequences including the crowding out of private expenditures. Finally, UPF provides insurance either by covering catastrophic expenditures, which would otherwise throw households into poverty or by preventing diseases that cause them. This paper develops a method-extended cost-effectiveness analysis (ECEA)-for evaluating the consequences of UPF in each of these domains. It then illustrates ECEA with an evaluation of UPF for tuberculosis treatment in India. Using plausible values for key parameters, our base case ECEA concludes that the health gains and insurance value of UPF would accrue primarily to the poor. Reductions in out-of-pocket expenditures are more uniformly distributed across income quintiles. A variant on our base case suggests that lowering costs of borrowing for the poor could potentially achieve some of the health gains of UPF, but at the cost of leaving the poor more deeply in debt.

[Global health 2035: a world converging within a generation]. / Salud global 2035: un mundo convergiendo en el lapso de una generación.

Prompted by the 20th anniversary of the 1993 World Development Report, a Lancet Commission revisited the case for investment in health and developed a new investment framework to achieve dramatic health gains by 2035. The Commission's report has four key messages, each accompanied by opportunities for action by national governments of low-income and middle-income countries and by the international community. First, there is an enormous economic payoff from investing in health. The impressive returns make a strong case for both increased domestic financing of health and for allocating a higher proportion of official development assistance to development of health. Second, modeling by the Commission found that a "grand convergence" in health is achievable by 2035-that is, a reduction in infectious, maternal, and child mortality down to universally low levels. Convergence would require aggressive scale up of existing and new health tools, and it could mostly be financed from the expected economic growth of low- and middle-income countries. The international community can best support convergence by funding the development and delivery of new health technologies and by curbing antibiotic resistance. Third, fiscal policies -such as taxation of tobacco and alcohol- are a powerful and underused lever that governments can use to curb non-communicable diseases and injuries while also raising revenue for health. International action on NCDs and injuries should focus on providing technical assistance on fiscal policies, regional cooperation on tobacco, and funding policy and implementation research on scaling-up of interventions to tackle these conditions. Fourth, progressive universalism, a pathway to universal health coverage (UHC) that includes the poor from the outset, is an efficient way to achieve health and financial risk protection. For national governments, progressive universalism would yield high health gains per dollar spent and poor people would gain the most in terms of health and financial protection. The international community can best support countries to implement progressive UHC by financing policy and implementation research, such as on the mechanics of designing and implementing evolution of the benefits package as the resource envelope for public finance grows.