One vaccine to counter many diseases? Modeling the economics of oral polio vaccine against child mortality and COVID-19.

Introduction: Recent reviews summarize evidence that some vaccines have heterologous or non-specific effects (NSE), potentially offering protection against multiple pathogens. Numerous economic evaluations examine vaccines' pathogen-specific effects, but less than a handful focus on NSE. This paper addresses that gap by reporting economic evaluations of the NSE of oral polio vaccine (OPV) against under-five mortality and COVID-19. Materials and methods: We studied two settings: (1) reducing child mortality in a high-mortality setting (Guinea-Bissau) and (2) preventing COVID-19 in India. In the former, the intervention involves three annual campaigns in which children receive OPV incremental to routine immunization. In the latter, a susceptible-exposed-infectious-recovered model was developed to estimate the population benefits of two scenarios, in which OPV would be co-administered alongside COVID-19 vaccines. Incremental cost-effectiveness and benefit-cost ratios were modeled for ranges of intervention effectiveness estimates to supplement the headline numbers and account for heterogeneity and uncertainty. Results: For child mortality, headline cost-effectiveness was $650 per child death averted. For COVID-19, assuming OPV had 20% effectiveness, incremental cost per death averted was $23,000-65,000 if it were administered simultaneously with a COVID-19 vaccine <200 days into a wave of the epidemic. If the COVID-19 vaccine availability were delayed, the cost per averted death would decrease to $2600-6100. Estimated benefit-to-cost ratios vary but are consistently high. Discussion: Economic evaluation suggests the potential of OPV to efficiently reduce child mortality in high mortality environments. Likewise, within a broad range of assumed effect sizes, OPV (or another vaccine with NSE) could play an economically attractive role against COVID-19 in countries facing COVID-19 vaccine delays. Funding: The contribution by DTJ was supported through grants from Trond Mohn Foundation (BFS2019MT02) and Norad (RAF-18/0009) through the Bergen Center for Ethics and Priority Setting.

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.

The challenges of tuberculosis control in protracted conflict: The case of Syria.

OBJECTIVES: Syria's protracted conflict has resulted in ideal conditions for the transmission of tuberculosis (TB) and the cultivation of drug-resistant strains. This paper compares TB control in Syria before and after the conflict using available data, examines the barriers posed by protracted conflict and those specific to Syria, and discusses what measures can be taken to address the control of TB in Syria. RESULTS: Forced mass displacement and systematic violations of humanitarian law have resulted in overcrowding and the destruction of key infrastructure, leading to an increased risk of both drug-sensitive and resistant TB, while restricting the ability to diagnose, trace contacts, treat, and follow-up. Pre-conflict, TB in Syria was officially reported at 22 per 100 000 population; the official figure for 2017 of 19 per 100 000 is likely a vast underestimate given the challenges and barriers to case detection. Limited diagnostics also affect the diagnosis of multidrug- and rifampicin-resistant TB, reported as comprising 8.8% of new diagnoses in 2017. CONCLUSIONS: The control of TB in Syria requires a multipronged, tailored, and pragmatic approach to improve timely diagnosis, increase detection, stop transmission, and mitigate the risk of drug resistance. Solutions must also consider vulnerable populations such as imprisoned and besieged communities where the risk of drug resistance is particularly high, and must recognize the limitations of national programming. Strengthening capacity to control TB in Syria with particular attention to these factors will positively impact other parallel conditions; this is key as attention turns to post-conflict reconstruction.

The Ongoing Ebola Epidemic in the Democratic Republic of Congo, 2018-2019.

The international response to the evolving Ebola epidemic in eastern Democratic Republic of Congo (DRC) has had interim successes while facing ongoing difficulties. The outbreak has occurred in an area of intractable conflict among multiple armed groups at a time of contentious national elections. Despite porous international borders and considerable population movement, however, transmission has been confined to North Kivu and Ituri provinces. Factors potentially contributing to this containment include conduct of about 55 million screenings, surveillance of contacts (12,591 under surveillance currently), testing of 280 samples per day, provision of safe and dignified burials for most deaths, vaccination of high-risk people (112,485 vaccinated as of May 7, 2019), and medical treatment including four investigational therapies. Major challenges remain. Since late February 2019, a sharp rise in cases and increased transmission have been observed. These coincide with organized attacks by armed groups targeting response teams, deteriorating security, and the population's increasing distrust of the response effort. The risk of local and regional spread remains high given the high proportion of deaths occurring outside treatment facilities, relatively low proportions of new patients who were known contacts, ongoing nosocomial transmission, and persistent delays in detection and reporting. Stopping this epidemic will require the alignment of the principal political and armed groups in eastern DRC in support of the response.

A summary and appraisal of existing evidence of antimicrobial resistance in the Syrian conflict.

Antimicrobial resistance (AMR) in populations experiencing war has yet to be addressed, despite the abundance of contemporary conflicts and the protracted nature of twenty-first century wars, in combination with growing global concern over conflict-associated bacterial pathogens. The example of the Syrian conflict is used to explore the feasibility of using existing global policies on AMR in conditions of extreme conflict. The available literature on AMR and prescribing behaviour in Syria before and since the onset of the conflict in March 2011 was identified. Overall, there is a paucity of rigorous data before and since the onset of conflict in Syria to contextualize the burden of AMR. However, post onset of the conflict, an increasing number of studies conducted in neighbouring countries and Europe have reported AMR in Syrian refugees. High rates of multidrug resistance, particularly Gram-negative organisms, have been noted amongst Syrian refugees when compared with local populations. Conflict impedes many of the safeguards against AMR, creates new drivers, and exacerbates existing ones. Given the apparently high rates of AMR in Syria, in neighbouring countries hosting refugees, and in European countries providing asylum, this requires the World Health Organization and other global health institutions to address the causes, costs, and future considerations of conflict-related AMR as an issue of global governance.

Antimicrobial resistance in the context of the Syrian conflict: Drivers before and after the onset of conflict and key recommendations.

Current evidence describing antimicrobial resistance (AMR) in the context of the Syrian conflict is of poor quality and sparse in nature. This paper explores and reports the major drivers of AMR that were present in Syria pre-conflict and those that have emerged since its onset in March 2011. Drivers that existed before the conflict included a lack of enforcement of existing legislation to regulate over-the-counter antibiotics and notification of communicable diseases. This contributed to a number of drivers of AMR after the onset of conflict, and these were also compounded by the exodus of trained staff, the increase in overcrowding and unsanitary conditions, the increase in injuries, and economic sanctions limiting the availability of required laboratory medical materials and equipment. Addressing AMR in this context requires pragmatic, multifaceted action at the local, regional, and international levels to detect and manage potentially high rates of multidrug-resistant infections. Priorities are (1) the development of a competent surveillance system for hospital-acquired infections, (2) antimicrobial stewardship, and (3) the creation of cost-effective and implementable infection control policies. However, it is only by addressing the conflict and immediate cessation of the targeting of health facilities that the rehabilitation of the health system, which is key to addressing AMR in this context, can progress.

Health workers and the weaponisation of health care in Syria: a preliminary inquiry for The Lancet-American University of Beirut Commission on Syria.

The conflict in Syria presents new and unprecedented challenges that undermine the principles and practice of medical neutrality in armed conflict. With direct and repeated targeting of health workers, health facilities, and ambulances, Syria has become the most dangerous place on earth for health-care providers. The weaponisation of health care-a strategy of using people's need for health care as a weapon against them by violently depriving them of it-has translated into hundreds of health workers killed, hundreds more incarcerated or tortured, and hundreds of health facilities deliberately and systematically attacked. Evidence shows use of this strategy on an unprecedented scale by the Syrian Government and allied forces, in what human rights organisations described as a war-crime strategy, although all parties seem to have committed violations. Attacks on health care have sparked a large-scale exodus of experienced health workers. Formidable challenges face health workers who have stayed behind, and with no health care a major factor in the flight of refugees, the effect extends well beyond Syria. The international community has left these violations of international humanitarian and human rights law largely unanswered, despite their enormous consequences. There have been repudiated denunciations, but little action on bringing the perpetrators to justice. This inadequate response challenges the foundation of medical neutrality needed to sustain the operations of global health and humanitarian agencies in situations of armed conflict. In this Health Policy, we analyse the situation of health workers facing such systematic and serious violations of international humanitarian law. We describe the tremendous pressures that health workers have been under and continue to endure, and the remarkable resilience and resourcefulness they have displayed in response to this crisis. We propose policy imperatives to protect and support health workers working in armed conflict zones.

War is the Enemy of Health. Pulmonary, Critical Care, and Sleep Medicine in War-Torn Syria.

The Syrian crisis, now in its fifth year, has created an unprecedented strain on health services and systems due to the protracted nature of the warfare, the targeting of medics and health care infrastructure, the exodus of physicians and nurses, the shortage of medical supplies and medications, and the disruption of medical education and training. Within a few short years, the life expectancy of resident Syrians has declined by 20 years. Over the first 4 years of the conflict, more than 75,000 civilians died from injuries incurred in the violence. More than twice as many civilians, including many women and children, have died prematurely of infectious and noninfectious chronic diseases for want of adequate health care. Doctors, local administrators, and nongovernmental organizations are struggling to manage the consequences of the conflict under substandard conditions, often using unorthodox methods of health care delivery in field hospitals and remotely by telehealth communication. Much-needed medical supplies are channeled through dangerous routes across the borders from Lebanon, Jordan, and Turkey. Physicians in the United States and other western nations have helped Syrian physicians make the most of the situation by providing training on introducing innovations in technology and treatment. Portable ultrasound machines have been introduced and are being used extensively in the management of trauma and shock. This report, prepared by members of the Syrian American Medical Society, documents current needs for health care relief within Syria, focusing on pulmonary, critical care, and sleep medicine, and some of the efforts currently underway to meet those needs.

Cholera in the time of war: implications of weak surveillance in Syria for the WHO's preparedness-a comparison of two monitoring systems.

BACKGROUND: Public health breakdown from the Syrian government's targeting of healthcare systems in politically unsympathetic areas has yielded a resurgence of infectious diseases. Suspected cholera recently reappeared but conflict-related constraints impede laboratory confirmation. Given the government's previous under-reporting of infectious outbreaks and the reliance of the WHO on government reporting, we sought to assess the reliability of current surveillance systems. METHODS: We compared weekly surveillance reports of waterborne diseases from the Syrian government's (WHO-associated) Early Warning and Response System (EWARS), based in Damascus, and the independent, non-governmental Early Warning and Response Network (EWARN) headquartered in Gaziantep, Turkey. We compared raw case rates by EWARS and EWARN and assessed the quality of reporting against the WHO benchmarks. RESULTS: We identified significant under-reporting and delays in the government's surveillance. On average, EWARS reports were published 24 days (range 12-61) after the reference week compared with 11 days (5-21) for EWARN. Average completeness for EWARS was 75% (55-84%), compared with 92% for EWARN (85-99%). Average timeliness for EWARS was 79% (51-100%), compared with 88% for EWARN (70-97%). EWARS made limited use of rapid diagnostic tests, and rates of collection of stool samples for laboratory cholera testing were well below reference levels. CONCLUSIONS: In the context of the current Syrian war, the government's surveillance is inadequate due to lack of access to non-government held territory, an incentive to under-report the consequence of government attacks on health infrastructure, and an impractical insistence on laboratory confirmation. These findings should guide the WHO reform for surveillance in conflict zones.

Defining Polio: Closing the Gap in Global Surveillance.

BACKGROUND: By late 2012 the Global Polio Eradication Initiative (GPEI) had nearly eradicated this ancient infectious disease. Successful surveillance programs for acute flaccid paralysis however rely on broad governmental support for implementation. With the onset of conflict, public health breakdown has contributed to the resurgence of polio in a number of regions. The current laboratory based case definition may be a contributory factor in these regions. OBJECTIVE: We sought to compare case definition rates using strict laboratory based criteria to rates obtained using the clinical criteria in modern day Syria. We also sought to examine this distribution of cases by sub-region. METHODS: We examined the World Health Organization (WHO) reported figures for Syria from 2013-2014 using laboratory based criteria. We compared these with cases obtained when clinical criteria were applied. In addition we sought data from the opposition controlled Assistance Coordination Unit which operates in non-Government controlled areas where WHO data maybe incomplete. Cases were carefully examined for potential overlap to avoid double reporting. FINDINGS: Whilst the WHO data clearly confirmed the polio outbreak in Syria, it did so with considerable delay and with under reporting of cases, particularly from non-government controlled areas. In addition, laboratory based case definition led to a substantial underestimate of polio (36 cases) compared with those found with the clinically compatible definition (an additional 46 cases). Rates of adequate diagnostic specimens from suspected cases are well below target, no doubt reflecting the effect of conflict in these areas. CONCLUSIONS: We have identified a gap in the surveillance of polio, a global threat. The current laboratory based definition, in the setting of conflict and insecurity, leads to under diagnosis of polio with potential delays and inadequacies in coordinating effective responses to contain outbreaks and eradicate polio. Breakdown in public health measures as a contributing factor is likely to result in a resurgence of previously controlled infectious diseases. The clinical definition should be reinstituted to supplement the lab-based definition.

Children's Nomenclatural Adventurism and Medical Evaluation study.

AIM: The aim of this study was to determine whether there is an association between a child's first name and the likelihood of inpatient admission following presentation to a paediatric emergency department (ED). METHODS: This was a retrospective review of electronic records held in the ED of an urban tertiary paediatric hospital. Data were obtained for all presentations up to the age of 16 years for a single month (n= 4260), each being allocated to 1 of the 10 predetermined first name categories. RESULTS: A statistically significant increased risk for hospital admission was found for the following first name categories: popular culture (relative risk (RR) = 1.91, P= 0.000, 95% confidence interval (CI) = 1.60-2.28), apparently unique (RR = 1.52, P= 0.000, 95% CI = 1.23-1.87), Old Testament (RR = 1.39, P= 0.001, 95% CI = 1.14-1.69) and surname as first name (RR = 1.36, P= 0.015, 95% CI = 1.07-1.72). CONCLUSIONS: Our data confirm the impression that children with certain categories of first names have an increased likelihood of admission to hospital after presenting to the ED. We speculate that our findings, which are in concordance with those from educational and psychological literature, may reflect socio-economic status and/or a 'self-fulfilling prophecy'. Further research may make it possible to assign names an RR rating (e.g. for hospital admission in the first 16 years of life), thus providing parents with another factor to consider when choosing names for their children. More studies are of course needed.

Management of septic shock in childhood.

OBJECTIVE: The object of this review is to discuss the recognition and treatment of septic shock in children based on principles of resuscitation, antibiotic use and recent therapeutic advances. METHODS: A comprehensive literature search combining these METHODS: on-line searches of Ovid, PubMed, and Medline; hand searches of 25 international journals; a trawl of 26 textbooks; searches of reference lists of pertinent articles; and scans of abstracts of recent international meetings. Various national and international units were contacted with regard to current research therapeutic strategies, both published and unpublished. CONCLUSIONS: Septic shock remains a leading cause of morbidity and mortality in children. Early administration of empirical antibiotic therapy reduces mortality. The keystone of resuscitation is aggressive volume replacement. Adjunctive therapies to modulate the inflammatory response may further enhance outcome, but do not replace principles of resuscitation.