Analyzing Health of Forcibly Displaced Communities through an Integrated Ecological Lens.

Health care among forcibly displaced persons is frequently driven by siloed approaches. Aspects of the built environment, social factors, and the bidirectional relationship between the changing ecosystem and residents are often ignored in health policy design and implementation. While recognizing factors that create a preference for siloed approaches and appreciating the work of humanitarian agencies, we argue for a new data-driven and holistic approach to understand the health of the forcibly displaced. It should be rooted in the realities of the emergence of new diseases, dynamic demographics, and degrading environments around the displaced communities. Such an approach envisions refugee and internally displaced camps as dynamic, complex ecosystems that alter, and are altered by, spatial and temporal factors. At the root of this approach is the necessity to work across disciplines, to think holistically, to go beyond treating single ailments, and to develop ethical approaches that provide dignity to those who are forcibly displaced.

Relative Risk Assessment for Substandard Antibiotics Along the Manufacturing and Supply Chain: A Proof-of-Concept Study.

BACKGROUND: Ensuring good quality of antibiotics is essential for desired health outcomes. Risk assessment of products for quality issues arising along the manufacturing and supply chain can thus have an important role in surveillance and management of interventions designed to reduce the burden of substandard antibiotics. Demonstrated and validated risk assessments are currently limited. OBJECTIVES: The objective of this study was to investigate whether a comparative risk assessment framework, which adapts the WHO criteria for estimating risks for quality issues posed by individual medicines, is applicable and can identify antibiotics with a higher relative risk of substandard prevalence. METHODS: For a proof-of-concept study, a set of antibiotics from the WHO essential medicines list was selected. Quantitative and qualitative data were extracted for each risk assessment criteria pertaining to severity and probability. A final risk matrix was then compared to field data for validation. RESULTS: Antibiotic products were classified by relative risk. Of all the antibiotic products assessed (n = 28), 32% were categorized as highest risk, 46% as high risk, 18% as medium risk, and 4% as lowest risk. The comparison of the risk scores and incidence of quality failure from the USP Medicines Quality Database showed significant correlation. CONCLUSION: The framework and extracted data sets appear applicable to determine relative risk for substandard antibiotics. Results of the risk matrix may be valuable for guiding pharmacovigilance, surveillance strategies, standardizing risk-based approaches, and mitigation efforts. Refinement with increased data availability may improve results.

Continued Outbreak of Ceftriaxone-Resistant Salmonella enterica Serotype Typhi across Pakistan and Assessment of Knowledge and Practices among Healthcare Workers.

Pakistan is experiencing the first known outbreak of extensively drug-resistant (XDR) Salmonella enterica serotype Typhi (resistant to third-generation cephalosporins). The outbreak originated in Hyderabad in 2016 and spread throughout the Sindh Province. Whereas focus has remained on Sindh, the burden of XDR typhoid in Punjab, the most populous province, and the rest of the country is understudied. Using laboratory data from Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore (Punjab Province) and its network of more than 100 collection centers across the country, we determined the frequency of blood culture-confirmed XDR typhoid cases from 2017 to 2019. We observed an increase in XDR typhoid cases in Punjab, with the percent of ceftriaxone resistance among Salmonella Typhi cases increasing from no cases in 2017, to 30% in 2018, and to 50% in 2019, with children bearing the largest burden. We also observed spread of XDR typhoid to the two other provinces in Pakistan. To assess prevailing knowledge and practices on XDR typhoid, we surveyed 321 frontline healthcare workers. Survey results suggested that inappropriate diagnostic tests and antibiotic practices may lead to underdiagnosis of XDR typhoid cases, and potentially drive resistance development and spread. Of those surveyed, only 43.6% had heard of XDR typhoid. Currently, serological tests are more routinely used over blood culture tests even though blood culture is imperative for a definitive diagnosis of typhoid fever. We recommend stronger liaisons between healthcare providers and diagnostic laboratories, and increased promotion of typhoid vaccination among healthcare workers and the general population.

Economic Evaluation of Screening Interventions for Drug-induced Liver Injury.

BACKGROUND: Human immunodeficiency virus (HIV)/AIDS and tuberculosis (TB) continue to be a significant global burden, disproportionately affecting low- and middle-income countries (LMICs). While much progress has been made in treating these epidemics, this has led to a rise in liver complications, as patients on ARTs and anti-TBs are at an increased risk of drug-induced liver injury (DILI). Therefore, patients on these medicines require consistent screening of liver function. Due to logistical barriers, gold standard DILI screening fails to be executed at the point-of-care in LMICs. For this reason, we used cost-effectiveness analysis to gauge the efficacy of a paper-test that could be implemented in these settings. METHODS: We used a Markov Model to simulate HIV and TB coinfected patient care in LMICs using both publicly available data and data from Village Health Works in Burundi. We compared the cost-effectiveness of two screening interventions for liver function monitoring: 1. paper-based point-of-care testing, and 2. gold-standard laboratory testing. These interventions were compared against baseline clinical monitoring. RESULTS: The paper test showed a 56% increase in efficacy over clinical monitoring alone. The paper-test is more cost-effective than the gold-standard method, at a ceiling cost of $1.60 per test. CONCLUSIONS: With this information, policy makers can be informed as to the large potential value of paper-based tests when gold standard monitoring is not achievable. Scientists and engineers should also keep these analyses in mind and while in development limit the cost of an ALT screening test to $1.60.

Veterinary antimicrobial resistance containment in Bangladesh: Evaluating the national action plan and scoping the evidence on implementation.

OBJECTIVES: In 2015, the World Health Organization (WHO) released its global action plan (GAP) on antimicrobial resistance (AMR) as a blueprint for the design of national action plans for AMR containment. Bangladesh, with 80% rural household ownership of at least one livestock, introduced its national action plan in May 2017. The objective of this study was two-fold: (i) to perform a policy content evaluation of the Bangladesh National Action Plan (BNAP) against the GAP with a focus on veterinary AMR containment strategies; and (ii) to assess the evidence on the implementation of veterinary AMR containment strategies of the BNAP. METHODS: The BNAP was evaluated against the GAP to identify commonalities and policy gaps. A scoping review of peer-reviewed and grey literature was performed to identity evidence of policy implementation and practice gaps. RESULTS: The BNAP is strongly aligned with the GAP. However, the study identified policy gaps, including an explicit financing modality, specifications for antimicrobial stewardship (AMS) in the veterinary sector, and rigorous operational and monitoring & evaluation frameworks. More evidence on implementation is needed in terms of incorporation of AMR in the curriculum of veterinarians, AMS plans throughout the veterinary sector, and infection prevention and control protocols and implementation. CONCLUSION: Closing the identified gaps is essential for successful veterinary AMR containment in Bangladesh but will require sustained and significant investment in institutional and human resource development in the coming years.

Controlling uncertainty in aptamer selection.

The search for high-affinity aptamers for targets such as proteins, small molecules, or cancer cells remains a formidable endeavor. Systematic Evolution of Ligands by EXponential Enrichment (SELEX) offers an iterative process to discover these aptamers through evolutionary selection of high-affinity candidates from a highly diverse random pool. This randomness dictates an unknown population distribution of fitness parameters, encoded by the binding affinities, toward SELEX targets. Adding to this uncertainty, repeating SELEX under identical conditions may lead to variable outcomes. These uncertainties pose a challenge when tuning selection pressures to isolate high-affinity ligands. Here, we present a stochastic hybrid model that describes the evolutionary selection of aptamers to explore the impact of these unknowns. To our surprise, we find that even single copies of high-affinity ligands in a pool of billions can strongly influence population dynamics, yet their survival is highly dependent on chance. We perform Monte Carlo simulations to explore the impact of environmental parameters, such as the target concentration, on selection efficiency in SELEX and identify strategies to control these uncertainties to ultimately improve the outcome and speed of this time- and resource-intensive process.

Engineering, global health, and inclusive innovation: focus on partnership, system strengthening, and local impact for SDGs.

The recent drafting of the Sustainable Development Goals challenges the research community to rethink the traditional approach to global health and provides the opportunity for science, technology, engineering, and mathematical (STEM) disciplines, particularly engineering, to demonstrate their benefit to the field. Higher education offers a platform for engineering to intersect with global health research through interdisciplinary partnerships among international universities that provide excellence in education, attract nontraditional STEM students, and foster a sense of innovation. However, a traditional lack of engineering-global health collaborations, as well as limited faculty and inadequate STEM research funding in low-income countries, has stifled progress. Still, the impact of higher education on development efforts holds great potential. This value will be realized in low-income countries through strengthening local capacity, supporting innovation through educational initiatives, and encouraging the inclusion of women and minorities in STEM programs. Current international university-level partnerships are working towards integrating engineering into global health research and strengthening STEM innovation among universities in low-income countries, but more can be done. Global health research informs sustainable development, and through integrating engineering into research efforts through university partnerships, we can accelerate progress and work towards a healthier future for all.

Low-cost tools for diagnosing and monitoring HIV infection in low-resource settings.

Low-cost technologies to diagnose and monitor human immunodeficiency virus (HIV) infection in developing countries are a major subject of current research and health care in the developing world. With the great need to increase access to affordable HIV monitoring services in rural areas of developing countries, much work has been focus on the development of point-of-care technologies that are affordable, robust, easy to use, portable and of sufficient quantitative accuracy to enable clinical decision-making. For diagnosis of HIV infection, some low-cost tests, such as lateral flow tests and enzyme-linked immunosorbent assays, are already in place and well established. However, portable quantitative tests for rapid HIV monitoring at the point of care have only recently been introduced to the market. In this review, we discuss low-cost tests for HIV diagnosis and monitoring in low-resource settings, including promising technologies for use at the point of care, that are available or close to market.

Tackling HIV through robust diagnostics in the developing world: current status and future opportunities.

Over the last thirty years, the world has seen HIV circulate the globe, affecting 33 million people to date and killing 2 million people a year. The disease has affected developed and developing countries alike, and in the U.S., remains one of the top ten leading causes of death. Many regions of the world are highly impacted by this disease, including sub-Saharan Africa, South and South-East Asia, and Eastern Europe. Fortunately, multilateral, global efforts, along with successful developments in diagnostic tools and anti-retroviral drugs (ARVs) have successfully curbed the spread of HIV over the last ten years. In spite of this fact, access to HIV treatment and preventive healthcare is varying and limited in developing countries. A lack of healthcare infrastructure, financial support, and healthcare workers are some logistical factors that are responsible. HIV stigmatization, discrimination, and inadequate education pose additional social challenges that are hindering countries from advancing in HIV prevention. This review focuses on current technological tools that are used for HIV diagnosis and ongoing research that is aimed at addressing the conditions in low-resource settings. Recent developments in microfluidic applications and mobile health technologies are promising approaches to building a compact, portable, and robust device that can provide information-rich, real-time diagnoses. We also discuss the role that governments, healthcare workers, and even researchers can play in order to increase the acceptance of newly introduced devices and treatments in rural communities.

Modeling cell migration in 3D: Status and challenges.

Cell migration is a multi-scale process that integrates signaling, mechanics and biochemical reaction kinetics. Various mathematical models accurately predict cell migration on 2D surfaces, but are unable to capture the complexities of 3D migration. Additionally, quantitative 3D cell migration models have been few and far between. In this review we look and characterize various mathematical models available in literature to predict cell migration in 3D matrices and analyze their strengths and possible changes to these models that could improve their predictive capabilities.

A multiscale probabilisitic framework to model early steps in tumor metastasis.

Tumor metastasis is the leading cause of nearly all cancer related deaths. While several experimental and computational studies have addressed individual stages of the complex metastasis process, a comprehensive systems-biology model that links various stages of metastasis has not been put forth as of yet. In this paper we discuss the formulation and application of such a model that utilizes basic principles of cell biology, physics and mechanics to study the migratory patterns of tumor cells as they move from the parent tumor site to the connective tissue via the basement membrane. The model is first of its kind in capturing the essential early features of metastasis in a single simulation and shows good agreement with recent experimental studies.