Neglected Tropical Diseases (NTDs) are infectious diseases and other conditions that cause physical and cognitive impairments, contribute to mother and child illness and death, and make it difficult to earn a living, thereby disproportionately affecting the world’s poorest populations. The World Health Organization (WHO) has a list of 21 NTDs that, combined, cause substantial illness for more than one billion people globally. These diseases thrive in conditions of extreme poverty; areas that generally have unsafe water, poor sanitation, substandard housing, and limited access to health care or essential medicines. In some countries this includes most rural areas, urban slums, or conflict zones, however, it is increasingly recognized that emerging middle-income countries (Brazil, Russia, India, China, and South Africa) contain the highest numbers of people affected. Unfortunately, particularly in the past 20 years, the development of novel pharmacological targets and new interventions based on these targets to treat NTDs has been limited. However, in recent years there has been a resurgence of research in these areas and several successes. The purpose of this article is to highlight the recent work that has been done in developing new targets and interventions to treat NTDs.
Neglected Global Diseases (NTDs) encompass several infectious diseases and other conditions that inflict physical and cognitive impairments, exacerbate maternal and child illness rates, and impede economic prosperity, disproportionately affecting the world's poorest populations. According to the World Health Organization (WHO), the list of 21 NTDs alone inflicts substantial illness upon over one billion people globally (1).
As described by the WHO “Neglected tropical diseases (NTDs) are a diverse group of conditions (5) caused by a variety of pathogens (including viruses, bacteria, parasites, fungi and toxins) and associated with devastating health, social and economic consequences. NTDs are mainly prevalent among impoverished communities in tropical areas, although some have a much larger geographical distribution. It is estimated that NTDs affect more than 1 billion people, while the number of people requiring NTD interventions (both preventive and curative) is 1.6 billion. The epidemiology of NTDs is complex and often related to environmental conditions. Many of them are vector-borne, have animal reservoirs and are associated with complex life cycles. All these factors make their public-health control challenging.” World Health Organization. (2024). Neglected tropical diseases.
These diseases find fertile ground in conditions of extreme poverty, manifesting in areas plagued by unsafe water, poor sanitation, substandard housing, and limited access to healthcare or essential medicines. While historically associated with rural regions, urban slums, or conflict zones, emerging middle-income countries like Brazil, Russia, India, China, and South Africa are now bearing the brunt of NTDs (2).
Despite their pervasive impact, funding for research and treatment of NGDs remains woefully inadequate compared to diseases that predominantly afflict developed nations.
In recent years, however, there has been a resurgence of research aimed at developing novel pharmacological targets and interventions to address NTDs. Low- and middle-income countries (LMICs) researchers in collaboration with many universities have taken the lead in this effort, recognizing the urgent need to combat these diseases that disproportionately affect their populations (3).
For example, the University of British Columbia -Neglected Global Diseases Initiative (NGDI-UBC; https://ngdi.ubc.ca/ ), scientists are spearheading studies to tackle NTDs comprehensively. Recognizing that addressing NTDs demands an integrated approach, UBC's initiatives encompass bench science, biotechnology, pharmaceutical and health research, business, social policy, economics, law, and more. This interdisciplinary approach ensures that new medications reach those in need by navigating the complex landscape of global health delivery.
NGDI-UBC (4), p, embodies a commitment to ensuring equitable access to medical innovations for developing countries. By harnessing the economic potential of university discoveries while prioritizing social benefit and affordability, this initiative represents a pioneering effort in Canadian universities.
This initiative serves as a hub for collaboration among various stakeholders, fostering synergies to enhance research outcomes and facilitate the delivery of life-saving medicines to underserved populations. By integrating technical expertise from diverse disciplines, this initiative seeks to overcome barriers to the generation of affordable, life-sustaining medicines for developing countries.
UBC's research clusters, focused on developing new drugs, nanomedicines, vaccines, therapeutics, diagnostics, micronutrients, and prophylactic measures, underscore the university's commitment to combating NGDs comprehensively. By fostering collaboration and feedback between discovery, development, delivery, and policy realms, UBC is charting a new path in the fight against NGDs.
Despite strides in research and development, challenges persist, particularly concerning emerging threats like the JN1 variant. While advanced treatments like Paxlovid offer hope, the exorbitant costs pose a significant barrier to access, especially in LMICs where most citizens cannot afford a treatment priced at $1400 without insurance or government subsidy treatment. Pepperrell T, Ellis L, Wang J, Hill A. Barriers to Worldwide Access for Paxlovid, a New Treatment for COVID-19. Open Forum Infect Dis. 2022 Apr 7;9(9):ofac174. doi: 10.1093/ofid/ofac174. PMID: 36176569; PMCID: PMC9383702.
Furthermore, the issue of Long COVID looms large, particularly for the globally impoverished populations who lack access to adequate healthcare resources. Furthermore, there are examples of healthcare inequities in the Medicare population that need systematic review, a study conducted by Harvard researchers suggests that in 2022, Paxlovid, a medication used for treating COVID-19, was not distributed efficiently. Instead, it was found to be disproportionately given to Medicare patients with lower risks of severe infection. This means that those who were at higher risk, and hence stood to benefit more from the medication, were less likely to receive it. The authors of the study estimated that had Paxlovid been properly utilized, more than 16,000 COVID-19 deaths could have been prevented. This indicates a significant missed opportunity in the management of the pandemic and highlights the importance of equitable distribution of resources, especially in healthcare settings. This also proves the need for real time testing, next day postal delivery of safe, cost-effective treatments, and a prioritization metric based on medical health record analysis, all of which can be done by a centralized system by unleashing the power of AI powered analytics.
Wilcock AD, Kissler S, Mehrotra A, et al. Clinical Risk and Outpatient Therapy Utilization for COVID-19 in the Medicare Population. JAMA Health Forum. 2024;5(1):e235044. doi:10.1001/jamahealthforum.2023.5044
Long COVID, characterized by persistent symptoms lasting weeks, months, or even years after the initial infection, presents a significant challenge for both individuals and healthcare systems.
Higgins V, Sohaei D, Diamandis EP, Prassas I. COVID-19: from an acute to chronic disease? Potential long-term health consequences. Crit Rev Clin Lab Sci. 2021 Aug;58(5):297-310. doi: 10.1080/10408363.2020.1860895. Epub 2020 Dec 21. PMID: 33347790.
The lack of a clear treatment for Long COVID exacerbates the suffering of those afflicted, especially in resource-constrained settings where access to specialized care is limited. The attached diagram illustrates the critical need to address treatment during the pre infection and acute infection periods, highlighting a need for rapid testing and deployment of a covid positive therapeutic treatment through USPS,FedEx, UPS, Amazon within the first 48 hours of testing positive.
As the global population continues to grapple with the aftermath of COVID-19, the impact of Long COVID on children emerges as a growing concern. The long-term consequences of Long COVID on children's physical and cognitive development are yet to be fully understood, underscoring the urgent need for effective treatments and interventions.
Suchitra Rao, Rachel S. Gross, Sindhu Mohandas, Cheryl R. Stein, Abigail Case, Benard Dreyer, Nathan M. Pajor, H. Timothy Bunnell, David Warburton, Elizabeth Berg, Jonathan B. Overdevest, Mark Gorelik, Joshua Milner, Sejal Saxena, Ravi Jhaveri, John C. Wood, Kyung E. Rhee, Rebecca Letts, Christine Maughan, Nick Guthe, Leah Castro-Baucom, Melissa S. Stockwell; Postacute Sequelae of SARS-CoV-2 in Children. Pediatrics 2024; e2023062570. 10.1542/peds.2023-062570
Model of Collaboration: The NGDI-UBC model of Collaboration is partially adapted from Frost & Reich’s Four A; s framework and the traditional pharmaceutical pipeline (6)
“Our framework is based on four A’s: architecture, the organizational structure and relationships for access; availability, which emphasizes the supply components of access; affordability, the cost issues for various players; and adoption, which includes demand factors and acceptance.”1
This new model provides a research roadmap that embraces multi-disciplinary collaboration, and recognizes the necessity of fundamental feedback between the discovery and development of interventions, and delivery and policy work on affordability and adoption. Drug and delivery interventions such as vaccines, essential medicines, and micronutrients can be developed alongside non-drug counterparts such as sustainable vector control, new tools and diagnostics. Delivery research into supply chain dynamics, health systems and strengthening – recently defined as operational, implementation and health systems research2 – is as crucial as affordability (patents, IP agreements)
Conclusions: In the battle against NTDs, concerted efforts are required to bridge the gap between scientific innovation and global health delivery. Through collaboration, innovation, and a commitment to equity, institutions like UBC are pioneering new approaches to combatting NGDs and ensuring that life-saving interventions reach those who need them most.
References:
(1) World Health Organization. (2024). Neglected tropical diseases
(2) Leonardo L.G. Ferreira, Josué de Moraes, Adriano D. Andricopulo, Approaches to advance drug discovery for neglected tropical diseases, Drug Discovery Today, Volume 27, Issue 8, 2022, Pages 2278-2287, ISSN 1359-6446
(3) Ibid. WHO. COVID-19 Dashboard CDC. COVID-19 Data Tracker CDC. Long COVID
(4) Gallini N, Hancock REW, Lester R, Sharp B, Wasan KM. Implementation and impact of the global access principles at the University of British Columbia: current successes and future challenges. Front Pharmacol. 2023 Dec 15;14:1271618. doi: 10.3389/fphar.2023.1271618. PMID: 38169728; PMCID: PMC10758455.
(5) NTDs include: Buruli ulcer; Chagas disease; dengue and chikungunya; dracunculiasis; echinococcosis; foodborne trematodiases; human African trypanosomiasis; leishmaniasis; leprosy; lymphatic filariasis; mycetoma, chromoblastomycosis and other deep mycoses; noma; onchocerciasis; rabies; scabies and other ectoparasitoses; schistosomiasis; soil-transmitted helminthiases; snakebite envenoming; taeniasis/cysticercosis; trachoma; and yaws. Neglected tropical diseases
(6) LJ Frost, MR Reich. (2008). ACCESS: How do good health technologies get to poor people in poor countries? Chapter 2: The Access Framework. Harvard Series on Population and International Health. Pp. 16. 2. JHF Remme, T Adam, F Becerra-Posada, C D’Arcangues, M Devlin, et al. (2010) Defining research to improve health systems. PLoS Med 7(11); e1001000. Doi:10.1371/journal.pmed.1001000.