Authors:
Javier Casellas, M.D., Ph.D.
Enrique Chacon-Cruz, M.D., MSc
Felicitas Colombo, MPA
Prof. Steven Black is a pediatric infectious disease specialist with degrees in Biology and Chemistry from the University of California, Santa Barbara, and an MD from the University of California, San Diego. He completed a fellowship in pediatric infectious diseases at the University of California, San Francisco.
With over 30 years of experience, Prof. Black has conducted numerous clinical trials and vaccine safety studies. He has served as the principal investigator for five pivotal Phase III clinical trials, six Phase IV post-licensure vaccine safety assessments, and the CDC-funded multinational SOMNIA project, which evaluated the risk of narcolepsy following adjuvanted 2009 pandemic influenza vaccines. Additionally, he founded the Kaiser Permanente Vaccine Study Center and was Co-Director from 1985 to 2007.
Prof. Black was actively involved in the WHO-funded Global Vaccine Safety Initiative (GVSI) pilot project, which linked data from various countries to assess vaccine safety. He led international efforts to emphasize the importance of background rates in evaluating the safety of pandemic vaccines. He has been an elected member of the International Brighton Collaboration Science Board and served as the work package lead for Data and Safety Monitoring Board (DSMB) activities in the Safety Platform for Emergency Vaccine (SPEAC) project, funded by the Coalition for Epidemic Preparedness Innovations (CEPI).
Currently, he is co-director of the Global Vaccine Data Network through which he is the principal investigator for the CEPI-funded BRAVE project, which aims to develop background rates for potential vaccine adverse events in Africa, and serves as the Meta DSMB lead for the CEPI-funded SPEAC project. Prof. Black is also an Emeritus Professor of Pediatrics at the University of Cincinnati Children’s Hospital in Ohio, USA, and an Honorary Professor of Pediatrics at the University of Auckland in New Zealand. Among his many contributions, he serves as the editor-in-chief of the Pediatric Infectious Disease Journal.
The basics of Neglected Tropical Diseases
Neglected Tropical Diseases (NTDs) are a diverse group of conditions, many of which are vector-borne and have animal reservoirs. They are associated with complex life cycles caused by various pathogens, including viruses, bacteria, parasites, fungi, and toxins. The epidemiology of NTDs is intricate and often linked to environmental conditions.
As global interconnections increase, NTDs are becoming a topic of heightened interest due to their significant contribution to global morbidity, social and economic hardship. These diseases cause chronic illness, disability, and stigmatization. According to the World Health Organization (WHO), NTDs affect over 1 billion people, with an estimated 1.6 billion individuals requiring preventive and curative interventions. Additionally, NTDs contribute to approximately 200,000 deaths and result in 19 million disability-adjusted life years (DALYs) lost annually.
The recent global experience with COVID-19 has underscored that diseases do not remain confined to their communities of origin. Other recent outbreaks, such as those of Ebola, Mpox, and Marburg virus, have further highlighted this reality. Consequently, there is growing global interest in NTDs.
“I think that’s good because that means that public health dollars and public health interventions such as vaccines are more likely to be targeted to them if rich people are threatened by them than if, unfortunately, if [only] poor people are threatened by them,” notes Prof. Black. He emphasizes that while the focus often leans toward respiratory viruses due to their contagious nature, the scope of infectious diseases is much broader.
NTDs and vaccines
Neglected Tropical Diseases (NTDs) live up to their name as they are not prioritized on the public health agenda, resulting in limited attention and funding. Prof. Black highlights two major concerns: a general lack of confidence in public health and the significant under-resourcing of public health systems, especially during non-crisis periods.
Despite inadequate funding, some research and development (R&D) efforts are underway for NTDs. However, predicting which of the many ongoing vaccine trials for these diseases will succeed and reach the market remains challenging. Prof. Black believes that the CEPI approach, where multiple developers tackle the same problem in parallel, will increase the chances of identifying an optimal vaccine candidate.
However, researchers face numerous hurdles in developing vaccines for NTDs. One significant challenge arises from the pathogens themselves, particularly parasitic diseases, which have complex life cycles that complicate vaccine development. A prime example of this is the malaria vaccine.
The inequity of NTDs
The inequity surrounding the development of vaccines for NTDs can be difficult to comprehend. For Prof. Black, the answer is straightforward: money. The estimated cost of bringing a new vaccine to market can exceed $1 billion from inception to commercialization.
In fact, much of the initial R&D for NTD vaccines has originated from academics and smaller companies willing to take risks, often with funding from sources like CEPI, rather than from major pharmaceutical companies. Unfortunately, many of these companies have invested in developing NTD vaccines without seeing a return on their investment.
Given the economic burden of NTDs, the scope of diseases involved, and the amount of R&D funding directed toward vaccine development is minuscule. Less than $100 million is typically spent on R&D for most NTDs, despite millions of people being affected by these diseases.
“That doesn’t make sense from a public health perspective, but from a health economic perspective, it does. TB [tuberculosis] is not a big issue in high-income countries. Then the investment dollars go elsewhere,” Prof. Black points out.
Similarly, the world largely overlooked the onset of the MPOX outbreak in 2022. To date, according to the Center for Disease Control, the ongoing global outbreak of clade II MPOX has resulted in over 100,000 cases across 122 countries, including 115 where MPOX had not been previously reported.
Prof. Black notes that MPOX received little attention until the virus mutated and became a sexually transmitted disease (STD). It appears that it is no longer classified as an NTD, as it is now affecting populations worldwide.
Organizations such as CEPI, the Gates Foundation, the International Vaccine Institute, the Sabin Vaccine Institute, and the Clinton Foundation play vital roles in addressing these challenges. However, many of these organizations compete for the same donor resources.
“So, what motivates people with money is that they’re threatened by it or think their well-being or economic health is going to be improved. So, if you can show that, then you will get more funding,” expresses Prof. Black with concern about the lack of a centralized authority to set priorities and coordinate efforts effectively.
Priorities
Developing a framework for prioritizing NTDs and allocating resources depends significantly on the target audience. Prof. Black emphasizes that diseases such as dengue, chikungunya, Zika, Chagas, schistosomiasis, leishmaniasis, and tuberculosis have a global presence and are particularly problematic in developing countries.
From a strictly health economics perspective, the global impact of these diseases is substantial. Prof. Black is convinced that even small technological or lifestyle interventions can yield significant health and economic benefits.
AMR vaccines
Antimicrobial Resistance (AMR) occurs when bacteria, viruses, fungi and parasites no longer respond to antimicrobial medicines. According to WHO, bacterial AMR was directly responsible for approximately 1.27 million deaths globally in 2019 and contributed to a total of 4.95 million deaths. In addition to the toll on health, AMR incurs significant economic costs. The World Bank estimates that AMR could result in an additional $1 trillion in healthcare costs by 2050 and losses of $1 trillion to $3.4 trillion in gross domestic product (GDP) annually by 2030.
AMR has posed a global public health threat for many years, with more deaths from these infections than from tuberculosis and malaria combined. While many have proposed developing vaccines to combat AMR, significant challenges remain. Prof. Black highlights that testing these vaccines and determining who should be vaccinated are the primary obstacles.
With some bacteria now completely resistant to antibiotics, developing vaccines to combat AMR is complex. However, Prof. Black believes the necessary technology is available. He notes that at least one trial is underway for urinary tract infections, but he emphasizes that prioritizing the prevention of antibiotic-resistant sepsis is crucial.
“Try and think about how you would do a clinical trial for that. I mean, you could vaccinate everybody coming into the ICU, but that isn’t a great time to vaccinate people. Their immune system is probably not optimally there,” he reflects, questioning how to control those cohorts and measure outcomes effectively.
Additionally, identifying at-risk individuals may be challenging, and vaccinating the entire population could prove prohibitively expensive.
Vaccine sckepticim
Vaccination resistance has been a long-standing concern, and it has intensified following the pandemic. Prof. Black explains that, given the current erratic political environment worldwide, compulsory vaccination may not be the best solution. He believes that communities often need to experience the impact of disease firsthand to combat skepticism and improve vaccination rates. From his experience, people are generally poor at rationally evaluating risks and benefits.
“I don’t think the coverage is high in Argentina or Brazil or Chile because of it being compulsory. I think it’s because there’s trust in the immunization program and the risk of the diseases has been well communicated,” he sustains, adding that case studies in South America could help us understand why these National Immunization Programs (NIPs) are so successful.
Prof. Black is among many experts alarmed by the potential disaster posed by an avian flu pandemic, which he believes has not received the attention it warrants. His concern centers on the likely emergence of a more highly communicable H5N1 virus, coupled with the absence of preventive measures such as raising public awareness and stockpiling vaccines.
Despite many efforts, vaccine hesitancy remains widespread and skepticism persists globally. Prof. Black acknowledges that credibility is undermined when the scientific community denies risks and insists that vaccines are “totally safe.”
“I think it’s better to acknowledge that there’s a risk to anything and try and frame it in terms of the benefit again,” he concludes, adding that the causative agents for most vaccine preventable diseases are still out there waiting to return if we don’t vaccinate.
