The story so far
The recent outbreak reported in the first week of December 2024 in the Democratic Republic of Congo, which has claimed over 400 lives and remains unclassified, has raised concerns that it could be an instance of Disease X. This unsettling event has reignited discussions about “Disease X.” Disease X is not an actual but a hypothetical disease. The World Health Organization (WHO) coined the term in 2018 to describe an unknown pathogen that could potentially unleash a devastating epidemic or pandemic. It was conceptualised by the WHO to prepare for future outbreaks that are difficult to predict or identify. While investigations continue to determine the cause in Congo, the outbreak underscores the importance of Disease X.
WHO’s priority list of pathogens?
COVID-19 is widely regarded as the first instance of a real Disease X after the WHO introduced the concept in 2018. When SARS-CoV-2 emerged as an unknown pathogen causing a global pandemic, it exemplified the scenario that Disease X was meant to represent — an unpredictable, novel threat requiring rapid global response and adaptation. The concept of Disease X traces its origins in the aftermath of the West African Ebola epidemic of 2014–2016, which resulted in over 11,000 deaths and revealed significant gaps in global epidemic preparedness. After the outbreak, the WHO brought together scientists and public health experts to address how future outbreaks of similar scale could be prevented.
Swab samples being taken for a COVID-19 test. File
| Photo Credit:
The Hindu
The WHO’s priority list of pathogens is a strategic tool published in 2018 that is designed to focus global attention and resources on the most serious infectious disease threats. This list identifies diseases that have epidemic or pandemic potential for which there are insufficient or no medical countermeasures such as vaccines or treatments. The need for such a list arises from the urgency to guide research and development, allocate funding, and enhance preparedness. It helps policymakers, researchers, and health organisations prioritise efforts toward controlling the diseases. The current list (not exhaustive ) includes Ebola virus disease, Marburg virus disease, Lassa fever, Nipah virus, Rift Valley fever, Crimean-Congo haemorrhagic fever, Zika virus, and Disease X. Each of these pathogens has been flagged due to factors like high mortality rates, potential for rapid spread, and the lack of adequate preventive or therapeutic options.
What is Disease X?
Disease X is not a specific illness but a placeholder for an unpredictable and as-yet-undiscovered pathogen capable of sparking a global health crisis. The WHO included it in the Blueprint for Priority Diseases in 2018 to focus on the risks of emerging diseases that science has yet to encounter. The term sits at the intersection of two categories (among four) popularised by Donald Rumsfeld’s matrix: “known unknowns” (threats we are aware of but cannot fully understand) and “unknown unknowns” (threats we are not aware of and understand). Disease X embodies both, as it acknowledges the likelihood of a future pandemic without specifying when, where, or how it might arise.
The potential culprits behind Disease X are varied. It originates from Pathogen X, which could be a virus, a bacterium, a parasite, fungi, helminths, or even a prion — a misfolded protein capable of causing severe neurological diseases. Historical data supports this uncertainty. Since 1940 (from where authentic records are available), researchers have identified more than 300 emerging infectious diseases, about 70% of which have zoonotic origins, meaning they are transmitted from animals to humans. This process, known as zoonotic spillover, is often linked to human encroachment on wildlife habitats, deforestation, and the intensification of agriculture. Meanwhile, the growing risks of antimicrobial resistance, bioterrorism, and accidental lab leaks add further layers of unpredictability.
Patterns in emerging diseases
While the exact nature of Disease X remains unknown, epidemiological patterns provide critical insights into how new diseases emerge and spread. The emergence of viruses such as HIV, SARS, MERS, and Ebola was closely linked to ecological disruptions caused by human activity. Deforestation, urbanisation, and climate change have pushed humans and wildlife into closer contact, increasing the likelihood of pathogen transmission. Epidemiologists estimate that over 1.7 million undiscovered viruses exist in wildlife, with hundreds of thousands potentially capable of infecting humans. The frequency of novel outbreaks has also increased significantly since the mid-20th century, reflecting a combination of environmental, demographic, and global factors.
Regions with high biodiversity and inadequate healthcare systems, like the Congo Basin, are particularly vulnerable. The interconnectedness of our world, with frequent international travel and trade, makes it easier for localised outbreaks to escalate into pandemics, as seen with COVID-19. While epidemiology cannot predict the exact moment or source of Disease X, it can help identify high-risk regions and behaviours that increase the likelihood of its emergence.
Challenges of predicting Disease X
Forecasting the next Disease X is daunting, as its emergence depends on numerous unpredictable factors. Zoonotic diseases are the most likely source, given their history of driving major epidemics. However, other scenarios, such as pathogens mutating to evade treatment, laboratory mishaps, or deliberate biological attacks, cannot be ruled out. Climate change is also reshaping disease transmission dynamics, expanding the range of vector-borne illnesses like malaria and dengue fever while pushing pathogens to adapt to new hosts and environments.
The sheer number of potential pathogens adds to the complexity. Scientists estimate that only a fraction of viruses capable of infecting humans have been identified, leaving a vast pool of unknown threats. Genomic sequencing and artificial intelligence are beginning to play an important role in narrowing this vast field of possibilities, but even with these tools, predicting the exact origin, timing, and behaviour of Disease X remains out of reach. What is certain, however, is that the conditions that gave rise to pandemics like COVID-19 and SARS continue to exist, making the emergence of Disease X a question of when, not if.
At the heart of preparation is the need for robust surveillance systems to detect new outbreaks early. Advances in genomic sequencing, artificial intelligence, and real-time data sharing are essential tools for developing diagnostics, therapeutics, and vaccines. Strengthening healthcare infrastructure, particularly in low- and middle-income countries, is also crucial. Organisations like the Coalition for Epidemic Preparedness Innovations (CEPI) are now investing in “prototype pathogen” platforms that can be adapted to target unknown diseases within 100 days of their identification.
Need for global collaboration
Fighting Disease X will require an unprecedented level of international cooperation. The WHO’s ongoing efforts, such as its list of priority pathogens and the proposed Pandemic Treaty, aim to foster a unified global response to health emergencies. These initiatives recognize that pandemics do not respect borders and that fragmented efforts will be insufficient to counter a threat as elusive as Disease X. Governments must work together to share data, pool resources, and ensure equitable access to diagnostics, treatments, and vaccines.
The outbreak in the DRC serves as a sobering reminder of the risks the world faces. Disease X is no longer a distant hypothetical but an urgent call to action. By strengthening public health systems, investing in research and innovation, and fostering global solidarity, the world can prepare for the unpredictable and safeguard future generations from the devastating consequences of the next pandemic. Frameworks like the Nagoya Protocol, which ensure equitable sharing of benefits from genetic resources, could be expanded to include biological materials like pathogens. It would promote global collaboration, ensuring fair access to research and medical countermeasures during outbreaks. A novel disease anywhere is a threat to everyone.
(Dr. C. Aravinda is an academic and public health physician. The views expressed are personal. aravindaaiimsjr10@hotmail.com)
Published – December 12, 2024 11:18 pm IST
