Disease X
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Disease X is a
placeholder name Placeholder names are intentionally overly generic and ambiguous terms referring to things, places, or people, the names of which or of whom do not actually exist; are temporarily forgotten, or are unimportant; or in order to avoid stigmat ...
that was adopted by the
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
(WHO) in February 2018 on their shortlist of blueprint priority diseases to represent a hypothetical, unknown
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
. The WHO adopted the placeholder name to ensure that their planning was sufficiently flexible to adapt to an unknown pathogen (e.g., broader vaccines and manufacturing facilities). Former Director of the US
National Institute of Allergy and Infectious Diseases The National Institute of Allergy and Infectious Diseases (NIAID, ) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services. NIAID's mis ...
Anthony Fauci Anthony Stephen Fauci ( ; born December 24, 1940) is an American physician-scientist and immunologist who served as the director of the National Institute of Allergy and Infectious Diseases (NIAID) from 1984 to 2022, and the chief medical ...
stated that the concept of Disease X would encourage WHO projects to focus their research efforts on entire classes of viruses (e.g.,
flaviviruses ''Flavivirus'', renamed ''Orthoflavivirus'' in 2023, is a genus of positive-strand RNA viruses in the family ''Flaviviridae''. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika viru ...
), instead of just individual strains (e.g.,
zika virus Zika virus (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active ''Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, where ...
), thus improving WHO capability to respond to unforeseen strains. In 2020, experts, including some of the WHO's own expert advisors, speculated that
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
, caused by the
SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...
virus strain, met the requirements to be the first Disease X. In December 2024, an unidentified disease in the
Democratic Republic of the Congo The Democratic Republic of the Congo (DRC), also known as the DR Congo, Congo-Kinshasa, or simply the Congo (the last ambiguously also referring to the neighbouring Republic of the Congo), is a country in Central Africa. By land area, it is t ...
was sometimes referred to as Disease X, after infecting over 400 people and killing at least 79, later revealed to be an aggressive strain of malaria.


Rationale

In May 2015, in pandemic preparations prior to the COVID-19 pandemic, the WHO was asked by member organizations to create an "R&D Blueprint for Action to Prevent Epidemics" to generate ideas that would reduce the time lag between the identification of viral outbreaks and the approval of vaccines/treatments, to stop the outbreaks from turning into a "public health emergency". The focus was to be on the most serious
emerging infectious disease An emerging infectious disease (EID) refer to infectious diseases that have either newly appeared in a population or have existed but are rapidly increasing in incidence, geographic range, or severity due to factors such as environmental change ...
s (EIDs) for which few preventive options were available. A group of global experts, the "R&D Blueprint Scientific Advisory Group", was assembled by the WHO to draft a shortlist of less than ten "blueprint priority diseases". Since 2015, the shortlist of EIDs has been reviewed annually and originally included widely known diseases such as
Ebola Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after in ...
and
Zika Zika fever, also known as Zika virus disease or simply Zika, is an infectious disease caused by the Zika virus. Most cases have no symptoms, but when present they are usually mild and can resemble dengue fever. Symptoms may include fever, conju ...
which have historically caused epidemics, as well as lesser known diseases which have potential for serious outbreaks, such as
SARS Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the virus SARS-CoV-1, the first identified strain of the SARS-related coronavirus. The first known cases occurred in November 2002, and the ...
,
Lassa fever Lassa fever, also known as Lassa hemorrhagic fever, is a type of viral hemorrhagic fever caused by the Lassa virus. Many of those infected by the virus asymptomatic, do not develop symptoms. When symptoms occur they typically include fever, wea ...
,
Marburg virus Marburg virus (MARV) is a hemorrhagic fever virus of the '' Filoviridae'' family of viruses and a member of the species '' Marburg marburgvirus'', genus '' Marburgvirus''. It causes Marburg virus disease in primates, a form of viral hemorrhag ...
,
Rift Valley fever Rift Valley fever (RVF) is a viral disease of humans and livestock that can cause mild to severe symptoms. The mild symptoms may include: fever, muscle pains, and headaches which often last for up to a week. The severe symptoms may include: loss ...
, and
Nipah virus Nipah virus (''Henipavirus nipahense'') is a bat-borne, Zoonosis, zoonotic virus that causes Nipah virus infection in humans and other animals, a disease with a very high mortality rate (40-75%). Numerous disease outbreaks caused by Nipah virus ...
. Since then,
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
has been added to the list. In February 2018, after the "2018 R&D Blueprint" meeting in
Geneva Geneva ( , ; ) ; ; . is the List of cities in Switzerland, second-most populous city in Switzerland and the most populous in French-speaking Romandy. Situated in the southwest of the country, where the Rhône exits Lake Geneva, it is the ca ...
, the WHO added Disease X to the shortlist as a placeholder for a " knowable unknown" pathogen. The Disease X placeholder acknowledged the potential for a future epidemic that could be caused by an unknown pathogen, and by its inclusion, challenged the WHO to ensure their planning and capabilities were flexible enough to adapt to such an event. At the 2018 announcement of the updated shortlist of blueprint priority diseases, the WHO said: "Disease X represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease". John-Arne Røttingen, of the R&D Blueprint Special Advisory Group, said: "History tells us that it is likely the next big outbreak will be something we have not seen before", and "It may seem strange to be adding an 'X' but the point is to make sure we prepare and plan flexibly in terms of vaccines and diagnostic tests. We want to see 'plug and play' platforms developed which will work for any or a wide number of diseases; systems that will allow us to create countermeasures at speed". US expert
Anthony Fauci Anthony Stephen Fauci ( ; born December 24, 1940) is an American physician-scientist and immunologist who served as the director of the National Institute of Allergy and Infectious Diseases (NIAID) from 1984 to 2022, and the chief medical ...
said: "WHO recognizes it must 'nimbly move' and this involves creating platform technologies", and that to develop such platforms, WHO would have to research entire classes of viruses, highlighting
flavivirus ''Flavivirus'', renamed ''Orthoflavivirus'' in 2023, is a genus of positive-strand RNA viruses in the family ''Flaviviridae''. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika viru ...
es. He added: "If you develop an understanding of the commonalities of those, you can respond more rapidly".


Adoption

Jonathan D. Quick, the author of ''End of Epidemics'', described the WHO's act of naming Disease X as "wise in terms of communicating risk", saying "panic and complacency are the hallmarks of the world's response to infectious diseases, with complacency currently in the ascendance". ''
Women's Health Women's health is an example of population health, where health is defined by the World Health Organization (WHO) as "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity". Often treated ...
'' wrote that the establishment of the term "might seem like an uncool move designed to incite panic" but that the whole purpose of including it on the list was to "get it on people's radars".
Richard Hatchett Richard Hatchett is an American oncologist and epidemiologist who has been serving as chief executive officer of the Coalition for Epidemic Preparedness Innovations (CEPI) in Oslo and London since 2017. He was awarded the Secretary of Health and ...
of the
Coalition for Epidemic Preparedness Innovations The Coalition for Epidemic Preparedness Innovations (CEPI) is a foundation that takes donations from public, private, philanthropic, and civil society organisations, to finance independent research projects to develop vaccines against emerging ...
(CEPI), wrote "It might sound like science fiction, but Disease X is something we must prepare for", noting that despite the success in controlling the 2014
Western African Ebola virus epidemic The 2013–2016 epidemic of Ebola virus disease, centered in West Africa, was the most widespread outbreak of the disease in history. It caused major loss of life and socioeconomic disruption in the region, mainly in Guinea, Liberia and Sie ...
, strains of the disease had returned in 2018. In February 2019, CEPI announced funding of US$34 million to the German-based CureVac
biopharmaceutical A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, t ...
company to develop an "RNA Printer prototype", that CEPI said could "prepare for rapid response to unknown pathogens (i.e., Disease X)". Parallels were drawn with the efforts by the
United States Agency for International Development The United States Agency for International Development (USAID) is an agency of the United States government that has been responsible for administering civilian foreign aid and development assistance. Established in 1961 and reorganized in 1998 ...
(USAID) and their PREDICT program, which was designed to act as an early warning pandemic system, by sourcing and researching animal viruses in particular "hot spots" of animal-human interaction. In September 2019, ''
The Daily Telegraph ''The Daily Telegraph'', known online and elsewhere as ''The Telegraph'', is a British daily broadsheet conservative newspaper published in London by Telegraph Media Group and distributed in the United Kingdom and internationally. It was found ...
'' reported on how
Public Health England Public Health England (PHE) was an executive agency of the Department of Health and Social Care in England which began operating on 1 April 2013 to protect and improve health and wellbeing and reduce health inequalities. Its formation came as a ...
(PHE) had launched its own investigation for a potential Disease X in the United Kingdom from the diverse range of diseases reported in their health system; they noted that 12 novel diseases and/or viruses had been recorded by PHE in the last decade. In October 2019 in New York, the WHO's Health Emergencies Program ran a "Disease X dummy run" to simulate a global pandemic by Disease X, for its 150 participants from various world health agencies and public health systems to better prepare and share ideas and observations for combatting such an eventuality. In March 2020, ''
The Lancet Infectious Diseases ''The Lancet'' is a weekly peer-reviewed general medical journal, founded in England in 1823. It is one of the world's highest-impact academic journals and also one of the oldest medical journals still in publication. The journal publishes o ...
'' published a paper titled "Disease X: accelerating the development of medical countermeasures for the next pandemic", which expanded the term to include Pathogen X (the
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
that leads to Disease X), and identified areas of product development and international coordination that would help in combatting any future Disease X. In April 2020, ''The Daily Telegraph'' described
remdesivir Remdesivir, sold under the brand name Veklury, Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. is a Broad-spectrum antiviral drug, broad-spectrum ...
, a drug being trialed to combat COVID-19, as an anti-viral that
Gilead Sciences Gilead Sciences, Inc. () is an American biopharmaceutical company headquartered in Foster City, California, that focuses on researching and developing antiviral drugs used in the treatment of HIV/AIDS, hepatitis B, hepatitis C, influenza, and CO ...
started working on a decade previously to treat a future Disease X. In August 2023, the UK Government announced the creation of a new research center, located on the Porton Down campus, which is tasked at researching pathogens with the potential to emerge as Disease X. Live viruses will be kept in specialist containment facilities in order to develop tests and potential vaccines within 100 days in case a new threat is identified. In January 2024, during the
World Economic Forum The World Economic Forum (WEF) is an international non-governmental organization, international advocacy non-governmental organization and think tank, based in Cologny, Canton of Geneva, Switzerland. It was founded on 24 January 1971 by German ...
's annual meeting, Disease X was once again discussed as being a potential threat following the COVID-19 pandemic.


Strategy

A paper published in 2022 listed the following strategies in preparation for Disease X: * steps to reduce the risk of
spillover Spillover may refer to: * Adsorption spillover, a chemical phenomenon involving the movement of atoms adsorbed onto a metal surface * Catalyst support#Spillover * Behavioral spillover, the effect that one behavior has on other behaviors with a s ...
and the consequent introduction and spread of a new disease in humans; * improving
disease surveillance Disease surveillance is an epidemiological practice by which the spread of disease is monitored in order to establish patterns of progression. The main role of disease surveillance is to predict, observe, and minimize the harm caused by outbrea ...
in humans and animals, to rapidly detect and
sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is cal ...
the infectious agent; * strengthening research programs to shorten the time lag between the development and production of medical countermeasures; * rapid implementation of pharmaceutical (e.g. vaccination) and non-pharmaceutical (e.g.
social distancing In public health, social distancing, also called physical distancing, (NB. Regula Venske is president of the PEN Centre Germany.) is a set of non-pharmaceutical interventions or measures intended to prevent the spread of a contagious dise ...
) measures, to contain a large-scale epidemic; * develop international protocols to ensure fair distribution and global coverage of drugs and vaccines.


Candidates


Zoonotic viruses

On the addition of Disease X in 2018, the WHO said it could come from many sources citing
hemorrhagic fever Viral hemorrhagic fevers (VHFs) are a diverse group of diseases. "Viral" means a health problem caused by infection from a virus, " hemorrhagic" means to bleed, and "fever" means an unusually high body temperature. Bleeding and fever are comm ...
s and the more recent non-polio enterovirus. However, Røttingen speculated that Disease X would be more likely to come from
zoonotic A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a virus, bacterium, parasite, fungi, or prion) that can jump from a non-human vertebrate to a human. When h ...
transmission (an animal virus that jumps to humans), saying: "It's a natural process and it is vital that we are aware and prepare. It is probably the greatest risk". WHO special advisor Professor Marion Koopmans, also noted that the rate at which zoonotic diseases were appearing was accelerating, saying: "The intensity of animal and human contact is becoming much greater as the world develops. This makes it more likely new diseases will emerge but also modern travel and trade make it much more likely they will spread".


COVID-19 (2019–present)

From the outset of the
COVID-19 pandemic The COVID-19 pandemic (also known as the coronavirus pandemic and COVID pandemic), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began with an disease outbreak, outbreak of COVID-19 in Wuhan, China, in December ...
, experts have speculated whether
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
met the criteria to be Disease X. In early February 2020, Chinese virologist Shi Zhengli from the
Wuhan Institute of Virology The Wuhan Institute of Virology, Chinese Academy of Sciences (WIV; zh, s=中国科学院武汉病毒研究所) is a research institute on virology under the Wuhan Branch of the Chinese Academy of Sciences. Located in Jiangxia District, Wuh ...
wrote that the first Disease X is from a coronavirus. Later that month,
Marion Koopmans Maria Petronella Gerarda Koopmans (born 21 September 1956) is a Dutch virologist who is Head of the Erasmus MC Department of Viroscience. Her research considers emerging infectious diseases, noroviruses and veterinary medicine. In 2018 she was aw ...
, Head of Viroscience at Erasmus University Medical Center in
Rotterdam Rotterdam ( , ; ; ) is the second-largest List of cities in the Netherlands by province, city in the Netherlands after the national capital of Amsterdam. It is in the Provinces of the Netherlands, province of South Holland, part of the North S ...
, and a member of the WHO's R&D Blueprint Special Advisory Group, wrote in the scientific journal ''
Cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...
'', "Whether it will be contained or not, this outbreak is rapidly becoming the first true pandemic challenge that fits the disease X category". At the same time, Peter Daszak, also a member of the WHO's R&D Blueprint, wrote in an opinion piece in ''
The New York Times ''The New York Times'' (''NYT'') is an American daily newspaper based in New York City. ''The New York Times'' covers domestic, national, and international news, and publishes opinion pieces, investigative reports, and reviews. As one of ...
'' saying: "In a nutshell, Covid-19 is Disease X".


Synthetic viruses/bioweapons

At the 2018 announcement of the updated shortlist of blueprint priority diseases, the media speculated that a future Disease X could be created intentionally as a
biological weapon Biological agents, also known as biological weapons or bioweapons, are pathogens used as weapons. In addition to these living or replicating pathogens, toxins and Toxin#Biotoxins, biotoxins are also included among the bio-agents. More than 1,2 ...
. In 2018, WHO R&D Blueprint Special Advisor Group member Røttingen was questioned about the potential of Disease X to come from the ability of gene-editing technology to produce synthetic viruses (e.g., the 2017 synthesis of
Orthopoxvirus ''Orthopoxvirus'' is a genus of viruses in the family ''Poxviridae'' and subfamily ''Chordopoxvirinae''. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated wi ...
in Canada was cited), which could be released through an accident or even an act of terror. Røttingen said it was unlikely that a future Disease X would originate from a synthetic virus or a bio-weapon. However, he noted the seriousness of such an event, saying, "Synthetic biology allows for the creation of deadly new viruses. It is also the case that where you have a new disease there is no resistance in the population and that means it can spread fast".


Bacterial infection

In September 2019, Public Health England (PHE) reported that the increasing
antibiotic resistance Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resis ...
of bacteria, even to "last-resort" antibiotics such as
carbapenem Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Si ...
s and colistin, could also turn into a potential Disease X, citing the antibiotic resistance in gonorrhea as an example.


In popular culture

In 2018, the
Museum of London London Museum (known from 1976 to 2024 as the Museum of London) is a museum in London, covering the history of the city from prehistoric to modern times, with a particular focus on social history. The Museum of London was formed in 1976 by ama ...
ran an exhibition titled "Disease X: London's next epidemic?", hosted for the centenary of the
Spanish flu The 1918–1920 flu pandemic, also known as the Great Influenza epidemic or by the common misnomer Spanish flu, was an exceptionally deadly global influenza pandemic caused by the H1N1 subtype of the influenza A virus. The earliest docum ...
epidemic from 1918. The term features in the title of several works of fiction that involve global pandemic diseases, such as ''Disease '' (2020), and ''Disease X: The Outbreak'' (2019).


Conspiracy theories

Disease X has become the subject of several
conspiracy theories A conspiracy theory is an explanation for an event or situation that asserts the existence of a conspiracy (generally by powerful sinister groups, often political in motivation), when other explanations are more probable.Additional sources: * ...
, claiming that it may be a real disease, or conceived as a biological weapon, or engineered to create a planned epidemic.


See also

*
Bioterrorism Bioterrorism is terrorism involving the intentional release or dissemination of biological agents. These agents include bacteria, viruses, insects, fungi, and/or their toxins, and may be in a naturally occurring or a human-modified form, in mu ...
*
Coalition for Epidemic Preparedness Innovations The Coalition for Epidemic Preparedness Innovations (CEPI) is a foundation that takes donations from public, private, philanthropic, and civil society organisations, to finance independent research projects to develop vaccines against emerging ...
(CEPI) *
Global Research Collaboration for Infectious Disease Preparedness The Global Research Collaboration for Infectious Disease Preparedness (GloPID-R) is an international initiative to anticipate and prepare for future threats from infectious diseases. GloPID-R is intended to be a means for facilitating communication ...
(GloPIR-R) * Synthetic virology *
Nuremberg Code The Nuremberg Code () is a set of research ethics, ethical research principles for human experimentation created by the court in ''Doctors' trial, U.S. v Brandt'', one of the Subsequent Nuremberg trials that were held after the World War II, Seco ...


References


External links


Blueprint priority diseases
()—World Health Organization (6–7 February 2018)
Prioritizing diseases for research and development in emergency contexts
€”World Health Organization (March 2018)
(Video) What is Disease X
€”World Health Organization (16 March 2018)
The mystery viruses far worse than flu
€”
BBC News BBC News is an operational business division of the British Broadcasting Corporation (BBC) responsible for the gathering and broadcasting of news and current affairs in the UK and around the world. The department is the world's largest broad ...
(November 2018) {{authority control Disaster management Pandemics Placeholder names Viruses World Health Organization