Disease X

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Scanning electron microscopy (SEM) of SARS-CoV-2, speculated in 2020 as being the first real-world virus to create Disease X SARS-CoV-2 (yellow).jpg
Scanning electron microscopy (SEM) of SARS-CoV-2, speculated in 2020 as being the first real-world virus to create Disease X

Disease X is a placeholder name that was adopted by the World Health Organization (WHO) in February 2018 on their shortlist of blueprint priority diseases to represent a hypothetical, unknown pathogen that could cause a future epidemic. [4] [5] 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). [4] [6] Director of the US National Institute of Allergy and Infectious Diseases Anthony Fauci stated that the concept of Disease X would encourage WHO projects to focus their research efforts on entire classes of viruses (e.g., flaviviruses), instead of just individual strains (e.g., zika virus), thus improving WHO capability to respond to unforeseen strains. [7] In 2020, it was speculated, including among some of the WHO's own expert advisors, that COVID-19, caused by SARS-CoV-2 virus strain, met the requirements to be the first Disease X. [1] [2] [3]

Contents

Rationale

Jeremy Farrar, Chair of the WHO R&D Blueprint Scientific Advisory Group Jeremy Farrar C0058569 Wellcome Images.jpg
Jeremy Farrar, Chair of the WHO R&D Blueprint Scientific Advisory Group

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". [4] [9] The focus was to be on the most serious emerging infectious diseases (EIDs) for which few preventive options were available. [9] [10] A group of global experts, the "R&D Blueprint Scientific Advisory Group", [11] was assembled by the WHO to draft a shortlist of less than ten "blueprint priority diseases". [4] [5] [9]

Since 2015, the shortlist of less than 10 EIDs has been updated annually and has consistently included widely known names such as Ebola, Zika and SARS (e.g., cause of large-scale infections), and more geographically specific names such as Lassa fever, Marburg virus, Rift Valley fever, and Nipah virus. [5] [10]

In February 2018, after the "2018 R&D Blueprint" meeting in Geneva, the WHO added Disease X to the shortlist as a placeholder for a "knowable unknown" pathogen. [4] [6] [12] 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. [5] [13] [14]

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". [5] [6] [15] John-Arne Røttingen, of the R&D Blueprint Special Advisory Group, [8] 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". [6] [10] US expert Anthony Fauci 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 flaviviruses. He added: "If you develop an understanding of the commonalities of those, you can respond more rapidly". [7]

Adoption

Jonathan D. Quick, 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". [16] Women's Health 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". [17]

Richard Hatchett of the Coalition for Epidemic Preparedness Innovations (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, strains of the disease had returned in 2018. [18] In February 2019, CEPI announced funding of US$34 million to the German-based CureVac biopharmaceutical company to develop an "RNA Printer prototype", that CEPI said could "prepare for rapid response to unknown pathogens (i.e., Disease X)". [19]

Parallels were drawn with the efforts by the United States Agency for International Development (USAID) and their PREDICT programme, 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. [20]

In September 2019, The Daily Telegraph reported on how Public Health England (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. [21]

In October 2019 in New York, the WHO's Health Emergencies Programme ran a "Disease X dummy run" to simulate a global pandemic by a Disease X, in order 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. [22] [23]

In March 2020, The Lancet Infectious Diseases 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 that leads to Disease X), and identified areas of product development and international coordination that would help in combatting any future Disease X. [24]

In April 2020, The Daily Telegraph described remdesivir, a drug being trialed to combat COVID-19, as an anti-viral that Gilead Sciences started working on a decade previously to treat a future Disease X. [25]

Candidates

Zoonotic viruses

On the addition of Disease X in 2018, the WHO said it could come from many sources citing haemorrhagic fevers and the more recent non-polio enterovirus. [6] However, Røttingen speculated that Disease X would be more likely come from zoonotic 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". [6] [10] 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". [10] [26]

H7N9 (2018)

In 2018, a new strain of the H7N9 "bird flu" virus, with a 38 percent mortality rate, was likened to a potential Disease X by some international health authorities (but not the WHO, or the R&D Blueprint group). [27] [28] China would not share samples of the new H7N9 strain. However, they eventually brought the outbreak under control and the urgency dissipated. [29]

COVID-19 (2019–present)

Marion Koopmans, member of the WHO R&D Blueprint Special Advisory Group MarionKoopmans2018.jpg
Marion Koopmans, member of the WHO R&D Blueprint Special Advisory Group

From the outset of the COVID-19 pandemic, experts have speculated whether COVID-19 met the criteria to be Disease X. [30] [31] In early February 2020, Chinese virologist Shi Zhengli from the Wuhan Institute of Virology, wrote that the first Disease X is from a coronavirus. [3] Later that month, Marion Koopmans, Head of Viroscience at Erasmus University Medical Center in Rotterdam, and a member of the WHO's R&D Blueprint Special Advisory Group, [8] [32] wrote in scientific journal Cell , "Whether it will be contained or not, this outbreak is rapidly becoming the first true pandemic challenge that fits the disease X category". [2] [33] [34] 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 saying: "In a nutshell, Covid-19 is Disease X". [1]

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. [35] 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 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". [10]

Bacterial infection

In September 2019, Public Health England (PHE) reported that the increasing antibiotic resistance of bacteria, even to "last-resort" antibiotics such as carbapenems and colistin, could also turn into a potential Disease X, citing the antibiotic resistance in gonorrhea as an example. [36]

In 2018, the Museum of London ran an exhibition titled "Disease X: London's next epidemic?", hosted for the centenary of the Spanish flu epidemic from 1918. [37] [38]

The term features in the title of several fiction books that involve global pandemic diseases, such as Disease (2020), [39] and Disease X: The Outbreak (2019). [40]

See also

Related Research Articles

Pandemic Global epidemic of infectious disease

A pandemic is an epidemic of an infectious disease that has spread across a large region, for instance multiple continents or worldwide, affecting a substantial number of individuals. A widespread endemic disease with a stable number of infected individuals is not a pandemic. Widespread endemic diseases with a stable number of infected individuals such as recurrences of seasonal influenza are generally excluded as they occur simultaneously in large regions of the globe rather than being spread worldwide.

Zoonosis Disease that can be transmitted from other species to humans

A zoonosis is an infectious disease caused by a pathogen that has jumped from an animal to a human. Typically, the first infected human transmits the infectious agent to at least one other human, who, in turn, infects others.

Epidemic Rapid spread of disease affecting a large number of people in a short time

An epidemic is the rapid spread of disease to a large number of hosts in a given population within a short period of time. For example, in meningococcal infections, an attack rate in excess of 15 cases per 100,000 people for two consecutive weeks is considered an epidemic.

Spanish flu 1918–1920 global influenza pandemic caused by the H1N1 influenza A virus

Spanish flu, also known as the Great Influenza epidemic or the 1918 influenza pandemic, was an exceptionally deadly global influenza pandemic caused by the H1N1 influenza A virus. The earliest documented case was March 1918 in Kansas, United States, with further cases recorded in France, Germany and the United Kingdom in April. Two years later, nearly a third of the global population, or an estimated 500 million people, had been infected in four successive waves. Estimates of deaths range from 17 million to 50 million, and possibly as high as 100 million, making it one of the deadliest pandemics in human history.

Hong Kong flu 1986-89 flu pandemic

The Hong Kong flu, also known as the 1968 flu pandemic, was a flu pandemic whose outbreak in 1968 and 1969 killed between one and four million people globally. It is among the deadliest pandemics in history, and was caused by an H3N2 strain of the influenza A virus. The virus was descended from H2N2 through antigenic shift—a genetic process in which genes from multiple subtypes are reassorted to form a new virus.

Influenza pandemic Epidemic of a flu that spreads on a worldwide scale and infects a large proportion of the human population

An influenza pandemic is an epidemic of an influenza virus that spreads across a large region and infects a large proportion of the population. There have been six major influenza epidemics in the last 140 years, with the 1918 flu pandemic being the most severe; this is estimated to have been responsible for the deaths of 50–100 million people. The most recent, the 2009 swine flu pandemic, resulted in under 300,000 deaths and is considered relatively mild. These pandemics occur irregularly.

Emerging infectious disease Infectious disease of emerging pathogen, often novel in its outbreak range or transmission mode

An emerging infectious disease (EID) is an infectious disease whose incidence has increased recently, and could increase in the near future. The minority that are capable of developing efficient transmission between humans can become major public and global concerns as potential causes of epidemics or pandemics. Their many impacts can be economic and societal, as well as clinical. EIDs have been increasing steadily since at least 1940. For every decade since 1940, there has been a consistent increase in the number of EID events from wildlife-related zoonosis. Human activity is the primary driver of this increase, with loss of biodiversity a leading mechanism.

2009 swine flu pandemic 2009–2010 pandemic of swine influenza caused by H1N1 influenza virus

The 2009 swine flu pandemic, caused by the H1N1 influenza virus and declared by the World Health Organization (WHO) from June 2009 to August 2010, is the third recent flu pandemic involving the H1N1 virus. The first two cases were discovered independently in the United States in April 2009. The virus appeared to be a new strain of H1N1 that resulted from a previous triple reassortment of bird, swine, and human flu viruses which further combined with a Eurasian pig flu virus, leading to the term "swine flu".

<i>Plague Inc.</i> Mobile strategy video game

Plague Inc. is a real-time strategy simulation video game, developed and published by UK-based independent video game studio Ndemic Creations. The player creates and evolves a pathogen in an effort to annihilate the human population with a deadly pandemic. The game uses an epidemic model with a complex and realistic set of variables to simulate the spread and severity of the plague. It was released on 26 May 2012 for iOS and Microsoft Windows, 4 October 2012 for Android and 2015 for Windows Phone.

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 infectious diseases (EID).

Neil Ferguson (epidemiologist) British epidemiologist and researcher

Neil Morris Ferguson is a British epidemiologist and professor of mathematical biology, who specialises in the patterns of spread of infectious disease in humans and animals. He is the director of the Jameel Institute for Disease and Emergency Analytics (J-IDEA), director of the MRC Centre for Global Infectious Disease Analysis, and head of the Department of Infectious Disease Epidemiology in the School of Public Health and Vice-Dean for Academic Development in the Faculty of Medicine, all at Imperial College London.

Richard Hatchett American epidemiologist

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 Human Services’s Award for Distinguished Service.

Syra Madad is an American pathogen preparedness expert and infectious disease epidemiologist. Madad is the Senior Director of the System-wide Special Pathogens Program at NYC Health + Hospitals where she is part of the executive leadership team which oversees New York City's response to the Coronavirus disease 2019 pandemic in the city's 11 public hospitals. She was featured in the Netflix documentary series Pandemic: How to Prevent an Outbreak and the Discovery Channel documentary The Vaccine: Conquering COVID.

Pandemic prevention is the organization and management of preventive measures against pandemics. Those include measures to reduce causes of new infectious diseases and measures to prevent outbreaks and epidemics from becoming pandemics.

Nahid Bhadelia Indian-American infectious diseases physician and researcher

Nahid Bhadelia is an American infectious-diseases physician, founding director of Center for Emerging Infectious Diseases Policy and Research (CEID), an associate director at National Emerging Infectious Diseases Laboratories (NEIDL) at Boston University, and an associate professor at the Boston University School of Medicine.

1957–1958 influenza pandemic

The 1957–1958 Asian flu pandemic was a global pandemic of influenza A virus subtype H2N2 that originated in Guizhou in southern China. The number of excess deaths caused by the pandemic is estimated to be 1-4 million around the world, making it one of the deadliest pandemics in history. A decade later, a reassorted viral strain H3N2 further caused the Hong Kong flu pandemic (1968–1969).

Planning and preparing for pandemics has happened in countries and international organizations. The World Health Organization writes recommendations and guidelines, though there is no sustained mechanism to review countries' preparedness for epidemics and their rapid response abilities. National action depends on national governments. In 2005–2006, before the 2009 swine flu pandemic and during the decade following it, the governments in the United States, France, UK, and others managed strategic health equipment stocks, but they often reduced stocks after the 2009 pandemic in order to reduce costs.

Peter Daszak British-American zoologist

Peter Daszak is a British zoologist, consultant and public expert on disease ecology, in particular on zoonosis. He is the president of EcoHealth Alliance, a nonprofit non-governmental organization that supports various programs on global health and pandemic prevention. He is also a member of the Center for Infection and Immunity at the Columbia University Mailman School of Public Health.

William John Edmunds is a British epidemiologist, and a professor in the Faculty of Epidemiology and Population Health at the London School of Hygiene & Tropical Medicine.

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