Disease-X: Accounting for the unknown

Gentlemen, it is the microbes who will have the last word. Currently, there are a large number of pathogens that are a potential threat to public health due to their attributes of causing an epidemic and the limitations in measures to control them. “Disease X” is a part of the list of such infections. The WHO says, “Disease X represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease.”1 Various pathogens, including viruses, bacteria, fungi, parasites, and prions, can potentially be pathogen X. Bacteria (including rickettsia) account for about 54% of more than 300 emerging infectious disease episodes documented from the year 1940 to 2004. This number concerningly includes drug-resistant bacteria. Viral or prion pathogens (about 25%), protozoa (about 11%), fungi (about 6%), and helminths (about 3%) are less frequent and are more often found to be evolving zoonotic infections.2 It has been noted as a global concern that the introduction of pathogens that are engineered, whether through laboratory mishaps or as a result of bioterrorism, can also result in a devastating Disease X.3 This reinforces the potential for a developed pandemic pathogen, a hazard that must be monitored. In its recent update, the WHO has decided to renew the list of priority infections that can give rise to outbreaks, and it is advised that they need close watch by countries over the globe. They also stated that a new disease, called Disease X, would be added to the list. The list was initially released in 2017, with the most recent prioritization being completed in the year 2018. Covid-19, Ebola and Marburg virus, Crimean-Cong hemorrhagic fever, Lassa fever, Middle East respiratory syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), Rift valley fever, Zika fever, Nipah and Henipaviral diseases and Disease X are all on the list at the moment. The updated list of pathogens is anticipated to be issued in the first few months of 2023. The list is designed to serve as a tool to address gaps in knowledge and to convey priority in view of research and development with a view that it will aid the development of investments in management options, including vaccines. WHO's executive director for the Health Emergencies Program brought to light that choosing priority infections and families of viruses for research and development and looking for measures to tackle them is crucial for a quicker and more efficient response to an epidemic or a pandemic. To emphasize this, he added that with noteworthy research and investments done before the Covid-19 pandemic times, it would be easier to come up with effective and safe vaccines within the desperate limitation of time.4 Looking at the ongoing trends, a majority of recent catastrophic onsets have involved RNA viruses, contradictory to the fact that viral pathogens only make up a small component of the pathogens responsible for emerging infectious diseases.5 HIV/AIDS, influenza virus, SARS-causing coronavirus, monkeypox, MERS, Ebola, Zika, and henipavirus outbreaks are among the recent viral outbreaks. The viruses that replicate within the cytoplasm are known to be more associated with spread. Limitations in transmission, special growth requirements, and availability of antimicrobials are thought to be the reasons for the lower risk of outbreaks from other pathogens when compared to viruses.5-7 Error-prone RNA viruses have evolved, allowing for great mutability, which allows them to evade host defenses. They can reproduce across a variety of host species. The recent spread of Ebola, Nipah virus encephalitis, and severe acute respiratory syndrome make the role of wildlife zoonotic transmission evident. Furthermore, RNA viruses make up about 94% of zoonotic viruses that infect people.8 Zoonotic transmission is multifactorial and frequently takes place in areas where people interact with a variety of mammals. Changes in patterns of human use of land for agriculture, trading, raising of livestock, and travel facilitates human exposure to diverse wildlife and microbial environment, resulting in viruses having the chance to cross different species and leading to localized emergence.6 The PREDICT project by United States Agency for International Development (USAID) has come up with a surveillance program to control viruses before they spread to humans and at a level where management strategies can be implemented. It focuses on regions considered as more likely o be involved in emerging infectious diseases, including Asia, central Africa, and regions of Latin America.7, 9 The transformation from self-limiting emerging episodes into persistent person-to-person transmission is driven by a combination of improved virulence and population dynamics. As an agency with lower funds and poor political influence, the WHO frequently loses to take prompt, decisive action to stop the spread of transmissible illnesses. WHO has come under fire for failing to respond to pandemics like the 2014 Ebola pandemic. According to research conducted to determine who should be held accountable for the 2014 Ebola outbreak, the WHO may have contributed to the problem, but lack of cooperation from governments and delayed financing have also been identified as contributing factors.10 The COVID-19 pandemic has shown the scale at which these novel pathogens can be a threat and the mass destruction that they can cause. Despite not being the first to cause chaos on our planet, it most definitely won't be the last. This proposes the need to be prepared for the next upcoming novel or re-emerging diseases by bridging organizational inadequacies, identifying key infections and hazardous regions, and highlighting alleged risk factors. The need to significantly fund the monitoring, study, and management of newly evolving potential pandemic agents that may result in disease X is urgent. Creating new research Laboratories in all countries is very important. Funds should be distributed equally so that scientists from every part of the world can collaborate. “Without laboratories, men of science are soldiers without arms,” said Louis Pasteur. The emergence of a pandemic can be mitigated by controlling the following related risk factors; human activity close to wildlife, production of foods containing animal products with insufficient employee oversight, and an unclear chain of supply, vectors including insects and ticks, extremely high density of population, and limited inspection and laboratory capacity. The steps that can be taken to contain Disease X include a collaborative and multidisciplinary approach from local to global levels developing international guidelines to contain bioterrorism, taking advice from scientists without any political hindrance, travel restrictions, and screenings.3 The use of antibiotics should be controlled to reduce the chance of resistance. We should give more focus and funds to vaccine research and communicable disease-based research. Apart from infectious diseases, public health courses are equally important. All the universities in the world should incorporate public health and infectious disease courses. Students should be encouraged in these courses. The Medical Council of the country should recognize these degrees. Climate changes are also a big reason behind these outbreaks. Recently, globally people are showing concerns over climate change. Many conferences are being held on this topic. We should incorporate the steps and decisions in society, and we should observe these parts very strictly. We can use Artificial Intelligence (AI) to mitigate the disease outbreak. Joint efforts from scientists, public health experts, and epidemiologists all over the world to eliminate the disease within a particular time, mass testing, and contact tracing will be helpful. The creation, availability, and approval of acceptable countermeasures, principally vaccinations, and clinical trials that are necessary before and during the pandemic, accelerated with timely funding, will prevent a potential release of a novel virus or pathogen which is currently unknown. Sumitaksha Banerjee: Writing—original draft. Qamar Sultana: Conceptualization; Writing—original draft. Dattatreya Mukherjee: Writing—original draft; Writing—review & editing. Vibhor Agrawal: Supervision; Writing—review & editing. Vikash Jaiswal: Conceptualization; Resources; Supervision. Kusum Paudel: Resources. The authors declare no conflict of interest. The lead author Kusum Paudel affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. N/A.