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Will Monkeypox go Corona way? 

COMMENTARYWill Monkeypox go Corona way? 

Monkeypox virus (MPXV) is closely related to smallpox, the deadliest virus in history responsible for unparalleled devastation of human population in the past centuries accounting for more deaths than any other single infectious disease, even plague and cholera. With the complete eradication of smallpox about 50 years ago and subsequent cessation of smallpox vaccination programme (which had provided some cross protection against monkeypox virus as well), the current human population has much reduced levels of immunity against this group of viruses. This reasonably explains the current rise and spread of monkeypox virus from its endemic regions in Africa to North America, Europe and Australia. Further, in addition to the spread through close contact, there are indications that monkeypox virus may spread through respiratory droplets (and possibly short-range aerosols), or by being in contact with contaminated materials as well. This situation calls for heightened surveillance and development of novel solutions to combat the virus from spreading. The need may arise not only to develop novel diagnostics tools for early detection of the disease but also suitable and effective vaccines together with relevant therapeutics. This could be based on viral immunomodulatory proteins that interfere with the human immune system. The present commentary talks about the measures required to avoid the monkeypox going corona way. 

While COVID-19 pandemic seems to be subsiding, at least in terms of high severity requiring hospitalisation and mortality, monkeypox disease caused by monkeypox virus (MPXV) is very much in news these days for its extensive geographic spread from its endemic regions in Africa to countries in North America, Europe and Australia. Although monkeypox is not a novel virus nor it is smallpox (one of history’s deadliest virus responsible for over 300 million deaths since 1900 alone(1) that caused unparalleled devastation of human populations accounted for more deaths than any other single infectious disease, even plague and cholera)(2), it has raised global alarm making many to think of it as a probable next corona-like pandemic in near future especially in view of the fact that monkeypox virus is closely related to smallpox virus and the current human population has reduced immunity against pox viruses due to eradication of smallpox and subsequent cessation of smallpox vaccination programme which provided some cross protection against monkeypox virus as well.   

Monkeypox virus (MPXV), the virus responsible for smallpox-like disease in humans, is a DNA virus belonging to Poxviridae family and Orthopoxviral genus. It is closely related to variola virus that causes smallpox disease. Monkeypox virus is naturally transmitted from animal to human and vice versa. It was first discovered in monkeys in 1958 (hence the name monkeypox). The first case among human was reported in 1970 in Congo. Since then, it has been endemic to areas in Africa. Outside Africa, it was first reported in 2003(3). There has been a steady increase in the number of cases since it was first reported in 1970 from a mere 47 from 1970-79 to around 9400 confirmed cases in the year 2021 alone. WHO has classified the threat from monkey pox as moderate as there has been 2103 confirmed cases from Jan 2022 with 98% cases occurring in May and June 2022. 

Monkeypox can soon become a global threat due to the phenomena of waning immunity that has happened due to the eradication of small pox almost 50 years ago. In addition, although the MPXV has a lower mutation rate, there is a possibility of acquiring mutations that provide ability to infect and cause severe disease in humans, due to selection pressure (4). In fact, the latest outbreak shows presence of such mutations resulting in altered proteins being made that provide MPXV ability to cause disease leading to morbidity and mortality in humans, compared to previous outbreaks (4). Another challenge posed by MPXV, that has arisen out of the UK study (5) recently, is the prolonged virus presence experienced by several patients due to upper respiratory tract viral shedding, after crusting of all cutaneous lesions. This can lead to potential spread of virus through sneezing by coming into contact with the droplets released. This suggests that MPXV has the capability of spreading the way SARS CoV2 engulfed the world, through the respiratory route, thereby causing the full-blown disease. WHO, in its recent situation update (6) says, ‘’Human-to-human transmission occurs through close proximity or direct physical contact (e.g., face-to-face, skin-to-skin, mouth-to-mouth, mouth-to-skin contact including during sex) with skin or mucous membranes that may have recognized or unrecognized infectious lesions such as mucocutaneous ulcers, respiratory droplets (and possibly short-range aerosols), or contact with contaminated materials (e.g., linens, bedding, electronics, clothing)’’. 

Considering the potential of a pandemic scenario being created and due to the recent outbreak and surge of cases outside Africa, there is a need for heightened surveillance (although the surveillance at present but there is a need to increase the same) and detection mechanisms to understand the epidemiology of this resurgent disease in order to prevent it from becoming a pandemic (3). The lack of surveillance and awareness may contribute to a potential global outbreak. Because monkeypox being a rare disease, its diagnosis has been based on clinical manifestation of symptoms (swollen lymph nodes to distinguish monkeypox from other poxes and characteristic lesions on skin) and confirmation by histopathology and virus isolation. Considering the recent outbreaks across several continents, there is a definite requirement for developing novel molecular diagnostics tools to detect MPVX, before it presents as a full-blown disease, implement measures for infection control and introducing treatment strategies using currently available drugs (5) against small pox along with developing new and effective therapies for MPVX. A need may also arise to either start small pox vaccination again or by developing novel and more effective vaccines against monkey pox. The capabilities developed by pharma companies worldwide for vaccine development and manufacturing caused by the corona pandemic will certainly provide an edge in designing new vaccines quickly against MPXV and may help in preventing MPXV going the corona way. 

The novel molecular diagnostics can be based on detection of virus coded immunomodulatory proteins (7) such as IFN gamma binding protein gene that is common to all orthopoxviruses(8). In addition, therapeutics can be developed (both small molecule and protein based) targeting the IFN gamma binding protein from the monkey pox virus that disrupts IFN gamma signalling. The IFN gamma binding protein can also be exploited as a vaccine candidate against monkeypox virus. 

It seems that the complete eradication of Smallpox was not a good Idea. In fact, infections could be allowed to remain at a harmless lowest level in the population to maintain a minimal level of immunity. Perhaps, not eradicating any disease completely could be a well thought of strategy!!!   

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References:  

  1. American Museum of Natural History 2022. Smallpox – Lessons from the Past. Available online at https://www.amnh.org/explore/science-topics/disease-eradication/countdown-to-zero/smallpox#:~:text=One%20of%20history’s%20deadliest%20diseases,the%20first%20disease%20ever%20eradicated. Accessed 20 June 2022.  
  1. Krylova O, Earn DJD (2020) Patterns of smallpox mortality in London, England, over three centuries. PLoS Biol 18(12): e3000506. DOI: https://doi.org/10.1371/journal.pbio.3000506 
  1. Bunge E., et al 2022. The changing epidemiology of human monkeypox—A potential threat? A systematic review. PLOS Neglected diseases. Published: February 11, 2022. DOI: https://doi.org/10.1371/journal.pntd.0010141 
  1. Zhang, Y., Zhang, JY. & Wang, FS. Monkeypox outbreak: A novel threat after COVID-19?. Military Med Res 9, 29 (2022). https://doi.org/10.1186/s40779-022-00395-y 
  1. Adler H., et al 2022. Clinical features and management of human monkeypox: a retrospective observational study in the UK, The Lancet Infectious Diseases. DOI: https://doi.org/10.1016/S1473-3099(22)00228-6 
  1. WHO 2022. Multi-country monkeypox outbreak: situation update. Published 4 June 2022. Available online at https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON390. Accessed on 21 June 2022. 
  1. Mike Bray, Mark Buller, Looking Back at Smallpox, Clinical Infectious Diseases, Volume 38, Issue 6, 15 March 2004, Pages 882–889, https://doi.org/10.1086/381976   
  1. Nuara A., et al 2008. Structure and mechanism of IFN-γ antagonism by an orthopoxvirus IFN-γ-binding protein. PNAS. February 12, 2008. 105 (6) 1861-1866. DOI: https://doi.org/10.1073/pnas.0705753105 

Bibliography 

  1. Unbound Medicine. Researches on Monkeypox – https://www.unboundmedicine.com/medline/research/Monkeypox 
  1. Edouard Mathieu, Saloni Dattani, Hannah Ritchie and Max Roser (2022) – “Monkeypox”. Published online at OurWorldInData.org. Retrieved from: ‘https://ourworldindata.org/monkeypox ‘ [Online Resource] 
  1. Farahat, R.A., Abdelaal, A., Shah, J. et al. Monkeypox outbreaks during COVID-19 pandemic: are we looking at an independent phenomenon or an overlapping pandemic?. Ann Clin Microbiol Antimicrob 21, 26 (2022). DOI: https://doi.org/10.1186/s12941-022-00518-22 or https://ann-clinmicrob.biomedcentral.com/articles/10.1186/s12941-022-00518-2#citeas  
  1. Pittman P. et al 2022. Clinical characterization of human monkeypox infections in the Democratic Republic of the Congo. Preprint in medRixv. Posted May 29, 2022. DOI: https://doi.org/10.1101/2022.05.26.222733799  
  1. Yang, Z., Gray, M. & Winter, L. Why do poxviruses still matter?. Cell Biosci 11, 96 (2021). https://doi.org/10.1186/s13578-021-00610-88  
  1. Yang Z. Monkeypox: A potential global threat? J Med Virol. 2022 May 25. doi: https://doi.org/10.1002/jmv.27884 . Epub ahead of print. PMID: 35614026. 
  1. Zhilong Yang. Twitter. https://mobile.twitter.com/yang_zhilong/with_replies 

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