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Monkeypox goes global: try to remain calm

Morgan Mathieu
Tags: Immunity, In the News

  • Background information on smallpox.
  • Current multi-country outbreak of monkeypox, origin, transmission, testing, symptoms, and replication.
  • Smallpox-based prevention to protect against monkeypox and current treatments.

We all have memories of our history classes and heard stories of smallpox epidemics often accompanied by gruesome images of bodies covered with these characteristic fluid-filled blisters. Smallpox (also called variola) is an infectious, scarring, and often lethal disease caused by the variola virus of the genus Orthopoxvirus. Although its actual origin remains unknown, there are evidence of the disease back to the time of the Egyptian mummies. The term “smallpox” was originally quoted in Britain’s 16th century to distinguish the disease from syphilis, referred to at the time as the “great pox”. It is estimated that 400,000 people died from the disease every year in Europe during the 18th century and that that number went up to 2 million people for a total of 15 million cases just in 1967 alone1.
The earliest hints of inoculation or ‘variolation’ allegedly took place during the 10th century. At the time, it consisted mostly in blowing powdered smallpox scabs up the noses of healthy individuals. In the 18th century, physicians in Europe further improved the process of variolation by simply exposing shallow skin incisions to smallpox pus. By the end of the 18th century, Edward Jenner revisited the connection between smallpox and cowpox, a virus later identified as a member of the genus Orthopoxvirus, and demonstrated the effectiveness of cowpox virus to vaccinate and protect humans from smallpox. In the 19th century, cowpox virus used for smallpox vaccination was replaced by another virus of the same genus called vaccinia virus, which is still used to this day in the current formulation of the smallpox vaccine as a live virus preparation. After mass vaccination efforts of the World Health Organization in the sixties and seventies, smallpox was deemed to be completely eradicated in 1980. Unfortunately, the very sudden and multi-country outbreak of monkeypox infections reopened the specter of smallpox because of the similarity of the symptoms, albeit milder.

Monkeypox multi-country outbreak of May 2022

As we are still dealing with the aftermath of the COVID-19 pandemic and learning to live with SARS-CoV-2, the world is facing yet another threat that has been making the headlines with cases of monkeypox cropping up across the globe. As of June 8th 2022, the monkeypox outbreak reached more than 1000 confirmed cases worldwide with cases throughout Africa but also in France, Israel, Singapore, the US, and the UK. Endemic to the tropical forest in Central and West Africa, monkeypox was first discovered in 1958 among laboratory monkeys in Denmark, hence its name. Although its natural reservoir is actually unknown, it is thought to come mainly from rodents (e.g. rats and/or squirrels) and may be spread via handling of bushmeat, an animal bite or a scratch, contact with body fluids or contaminated objects, or even skin-to-skin contact with an infected individual. As monkeypox virus does not remain long in the blood, PCR testing is often inconclusive and diagnosis is typically achieved by clinical differential diagnosis2.

Monkeypox see, monkeypox do: not entirely

Although similar in many ways, there are noticeable differences between monkeypox and smallpox. Monkeypox begins with fever, headache, muscle pains, and exhaustion. Contrary to smallpox, individuals afflicted by monkeypox develop lymphadenopathy. The period from exposure to onset can range from 5 to 21 days. Within a few days since the appearance of symptoms, individuals develop a rash often beginning on the face and then spreading to other parts of the body including the palms of the hands and the soles of the feet. Lesions progress through the stages of macules, papules, vesicles, pustules, and scabs before finally falling off. Unlike smallpox, the illness is considered to be self-limiting and typically lasts for two to four weeks. Nevertheless, severe cases can occur, notably in children, immunosuppressed individuals, and pregnant women. In Africa, about 1 in 10 individuals who contract the disease may die2.
Like other pox virions, monkeypox viral particles are large, enveloped, and brick-shaped entities. At the onset of infection, initial attachment of monkeypox virions to the host cell surface occurs through interactions between multiple viral ligands and cell surface receptors such as chondroitin sulfate or heparan sulfate depending on the type of cells. Instead of the nucleus, replication takes place in the cytoplasm following the remodeling of the host’s endoplasmic reticulum to create virion factories and the utilization of the host’s ribosomes to manufacture components of the virions. Newly formed viral particles are finally released by merging with the cell membrane.

Prevention and treatment

Each virion contains a linear double-stranded DNA. The nucleotide sequence within the central region of monkeypox virus genome encodes essential enzymes and structural proteins while the terminal regions encode virulence and other host-range factors. Comparison of the central region of monkeypox virus genome showed 96.3% identities with smallpox virus. Interestingly, the terminal regions of monkeypox virus and smallpox virus are significantly dissimilar, which seems to indicate that monkeypox virus is not a direct predecessor of smallpox virus and unlikely to obtain all the properties of the latter3.
Because the monkeypox virus is so closely related to the smallpox virus, it has been shown that the smallpox vaccine can protect individuals from getting monkeypox. Data obtained in Africa in the early eighties seem to indicate that the smallpox vaccine is at least 85% effective in preventing monkeypox4,5. Although it is possible that some of the older generations may still have some levels of immunity against smallpox6 and therefore monkeypox, the routine vaccinations against smallpox ended in the seventies and it is estimated that roughly 70% of the world population has no immunity to smallpox today, which could account for the multiple outbreaks of monkeypox seen in the last twenty years7.
It is currently recommended for the persons investigating monkeypox, or caring for infected individuals, or who had close contact with confirmed cases of monkeypox to get vaccinated8. The smallpox vaccine is typically administered, preferentially on the upper arm, with a bifurcated needle by rapidly pricking the skin about 15 times within an area of 5mm in diameter. The vaccination site should be covered with gauze to avoid spreading the virus to other sites of the body or to other people and checked after six to eight days. Regarding treatments of patients confirmed to be positive for monkeypox, they can be treated with tecovirimat, an antiviral medication approved for the treatment of several poxviruses including monkeypox. Brincidofovir, another antiviral drug, may also be used. These may be accompanied with supportive care to help regulate body temperature, fluids, and oxygenation9.

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  1. Smallpox: World Health Organization.
  2. Monkeypox: World Health Organization.
  3. S.N. Shchelkunow, et al. (2001) Human monkeypox and smallpox viruses: genomic comparison. FEBS Letters. 509, 66. Abstract.
  4. Vaccine effectiveness: Centers for Disease Control and Prevention.
  5. P.E. Fine, et al. (1988) The transmission potential of monkeypox virus in human populations. Int. J. Epidemiol. 17, 643. Abstract.
  6. D.D. Taub, et al. (2008) Immunity from smallpox vaccine persists for decades: a longitudinal study. Am. J. Med. 121, 1058. Abstract.
  7. K. Simpson, et al. (2020) Human monkeypox – After 40 years, an unintended consequence of smallpox eradication. Vaccine. 38, 5077. Abstract.
  8. Vaccines and immunization. World Health Organization.
  9. Vaccine administration. Centers for Disease Control and Prevention.

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