For thousands of years, the smallpox virus (Variola) was a major scourge on human populations, sickening and killing hundreds of millions. As early as the 10^th C a prevention method, called variolation, was developed and used in Asia, India, and Africa. Variolation involved the use of material taken from a smallpox sore, which was inhaled or scratched into the skin. The procedure was introduced in Europe during the 18^th C by Lady Mary Worley Montague, who had her children variolated against the disease. Later in that same century, Edwin Jenner made an interesting observation regarding a related disease that infected cattle, called cowpox. He noted that milkmaids, who had experienced the milder cowpox disease, seemed resistant to smallpox. After inoculating a young boy with cowpox sore material, he found that the child did not develop smallpox. Hence, vaccinations against smallpox gradually replaced variolation for protection against serious disease.³

The World Health Organization (WHO), utilizing mandated childhood immunizations or mass vaccinations, followed by dedicated vigilance to contain isolated outbreaks, eliminated smallpox in 1980. The last known, naturally occurring case was in Somalia in 1977. Eradicating this human scourge was one of the greatest achievements in the history of public health.³

Today, monkeypox or Mpox virus, which is closely related to the smallpox virus, has caused outbreaks of a less deadly disease (Figures 1 & 2). (Scientist now are convinced that the virus was spread first from rodents, so that the disease is no longer called monkeypox.) Both viruses are DNA viruses. Although smallpox vaccinations are somewhat effective in preventing monkeypox, routine smallpox vaccination ended after the virus was declared eradicated.³ Those routine vaccinations might have kept Mpox at bay.^{6, 7, 8} DNA viruses like Mpox and smallpox generally do not mutate as fast as RNA viruses, because there are correction mechanisms during replication that proofread and repair incorrect DNA sequences. Nevertheless, some changes take place over time, and there are now new clades, or groups of different genetic ancestry.

Figure 2. Smallpox viruses

Source: CDC/ Dr. Fred Murphy; Sylvia Whitfield, https://commons.wikimedia.org/wiki/File:Smallpox_virus_virions_TEM_PHIL_1849.JPG

Monkeypox was first observed in a group of monkeys shipped to Denmark in 1958, but the original human case was diagnosed in the Democratic Republic of Congo (DRC) in an infant boy, who was not vaccinated against smallpox and died. Although Mpox is typically a relatively mild disease, with rash and flu-like symptoms, individuals with immune problems or certain other health issues have died from Mpox (Figure 3). After the first case, scattered/isolated cases appeared in children living in rural areas of western and central Africa.^{2, 5, 6} Mpox samples from patients were analyzed from clinical data and genomic sequencing, revealing two clades of the virus – clades I and II. For almost three decades, sporadic cases in the DRC, with fatality rates of 1-12%, occurred from clade 1.⁵ In 2017, another outbreak occurred, this time in Nigeria. These cases were caused by viruses from clade II. Most of the globe ignored the outbreak, even though it caught the attention of the international community in 2003, when an outbreak occurred in 71 people in the U.S. Travel-related cases occurred in Europe, Asia, and Europe between 2003 and 2021; and during 2022, a truly global community outbreak occurred, with more than 102,000 cases from Clade II detected in more than 100 countries.¹ Most cases came from close contacts between males having sex with males, but in many circumstances, it is children and women at the greatest risk.¹

Figure 3. Child with characteristic rash of monkeypox, which resembles that of smallpox

Source: CDC/ Brian W.J. Mahy, BSc, MA, PhD, ScD, DSc, https://commons.wikimedia.org/wiki/File:12783_lores.jpg#

The World Health Organization has declared Mpox a global health emergency. A new version of the virus (Clade 1B) has spread into areas where it had not appeared before and seems to be more dangerous, causing more deaths. The initial outbreak in the DRC has now spread to adjacent countries in Africa, but new, confirmed cases have appeared in Europe and the U.S.⁷ Fortunately, a vaccine (JYNNEOS), administered in two doses a month apart, protects an individual from Mpox and smallpox. However, there are shortages of the vaccine in Africa. Additionally, the public health systems in poorer nations are meager, and some of the most vulnerable people are found in rural areas.

If the COVID pandemic has taught us any lessons, we may expect other disease-causing viruses that can make human beings sick, perhaps leading to hospitalization or even death. As human populations increase in number and in exploitation of previously unexploited territories, the risks will continue and escalate.

References

1. CDC. “Ongoing clade II Mpox Global Outbreak” Center for Disease Control and Prevention. https://www.cdc.gov/mpox/outbreaks/2022/index-1.html

2. Gessain, Antoine M.D., Emmanuel Nakoune, Ph.D., and Yazdan Yazdanpanah, M.D. Monkeypox. N Engl J Med 2022;387:1783-1793. DOI: 10.1056/NEJMra2208860

3. History of the Smallpox Vaccine – World Health Organization https://www.who.int/news-room/spotlight/history-of-vaccination/history-of-smallpox-vaccination

4. Jezek Z, Marennikova SS, Mutumbo M, Nakano JH, Paluku KM, Szczeniowski M. Human monkeypox: a study of 2,510 contacts of 214 patients. J Infect Dis 1986; 154: 551–55.

5. Likos AM, Sammons SA, Olson VA, et al. A tale of two clades: monkeypox viruses. J Gen Virol 2005; 86: 2661–72.

6. Mitjà, Oriol, Dimie Ogoina, Boghuma K. Titanji, Cristina Galvan, Jean-Jacques Muyembe, Michael Marks, and Chloe M. Orkin. "Monkeypox." The Lancet 401, no. 10370 (2023): 60-74.

7. Nirappil, Fenit and Annabelle Timsit. “What to know about mpox after WHO declared it a global health emergency” Washington Post August 14, 2024. https://www.washingtonpost.com/health/2024/08/15/mpox-public-health-emergency-causes-symptoms/

8. Rimoin AW, Mulembakani PM, Johnston SC, et al. Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo. Proc Natl Acad Sci USA 2010; 107: 16262–67.

Emerging Viral Concerns – Mpox (Monkeypox)

by George Shiflet
Copyright © 2025 George Shiflet. All rights reserved.

References