By Col. (Ret.) Zygmunt Dembek
Mpox disease – formerly known as monkeypox – caught the headlines in 2024 as rising cases in Africa and limited outbreaks around the world led to fears of another pandemic. Col. (Ret.) Zygmunt Dembek provides an update.
Mpox disease is caused by infection with the monkeypox virus, an enveloped double-stranded DNA virus belonging to the Orthopoxvirus genus of the Poxviridae family. Human mpox was discovered in 1970 when the first case occurred in the Democratic Republic of the Congo (DRC).
Today, the disease originates in many central and west African nations. It has become endemic and is assumed to be consistently present within this large geographic area. Mpox symptoms can be mild or severe, and often include fever of over 38°C, a rash, headache, fatigue, muscle aches, and swollen lymph nodes.
The first mpox outbreak outside of Africa occurred in the U.S. in 2003. Humans contracted the disease from handling prairie dogs that were infected with mpox virus from co-location or transport with African rodents imported from Ghana. This zoonotic outbreak, meaning disease transmission from animals to people, demonstrated the potential for mpox to spread globally.
Zoonotic and Human-to-Human Mpox Transmission
Zoonotic transmission of monkeypox virus occurs by direct contact with bodily fluids, blood, or lesions of infected animals. Human-to-human mpox transmission stems from direct contact with skin lesions of an infected person, sexual contact, contact with materials contaminated with live virus – known as fomite transmission – or from respiratory droplets. Respiratory droplet transmission requires prolonged face-to-face contact, unlike aerosol transmission of more readily transmitted airborne viruses such as COVID-19. The incubation period for human mpox infection, or the time from exposure to symptom development, ranges from five to 21 days.
There are two types of monkeypox virus clades, or groups of genetically related viruses. Monkeypox virus clade 1 is associated with a greater percentage of infected individuals developing severe illness and death, as compared to clade 2 viruses. The global mpox clade 2 outbreak in 2022 caused over 90,000 global cases and peaked that August, primarily spread by sexual contact. Clade 1b mpox was initially detected in September 2023.

Global Mpox Transmission
Sustained global transmission of human mpox infection occurred in May 2022 with the first case confirmed in the U.K. Human mpox cases have since occurred in many countries outside Africa, including Portugal, Spain, the U.S., Sweden, Italy, Belgium, Canada, Australia, Thailand, India, France, Germany, the Netherlands, Switzerland, Israel, Austria, Denmark, the Czech Republic, the United Arab Emirates, Slovenia, Argentina, Finland, Ireland, and Mexico.
The Democratic Republic of the Congo reported over 14,000 suspected mpox cases in 2023, over three times as many as had occurred in the previous year. This country reported 95% of the total number of global mpox cases and 99% of deaths in 2024. As of mid-November 2024, there have been over 29,000 suspected mpox cases and over 800 deaths so far this year. An outbreak of clade 1b mpox has currently spread in central and eastern Africa with ongoing person-to-person mpox transmission in Burundi, Central African Republic, DRC, the Republic of Congo, Rwanda, and Uganda. It has also spread to Africa, Europe, Asia, and Australia. The first case of clade 1 mpox in the U.S. was confirmed in November 2024 following the infected individual’s recent return from an area experiencing clade 1 mpox transmission.
In August 2024, the WHO declared the ongoing mpox outbreak a public health emergency of international concern in the DRC. In the same month, the Africa Centres for Disease Control and Prevention classified mpox as a public health emergency of continental security, the first such declaration by the agency since its inception in 2017.
At the time of writing, the ongoing global outbreak of clade 2b mpox has caused more than 100,000 cases in 122 total countries, including in 115 countries where mpox was not previously reported. The total number of cases are almost equally caused by both clades. As of mid-September 2024, there have been almost 13,000 mpox cases in the U.S. in 2024.
Particularly within Africa, transmission of mpox continued to grow towards the end of 2024 and into 2025. According to a World Health Organization report published on January 11, 2025, confirmed cases of mpox in the DRC between November 25 and January 5 totaled 2,464, including five deaths. 798 cases and no deaths had been registered in Burundi within that period, while Uganda registered 767 cases and eight deaths. Rwanda and Kenya registered 17 and 12 cases, respectively, in that period, with no deaths.
Most recently, on January 9, Chinese authorities reported a cluster of clade 1b mpox infections that began with a foreigner who has a history of travel and residence in the DRC. Then, on January 13, Sierra Leone declared a public health emergency after two cases of mpox were reported.

Childhood Risk of Mpox
In Africa, where the disease is endemic, children often contract mpox through contact with infected wild animals. Infected humans can then spread mpox to close household contacts. Animals outside of Africa do not normally carry mpox and are not considered to be mpox disease reservoirs. The high number of children with mpox reported in the DRC is thought to be the result of disease spread within and between households. Contributing factors include crowding and lack of information about the spread of mpox.
Childhood risk of contracting mpox is not thought to be an issue in nations with different household composition, capacity for cleaning, improved access to medical care, and patient care. Disease modeling simulation for clade 1 mpox outbreaks from close-contact transmission within and between households in the U.S. has shown that close-contact transmission is unlikely to result in large numbers of mpox clade 1 cases.
Mpox Vaccines
Mpox vaccines are available for those at risk of contracting the disease, particularly from engaging in various sexual activities. Two vaccines are approved by the U.S. Food and Drug Administration (FDA) and are available in the U.S. to prevent smallpox and mpox disease. These are JYNNEOS and ACAM2000. Both vaccines are maintained in the U.S. Strategic National Stockpile managed by the Department of Health and Human Services’ Assistant Secretary for Preparedness and Response. The Strategic National Stockpile helps ensure that these vaccines are accessible as needed.
JYNNEOS is a live virus vaccine containing Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) a weakened, non-replicating Orthopoxvirus. This vaccine is administered subcutaneously in two doses, four weeks apart, and is the most widely used vaccine for mpox prevention. JYNNEOS has been approved by the U.S. FDA for use in those determined to be at high risk for mpox infection.

ACAM2000 is a live replicating vaccinia virus vaccine developed for protection against smallpox, and is also protective against other Orthopoxviruses, including monkeypox virus. The risk from medical complications is greatest with the ACAM2000 live virus vaccine, including myocarditis and pericarditis, swelling of the brain and spinal cord, and accidental eye infection.
Vaccination against mpox disease has not always been reliable. From May 2022 to May 2024, there were 271 reported cases of mpox in fully vaccinated individuals having had two doses of JYNNEOS vaccine. Overall, mpox infections were reported from less than 1% of fully vaccinated individuals. It is estimated that only 25% of the total U.S. population at risk of contracting mpox has been fully vaccinated.
A November 2024 World Health Organization announcement outlined the current effort to distribute 899,000 mpox doses of the MVA-BN vaccine to nine African nations. Over 5.85 million vaccine doses were expected to be made available by the end of 2024.
Mpox Treatment
While treatments approved by the FDA exist for mpox disease, antiviral compounds may potentially treat human mpox. In the U.S. these are only available through clinical trials or through the FDA’s expanded access program, also known as “compassionate use.”
TPOXX (tecovirimat) and Tembexa (brincidofovir) are FDA-approved antiviral compounds for the treatment of smallpox in adults and children, and Tembexa is also approved for treating newborns. Unfortunately, the safety and efficacy of TPOXX and Tembexa for treating human mpox cases is unknown. Further, there are serious safety issues known to be associated with the Tembexa use, including risks of liver toxicity, birth defects, cancer, and male infertility.
The World Health Organization recently approved the first mpox diagnostic test under an emergency authorization procedure. The Alinity m MPXV assay is a reverse transcription polymerase chain reaction test that enables the detection of the virus by testing swabs of skin lesions.
Conclusion
While global transmission of mpox continues, the hardest-hit nations are in Africa where endemic transmission occurs, particularly the DRC. It is hoped that the vaccination effort that has now begun will eventually contribute to ending endemic mpox transmission and end the global spread of this disease.
Col. (Ret.) Zygmunt F. Dembek is an epidemiologist and biochemist. He has written extensively on biodefense and has conducted pandemic preparedness exercises worldwide.