Mpox, formerly known as monkeypox, is a viral disease caused by the monkeypox virus (MPXV), a member of the Orthopoxvirus genus within the Poxviridae family. Historically, mpox has been confined to certain regions in West and Central Africa, where the virus is believed to be naturally carried by animals, particularly rodents such as squirrels, found in forested areas. Although historically human cases have been rare, the number of mpox cases in humans has steadily increased since the 1990s, particularly in countries where the virus is endemic. Since 2022, human mpox cases have been reported from 130 countries including mostly non-endemic countries. One factor contributing to this rise may be the discontinuation of the smallpox vaccination in the early 1980s after smallpox was eradicated. Smallpox vaccines provided some cross-protection against MPXV infection, and the cessation of vaccinations has led to a growing population that is increasingly susceptible to mpox. Other potential factors, still not fully understood, may also be increasing the risk of zoonotic spillover—where the virus jumps from animals to humans in endemic countries.

While the disease was once largely restricted to certain West and Central African countries, the first expansive multi-country outbreak of mpox were reported since May 2022. Since then, more than 130,000 laboratory-confirmed cases have been reported according to the World Health Organization (WHO). Since 2022, mpox cases have been primarily been linked to the Clade IIb variant MPXV. In 2023, however, the Democratic Republic of Congo (DRC) reported a significant rise in cases, associated with a new variant, Clade Ib MPXV, characterized by sustained human-to-human transmission of the virus. This variant, initially confined to the DRC, has spread to other parts Africa and beyond the continent since September 2024, albeit not to the extent of what has been reported since 2022 for Clade IIb MPXV. On September 5, 2025, the WHO changed the emergency declaration status of the outbreak, no longer classifying it as a Public Health Emergency of International Concern (or PHEIC). The Clade IIb and Clade Ib associated mpox outbreaks since 2022 have both been PHEIC during the course of the past three years. The recent decision to change this status, was based on a significant decline in cases and deaths, particularly in Africa, as well as a better understanding of the virus’s transmission dynamics allowing for improved data-driven decision making for prevention and control going forward. However, the WHO emphasized that the situation remains serious and that countries must continue to maintain vigilance. At 17 September 2025, the Africa Centres for Disease Control and Prevention (Africa CDC) has maintained the status of the mpox outbreaks in African countries as a Public Health Emergency of Continental Security (PHECS), urging for continued international support and surveillance.

In South Africa, mpox was first detected in 2022 during the peak of the multi-country outbreak, with 5 confirmed cases associated with the Clade IIb (sub-lineage B.1.7) MPXV. Three of the cases had a travel history to countries with ongoing outbreaks. No cases were reported for 2023 in South Africa. During 2023, marked decrease in number of cases were noted globally. From May – August 2024, 25 confirmed cases were reported, including three deaths. These cases were associated with the Clade IIb (sub-lineage B.1.20) MPXV. All but one case identified during 2024 had no travel history outside of South Africa prior to developing mpox. As of 28 October 2025, a total of 12 mpox cases   were confirmed during 2025. These included ten cases associated with the Clade Ib MPXV and two cases linked to the Clade IIb (sublineage F2) MPXV. These cases were found in Gauteng (n=8), KwaZulu Natal (n=2), North West (n=1) and Western Cape (n=1) provinces. No deaths were recorded among these cases. For South Africa, the risk of imported cases mpox remains as cases are reported elsewhere globally. In South Africa, mpox is a Category I notifiable medical condition. Laboratory testing for mpox is available through the National Institute for Communicable Diseases and private pathology services. The NICD also performs routine and national-level wastewater surveillance in order to provide an alternative approach for the monitoring of mpox in the country and support early detection of possible outbreaks of the disease. In July 2025, the South African government launched a mpox vaccination program prioritizing access to targeted and higher risk populations in the Gauteng, Western Cape, and KwaZulu-Natal where nearly all confirmed cases of mpox have been found since 2022.

For the latest updates on mpox, visit the NICD Disease Index mpox page.