Mpox is a rare viral infection caused by an orthopoxvirus, which is a relatively large DNA virus that is related to smallpox. Mpox was originally named Monkeypox because it was discovered in a group of Asian monkeys in a Danish laboratory in 1958. However, monkeypox was a misnomer because the natural hosts were discovered to be forest-dwelling rodents in Africa and not monkeys. The natural hosts included Gambian pouched rats, rope squirrels, and dormice.
Occasionally, mpox causes zoonotic infections in which animal-to-human transmission occurs by a bite or scratch, bush meat preparation, or direct contact with body fluids. The first human case of mpox was reported n 1970 in the Democratic Republic of the Congo.
Human to human transmission occurs through direct contact with:
- Blisters or lesions on the skin of an infected person
- Other body fluids such as respiratory droplets, after prolonged face to face contact
- Clothing or linen contaminated with fluid from blisters.
A study published in Eurosurveillance detected high mpox DNA viral loads in saliva, rectal swabs, nasopharyngeal swabs, semen, urine, and feces. These results suggested the possibility of sexual transmission in addition to skin-to-skin contact. There have been no documented cases of transfusion-transmitted monkeypox infections.
The incubation period from infection to the appearance of symptoms ranges from 5 to 21 days. Patients infected with mpox typically experience a febrile prodrome that lasts 4 to 17 days after exposure. Symptoms include fever and chills, headache, muscle aches, malaise, and swollen lymph nodes. The prodrome is followed 1 to 4 days later by the onset of a vesicular or pustular rash that often begins on the face and then spreads to other parts of the body including the palms of the hand and soles of the feet. The rash progresses from flat to raised lesions, and eventually to fluid filled vesicles that rupture and scab over. Patients are considered to be infectious until all lesions have crusted over, crusts have separated, and healthy skin has formed under the crust. The case-fatality rate of mpox in Africa has ranged from 1% to 10%, with the highest risk of death among children.
In an average year, a few thousand cases occurred in western and central Africa. Nigeria had an outbreak involving 450 people in 2017. In the past, cases outside Africa had been associated with travel to Africa or the importation of infected animals. The United States had an outbreak in 2003, when a shipment of rodents from Ghana spread the virus to pet prairie dogs in Illinois and infected 72 people. No one died and the outbreak ended within one month.
Beginning in May 2022, the United Kingdom, Spain, and the United States detected an increasing number of cases of mpox among men who had sex with men (MSM). The men had not traveled to countries where the virus was endemic but did report sexual contact at common events. On May 23, 2022, the United States Centers for Disease Control and Prevention (CDC) activated an emergency outbreak response. The World Health Organization (WHO) declared a Public Health Emergency of International Concern on July 23, 2022.
From January 1, 2022 to September 30, 2024, the World Health Organization (WHO) had confirmed 109,699 global cases of mpox and 236 fatalities. Cases had been detected in 123 different countries.
As of September 30, 2024, the Region of the Americas had 65,877 cases and 150 deaths. The United States had 34,063 cases and 63 deaths. European countries had 28,176 cases and 9 deaths. In Europe, most cases have occurred in Spain, France, the United Kingdom, Germany, Netherlands, Portugal, Italy, Belgium, and Switzerland.
Of those cases with available data, 96% have been male with a median age of 34 years. Only 3.7% have been female. The most commonly reported form of transmission has been via sexual encounters.
Patients have most frequently presented with a rash on the genitalia or surrounding area, indicating that transmission likely occurred during close physical contact during sexual activities. Other patients have experienced a single painful ulcer in their mouth, anus, or on their genitals. Some patients have developed severe disease, requiring hospitalization. These patients developed severe dermatologic manifestations, severe mucosal lesions. Some also had involvement of other organs such as the eyes, lungs, brain, and spinal cord.
There are two distinct types of mpox: Clade I and clade II. Clade 1 has been further divided into clade 1a and clade 1b. The mpox global epidemic that began in 2022 was caused by clade II virus and was spread primarily through sexual contact among men who had sex with men. The clade II epidemic had a relatively low case fatality risk (CFR) of 1%.
This was the first time that chains of transmission had been reported in multiple countries without known epidemiological links to West or Central Africa, where mpox is endemic. These were also the first cases reported among men who have had sex with men. WHO’s outbreak bulletin stated: “The sudden and unexpected appearance of monkeypox simultaneously in several non-endemic countries suggests that there might have been undetected transmission for some unknown duration of time followed by recent amplifier events."
Mpox may have become more prevalent due to waning immunity in people who received the smallpox vaccine and no immunity in those who never received it because smallpox had been eradicated. The last smallpox vaccine was administered in the United States in 1972.
The Democratic Republic of Congo (DRC) declared an mpox epidemic in December 2022. On November 14, 2024, the African CDC reported that Africa had 53,903 mpox cases and 1,109 deaths since the start of 2024. Mpox had spread to 20 African countries. The DRC, Burundi, and Uganda accounted for most cases and deaths. Children have accounted for 36% of cases.
Children aged 15 years or younger have been disproportionally affected. The outbreak was caused by the clade Ia virus and was spread by animal-to-human contact, household transmission, and sexual contact. The case fatality rate for clade I outbreaks has ranged between 3 and 5%.
Complicating these outbreaks has been the emergence of clade Ib mpox virus. This strain has obtained genetic mutations that make it more transmissible and deadly. Clade 1b has spread largely through sexual contact, with a large proportion of it heterosexual. Approximately 50% of cases involved women and nearly a third of them were sex workers. Cases of mpox caused by clade 1b have presented as a whole-body rash or long-lasting genital lesions. The case fatality rate for clade 1b has been as high at 5% in adults and 10% in children.
On October 13, 2024, Zimbabwe reported its first two cases of mpox. A child and a man from two separate towns had traveled to South Africa and Tanzania, respectively. A total of 17 African countries had now reported mpox cases.
On October 22, 2024, the Robert Koch Institut in Germany reported the country’s first case caused by mpox clade 1b. The patient had recently traveled abroad.
On November 6, 2024, The United Kingdom Health Security Agency confirmed 4 cases of clade 1b mpox in London. One person had recently traveled to several countries in Africa. The other 3 cases were household contacts. All 4 patients had been hospitalized.
On November 15, the California Department of Public Health confirmed the first case of clade 1b mpox in the United States.The patient had recently traveled to countries experiencing clade 1b mpox transmission.
The United States became the sixth country outside of Africa to report an imported clade 1 case. The other countries included Germany, India, Sweden, Thailand, and the United Kingdom.
Timeline of Notable Events
On May 23, 2022, the United States Centers for Disease Control and Prevention (CDC) activated an emergency outbreak response.
On June 6, 2022, the US CDC raised the mpox travel alert to level 2, warning Americans to practice enhanced precautions when traveling to both endemic and non-endemic countries that are experiencing mpox outbreaks. Enhanced precautions included avoiding contact with sick people, including genital contact, avoiding contact with dead or live animals, and avoiding contact with contaminated materials, such as bedding.
On June 28, the US CDC activated its Emergency Operations Center (EOC) which increased access to testing and vaccination. Everyone with a presumed mpox exposure became eligible for a vaccine.
On July 23, 2022, The WHO declared mpox a public health emergency of international concern (PHEOIC) because it was spreading around the world rapidly through new modes of transmission which were not fully understood.
On August 2, the White House announced the creation of a federal mpox response team that will coordinate efforts between the federal government and state and local authorities, including managing adequate supplies for testing, treating, and vaccinating.
On August 2, 2022, the Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA) declared the ongoing mpox outbreak in the United States to be a public health emergency, paving the way for increased funding for tests, vaccines, and treatments.
On Friday, September 2, 2022, the US CDC released a laboratory alert regarding rare false-negative results for the mpox virus that were obtained when using assays with the CDC's published primers and probes.
On November 2, 2022, the US Department of Health and Human Services (HHS) renewed the mpox public health emergency.
On Monday, November 28, 2022, the WHO announced it was recommending mpox as the new name for monkeypox disease. Both names would be used simultaneously for 1 year while the monkeypox term was phased out. During the current outbreak, the name monkeypox had been associated with racism and stigmatism.
On January 31, 2023, HHS allowed the mpox public health emergency to expire because the number of cases had expired steadily since the peak in mid-August 2022. By the first weeks of January 2023, the United States was averaging just two new cases a day.
On February 15, 2023, the WHO decided the mpox outbreak would remain a global public health emergency because 18 countries continued to report local transmission.
On May 11, 2023, the WHO announced it would no longer classify mpox as a public health emergency of international concern, nearly a year after the virus emerged as a global threat.
On December 7, 2023, the CDC issued a Health Alert Network (HAN) message about the occurrence, geographic spread, and sexually associated human-to-human transmission of mpox cases in the DRC. Clinicians and laboratories should be aware of possible mpox cases among individuals who had traveled to the DRC in the last 21 days. Physicians should contact their state public health laboratory to determine if additional testing might be needed to determine the clade.
On August 7, 2024, Director-General Tedros announced he would convene an emergency committee of independent experts to advise him as to whether the WHO should declare a public health emergency of international concern.
On August 7, 2024, the CDC issued a HAN Update to provide additional information about the mpox outbreak in Africa. CDC alerted physicians in the United States to be on the lookout for the more deadly clade 1 strain of mpox that was spreading through central and eastern Africa. CDC was monitoring the presence of clade 1 and 2 in wastewater samples, include from select airports.
On August 7, 2024, The United States Agency for International Development (USAID) announced $10 million for public health interventions in response to the mpox outbreak in the DRC and other affected African countries. The agency also donated 50,000 mpox vaccines to DRC.
On August 13, 2024, the Africa CDC declared the mpox outbreak was a public health emergency of continental security (PHECS). This was the first time the agency had made such a declaration since its inception in 2017.
On August 14, 2024, the WHO declared a public health emergency of international concern (PHEIC) regarding mpox because of the high risk of cross-border spread. The new clade 1b strain of mpox had already spread beyond the DRC to at least 12 other African countries. The number of cases was 160% higher compared with the same period in 2023. More than 500 people have died since January.
The PHECS and PHEIC declarations are meant to mobilize international resources, enhance collaboration, and accelerate research to control the mpox outbreaks. They provide a framework for countries to implement necessary public health measures and improve acquisition and distribution of medical countermeasures such as vaccines, treatments, and diagnostics, as well as personal protective equipment and disinfectants.
On August 15, 2024, Sweden confirmed a case of mpox caused by the new clade 1b virus in a person who had traveled to Africa. This case emphasized the risk of the new clade spreading beyond Africa’s borders.
Laboratory Testing
CDC recommended collection of two specimens, each from multiple lesions, preferably from different locations on the body and from lesions with differing appearances. Specimens are sent to a laboratory participating in the Laboratory Response Network (LRN) that has been validated to perform the non-variola Orthopoxvirus (NVO) assay. NVO assays can detect mpox clades I and II. However they cannot differentiate mpox virus from other Orthopoxviruses.
Laboratory Response Network laboratories and commercial laboratories using CDC’s NVO PCR test should submit duplicate specimens to CDC from all patients with positive NVO PCR test results for MPXV clade-specific testing.
On June 22, 2023, HHS announced that five commercial laboratory companies were offering mpox testing using a CDC developed test. The five laboratories are Quest Diagnostics, LabCorp, Sonic, ARUP, and Mayo Clinic Laboratories. The five laboratories combined with the CDC’s Laboratory Response Network, have increased testing capacity to 80,000 specimens per week.
On September 7, 2023, the FDA declared a public emergency requiring clinical laboratory tests for mpox to obtain emergency use authorization (EUA) before offering the test clinically.
As of September 6, 2024, only 30% of suspected mpox cases in the DRC were being confirmed by molecular testing. Most were being diagnosed based on clinical symptoms. WHO has established 6 new labs in affected DRC provinces and updated its diagnostic testing guidance to include clade 1b. WHO had delivered about 150,000 diagnostic tests for mpox globally.
On October 3, 2024, the WHO authorized the first mpox in vitro diagnostic test under its Emergency Use Listing (EUL) procedure. Alinity m MPXV assay is a PCR test that detects mpox virus in swabs of human skin lesions .
On October 14, the WHO also authorized Cobas MPXV assay, that was developed by Roche Molecular Systems, Inc. The test was designed to run on Cobas 6800 and 8800 systems.
On October 25, the WHO listed the Xpert Mpox PCR test by Cepheid mpox tests under its EUL. The test will be performed on GeneXpert systems.
On November 12, 2024, Africa’s CDC diagnostic advisory committee recommended the first locally-manufactured real-time PCR test for mpox. The test is made by Moldiag in Morocco.
Vaccination and Treatment
A positive test result for an Orthopoxvirus using the NVO assay is immediately actionable. Tecovirimat (TPOXX) can be prescribed as treatment for people with mpox, and two vaccines, JYNNEOS and ACAM2000 can be provided to close contacts as postexposure prophylaxis.
The first vaccine option is ACAM2000, which is the second generation of the smallpox vaccine that was named Dryvax. ACAM2000 was licensed in 2007 and stockpiled in case of a bioterrorism event. It is a replication-competent vaccine, which means it uses live vaccinia virus, which belongs to smallpox family. The vaccine is very effective because monkeypox is so closely related to smallpox.
A single dose is administered by a skin prick with a two-pronged needle that’s dipped into vaccine solution. Virus replicates at the injection site causing a red, itchy blister within 3 to 4 days that dries up forming a scab that falls off around week 3. This leaves a small scar. Unvaccinated people can be accidentally infected by someone who recently received the vaccine.
Jynneos is a much newer smallpox vaccine made by Bavarian Nordic that was licensed in 2019. It uses attenuated variola virus that is non-replicating. It is administered by intramuscular injection in two doses given 28 days apart. Recipients are not fully protected until 14 days after the second dose. Jynneos has been shown to be 85% effective in preventing mpox in humans. As of July 16, CDC recommends giving Jynneos vaccine within four days of exposure to prevent disease onset. It can be given later to reduce symptoms. The Department of Health and Human Services (HHS) has distributed 240,000 doses to the states. DHHS anticipates making approximately 1.9 million doses available in 2022 and another 2.2 million doses in the first half of 2023.
On August 10, 2022, the US Food and Drug Administration issued an emergency use authorization (EUA) that allowed healthcare workers to administer the Jynneos vaccine by intradermal injection to individuals 18 years of age and older who were determined to be at high risk for mpox infection. This change increased the total number of doses available for use by up to five-fold. On May 23, 2023, CDC reported that 1.2 million doses of the Jynneos mpox vaccine had been administered in the United States.
There are no Food and Drug Administration (FDA)–approved treatments for mpox. However, drugs that are approved for treatment of smallpox and cytomegalovirus might have activity against mpox virus. Tecovirimat (Tpocc) is an antiviral medication available in oral and intravenous formulations. Animal studies have shown that tecovirimat is effective in treating orthopoxvirus-induced disease. CDC recommended prescribing Tpoxx for patients with severe disease such as hemorrhagic disease, large number of confluent lesions, sepsis, encephalitis, and ocular or periorbital infections. Pregnant women and children over 8 years old should be offered treatment.
Africa CDC estimated at least 10 million mpox vaccine doses were needed to contain the mpox outbreak.
On September 6, 2024, the Democratic Republic of Congo received its first shipment of 99,100 doses of the 2-dose Jynneos mpox vaccine from the European Union and vaccine manufacturer Bavarian Nordic. Overall, European nations planned to deliver 566,500 doses of vaccine.
On September 11, a preprint was published on medRxiv that demonstrated antibody levels fall rapidly after receiving the Jynneos mpox vaccine. Antibody levels peak approximately 3 weeks after vaccination but are undetectable in most recipients at 3 months.
On September 13, WHO prequalified Bavarian Nordic’s MVA-BN vaccine (also known as Jynneos, Imvanex, and Imvamune). Prequalification facilitated the procurement and distribution of the vaccine by organizations such as Gavi and UNICEF, particularly in those low- and middle-income countries that could not afford to purchase supplies.
On September 13, 2024, African CDC estimated 18 to 22 million doses of mpox vaccine would be needed to vaccinate 10 million people over the next 6 months. DRC had received only 250,000 doses from the European Union and United States. Japan announced it would donate 3 million doses of KM Biologics’ LC26 mpox vaccine to DRC.
On September 24, President Biden announced the U.S. would donate 1 million mpox vaccine doses and at least $500 million to African countries to support their response to the mpox outbreak.
On October 5, 2024, the DRC began vaccinating against mpox in the eastern North Kivu province. DRC had received 265,000 doses of the MVA-BN vaccine donated by the European Commission’s Health Emergency Preparedness and Response Authority, Gavi, the Vaccine Alliance, and the United States Government.
On October 10, 2024, the CDC reported it had identified 18 mpox cases cases caused by a variant resistant to Tecovirimat (TPoxx). The cases involved patients across five states who had never taken this medication. Tecovirimat is the first-line drug for treatment of smallpox and mpox.
By November 6, 2024, the WHO and its partners had allocated 899,000 vaccine doses to 9 African countries. Most of those doses went to the DRC, which had reported 80% of the confirmed cases in Africa this year.
Healthcare Worker Precautions
Current CDC recommendations suggest HCWs wear a gown, gloves, eye protection, and an N95 (or higher-level) respirator while caring for patients who have suspected or confirmed mpox.
Blood Donation
On August 12, FDA reiterated that there had been no reports of transmission of mpox through blood transmission and that the risk of transfusion-transmission remained theoretical.
Given the robustness of the existing safeguards for blood safety, it did not recommend that blood establishments ask donors additional, specific questions about possible exposure to mpox virus or screen blood donors FDA for monkeypox virus.
References
Kozlov M, Monkeypox goes global: why scientists are on alert. Nature News, May 20, 2022.
Soucheray, S. Officials confirm 226 monkeypox cases in 21 countries. CIDRAP News, may 25, 2022.
Alakunle E, Moens U, Nchinda G, Okeke MI. Monkeypox virus in Nigeria: infection biology, epidemiology, and evolution. Viruses. 2020;12(11):1257. doi:10.3390/v12111257
Bunge EM, Hoet B, Chen L, et al. The changing epidemiology of human monkeypox—A potential threat? A systematic review. PLoS Negl Trop Dis. 2022;16(2):e0010141. doi:10.1371/journal.pntd.0010141
Guagliardo SAJ, Monroe B, Moundjoa C, et al. Asymptomatic Orthopoxvirus Circulation in Humans in the Wake of a Monkeypox Outbreak among Chimpanzees in Cameroon. Am J Trop Med Hyg. 2020;102(1):206-212. doi:10.4269/ajtmh.19-0467
Kugelman JR, Johnston SC, Mulembakani PM, et al. Genomic variability of monkeypox virus among humans, Democratic Republic of the Congo. Emerg Infect Dis. 2014;20(2):232-239. doi:10.3201/eid2002.130118
McCollum AM, Damon IK. Human Monkeypox. Clin Infect Dis. 2014;58(2):260-267. doi:10.1093/cid/cit703
Nolen LD, Osadebe L, Katomba J, et al. Extended Human-to-Human Transmission during a Monkeypox Outbreak in the Democratic Republic of the Congo. Emerg Infect Dis. 2016;22(6):1014-1021. doi:10.3201/eid2206.150579
Patrono LV, Pléh K, Samuni L, et al. Monkeypox virus emergence in wild chimpanzees reveals distinct clinical outcomes and viral diversity. Nat Microbiol. 2020;5(7):955-965. doi:10.1038/s41564-020-0706-0
Petersen E, Kantele A, Koopmans M, et al. Human Monkeypox. Infect Dis Clin North Am. 2019;33(4):1027-1043. doi:10.1016/j.idc.2019.03.001
Russo AT, Berhanu A, Bigger CB, et al. Co-administration of tecovirimat and ACAM2000™ in non-human primates: Effect of tecovirimat treatment on ACAM2000 immunogenicity and efficacy versus lethal monkeypox virus challenge. Vaccine. 2020;38(3):644-654. doi:10.1016/j.vaccine.2019.10.049
Simpson K, Heymann D, Brown CS, et al. Human monkeypox—After 40 years, an unintended consequence of smallpox eradication. Vaccine. 2020;38(33):5077-5081. doi: 10.1016/j.vaccine.2020.04.06
Soucheray S. CDC raises travel alert level for monkeypox. CIDRAP News, June 07, 2022.
Jetelina K. Monkeypox Vaccine 101, July 1, 2022,
Peiro-Mestres A, et al. Frequent detection of monkeypox virus DNA in saliva, semen, and other clinical samples from 12 patients, Barcelona, Spain, May to June 2022, Eurosurveillance 2022;27: pii=2200503.https://doi.org/10.2807/1560-7917.ES.2022.27.28.2200503
O’Shea J, Filardo TD, Morris SB, Weiser J, Petersen B, Brooks JT. Interim Guidance for Prevention and Treatment of Monkeypox in Persons with HIV Infection — United States, August 2022. MMWR Morb Mortal Wkly Rep 2022;71:1023-1028. DOI: http://dx.doi.org/10.15585/mmwr.mm7132e4
Van Beusekom M. More than 600 dead in spreading DR Congo mpox outbreak as Republic of Congo reports its first cases, CIDRAP, March 15, 2024
CDC Health Alert Network, Mpox caused by human-to-human transmission of monkeypox virus in the Democratic Republic of Congo with spread to neighboring countries. CDCHAN-00513, August 7, 2024.
Rivers C, Watson C, Phelan AL. The Resurgence of Mpox in Africa, JAMA Network, published online August 20, 2024. doi:10.1001/jama.2024.17829
Collier AY et al. Rapid Decline of Mpox Antibody Responses Following MVA-BN Vaccination. medRxiv 2024.09.10.24313399; doi: https://doi.org/10.1101/2024.09.10.24313399
How to resolve AdBlock issue?