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. By December 2024, the African CDC reported that 20 countries had reported nearly 70,000 mpox cases and 1,200 deaths during this time. The outbreak in in the DRC lead to sustained transmission in neighboring Burundi and Uganda.
The outbreak was caused by the clade Ia virus and was spread by animal-to-human contact, household transmission, and sexual contact. Children aged 15 years or younger have been disproportionally affected. The case fatality rate for clade Ia outbreaks has ranged between 3 and 5%.
Complicating these outbreaks has been the emergence of clade 1b 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. By February 10, 2025, a total of 22 African countries had now reported clade 1b 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 patients had been hospitalized. These cases represented the first locally transmitted clade Ib mpox infections in the WHO European Region and the first outside Africa. On November 30, the UK reported its 5th case of clade Ib mpox. The 5th involved a person who had recently traveled to Uganda and had no links to the previous cases.
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.
On November 22, Canada confirmed its first imported case of clade 1b mpox. Canada became the 7th country outside of Africa to report an imported clade 1 case. The other countries included Germany, India, Sweden, Thailand, the United Kingdom and the United States.
On December 28, the European Centre for Disease Prevention and Control announced that Oman and Pakistan had reported clade 1b mpox cases. The patients had not traveled to Africa, but did have a history of travel to the United Arab Emirates. UAE had not reported any known clade 1 cases.
On January , 2025, China reported a cluster of 5 people with clade 1b mpox. One of the patients had a history of living in DRC, and the other 4 patients had close contact with that person.
As of February 13, 2025, a total of 14 countries outside of Africa had reported clade 1b mpox cases: Belgium, Canada, China, France, Germany, India, Ireland, Oman, Pakistan, Sweden, Thailand, the United Arab Emirates, the United Kingdom, and the United States.
On February 10, 2025, the New Hampshire Department of Health and Human Services announced a person from Merrimack County had been diagnosed with clade 1b mpox. This infection raised the total number of clade 1 cases in the US to three.
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.
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