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For the ongoing outbreak, see 2022 monkeypox outbreak.
Mpox
Monkeypox rash in a 4-year-old girl (1971)
SpecialtyInfectious disease[1]
SymptomsFever, headache, muscle pains, shivering, blistering rash, swollen lymph nodes[2]
ComplicationsSecondary infections, eye infection, visual loss, scarring[3][2]
Usual onset5–21 days post exposure[4]
Duration2 to 4 weeks[4]
TypesCentral African (Congo Basin), West African[5]
CausesMonkeypox virus[6]
Diagnostic methodTesting for viral DNA[7]
Differential diagnosisChickenpox, smallpox[8]
PreventionSmallpox vaccine, hand washing, covering rash, PPE, keep away from sick people[9][10]
TreatmentSupportive, antivirals, vaccinia immune globulin[11]
MedicationTecovirimat[3]
PrognosisMost recover[12]
FrequencyNot as rare as previously thought[13]
Deathsup to 3.6% (Western Africa clade),[14] up to 10.6%[14] (Congo Basin clade, untreated)[15]

Monkeypox is an infectious viral disease that can occur in both humans and some other animals.[1] Symptoms include fever, swollen lymph nodes, and a rash that forms blisters and then crusts over.[1] The time from exposure to onset of symptoms ranges from 5-to-21 days.[3][4] The duration of symptoms is typically 2 to 4 weeks.[4] There may be mild symptoms, but to what extent it may occur without symptoms is not known.[3][16] The classic presentation of fever and muscle pains, followed by swollen glands, with lesions all at the same stage, has not been found to be common to all outbreaks.[1][17] Cases may be severe, especially in children, pregnant women or people with suppressed immune systems.[18]

The disease is caused by monkeypox viruses, a type of Orthopoxvirus.[2] Of the two types in humans, the West African type causes a less severe disease than the Central African (Congo Basin) type.[19] It may spread from handling bushmeat, animal bites or scratches, body fluids, contaminated objects, or other close contact with an infected person.[20][21] Spread can occur by small droplets and possibly the airborne route.[1][10] People can spread the virus from the onset of symptoms until all the lesions have scabbed and fallen off; with some evidence of spread for more than a week after lesions have crusted.[19] The virus is believed to normally spread among certain rodents in Africa.[20] Diagnosis can be confirmed by testing a lesion for the virus's DNA.[7] The disease can appear similar to chickenpox.[8]

There is no known cure.[22] The smallpox vaccine was found to be around 85% protective in preventing infection in close contacts and in lessening the severity of the disease.[2] A newer smallpox and monkeypox vaccine based on modified vaccinia Ankara has been approved, but with limited availability.[3][9][23] Other measures include regular hand washing and avoiding sick people and other animals.[24] Antiviral drugs, cidofovir and tecovirimat, vaccinia immune globulin and the smallpox vaccine may be used during outbreaks.[11][12] The risk of death has varied from 0% to 11%.[3] Most people recover.[12]

The disease is no longer believed to be as rare as previously thought;[13][25] possibly as a result of waning immunity since the stopping of routine smallpox vaccination.[8] Cases have significantly increased since the 1980s.[26] Sporadic cases occur frequently in Central and West Africa, and it is highly endemic in the Democratic Republic of Congo (DRC).[25] Hunters in the tropical forests of Central and West Africa are most at risk.[27] It was first identified as a distinct illness in 1958 among laboratory monkeys in Copenhagen, Denmark.[28] Monkeys are not a natural reservoir of the virus.[29] The first cases in humans were found in 1970 in the Democratic Republic of the Congo.[28] An outbreak that occurred in the United States in 2003 was traced to a pet store where rodents imported from Ghana were sold.[7] Since 2017, a large outbreak has been occurring in Nigeria.[30] The 2022 monkeypox outbreak represents the first incidence of widespread community transmission outside of Africa, which was initially identified in the United Kingdom in May 2022, with subsequent cases confirmed in at least 20 countries,[31] in Europe, North America, South America, Asia, Africa, and Australia.[32][33][34][35][36][37]

Definition and types

Monkeypox is a zoonotic poxvirus infection that can occur in both humans and some other animals.[2] Two recognised distinct types are described as the Congo Basin clade and the milder West African clade.[2]

Signs and symptoms

Stages of monkeypox lesion development

Early symptoms include headache, muscle pains, fever and fatigue.[38][39] It may initially appear like flu.[40] The disease can resemble chickenpox, measles and smallpox, but is distinguished by the presence of swollen glands.[38][39] These characteristically appear behind the ear, below the jaw, in the neck or in the groin, before the onset of the rash.[8] Within a few days of the fever, lesions characteristically appear on the face before appearing elsewhere such as palms of the hands and soles of the feet in a centrifugal distribution.[38][39] Symptoms may vary in people with HIV.[16] Many cases in the 2022 monkeypox outbreak presented with genital and peri-anal lesions, fever, swollen lymph nodes, and pain when swallowing.[1]

Three-quarters of affected people have lesions on the palms and soles, more than two-thirds in the mouth, a third on the genitals and one in five have lesions in the eyes.[38] They begin as small flat spots, before becoming small bumps which then fill with at first clear fluid and then yellow fluid, which subsequently burst and scab over.[4][39] There may be a few lesions or several thousand, sometimes merging to produce large lesions.[38]

In each part of the body affected, the lesions evolve in the same stage.[2] It looks identical to the rash of smallpox.[41] The rash typically lasts around 10-days.[40] An affected person may remain unwell for two to four weeks.[4] After healing, the lesions may leave pale marks before becoming dark scars.[2]

Limited person-to-person spread of infection has been reported in disease-endemic areas in Africa.[42]

Complications

Complications include secondary infections, pneumonia, sepsis, encephalitis, and loss of vision if severe eye infection.[38] If infection occurs during pregnancy, still birth or birth defects may occur.[43] The disease may be milder in people vaccinated against smallpox in childhood.[12]

Causes

A cynomolgus monkey, or crab-eating macaque

Monkeypox in both humans and animals is caused by infection with the monkeypox virus – a double-stranded DNA virus in the genus Orthopoxvirus, family Poxviridae.[6] The virus is found mainly in tropical rainforest regions of Central and West Africa.[6] The virus is split into Congo Basin and West African clades, matching the geographical areas.[15]

Most human cases of monkeypox are acquired from an infected animal, though the route of transmission remains unknown. The virus is thought to enter the body through broken skin, the respiratory tract, or the mucous membranes of the eyes, nose, or mouth.[5] Once a human is infected, transmission to other humans is common, with family members and hospital staff at particularly high risk of infection.[5]

Human-to-human transmission is thought to occur primarily through close contact with an infected subject. There are indications that transmission occurs during sexual intercourse.[44] Animal-to-human transmission may occur by bite or scratch, bush meat preparation, direct contact with body fluids or lesion material, or indirect contact with lesion material, such as through contaminated bedding.[45]

Humans can be infected by an animal via a bite, or by direct contact with an infected animal’s bodily fluids. The virus can also spread from human to human, by respiratory (airborne) contact or by contact with an infected person's bodily fluids.[14] Risk factors for transmission include sharing a bed or room, or using the same utensils as an infected person. Increased transmission risk is associated with factors involving the introduction of virus to the oral mucosa.[39]

Monkeypox symptoms tend to begin 5 to 21 days after infection.[5] Further research about the transmission of the strain responsible for the 2022 outbreak is ongoing, but it is not thought to be different to other strains of the West African clade.[46][47]

Reservoir

In addition to monkeys, the virus is found in Gambian pouched rats (Cricetomys gambianus), dormice (Graphiurus spp.) and African squirrels (Heliosciurus, and Funisciurus). The use of these animals as food may be an important source of transmission to humans.[48]

No specific reservoir for monkeypox has been found. Monkeys are not a main reservoir, contrary to the name. It is believed African rodents, such as the ones listed above, serve as the actual reservoir.[29]

Diagnosis

The clinical presentation of monkeypox

Clinical differential diagnosis must consider other rash illnesses, such as chickenpox, measles, bacterial skin infections, scabies, syphilis and medication-associated allergies. Lymphadenopathy during the prodromal stage of illness can distinguish monkeypox from chickenpox or smallpox. Diagnosis can be verified by testing for the virus.[49]

Polymerase chain reaction (PCR) testing of samples from skin lesions is the preferred laboratory test. PCR blood tests are usually inconclusive because the virus does not remain very long in the blood. To interpret test results, information is required on date of onset of fever, date of onset of rash, date of specimen collection, current stage of rash, and patient age.[49]

Prevention

Vaccination against smallpox is assumed to provide protection against human monkeypox infection because they are closely related viruses and the vaccine protects animals from experimental lethal monkeypox challenges.[50] This has not been conclusively demonstrated in humans because routine smallpox vaccination was discontinued following the eradication of smallpox.[51]

Smallpox vaccine has been reported to reduce the risk of monkeypox among previously vaccinated persons in Africa. The decrease in immunity to poxviruses in exposed populations is a factor in the prevalence of monkeypox. It is attributed both to waning cross-protective immunity among those vaccinated before 1980 when mass smallpox vaccinations were discontinued, and to the gradually increasing proportion of unvaccinated individuals.[39]

The United States Centers for Disease Control and Prevention (CDC) recommends that persons investigating monkeypox outbreaks and involved in caring for infected individuals or animals should receive a smallpox vaccination to protect against monkeypox. Persons who have had close or intimate contact with individuals or animals confirmed to have monkeypox should also be vaccinated.[6]

The CDC does not recommend pre-exposure vaccination for unexposed veterinarians, veterinary staff, or animal control officers, unless such persons are involved in field investigations.[6]

The CDC recommends that healthcare providers don a full set of personal protective equipment (PPE) before caring for an infected person. This includes a gown, mask, goggles, and a filtering disposable respirator (such as an N95). An infected person should be isolated in preferably a negative air pressure room or at least a private exam room to keep others from possible contact.[52]

Treatment

In the European Union and the United States, tecovirimat is approved for the treatment of several poxviruses, including monkeypox.[53] BMJ Best Practice recommends tecovirimat or the smallpox treatment brincidofovir as the first line antiviral treatment if required, alongside supportive care (including antipyretic, fluid balance and oxygenation). Empirical antibiotic therapy or aciclovir may be used if secondary bacterial or varicella zoster infection is suspected, respectively.[54]

Outcome

After healing, they may leave pale marks before becoming darker scars.[2] The risk of death in those infected ranges from 0% to 11%, depending on the type of monkeypox and location in the world.[3][25] Fatality rates have been reported as around 3.6% in West Africa and 10.6% in Central Africa.[25] Most reported deaths have occurred in young children and people with HIV.[19]

Epidemiology

A map of the spread of the monkeypox virus globally.
  Endemic West African clade
  Endemic Congo Basin clade
  Both clades recorded
  West African clade outbreak in 2022

Monkeypox as a disease in humans was first associated with an illness in the Democratic Republic of the Congo (formerly Zaire), in the town of Basankusu, Équateur Province, in 1970.[55] WHO surveillance between 1981 and 1986 in DRC/Zaire recorded 338 confirmed cases and 33 deaths (CFR 9.8%).[56] A second outbreak of human illness was identified in DRC/Zaire in 1996–1997.[57] 511 cases were reported in DRC/Zaire between 1991 and 1999.[56] The Congo Basin clade of disease remains endemic in DRC and has a high CFR.[56]

The other genetic clade of MPXV occurs in Western Africa. The case fatality rate (CFR) is less than 1%. No human-to-human transmission was documented[56] until the 2022 monkeypox outbreak in Europe.[58] The West African clade had an outbreak – the first outbreak of monkeypox outside of Africa – in Midwestern United States among owners of pet prairie dogs in 2003. Seventy-one people were reportedly infected, of whom none died.[59]

Monkeypox is traditionally restricted to the ecology of tropical rainforests.[56] The pattern was broken in 2005, when 49 cases were reported in Sudan (areas now South Sudan), with no fatalities.[60] The genetic analysis suggests that the virus did not originate in Sudan but was imported, most likely from DRC.[61]

Many more monkeypox cases have been reported in Central and West Africa, and in the Democratic Republic of Congo in particular: 2000 cases per year are known between 2011 and 2014. The collected data is often incomplete and unconfirmed, which hinders realistic estimations of the number of cases of monkeypox over time. Nevertheless, it was suggested that the number of reported monkeypox cases had increased and the geographical occurrence broadened as of 2018.[56]

2003 U.S. outbreak

Gambian pouched rat
Main article: 2003 Midwest monkeypox outbreak

In May 2003, a young child became ill with fever and rash after being bitten by a prairie dog purchased at a local swap meet near Milwaukee, Wisconsin.[62] In total, 71 cases of monkeypox were reported through June 20, 2003. All cases were traced to Gambian pouched rats imported from Accra, Ghana, in April 2003 by a Texas exotic animal distributor. No deaths resulted.[63] Electron microscopy and serologic studies were used to confirm that the disease was human monkeypox.[64]

People with monkeypox typically experienced prodromal symptoms of fever, headaches, muscle aches, chills, and drenching sweats. Roughly one-third of infected people had nonproductive coughs. This prodromal phase was followed 1–10 days later by the development of a papular rash that typically progressed through stages of vesiculation, pustulation, umbilication, and crusting. In some people, early lesions had become ulcerated.[65]

Rash distribution and lesions occurred on head, trunk, and extremities. Many of the people had initial and satellite lesions on palms, soles, and extremities. Rashes were generalized in some people. After onset of the rash, people generally manifested rash lesions in different stages. Everyone affected reported direct or close contact with prairie dogs, later found to be infected with the monkeypox virus.[65]

2017–2019 Nigeria outbreak

Main article: Monkeypox in Nigeria

Monkeypox has been reportedly spread around southeast and south Nigeria. Some states and the federal government of Nigeria are currently seeking a way to contain it, as well as find a cure for the infected ones.[66] It has spread to Akwa Ibom, Abia, Bayelsa, Benue, Cross River, Delta, Edo, Ekiti, Enugu, Imo, Lagos, Nasarawa, Oyo, Plateau, Rivers and Federal Capital Territory.[67][68] The outbreak started in September 2017 and remained ongoing across multiple states as of May 2019.[69]

Confirmed cases of Monkeypox by state in Nigeria[70]
State Sep 2017 – Dec 2019 Jan 2020 – Feb 2022
Abia 3 0
Adamawa 0 1
Akwa Ibom 7 0
Anambra 2 0
Bayelsa 37 6
Benue 2 0
Cross River 13 1
Delta 19 10
Ebonyi 0 1
Edo 6 4
Ekiti 2 0
Enugu 4 0
Federal Capital Territory 5 2
Imo 8 1
Lagos 20 11
Nasarawa 2 0
Niger 0 1
Ogun 0 1
Oyo 6 0
Plateau 2 1
Rivers 46 6
Totals 184 46

According to information provided by the Nigeria Centre for Disease Control, between 1971 and 1978, 10 human Monkeypox infections were reported in the country.[71] In September 2017, human monkeypox re-emerged in Nigeria, after 39 years when it was last reported.[72] The 2017 human monkeypox outbreak in the country was large. Bayelsa state was the first state in Nigeria to have reported the 2017 outbreak. Unlike previous reports of the West African clade, the outbreak was characterized by infection predominantly among young male adults with significant transmission to others. The Niger Delta University Teaching Hospital reported that a substantial number of its young adult cases had concomitant genital ulcers, syphilis and HIV infection.[73] The CDC has reported cases of American travelers contracting Monkeypox upon return from Lagos and Ibadan.[74] Agam Rao, a medical officer in the Division of Pathogens and High Consequence Pathology at the Centers for Disease Control and Prevention, said that since 2018 all cases reported outside Africa have come from Nigeria.[75]

In an article published by The Conversation, Oyewale Tomori pointed out that the number of Monkeypox infections in Nigeria through 2021 is likely to be under-represented, because much of the Nigerian population has been avoiding healthcare facilities due to fear of contracting COVID-19.[71]

As British health authorities reported the first case of Monkeypox in the UK in May 2022, the Nigerian government has released to the public information and statistics on reported cases and deaths in the country. In a report released on May 9, 2022, the NCDC states that 230 cases were confirmed across 20 states and the Federal Capital Territory between 2017 and 2022. In 2022, NCDC has implemented National Technical Working Group, abbreviated as NTWG, for the purpose of reporting and monitoring infections, in addition to strengthening response capacity. In the NCDC report, Rivers State was the most affected by Monkeypox followed by Bayelsa and Lagos. In the span from 2017 to 2022, the NCDC reported 6 deaths in 6 different states, making for a 3.3% Case Fatality Ratio.[76]

2018 United Kingdom cases

In September 2018, the United Kingdom's first case of monkeypox was recorded. The person, a Nigerian national, is believed to have contracted monkeypox in Nigeria before travelling to the United Kingdom.[77] According to Public Health England, the person was staying in a naval base in Cornwall before being moved to the Royal Free Hospital's specialised infectious disease unit. People who had been in contact with the person since he contracted the disease were contacted.[78]

A second case was confirmed in the town of Blackpool,[79][80] with a further case that of a medical worker who cared for the case from Blackpool.[81] A fourth case occurred on 3 December 2019, when monkeypox was diagnosed in a person in south west England. They were travelling to the UK from Nigeria.[82]

2019 Singapore case

On 8 May 2019, a 38-year-old man who travelled from Nigeria was hospitalised in an isolation ward at the National Centre for Infectious Diseases in Singapore, after being confirmed as the country's first case of monkeypox. As a result, 22 people were quarantined.[83] The case may have been linked to a simultaneous outbreak in Nigeria.[69]

2021 cases

On 24 May in the UK, three cases of monkeypox from a single household were identified by Public Health Wales. The cases were also announced by Health Secretary Matt Hancock while addressing MPs. The index case was diagnosed on 24 May after traveling from Nigeria. The second case was reported on 2 June, and the third on 24 June.[84][85] One of the three patients, an adult female, was treated with tecovirimat.[19] On day 7 of tecovirimat, she was discharged from hospital to complete her second week of treatment at home.[19]

On 14 July in the US, an American returning from a trip in Nigeria was diagnosed with monkeypox. Subsequent testing identified the virus as belonging to the West African clade. The patient was hospitalized and treated with tecovirimat and was discharged after 32 days, at which time monkeypox virus DNA could no longer be detected in residual skin lesions.[86]

2022 outbreak

Main article: 2022 monkeypox outbreak

In May 2022, the World Health Organization (WHO) made an emergency announcement of the existence of a multi-country outbreak of mpox, a viral disease then commonly known as "monkeypox".[87] The initial cluster of cases was found in the United Kingdom,[88] where the first case was detected in London on 6 May 2022[89] in a patient with a recent travel history from Nigeria where the disease has been endemic.[90] On 16 May, the UK Health Security Agency (UKHSA) confirmed four new cases with no link to travel to a country where mpox is endemic.[89] Subsequently, cases have been reported from many countries and regions.[91] The outbreak marked the first time mpox had spread widely outside Central and West Africa. The disease had been circulating and evolving in human hosts over several years before the outbreak and was caused by the clade IIb variant of the virus.[92]

In May 2023, the World Health Organization declared an end to the PHEIC, citing steady progress in controlling the spread of the disease.[93]

Relatively low levels of cases continued to occur, and as of 11 November 2024, there have been a total of 116,015 confirmed cases and 255 deaths in 126 countries.[94][95][96]

History

Between 1958 and 1968, mainly for the purpose of producing and testing the polio vaccine, a small number of primates were being imported from Africa to Europe and the US, but most were from Asia.[97] During transit, there were often other wild animals and spread of infection had many opportunities.[97] In 1958, Preben von Magnus first identified monkeypox as a distinct pox illness in two non-fatal outbreaks in laboratory cynomolgus monkeys at the State Serum Institute, Copenhagen, Denmark, 51 and 62 days after the shipments arrived from Singapore by air.[98][99] Subsequent investigations detected the monkeypox virus in the kidneys of some monkeys that had no symptoms and were otherwise healthy.[100] The virus was never found in Asia, and the occurrence in Asian monkeys was likely due to contracting the disease in captivity and transit, or contamination.[97] Some previous pox illnesses among monkeys, assumed to be smallpox, may have been monkeypox.[98] During the 1960s, monkeypox was detected in several laboratory monkeys in Europe and the US, including in 1962 at the Walter Reed Army Institute of Research, where following exposure, several monkeys had antibodies but no symptoms.[100] No further cases in laboratory monkeys occurred after 1968 as conditions for monkeys improved and the requirement for monkeys from Asia and Africa, fell.[97] Until the outbreak of monkeypox at Rotterdam Zoo in 1964, monkeypox was thought to occur only in primates.[101] There, Central/South American giant anteaters first developed the disease before several orangutans, chimpanzees, gorillas, guenons, squirrel monkeys, macaques, marmosets and gibbons, and 11 of the 23 animals died.[100] The disease was particularly severe in orangutans.[102] At the time, monkeypox virus was also isolated from kidneys of healthy monkeys, but later found to be most likely due to contamination by the Zoo samples that were being looked at at the same laboratory.[97][100]

The first documented cases in humans was in 1970, in six unvaccinated children during the smallpox eradication efforts; the first being a 9-month old boy in the Democratic Republic of the Congo (formerly Zaire).[25][100] The others, including three who were playmates, were in Liberia and Sierra Leone.[100][103] It was noted to be less easily transmissible than smallpox.[2] From 1981 to 1986, over 300 cases of human monkeypox were reported in the DRC, the majority being due to contact with animals.[104] In 1996, the disease reemerged in the DRC with 88% of cases resulting from human-to-human transmission.[2] Small viral outbreaks with a death rate in the range of 10% and a secondary human-to-human infection rate of about the same amount occur routinely in equatorial Central and West Africa.[104] In humans, the disease remained confined to the rain forests of Western and Central Africa until 2003, when an outbreak of monkeypox occurred in the US.[105] All cases were traced to sick rodents imported from Ghana.[2] Local prairie dogs caught the infection and passed it onto their owners.[2] The disease was found to be mild and there were no deaths.[2] Between 1970 and 2019 the disease was reported in 10 African countries; mostly in Central and West Africa.[25]

In 2018, cases of monkeypox were diagnosed in the UK in two unrelated travellers from Nigeria.[106] That year the first human-to-human transmission outside of Africa was confirmed in the UK.[30] This person was a healthcare worker who possibly contracted the disease from contaminated bedlinen.[106] Cases were also reported in travellers to Israel and Singapore.[30] The UK saw further cases in 2019 and 2021.[12]

Other animals

Signs and symptoms in animals vary among different species.[107] Monkeypox infected Gambian pouched rats may have mild symptoms.[108] During the 2003 US outbreak, affected prairie dogs presented with fever, cough, sore eyes, poor feeding and rash.[107] Non-human primates present similarly.[107] They may have breathing problems, facial swelling, mouth ulcers and swollen glands.[108] In cynomolgus monkeys, the time from exposure to symptoms was noted to be around a week.[108] Rabbits and rodents typically present with fever, cough, runny nose, sore eyes and swollen glands.[108] They develop small bumps that fill with yellow fluid and may have patches of hair loss and pneumonia.[108] The disease has also been reported in dormice, tree squirrels and rope squirrels.[3] Other animals are likely susceptible but not known.[108]

Spread among animals occurs via the fecal-oral route and through the nose, through wounds and eating infected meat.[108] Death is more likely in baby monkeys.[108] The CDC recommend that animals exposed to monkeypox be quarantined for six weeks.[108]

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