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Mpox

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Mpox
The rash of monkeypox in 4 year-old girl
SpecialtyInfectious disease
SymptomsFever, headache, muscle pains, blistering rash, swollen lymph nodes[1]
Usual onset5–21 days post exposure[1]
Duration2 to 4 weeks[1]
CausesMonkeypox virus[2]
Diagnostic methodTesting for viral DNA[3]
Differential diagnosisChickenpox, smallpox[4]
PreventionSmallpox vaccine[3]
MedicationTecovirimat
FrequencyRare[2]
Deathsless than 1% (Western Africa clade),[5] up to 10%[1] (Congo Basin clade, untreated)[6]

Monkeypox is an infectious disease caused by the monkeypox virus (MPXV) that can occur in certain animals, including humans.[2] Symptoms begin with fever, headache, muscle pains, swollen lymph nodes, and feeling tired.[1] This is followed by a rash that forms blisters and crusts over.[1] The time from exposure to onset of symptoms is around 10 days.[1] The duration of symptoms is typically two to four weeks.[1]

Monkeypox may be spread from handling bushmeat, an animal bite or scratch, body fluids, contaminated objects, or close contact with an infected person.[7] The virus normally circulates among certain rodents in Africa.[7] Diagnosis can be confirmed by testing a lesion for the virus's DNA.[3] The disease can appear similar to chickenpox.[4]

The smallpox vaccine can prevent infection with 85% effectiveness.[3][8] In 2019, a monkeypox vaccine, Jynneos, was approved for adults in the United States.[9] The current standard for treatment is Tecovirimat, an antiviral that is specifically intended to treat infections with orthopoxviruses such as smallpox and monkeypox. It is approved for the treatment of monkeypox in the European Union and the United States. Cidofovir or brincidofovir may also be useful. [4][10] In Africa, reports of the risk of death, if untreated, are as high as 10% to 11% in The Central African clade of monkeypox.[1][11]

[12] Monkeypox was first identified in 1958 among laboratory monkeys in Copenhagen, Denmark.[13] The first cases in humans were found in 1970 in the Democratic Republic of the Congo.[13] An outbreak that occurred in the United States in 2003 was traced to a pet store where rodents imported from Ghana were sold.[3] The first cases of widespread community transmission of monkeypox outside of Africa occurred in an outbreak in the United Kingdom in May 2022, which is currently ongoing.

Signs and symptoms

Symptoms begin with fever, headache, muscle pains and feeling tired.[1] Unlike the more severe smallpox, there are also swollen glands.[1] Within a few days or longer of the high temperature, lesions appear typically on the face first before spreading to other parts of the body.[1] They begin as small flat spots, before becoming small bumps which then fill with at first clear fluid and then pus, which subsequently burst and scab over.[1] It looks identical to the rash of smallpox.[14] An affected person may remain unwell for two to four weeks.[1]

Limited person-to-person spread of infection has been reported in disease-endemic areas in Africa.[15]

Cause

Monkeypox virus

Main article: Monkeypox virus
A cynomolgus monkey, or crab-eating macaque

Monkeypox virus causes the disease in both humans and animals. It was first identified by Preben von Magnus in 1958 as a pathogen of crab-eating macaque monkeys (Macaca fascicularis) being used as laboratory animals, when two outbreaks of a smallpox-like disease occurred in colonies of monkeys kept for research.[2] The crab-eating macaque is often used for neurological experiments. Monkeypox virus is an Orthopoxvirus, a genus of the family Poxviridae that contains other viral species that target mammals. The virus is found mainly in tropical rainforest regions of Central and West Africa.[2] The virus is split into Congo Basin and West African clades, matching the geographical areas.[6]

The virus was first discovered in monkeys (hence the name) in 1958, and in humans in 1970. Almost 50 cases were reported between 1970 and 1979, with more than two thirds of these being from Zaire. The other cases originated from Liberia, Nigeria, Ivory Coast and Sierra Leone.[16] By 1986, over 400 cases in humans were reported. 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.[17] The primary route of infection is thought to be contact with the infected animals or their bodily fluids.[17] The first reported outbreak outside of the African continent occurred in the United States in 2003 in the Midwestern states of Illinois, Indiana, and Wisconsin, with one occurrence in New Jersey. The outbreak was traced to a prairie dog infected from an imported Gambian pouched rat.[3] No deaths occurred.[18]

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. Risk factors for transmission include sharing a bed or room, or using the same utensils as an infected person. An increased transmission risk is associated with factors involving the introduction of virus to the oral mucosa.[19] The incubation period is 10–14 days. Prodromal symptoms include swelling of lymph nodes, muscle pain, headache, and fever prior to the emergence of the rash. The rash is usually only present on the trunk, but may spread to the palms and soles of the feet in a centrifugal distribution. The initial macular lesions exhibit a papular, then vesicular and pustular appearance.[19]

Reservoir

In addition to monkeys, reservoirs for the virus are 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.[20]

Diagnosis

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. 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.[21]

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.[11] This has not been conclusively demonstrated in humans, because routine smallpox vaccination was discontinued following the eradication of smallpox.[22]

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.[19] 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.[23]

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.[23]

Treatment

In the European Union, tecovirimat is approved for the treatment of several poxviruses, including monkeypox.[24]

Epidemiology

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.[25] WHO surveillance between 1981 and 1986 in DRC/Zaire recorded 338 confirmed cases and 33 deaths (CFR 9.8%).[5] A second outbreak of human illness was identified in DRC/Zaire in 1996–1997.[citation needed] 511 cases were reported in DRC/Zaire between 1991–1999.[5] The Congo Basin clade of disease remains endemic in DRC and has a high CFR.[5]

The other genetic clade of MPXV occurs in Western Africa. The case fatality rate is less than 1%. No human-to-human transmission was documented[5] until the 2022 monkeypox outbreak in Europe.[26] The WA clade had an outbreak – 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.[27]

Monkeypox is traditionally restricted to the ecology of tropical rainforests.[5] The pattern was broken in 2005, when 49 cases were reported in Sudan (areas now South Sudan), with no fatalities.[28] The genetic analysis suggests that the virus did not originate in Sudan but was imported, most likely from DRC.[29]

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.[5]

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.[30] 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.[31] Electron microscopy and serologic studies were used to confirm that the disease was human monkeypox.[32]

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. 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.[33]

2017–2019 Nigeria outbreak

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.[34] 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.[35][36] The outbreak started in September 2017 and remains ongoing across multiple states as of May 2019.[37]

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.[38] 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.[39] A second case was confirmed in the town of Blackpool,[40][41] with a further case that of a medical worker who cared for the case from Blackpool.[42] 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.[43]

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.[44] The case may be linked to the ongoing outbreak in Nigeria.[37]

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.[45][46]

On 16 July in the US, an American returning from a trip in Nigeria was diagnosed with monkeypox. They were promptly hospitalized and were reportedly in stable condition.[47]

2022 outbreak

Main article: 2022 monkeypox outbreak

In May 2022, several cases were identified in London and one in northeast England, according to the UK Health Security Agency. It was emphasised in public announcements that monkeypox did not spread easily between people.[48] In the same month, both Portugal and Spain reported several cases.[49] Said cases in Europe have been classified as belonging to the West African clade, which has a fatality rate of <1%.[50]

On 18 May in Massachusetts, United States, a case was confirmed after a man traveled to Canada. He was hospitalized, and was known to have been in good condition.[51]

References

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