Mpox

Mpox (formerly known as monkeypox) is an infectious viral disease that can occur in humans and other animals. Symptoms include a rash that forms blisters and then crusts over, fever, and swollen lymph nodes. The illness is usually mild and most of those infected will recover within a few weeks without treatment. The time from exposure to onset of symptoms ranges from five to twenty-one days and symptoms typically last from two to four weeks. Cases may be severe, especially in children, pregnant women or people with suppressed immune systems.

The disease is caused by the monkeypox virus, a zoonotic virus in the genus Orthopoxvirus. The variola virus, the causative agent of the disease smallpox, is also in this genus. Human-to-human transmission can occur through direct contact with infected skin or body fluids, including sexual contact. People remain infectious from the onset of symptoms until all the lesions have scabbed and healed. It may spread from infected animals by handling infected meat or via bites or scratches. Diagnosis can be confirmed by PCR testing a lesion for the virus' DNA.

Vaccination is recommended for those at high risk of infection. Evidence shows that the MVA-BN vaccine is 86% effective at reducing the risk of mpox illness. The aim of treatment is to manage the symptoms and prevent complications as there is no specific treatment for the disease. Antiviral drugs such as tecovirimat can be used to treat mpox, although their effectiveness has not been proved.

Mpox is endemic in central and western Africa, where several species of mammals are suspected to act as a natural reservoir of the virus. The first human cases were diagnosed in 1970 in Basankusu, Democratic Republic of the Congo. Since then the frequency and severity of outbreaks has significantly increased, possibly as a result of waning immunity since the cessation of routine smallpox vaccination. The 2022–2023 mpox outbreak represents the first incidence of widespread community transmission outside of Africa. This was initially identified in the United Kingdom in May 2022, with subsequent cases confirmed in 111 countries as of May 2023. The World Health Organization (WHO) declared the outbreak a Public Health Emergency of International Concern (PHEIC) between 23 July 2022 and 10 May 2023.

Nomenclature
The name monkeypox was originally coined because the disease was first identified in laboratory monkeys. This was subsequently criticised as a misnomer, because monkeys are not the main host or reservoir. It was also criticized because the name reinforced stigma about African countries as a source of disease.

After requests by a number of public health organisations and scientists, who argued that these issues were harming the fight to contain the disease outbreak, the subtypes of monkeypox virus were renamed cladeI and cladeII in August 2022. The World Health Organization announced in November 2022 that it "will adopt the term mpox in its communications, and encourages others to follow these recommendations".

Signs and symptoms
Initial symptoms of mpox infection are fever, muscle pains, and sore throat, followed by an itchy or painful rash, headache, swollen lymph nodes, and fatigue. Not everyone will exhibit the complete range of symptoms.

Most mpox patients become symptomatic 4–11 days after infection. However, the incubation period can be as short as 1 day. The 2022–2023 outbreak revealed that incubation periods of up to 4 weeks are possible, with 5% of cases having incubation periods longer than the previously assumed 21 days.

The rash comprises many small lesions which may appear on the palms and soles, face, mouth and throat, genitals or anus. They begin as small flat spots, before becoming small bumps which then fill with fluid and subsequently burst and scab over, persisting for around ten days.

Some patients may manifest only a single sore from the disease while others may have hundreds. It is possible for a person to be infected with monkeypox virus without showing any symptoms. Symptoms typically last for two to four weeks, but may last longer if the patient has a weakened immune system.

The ocular manifestations of monkeypox generally includes the eyelid and adnexa. Several systematic reviews indicated that eye manifestations may include vesicular rash of the peri-ocular skin, deformity and edema of the eyelids, focal lesions on conjunctival, conjunctivitis, blepharitis, blepharoconjunctivitis, scleritis, corneal opacities and ulcerations, corneal melt, keratitis, uveitis, and finally, blindness.

Complications
Complications include secondary infections, pneumonia, sepsis, encephalitis, and loss of vision following corneal infection. Persons with weakened immune systems, whether due to medication, medical conditions, or HIV, are more likely to develop severe disease. If infection occurs during pregnancy, this may lead to stillbirth or other complications.

Outcome
Provided there are no complications, sequelae are rare; after healing, the scabs may leave pale marks before becoming darker scars.

Prior to the 2022 outbreak, the risk of death in those infected was estimated from 0% to 11%. With other historic case fatality rates being reported as 6% in Nigeria and 10-15% in the Democratic Republic of Congo and the Central African Republic, with a higher death rate in the more virulent clade 1 variant that is endemic to central Africa. However, in the 2022 global outbreak 112 deaths were reported in 87,000 cases, with other sources reporting a risk of death as high as 0.025%. Most reported deaths in this outbreak were among those who were immunocompromised either due to medication or poorly controlled HIV infection.

In other animals
It is thought that small mammals provide a reservoir for the virus in endemic areas. Spread among animals occurs via the fecal–oral route and through the nose, through wounds and eating infected meat. The disease has also been reported in a wide range of other animals including monkeys, anteaters, hedgehogs, prairie dogs, squirrels, and shrews. Signs and symptoms in animals are not well researched and further studies are in progress.

There have been instances of animal infection outside of endemic Africa; during the 2003 US outbreak, prairie dogs (Cynomys ludovicianus) became infected and presented with fever, cough, sore eyes, poor feeding and rash. There has also been an instance of a domestic dog (Canis familiaris) which became infected displaying lesions and ulceration.

Cause
Mpox in both humans and animals is caused by infection with the monkeypox virus – a double-stranded DNA virus in the genus Orthopoxvirus, family Poxviridae, making it closely related to the smallpox, cowpox, and vaccinia viruses. The two subtypes of virus are cladeI and cladeII. CladeII is further divided into subclades: cladeIIa and cladeIIb. Cases identified as part of the 2022-2023 global outbreak are caused by cladeIIb. CladeI is largely limited to the DRC and is estimated to cause more severe disease and higher mortality than clades IIa and IIb. The virus is considered to be endemic in tropical rainforest regions of Central and West Africa. In addition to monkeys, the virus has been identified 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.

Transmission
Mpox can be transmitted from one person to another through contact with infectious lesion material or fluid on the skin, in the mouth or on the genitals; this includes touching, close contact and during sex. It may also spread by means of respiratory droplets from talking, coughing or sneezing. During the 2022–2023 outbreak, transmission between people was almost exclusively via sexual contact. There is a lower risk of infection from fomites (objects which can become infectious after being touched by an infected person) such as clothing or bedding, but precautions should be taken.

The virus then enters the body through broken skin, or mucosal surfaces such as the mouth, respiratory tract, or genitals.

The natural reservoir of monkeypox virus is thought to be small mammals in tropical Africa. The virus can be transmitted from animal to human from bites or scratches, or during activities such as hunting, skinning, or cooking infected animals.

Diagnosis
Clinical differential diagnosis must consider other rash illnesses, such as chickenpox, measles, bacterial skin infections, scabies, syphilis and medication-associated allergies. Diagnosis can be verified by testing for the virus. Polymerase chain reaction (PCR) testing of samples from skin lesions is the preferred laboratory test.

Prevention
The MVA-BN vaccine, originally developed for smallpox, has been approved for use by persons who are either considered at high risk of exposure to mpox, or who may have recently been exposed to it. The United States Centers for Disease Control and Prevention (CDC) recommends that persons investigating mpox outbreaks, those caring for infected individuals or animals, and those exposed by close or intimate contact with infected individuals or animals should receive a vaccination.

Historically, smallpox vaccine had been reported to reduce the risk of mpox among previously vaccinated persons in Africa. The decrease in immunity to poxviruses in exposed populations is a factor in the increasing prevalence of human mpox. It is attributed 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.

The CDC has made detailed recommendations in addition to the standard precautions for infection control. These include that healthcare providers don a gown, mask, goggles, and a disposable filtering respirator (such as an N95), and that an infected person should be isolated a private room to keep others from possible contact.

Those living in countries where mpox is endemic should avoid contact with sick mammals such as rodents, marsupials, non-human primates (dead or alive) that could harbour monkeypox virus and should refrain from eating or handling wild game (bush meat).

During the 2022–2023 outbreak, several public health authorities launched public awareness campaigns in order to reduce spread of the disease.

Treatment
Most cases of mpox present with mild symptoms and there is complete recovery within 2 to 4 weeks. There is no specific treatment for the disease, although antivirals such as tecovirimat have been approved for the treatment of severe mpox. A 2023 Cochrane review found no completed randomised controlled trials studying therapeutics for the treatment of Mpox. The review identified non-randomised controlled trials which evaluated the safety of therapeutics for Mpox, finding no significant risks from tecovirimat and low certainty evidence that suggests brincidofovir may cause mild liver injury. Pain is common and may be severe; supportive care such as pain or fever control may be administered. Patients with mild disease should isolate at home, stay hydrated, eat well, and take steps to maintain their mental health.

Patients who are at high risk from the disease include children, pregnant women, the elderly and those who are immunocompromised. For these patients, or those who have severe disease, hospital admission and careful monitoring of symptoms is recommended, Symptomatic treatment is recommended for complications such as proctitis, and pruritis.

History
Mpox was first identified as a distinct illness in 1958 among laboratory monkeys in Copenhagen, Denmark. The first documented cases in humans were 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 (DRC). From 1981 to 1986, over 300 cases of human mpox were reported in the DRC, the majority being due to contact with animals. The virus has been detected In Gambian pouched rats, dormice and African squirrels, which are often used as food.

Many more mpox cases have been reported in Central and West Africa, and in the Democratic Republic of the Congo in particular: 2,000 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 mpox over time. Originally thought to be uncommon in humans, cases increased since the 1980s, possibly as a result of waning immunity since the stopping of routine smallpox vaccination.

Deaths
Historically, the case fatality rate (CFR) of past outbreaks was estimated at between 1% and 10%, with clade I considered to be more severe than clade II. However the case fatality rate of the 2022–2023 global outbreak caused by clade IIb has been very low, estimated at 0.16%, with the majority of deaths in individuals who were already immunocompromised. The huge difference between these estimates is attributed to: -
 * under-reporting of mild cases in the endemic areas
 * evolution of the virus to cause milder disease in humans
 * better general health, and better health care, in the populations most affected by the 2022–2023 global outbreak.

Future threat
The natural reservoir of monkeypox virus has not been conclusively determined, although small rodents are the most likely candidate. Without a major vaccination campaign, mpox outbreaks in humans will continue indefinitely in the endemic areas, with an ongoing risk that disease outbreaks will spread to non-endemic areas. Other evidence – that the virus is evolving to be more transmissible among humans, that it can infect a wide range of host species, and that human-to-animal transmission can occur – led to concerns that mpox may either become established in new natural reservoirs outside of Africa, or cause future global epidemics.

Following the 2022–2023 outbreak, mpox (clade IIb) remains present in the human population outside Africa at very low levels. In November 2023, the WHO reported increasing numbers of cases of mpox (clade I) in the Democratic Republic of the Congo, with 12,569 cases year-to-date and 651 fatalities; there was also the first evidence of sexual transmission of clade I.

Outbreaks
This section is an incomplete list of disease outbreaks which have been reported, including significant outbreaks in the endemic countries in tropical Africa (Benin, Cameroon, the Central African Republic, the Democratic Republic of the Congo, Gabon, Ghana, Ivory Coast, Liberia, Nigeria, the Republic of the Congo, Sierra Leone, and South Sudan). Outbreaks of mpox are frequent in areas where the disease is endemic - these areas often have poor healthcare infrastructure and outbreaks are rarely documented.

United States
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. In total, 71 cases of mpox were reported through 20 June 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. Electron microscopy and serologic studies were used to confirm that the disease was human mpox. Everyone affected reported direct or close contact with prairie dogs, later found to be infected with the monkeypox virus.

In July 2021, in the US, an American returning from a trip in Nigeria was diagnosed with mpox. Subsequent testing identified the virus as belonging to cladeII. The patient was hospitalized and treated with tecovirimat and was discharged after 32 days.

Sudan
During 2022, an outbreak of clade I mpox was reported in refugee camps in Sudan.

Nigeria
In September 2017, monkeypox virus was reported in Nigeria. The subsequent outbreak was, at that time, the largest ever outbreak of cladeII of the virus, with 118 confirmed cases. Unlike previous outbreaks of this clade, infection was predominantly among young male adults and human-to-human transmission appears to have readily occurred. Seven deaths (5 male, 2 female, case fatality rate of 6%) were reported, including a baby and four HIV/AIDS patients. Additionally, a pregnant woman in her second trimester had a spontaneous miscarriage attributed to monkeypox virus infection.

In May 2022, the Nigerian government released a report stating that between 2017 and 2022, 558 cases were confirmed across 32 states and the Federal Capital Territory. There were 8 deaths reported, making for a 1.4% Case Fatality Ratio. In 2022, NCDC implemented a National Technical Working Group for reporting and monitoring infections, strengthening response capacity.

United Kingdom
In September 2018, the United Kingdom's first case of mpox was recorded. The person, a Nigerian national, is believed to have contracted mpox in Nigeria before travelling to the United Kingdom. A second case was confirmed in the town of Blackpool, with a further case that of a medical worker who cared for the case from Blackpool.

In December 2019, mpox was diagnosed in a person in South West England who had travelled to the UK from Nigeria.

In May 2021, in the UK, three cases of mpox from a single household were identified by Public Health Wales. The index case had travelled from Nigeria.

Singapore
In 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 mpox. As a result, 22 people were quarantined. The case may have been linked to a simultaneous outbreak in Nigeria.

2022–2023 Global outbreak
An outbreak of mpox caused by clade IIb of the virus was first identified in May 2022. The first case was detected in London, United Kingdom, on 6 May in a patient with a recent travel history from Nigeria (where the disease is endemic). Subsequent cases were reported from an increasing number of countries and regions. In July 2022, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern (PHEIC); in May 2023, the PHEIC was terminated due to steady progress in controlling the spread of the disease. As of January 2024, clade IIb mpox cases outside of endemic regions in Africa continue to be reported at a low level.

2023–2024 Democratic Republic of Congo outbreak
During 2023, a clade I outbreak of mpox disease in the Democratic Republic of Congo (DRC) resulted in 14,626 suspected cases being reported, with 654 associated deaths, making for a case-fatality rate of 4.5%. The outbreak continued into 2024 with an additional 3,576 suspected mpox cases and 265 deaths being reported in the DRC through the first 9 weeks of the year, making for an estimated CFR of 7.4%.

The outbreak appears to be of a primarily sexually transmitted nature and cases are occurring in areas without a history of mpox, such as South Kivu and Kinshasa. The outbreak seems to consist of two separate sub-variants of clade I, with one of the sub-variants having a novel mutation making detection with standard assays unreliable.

The outbreak spread to the neighbouring country of the Republic of Congo, with 43 mpox cases being reported in March 2024.