Monkeypox is a viral zoonosis (a virus transmitted to humans from animals) with symptoms similar to those seen in the past in smallpox patients, although it is clinically less severe. With the eradication of smallpox in 1980 and subsequent cessation of smallpox vaccination, it has emerged as the most important orthopoxvirus. Monkeypox occurs in Central and West Africa, often in proximity to tropical rainforests.
Human monkeypox was first identified in humans in 1970 in the Democratic Republic of the Congo (then known as Zaire) in a 9-year-old boy in a region where smallpox had been eliminated in 1968. Since then, most cases have been reported from rural, rainforest regions of the Congo Basin, particularly in the Democratic Republic of the Congo, where it is considered to be endemic.
Since 1970, human cases of monkeypox have been reported from 11 African countries – Benin, Cameroon, the Central African Republic, the Democratic Republic of the Congo, Gabon, Ivory Coast, Liberia, Nigeria, the Republic of the Congo, Sierra Leone, and South Sudan. In 2017 Nigeria experienced the largest documented outbreak, 40 years after the last confirmed case. The true burden of monkeypox is not known. For example, in 1996–97, a major monkeypox outbreak was suspected in the Democratic Republic of Congo with, however, a lower case fatality and a higher attack rate than usual. Some patient samples tested positive for varicella virus and some contained both varicella and monkeypox viruses. Concurrent outbreaks of chickenpox and monkeypox could explain a change in transmission dynamics in this case.
The virus has been exported from Africa a few times. In the spring of 2003, monkeypox cases were confirmed in the United States of America. Most patients were reported to have had close contact with pet prairie dogs that were infected by African rodents that had been imported into the country from Ghana. Recently, monkeypox was carried to Israel in September 2018, to the United Kingdom in September 2018 and December 2019 and to Singapore in May 2019 by travelers from Nigeria who fell ill with monkeypox after arrival. A health worker was infected and became ill.
Two distinct genetic clades of the virus have been identified – the Congo Basin and the West African clades – with the former found to be more virulent and transmissible. The geographical division between the two clades is thought to be in Cameroon as this is the only country where both monkeypox virus clades were detected.
Infection of index cases results from direct contact with the blood, bodily fluids, or cutaneous or mucosal lesions of infected animals. In Africa, evidence of monkeypox virus infection has been found in many animals including rope squirrels, tree squirrels, Gambian poached rats, dormice, different species of monkeys and others. The natural reservoir of monkeypox has not yet been identified, though rodents are the most likely. Eating inadequately cooked meat and other animal products of infected animals is a possible risk factor.
Secondary, or human-to-human, transmission is relatively limited. Infection can result from close contact with respiratory secretions, skin lesions of an infected person or recently contaminated objects. Transmission via droplet respiratory particles usually requires prolonged face-to-face contact, which puts health workers and household members of active cases at greater risk. The longest documented chain of transmission in a community was six successive person-to-person infections. Transmission can also occur via the placenta from mother to fetus (congenital monkeypox).
Signs and symptoms
The incubation period (interval from infection to onset of symptoms) of monkeypox is usually from 6 to 13 days but can range from 5 to 21 days.
The infection can be divided into two periods:
- the invasion period (lasts between 0-5 days) characterized by fever, intense headache, lymphadenopathy (swelling of the lymph nodes), back pain, myalgia (muscle aches) and an intense asthenia (lack of energy). Lymphadenopathy is a distinctive feature of monkeypox compared to other diseases that may initially appear similar (chickenpox, measles, smallpox).
- the skin eruption usually begins within 1-3 days of appearance of fever. The rash tends to be more concentrated on the face and extremities rather than on the trunk. It affects the face (in 95% of cases), and palms of the hands and soles of the feet (in 75% of cases). Also affected are oral mucous membranes (in 70% of cases), genitalia (30%), and conjunctivae (20%), as well as the cornea. The rash evolves sequentially from macules (lesions with a flat base) to papules (slightly raised firm lesions), vesicles (lesions filled with clear fluid), pustules (lesions filled with yellowish fluid), and crusts which dry up and fall off. The number of the lesions varies from a few to several thousand. In severe cases, lesions can coalesce until large sections of skin slough off.
Monkeypox is usually a self-limited disease with the symptoms lasting from 2 to 4 weeks. Severe cases occur more commonly among children and are related to the extent of virus exposure, patient health status and nature of complications. Complications of monkeypox can include secondary infections, bronchopneumonia, sepsis, encephalitis, and infection of the cornea with ensuing loss of vision.
People living in or near forested areas may have indirect or low-level exposure to infected animals, possibly leading to subclinical (asymptomatic) infection.
The case fatality ratio of monkeypox has varied between 0 and 11 % in the general population, and has been higher among young children. In addition, persons younger than 40 or 50 years of age (depending on the country) may be more susceptible to monkeypox as a result of the termination of routine smallpox vaccination worldwide after the eradication of smallpox.
The clinical differential diagnosis that must be considered includes other rash illnesses, such as chickenpox, measles, bacterial skin infections, scabies, syphilis and medication-associated allergies. Lymphadenopathy during the prodromal stage of illness can be a clinical feature to distinguish monkeypox from chickenpox or smallpox. If monkeypox is suspected, health workers should collect an appropriate sample and transport it safely to a laboratory with appropriate capability. Confirmation of monkeypox depends on the type and quality of the specimen and the type of laboratory test. Thus, specimens should be packaged and shipped in accordance with national and international requirements. Polymerase chain reaction (PCR) is the preferred laboratory test given its accuracy and sensitivity. For this, optimal diagnostic samples for monkeypox are from skin lesions – the roof or fluid from vesicles and pustules, and dry crusts. Where feasible, biopsy is an option. Lesion samples must be stored in a dry, sterile tube (no viral transport media) and kept cold. PCR blood tests are usually inconclusive because of the short duration of viremia relative to the timing of specimen collection after symptoms begin and should not be routinely collected from patients.
As orthopoxviruses are serologically cross-reactive, antigen and antibody detection methods do not provide monkeypox-specific confirmation. Serology and antigen detection methods are therefore not recommended for diagnosis or case investigation where resources are limited. Additionally, recent or remote vaccination with vaccinia vaccine (e.g. anyone vaccinated before smallpox eradication, or more recently vaccinated due to higher risk such as orthopoxvirus laboratory personnel) might lead to false positive results.
In order to interpret test results, it is critical that patient information be provided with the specimens including: a) date of onset of fever, b) date of onset of rash, c) date of specimen collection, d) current status of the individual (stage of rash), and e) age.
Treatment and vaccine
There is currently no specific treatment recommended for monkeypox. Vaccination against smallpox with vaccinia vaccine was demonstrated through several observational studies to be about 85% effective in preventing monkeypox. Thus, prior childhood smallpox vaccination may result in a milder disease course.
However at the present time, the original (first-generation) smallpox vaccines are no longer available to the general public. A newer vaccinia-based vaccine was approved for the prevention of smallpox and monkeypox in 2019 and is also not yet widely available in the public sector.
Natural host of monkeypox virus
Various animal species have been identified as susceptible to monkeypox virus infection through laboratory experiments, outbreaks among captive animals and field investigations. This includes rope squirrels, tree squirrels, Gambian poached rats, dormice, primates and other species. Doubts persist on the natural history of the virus and further studies are needed to identify the exact reservoir(s) of the monkeypox virus and how it is maintained in nature.
Raising awareness of risk factors and educating people about the measures they can take to reduce exposure to the virus is the main prevention strategy for monkeypox. Scientific studies are now underway to assess the feasibility and appropriateness of using vaccinia vaccine for the prevention and control of monkeypox. Some countries have, or are developing, policies for use of vaccinia vaccine to prevent infection, for example in laboratory staff and health workers who may be at risk of exposure.
Reducing the risk of zoonotic transmission
Most human infections result from a primary, animal-to-human transmission. Unprotected contact with wild animals, especially those sick or dead, including their meat, blood and other parts must be avoided. Additionally, all foods containing animal meat or parts must be thoroughly cooked before eating.
Reducing the risk of human-to-human transmission
Surveillance and rapid identification of new cases is critical for outbreak containment. During human monkeypox outbreaks, close contact with monkeypox patients is the most significant risk factor for monkeypox virus infection. Health workers and household members are at a greater risk of infection.
Health workers caring for patients with suspected or confirmed monkeypox virus infection, or handling specimens from them, should implement standard infection control precautions. If possible, persons previously vaccinated against smallpox should be selected to care for the patient.
Samples taken from people and animals with suspected monkeypox virus infection should be handled by trained staff working in suitably equipped laboratories. Patient specimens must be safely prepared for transport with triple packaging in accordance with WHO guidance for transport of infectious substances (category A).
Preventing monkeypox expansion through restrictions on animal trade
Some countries have put in place regulations restricting the importation of rodents and non-human primates.
Captive animals that are potentially infected with monkeypox should be isolated from other animals and placed into immediate quarantine. Any animals that might have come into contact with an infected animal should be quarantined, handled with standard precautions and observed for monkeypox symptoms for 30 days.