Monkeypox virus is an enveloped double-stranded DNA virus that belongs to the
Orthopoxvirus genus of the Poxviridae family. There are two distinct genetic
clades of the monkeypox virus: the central African (Congo Basin) clade and the
west African clade. The Congo Basin clade has historically caused more severe
disease and was thought to be more transmissible. The geographical division
between the two clades has so far been in Cameroon, the only country where both
virus clades have been found.
Natural host of monkeypox virus Various animal species have been identified as
susceptible to monkeypox virus. This includes rope squirrels, tree squirrels,
Gambian pouched rats, dormice, non-human primates and other species. Uncertainty
remains on the natural history of monkeypox virus and further studies are needed
to identify the exact reservoir(s) and how virus circulation is maintained in
nature. Outbreaks Human monkeypox was first identified in humans in 1970 in the
Democratic Republic of the Congo in a 9-month-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 and human cases have increasingly been reported from
across central and west Africa. Since 1970, human cases of monkeypox have been
reported in 11 African countries: Benin, Cameroon, the Central African Republic,
the Democratic Republic of the Congo, Gabon, Cote d’Ivoire, Liberia, Nigeria,
the Republic of the Congo, Sierra Leone and South Sudan. The true burden of
monkeypox is not known. For example, in 1996–97, an outbreak was reported in the
Democratic Republic of the Congo with a lower case fatality ratio and a higher
attack rate than usual. A concurrent outbreak of chickenpox (caused by the
varicella virus, which is not an orthopoxvirus) and monkeypox was found, which
could explain real or apparent changes in transmission dynamics in this case.
Since 2017, Nigeria has experienced a large outbreak, with over 500 suspected
cases and over 200 confirmed cases and a case fatality ratio of approximately
3%. Cases continue to be reported until today. Monkeypox is a disease of global
public health importance as it not only affects countries in west and central
Africa, but the rest of the world. In 2003, the first monkeypox outbreak outside
of Africa was in the United States of America and was linked to contact with
infected pet prairie dogs. These pets had been housed with Gambian pouched rats
and dormice that had been imported into the country from Ghana. This outbreak
led to over 70 cases of monkeypox in the U.S. Monkeypox has also been reported
in travelers from Nigeria to Israel in September 2018, to the United Kingdom in
September 2018, December 2019, May 2021 and May 2022, to Singapore in May 2019,
and to the United States of America in July and November 2021. In May 2022,
multiple cases of monkeypox were identified in several non-endemic countries.
Studies are currently underway to further understand the epidemiology, sources
of infection, and transmission patterns.
Transmission Animal-to-human (zoonotic) transmission can occur 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 pouched
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. People living in or near forested areas may have
indirect or low-level exposure to infected animals. Human-to-human transmission
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, household members and other close contacts of active cases
at greater risk. However, the longest documented chain of transmission in a
community has risen in recent years from 6 to 9 successive person-to-person
infections. This may reflect declining immunity in all communities due to
cessation of smallpox vaccination. Transmission can also occur via the placenta
from mother to fetus (which can lead to congenital monkeypox) or during close
contact during and after birth. While close physical contact is a well-known
risk factor for transmission, it is unclear at this time if monkeypox can be
transmitted specifically through sexual transmission routes. Studies are needed
to better understand this risk.
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 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 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. Underlying
immune deficiencies may lead to worse outcomes. Although vaccination against
smallpox was protective in the past, today persons younger than 40 to 50 years
of age (depending on the country) may be more susceptible to monkeypox due to
cessation of smallpox vaccination campaigns globally after eradication of the
disease. Complications of monkeypox can include secondary infections,
bronchopneumonia, sepsis, encephalitis, and infection of the cornea with ensuing
loss of vision. The extent to which asymptomatic infection may occur is unknown.
The case fatality ratio of monkeypox has historically ranged from 0 to 11 % in
the general population and has been higher among young children. In recent
times, the case fatality ratio has been around 3–6%.
Diagnosis
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 have it transported 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 a vaccinia-based
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.
Therapeutics Clinical care for monkeypox should be fully optimized to alleviate
symptoms, manage complications and prevent long-term sequelae. Patients should
be offered fluids and food to maintain adequate nutritional status. Secondary
bacterial infections should be treated as indicated. An antiviral agent known as
tecovirimat that was developed for smallpox was licensed by the European
Medicines Agency (EMA) for monkeypox in 2022 based on data in animal and human
studies. It is not yet widely available. If used for patient care, tecovirimat
should ideally be monitored in a clinical research context with prospective data
collection.
Vaccination
Vaccination against smallpox was demonstrated through several
observational studies to be about 85% effective in preventing monkeypox. Thus,
prior smallpox vaccination may result in milder illness. Evidence of prior
vaccination against smallpox can usually be found as a scar on the upper arm. At
the present time, the original (first-generation) smallpox vaccines are no
longer available to the general public. Some laboratory personnel or health
workers may have received a more recent smallpox vaccine to protect them in the
event of exposure to orthopoxviruses in the workplace. A still newer vaccine
based on a modified attenuated vaccinia virus (Ankara strain) was approved for
the prevention of monkeypox in 2019. This is a two-dose vaccine for which
availability remains limited. Smallpox and monkeypox vaccines are developed in
formulations based on the vaccinia virus due to cross-protection afforded for
the immune response to orthopoxviruses.
Prevention
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 vaccination for the prevention and control of monkeypox. Some
countries have, or are developing, policies to offer vaccine to persons who may
be at risk such as laboratory personnel, rapid response teams and health
workers. 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 infected persons 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. The identification in May 2022 of clusters of monkeypox cases in
several non-endemic countries with no direct travel links to an endemic area is
atypical. Further investigations are underway to determine the likely source of
infection and limit further onward spread. As the source of this outbreak is
being investigated, it is important to look at all possible modes of
transmission in order to safeguard public health. Preventing monkeypox through
restrictions on animal trade Some countries have put in place regulations
restricting 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. How monkeypox
relates to smallpox The clinical presentation of monkeypox resembles that of
smallpox, a related orthopoxvirus infection which has been eradicated. Smallpox
was more easily transmitted and more often fatal as about 30% of patients died.
The last case of naturally acquired smallpox occurred in 1977, and in 1980
smallpox was declared to have been eradicated worldwide after a global campaign
of vaccination and containment. It has been 40 or more years since all countries
ceased routine smallpox vaccination with vaccinia-based vaccines. As vaccination
also protected against monkeypox in west and central Africa, unvaccinated
populations are now also more susceptible to monkeypox virus infection. Whereas
smallpox no longer occurs naturally, the global health sector remains vigilant
in the event it could reappear through natural mechanisms, laboratory accident
or deliberate release. To ensure global preparedness in the event of reemergence
of smallpox, newer vaccines, diagnostics and antiviral agents are being
developed. These may also now prove useful for prevention and control of
monkeypox.
WHO response WHO supports Member States with surveillance, preparedness and
outbreak response activities for monkeypox in affected countries. More
information can be found
