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Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)

Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)
Stuart N Isaacs, MD
Oriol Mitjà, MD, PhD, DTMH
Section Editor:
Martin S Hirsch, MD
Deputy Editor:
Jennifer Mitty, MD, MPH
Literature review current through: Dec 2022. | This topic last updated: Dec 07, 2022.

INTRODUCTION — Mpox (previously referred to as monkeypox) is a viral zoonotic infection that is caused by monkeypox virus and results in a rash similar to that of smallpox. However, historically, person-to-person spread outside the household and mortality from mpox are significantly less than for smallpox. The rash of mpox can also be similar in appearance to more common infectious rashes, such as those observed in secondary syphilis, herpes simplex infection, and varicella-zoster virus infection.

This topic will review the virology, epidemiology, clinical manifestations, and diagnosis of mpox. Topic reviews that discuss the treatment and prevention of mpox are presented separately. (See "Treatment and prevention of mpox (monkeypox)" and "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses".)

TERMINOLOGY — In November 2022, the World Health Organization, who is responsible for naming and renaming of diseases under the International Classification of Diseases (ICD), changed the name of the disease referred to as “monkeypox” to “mpox” [1]. This change was made to follow current best practices of not naming diseases after animals or geographic locations and to reduce any stigma that could be associated with the original name.

The virus that causes mpox will continue to be referred to as monkeypox virus until the International Committee on the Taxonomy of Viruses (ICTV) officially decides what the name of the virus should be. However, the former Congo Basin (Central African) clade was renamed as Clade one (I) and the former West African clade was renamed as Clade two (II). Clade II consists of two subclades, IIa and IIb. (See 'Virology' below.)

VIROLOGY — Monkeypox virus is an orthopoxvirus that is in the same genus as variola (the causative agent of smallpox) and vaccinia viruses (the virus used in the smallpox vaccine). Electron microscopy of cells infected with monkeypox virus shows a brick-like virion, indistinguishable from the virions of variola or vaccinia viruses (picture 1).

Two distinct strains of monkeypox virus have existed in different geographic regions of Africa, as suggested by epidemiologic, animal, and molecular evidence [2]. Clade one (I) has been responsible for disease in the Congo basin whereas clade two (II) has been isolated in West Africa. The strain isolated from West Africa is less virulent and lacks several genes present in the strain from Central Africa [2,3].

Clade II consists of two subclades, clades IIa and IIb [1]. The existence of these two subclades was recognized during the 2022 global outbreak [4,5]. (See '2022 global outbreak' below and 'Terminology' above.)

Early analyses of viruses from this outbreak reveal that they are similar to sequences of strains circulating in Nigeria from the 2018 to 2019 outbreak. Initial sequence data from 15 isolates indicate that there are more mutations than expected in the DNA genome, raising the possibility that the circulating virus is undergoing accelerated human adaptation [5].

EPIDEMIOLOGY — Monkeypox virus was first isolated in Denmark in the late 1950s from a colony of laboratory monkeys from Singapore that were going to be used for polio virus research [6]. During the following decade, additional outbreaks of mpox were seen in laboratory animals in the United States as well as zoo animals in Rotterdam [7]. Monkeypox virus was first identified as a cause of disease in humans in the 1970s in what is now the Democratic Republic of the Congo.

Geographic distribution — Since the discontinuation of smallpox immunization, which also protects against mpox, cases of mpox have generally occurred in Central and West Africa. The first outbreak of mpox in the Western hemisphere occurred in the United States in 2003 [8-10]. Since then, sporadic cases have been reported in several nonendemic countries, mostly related to travel. However, an ongoing global outbreak associated with person-to-person transmission was reported in May 2022 and has involved thousands of individuals in dozens of countries [11,12]. Transmission of monkeypox virus is discussed below. (See 'Transmission' below.)

Central and West Africa — Monkeypox virus was first identified as a cause of disease in humans in the 1970s in the Democratic Republic of the Congo (formerly the Republic of Zaire) [13-17]. Following its recognition as a human pathogen, 59 cases of human mpox were reported between 1970 and 1980 in West Africa and Central Africa, with a mortality rate of 17 percent in children under 10 years of age [18,19]. All of these cases occurred in the rain forests of West and Central Africa among individuals exposed to small forest animals (eg, rodents, squirrels, and monkeys).

After the eradication of naturally occurring smallpox in 1977 and the discontinuation of routine smallpox immunization (ie, vaccinia virus vaccine) in 1980 [20], the World Health Organization (WHO) monitored subsequent human mpox cases [21]. The WHO was concerned that discontinuation of the vaccinia virus vaccine, which also protects against mpox, would lead to increased susceptibility of the population and the possibility of an increased incidence of mpox.

A population-based surveillance study from 2005 to 2007 reported a 20-fold increase in incidence of mpox compared with that seen in the 1980s in the Democratic Republic of the Congo [22]. From 2005 to 2007, 760 laboratory-confirmed human mpox cases were identified. This study supported concerns of increased human cases of mpox due to the lack of prior smallpox vaccination as persons with a history of smallpox immunization had a fivefold lower risk of mpox compared with unvaccinated persons. Other factors associated with an increased risk of infection included living in forested areas, male sex, and age <15 years.

Since 2017, there has been an increase in mpox cases in Nigeria; this occurred after almost 40 years with no reported cases [23]. Some cases from this outbreak have occurred in travelers returning to nonendemic countries. (See 'Sporadic cases related to travel from endemic countries' below.)

In 2022, the WHO reported that mpox was endemic in several African countries including Benin, Cameroon, the Central African Republic, the Democratic Republic of the Congo, Gabon, Ghana (identified in animals only), Ivory Coast, Liberia, Nigeria, the Republic of the Congo, Sierra Leone, and South Sudan. From January to May 2022, most suspected cases of mpox occurred in the Democratic Republic of the Congo, with 1284 cases and 58 deaths reported [11,24].

Nonendemic countries

2022 global outbreak — A global outbreak of mpox was first recognized in Europe in May 2022 [25]. Cases related to this outbreak have continued to be reported in nonendemic countries worldwide, providing evidence of community spread. On July 23, 2022, the WHO declared this outbreak of mpox a public health emergency of international concern [26].

Most cases have been identified in men who have sex with men (MSM), leading to the hypothesis that there may be spread due to close contact during sexual activity. In a report of 528 cases of confirmed human mpox infection from 16 countries, 98 percent of the persons were MSM [27].

Household transmission has also occurred, including young children [28-31]. However, the incidence of such transmissions is rare. In the United States, children under age 15 represent only 0.18 percent of cases [32].

Burden of disease – The first cases of mpox in this outbreak were identified in the United Kingdom in mid-May 2022. These were not associated with recent travel to an endemic area or close contact with a person known to have mpox. Although mpox was identified in the UK in a person with recent travel to Nigeria on May 7, 2022, the cases did not appear to be related [33].

Nontravel-related cases of mpox were subsequently reported in other parts of Europe [34]. As an example, in Portugal, five confirmed cases and more than 20 suspected cases of mpox were reported in May 2022. All were in young men in Lisbon and the Tagus Valley. Spain also reported several suspected cases around this time [35].

In the United States, the first mpox case was also reported in May 2022 [36,37]. Genome sequencing results from virus recovered from this patient displayed similarities to other published genomes in this outbreak from Europe and are related to the mpox outbreak in Nigeria that occurred from 2017 to 2018. (See 'Central and West Africa' above and 'Virology' above.)

Thousands of confirmed mpox/orthopoxvirus cases in dozens of countries have since been reported. An updated list of case counts and countries involved in this outbreak can be found on the Centers for Disease Control and Prevention (CDC) website and the European Centers for Disease Control website.

Association with sexual activity – In the 2022 outbreak, most patients diagnosed with mpox reported high-risk sexual behavior (eg, sex with multiple partners) as a potential risk factor. Many early cases occurred in people who had attended an international pride event held on the Spanish island of Gran Canaria that was linked to transmission chains in several European countries [35,38-40].

However, by the end of May, locally acquired infections and community transmission became predominant in all affected countries [38]. Some of the patients diagnosed with mpox have reported having multiple or anonymous sexual partners in the previous two weeks, attending 'sex-on-premises' venues (eg, gay bathhouses, backrooms, clubs) or 'group sex' sessions, and using recreational drugs during sex. About 40 percent of patients infected with monkeypox virus are people taking pre-exposure prophylaxis to prevent acquiring HIV [27,41]. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis".)

Although most of the initial cases during this outbreak have been associated with close contact in the context of sexual activity, anyone who has direct skin-to-skin contact or live in a home with someone who has mpox is at risk, and there have been cases of mpox in household contacts. (See 'Human-to-human transmission' below.)

Concomitant sexually transmitted infections have been reported in a range of 16 to 29 percent of individuals tested in the published cohorts of the 2022 outbreak with gonorrhea, chlamydia, and syphilis being the most common infections.

Association with HIV – In the published cohorts of the 2022 outbreak, the percentage of people living with human immunodeficiency virus (HIV) is high, ranging from 36 to 42 percent among cases diagnosed with mpox infection [27,42,43]. It is not yet known whether HIV infection affects a person's risk for acquiring mpox; however, the risk of progressing to severe disease has been reported to be higher in those with low CD4 counts [44]. (See 'Other complications' below and 'Prognosis and risk for severe disease' below.)

Role of prior smallpox vaccination – Previous smallpox vaccination provides some protection against severe disease, but it does not provide lifelong protection from getting infected and infecting someone else. During the 2022 outbreak, several people who were infected with monkeypox virus had previously been vaccinated against smallpox decades earlier [39,40,42]. In a report of 181 cases of confirmed mpox in Spain, 32 (18 percent) had a history of smallpox vaccination in their childhood [42].

2003 United States outbreak — Between May 15 and June 2003, an outbreak of 71 cases (confirmed and probable) of human mpox in six states (Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin) was investigated by the CDC; 35 cases were laboratory confirmed [8-10]. Prior to this cluster of cases, mpox had not been previously found in the Western hemisphere.

The investigation demonstrated that the onset of a febrile illness, with subsequent appearance of a pustular rash, had developed in patients who had recently purchased or had contact with pet prairie dogs. The prairie dogs appeared to have acquired the virus from African rodents from Ghana when the two species were housed at a distribution center in Illinois.

Mpox was confirmed by DNA sequences obtained from skin lesions from 9 of 10 patients from Illinois, Indiana, and Wisconsin and in lymph node tissue of one pet prairie dog that died [8]. Direct exposure to animals (including exposure to ill prairie dogs' urine and feces) without personal protection equipment (PPE) was felt to be the likely source of transmission [45], although person-to-person transmission could not be entirely excluded. Of the cases reported in Wisconsin, the veterinary staff who were exposed to an outbreak-associated prairie dog were at particularly high risk, with an attack rate of 23 percent (range 7 to 67 percent) [46].

Because of this outbreak, the transportation, sale, or release into the wild of prairie dogs and animals from Africa (including tree squirrels, rope squirrels, dormice, brush-tailed porcupines, and striped mice in addition to Gambian giant rats) was subsequently prohibited by the CDC and the US Food and Drug Administration (FDA) [10]. There have been no other United States outbreaks related to imported animals since the time of this prohibition.

Sporadic cases related to travel from endemic countries — Several sporadic cases of mpox have been reported after travel to endemic areas [47-51]. In one study evaluating the 2017 outbreak in Nigeria, a small pool of related isolates was the likely source for the exported infections [52].

Between 2018 and 2021, seven cases of mpox were diagnosed in the United Kingdom; four cases were related to travel from endemic countries, two cases resulted from household transmission from one of the index cases, and one case occurred in a health care worker who acquired infection nosocomially [53,54].

In July 2021, a patient was diagnosed with mpox in Dallas, Texas [55,56]. This patient developed symptoms during his return trip from Nigeria. In November 2021, another travel-related case was reported in a United States resident in Maryland who had recently returned from Nigeria [51]. No additional cases were linked to these two patients.

More detailed information on human-to human transmission of monkeypox virus is found below. (See 'Human-to-human transmission' below.)

Transmission — Animal-to-human and human-to-human transmission can occur.

Animal-to-human transmission — Monkeypox virus can be acquired through contact with an infected animal's bodily fluids or through a bite. It can also be acquired through preparation of bushmeat (raw or minimally processed meat that comes from wild animals in certain regions of the world, including Africa).

In Africa, evidence of monkeypox virus infection has been found in many types of animals, including rope squirrels, tree squirrels, Gambian pouched rats, dormice, and different species of monkeys [57]. Monkeys and humans are incidental hosts; the reservoir remains unknown but is likely to be rodents [21].

Findings from the 2003 United States prairie dog outbreak highlighted the importance of type of exposure and risk of infection (eg, bite wound versus touching an infected animal) as well as severity of clinical manifestations of mpox, presumably related to level of exposure. As an example, one study categorized exposures to a prairie dog as noninvasive (eg, the person touched an infected animal, cleaned an infected animal's cage) or "complex" (eg, invasive bite or scratch from an ill prairie dog) [58]. Patients with complex exposures were more likely than patients with noninvasive exposures to develop signs of systemic illness. (See '2022 global outbreak' above.)

Human-to-human transmission

Routes of person-to-person transmission — Human-to-human transmission of monkeypox virus can occur in several ways:

Direct contact – Spread of monkeypox virus is thought to occur primarily through direct contact with infectious sores, scabs, or body fluids [59]. As such, mpox can spread during activities that include close, personal contact with an infected individual. Transmission may be facilitated by a breach in the skin or mucosa of the recipient. (See 'Pathophysiology' below.)

During the ongoing worldwide outbreak of mpox reported beginning in May 2022 in nonendemic countries, close contact with infectious material from skin lesions or lesions on mucous membranes (eg, occurring during sexual and/or close intimate contact) is considered the main risk factor for acquisition [11,31,60]. (See 'Viral shedding and period of infectiousness' below.)

Further research is needed to determine the relative transmissibility by type of sexual exposure. The risk of transmission after specific types of nonsexual exposures is discussed separately. (See "Treatment and prevention of mpox (monkeypox)", section on 'Exposure definition and risk stratification'.)

Indirect contact through fomites – Transmission can occur through contact with materials or fomites that have become contaminated with infected material in the household or patient care environment, such as clothing or linens contaminated with infectious material from body fluids or sores [59,61,62]. In one report that investigated respiratory isolation rooms, viral DNA was found in rooms, bathrooms, anterooms, and on nontouch surfaces (eg, >1.5 meters from the bed) as well as on health care workers' PPE [63].

It is unclear whether contact through fomites is a common source of transmission however, the widespread surface contamination of the patient care environment calls for a systematic approach to the use of infection prevention precautions in the home and healthcare settings, which is discussed elsewhere. (See "Treatment and prevention of mpox (monkeypox)", section on 'Infection prevention and control'.)

Respiratory secretions – Monkeypox virus is also thought to be spread through respiratory secretions, although prolonged face-to-face contact may be required for transmission to occur via this route [55]. During the 2022 outbreak a study evaluating 181 mpox cases found that samples from skin lesions contain much more viral DNA than do those from the throat [42].

Activities resulting in resuspension of dried material from lesions (eg, shaking contaminated linens) may also present a risk and should be avoided.

Vertical transmission – The virus can cross the placenta from the mother to her fetus, which can lead to congenital mpox, although the rate of transmission or risk by trimester is not known [57]. In a report of four pregnant women with mpox from the Democratic Republic of the Congo, one gave birth to a healthy infant, two had miscarriages in the first trimester, and one had fetal death with the stillborn showing diffuse cutaneous maculopapular skin lesions consistent with vertical transmission [64]. During the global outbreak, one case of perinatal transmission has been reported [65], but pregnancy has not always resulted in transmission to the baby [66].

Percutaneous inoculation – There have been case reports of transmission via needlestick injuries from supplies used to collect cutaneous lesion samples. The mpox lesions appeared at the site of the needlestick [67,68]. While these cases resulted in a localized lesion, a systemic infection could result.

Risk of spread through other body fluids – At this time, it is not known if mpox can spread through semen, vaginal fluids, or other body fluids, although viral DNA has been detected in semen [27,39,69]. In a report of 12 cases from Spain during the 2022 outbreak, there were high rates of polymerase chain reaction (PCR) positivity in specimens collected from saliva (12 of 12), semen (7 of 9), urine (9 of 12), and feces (8 of 12) [70]. In a multi-country study, 29 of 32 semen samples had detectable monkeypox virus DNA [27]. In at least one case, monkeypox virus isolated from a semen sample was replication competent in cell culture, but it is still unknown if semen can transmit an infection [71]. Thus, testing of semen should not be used to guide precautions after recovery or assessing the risk of onward transmission given lack of data. (See "Treatment and prevention of mpox (monkeypox)", section on 'When to discontinue isolation'.)

Risk of transmission in different settings — The risk of transmission may vary depending upon the setting.

In the community – In the 2022 outbreak, the vast majority of cases have been associated with community transmission due to direct intimate contact. (See 'Routes of person-to-person transmission' above.)

One study found that the reproductive number of the virus ranged from 1.40 to 1.80, which implies a potential for sustainable local transmission [72]. Prior to this outbreak, transmission outside of a household and sustained human-to-human spread had been rare. (See 'Sporadic cases related to travel from endemic countries' above.)

In the household – Transmissibility from person to person within the household can vary. In one report from the Democratic Republic of the Congo, the secondary attack rate in households has been reported to be as high as 9 percent [73]. By contrast, a very limited number of transmission chains have been linked to households during the 2022 outbreak. As an example, in a study of 528 mpox cases from multiple countries, 0.8 percent were likely due to nonsexual close contact, and 0.6 percent were due to household contact [27]. Similarly, in another study of 181 cases from Spain, 3 percent of infections resulted from household contact [42].

In congregate living situations – There are limited data on the risk of monkeypox virus transmission in congregate living situations. In March 2022, an outbreak of mpox was described among 28 persons in a prison in Nigeria [74]. By contrast, in a report from the United States, no known cases developed in 57 jail residents who had a potential intermediate-risk exposure to a resident with mpox, even though monkeypox virus DNA was detected on at least one surface in the living quarters [75]. However, in this report there was loss of follow-up in about a third of the residents and receipt of post-exposure vaccination among almost a third of those who were followed. (See "Treatment and prevention of mpox (monkeypox)", section on 'Post-exposure prophylaxis'.)

In health care facilities – The risk of monkeypox virus transmission in well-resourced health care settings is low [53,76]. During the 2003 outbreak in the United States, there were no instances of nosocomial transmission in health care facilities. In a study of 57 health care personnel who were exposed to patients with mpox, none reported signs and symptoms of disease [77].

In a report that evaluated nosocomial transmission of monkeypox virus outside endemic regions during the 22 years prior to the global outbreak reported in May 2022, only one transmission event was reported [53]. During the 2022 outbreak, two cases occurred in HCP after needlestick injury from supplies used to collect samples from cutaneous lesion samples. (See 'Routes of person-to-person transmission' above.)

A detailed discussion of infection prevention measures for persons with mpox in healthcare settings is presented separately. (See "Treatment and prevention of mpox (monkeypox)", section on 'Infection prevention and control'.)

Viral shedding and period of infectiousness — Historically, a person is considered infectious from the onset of clinical manifestations until all skin lesions have scabbed over and re-epithelialization has occurred. (See "Treatment and prevention of mpox (monkeypox)", section on 'When to discontinue isolation'.)

During the 2022 outbreak, several studies have evaluated viral shedding, and estimated viral loads appear higher in skin lesions than at other sites [42,70,78]. As an example, in a prospective study of 181 patients with mpox, higher viral DNA loads were found on skin than on pharyngeal swabs [42]. In another report, higher viral DNA loads were consistently found in skin lesions and anogenital samples compared with throat, blood, urine or semen samples [78].

The duration of viral shedding can vary. In an analysis of 107 samples taken from 24 patients during the 2022 outbreak, the proportion of PCR positive samples decreased between days 0 and 14 at all sites [78]. However, in a different report, which followed seven patients with mpox in the United Kingdom between 2018 and 2021, PCR positivity in blood and upper respiratory tract samples was detected for at least three weeks in three of the patients [54]. The correlation of PCR positivity and infectivity was not established in these studies, and pending additional data, the duration of isolation should continue to be based on clinical evaluation. (See "Treatment and prevention of mpox (monkeypox)", section on 'When to discontinue isolation'.)

The infectiousness of individuals who have no symptoms is uncertain, as discussed below. (See 'Rare asymptomatic infection' below.)


Pathophysiology — Infections caused by orthopoxviruses can be classified as either systemic or localized (at the site of virus entry). The type of infection depends on the species of orthopoxvirus and the route of entry. Generalized disease usually manifests as a diffuse rash. In contrast, after cutaneous inoculation, a localized rash may appear at the site of virus entry, followed or not by disseminated lesions due to a viremia [79,80].

Infection via cutaneous inoculation – Monkeypox viruses can enter the human host through microabrasions in the skin (figure 1) [81]. The pathogenesis of human mpox following skin inoculation is felt to be similar to that of smallpox and other orthopoxviruses. Several orthopoxviruses can cause infection in animals after being introduced through the skin as well; this includes monkeypox virus and variola virus in nonhuman primates and ectromelia virus (ECTV) in mice [82].

Using a monkeypox virus animal model, after subcutaneous inoculation of a West African strain, viral replication was observed only in the skin and lymphatic system, while intranasal inoculation resulted in diffuse viral replication throughout the body tissues, including the lungs [81]. Human data are limited to those obtained from accidental or intentional skin inoculations of the vaccinia virus or variola virus (ie, variolation), which was observed to result in locally restricted lesions around the point of entry [82].

Infection via respiratory route – Monkeypox viruses can enter through the respiratory system in experimental models [81,83,84]. These types of animal models were a way to study pathogenesis and effectiveness of new drugs and vaccines, but it is unclear how closely these experimental models correspond to monkeypox virus transmission and pathogenesis in humans. (See 'Human-to-human transmission' above.)

Using a nonhuman primate model of respiratory monkeypox virus with histopathological examinations at several time points postchallenge, it was demonstrated that during the incubation period, the virus is first seen in respiratory bronchioles and alveoli in the lungs (postchallenge day 4) [84]. The virus then spreads to the regional lymph nodes and organs of the reticuloendothelial system (day 6), including the tonsils, spleen, liver, and colon, where it replicates. Virus was ultimately detected in the blood on day 8, and its concentration increased through day 10 along with widespread lesions in the skin.

Immunology — Monkeypox virus infection stimulates an adaptative immune response comprising activated effector CD4+ and CD8+ T-cells [85]; neutralizing antibodies (IgM and IgG); and the production of Th1-inflammatory cytokines (gamma interferon [IFN-γ], IL-1ra, IL-6, IL-8, and TNF) [86]. These immune responses restrict viral replication and induce prolonged immunity in recovering patients. However, it is unknown whether the pauci-symptomatic or localized presentation seen in the 2022 outbreak compared to the disseminated presentation of mpox disease is associated with a lower degree of the immune response following infection.

Histopathology — Mpox skin lesions in the vesicular stage consist of epidermal acanthosis and spongiosis with exocytosis of lymphocytes and neutrophils. In the center of the lesion, a vesicle affecting the entire epidermis is formed by ballooning degeneration of keratinocytes and accumulation of intercellular fluid [87]. A mixed inflammatory infiltrate is present at the dermal-epidermal junction at the base of the vesicle composed of lymphocytes, eosinophils, and neutrophils.

The lesion develops into a pustule containing apoptotic keratinocyte debris, a few viable keratinocytes, and inflammatory cells. Viable keratinocytes may be multinucleated or exhibit cytopathic damage, such as eosinophilic inclusion bodies, prominent nucleoli, and "ground glass" chromatin. A mixed inflammatory infiltrate is also present in the perivascular, perieccrine, and dermal regions. Finally, the pustule becomes desiccated and forms a crust.

Immunohistochemistry shows no virus in the nonaffected epidermis, but the virus is present in the cytoplasm all keratinocytes within the affected epidermis. The lymphocytic infiltrate is predominantly T-cell with CD4- and CD-8-positive elements [88].

The histologic features of mpox are very similar to those described in the literature for smallpox, vaccinia, and cowpox. Herpesviridae, including herpes simplex virus (HSV) and varicella, have been historically differentiated by the appearance of the viral cytopathic effect and further differentiated by immunohistochemistry.


Incubation period — The incubation period of monkeypox virus infection is usually from 5 to 13 days but can range from 4 to 21 days [36]. The 2003 United States outbreak described above allowed estimation of time from exposure to onset of symptoms [89]. For 29 patients, the estimated incubation time from exposure to illness was 12 days. Persons with a history of an animal bite or scratch may have a shorter incubation period than those with only tactile exposures (9 versus 13 days, respectively) [58].

During the 2022 outbreak, the incubation period has generally ranged from 7 to 10 days following exposure [42,90,91]. In an initial study of 18 cases in the Netherlands, the mean incubation period was found to be 8.5 days (5th to 95th percentiles: 4.2 to 17.3) [90]. Later in the outbreak, an analysis of 144 patients in Spain reported an incubation period of seven days (range 5 to 10) [42].

Clinical presentation during the 2022 outbreak — Mpox has traditionally caused a systemic illness that includes fevers, chills, and myalgias, with a characteristic rash that is important to differentiate from that of other vesicular eruptions (eg, varicella, smallpox). However, during the 2022 mpox outbreak, some patients have presented with genital, anal, and/or oral lesions without the systemic illness [36]. In the United States, the percent of patients presenting with these different manifestations can be found on the Centers for Disease Control and Prevention (CDC) website.

Systemic illness — Systemic symptoms are common and may occur before the rash appears (prodromal stage) or shortly thereafter (early clinical stage). These symptoms are attributable to a viremic phase of illness. (See 'Pathophysiology' above.)

Systemic symptoms typically last one to five days and are characterized by fever, headache, sore throat, back pain, myalgia, and fatigue. In a study of 181 cases in Spain, 160 (88 percent) reported at least one systemic symptom during the course of the disease, 87 (48 percent) presented with systemic symptoms before the onset of the rash, and 73 (59 percent) afterward [42].

During the global outbreak of mpox that started in May 2022, some patients have presented with lesions without the systemic illness [36]. In addition, generalized swelling of the lymph nodes has not been commonly seen during the prodromal or early clinical stages in the 2022 outbreak; however, regional lymphadenopathy is often associated with skin rash. (See 'Rash' below.)

Rash — The skin eruption usually occurs between one to two days before and three to four days after the onset of the systemic symptoms and continues for two to three weeks, although rashes without systemic illness have been reported [36].

Appearance – The rash associated with mpox progresses through several stages:

The rash typically begins as 2 to 5 mm diameter macules.

The lesions subsequently evolve to papules, vesicles, and then pseudo-pustules (papules that simulate pustules but are predominantly filled with cell debris and do not contain fluid or pus) [92]. Lesions are well circumscribed, deep seated, and often develop umbilication (a central depression on the top of the lesion). Additional images can be found on the CDC website.

The lesions eventually crust over, and these crusts dry up and then fall off. This typically occurs 7 to 14 days after the rash begins.

The lesions typically begin to develop simultaneously and evolve together on any given part of the body [93]. However, during the global outbreak of mpox beginning in May 2022, not all lesions were in the same stage of development [94].

The rash associated with mpox is often described as painful, but in the healing phase (crusts), it can become itchy [93].

The number of lesions varies from a few to one hundred. Most commonly, there are 1 to 20 lesions on the skin. Cases with more than 100 lesions have been extremely rare during the 2022 outbreak. In one report, eight cases with more than 100 lesions were identified in an investigation of 197 patients in central London, United Kingdom [43].

Location – During the 2022 outbreak, it was noted that patients frequently present with lesions located on the anogenital and perioral areas alone, with some developing a small number of lesions in the trunk or acral areas of the body [42,43].

Genital lesions may present in the form of one or two solitary penile lesions (picture 2) or multiple lesions that affect the penis, scrotum, and pubis. Genital lesions are commonly accompanied by surrounding edema (picture 3), which in some instances may progress to severe swelling of the penile glans or foreskin so that the retracted foreskin cannot be returned to its normal position (ie, paraphimosis). Large ulcers or necrotic crusts have also been reported as complications.

Lesions in the perianal region may present in the form of lesions in the buttocks and/or lesions involving the anal margin and perianal skin (picture 4). The latter are often associated with rectal pain or pain on defecation.

Perioral lesions include lesions of the tongue (picture 5), which are usually circular white lesions with a depression in the center, or ulcerated lesions of the oral mucosa or lips.

During the 2022 outbreak, some cases started with the rash presenting in the genital and oral areas (possibly the site of inoculation) with subsequent spread to the face and trunk after that [35]; in other cases, the lesions have not involved the face or extremities at all.

The lesions in distant regions have sometimes been in different stages of progression than the rash at the site of inoculation. Some cases presented with solitary primary lesions in the face or fingers in the absence of lesions in the genital and oral mucosa. Sometimes coalescing lesions result in large plaques, ulcerations, or crusts.

There are data to suggest that location of the lesions is consistent with the site of inoculation [31,42]. A study of 181 patients with mpox reported information on specific types of sexual practice and how these practices related to clinical presentation [42]. As an example, men who have sex with men (MSM) who engaged in anal-receptive sex presented with proctitis more frequently than MSM who did not engage in anal-receptive sex (41 [38 percent] of 108 versus four [7 percent] of 58, absolute difference 31 percent [95% CI 19-44]). In addition, 18 of the 19 participants with tonsillitis reported practicing oral-receptive sex.

Proctitis/tonsillitis — During the 2022 outbreak, patients with mpox have presented with proctitis or tonsillitis.

Proctitis – Some patients have presented with clinical manifestations of proctitis (eg, anorectal pain, tenesmus, and purulent discharge or bleeding), which may or not be associated with visible vesicular or pustular lesions on the perianal area; in some instances, hospitalization has been required for management of pain [27,42,43,92]. Patients with proctitis usually have a history of engaging in anal-receptive sex and have more often early systemic symptoms before developing skin lesions [43].

In patients with proctitis, proctoscopy may show evidence of mucosal inflammation or friability, though with visual inspection alone it is difficult to distinguish mpox from other infections (eg, lymphogranuloma venereum, herpes simplex virus [HSV], or syphilis) (see 'Differential diagnosis' below). However, we do not routinely perform proctoscopy in patients with suspected mpox proctitis since proctitis it is often associated with severe pain. If rectal wall perforation is suspected (severe pain or sepsis), a rectal magnetic resonance imaging (MRI) should be performed as part of the evaluation.

Ulcerative pharyngitis or tonsillitis – Some patients have presented with sore throat and difficulty swallowing that may limit or prevent oral intake. Ulcerative lesions may be seen on the palatine tonsils or the pharynx. The presence of these symptoms with a negative result on the Strep A rapid test suggests mpox as a possible cause, particularly in individuals with epidemiologic risk factors for mpox (table 1).

Ocular infections — Ocular mpox can present as conjunctivitis, blepharitis, keratitis, and loss of vision. Subconjunctival nodules have also been described [95]. In a report of five patients with ocular manifestation, all had concurrent nonocular manifestations [96]. Consultation with an ophthalmologist should be obtained if ocular infection is suspected.

Other complications — Several severe complications of mpox have been reported. Complications seen during the 2022 outbreak include the evolution of genital, perianal, or facial lesions into a coalescing large plaque, ulceration, or crust and superimposed cellulitis requiring antibiotic treatment (range of 3 to 4 percent of mpox cases in the largest series published) [27,42,43,92]. In some cases, surgical debridement of an affected extremity has been required [44].

Other complications include bowel lesions that are exudative or cause significant tissue edema leading to obstruction [44]. Preputial edema or gross edema of the penile glans resulting in paraphimosis has also been reported. (See "Paraphimosis: Clinical manifestations, diagnosis, and treatment".)

Neurologic complications (eg, encephalitis/encephalomyelitis) can also occur [97]. During the 2022 outbreak, deaths have been reported in patients who developed encephalitis (see 'Prognosis and risk for severe disease' below). One report describes two patients who presented with encephalomyelitis within five and nine days of their initial monkeypox virus infection [98]; radiographic imaging was consistent with acute demyelinating encephalitis, but polymerase chain reaction of cerebrospinal fluid was negative for poxvirus DNA. The pathogenesis of this complication remains unclear.

Other complications include bronchopneumonia, sepsis, myocarditis, infection of the cornea with loss of vision, epiglottitis, peritonsillar abscess, severe lymphadenopathy that can be necrotizing or obstructing, rectal wall perforation in patients with mpox proctitis, and hemophagocytic lymphohistiocytosis [27,43,44,57,99]. In addition, some patients have presented with a morbilliform rash of pink-to-red spots on the trunk, arms, and legs following administration of certain antibiotics (eg, ampicillin or amoxicillin) [42].

Laboratory findings — Multiple nonspecific laboratory findings can be seen in patients with mpox. These include abnormal aminotransferases, leukocytosis, thrombocytopenia, and hypoalbuminemia [89]. Diagnostic testing for mpox is described below. (See 'Diagnostic testing' below.)

Clinic presentation during previous outbreaks — Prior descriptions of mpox have primarily come from reports in Africa. During the 2017 to 2018 outbreak in Nigeria, a report of 122 confirmed or probable cases of human mpox were described [23]. The rash was present in all patients and involved all parts of the body, with the face being most affected; fever, pruritus, headache, and generalized lymphadenopathy were also common. In an unpublished report of 216 confirmed cases from the Democratic Republic of the Congo (2007 to 2011), the mean count of lesions at presentation was 370, and progression of lesions from one stage to another occurred in order [100].

In endemic areas, when the likely source of infection is due to the respiratory route of transmission via a household contact, the rash tends to be more concentrated on the face but can also occur on the trunk, arms, palms of the hands, legs, and soles of the feet. Other sites may include oral mucous membranes, conjunctivae, anus, and genitalia.

During the 2003 United States outbreak, a detailed review of 34 patients reported that the predominant signs and symptoms were rash (97 percent), fever (85 percent), chills (71 percent), lymphadenopathy (71 percent), headache (65 percent), and myalgias (56 percent) [89]. The onset of fever preceded the rash by approximately two days, but the median duration of fever was shorter than the rash (8 and 12 days, respectively). The following clinical pictures of the initial case identified in the United States were taken at the Marshfield Clinic in Wisconsin (picture 6A-D).

In a case series of seven patients diagnosed with mpox between 2018 and 2021 in the United Kingdom, the clinical features were similar to those seen in outbreaks of the West African clade of monkeypox virus in Nigeria [54]. All patients in this report developed facial rash; five of the seven also had lesions present in the genital area.

Prognosis and risk for severe disease — For most individuals, mpox is a self-limited disease with the symptoms lasting from two to four weeks. However, some patients may develop complications or severe disease. (See 'Other complications' above.)

Hospitalization rate – During the 2022 global outbreak, few hospitalizations have been reported and most were for the purpose of isolating the patient [101]. Other reasons for hospitalization included provision of adequate pain management and the need to treat secondary infections [27,34,37].

During the 2003 outbreak in the United States, 9 of the 34 patients had been hospitalized for a variety of reasons, including nausea, vomiting, and dysphagia [37,89]. The discharge diagnoses of two of the most seriously ill patients were encephalopathy and a retropharyngeal abscess. All of the patients in this case series survived with supportive therapy; no antiviral therapy was administered.

Mortality – The mortality associated with mpox has varied. In Central Africa, where the Central African clade (clade 1) is prevalent, the fatality rate has been reported as approximately 10 percent, with deaths generally occurring in the second week of illness [17,102].

In West Africa, where clade 2 is prevalent, the historical case fatality rates are <0.1 percent, except for the 2017 to 2018 outbreak in Nigeria that resulted in a fatality rate of 3.6 percent, with several deaths occurring in immunocompromised persons with HIV [23,103].

There were no deaths in the 2003 outbreak in the United States, which was likely due to the less virulent strain of monkeypox virus (clade II) [89]. In addition, in the case series of seven patients diagnosed with mpox between 2018 and 2021 in the United Kingdom, all patients made a full recovery [54].

During the 2022 outbreak, deaths have been reported [104]. Cases have been described in immunocompromised persons [105] and in those who developed encephalitis [106,107].

Risk factors for severe disease – Underlying immune deficiencies may lead to worse outcomes. Although data in immunocompromised patients with mpox are lacking, severe complications have been historically seen in immunocompromised patients who have had smallpox or have received smallpox vaccination with a replication-competent vaccinia virus. (See "Variola virus (smallpox)" and "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses" and 'Clinical presentation during the 2022 outbreak' above.)

In persons with HIV, data from endemic countries indicate that those with advanced and uncontrolled HIV infection might be at higher risk for severe or prolonged mpox following infection [23,105]. During the outbreak that began in 2022, persons with HIV and CD4 counts <200 cells/microL with severe manifestations of mpox have been particularly difficult to manage, some have presented with severe manifestations and some have died [44,105]. In certain cases, this may have been due in part to delays in therapy. In one report, some patients experienced delays of up to four weeks from the time of presentation to when treatment was initiated [105].

However, in reports where most patients are receiving effective antiretroviral therapy (ART), there has been no evident excess in complications, hospitalizations, or deaths among persons with HIV infection and mpox [41,42]. As an example, in two studies that together included 313 people living with controlled HIV, there were no differences in clinical features or clinical outcomes between those with or without HIV [27,42]. Another report found that patients with HIV were more likely to have a higher rash burden, but there was no association between HIV status and severe illness [108].

Historically, severe disease has been more likely to occur in children [89,109], but there does not appear to be an increase in the severity of disease among the few children and adolescents affected during the 2022 outbreak. In a case series that included four children less than four years of age and 12 adolescents (13 to 17 years of age), none required hospitalization or antiviral therapy [29].

Rare asymptomatic infection — Asymptomatic infections have been reported but appear to be rare [34,110-112]. Seroepidemiological studies in Africa suggest some patients may have subclinical or asymptomatic mpox [111]. In a study from France, polymerase chain reaction (PCR) testing was performed on 200 samples from asymptomatic men and 13 (6.5 percent) were positive for monkeypox virus; two patients subsequently developed symptoms [112].

The potential for transmission from an individual with asymptomatic infection is uncertain [112]. In a study performed at the beginning of the 2022 outbreak in Europe, stored anogenital and oropharyngeal specimens from 224 men who had been tested for gonorrhea and chlamydia were PCR tested for mpox; three men had anorectal specimens positive for monkeypox virus DNA despite absence of symptoms or exposure to a person with mpox [110]. Monkeypox virus was able to be grown from two samples. Although this finding raises concern that people with asymptomatic or mild disease could contribute to ongoing transmission, it is not yet clear such patients can transmit the virus

EVALUATION AND DIAGNOSIS — The diagnosis of mpox takes into account epidemiologic, clinical, and laboratory findings. Several authorities have put forth case definitions for suspected mpox during the 2022 outbreak. Definitions from the World Health Organization (WHO) and the United States Centers for Disease Control and Prevention (CDC) can be found on their websites.

When to suspect the diagnosis — The diagnosis of mpox should be suspected in patients who:

Present with a rash or other symptoms that could be consistent with mpox (eg, proctitis) (see 'Clinical manifestations' above)


Have epidemiologic risk factors for infection (eg, close or intimate in-person contact with individuals who have suspected or confirmed mpox or are part of a social network or community experiencing mpox; recent travel to Central or West Africa or other areas where large outbreaks of mpox have been reported) (table 1). If testing is done on lesions from a patient at low risk for mpox disease, false-positive results can be seen [113].

If the diagnosis of mpox is being considered, infection prevention and control measures should be implemented to reduce the risk of transmission. These include standard and droplet precautions and are discussed in detail separately. (See "Treatment and prevention of mpox (monkeypox)".)

Diagnostic testing — If the diagnosis of mpox is suspected, providers should send specimens for testing [114]. This can be done either through consultation with public health authorities or by sending swabs to select commercial labs. A confirmed or probable diagnosis requires supporting laboratory evidence such as detection of virus or the development of immunoglobulin (Ig)M antibodies (table 1).

Viral testing – Polymerase chain reaction (PCR) testing for orthopoxvirus DNA should be performed on lesion samples. Lesions should be vigorously swabbed to collect skin cells that come off the lesion [115]. Unlike the lesions seen in herpes simplex virus, which are usually filled with fluid and easily unroofed, mpox lesions can be filled with solid material, making them difficult to unroof with a swab. As discussed above, sharps should not be used to collect samples for testing due to the risk of infection via percutaneous inoculation. (See 'Routes of person-to-person transmission' above.)

If there are multiple lesions, a few of them can be sampled (using separate swabs). It is recommended to take two swabs from each specimen. Additional information on laboratory testing, including the approach to specimen collection, can be found on the CDC website; clinicians should also verify any specific specimen collection instructions with their local public health department.

In the United States, this testing can be done at a Laboratory Response Network site or certain commercial laboratories. In the 2022 global outbreak, the CDC considers a patient with a positive orthopoxvirus PCR result to have a probable case of mpox (table 1). However, on occasion, a PCR test may be positive with low amounts of viral DNA detected; in this setting, a repeat test should be performed if the patient has an atypical clinical presentation or a low-risk exposure (table 2). In one report, false positive results were reported in three patients who were at low risk of mpox; cycle threshold values were all ≥34 [113].

Viral testing of a throat swab may also be performed for epidemiologic purposes but is generally not used to confirm the diagnosis in the clinical setting. Similarly, although a positive PCR result has been found in some blood specimens, the clinical significance of viremia is not established.

Serologic testing – Serologic testing for monkeypox virus can be used to support a diagnosis of mpox (table 1) and may be particularly helpful if viral testing is not able to be performed. The decision to obtain serologic testing is generally made in conjunction with public health officials.

Patients with mpox typically have detectable levels of antiorthopoxvirus IgM antibody during the period of 4 to 56 days after rash onset. The CDC developed an IgM capture and an IgG enzyme-linked immunosorbent assay (ELISA) that demonstrated recent monkeypox virus infection. Serum IgM and IgG antibodies were detected five and eight days after onset of rash, respectively [116].

Orthopoxvirus can also be identified through electron microscopy, in which characteristic brick-shaped poxvirus virions can be seen. (See 'Virology' above.)

Histopathologic analysis may demonstrate ballooning degeneration of keratinocytes, prominent spongiosis, dermal edema, and acute inflammation; however, these findings can also be seen in other viral infections [87]. (See 'Histopathology' above.)

DIFFERENTIAL DIAGNOSIS — Several infections need to be considered in the differential diagnosis of mpox [114]; these include:

Varicella – Given the worldwide eradication of smallpox, the most likely diagnostic consideration in a patient presenting with a vesicular rash is varicella (chickenpox). In several outbreaks, it has been difficult to distinguish the two [13,16,73,117]. One feature that historically helped distinguish these infections is lymphadenopathy, which is often a distinctive feature of mpox compared with varicella. In addition, unlike varicella lesions, which are vesicular fluid filled lesions, mpox lesions are typically pseudo-pustules, which are papules that simulate pustules but do not contain fluid or pus. Furthermore, varicella lesions are usually in different stages of development and healing, whereas mpox lesions are typically at the same stage. However, during the global mpox outbreak that started in May 2022, some reports describe lesions that were in different stages of development [94]. Detailed discussions of the clinical manifestations and diagnosis of varicella infection are presented elsewhere. (See "Clinical features of varicella-zoster virus infection: Chickenpox".)

Herpes simplex virus – Herpes simplex virus (HSV) can present with both oral and genital lesions similar to mpox. Although persons with primary HSV may present with systemic symptoms such as fever and myalgias, those with recurrent HSV typically have milder symptoms. The best way to confirm the diagnosis of HSV infection is through polymerase chain reaction (PCR) testing of the lesions, which is readily available. (See "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection" and "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection".)

Other sexually transmitted infections – In addition to genital herpes, other sexually transmitted infections may present with signs and symptoms that overlap with those of mpox. For those who present with penile, vaginal, or perianal ulcerated lesions, primary syphilis, lymphogranuloma venereum, or Haemophilus ducreyi should be considered in the differential diagnosis. In patients with inflammation of the rectum (ie, proctitis), lymphogranuloma venereum, chlamydia, gonorrhea, and syphilis should be considered. Throat features of mpox may be mistaken for bacterial tonsillitis or primary syphilis. (See "Approach to the patient with genital ulcers" and "Evaluation of anorectal symptoms in men who have sex with men", section on 'Proctitis'.)

Impetigo – Impetigo presents with vesicles, pustules, and golden adherent crusts caused by infection with group A Streptococcus (GAS; Streptococcus pyogenes) and Staphylococcus aureus. Recognition of the characteristic golden crust should raise suspicion for impetigo. (See "Impetigo".)

Molluscum contagiosum – Molluscum contagiosum is a localized skin infection that is typically seen in children but can also occur in adults. Similar to mpox, it is caused by a poxvirus and is transmitted through direct skin contact or fomites. Molluscum contagiosum infection in the genital region may result from transmission during sexual activity. This infection most commonly presents as single or multiple small, skin-colored papules with central umbilication (picture 7A-G). Immunocompromised individuals have an increased risk for larger lesions and more widespread disease (picture 8A-B). The diagnosis is usually based upon the clinical appearance of skin lesions, but a biopsy can confirm the diagnosis when necessary. (See "Molluscum contagiosum".)

Smallpox – Because of concerns regarding bioterrorism, it is also important to consider the possibility of smallpox in the differential diagnosis of a patient presenting with a pox-like rash [15]. (See "Identifying and managing casualties of biological terrorism" and "Variola virus (smallpox)".)

Vaccinia virus – The replication-competent smallpox vaccine (ACAM2000) generates local skin lesions that could be spread to other areas of the body. As such, it may be unclear if the patient is experiencing breakthrough mpox versus an adverse event related to the vaccine. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses", section on 'Complications'.)

Other pox viruses – Also in the differential diagnosis is tanapox, another African poxvirus that causes a febrile prodrome and skin lesions that resolve over several weeks without sequelae. A case of tanapox infection was diagnosed using electron microscopy and DNA analysis (PCR testing) of a biopsied skin lesion in an American college student who had worked in the Republic of the Congo for eight weeks caring for chimpanzees; none of the others working with these animals developed the infection [118].

Orf and bovine stomatitis (also caused by parapoxviruses) can produce localized skin lesions similar to those of mpox but are difficult to distinguish clinically. It is possible to differentiate between these conditions based on their epidemiological characteristics and previous animal contact history. In research laboratories, they can be differentiated by an experienced microscopist by morphologic features on electron microscopy. Parapoxvirions are slightly smaller than orthopoxvirus virions and have a more regular surface pattern than orthopoxviruses. (See "Orf virus infection".)

Other novel orthopoxvirus infections can also be considered. These include Alaskapox virus, camelpox, cowpox, Orthopoxvirus Abatino, and Akhmeta virus [119-121].

The lesions associated with mpox can also be confused with noninfectious etiologies. These are discussed in detail elsewhere. (See "Vesicular, pustular, and bullous lesions in the newborn and infant" and "Approach to the patient with pustular skin lesions" and "Approach to the patient with cutaneous blisters" and "Skin lesions in the returning traveler" and "Approach to adult patients with anorectal complaints".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Mpox (monkeypox) (The Basics)")

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Orthopoxvirus (smallpox and monkeypox)".)


Virology – Mpox (previously referred to as monkeypox) is a viral zoonotic disease that is caused by monkeypox virus. (See 'Terminology' above.)

Monkeypox virus is an orthopoxvirus that is in the same genus as variola virus (the causative agent of smallpox) and vaccinia virus (the virus used in the available smallpox vaccines). Distinct strains of monkeypox virus exist in different geographic regions. The strain isolated from West Africa appears to be less virulent than the one from Central Africa. (See 'Virology' above.)

Geographic distribution Historically, most cases of mpox have occurred in Central and West Africa. However, since May 2022, there has been a global outbreak of mpox in many nonendemic countries. On July 23, 2022, the World Health Organization (WHO) declared this outbreak a public health emergency of international concern.

Prior to 2022, most cases in nonendemic countries were reported in travelers who were returning from endemic regions. There was also an outbreak of human mpox in the United States in 2003 associated with infected prairie dogs who were exposed to imported animals from Africa. (See 'Geographic distribution' above.)

Transmission – Human-to-human transmission of monkeypox virus can occur through several routes. These include (see 'Human-to-human transmission' above):

Close contact with infectious skin lesions. The current global outbreak in nonendemic countries has been primarily associated with close intimate contact, such as during sexual activity.

Indirect contact with infectious fluid (eg, on contaminated linens).

Percutaneous inoculation via needlestick injuries from supplies used to collect cutaneous lesion samples.

Large respiratory droplets. For this to occur, prolonged face-to-face contact may be required (eg, within a six-foot radius for ≥3 hours in the absence of personal protection equipment [PPE]). Activities resulting in resuspension of dried material from lesions (eg, shaking contaminated linens) may also present a risk and should be avoided.

Monkeypox virus can also been acquired through contact with an infected animal's bodily fluids or through a bite. Monkeys and humans are incidental hosts; the reservoir is likely to be certain rodents. (See 'Animal-to-human transmission' above.)

Clinical features – In patients with mpox, the incubation period from time of exposure to clinical illness is usually 5 to 13 days. During the global mpox outbreak in 2022, the incubation period has generally ranged from 7 to 10 days. (See 'Incubation period' above.)

Patients often present with a systemic illness that includes fevers, chills, and myalgias followed by a characteristic rash. The rash typically begins as macules and evolves to papules, vesicles, and then pseudo-pustules. The lesions eventually crust over, and these crusts dry up and then fall off. (See 'Clinical presentation during the 2022 outbreak' above and 'Clinic presentation during previous outbreaks' above.)

During the current outbreak of mpox, some patients have presented with genital, rectal, and/or oral lesions without the initial prodrome (figure 1). Patients have also presented with proctitis, tonsillitis, ocular disease, and/or other complications (eg, encephalomyelitis). (See 'Rash' above and 'Proctitis/tonsillitis' above and 'Ocular infections' above and 'Other complications' above.)

Disease course – Most patients with mpox have a self-limited illness. In the 2022 global outbreak, rare deaths have been reported. By contrast, in Central Africa, where infection is caused by a different strain (clade 1), the fatality rate has been reported to be as high as 10 percent. (See 'Prognosis and risk for severe disease' above.)

Evaluation and diagnosis – The diagnosis of mpox should be suspected in patients who present with a rash or other symptoms that could be consistent with mpox and have epidemiologic risk factors for infection (table 1). (See 'Evaluation and diagnosis' above.)

A diagnosis of monkeypox virus infection can be made through demonstration of orthopoxvirus DNA (eg, by polymerase chain reaction [PCR] testing or next-generation sequencing of a clinical specimen) or through isolation of monkeypox virus in culture from a clinical specimen.

Differential diagnosis – When evaluating a patient with suspected mpox, varicella zoster virus (presenting as chickenpox or herpes zoster), herpes simplex, smallpox, and other poxvirus infections should be included in the differential diagnosis. (See 'Differential diagnosis' above.)

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