Ron Smith, MD

Monkeypox in the News

This digitally-colorized electron microscopic (EM) image depicted monkeypox virus particles, obtained from a clinical sample associated with the 2003 prairie dog outbreak. It was a thin section image from of a human skin sample. On the left were mature, oval-shaped virus particles, and on the right were the crescents, and spherical particles of immature virions.

Quick Overview

Monkeypox Clinical History and Features

Ryan, Edward, T. et al. Hunter’s Tropical Medicine and Emerging Infectious Diseases E-Book. Available from: Elsevier eBooks+, (10th Edition). Elsevier – OHCE, 2019.

Natural History and Pathogenesis

Monkeypox begins with infection of either the dermis (after transmission from infected animals) or the respiratory epithelium (after transmission from an infected person). The virus disseminates through the lymphatic system, resulting in primary viremia and systemic infection. A secondary viremia results in infection of the epithelium, producing skin and mucosal lesions. As a consequence of replication in mucosal surfaces the virus can be transmitted through oropharyngeal secretions to close contacts. The risk of transmission likely depends on the density of oropharyngeal lesions, the proximity and duration of contact, and virus survival, despite host immune responses. Monkeypox virus, like other poxviruses, has evolved mechanisms to evade host immune responses. Monkeypox virus is likely to be stable on fomites, and the number of virions required for infection is thought to be low based on potential similarities with variola virus. Strain differences may exist—monkeypox strains circulating in western Africa appear to be more attenuated and less transmissible than those in the Congo basin. 21

The incubation period from exposure to the onset of clinical symptoms and signs is 10 to 14 days. Patients are infectious during the first week of rash and should be isolated. 13 Most people infected with monkeypox virus are symptomatic, but sub-clinical infection can occur. Serologic studies of household contacts of acutely infected cases in the Democratic Republic of Congo suggest that approximately 28% of all monkeypox infections are sub-clinical. More recently, immunologic evidence of exposure to monkeypox virus was identified in several asymptomatic contacts of infected people in the United States.22,23
HIV and other conditions that suppress cell-mediated immunity may alter the natural history of disease. No data exist for monkeypox, but other poxvirus infections, specifically vaccinia and molluscum contagiosum viruses, are more severe in those who are infected with HIV.

Clinical Features

The clinical features of monkeypox resemble those of smallpox (variola) ( Table 32.2.3). Symptoms begin with a prodromal illness of fever and malaise lasting 1 to 3 days, followed by the characteristic rash. In contrast to smallpox, prominent sub-mandibular, cervical, post-auricular, axillary, or inguinal lymphadenopathy occurs in many infected persons 1 to 2 days before rash onset. Lymphadenopathy is not a typical feature of smallpox and can serve to clinically distinguish monkeypox from smallpox ( Fig. 32.2.2; see Table 32.2.3). As with smallpox, lesions develop concurrently and progress at a similar rate over 2 to 4 weeks, depending on the disease severity. The rash begins as small, 2- to 5-mm papules and progresses through vesicular, pustular, and crusted stages over 2 to 3 weeks ( Fig. 32.2.3). Like smallpox, it tends to be more severe on the head and extremities, including the palms and soles, and less intense on the trunk. The scabs slough off during recovery, leaving de-pigmented scars. Complications of monkeypox include secondary bacterial infection of the skin lesions, pneumonitis, and eye involvement. Death occurs during the second week of illness in approximately 10% of cases. Prior vaccination with vaccinia virus (smallpox vaccine) results in milder disease with fewer skin lesions, less lymphadenopathy, and significantly lower mortality. 24

TABLE 32.2.4 Centers for Disease Control and Prevention Case Definition for Monkeypox

Ryan, Edward, T. et al. Hunter's Tropical Medicine and Emerging Infectious Diseases E-Book. Available from: Elsevier eBooks+, (10th Edition). Elsevier - OHCE, 2019.
Incubation period
Prodrome period
Depth (diameter in mm)
Time to desquamation
Frequency of lesions on palms or soles of feet
Superficial to deep (4–6)
Centrifugal (mainly)
Homogeneous rash
Deep (4–6)
Homogeneous rash
Mild or none
Superficial (2–4)
Heterogeneous rash
Clinical Criteria
• Rash (macular, papular, vesicular, or pustular; generalized or localized; discrete or confluent)
• Fever (subjective or measured temperature of ≥99.3°F [≥37.4°C])
• Other signs and symptoms:
• Chills and/or sweats
• Headache
• Backache
• Lymphadenopathy
• Sore throat
• Cough
• Shortness of breath
Epidemiologic Criteria
• Exposure * to an exotic wild mammalian pet † obtained on or after April 15, 2003, with clinical signs of illness (e.g., conjunctivitis, respiratory symptoms, and/or rash)
• Exposure * to an exotic or wild mammalian pet † with or without clinical signs of illness that has been in contact with either a mammalian pet § or a human with monkeypox
• Exposure ¶ to a suspect, probable, or confirmed human case of monkeypox
Laboratory Criteria
• Isolation of monkeypox virus in culture
• Demonstration of monkeypox virus DNA by polymerase chain reaction testing of a clinical specimen
• Demonstration of virus morphologically consistent with an Orthopoxvirus by electron microscopy in the absence of exposure to another Orthopoxvirus
• Demonstration of presence of Orthopoxvirus in tissue using immunohistochemical testing methods in the absence of exposure to another Orthopoxvirus
Suspect Case
• Meets one of the epidemiologic criteria, AND
• Fever or unexplained rash, AND
• Two or more signs or symptoms with onset of first sign or symptoms less than 21 days after last exposure meeting epidemiologic criteria
Probable Case
• Meets one of the epidemiologic criteria, AND
• Fever, AND
• Vesicular-pustular rash with onset of first sign or symptom less than 21 days after last exposure meeting epidemiologic criteria, OR
• If rash is present but the type is not described, demonstrates elevated levels of IgM antibodies reactive with Orthopoxvirus between at least days 7–56 after rash onset
Confirmed Case
• Meets one of the laboratory criteria
• An alternative diagnosis can fully explain the illness, OR
• The case was reported on the basis of primary or secondary exposure to an exotic or wild mammalian pet or a human (see epidemiologic criteria) subsequently determined not to have monkeypox, provided other possible epidemiologic exposure criteria are not present, OR
• A case without a rash does not develop a rash within 10 days of onset of clinical symptoms consistent with monkeypox.
• The case is determined to be negative for non-variola generic Orthopoxvirus by polymerase chain reaction testing of a well-sampled rash lesion by the approved Laboratory Response Network (LRN) protocol, OR
• The case is determined to have undetectable levels of IgM antibody during the period 7–56 days after rash onset.