Updated Interim Case Definition for Human Monkeypox, January 2004

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The previous case definition (published July 2, 2003) has been updated as follows:

• Exclusion criteria have been revised
• Probable case classification has been edited

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

• Exposure¹ to an exotic or wild mammalian pet² obtained on or after April 15, 2003, with clinical signs of illness (e.g., conjunctivitis, respiratory symptoms, and/or rash)
• Exposure¹ to an exotic or wild mammalian pet² with or without clinical signs of illness that has been in contact with either a mammalian pet³ or a human with monkeypox
• Exposure⁴ 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.

Case Classification

Suspect Case

• Meets one of the epidemiologic criteria

AND

• Fever or unexplained rash AND two or more other signs or symptoms with onset of first sign or symptom <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 <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 orthopox virus between at least days 7 to 56 after rash onset⁵

Confirmed Case

• Meets one of the laboratory criteria

Exclusion Criteria

A case may be excluded as a suspect or probable monkeypox case if:

• An alternative diagnosis can fully explain the illness⁶, 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 monkeypox⁷.
• 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.
• The case is determined to have undetectable levels of IgM antibody during the period of 7-56 days after rash onset.⁸