Case definitions

Case definitions are presented here from the World Health Organization, the UK Health Security Agency, and the Centers for Disease Control and Prevention. Case definitions may vary between regions. Consult your local public health authority for the most current case definition. Other case definitions may be available.

World Health Organization: surveillance case definitions[92]

Last updated: 22 December 2022

Suspected case:

  • A person who is a contact of a probable or confirmed mpox case in the 21 days before the onset of signs or symptoms, and who presents with any of the following: acute onset of fever (>101.3°F [>38.5°C]); headache; myalgia; back pain; profound weakness; or fatigue.

  • A person presenting since 1 January 2022 with an unexplained acute skin rash, mucosal lesions, or lymphadenopathy AND for which the following causes of acute rash or skin lesions do not fully explain the clinical picture: varicella zoster, herpes zoster, measles, herpes simplex, bacterial skin infections, disseminated gonococcus infection, primary or secondary syphilis, chancroid, lymphogranuloma venereum, granuloma inguinale, molluscum contagiosum, allergic reaction (e.g., to plants), and any other locally relevant common causes of papular or vesicular rash (it is not necessary to obtain negative laboratory results for listed common causes of rash illness in order to classify a case as suspected).

    • The skin rash may include single or multiple lesions in the anogenital region or elsewhere on the body. Mucosal lesions may include single or multiple oral, conjunctival, urethral, penile, vaginal, or anorectal lesions. Anorectal lesions can also manifest as anorectal inflammation (proctitis), pain, and/or bleeding.

Probable case:

  • A person presenting with an unexplained acute skin rash, mucosal lesions, or lymphadenopathy (see above for description of rash/lesions); AND

  • One or more of the following:

    • An epidemiologic link to a probable or confirmed case of mpox in the 21 days before symptom onset

    • Identifies as gay, bisexual, or other cisgender or transgender man who has sex with men

    • Multiple and/or casual sexual partners in the 21 days before symptom onset

    • Detectable levels of anti-Orthopoxvirus IgM antibody (during the period of 4 to 56 days after rash onset), or a four-fold rise in IgG antibody titer based on acute (up to day 5 to 7) and convalescent (day 21 onwards) samples, in the absence of a recent smallpox/mpox vaccination or other known exposure to Orthopoxvirus

    • A positive test result for orthopoxviral infection (e.g., Orthopoxvirus-specific polymerase chain reaction [PCR] without monkeypox virus-specific PCR or sequencing).

Confirmed case:

  • Laboratory-confirmed monkeypox virus by detection of unique sequences of viral DNA by real-time PCR and/or sequencing.

Discarded case:

  • A suspected or probable case for which laboratory testing of lesion fluid, skin specimens, or crusts by PCR and/or sequencing is negative for monkeypox virus

  • Conversely, a retrospectively detected probable case for which lesion testing can no longer be adequately performed (i.e., after the crusts fall off) and no other specimen is found PCR-positive would remain classified as a probable case

  • A suspected or probable case should not be discarded based on a negative result from an oropharyngeal, anal, or rectal swab.

As of 3 September 2022, the European Centre for Disease Prevention and Control follows the WHO case definition.[213]

UK Health Security Agency: mpox (monkeypox) – case definitions[155]

Last updated: 23 January 2023

Possible case:

  • A person with a febrile prodrome (i.e., fever ≥100.4°F [≥38°C], chills, headache, exhaustion, myalgia, arthralgia, backache, and lymphadenopathy) compatible with mpox where there is known prior contact with a confirmed case in the 21 days before symptom onset; AND/OR

  • A person with an illness where the clinician has a high suspicion of mpox such as unexplained lesions, including but not limited to:

    • Genital, anogenital, or oral lesion(s) (e.g., ulcers, nodules)

    • Proctitis (e.g., anorectal pain, bleeding).

Probable case:

  • A person with unexplained rash or lesion(s) on any part of their body (including genital/perianal or oral) or proctitis (e.g., anorectal pain, bleeding) AND either:

    • Has an epidemiologic link to a confirmed, highly probable, or probable case of mpox in the 21 days before symptom onset; or

    • Identifies as gay, bisexual, or other man who has sex with men; or

    • Has had one or more new sexual partners in the 21 days before symptom onset.

Highly probable case:

  • A person with an orthopox virus PCR-positive result where monkeypox remains the most likely diagnosis.

Confirmed case:

  • A person with a laboratory-confirmed mpox infection (monkeypox virus PCR-positive).

All confirmed or highly probable cases should be notified to the local health protection team by the clinician.

Centers for Disease Control and Prevention: case definitions for use in the 2022 mpox response[156]

Last updated: 22 July 2022

Suspected case:

  • New characteristic rash; OR

  • Meets one of the epidemiologic criteria and has a high clinical suspicion for mpox.

Probable case:

  • No suspicion of other recent Orthopoxvirus exposure (e.g., vaccinia virus from ACAM2000® vaccine); AND the presence of:

    • Orthopoxvirus DNA by polymerase chain reaction of a clinical specimen; OR

    • Orthopoxvirus using immunohistochemical or electron microscopy testing methods; OR

    • Demonstration of detectable levels of anti-Orthopoxvirus IgM antibody during the period of 4 to 56 days after rash onset.

Confirmed case:

  • Demonstration of the presence of monkeypox virus DNA by polymerase chain reaction testing or next-generation sequencing of a clinical specimen OR isolation of monkeypox virus in culture from a clinical specimen.

Epidemiologic criteria (within 21 days of illness onset):

  • Reports having contact with a person or people with a similar-appearing rash or who received a diagnosis of confirmed or probable mpox; OR

  • Had close or intimate in-person contact with individuals in a social network experiencing mpox activity; this includes men who have sex with men who meet partners through an online website, digital application ("app"), or social event (e.g., a bar or party); OR

  • Traveled outside the US to a country with confirmed cases of mpox or where monkeypox virus is endemic; OR

  • Had contact with a dead or live wild animal or exotic pet that is an African-endemic species or used a product derived from such animals (e.g., game meat, creams, lotions, powders, etc).

Exclusion criteria:

  • A case may be excluded as a suspect, probable, or confirmed case if:

    • An alternative diagnosis can fully explain the illness; OR

    • An individual with symptoms consistent with mpox does not develop a rash within 5 days of illness onset; OR

    • A case where high-quality specimens do not demonstrate the presence of Orthopoxvirus or monkeypox virus or antibodies to Orthopoxvirus.

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