Criteria

Multi-country outbreak (2022): case definitions

Case definitions for the current ongoing multi-country outbreak are presented here from the World Health Organization, the UK Health Security Agency, the European Centre for Disease Prevention and Control, and the US Centers for Disease Control and Prevention. Case definitions vary between regions and may evolve due to the rapidly evolving nature of the outbreak. Consult your local public health authority for the most current case definition. Other case definitions may be available.

World Health Organization: surveillance case definitions[78]

Last updated: 25 August 2022

Suspected case:

  • A person who is a contact of a probable or confirmed monkeypox case in the 21 days before the onset of signs or symptoms, and who presents with any of the following: acute onset of fever (>38.5°C [>101.3°F]); 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 epidemiological link to a probable or confirmed case of monkeypox in the 21 days before symptom onset

    • Identifies as gay, bisexual, or other 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 titre based on acute (up to day 5 to 7) and convalescent (day 21 onwards) samples, in the absence of a recent smallpox/monkeypox 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.[188]

UK Health Security Agency: monkeypox – case definitions[135]

Last updated: 9 August 2022

Possible case:

  • A person with a febrile prodrome (i.e., fever ≥38°C [≥100.4°F], chills, headache, exhaustion, myalgia, arthralgia, backache, and lymphadenopathy) compatible with monkeypox infection 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 monkeypox 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 epidemiological link to a confirmed, highly probable, or probable case of monkeypox 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 in 2022 and where monkeypox remains the most likely diagnosis.

Confirmed case:

  • A person with a laboratory-confirmed monkeypox infection (monkeypox PCR-positive) in 2022.

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 monkeypox response[136]

Last updated: 22 July 2022

Suspected case:

  • New characteristic rash; OR

  • Meets one of the epidemiological criteria and has a high clinical suspicion for monkeypox.

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.

Epidemiological 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 monkeypox; OR

  • Had close or intimate in-person contact with individuals in a social network experiencing monkeypox 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

  • Travelled outside the US to a country with confirmed cases of monkeypox 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 monkeypox 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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