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 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[46]

Last updated: 24 June 2022

Suspected case:

  • A person of any age presenting since 1 January 2022 with an unexplained rash or one or more acute skin lesions; AND

  • One or more of the following signs or symptoms: headache; acute onset of fever (>101.3°F [>38.5°C]); lymphadenopathy; myalgia; backache; asthenia; AND

  • For which the following causes of acute rash do not 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.

Probable case:

  • A person meeting the case definition for a suspected case; AND

  • One or more of the following:

    • An epidemiologic link to a probable or confirmed case of monkeypox in the 21 days before symptom onset including: prolonged face-to-face exposure in close proximity, including health workers without appropriate personal protective equipment; direct physical contact with skin or skin lesions, including sexual contact; or contact with contaminated materials such as clothing, bedding, or utensils

    • Multiple or anonymous 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/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, regardless of associated symptoms or their absence (to more fully characterize presymptomatic, paucisymptomatic, or asymptomatic infections).

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.

UK Health Security Agency: monkeypox – case definitions[73]

Last updated: 25 July 2022

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 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 - this could include unexplained genital, anogenital, or oral lesion(s) (e.g., ulcers, nodules) or proctitis (e.g., anorectal pain, bleeding).

Probable case:

  • A person with unexplained rash on any part of their body (including genital/perianal or oral) or proctitis AND either:

    • Has an epidemiologic link to a confirmed 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; or

    • Reports a travel history to West or Central Africa in the 21 days before symptom onset.

Highly probable case:

  • A person with an orthopox virus positive result since 15 March 2022 and where monkeypox remains the most likely diagnosis.

Confirmed case:

  • A person with a laboratory-confirmed monkeypox infection (monkeypox polymerase chain reaction-positive).

European Centre for Disease Prevention and Control: monkeypox – case definition[94]

Last updated: 23 May 2022

Probable case:

  • A person with an unexplained rash on any part of their body AND one or more other symptom(s) of monkeypox infection (fever, headache, backache, fatigue, lymphadenopathy) with symptom onset since 1 March 2022 AND one of the following:

    • Has a positive laboratory test result on Orthopoxvirus infection (e.g., Orthopoxvirus-specific positive polymerase chain reaction [PCR] without sequencing, electron microscopy, serology)

    • Has an epidemiologic link to a confirmed or probable case of monkeypox in the 21 days before symptom onset

    • Reports travel to monkeypox-endemic countries in the 21 days before symptom onset

    • Is a person (of any sexual orientation) who had multiple or anonymous sexual partners in the 21 days before symptom onset

    • Is a man who has sex with men.

  • A person with an unexplained generalized or localized maculopapular or vesiculopustular rash with centrifugal spread, with lesions showing umbilication or scabbing, lymphadenopathy, and one or more other monkeypox-compatible symptoms (fever, headache, backache, fatigue, lymphadenopathy).

Confirmed case:

  • A person with a laboratory-confirmed monkeypox infection (i.e., monkeypox virus-specific PCR assay positive result, or Orthopoxvirus-specific PCR assay positive result that is then confirmed by nucleotide sequence determination of the detected virus as monkeypox virus), with symptom onset since 1 March 2022.

Centers for Disease Control and Prevention: case definitions for use in the 2022 monkeypox response[74]

Last updated: 22 July 2022

Suspected case:

  • New characteristic rash; OR

  • Meets one of the epidemiologic 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.

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 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

  • Traveled 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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