Criteria

Case definitions

Case definitions are presented here from the World Health Organization (WHO), the UK Health Security Agency (UKHSA), and the Centers for Disease Control and Prevention (CDC). 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 (WHO): surveillance case definitions[90]

Last updated: 27 November 2024

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 symptoms but without lesions: acute onset of fever (>101.3°F [>38.5°C]); headache; myalgia; back pain; profound weakness; or fatigue.

  • A person presenting with an 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, scabies, 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 on the face, palms of hands and feet, genital area (penis, scrotum, vulva), perianal area, mouth, 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 acute skin rash, mucosal lesions, or lymphadenopathy (see above for description of rash/lesions); AND

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

Confirmed case:

  • A person who meets either of the following laboratory criteria:

    • Detection of monkeypox virus DNA by real-time polymerase chain reaction (PCR) and/or sequencing.

    • Detection of orthopoxvirus DNA by PCR in settings where: an mpox outbreak has been confirmed through monkeypox virus-specific PCR or sequencing; AND no other orthopoxviruses are known to circulate in human populations.

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, or from a blood test alone.

Mpox reinfection:

  • Suspected: a person who currently meets the criteria for a confirmed case AND has a documented history of a previous episode of mpox (as a suspected, probable, or confirmed case) and it is unclear if the person presented a full clinical resolution of the previous episode.

  • Probable: a person who currently meets the criteria for a confirmed case AND has a documented history of a previous episode of mpox (as a probable or confirmed case) and full clinical resolution of the previous episode occurred and the time between the resolution of the first episode and onset of new symptoms is less than 3 months.

  • Confirmed: a person who currently meets the criteria for a confirmed case AND has a documented history of a previous episode of mpox (as a confirmed case) and full clinical resolution of the previous episode occurred and the time between the resolution of the first episode and onset of new symptoms is 3 months or more. When possible, strain differentiation should be undertaken using genetic sequencing. Alternatively, confirmed reinfection may be defined as a probable reinfection (as above) with significant strain differentiation between the two infections (e.g., different lineage and descendent lineages) using genetic sequencing.

An individualized approach is recommended when applying these definitions to immunosuppressed patients.

UK Health Security Agency (UKHSA): mpox - case definitions[201]

Last updated: 04 April 2025

Suspected mpox

  • A case presents with a prodrome (i.e., fever, chills, headache, exhaustion, myalgia, arthralgia, backache, lymphadenopathy), and where there is known prior contact with a confirmed or suspected case of mpox in the 21 days before symptom onset; OR

  • A case presents with an mpox-compatible rash anywhere on the skin (face, limbs, extremities, torso), mucosae (including oral, genital, anal), or symptoms of proctitis, and at least one of the following in the 21 days before symptom onset:

    • Recent new sexual partner

    • Contact with known or suspected case of mpox

    • A travel history to a country where mpox is currently common (this does not include people transiting through the affected country where they do not leave the airport)

    • Link to an infected animal or meat; OR

  • A case presents with an mpox-compatible rash anywhere on the skin (face, limbs, extremities, torso), mucosae (including oral, genital, anal), or symptoms of proctitis, where there is no risk factor and no alternative common differential diagnosis (note: these patients should be discussed with local infection services to determine the approach to investigation and management).

Confirmed case:

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

All suspected cases should undergo testing and the case should be discussed with local infection specialists. Confirmed cases should be urgently reported to the health protection team. Severe (suspected or confirmed) cases should be discussed with the local infection team. All cases may also be discussed with the Imported Fever Service.

For more detailed information, see the following guidance:

Centers for Disease Control and Prevention (CDC): mpox case definitions[202]

Last updated: 12 September 2024

Suspect 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 4-56 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.

The CDC also offers an interim case definition specifically for clade I mpox, which includes specific epidemiologic and laboratory testing/sequencing criteria.

  • Suspect case (clade I): probable or confirmed mpox as defined above AND at least one clade I epidemiologic criteria.

  • Probable case (clade I): probable or confirmed mpox as defined above AND at least one clade I epidemiologic criteria AND clade I and clade II monkeypox virus-positive by polymerase chain reaction testing without next-generation sequencing of a clinical specimen to confirm clade.

  • Confirmed case, clade I: demonstration of the presence of clade I monkeypox virus DNA by polymerase chain reaction testing or next-generation sequencing of a clinical specimen.

  • Epidemiologic criteria, clade I: within 21 days of illness onset:

    • Traveled to an area with evidence of sustained human to human transmission of clade I mpox or where clade I monkeypox virus is endemic; OR

    • Reports having contact with person with confirmed, probable, or suspect clade I mpox; OR

    • Had close or intimate in-person contact with individuals in a social network currently experiencing clade I mpox activity; OR

    • Had contact with a dead or live wild animal or exotic pet that is a central African endemic species or used a product derived from such animals.

Mpox reinfection:

  • When a person who was classified as a confirmed or probable case has a recurrence of mpox symptoms after complete resolution of the initial infection (i.e., disappearance of all clinical symptoms including fever, chills, lymphadenopathy, skin rashes, lesions, or other skin disturbances, and any other persistent symptoms associated with infection).

  • Suspect reinfection case: a case that meets the clinical description of reinfection (above) and meets any of the following criteria:

    • New characteristic rash; OR

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

  • Probable reinfection case: a case that meets the criteria for a suspect reinfection case and demonstrates one of the following from a patient specimen:

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

    • Orthopoxvirus using immunohistochemical or electron microscopy testing methods; OR

    • Demonstrable increase in anti-Orthopoxvirus IgG antibodies in paired serum samples collected within 3 days of symptom onset and 7-14 days after symptom onset, for patients with no prior vaccination or vaccinated ≥180 days prior to symptom onset. 

  • Confirmed reinfection case: a case that meets the criteria for a probable reinfection case AND has significant single nucleotide polymorphisms (SNPs) or genetic variation between monkeypox virus genetic sequences from clinical specimens obtained from two or more episodes of infection separated by complete resolution of symptoms within the same individual.

Other definitions:

  • Persistent infection:

    • Infection without clinical improvement or resolution of symptoms.

  • Relapsed infection:

    • Infection that has improved, but not completely resolved, followed by clinical worsening or new symptoms.

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