Criteria

Case definitions

Case definitions are presented here from the World Health Organization, the UK Health Security Agency, and the US 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[116]

Last updated: 20 March 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: acute onset of fever (>38.5°C [>101.3°F]); headache; myalgia; back pain; profound weakness; or fatigue.

  • A person presenting 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 mpox in the 21 days before symptom onset.

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

    • 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 RT-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, or from a blood test alone.

Mpox re-infection:

  • 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 re-infection may be defined as a probable re-infection (as above) with significant strain differentiation between the two infections (e.g., different lineage and descendent lineages) using genetic sequencing.

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

UK Health Security Agency: mpox - case definitions[193]

Last updated: 14 October 2024

Suspected mpox

  • A case presents with a prodrome (i.e., fever, chills, headache, exhaustion, myalgia, arthralgia, backache, and 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

    • Link to an infected animal or meat

Highly probable case:

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

Confirmed case:

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

All suspected cases undergoing testing, or confirmed and highly probable cases should be notified to the local health protection team by the clinician. If the rash is clinically suggestive of mpox, but there are no identifiable risk factors, discuss with the local infection services as to whether to consider mpox testing alongside the more common differential diagnosis.

Be alert to the possibility of clade I mpox. Consider clade I mpox in a person with clinically suspected mpox who meet one or more of the following criteria:

  • Has a travel history to specified countries where there may be a risk of clade I exposure in the 21 days before symptom onset

  • Has an epidemiological link to a confirmed or suspected case of clade I mpox in the 21 days before symptom onset

  • Has a relevant zoonotic link, including contact with a wild or captive mammal that is an African native species (including contact with derived products such as game meat)

All patients who meet the case definition for clade I mpox or with laboratory confirmed clade I mpox should be managed as a high consequence infectious disease (HCID).

For more detailed information, see the following guidance:

Centers for Disease Control and Prevention: mpox case definitions[194]

Last updated: 12 September 2024

Suspect case:

  • New characteristic rash; OR

  • Meets one of the epidemiological 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.

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 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

  • Travelled 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 epidemiological and laboratory testing/sequencing criteria.

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

  • Probable case (clade I): probable or confirmed mpox as defined above AND at least one clade I epidemiological 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.

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

    • Travelled 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 re-infection:

  • 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 re-infection case: a case that meets the clinical description of re-infection (above) and meets any of the following criteria:

    • New characteristic rash; OR

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

  • Probable re-infection case: a case that meets the criteria for a suspect re-infection 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 re-infection case: a case that meets the criteria for a probable re-infection 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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