Criteria
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[108]
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 (>101.3°F [>38.5°C]); 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 epidemiologic 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 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 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.
As of 3 September 2022, the European Centre for Disease Prevention and Control follows the WHO case definition.[243]
UK Health Security Agency: mpox (monkeypox) - case definitions[178]
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.
The UKHSA have also published an operational case definition for clade I cases which should be managed as a high consequence infectious disease (HCID). Patients with clinically suspected mpox where the clade is not yet known should be managed as a HCID case until results are available if either (or both):[244]
There is a travel history to the Democratic Republic of the Congo (DRC) or specified countries where there may be a risk of clade I exposure, or a link to a suspected case from those countries within 21 days of symptom onset.
There is an epidemiologic link to a case of clade I mpox within 21 days of symptom onset.
For more detailed information, see the following guidance:
Centers for Disease Control and Prevention: mpox case definitions[179]
Last updated: 10 June 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 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.
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 mpox/smallpox 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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