Mpox Case Definitions

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 in ACAM2000 vaccination) AND demonstration of 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 (MPXV) DNA by polymerase chain reaction testing or Next-Generation sequencing of a clinical specimen OR isolation of MPXV 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 (MSM) 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 MPXV 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 MPXV or antibodies to orthopoxvirus

Interim Case Definitions for Clade I Mpox*

As of June 10, 2024

Suspect Case, Clade I

• Probable or confirmed mpox as defined above AND
• At least one of the Clade I Epidemiologic Criteria (below)

Probable Case, Clade I

• Probable or confirmed mpox as defined above AND
• At least one of the Clade I Epidemiologic Criteria (below) AND
• Clade I and clade II MPXV-negative 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 MPXV DNA by polymerase chain reaction testing OR
• Next-Generation sequencing of a clinical specimen

Clade I Epidemiologic Criteria

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 MPXV 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 (e.g., game meat, creams, lotions, powders, etc.)

*This interim definition applies to the current situation with clade I outbreaks limited to known endemic areas in Africa, and no evidence of widespread transmission in other continents. If the situation changes, this interim definition will be updated accordingly.

Case Definition of Mpox Reinfection

Mpox reinfection occurs when a person who was classified as a confirmed or probable mpox case, has a recurrence of mpox symptoms after complete resolution† of the initial confirmed or probable MPXV infection.

Suspect Mpox Reinfection Case

A case that fits the clinical description of mpox reinfection and meets any of the following criteria:

• New rash*, OR
• Meets one of the epidemiologic criteria and has a high clinical suspicion for mpox

Probable Mpox Reinfection Case

A case that meets the criteria for a suspect mpox reinfection case AND demonstrates one of the following from a patient specimen:

• Orthopoxvirus or MPXV 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 Mpox Reinfection Case:

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

Considerations for Mpox Reinfection

• Persistent MPXV infection is defined as MPXV infection without clinical improvement or resolution of symptoms.
• Relapsed MPXV infection is defined as MPXV infection that has improved, but not completely resolved, followed by clinical worsening or new mpox symptoms.
• Patients with severe immunodeficiency such as in people living with HIV with CD4 counts <200 can be at risk for persistent and/or relapsed MPXV infections.
• Patients may develop symptoms caused by other infections during MPXV infection or after their initial infection resolves.

*The characteristic rash associated with mpox lesions involve the following: deep-seated and well-circumscribed lesions, often with central umbilication; and lesion progression through specific sequential stages—macules, papules, vesicles, pustules, and scabs; this can sometimes be confused with other diseases that are more commonly encountered in clinical practice (e.g., secondary syphilis, herpes, and varicella zoster). Historically, sporadic accounts of patients co-infected with mpox virus and other infectious agents (e.g., varicella zoster, syphilis) have been reported, so patients with a characteristic rash should be considered for testing, even if other tests are positive. People with severe immunodeficiency (e.g., advanced HIV) may have skin lesions that are necrotic, diffuse, and plaque-like.

† Complete resolution is defined as disappearance of all clinical symptoms of mpox including fever, chills, lymphadenopathy, skin rashes, lesions, or other skin disturbances caused by MPXV, and any other persistent symptoms associated with MPXV infection.

‡ If there are no substantial single nucleotide polymorphisms (SNPs) or significant genetic variation between MPXV sequences from clinical specimens from two or more episodes of MPXV infection obtained from the same individual then the case should be classified as a probable case.

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