Mpox Virus Infection
2022 Case Definition

Background

Mpox (previously named monkeypox) is a zoonotic disease that is caused by infection with mpox virus. Monkeypox virus belongs to the Orthopoxvirus genus in the family Poxviridae. The Orthopoxvirus genus also includes variola virus (which causes smallpox), vaccinia virus (used in the smallpox vaccine), and cowpox virus. Mpox was first discovered in 1958 when two outbreaks of a pox-like disease occurred in monkeys kept for research. The first human case of mpox was recorded in 1970 in the Democratic Republic of the Congo (DRC) during a period of intensified effort to eliminate smallpox. Since then, mpox has been reported in people in several other central and western African countries: Cameroon, Central African Republic, Cote d’Ivoire, Democratic Republic of the Congo, Gabon, Liberia, Nigeria, Republic of the Congo, and Sierra Leone.¹

Until May 2022, mpox cases in people outside of Africa were linked to international travel or imported animals from endemic areas in Africa. Cases in the United States in 2003 were linked to imported rodents from Ghana;² two cases in 2021 were linked to international travel.³ Israel, Singapore, and the United Kingdom have also had cases linked to international travel.³ Beginning in May 2022, multiple countries that do not usually have mpox, including the United States, began to report cases not associated with the traditional epidemiologic risk factor of travel to places where the disease is endemic.

Testing for mpox virus is available through commercial laboratories and through public health laboratories that are part of the Laboratory Response Network (LRN).  LRN laboratories can provide real-time polymerase-chain-reaction (RT-PCR) to detect the presence of non-variola orthopoxvirus deoxyribonucleic acid (DNA). The Centers for Disease Control and Prevention (CDC) can confirm the presence of mpox virus and determine the clade (West African (Clade II) or Congo Basin clade (Clade I)) by mpox virus species-specific RT-PCR. Commercial testing became available during July 2022.

Mpox does not spread easily person-to-person, but transmission can occur through direct contact with lesions or bodily fluids, indirect contact through fomites (materials that were in contact with lesions or bodily fluids), and through exposure to large respiratory droplets from prolonged face-to-face contact.⁴ Individuals with exposures that support the highest likelihood of transmission should follow the latest guidance for post-exposure vaccine.⁵ No commercially available vaccines exist; products are only available through request from the federal government by a public health authority. All individuals with a potential exposure to an infected person should be monitored for 21 days post-exposure for the development of symptoms.⁵ Both vaccine acquisition for post-exposure and symptom monitoring should be coordinated with public health authorities.

As of June 2022, 13 jurisdictions in the U.S. have mandated reporting of mpox explicitly. One additional jurisdiction had orthopoxvirus as explicitly reportable to public health authorities. The apparent changing epidemiology of the disease, the current reliance on the public health system for testing and access to vaccine, and the need for prompt public health response to identified cases for the purposes of reducing spread all support the need for a standardized case definition and national notifiability for mpox virus infection.

Clinical Criteria

A person presenting with new onset of:

• clinically compatible rash lesions*; OR
• lymphadenopathy or fever**

*The presence of clinically compatible rash lesions should be combined with either a higher or lower epidemiologic linkage criterion for case classification.

**A person presenting with lymphadenopathy or fever without any clinically compatible rash lesions must meet a higher epidemiologic risk criterion for case classification.

Laboratory Criteria

Confirmatory laboratory evidence:

• Detection of mpox virus nucleic acid by molecular testing in a clinical specimen; OR
• Detection of mpox virus by genomic sequencing in a clinical specimen.

Presumptive laboratory evidence:

• Detection of orthopoxvirus nucleic acid by molecular testing in a clinical specimen AND no laboratory evidence of infection with another non-variola orthopoxvirus; OR
• Detection of presence of orthopoxvirus by immunohistochemistry in tissue; OR
• Detection of orthopoxvirus by genomic sequencing in a clinical specimen; OR
• Detection of anti-orthopoxvirus Immunoglobulin M (IgM) antibody using a validated assay on a serum sample drawn 4-56 days after rash onset, with no recent history (last 60 days) of vaccination***.

Supportive laboratory evidence:

 N/A

***Recent administration of ACAM2000 and JYNNEOS vaccines need to be considered when interpreting an antibody titer.  RABORAL V-RG, an oral rabies vaccine product for wildlife, is a recombinant vaccinia virus, and could lead to an antibody response in an individual exposed to the liquid vaccine; this is expected to be an extremely rare occurrence.

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.

Epidemiologic Linkage

Epidemiologic risk factors within 21 days of illness onset:

• Higher Risk Epidemiologic Linkages
  • Contact, without the use of appropriate personal protective equipment (PPE)^‡, with a person or animal with a known orthopoxvirus or mpox virus infection; OR
  • Contact, without the use of appropriate PPE^‡ or Biosafety Level (BSL) protocols^‡, with laboratory specimens or other items that could serve as fomites that have been in contact with a person or animal with a known orthopoxvirus or mpox virus infection; OR
  • Member of an exposed cohort as defined by public health authorities experiencing an outbreak (e.g., participated in activities associated with risk of transmission in a setting where multiple cases occurred).
• Lower Risk Epidemiologic Linkages
  • Member of a cohort as defined by public health authorities experiencing mpox activity; OR
  • Contact with a dead or live wild or exotic pet animal of an African species, or used or consumed a product derived from such an animal (e.g., game meat, powders, etc.); OR
  • Residence in or travel to a country where mpox is endemic.

^‡The language “without the use of appropriate PPE or Biosafety Level (BSL) protocols” includes breaches in the recommended PPE and deviations from appropriate BSL protocols.

Criteria to Distinguish a New Case from an Existing Case

For surveillance purposes, a new case of mpox virus infection meets the following criteria:

1. Healthy tissue has replaced the site of all previous lesions after they have scabbed and fallen off; AND
2. New lesions are present which have tested positive for orthopoxvirus or mpox virus DNA by molecular methods or genomic sequencing.

Suspect

• Meets clinical criteria AND epidemiologic criteria^ AND no evidence of a negative test for either non-variola orthopoxvirus or mpox virus

^The presence of clinically compatible rash lesions should be combined with either a higher or lower epidemiologic linkage criterion for case classification.  A person presenting with lymphadenopathy or fever without any clinically compatible rash lesions must meet a higher risk epidemiologic risk criterion for case classification.

Probable

• Meets presumptive laboratory criteria

Confirmed

• Meets confirmatory laboratory criteria