Monkeypox is caused by an orthopoxvirus that is related to the virus that causes smallpox. Symptoms of monkeypox include fever, headache, muscle aches, swollen lymph nodes, and a rash that resembles pimples or blisters. Monkeypox is spread from person to person through direct contact with rash, scabs, or body fluid or by respiratory secretions during close contact (eg, kissing, cuddling, or sexual contact). Monkeypox may also be spread through contact with shared objects such as linens, towels, or sexual implements. Pregnant individuals may also transmit the virus to a fetus through the placenta. Monkeypox is diagnosed using a polymerase chain reaction (PCR)-based assay to detect monkeypox virus DNA, or in some situations, orthopoxvirus DNA.
A current outbreak has spread across several regions that do not normally report monkeypox cases, including the United States. The CDC is tracking cases of monkeypox in the U.S. and urges healthcare providers to be alert for patients with symptoms consistent with monkeypox. The current outbreak is complicated by an atypical disease presentation in some patients that makes it difficult for clinicians to identify when diagnostic testing may be appropriate. The environment surrounding the monkeypox outbreak is evolving rapidly. Clinicians are advised to consult the CDC’s Monkeypox resources and ARUP’s Monkeypox Infection Testing web page for the most up-to-date information.
Quick Answers for Clinicians
The CDC provides detailed information about the current outbreak of monkeypox on its website. This is the best place to find up-to-date information on this rapidly evolving situation. For information about ARUP’s response to the monkeypox outbreak, including frequently asked questions about our laboratory testing, please visit ARUP’s Monkeypox Infection Testing page.
Monkeypox is diagnosed through laboratory testing. The recommended laboratory test is a polymerase chain reaction (PCR) assay that detects monkeypox DNA in a sample collected from an infected lesion. This test may be performed at a state health laboratory (recommended) or a reference laboratory. However, testing specifically for monkeypox is not necessary in some circumstances. According to the CDC, “Once results are received from the laboratory, a positive Orthopoxvirus test is considered to meet the case definition for probable Monkeypox virus infection since there are no other circulating Orthopoxviruses within the United States that cause systemic disease. Clinical care and prevention precautions should begin based on the Orthopoxvirus test result and should not wait for any additional viral characterization testing that may be performed.”
Monkeypox has a similar clinical presentation to several other diseases, particularly sexually transmitted infections. These include infections caused by Treponema pallidum (syphilis) and Herpes simplex virus (herpes). Varicella-Zoster virus (the virus that causes chickenpox/shingles), although not sexually transmitted, may resemble monkeypox in clinical presentation. Bacterial skin infections, scabies, and medication-associated allergies may also cause monkeypox-like rashes. Diagnosis of a sexually transmitted infection such as syphilis or herpes does not rule out the presence of monkeypox.
ARUP offers only an orthopoxvirus assay for the diagnosis of monkeypox. This is in accordance with the CDC’s recommendations for monkeypox screening/testing. Given the documented circulation of monkeypox in the United States during the current outbreak and the absence of any other orthopoxviruses in circulation, monkeypox-specific laboratory testing is not always necessary. Nucleic acid amplification (NAA)-based testing that detects orthopoxvirus DNA is sufficient to meet the case definition of probable monkeypox infection in the United States.
Indications for Testing
Testing may be appropriate in the presence of characteristic signs and symptoms (eg, rash), when a patient has had contact with someone with confirmed or probable monkeypox, when a patient has had close or intimate contact with a person in a community with high monkeypox activity, or when a patient has travelled to a region with confirmed cases of monkeypox. For more information, visit the CDC’s Case Definitions for Use in Monkeypox Response. Clinicians should consult their state health department if a monkeypox infection or exposure is suspected.
Laboratory Testing
The recommended laboratory test for the diagnosis of monkeypox is nucleic acid amplification (NAA), usually PCR. Detection of monkeypox DNA by PCR or other NAA-based techniques is considered diagnostic. However, testing specifically for monkeypox is not necessary in some circumstances. According to the CDC, “Once results are received from the laboratory, a positive Orthopoxvirus test is considered to meet the case definition for probable Monkeypox virus infection since there are no other circulating Orthopoxviruses within the United States that cause systemic disease. Clinical care and prevention precautions should begin based on the Orthopoxvirus test result and should not wait for any additional viral characterization testing that may be performed.”
A specimen should be collected from infected or healing lesions. It is recommended that the specimen be sent to a state health lab for testing, but testing is also available from reference laboratories.
Collection and transport guidelines may vary based on the performing laboratory. Clinicians should consult their laboratory for specific specimen collection and handling instructions for samples that may be infected with monkeypox. The CDC provides detailed information about specimen collection for monkeypox assays.
More information about ARUP’s specimen collection requirements can be found on ARUP’s Monkeypox Infection Testing page.
Viral culture and serology are not recommended for the diagnosis of monkeypox.
ARUP Laboratory Tests
Qualitative Polymerase Chain Reaction
References
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CDC - Monkeypox: update for clinicians on testing and treatment
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Update for clinicians on testing and treatment for monkeypox. [Updated; Jul 28, 2022; Accessed: Aug 1, 2022]
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CDC - Monkeypox: clinical recognition
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Monkeypox: clinical recognition. [Updated: Jun 24, 2022; Accessed: Jul 15, 2022]
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CDC - Monkeypox
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Monkeypox. [Last reviewed: Jun 30, 2022; Accessed: Jul 15, 2022]
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CDC - Monkeypox: US outbreak 2022
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Monkeypox: U.S. outbreak 2022: situation summary. [Updated: Jul 12, 2022; Accessed: Jul 15, 2022]
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CDC - Monkeypox: case definition
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Monkeypox: case definition. [Updated: Jun 8, 2022; Accessed: Jul 15, 2022]
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CDC - Monkeypox: specimen collection
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Monkeypox: specimen collection. [Updated: Jun 29, 2022; Accessed: Jul 15, 2022]
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