1st investigations to order
polymerase chain reaction (PCR)
Testing should be conducted in patients with suspected infection as soon as possible. Offer testing to any person who meets the case definition for a suspected, possible, or probable case. The decision to test should be based on both clinical and epidemiologic factors, linked to an assessment of the likelihood of infection. Patients should remain in isolation while their test result is pending.
Testing is available at regional public health laboratories. There are currently no commercial assays available.
Nucleic acid amplification testing (NAAT), using real-time PCR or conventional PCR, is the preferred laboratory test given its accuracy and sensitivity. NAAT can be generic to Orthopoxvirus or specific to monkeypox virus (preferable). Sequencing is useful to determine virus clade and to understand epidemiology.
Caution is required when interpreting a single test result in patients with a low pretest probability of infection (e.g., lack of epidemiologic link, non-MSM [men who have sex with men] populations, signs/symptoms inconsistent with monkeypox) due to the risk of a false-positive result. A positive test for Orthopoxvirus or monkeypox virus DNA in a person without epidemiologic criteria or known risk factors should be verified by repeat testing and/or confirmatory testing, and other possible causes of rash considered. Repeat testing (re-extraction and retesting of the specimen) is recommended in patients with high real-time (RT)-PCR cycle threshold values (i.e., ≥34), as this indicates a low level of viral DNA and poorly- or noninfectious specimens.
The recommended specimen type is skin lesion material, including swabs of lesion exudate, roofs from more than one lesion, or lesion crusts. Skin lesion swabs are the most effective means of detecting monkeypox virus DNA using PCR. Aspiration or unroofing of lesions before swabbing is not necessary (or recommended) due to the risk for sharps injury. Specimen type may vary depending on the phase of the rash. The reference laboratory may also ask for an oropharyngeal swab, ethylenediamine tetra-acetic acid (EDTA) blood, or urine. Oropharyngeal swabs are recommended for high-risk contacts of a confirmed or highly probable case who have developed systemic symptoms but do not have a rash or lesion for sampling. However, viral load is higher in lesion swabs than in pharyngeal specimens, and oropharyngeal swabs are known to be unreliable standalone specimen types for primary diagnosis. There are limited clinical data to support the use of sample types other than swab samples taken directly from a lesion (e.g., blood, saliva). Testing samples not taken from a lesion may lead to false positive results.
Collect, label, package, and send specimens according to local or national protocols. Notify the laboratory of the possibility of monkeypox prior to sending specimens. There are local protocols in place for the safe handling of these specimens in the laboratory and onward transport of virologic materials to the reference laboratory. Package samples for testing for other infections separately.
Testing the sample for varicella zoster virus should automatically be performed by the reference laboratory when undertaking PCR for poxviral DNA. It may be positive for varicella zoster virus DNA if coinfection is present.
positive for monkeypox or Orthopoxvirus DNA
Order in all patients with suspected infection.
Small studies have found that leukocytosis was common, and lymphocytosis and thrombocytopenia were seen in more than one third of patients during illness.
Leukocytosis and thrombocytopenia may be signs of severe or complicated disease.
may show leukocytosis, lymphocytosis, thrombocytopenia
urea and electrolytes
Order in all patients with suspected infection.
Small studies have found that elevated transaminases and hypoalbuminemia were common during illness. Elevated transaminases and hypoalbuminemia may be signs of severe or complicated disease. Severe hepatitis has been reported in patients with monkeypox and hepatitis coinfection.
may show elevated transaminases, hypoalbuminemia
sexually transmitted infection tests
Test all sexually active adults and adolescents for HIV infection and other STIs.
The clinical features of monkeypox may easily be confused with an STI. Therefore, it is important to comprehensively evaluate patients presenting with genital or perianal ulcers for STIs. Coinfections are possible, and the presence of an STI does not rule out monkeypox.
variable (depends on the infection present)
Investigations to consider
Consider a CT scan of the abdomen/pelvis in patients with severe anorectal proctitis.
Contrast-enhanced CT may reveal circumferential anorectal mural thickening with broad discrete nonenhancing hypoattenuated zones due to intramural ulcers. Additional findings may include perirectal fat infiltration, presacral edema, ascites, and an increased number of small inguinal lymph nodes.
anorectal mural thickening
Serology is not currently recommended by the World Health Organization (WHO) for diagnosis. Serology (paired serum samples collected at least 21 days apart, with the first collected during the first week of illness) can aid diagnosis if tested samples yield inconclusive results. Recent vaccination may interfere with serologic testing. However, the WHO and the Centers for Disease Control and Prevention include serologic testing as an option for testing in their case definitions. See Criteria.
Order while the patient is in isolation and prior to antibiotic therapy, if there is suspicion of bacterial superinfection of cutaneous lesions or bacterial infection in a very sick patient.
may show bacteremia
malaria antigen test
Order in all patients with suspected infection if there is a recent history of travel to a malaria-endemic area.
Always rule out coinfection with malaria in any febrile patient who has been to a malaria-endemic area, especially in the 3 weeks prior to the onset of fever.
An antigen detection test poses less of an infection hazard to laboratory staff than preparation of thick and thin films. The laboratory must first be notified of the risk of monkeypox and secure transportation of specimens organized as per local policies.
negative; may be positive if coinfection
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