MPXV Clade Ib Response: Resources for Pathologists and Laboratories

The World Health Organization (WHO) recently declared a public health emergency of international concern for a new strain of monkeypox virus (MPXV) designated MPXV clade Ib. While the U.S. Centers for Disease Control and Prevention (CDC) have indicated that the overall risk posed by the clade Ib outbreak is low in the general population, we must remain vigilant of emerging infectious threats to public health.

Pathologists and laboratories play a crucial role in the diagnosis of mpox. To further support you in your efforts, the CAP has compiled a list of frequently asked questions (FAQs) based on information from the WHO and CDC—as well as our members—to provide additional guidance.

What do pathologists and laboratories need to know about MPXV clade Ib?

In 2023, an MPXV strain designated as MPXV clade Ib began circulating in the Democratic Republic of the Congo (DRC). MPXV clade Ib is different from MPXV clade II which was responsible for an international outbreak in 2022. While early transmission events appeared to be primarily from zoonotic spillover, increasing rates of MPXV infection have been occurring through human-to-human contact with spread to countries neighboring the DRC. On August 15, Sweden reported the first case of MPXV clade Ib outside of the African continent in an individual with travel history to central Africa.

What assays are currently available to detect clade Ib?

Detection and specific identification of MPXV clade Ib will depend on the targets used in the assay. Laboratories which do not perform mpox testing in-house should be aware of which target(s) are used by their reference lab.

Assays using a non-variola orthopoxvirus (NVO) target can detect MPXV clade Ib; however, these assays cannot differentiate between clade Ib and clade II.

For assays with a dual target (NVO and clade II) design, the presence of clade Ib may be indicated when the NVO target is detected and the clade II target is not detected.

Laboratories should note that the CDC classifies MPXV clade I as a select agent. If high suspicion of MPXV clade I exists (i.e. the patient has an epidemiological link to clade I cases or recent travel to the DRC and surrounding countries), laboratories should directly contact state or local public health agencies for assistance in testing.

Is clade Ib more pathogenic than clade II?

Clade I has traditionally been viewed as more pathogenic than clade II, which is the MPXV strain responsible for the 2022 outbreak and which continues to circulate in the U.S. through the current time (2024). However, recent data suggests the pathogenicity of clade Ib may be lower than historical reports. A recent study reported a mortality rate of 1.4%, in contrast to the historical rate of 4-11%.

Is proficiency testing material for mpox available through the CAP?

Yes. For laboratories that may wish to develop an assay for the detection of MPXV, the CAP offers proficiency testing material to clients based in the United States. Shipping is not available to international clients.

How should specimens be collected for mpox testing?

Collection and transportation guidelines may vary based on the performing laboratory. Clinicians should consult their laboratory for specific specimen collection and handling instructions for samples suspected to contain MPXV. The CDC provides detailed information about specimen collection for mpox assays.

What biosafety measures should be taken during specimen collection and testing?

Routine clinical testing (e.g. complete blood count) of non-lesional specimens from individuals suspected or confirmed to have mpox should continue. Testing should be performed in BSL-2 facilities taking standard universal precautions and following site-specific and activity-specific biosafety risk assessments. However, these recommendations are subject to change as additional information regarding clade Ib emerges. CDC maintains Biosafety Laboratory Guidance for Handling and Processing Mpox Specimens (PDF) online, which laboratories are encouraged to use to guide its biosafety practices.

What should be done if a test result is positive for mpox?

Positive cases should be reported to public health authorities, and patients should be advised on isolation and treatment measures to prevent further spread. Laboratory Response Network laboratories and commercial laboratories using CDC’s NVO PCR test should continue submitting duplicate specimens to CDC from all patients with positive NVO PCR test results for routine MPXV clade-specific testing. Some non-CDC laboratories may also have other options available for clade-specific testing, such as molecular testing or genetic sequencing. These laboratories should alert their state health department and CDC if results from such tests indicate detection of clade I MPXV.

Are there special shipping and handling instructions for samples from patients with suspected or confirmed mpox?

Despite the categorization of MPXV clade I as a select agent, the U.S. Department of Transportation (DOT) issued a safety advisory notice in March 2024 stating that "most MPXV materials—including patient diagnostic samples and clinical waste—are appropriately classified for transportation as Category B infectious substances." The safety advisory notice also states: "[...] and patient diagnostic samples may be transported as 'UN3373, Biological substance, Category B, 6.2." Positive culture material or clinical waste from cultures of MPXV clade I should be transported as Category A infectious substances.

A special thanks to Council on Scientific Affairs Microbiology Committee Vice Chair Daniel Rhoads, MD, FCAP, and committee member Benjamin Bradley, MD, PhD, FCAP, for developing these testing recommendations. Additionally, thank you—pathologists and laboratory staff—for your continued dedication and hard work during these challenging times. Your expertise and commitment are vital to our collective efforts in managing the mpox outbreaks. Together, we will continue to provide exceptional care and uphold the highest standards of public health.

Bobbi Pritt, MD, MS, FCAP, is a Professor of Laboratory Medicine and Pathology and the Interim Chair of the Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minnesota. She is also the Chair of the Division of Clinical Microbiology and the Program Director of the ACGME Medical Microbiology fellowship at Mayo Clinic. She received her medical degree from the University of Vermont College of Medicine, followed by a residency in Anatomic and Clinical Pathology. She then completed a fellowship in Medical Microbiology at Mayo Clinic, Minnesota, and joined the staff to direct the Clinical Virology and Parasitology laboratories. Dr. Pritt serves on the Board of Governors, the Council on Scientific Affairs for the College of American Pathologists (CAP), and is the Vice Chair of the newly-formed Council on Informatics and Pathology Innovation. She also serves on the CAP Information Technology Leadership Committee and Finance Committee, and previously served as the Chair of the CAP Microbiology Committee during the start of the COVID-19 pandemic. Through her various roles, she has led efforts to provide testing options and associated quality assurance tools for SARS-CoV-2.