09/02/2022: Lab Alert: MPXV TNF Receptor Gene Deletion May Lead to False Negative Results with Some MPXV Specific LDTs

CDC's Laboratory Outreach Communication System (LOCS)

Audience: Clinical Laboratories

Level: Laboratory Alert

CDC is aware of three Monkeypox virus (MPXV) cases in California in which preliminary data show a significant deletion in the tumor necrosis factor (TNF) receptor gene. This gene is the target for the CDC West African MPXV and Generic MPXV real-time PCR tests. At this point, the TNF receptor gene deletion is rare. Molecular laboratory developed tests (LDTs) designed using the CDC published primers and probes that specifically target Monkeypox virus did NOT detect the virus because of the TNF receptor gene deletion in these specimens. These cases were still correctly diagnosed because they were also tested with an LDT that was developed based on CDC’s published non-variola Orthopoxvirus (NVO) test.

To prevent false negative results:

  • If your laboratory is using a MPXV-specific LDT, refer highly suspicious Monkeypox virus specimens that result as negative to your public health laboratory, or to CDC, to confirm results. Public health laboratories and select commercial laboratories use the CDC FDA cleared NVO test, which can correctly identify Orthopoxvirus when the TNF gene deletion occurs.
  • Use a multiplex assay that targets multiple viral genes, or an assay that targets an essential viral gene which is unlikely to mutate, or an assay that detects non-variola Orthopoxvirus.

CDC will update the published primer and probe sequence information to alert test developers of this TNF receptor gene deletion.

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The Laboratory Outreach Communication System

Laboratory Outreach Communication System (LOCS) | Division of Laboratory Systems (DLS)

Center for Surveillance, Epidemiology, and Laboratory Services (CSELS)

Centers for Disease Control and Prevention (CDC)

LOCS@cdc.gov

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Page last reviewed: September 2, 2022