Identification of Human Monkeypox Virus Genome Deletions That Impact Diagnostic Assays

In August 2022, the Los Angeles County Department of Public Health initiated an investigation into human monkeypox virus (MPXV) cases with unusual results from a multiplex laboratory-developed test used by Quest Diagnostics, which is based on the CDC nonvariola Orthopoxvirus (NVO) (1) and MPXV clade II (MPXV-WA) (2) real-time PCR assays. These specimens returned NVO–positive and either MPXV-WA–negative or positive results with high Ct values, which differ from the strong dual-positive results typically associated with the current outbreak. Since these patients met the case definition for probable human MPXV infection, (3) these discordant results were presumed to be due to a mutation affecting the performance of the MPXV-WA assay.