6/02/2022 UPDATE: This assay is designed to detect non-variola orthopoxviruses, including monkeypox virus. It is not intended to specifically detect monkeypox virus or to differentiate monkeypox virus from the other orthopoxviruses this assay detects. https://www.cdc.gov/csels/dls/locs/ 05/30/2022 “Physicians should use this algorithm to categorize a patient’s risk of smallpox –low, moderate, or high– when they present with an acute, generalized vesicular or pustular rash illness. Report a suspected case of smallpox immediately to the appropriate local, state or territorial health department.If, after their review, the patient meets the criteria for high-risk of smallpox, the case should be immediately reported to the CDC Emergency Operations Center (770-488-7100). https://www.cdc.gov/smallpox/pdfs/s *Real-time polymerase chain reaction (PCR) is the preferred method for detecting variola virus* PCR testing on specimens from low- to moderate-risk patients is available across the United States through reference level Laboratory Response Network (LRN) member laboratories. Variola virus-specific PCR testing on specimens from high-risk patients is limited to select reference level LRN member laboratories meeting additional facility and vaccination requirements and the CDC. CDC should be consulted prior to initiation of any testing on high-risk specimens. The type of specimen collected will vary depending upon disease progression. See table below for a list of acceptable specimens. Whole blood alone is not a suitable specimen for smallpox diagnosis by PCR as viremia generally concludes with rash onset. Although electron microscopy and antibody detection can aid in diagnosis, these assays alone are not definitive for variola virus. Review the Negative Staining Electron Microscope Protocol for Rash Illness” *** Report all HIGH RISK CASES immediately (without waiting for lab results) to hospital infection control and applicable public health department*** Additional resources: https://www.paho.org/en/file/109251 #SmallPox #Laboratory #Diagnosis #Clinicopathology