Orthopoxvirus Testing Challenges for Persons in Populations at low Risk or Without Known Epidemiologic Link to Monkeypox

United States, 2022

Faisal S. Minhaj, PharmD; Julia K. Petras, MSPH; Jennifer A. Brown, DVM; Anil T. Mangla, PhD; Kelly Russo, MD; Christina Willut; Michelle Lee, MPH; Jason Beverley, MS; Rachel Harold, MD; Lauren Milroy, MPH; Brian Pope; Emily Gould, MD; Cole Beeler, MD; Jack Schneider, MD; Heba H. Mostafa, MD, PhD; Shana Godfred-Cato, DO; Eleanor S. Click, MD; Brian F. Borah, MD; Romeo R. Galang, MD; Shama Cash-Goldwasser, MD; Joshua M. Wong, MD; David W. McCormick, MD; Patricia A. Yu, PharmD; Victoria Shelus, PhD; Ann Carpenter, DVM; Sabrina Schatzman, PhD; David Lowe, PhD; Michael B. Townsend, PhD; Whitni Davidson, MPH; Nhien T. Wynn, MS; Panayampalli S. Satheshkumar, PhD; Siobhán M. O'Connor, MD; Kevin O'Laughlin, MD; Agam K. Rao, MD; Andrea M. McCollum, PhD; María E. Negrón, DVM, PhD; Christina L. Hutson, PhD; Johanna S. Salzer, DVM, PhD


Morbidity and Mortality Weekly Report. 2022;71(36):1155-1158. 

In This Article


Evaluation of these three patients for monkeypox highlights the need for caution in interpreting single laboratory test findings in patients with a low pretest probability of infection; this includes lack of an epidemiologic link, non-MSM populations (e.g., women and children, who currently account for <2% of confirmed monkeypox cases), and signs, symptoms, or rash progression inconsistent with monkeypox. This approach is similar to the caution recommended in evaluating other laboratory tests when pretest probability is low (e.g., D-dimer results for a deep vein thrombosis or serology for Lyme disease)††.[10] Multiple clinical features in each of these three patients were inconsistent with monkeypox, including an atypical rash that was inconsistent with the characteristic progression of monkeypox lesions, as well as the absence of an epidemiologic link to a known case of monkeypox. The Ct values of all initial positive test results were high (≥34) indicating a low level of viral DNA. Cautious interpretation of test results is warranted when the pretest probability of monkeypox is low. As monkeypox testing has expanded, CDC recommends that laboratory professionals verify positive diagnostic results[8] for Orthopoxvirus or MPXV DNA in specimens with high Ct values, especially from persons who do not meet epidemiologic risk criteria for monkeypox or for whom lesions do not progress as expected. Molecular tests (e.g., real-time PCR tests) are highly specific and sensitive; however, when epidemiologic criteria are absent or unknown and the Ct value is high (generally ≥34), CDC recommends reextraction and retesting of the specimen.

Monkeypox currently occurs predominantly among MSM, although infection can occur in any person after close physical contact with persons with monkeypox or items that have been in contact with lesions, such as clothing or bedding. Because the positive predictive value in populations with low disease incidence is lower than that in populations with a higher disease incidence, laboratory results in persons with low pretest probability of infection should be carefully examined and reviewed, and other plausible diagnoses (e.g., hand, foot, and mouth disease; varicella; molluscum contagiosum) should be considered. The clinical course of illness should be reviewed, including documenting the lesions with photographs. CDC can be consulted for atypical or questionable cases and can perform additional viral-specific and clade-specific PCR testing and antiorthopoxvirus serology.