Monkeypox Testing: False-Positive Results in 3 Patients With Atypical Symptoms

Researchers described 3 patients with false-positive test results for monkeypox infection.

False-positive results for monkeypox infection were observed in 3 patients with no known risks or epidemiologic links to an individual with confirmed infection, highlighting the need for clinicians to practice caution when interpreting laboratory findings in those with low pretest probability for infection. These findings were published in Morbidity and Mortality Weekly Report.

In this report, researchers described 3 patients (Patients A, B, and C) with atypical rash who were diagnosed with real-time polymerase chain reaction (PCR)-confirmed monkeypox infection. For all 3 patients, the rash did not progress from pustular to deep-seated umbilicated lesions within the expected 2- to 4-week period. In addition, none of these patients had an epidemiologic link to an individual with confirmed infection.

Patient A was a healthy woman at an estimated 37 weeks’ gestation. Pruritic erythematous rash was noted over her upper extremities, abdomen, upper back, calves, and shins. Further evaluation showed lesions with irregular borders that varied in both size and stage of development. These lesions were in the same anatomic locations as the rash and included tan papules, crusted papules, pustules, and hyperpigmented macules; no genital lesions were observed. The patient reported no interstate or international travel within the 3 weeks prior to rash onset. She also noted varicella virus infection and vaccination against smallpox as a child. 

The patient tested negative for varicella zoster virus, syphilis, herpes simplex virus, cryptococcosis, and histoplasmosis. At day 53 following rash onset, she tested positive for nonvariola-orthopoxvirus. Two days later, she delivered a healthy newborn via uncomplicated vaginal delivery. Several measures were implemented as a result of the patient’s unresolved lesions, including preventing skin-to-skin contact between mother and newborn, assigning another household member as primary caregiver, delaying breastfeeding, and the disposal of breast milk. In addition, vaccinia immune globulin intravenous was administered to the newborn.

Serum samples obtained from the patient at day 42 after rash onset were then evaluated by the Centers for Disease Control and Prevention. Results were negative for antiorthopoxvirus antibodies, and the restrictive measures were discontinued. The patient’s rash was ultimately attributed to bed bugs.

Patient B was an elementary school-aged child with symptoms suggestive of influenza. Raised lesions were noted over the patient’s face, which subsequently spread over the trunk, back, and upper extremities after 1 day. A facial lesion specimen from the patient then tested positive for orthopoxvirus via generic laboratory developed testing. Owing to periorbital lesions and concerns for potential autoinoculation and sight-threatening disease, tecovirimat was initiated. In addition, the patient and all household family members received postexposure prophylaxis with the modified vaccinia Ankara vaccine.

Re-extraction and repeat PCR testing of the original specimen was positive for enterovirus, indicating a diagnosis of hand-foot-and-mouth disease.

Patient C was an infant who visited the United States with both parents for vacation and had traveled to another country with 4 other families. The patient initially had diarrhea and lymphadenopathy, followed by fever and rash 2 days later. The rash was maculopapular and vesicular, occurring over the upper and lower extremities, earlobe, chest, scalp, and lower abdomen. After an abdominal lesion specimen tested positive for nonvariola-orthopoxvirus, the patient was started on oral tecovirimat.

Results of additional testing for nonvariola-orthoxpoxvirus were negative or inconclusive among 4 children and 4 adults who had vacationed with the patient and had also developed lesions. Owing to exposure to the patient, a total of 12 adults and 7 children received postexposure prophylaxis with the modified vaccinia Ankara vaccine. However, serum samples obtained from the patient between 3 and 31 days after rash onset showed no antiorthopoxvirus antibodies; an alternative diagnosis is pending for this patient.  

“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 [monkeypox] infection should be carefully examined and reviewed, and other plausible diagnoses should be considered,” the researched noted.


Minhaj FS, Petras JK, Brown JA, et al. Orthopoxvirus testing challenges for persons in populations at low risk or without known epidemiologic link to monkeypox — United States, 2022. MMWR Morb Mortal Wkly Rep. Published online September 2, 2022. doi:10.15585/mmwr.mm7136e1