Mpox Analysis Reveals Substantial Suspected False Positives Associated with Contamination

Reliable confirmation of mpox can be difficult where multiple rash-causing illnesses co-circulate and laboratory capacity is limited. Although PCR is central to case detection, contamination during specimen collection or processing can produce misleading results and affect surveillance and patient management. New findings from the Democratic Republic of the Congo (DRC) show that many mpox PCR-positive results reflected environmental contamination rather than true infection.

The University of Geneva (UNIGE), together with the Institute of Tropical Medicine Antwerp and the National Institute of Biomedical Research in the DRC, analyzed more than 2,700 mpox PCR results from Goma, Kamituga, Kinshasa, and Uvira collected between April 2024 and April 2026. The analysis, published in The Lancet Infectious Diseases on September 15, 2026, indicates that 35% of results reported as PCR-positive likely reflected environmental contamination with mpox viral DNA rather than active infection. The work has implications for outbreak monitoring and individual patient management.

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The team examined cycle threshold (CT) values, which are inversely related to the amount of target DNA detected by PCR. Rather than forming a single distribution, CT values consistently separated into two clusters across study sites: one with low CT values consistent with high viral loads and another near the assay’s detection limit. To investigate whether contamination could explain the borderline results, researchers swabbed surfaces within treatment areas at two care centers. Mpox DNA was frequently detected on surfaces inside these areas but not on those outside them, supporting environmental contamination as a likely source of some positive results.

Serological findings further supported this interpretation. Among individuals the model classified as likely false positives, 89% had no detectable antibodies to mpox. In a separate, smaller assessment of patients with suspected mpox, most were found to have other viruses associated with rash, including varicella (chickenpox) and measles, while few tested positive for mpox. The Geneva Center for Emerging Viral Diseases, a World Health Organization collaborating center for diagnostics, contributed to the study and supports countries in strengthening diagnostic practices.

“The first group corresponds to low values, consistent with a high viral load and therefore a genuine active infection. The second cluster sat just at the detection threshold, pointing to an extremely low viral load — atypical for a real infection, but typical of a residual viral trace. What’s striking is that this clear split between the two groups appeared almost identically across all four sites, which is unlikely to be a coincidence,” said Andrew Azman, associate professor at the Institute of Global Health and the Center for Emerging Viral Diseases at the UNIGE Faculty of Medicine.

“The simplest and fastest fix is to lower the PCR positivity threshold. A lower threshold significantly reduces the number of false positives without meaningfully increasing false negatives — a proposal currently under discussion with decision-makers. In the long term, this shows that we need to improve the training of lab staff in low-resource settings like this so they can spot these anomalies in real time, rather than after the acute emergency is over,” added Azman.

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