Genetic sequencing has identified a second cluster of tecovirimat-resistant mpox infections in the United States—the first of its kind involving interstate spread. Researchers from the US Centers for Disease Control and Prevention (CDC) and partners from five affected states reported their findings yesterday in Morbidity and Mortality Weekly Report.
The first Tpoxx-resistant cluster was identified in California in late 2022 and early 2023 in people who hadn't previously been treated with the drug. The new report describes a new unrelated cluster among 18 people with no previous treatment across multiple states.
Sequencing identified a unique combination of resistance mutations in 20 specimens collected from 18 patients between October 2023 and February 2024. The patients were from five states: Illinois (8), California (5), Louisiana (2), Texas (2), and New York (1).
Of 16 patients with an available treatment history, one had received the drug before the sample was collected. Of 17 patients with available clinical data, illnesses were mild and similar to standard clade 2 infections, though two were hospitalized for pain management.
Findings likely underestimate spread of resistant variant
In vitro testing of seven samples showed resistance to Tpoxx. Whole-genome sequencing showed that the resistance mutations came from a common ancestor but were distinct from the earlier California cluster.
Researchers said because not all viruses from mpox cases are sequenced, the findings likely underestimate the prevalence of the newly identified drug-resistant variant. They added that more surveillance is needed, as well as adherence to CDC Tpoxx use protocols. Also, they wrote that the findings underscore the need for more treatments for mpox, along with smallpox biothreat preparedness.
