Operationalisation and findings of a First Few X (FFX) investigation of early mpox clade Ib cases and their close contacts in the United Kingdom

OBJECTIVES: In 2024, clade Ib mpox cases increased in Central and East Africa with some cases exported to other continents. The UK Health Security Agency launched a prospective "First Few X" (FFX) study to investigate clinical and epidemiological characteristics of UK mpox clade Ib cases and their close contacts. STUDY DESIGN: Prospective enhanced surveillance. METHODS: Laboratory-confirmed clade Ib mpox cases and their contacts were enrolled. Data was collected through structured interviews on days 1 and 21 following diagnosis (cases) or last known exposure (contacts), supplemented by case management records. Contacts were categorised by risk based on type of exposure. During follow-up, contacts were invited to self-collect throat swabs for PCR testing to assess asymptomatic carriage. RESULTS: As of 27 May 2025, there were 12 confirmed cases of mpox clade Ib in the UK, 8 of these were travel-associated, 3 secondary (household), and 1 sporadic. Among 368 identified contacts, 20 (aged 19-86 years) participated: 4/285 low-risk, 10/54 medium-risk and 6/29 high risk. Fourteen contacts provided at least one throat sample; all tested negative for mpox virus. CONCLUSIONS: No transmission of mpox was found outside of the household setting. This investigation contributed to the derogation of mpox clade I (including Ib) as a high-consequence infectious disease in the UK and informed vaccination strategies. Low participation among contacts highlights the need to optimise data and sample collection to improve engagement with future FFX studies.