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.