Emerging human pathogen: Identifying Spiroplasma ixodetis as a frequent cause of unlocalised febrile illness

Febrile illness without clear localisation presents a significant diagnostic challenge due to non-specific symptoms and diverse aetiologies. Spiroplasma ixodetis, an emerging tick-associated pathogen previously linked mainly to congenital cataracts, has not been well characterised in adults. We investigated the prevalence and clinical features of S. ixodetis infection in adults with acute febrile illness without localisation.

Shotgun metagenomic sequencing identified S. ixodetis in the initial 209 patient cohort and the sequences were used to developed a novel real-time PCR assay targeting the 23S rRNA gene. Initial cohort screening was followed by testing 128 patients from an additionally selected targeted cohort. Positive results were confirmed by sequencing of 16S and 23S rRNA genes.

S. ixodetis DNA was confirmed in 7.2% patients from the initial and in 35.2% patients from the additional cohort (60 in total). All were identified in the period from April to October and 57% reported a recent tick-bite. Clinical presentation was homogenous, characterised by fever, headache, bicytopenia and liver enzyme abnormalities. Outcomes were favourable, with 15% requiring hospitalisation.

This study identifies S. ixodetis as a previously unrecognised cause of adult febrile illness without localisation, bridging the gap between previously published data between tick studies and isolated human case reports.