Human Spiroplasmosis: Clinical Characterisation of a Newly Recognised Tick-Associated Febrile Illness

To characterise the clinical, epidemiological, and laboratory features associated with Spiroplasma ixodetis DNA detection in adults with unexplained acute febrile illness.

We retrospectively studied 337 adults evaluated in Slovenia between 2015 and 2025. All were tested using a species-specific real-time polymerase chain reaction (PCR) assay. PCR-positive and PCR-negative patients were compared within two source cohorts using cohort-stratified analyses; 182 healthy and disease control samples were tested with the same assay.

S. ixodetis DNA was detected in 60 of 337 patients: 15 of 209 (7.2%) in the initial cohort and 45 of 128 (35.2%) in the targeted cohort. PCR positivity was associated with recent tick bite, leukopenia, reactive lymphocytes, thrombocytopenia, and elevated aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. Headache occurred in 57 of 60 patients (95%), cerebrospinal fluid findings were normal in all 12 examined, and all 182 controls were PCR-negative. Nine patients (15%) were hospitalised; outcomes were favourable in all with available follow-up.

S. ixodetis DNAemia was associated with a reproducible tick-associated clinical and laboratory phenotype, supporting S. ixodetis as an under-recognised cause of human febrile illness. The targeted second cohort precludes interpreting overall PCR positivity as a prevalence estimate.