Six versus 2 weeks treatment with doxycycline in European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blinded, randomised and placebo-controlled trial.

BACKGROUND: There is limited evidence regarding optimal duration of antibiotic treatment in neuroborreliosis. We aimed to compare efficacy and safety of oral doxycycline for 2 and 6 weeks in European Lyme neuroborreliosis (LNB). METHODS: The trial had a randomised, double-blinded, placebo-controlled, non-inferiority design. Patients with LNB were recruited from eight Norwegian hospitals and randomised to doxycycline 200 mg once daily for 2 weeks, followed by 4 weeks of placebo, or doxycycline 200 mg once daily for 6 weeks. The primary endpoint was clinical improvement as measured by difference in a Composite Clinical Score (0-64 points) from baseline to 6 months. The non-inferiority margin was predetermined to 0.5 points. RESULTS: One hundred and twenty-one patients were included. Fifty-two treated for 2 weeks and 53 for 6 weeks were included in the intention-to-treat analyses, and 52 and 51 in per-protocol analysis. Mean difference in clinical improvement between the groups was 0.06, 95% CI -1.2 to 1.2, p=0.99 in the intention-to-treat population, and -0.4, 95% CI -1.4 to 0.7, p=0.51 in the per-protocol population and non-inferiority could not be established. There were no treatment failures and no serious adverse events. The groups did not differ in secondary outcomes including clinical scores at 10 weeks and 12 months, cerebrospinal fluid data and patient-reported outcome measures. Patients receiving 6 weeks doxycycline reported slightly more side effects in week 5. CONCLUSION: Our results strongly indicate that there are no benefits of doxycycline treatment beyond 2 weeks in European LNB. TRIAL REGISTRATION NUMBER: 2015-001481-25.

Detection of Neoehrlichia mikurensis in 11 persons who attribute their persistent health complaints to a tick-borne disease.

BACKGROUND: Neoehrlichia mikurensis infections can cause symptomatic disease, particular among immunosuppressed persons. Long-lasting asymptomatic carriage of N. mikurensis may be common in endemic areas. This study explores possible associations between carriage of N. mikurensis DNA and persistent health complaints in persons who attribute their symptoms to a tick-borne disease. METHODS: Eleven persons tested positive for N. mikurensis DNA by PCR in a study cohort of 285 persons reporting persistent health complaints. The 11 persons were tested again in a follow-up sample. Oral doxycycline treatment was given if the confirmatory PCR-test was positive. Treatment response was assessed by telephone interview. Demographics, clinical manifestations, tick exposure, physical health, somatic symptom burden and fatigue were compared to persons with negative N. mikurensis PCR (controls, N = 274). RESULTS: Six persons had detectable N. mikurensis DNA in a follow-up sample up to 9.5 months after the index sample. Seven persons (one without a positive confirmative test) received doxycycline treatment. Three reported symptom restitution after completed antibiotic treatment. However, their symptoms were not clearly attributed to infection by N. mikurensis. We did not find any significant differences between infected persons and non-infected controls regarding their clinical manifestations and health burdens. CONCLUSIONS: We corroborate previous evidence of long-term carriage of N. mikurensis, but cannot infer that to be causative of persistent health complaints.