Background: Borrelia species are divided into three groups depending on the induced disease and the tick vector. Borrelia miyamotoi is a relapsing fever Borrelia but can induce symptoms related to Lyme disease. Discovered in 1995, it is found in ticks around the world. In France, this species of Borrelia has been isolated in ticks and rodents, but was not yet observed in humans. Objective: The aim of the study was to look for B. miyamotoi in symptomatic patients. Methods: Real-time PCR was performed on 824 blood samples from patients presenting symptoms of persistent polymorphic syndrome possibly due to tick bite, a syndrome recognized by the French Authority for Health, which is close to the post-treatment Lyme disease syndrome. PCR was also performed on 24 healthy control persons. The primers were specifically designed for this particular species of Borrelia. The sequence of interest of 94 bp is located on the glpQ gene. Sequencing of amplification products, randomly chosen, confirmed the amplification specificity. To better investigate cases, a clinical questionnaire was sent to the patients PCR-positive for B. miyamotoi and to their physician. Results: This search revealed a positive PCR for B. miyamotoi in the blood from 43 patients out of 824 (5.22%). PCR was negative in all control persons. A clinical chart was obtained from 31 of the 43 patients. A history of erythema migrans was reported in five of these 31 patients (16%). All patients complained about fatigue, joint pain and neuro-cognitive disorders. Some patients complained about respiratory problems (chest tightness and/or lack of air in 41.9%). Episodes of relapsing fever were reported by 11 of the 31 patients (35.5%). Chilliness, hot flushes and/or sweats were reported by around half of the patients. B. miyamotoi may not cross-react with B. burgdorferi serology. Conclusion: This study is the first to detect B. miyamotoi in human blood in France. This series of human B. miyamotoi infection is the largest in patients with long term persistent syndrome. Our data suggest that this infection may be persistent, even on the long term.

Recently, disulfiram has been proposed as a promising treatment for people suffering from persistent symptoms of Lyme Disease. Disulfiram has several distinct molecular targets. The most well-known is alcohol dehydrogenase, a key enzyme for detoxifying the organism after alcohol ingestion. Other targets and modes of action of disulfiram, that may present problematic side effects, are less commonly mentioned. The French Federation against Tick Borne Diseases (French acronym, FFMVT), which associates three main Lyme patient organizations, MDs and PhDs, has recently been alerted to severe and persistent toxic events in a patient suffering from a late disseminated form of Lyme Disease following disulfiram intake. FFMVT reacted by launching a national call to examine whether other patients in France following a similar treatment could be identified, and what benefits, or side effects could be reported. The statements of 16 patients taking disulfiram have been collected and are presented here. Thirteen out of 16 patients reported toxic events, and seven out of 16 reported benefits for at least part of their symptoms. Based on the collected observations, it seems too early to promote disulfiram as a promising new treatment until the reasons underlying the reported toxicities have been explored, and the results of a well-conducted double blind clinical trial published. The importance of taking into account patient-reported outcomes in Lyme Disease is underlined by the present study.

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