## 3 Discussion  
Our case report describes an individual who was clinically diagnosed with Lyme borreliosis and who initially responded to mono-antibiotic therapy. The patient's symptoms returned, and he failed to respond to a second course of the same antibiotic. He was eventually diagnosed with both _Borrelia_ and _Anoplasma_ infections by antibody tests performed in a private laboratory. Following a two-month course of combination antibiotic therapy, the patient responded clinically, with a return to almost normal function. Patients who do not achieve total symptom resolution following initial treatment for Lyme borreliosis are often categorized under the umbrella of post-treatment Lyme disease syndrome (PTLDS). In longitudinal studies of patients with erythema migrants, subjective symptoms such as fatigue, cognitive impairment and musculoskeletal pain have shown to persist for \(\geq\) 6 months after antibiotic therapy in \(\sim\)10% of patients [22; 23]. In some cases, these symptoms may persist for more than 10 years [22]. PTLDS is recognized by guidelines from the IDSA and the United Kingdom's National Institute for Health and Care Excellence (NICE) [16; 24]. The pathogenesis of enduring symptoms remains unclear. Although it is most often recognized as a post-infectious condition, some would suggest that in at least a subset of patients, ongoing symptoms are indicative of persistent infection [25; 26; 27]. Placebo-controlled, randomized retreatment trials conducted using either parenteral antibiotic therapy alone or followed by a course of oral antibiotics in patients with PTLDS did not show any clinical benefit or showed only modest benefit that would be outweighed by potential adverse effects [28; 29; 30; 31; 32]. A reappraisal of retreatment trials published before 2012 was conducted independently by [PERSON] et al. and [PERSON] et al., each concluding that the results of these trials indicated that retreatment can be beneficial and that they were consistent with potential persistent infection [33; 34]. The claims of these reappraisal studies were disputed however by [PERSON] et al., who argue that neither analysis justifies the conclusion that there is meaningful clinical benefit to be gained from retreatment with parenteral antibiotic therapy [35]. Arguments for persistent infection with _Borrelia_ are supported by studies in a diversity of experimentally-infected animal models demonstrating ongoing spirochetal infection despite antibiotic therapy [36; 37; 38; 39; 40; 41; 42; 43; 44; 45]. Additionally, a recent study by [PERSON] et al. demonstrates the presence of persistent, intact, metabolically-active _B. burgdorferi_ following treatment of disseminated infection with recommended doses of doxycycline for 28 days in rhesus macaques [46]. Comparable findings in humans also suggest a potential role for bacterial persistence in the symptomatology of PTLDS [25; 47; 48]. Researchers have noted that patients diagnosed and treated later may develop a refractory arthritic syndrome, which may not respond to the standard recommended therapy [49]. Recent studies have sought to elucidate a plausible pathophysiology for treatment failure and persistent symptoms following antibiotic treatment. [PERSON] et al. propose that the stringent response mediated by the alarmone (p)ppGpp, a master regulator in _B. burgdorferi_, may be associated with persistence in human hosts and tolerance to otherwise lethal doses of antimicrobials [50]. Pre-clinical studies have demonstrated that a number of the drugs currently recommended to treat Lyme disease,such as amoxicillin and doxycycline, were unable to kill Borrelia burgdorferi persisters in vitro (42,43). [PERSON] et al. describe the ability of _Borrelia_ persisters to form round bodies, L-form bacteria, microcolonies, or biofilm-like aggregates. These persisters remain viable despite antibiotic therapy, and, in favorable growth environments, are able to reversibly convert into motile forms [27]. [PERSON] et al.