Persistence of borrelial DNA in the joints of Borrelia burgdorferi‐infected mice after ceftriaxone treatment

Abstract

We have earlier shown that Borrelia burgdorferi-infected and ceftriaxone-treated mice have viable spirochetes in their body, since immunosuppressive treatment allows B. burgdorferi to be detected by culture. However, the niche of the persisting spirochetes remained unknown. In the present study, we analyzed the tissues of B. burgdorferi-infected and ceftriaxone-treated mice by culture and PCR to reveal the foci of persisting spirochetes. C3H/HeN mice were infected via intradermal needle injection with B. burgdorferi s.s. N40. The mice were treated as follows: (i) short (5 days) and (ii) long (18 days) course of ceftriaxone at 2 weeks of infection and killed after either 10 or 30 weeks, or (iii) the mice received ceftriaxone for 5 days at 18 weeks of infection and were killed 21 weeks after the treatment. All samples of ceftriaxone-treated mice were culture negative, whereas all untreated controls were culture positive. Importantly, B. burgdorferi DNA was detected in the joints of 30-100% of the treated mice. In conclusion, these results combined with earlier results suggest that the joint or a tissue adjacent to the joint is the niche of persisting B. burgdorferi in ceftriaxone-treated mice.

The Ruggiero-Klinghardt (RK) Protocol for the Diagnosis and Treatment of Chronic Conditions with Particular Focus on Lyme Disease

“…Obviously, the presence of coinfections renders the treatment and the diagnosis rather difficult and contributes to patient morbidity and mortality as well as to the appearances of the so called "post-treatment Lyme disease" also known as "chronic Lyme" or, as we prefer to denominate it in this study, "persistent Lyme disease". Thus, persistence of Borrelia burgordferi in tissues after efficient antibiotic treatment has been demonstrated in a variety of experimental models that include primates, but there is currently no affordable, non-invasive, method to detect specific persistent microbes (or their metabolites) in vital organs such as the brain, spinal chord or heart (Straubinger et al, 1997;2000;Hodzic et al, 2008;Yrjänäinen et al, 2010;Embers et al, 2012).…”

“…However, persistence of Borrelia burgordferi in tissues after antibiotic treatment has been demonstrated in a variety of experimental models, which include primates, that were infected with Borrelia burgdorferi and then received aggressive and successful antibiotic treatment for 4-6 months (Straubinger et al, 1997;2000;Hodzic et al, 2008;Yrjänäinen et al, 2010;Embers et al, 2012).…”

Serum Matrix Metalloproteinase-8 and -9 Levels in Disseminated Lyme Borreliosis with Special Reference to Arthritis

“…In a subsequent study the niche of persisting B. burgdorferi in ceftriaxone-treated mice was obviously the joint or a tissue adjacent to the joint [29]. Also these recent animal model studies supports the view that a combination therapy could possibly lead to better outcome than single antibiotic therapy, at least to some subgroup of patients with disseminated LB.…”

Cutaneous and systemic Lyme disease

“…On the one side, there are studies that have assessed the posttreatment persistence of B. burgdorferi in animals, e.g., nonhuman primates [185] and rats [186,187]. Moreover, B. burgdorferi has been detected intracellularly in human endothelial cells [188], skin fibroblasts [189], synovial cells [190] and neuronal cells [191], which might appear as 'sanctuary sites', providing a protective niche during antibiotic treatment.…”