Late Disseminated Lyme Disease: Associated Pathology and Spirochete Persistence Post-Treatment in Rhesus Macaques

Nicholas A. Crossland, Xavier Alvarez, Monica E. Embers

Abstract

Non-human primates currently serve as the best experimental model for Lyme disease due to their close genetic homology with humans and demonstration of all three phases of disease following infection with Borreliella (Borrelia) burgdorferi (Bb). We investigated the pathology associated with late disseminated Lyme disease (12 to 13 months following tick inoculation) in doxycycline-treated (28 days; 5mg/kg, oral, 2x/day) and untreated rhesus macaques (Rm). Minimal to moderate lymphoplasmacytic inflammation, with a predilection for perivascular spaces and collagenous tissues, was observed in multiple tissues including the cerebral leptomeninges, brainstem, peripheral nerves from both fore and hind limbs, stifle synovium and perisynovial adipose tissue, urinary bladder, skeletal muscle, myocardium, and visceral pericardium. Indirect immunofluorescence assays (IFA) combining monoclonal (outer surface protein A) and polyclonal antibodies were performed on all tissue sections containing inflammation. Rare morphologically intact spirochetes were observed in the brains of two treated Rm, the heart of one treated Rm, and adjacent to a peripheral nerve of an untreated animal. Borreliaantigen staining of probable spirochete cross-sections was also observed in heart, skeletal muscle, and near peripheral nerves of both treated and untreated animals. These findings support the notion that chronic Lyme disease symptoms can be attributable to residual inflammation in and around tissues that harbor a low burden of persistent host-adapted spirochetes and/or residual antigen.

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