Remains of infection

In Lyme disease, musculoskeletal symptoms can persist after treatment, which has led to the hypothesis that the causal organism itself may escape antibiotic therapy. The controversy that surrounds this question extends beyond patients, physicians, and scientists, as public health organizations struggle with how the disease should be diagnosed and treated. Is Lyme disease an infection that resolves, or is the spirochetal agent resilient and evasive? In this issue of the JCI, Bockenstedt et al. address this issue and present compelling evidence that the residues of nonviable spirochetes can persist in cartilaginous tissue long after treatment and may contribute to antibiotic-refractory Lyme arthritis. The Oxford English Dictionary defines “remains” as “parts of a person’s body after death; a corpse” (1). We expect this fate for invading bacteria after a course of appropriately chosen, faithfully taken antibiotics and when the patient’s immune system is competent. A less common usage for the word is “the survivors of a war, battle, or other destructive event.” If the antibiotic course was inadequate in dosage or duration or if the patient had a deficiency in one or more innate or adaptive defenses, survival of some of the bacterial invaders would be no surprise. But what if even under the best of all therapeutic circumstances, bacteria, perhaps in unrecognizable forms, persisted through antibiotic therapy to prosper again, days to months after treatment? When the usual criteria for therapeutic success are met, may there be infection “remains,” in the survivorship sense, with a consequence of future pathogenicity? Think of the 1984 movie The Terminator: the assassin robot emerges first from an inferno and then from an explosion, now shorn of integument and limbs but still remorselessly pursuing the heroine. This distinction — between lifeless leftovers and viable hangers-on — is at the heart of a controversy over Lyme disease and one that Bockenstedt and coauthors address in their article in this issue (2).