Repeat Lyme Is Reinfection, Not Relapse

Nov. 15, 2012— -- All patients successfully treated for Lyme disease with antibiotics who then had another episode of erythema migrans -- the hallmark rash often described as a "bull's-eye" welt -- had a reinfection rather than a relapse, a small study found.

In 17 patients who suffered a total of 22 pairs of sequential episodes of erythema migrans, the hallmark lesion marking acute infection with the tick-borne Lyme parasite, Borrelia burgdorferi, genetic tests revealed that in every case that the second infections were with a different strain of the organism than the first, according to Dr. Robert Nadelman of New York Medical College in Valhalla, N.Y., and colleagues.

The patients had received antibiotic treatment after their initial infections, with tests confirming that the parasite had been eliminated. But controversy remains over whether B. burgdorferi can persist undetected after treatment, leading to reemergence of symptoms later on.

"These data, in conjunction with available clinical and epidemiologic evidence, show that repeat episodes of erythema migrans in appropriately treated patients were reinfections and not relapses," Nadelman and colleagues wrote in the Nov. 15 issue of the New England Journal of Medicine.

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They noted that recurrent infections after antibiotic treatment are not uncommon, with one earlier study showing a rate of 15 percent in patients followed for 5 years after an initial episode.

In such cases, patients, and occasionally their doctors, may think that the new episodes reflect a recrudescence of latent infection, rather than a new infection resulting from another tick bite.

Nadelman and colleagues collected data on all patients presenting with erythema migrans to a Lyme disease clinic at New York Medical College beginning in 1991 and who had agreed to participate in prospective studies.

The researchers searched the records for patients who showed a new erythema migrans lesion after successful treatment for an earlier episode -- with success defined as "subsequent resolution of the skin lesion or lesions." They identified 24 such "paired consecutive episodes." Individual patients had as many as four episodes of erythema migrans.

For 22 of these paired episodes, involving 17 patients, the clinic had collected B. burgdorferi isolates from both episodes, allowing for a genetic analysis of the organisms. If it appeared that the same strain was present in both the initial and recurrent episodes, that would suggest the possibility that "successful" treatment had not eradicated the parasite and that the second infection reflected relapse.

That was never the case, the researchers reported. In each paired episode, the first and second isolates had clear differences in outer-surface protein C (ospC) genotype.

Nadelman and colleagues said that it was theoretically possible that the patients had been infected with two different genotypes at the first infection, with antibiotic failure resulting in recrudescence of the lesions. But they estimated the probability that this would explain their results at 0.0000002 -- the chance that, in each of the 22 paired episodes, a different isolate would be detected in the second versus the first infection.

Even if patients had been initially infected with five different isolates, the researchers indicated, "the probability of the detection of a different genotype by chance alone is less than 0.01."

Repeat Lyme Caused by Reinfection

Another factor bolstering the conclusion of reinfection rather than relapse was the timing of second infections -- in 20 of the 22 cases, they occurred from June through August, when the ticks responsible for transmitting B. burgdorferi are most active in the New York area.

Also, the time between episodes was never less than 1 year and ranged up to 15 years. Nadelman and colleagues cited earlier research suggesting that, in cases of antibiotic failure, relapses occur within days to weeks.

In an accompanying editorial, Dr. Allen C. Steere of Massachusetts General Hospital in Boston, said the new study supports the conclusion that current antibiotic treatments are adequate to eliminate Lyme infections.

As a result, he suggested, reinfection is the best explanation when erythema migrans lesions are detected again after treatment.

"The issue of relapse versus reinfection has a broader context because of patient-advocacy groups that promote months or years of antibiotic therapy for 'chronic Lyme disease,'" Steere added.

Many patients and some physicians believe that B. burgdorferi can persist after antibiotic treatment and also evade detection with molecular and serological tests, producing long-term symptoms such as diffuse pain and fatigue. According to this theory, months or years of antibiotic therapy may be needed to manage the condition.

Although this theory has been soundly rejected by mainstream organizations such as the Infectious Diseases Society of America, a vocal movement continues to advocate it.

But Steere indicated that the current study is more evidence that the chronic-Lyme theory is false.

"Although B. burgdorferi infection may persist for years in untreated patients, the weight of evidence is strongly against persistent infection as the explanation for persistent symptoms in antibiotic-treated patients with Lyme disease," he wrote.