Comment on: Efficacy of antibiotic prophylaxis for the prevention of Lyme disease: an updated systematic review and meta-analysis

Abstract

Sir, The recent article by Warshafsky et al. may encourage the use of single-oral-dose doxycycline for tick-bite prophylaxis, which in my opinion and in the light of other evidence, is likely to be ineffective. The recommendation for single-dose prophylaxis was first made by Nadelman et al. in 2001 as a result of a randomized controlled trial in 482 patients and was included in the Infectious Diseases Society of America’s (IDSA’s) guidelines for the treatment of Lyme disease. Three of the authors of the Nadelman et al. article were also authors of the IDSA guidelines. In their original article, Nadelman et al. showed that their single-dose regimen was 87% effective in blocking both the erythema migrans (EM) and the appearance of anti-Borrelia antibodies expected with borreliosis, but they did not show that it blocked actual infection in the antibiotic recipients. This is analogous to observations made in the 1950s that low-dose penicillin blocked cutaneous lesions of syphilis in rabbits but not the infection. The study by Nadelman et al. did not comment on complaints of fever and flu-like illness and limited its follow-up to 6 weeks instead of the 1–2 years used in other studies and no normal control group was used to compare the incidence of fever and flu-like illness with that of the treated/placebo groups. However, investigators at the CDC in Fort Collins, Colorado, showed that 80% of newly infected mice treated with a comparable single oral dose of doxycycline developed persistent borreliosis, which was found by grinding up tissues and using culture and PCR for bacterial detection. The sera from these mice were discarded without testing for anti-Borrelia antibodies so we do not know if they remained seronegative despite proven infection. Not surprisingly when the same criteria are used in the recent meta-analysis a similar result is obtained, i.e. a single oral dose blocks both EM and antibodies. By promoting this potentially flawed recommendation, the authors and the IDSA may actually promote persistent borreliosis that will be seronegative, and therefore difficult to diagnose. Transparency declarations