Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Single-dose doxycycline prevented Lyme disease after an Ixodes scapularis tick bite

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ACP J Club. 2002 Mar-Apr;136:56. doi:10.7326/ACPJC-2002-136-2-056

Related Content in this Issue
• Companion Abstract and Commentary: Prolonged antibiotic treatment did not relieve chronic symptoms in Lyme disease


Source Citation

Nadelman RB, Nowakowski J, Fish D, et al., for the Tick Bite Study Group. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001 Jul 12;345:79-84. [PubMed ID: 11450675] (All 2002 articles were reviewed for relevancy, and abstracts were last revised in 2008.)


Abstract

Question

In patients with Ixodes scapularis tick bites, does single-dose doxycycline prevent Lyme disease?

Design

Randomized (unclear allocation concealment*), blinded (patients and study personnel),* placebo-controlled trial with 6-week follow-up.

Setting

A university hospital and a community hospital in Westchester County, New York, United States.

Patients

506 patients who were ≥ 12 years of age; had removed an attached I. scapularis tick from their bodies in the previous 72 hours; and were bitten in Westchester County, New York. Exclusion criteria were clinical signs of Lyme disease, current or recent completion of an antibiotic course that is effective against Borrelia burgdorferi, vaccination against Lyme disease, nonsubmission of the removed tick, or pregnancy or lactation. In 482 patients (median age 41 y, 53% men), the ticks were confirmed to be I. scapularis ticks. 85% of these patients completed follow-up.

Intervention

Patients were allocated to doxycycline, two 100-mg capsules (n = 235), or placebo (n = 247).

Main outcome measures

Development of erythema migrans at the site of the tick bite. Secondary outcomes were erythema migrans at a different site and laboratory evidence (positive skin culture or seroconversion) of B. burgdorferi infection in the absence of erythema migrans.

Main results

Fewer patients in the doxycycline group than the placebo group developed erythema migrans at the site of the tick bite (P < 0.04) (Table). The groups did not differ for secondary outcomes (Table). More patients in the doxycycline group than the placebo group had adverse events (30% vs 11%, P < 0.001), which were mainly nausea and vomiting; these adverse events were not serious and were self-limited.

Conclusion

In patients with Ixodes scapularis tick bites, single-dose doxycycline was effective in preventing Lyme disease.

*See Glossary.

Sources of funding: Tick-Borne Diseases Institute of the New York State Department of Health and Centers for Disease Control and Prevention.

For correspondence: Dr. R.B. Nadelman, Westchester Medical Center, Valhalla, NY, USA.


Table. Doxycycline vs placebo after an Ixodes scapularis tick bite†

Outcomes at 6 wk Doxycycline Placebo RRR (95% CI) NNT (CI)
Erythema migrans at tick site 0.4% 3.2% 87% (20 to 98) 36 (17 to 195)
Laboratory-confirmed Borrelia burgdorferi in absence of erythema migrans 0.4% 0.8% 47% (−299 to 93) Not significant
RRI (CI) NNH
Erythema migrans elsewhere 0.4% 0.4% 5.1% (−89 to 903) Not significant

†Abbreviations defined in Glossary; RRR, RRI, NNT, NNH, and CI calculated from data in article.


Commentary

The studies by Nadelman and Klempner and their colleagues address 2 important controversies about the treatment of Lyme disease: prophylaxis for tick bites and treatment of persistent symptoms after acute Lyme disease.

The possibility of a patient developing chronic symptoms despite treatment for acute Lyme disease creates pressure on physicians to give antibiotics for tick exposures. Prophylactic antibiotics for tick bites, however, have not previously been shown to be effective in preventing Lyme disease (1−5). The success of the trial by Nadelman and colleagues may have resulted from the regimen chosen or from the fact that the size of the trial allowed small differences in treatment effect to be detected. Since patients were followed for only 6 weeks, we cannot know whether post–Lyme-disease symptoms were prevented, either in patients who developed erythema migrans or in those who may have developed asymptomatic infection. However, in an endemic area with probable re-exposure (18% of the patients reported a subsequent tick bite in the 6-week trial period), it would be impossible to know whether post–Lyme-disease symptoms resulted from the tick bite that was treated or from previous or subsequent exposure.

For patients in endemic areas, feasibly implementing prophylaxis would require that a supply of doxycycline be kept and taken after each tick bite, without contacting a health care provider each time. For patients with only occasional tick bites in endemic areas, a single-dose regimen may be practical. For those with chronic exposure, given the risks for side effects and the public health issues of bacterial resistance, vaccination is probably indicated, although the duration of efficacy is not known. Because the vaccine for Lyme disease is not approved for children < 15 years of age (although it appears to be effective) and doxycycline is contraindicated in children < 9 years of age, prevention in children (and in adults unwilling to take the vaccine) continues to be based on avoidance of high-risk areas and daily tick checks.

Use of antibiotics for persistent symptoms after Lyme disease is also controversial. Symptoms that are similar to fibromyalgia may develop in some patients after Lyme disease despite appropriate early treatment (usually 3 to 4 wk of doxycycline or ceftriaxone) of acute symptoms (erythema migrans, Bell palsy, or acute arthritis). The study by Klempner and colleagues shows that prolonged antibiotic treatment in these patients is no better than placebo. No evidence of persistent Borrelia burgdorferi infection was found in study patients.

Unfortunately, this study may not convince proponents of long-term therapy who believe post–Lyme-disease symptoms may represent concurrent symptoms of ehrlichiosis and babesiosis (6), both of which should be treated with antibiotics. Part of the controversy results from the limitations in diagnostic testing for these infections. For patients with post–Lyme-disease symptoms, the best recommendation is referral to a rheumatologist or infectious-disease specialist knowledgeable about Lyme disease and experienced in fibromyalgia.

John Meyerhoff, MD
Johns Hopkins University/Sinai Hospital Program in Internal Medicine
Baltimore, Maryland, USA


References

1. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clin Infect dis. 2006;43:1089-143. [PubMed ID: 17029130]

2. Costello CM, Steere AC, Pinkerton RE, Feder HM Jr. A prospective study of tick bites in an endemic area for Lyme disease. J Infect Dis. 1989;159:136-9. [PubMed ID: 2642519]

3. Agre F, Schwartz R. The value of early treatment of deer tick bites for the prevention of Lyme disease. Am J Dis Child. 1993;147:945-7. [PubMed ID: 8362808]

4. Shapiro ED, Gerber MA, Holabird NB, et al. A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites. N Engl J Med. 1992;327:1769-73. [PubMed ID: 1435930]

5. Warshafsky S, Nowakowski J, Nadelman RB, et al. Efficacy of antibiotic prophylaxis for prevention of Lyme disease. J Gen Intern Med. 1996;11:329-33. [PubMed ID: 8803738]

6. Burrascano JJ Jr. Advanced topics in Lyme disease. Diagnostic hints and treatment guidelines for Lyme and other tick borne illnesses. 13th ed. May 2000. www2.lymenet.org/domino/file.nsf/UID/guidelines.