On 2015 May 25, Raphael Stricker commented:

Single-Dose Antibiotic Prophylaxis of Lyme Disease: Too Little Too Late?

Over the years since the article by Nadelman et al. was published in 2001 (1), doctors have been using single-dose doxycycline prophylaxis to treat patients following a tickbite. Newer research in animals and humans suggests that this prophylaxis may be ineffective.

The study by Nadelman et al. forms the basis for the Lyme prophylactic treatment guidelines of the Infectious Diseases Society of America (IDSA), and the IDSA guidelines recommend starting prophylaxis “within 72 hours of the time that the tick was removed.” However in 2004 Zeidner et al. noted that a single dose of doxycycline prevented infection in only 43% of mice exposed to Borrelia burgdorferi, the agent of Lyme disease, and a follow-up study in 2008 showed that only 20-30% of mice were protected from combined infection with B. burgdorferi and Anaplasma phagocytophilum following single-dose doxycycline prophylaxis (2). To explain prophylactic treatment failure, Piesman and Hojgaard recently published a mouse study showing the importance of the time interval between tick removal and prophylactic treatment (3).

In commenting on the study by Nadelman et al., Piesman and Hojgaard state: “The authors enrolled subjects if the tickbite occurred within 3 days of their clinical visit, but did not analyze the data based on the exact time between tick removal and delivery of prophylaxis….We found that two treatments of doxycycline delivered by oral gavage to mice on the day of removal of a single potentially infectious nymphal I. scapularis tick protected 74% of test mice compared to controls. When treatment was delayed until 24h after tick removal, only 47% of mice were protected; prophylactic treatment was totally ineffective when delivered ≥2 days after tick removal.” The loss of prophylactic efficacy over this time interval is supported by well-documented observations of rapid transmission of Lyme disease within 24 hours of a tickbite in humans (4). A review of the pertinent literature revealed that the risk of B. burgdorferi transmission within 24 hours of a tickbite was 7% under experimental conditions in mice and up to 25% in clinical studies involving humans (5).

In summary, animal and human studies of exposure to B. burgdorferi suggest that there may be a very narrow window for prophylactic treatment following tick removal. In failing to take this narrow prophylactic window into account, the study by Nadelman et al. appears to put patients at risk of developing Lyme disease following antibiotic prophylaxis that may be too little too late.

References

1. Nadelman RB, Nowakowski J, Fish D, Falco RC, Freeman K, McKenna D, Welch P, Marcus R, Aguero-Rosenfeld ME, Dennis DT, Wormser GP. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tickbite. N Engl J Med. 2001;345: 79-84.
2. Zeidner NS, Massung RF, Dolan MC, Dadey E, Gabitzsch E, Dietrich G, Levin ML. A sustained-release formulation of doxycycline hyclate (Atridox) prevents simultaneous infection of Anaplasma phagocytophilum and Borrelia burgdorferi transmitted by tick bite. J Med Microbiol. 2008;57(Pt 4):463-8.
3. Piesman J, Hojgaard A. Protective value of prophylactic antibiotic treatment of tickbite for Lyme disease prevention: An animal model. Ticks Tick Borne Dis. 2012;3:193-6.
4. Hynote ED, Mervine PC, Stricker RB. Clinical evidence for rapid transmission of Lyme disease following a tickbite. Diagn Microbiol Infect Dis. 2012;72:188-92.
5. Cook MJ. Lyme borreliosis: a review of data on transmission time after tick attachment. Int J Gen Med. 2014;8:1-8.

Disclosure: RBS is a member of the International Lyme and Associated Diseases Society (ILADS) and a director of LymeDisease.org. He has no financial or other conflicts to declare.

On 2015 May 25, Raphael Stricker commented:

Single-Dose Antibiotic Prophylaxis of Lyme Disease: Too Little Too Late?

Over the years since the article by Nadelman et al. was published in 2001 (1), doctors have been using single-dose doxycycline prophylaxis to treat patients following a tickbite. Newer research in animals and humans suggests that this prophylaxis may be ineffective.

The study by Nadelman et al. forms the basis for the Lyme prophylactic treatment guidelines of the Infectious Diseases Society of America (IDSA), and the IDSA guidelines recommend starting prophylaxis “within 72 hours of the time that the tick was removed.” However in 2004 Zeidner et al. noted that a single dose of doxycycline prevented infection in only 43% of mice exposed to Borrelia burgdorferi, the agent of Lyme disease, and a follow-up study in 2008 showed that only 20-30% of mice were protected from combined infection with B. burgdorferi and Anaplasma phagocytophilum following single-dose doxycycline prophylaxis (2). To explain prophylactic treatment failure, Piesman and Hojgaard recently published a mouse study showing the importance of the time interval between tick removal and prophylactic treatment (3).

In commenting on the study by Nadelman et al., Piesman and Hojgaard state: “The authors enrolled subjects if the tickbite occurred within 3 days of their clinical visit, but did not analyze the data based on the exact time between tick removal and delivery of prophylaxis….We found that two treatments of doxycycline delivered by oral gavage to mice on the day of removal of a single potentially infectious nymphal I. scapularis tick protected 74% of test mice compared to controls. When treatment was delayed until 24h after tick removal, only 47% of mice were protected; prophylactic treatment was totally ineffective when delivered ≥2 days after tick removal.” The loss of prophylactic efficacy over this time interval is supported by well-documented observations of rapid transmission of Lyme disease within 24 hours of a tickbite in humans (4). A review of the pertinent literature revealed that the risk of B. burgdorferi transmission within 24 hours of a tickbite was 7% under experimental conditions in mice and up to 25% in clinical studies involving humans (5).

In summary, animal and human studies of exposure to B. burgdorferi suggest that there may be a very narrow window for prophylactic treatment following tick removal. In failing to take this narrow prophylactic window into account, the study by Nadelman et al. appears to put patients at risk of developing Lyme disease following antibiotic prophylaxis that may be too little too late.

References

1. Nadelman RB, Nowakowski J, Fish D, Falco RC, Freeman K, McKenna D, Welch P, Marcus R, Aguero-Rosenfeld ME, Dennis DT, Wormser GP. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tickbite. N Engl J Med. 2001;345: 79-84.
2. Zeidner NS, Massung RF, Dolan MC, Dadey E, Gabitzsch E, Dietrich G, Levin ML. A sustained-release formulation of doxycycline hyclate (Atridox) prevents simultaneous infection of Anaplasma phagocytophilum and Borrelia burgdorferi transmitted by tick bite. J Med Microbiol. 2008;57(Pt 4):463-8.
3. Piesman J, Hojgaard A. Protective value of prophylactic antibiotic treatment of tickbite for Lyme disease prevention: An animal model. Ticks Tick Borne Dis. 2012;3:193-6.
4. Hynote ED, Mervine PC, Stricker RB. Clinical evidence for rapid transmission of Lyme disease following a tickbite. Diagn Microbiol Infect Dis. 2012;72:188-92.
5. Cook MJ. Lyme borreliosis: a review of data on transmission time after tick attachment. Int J Gen Med. 2014;8:1-8.

Disclosure: RBS is a member of the International Lyme and Associated Diseases Society (ILADS) and a director of LymeDisease.org. He has no financial or other conflicts to declare.