John A. Branda, MD; Eric S. Rosenberg, MD
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-1134.
Requests for Single Reprints: Eric S. Rosenberg, MD, Massachusetts General Hospital, Infectious Disease Division, Gray J-504, 55 Fruit Street, Boston, MA 02114.
Current Author Addresses: Dr. Branda: GRB-526 Microbiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114.
Dr. Rosenberg: Massachusetts General Hospital, Infectious Disease Division, Gray J-504, 55 Fruit Street, Boston, MA 02114.
Branda J., Rosenberg E.; Borrelia miyamotoi: A Lesson in Disease Discovery. Ann Intern Med. 2013;159:61-62. doi: 10.7326/0003-4819-159-1-201307020-00009
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Published: Ann Intern Med. 2013;159(1):61-62.
Recognition of novel infectious diseases has historically followed a prescribed course, which starts by defining a clinical syndrome. A prototypical example was the discovery of Lyme disease during the 1970s, which began with the description of epidemic oligoarticular arthritis (1), eventually followed by identification of the causative agent (2). In this issue, Chowdri and colleagues (3) contribute to the unfolding description of Borrelia miyamotoi infection—an illness with some similarities to Lyme disease but that was identified by reversing the traditional approach to disease discovery.
Durland Fish, Ph.D.
Yale School of Public Health
August 2, 2013
More lessons on disease discovery
I would like to thank Drs. Branda and Rosenberg for writing their excellent editorial on Borrelia miyamotoi (1). Readers may be interested to know that we discovered B. miyamotoi in Ixodes scapulars ticks more than 10 years ago and were able to show transmission by infected ticks to mice with subsequent antibody response and persistent infection at that time (2). We also showed this organism was wide-spread in I. scapularis with a mean prevalence of about 2%. We then applied 5 unsuccessful times to NIH and CDC for funding to determine whether this organism infects humans and causes disease. Each time the main criticism was lack of evidence for human infection, which was the objective of the proposal. In 2008, while attending a zoonoses conference in Cypress, I happened to pass by a poster authored by Russian investigator Alex Platonov describing infection with B. miyamotoi in ticks and in patients not having Lyme disease, but suspected tick-borne encephalitis. With my colleague Peter Krause, we collaborated with Platonov to publish these cases and compare them to Lyme disease cases in the US (3). Immediately after publication, we receive word that our most recent NIH R21 application would be funded. While I agree that this is a lesson in disease discovery, the real lesson should be that it could have happened a full decade earlier. A similar lesson should have been learned in 1994 when the first cases (some fatal) of human anaplasmosis were reported, even though ticks collected and preserved a decade earlier (1984) were found to be infected with the disease agent, Anaplasma phagocytophylum (4). We may again learn this lesson with a much more serious tick-borne infection, Powassan encephalitis virus, which has recently been found in I. scapularis ticks with prevalence rates of up to 5% (5), a rate exceeding that reported in areas highly endemic for tick-borne encephalitis in Eurasia. How many lessons does it take before it is realized that we are doing disease discovery backwards?
Durland Fish, Ph.D
Professor of Epidemiology
Yale School of Public Health
1. Branda JA Rosenberg ES. Borrelia miyamotoi: A lesson in disease discovery. Ann Int Med 1013;159:61-62
2. Scoles GA, Papero M, Beati L Fish D. A relapsing fever spirochete transmitted by Ixodes scapularis ticks. Vector Borne Zoonotic Dis. 2001:1:21-34.
3. Platonov AE, Karan LS, Kolyasnikova NM, Makhneva NA, Toporkova MG, Maleev VV, et al. Humans infected with relapsing fever spirochete Borrelia miyamotoi, Russia. Emerg Infect Dis. 2011;17:1816-23.
4. Schwartz I Fish D Daniels TJ. Prevalence of the rickettsial agent of human granulocytic ehrlichiosis in ticks from a hyperendemic focus of Lyme disease. N Engl J Med. 1997;337:49-51
5. Anderson JF, Armstrong PM. Prevalence and Genetic characterization of Powassan virus strains infecting Ixodes scapularis in Connecticut. Am J Trop Med Hyg. 2013;87:754-759.
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