Borrelia miyamotoi: An Emerging Tick-Borne Pathogen

Borrelia miyamotoi: An Emerging Tick-Borne Pathogen As of July 2018, 6 different infections have been recognized to be transmitted by Ixodes scapularis ticks in the United States, the most common of which is Lyme disease. The pathogen responsible for the vast majority of cases of Lyme disease in the United States is Borrelia burgdorferi. Another Lyme borrelia species, however, B. mayonii, has recently been recognized to cause Lyme disease in the North Central region of the United States. Four of these 6 infections are nationally reportable. In 2016, 36,429 con- firmed or probable cases of Lyme disease were reported, in comparison with 4151 cases of Anaplasma phagocytophi- lum infection, 1910 cases of Babesia microti infection, and 22 cases of Powassan virus infection. 1 Of the 2 remaining infections, one, caused by Ehrlichia muris eauclairensis (formerly known as Ehrlichia muris-like agent) is rare and has only been found in the North Central region of the United States. The other is caused by B. miyamotoi, which is a member of the relapsing fever group of borrelia, rather than the Lyme borrelia group. B. miyamotoi was detected in Ixodes scapularis ticks in Connecticut in 2001, 2 but the first human case in the United States was not reported until 2013. 3 Unlike with Lyme disease, patients in the United States with B. miyamotoi infections typically do not have skin lesions and instead present with a nonspecific febrile illness, potentially associated with leukopenia, thrombocytopenia, and elevated liver function tests. 4 Highly immunocompromised patients may develop chronic meningitis. 3 Untreated patients with B. miyamotoi infections may experience a limited number of recurrent epi- sodes of fever, similar to other relapsing fever borrelia infections. 5 The same antibiotic regimens used to treat Lyme disease (eg, 10-14-day courses of oral doxycycline or amox- icillin) are effective for B. miyamotoi infection, although par- enteral therapy with ceftriaxone would be preferred for infected patients with chronic meningitis. Unlike with Lyme disease, there are no US Food and Drug Administration-approved diagnostic tests for B. miyamotoi infection. Active infection is most appropriately diagnosed by a validated polymerase chain reaction assay on a blood sample targeting a specific B. miyamotoi gene segment. 4 Serologic testing targeting a particular protein of B. miyamotoi that is not found in B. burgdorferi (glycero- phosphodiester phosphodiesterase [GlpQ] protein) is highly sensitive, but only on convalescent-phase serum samples. 4,6 Of note, B. miyamotoi infections regularly lead to positive results on enzyme immunoassays (EIA) used as first-tier tests to diagnose Lyme disease, including even the other- wise highly specific Lyme C6 peptide EIA, potentially leading to misdiagnoses. 6 Such misdiagnoses would cer- tainly be expected when using a novel 2-tier testing strategy for Lyme disease that only uses EIAs and omits immuno- blots as the second tier test. 6 B. miyamotoi has been detected in all Ixodes species ticks that transmit B. burgdorferi worldwide (I. scapularis and I. pacificus in the US and I. ricinus and I. persulcatus in Eura- sia), indicating that B. miyamotoi-infected ticks are potentially just as widespread as B. burgdorferi-infected ticks, although the prevalence of B. miyamotoi infection in Ixodes ticks is only about 10% of that of B. burgdorferi. 7 However, B. miyamotoi is transmitted transovarially in ticks, 8 which results in infection of the larval tick stage, whereas this does not occur with Lyme borrelia, suggesting that the geographic range of B. miyamotoi-infected ticks may actually be even Funding: This publication was made possible in part by support from CTSA Grant Number UL1 TR001863 from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH), to EDS. The findings and conclusions of this paper are those of the authors and do not necessarily represent the official position of the NIH. Conflict of Interest: GPW reports receiving research grants from Immunetics, Inc, Institute for Systems Biology, Rarecyte, Inc, and Quidel Corporation. He owns equity in Abbott/AbbVie; has been an expert witness in malpractice cases involving Lyme disease; and is an unpaid board member of the American Lyme Disease Foundation. EDS has received royalty payments from UptoDate; has been an expert witness in malpractice cases involving Lyme disease; has consulted with Valneva about a Lyme vaccine; and is an unpaid board member of the American Lyme Dis- ease Foundation. DF has been an expert witness in malpractice cases involving tick-borne diseases; and is an unpaid board member of the Amer- ican Lyme Disease Foundation. Authorship: All authors had access to the data and a role in writing the manuscript. Requests for reprints should be addressed to Futoshi Nakagami, General Internal Medicine, Osaka University hospital, 2-2 Yamadaoka, Suita-shi, Osaka, Japan 565-0871. E-mail address: [email protected] 0002-9343/© 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.amjmed.2018.08.012 COMMENTARY

Borrelia miyamotoi: An Emerging Tick-Borne Pathogen

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