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Borrelia miyamotoi: An Emerging Tick-Borne Pathogen

 

Ixodes scapularis, the primary vector of Lyme disease in eastern North America. (Image Credit: Public Library of Science, Wiki CC License.)

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 confirmed or probable cases of Lyme disease were reported, in comparison with 4151 cases of Anaplasma phagocytophilum 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 episodes 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 amoxicillin) are effective for B. miyamotoi infection, although parenteral 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 (glycerophosphodiester 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 otherwise highly specific Lyme C6 peptide EIA, potentially leading to misdiagnoses.6Such misdiagnoses would certainly be expected when using a novel 2-tier testing strategy for Lyme disease that only uses EIAs and omits immunoblots as the second tier test.6

B. miyamotoi has been detected in all Ixodes species ticks that transmit B. burgdorferi worldwide (I. scapularisand I. pacificus in the US and I. ricinus and I. persulcatus in Eurasia), indicating that B. miyamotoi-infected ticks are potentially just as widespread as B. burgdorferi-infected ticks, although the prevalence of B. miyamotoiinfection 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 larger than that of B. burgdorferi-infected ticks and could occur throughout the entire species range of these ticks. This factor might contribute to a higher incidence rate of infection in humans than would be expected based on the ratio of B. miyamotoi to B. burgdorferi in infected nymphal- or adult-stage Ixodes ticks. Furthermore, B. miyamotoi is transmitted more rapidly from a tick bite than is B. burgdorferi,9 which also might contribute to a disproportionately higher incidence of B. miyamotoi infections.

With all tick stages as potential vectors, the risk of human infection is prolonged and could occur at any time of year that infected Ixodes ticks are active. Thus, assuming 300,000 cases of Lyme disease occur per year in the United States when unreported cases are included,10 it might be anticipated that the number of B. miyamotoiinfections would exceed 30,000 annually. However, given the infrequency with which B. miyamotoi infections have been recognized in the United States, it would not be surprising if a substantial proportion of infections are minimally symptomatic or asymptomatic and are self-resolving. However, an alternative explanation is the lack of general availability of polymerase chain reaction diagnostics for this infection and the frequent empiric use of doxycycline for unexplained summertime febrile illnesses without appropriate diagnostic testing to determine the etiology.

In conclusion, B. miyamotoi is a relapsing fever borrelia that is present in all species of Ixodes ticks that transmit B. burgdorferi infection, but a much lower proportion of these ticks are infected with B. miyamotoi compared with Lyme borrelia. B. miyamotoi infection can cause a febrile illness in association with leukopenia, thrombocytopenia, and abnormal liver function tests. Highly immunocompromised patients with infection due to B. miyamotoi may alternatively develop chronic meningitis. How frequently B. miyamotoi infections are asymptomatic and self-resolving is an important question. Available data indicate that symptomatic B. miyamotoi infections respond to the same antibiotics used to treat Lyme disease.

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– Gary P. Wormser, MDa, Eugene D. Shapiro, MDb,, Durland Fish, PhDc

This article originally appeared in the February issue of The American Journal of Medicine.

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