Borrelia miyamotoi infection in Nature and in humans
Abstract
Borrelia miyamotoi is a relapsing fever Borrelia group spirochete that is transmitted by the same hard-bodied (ixodid) tick species that transmit the agents of Lyme disease. It was discovered in 1994 in Ixodes persulcatus ticks in Japan. B. miyamotoi species phylogenetically cluster with the relapsing fever group spirochetes, which usually are transmitted by soft-bodied (argasid) ticks or lice. B. miyamotoi infects at least six Ixodes tick species in North America and Eurasia that transmit Lyme disease group spirochetes and may use small rodents and birds as reservoirs. Human cases of B. miyamotoi infection were first reported in 2011 in Russia and subsequently in the United States, Europe, and Japan. These reports document the public health importance of B. miyamotoi, as human B. miyamotoi infection appears to be comparable in frequency to babesiosis or human granulocytic anaplasmosis in some areas and may cause severe disease, including meningoencephalitis. The most common clinical manifestations of B. miyamotoi infection are fever, fatigue, headache, chills, myalgia, arthralgia, and nausea. Symptoms of B. miyamotoi infection generally resolve within a week of the start of antibiotic therapy. B. miyamotoi infection should be considered in patients with acute febrile illness who have been exposed to Ixodes ticks in a region where Lyme disease occurs. Because clinical manifestations are non-specific, etiologic diagnosis requires confirmation by blood smear examination, PCR, antibody assay, in vitrocultivation, and/or isolation by animal inoculation. Antibiotics that have been used effectively include doxycycline for uncomplicated B. miyamotoi infection in adults and ceftriaxone or penicillin G for meningoencephalitis.
It appears that B myamotoi can cause what some have termed “Lyme-like disease” as well as relapsing fever.
In the course of developing a DNA-based test system (which has gained full FDA approval) Lee and colleagues from the Milford Hospital in Connecticut analysed a set of archived sera from patients clinically diagnosed with Lyme disease. Of 14 patients with spirochetaemia, 3 had a B. myamotoi infection and 1 had both B. myamotoi and B. burgdorferei infections (see Lee et al.: Detection of borreliae in archived sera from patients with clinically suspect Lyme disease. Int J Mol Sci. 2014; 15: 4284-98).
They also found a new species; the individual in that case was seropositive.
These findings are especially important with regard to ELISA tests. B. myamotoi does not cross-react with any of the species whose antigens are currently used for ELISA and WB. There are no commercially available antigens for B. myamotoi. This means that the negative predictive value of any currently approved ELISA test anywhere is ZERO. A negative test is absolutely not evidence that the patient does not have a borelliosis.
This is a crucial point; and damning if the guidelines resulting from the 2015 IDSA review include a requirement for a positive or at least equivocal ELISA test as the primary diagnostic criterion.
A negative test result is meaningless in terms of diagnosis so long as there are pathogenic Borrelia for which there are no antigens in the test mix. That is an entirely separate issue from seronegativity.