New Tickborne Pathogen Found in U.S.
An elderly immunocompromised woman who developed meningoencephalitis was most likely infected with Borrelia miyamotoi, which is related to the spirochete that causes Lyme disease and may be an underappreciated cause of disease in locations where Lyme disease is endemic.
Real-time PCR testing of cerebrospinal fluid samples confirmed the presence of the Borrelia species in this patient, but ruled out the presence of the Lyme disease pathogenB. burgdorferi, according to Sam R. Telford III, ScD, of Tufts University in North Grafton, Mass., and colleagues.
Instead, amplification of two genes specific to B. miyamotoi implicated this organism, a finding that "was confirmed by sequencing and phylogenetic analysis of the 16S rRNA and flagellin genes," and "that definitively place the Borrelia from this patient within the American clade of the B. miyamotoi-like spirochetes," the researchers reported in the Jan. 17 issue of the New England Journal of Medicine.
The researchers noted that the patient had responded well to a course of treatment suitable for Lyme neuroborreliosis, and suggested that other cases of B. miyamotoi may have been misidentified if patients had received standard Lyme disease treatment and recovered uneventfully.
The patient was an 80-year-old resident of rural New Jersey who had been treated with several chemotherapeutic and immunomodulating agents for non-Hodgkin's lymphoma, and who had previously had two episodes of Lyme disease.
Over the course of several weeks, she experienced progressive deterioration in mental and physical functioning; oncologic work-up found no cancer recurrence.
However, examination of cerebrospinal fluid revealed the presence of spirochetes, and she was treated with intravenous penicillin G for 30 days, by which time her mental status and physical function had returned to normal.
Findings on numerous laboratory tests performed during her hospitalization found low levels of IgM and IgG and negative results for cryptococcal antigen and acid-fast bacilli.
Detailed analyses of CSF samples were then undertaken at a reference laboratory.
On microscopical and immunofluorescence examinations, coiled spirochetes were identified that belonged to the genus Borrelia. No Treponema spirochetes were found.
The motile organisms were notably different in appearance from B. burgdorferi, and no reactivity was seen with exposure to a monoclonal antibody that tests positive for all known U.S. strains of B. burgdorferi.
Real-time PCR testing then confirmed the species as being Borrelia rather than Treponema, and eliminated the possibility of B. burgdorferi with an assay that can detect that organism's OspA gene.
Detection of the two B. miyamotoi genes strongly supported that organism as the cause of the woman's disease, according to the authors.
Borrelia species are known to cause two types of illness -- Lyme disease and various relapsing fevers -- and all are carried by hard or soft ticks.
Borrelia miyamotoi was first identified in 1995 in Japan, and is now found worldwide.
It is carried by the same ticks as B. burgdorferi, but with a much lower prevalence.
A series of almost 50 cases was reported from Russia in 2011, with clinical manifestations of the relapsing fever form of illness.
Those patients showed seroreactivity to testing for the broader, worldwide range of B. burgdorferispecies, but DNA analysis of two specific genes identified B. miyamotoi as the most plausible causative pathogen.
Recent research has demonstrated seropositivity to B. miyamotoi in up to 3% of individuals residing in the northeastern U.S. where Lyme disease is endemic and numerous types of Borrelia-laden ticks are found.
Unlike the Russian cases, the elderly woman had not reacted to antigen testing for B. burgdorferi, even though the organisms are related. This lack of reactivity may have resulted from the patient's immunomodulating treatment with rituximab, according to Telford and colleagues.
Misdiagnosis of meningoencephalitis with B. miyamotoi may be particularly likely in elderly patients, in whom the mental changes may be attributed to dementia, they noted.
"Immunocompromise in older patients should always prompt a more rigorous laboratory analysis, because such persons may serve as sentinels for poorly recognized or novel pathogens," the researchers concluded.
In a letter in the same issue of NEJM, Peter J. Krause, MD, from Yale University and colleagues reported on 18 patients who showed evidence of antibodies to B. miyamotoi, and three whose titers were sufficiently high to suggest recent infection.
Those three patients were symptomatic, with fevers, arthralgias, and sweats, and received antibiotic therapy with amoxicillin or doxycycline. None were immunocompromised.
Echoing the observations of Telford and colleagues, Krause's group stated, "B. miyamotoi infection may be prevalent in areas where Lyme disease is endemic in the United States."
Two of the authors of the case report have received funding from the National Institutes of Health, the National Fund for Research on Tickborne Diseases, the Evelyn Lilly Lutz Foundation, and the Gordon and Llura Gund Foundation.
One author has consulted for Immunetics and Meridian Diagnostics, and another is an employee of Imugen.
Several of the authors of the letter have received funding from the same foundations and have consulted for Baxter and Abbott, and one has received grants from several companies such as Immunetics and BioRad for Lyme disease diagnostic tests.
Primary source: New England Journal of Medicine
