Neurological and Immunological Dysfunction in Two Patients with Bartonella Henselae Bacteremia  Clinical Case Reports March 10, 2017 David L. Kaufman1, Andreas M. Kogelnik1, Robert B. Mozayeni2, Natalie A. Cherry2 & Edward B. Breitschwerdt3  (please see link for specifics on the cases)

Key Clinical Message:  Recently, BAPGM enrichment culture has documented Bartonella bacteremia in previously healthy, “nonimmunocompromised” patients following arthropod exposures. Neurobartonellosis should be among the differential diagnoses for patients with persistent or recurrent neurological symptoms of undetermined etiology. Microbiological and immunological testing should be concurrently pursued to determine whether defective immune function accompanies Bartonella bacteremia.

Discussion:  Two important clinical observations evolved out of the microbiological, immunological, and therapeutic findings associated with the medical management of these two patients. First, persistent or recurrent neurological symptoms of undetermined etiology in patients with historical vector exposures should prompt testing for bartonellosis. Historically, B. henselae infections in immunocompetent individuals have been associated with self-limiting cat scratch disease, whereas recent research supports persistent and potentially relapsing bacteremia [1–3]. As previously reported [2,3], both of these B. henselae bacteremic patients experienced headaches and disequilibrium. Patient 1 also experienced seizures, episodic confusion, and aphasia, which resolved completely following antibiotic therapy, despite persistence of the MRI abnormalities [1].

Secondly, immunological testing should be concurrently pursued to determine whether defective immune function accompanies neurological symptoms. Both patients had immunological abnormalities, including suppression of NK function, despite lacking a prior medical history indicative of immunodeficiency. The extent to which persistent B. henselae bacteremia may have induced immunocompromise or whether a chronic latent infection resulted in bacterial reactivation is unknown. It is important to note that after 9 months of treatment, the CD3, CD4, and CD19 deficiencies in Patient 1 resolved, while Patient 2 remained immunologically impaired after 5 months of therapy. There remains a substantial need for sequential electroencephalographic, MRI, immunological, and bacteriological patient data to guide physician decision making in patients with longstanding B. henselae bacteremia. Using a previously validated diagnostic approach [3,4], B. henselae bacteremia was confirmed in both patients by BAPGM enrichment blood culture, PCR amplification, and DNA sequence confirmation. Importantly, PCR did not amplify B. henselae DNA from patient’s blood, serum, 8-day, or 14-day BAPGM enrichment blood cultures, supporting the need for prolonged bacterial incubation times to obtain PCR confirmation for some B. henselae bacteremic patients. Consistent with previous studies[3,5] in which a subset of patients with persistent bacteremia were not IFA seroreactive to a panel of Bartonella sp. antigens, neither patient was initially B. henselae or B. quintana IFA seroreactive, whereas antibody reactivity was documented after antibiotic treatment in Patient 1, potentially due to enhanced immunological recognition of antigenic epitopes. Based upon these patients and previously published studies [3,5], enrichment blood culture and PCR should be used in conjunction with Bartonella sp. serological analysis when attempting to confirm bacteremic infection with a Bartonella sp. Vector transmission of B. henselae was the suspected source of infection for both patients. The veterinarian had ongoing vector (flea, mite, and potentially ticks) and animal exposure, which are occupational risks for animal health workers [3,5]. The cat flea (Ctenocephalides felis) transmits B. henselae among cats that develop a relapsing bacteremia and remain persistently infected reservoir hosts for months to years [6].

Although there is no evidence that cat-associated mites (S. scabiei or N. cati) are vector competent for the transmission of Bartonella species, rat mite (Ornithonyssus bacoti) and pigeon mite (Dermanyssus spp.) transmissions of B. henselae and B. quintana, respectively, have been suspected [7,8]. Due to an acute-onset illness and presumed tick attachment in a Lyme-endemic region with the subsequent development of erythema chronicum migrans, Lyme disease was initially suspected in Patient 2. Rapid treatment with doxycycline may have prevented serodiagnostic confirmation of B. burgdorferi transmission, whereas testing for other tickborne pathogens was negative. Although tick transmission of B. henselae has not been proven, organism-specific DNA has been PCR-amplified and sequenced from Ixodes sp. ticks [9], vector competence for Bartonella transmission has been demonstrated in a rodent model [10], and French investigators have recently documented Bartonella spp. bacteremia in patients following tick exposures [11]. Historically, systemic bartonellosis has been reported in immunocompromised patients, such as those with HIV/ AIDS and transplant recipients. Recently, infection with Bartonella spp. has been reported in healthy asymptomatic Brazilian blood donor candidates[12] and in previously immunocompetent patients with chronic neurological or rheumatologic symptoms [2,3,5]. Because Bartonella spp. can infect erythrocytes, endothelial cells, and various macrophage-type cells, including brain-derived dendritic cells in vitro, the spectrum of neurological symptoms attributable to bartonellosis appear to be extremely diverse among patients [1,2]. Physicians should be aware of the rapidly increasing number of Bartonella spp., the large number of proven and suspected arthropod vectors, and the large number of reservoir hosts, all of which are collectively contributing to the enhanced recognition of neurobartonellosis as a medically important emerging infectious disease.

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