Bartonella Bacteremia

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RitaA
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Bartonella Bacteremia

Post by RitaA » Fri 20 Apr 2012 9:43

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Bartonella Bacteremia

Ricardo G. Maggi, B. Robert Mozayeni, Elizabeth L. Pultorak, Barbara C. Hegarty, Julie M. Bradley, Maria Correa, and Edward B. Breitschwerdt. Bartonella spp. Bacteremia and Rheumatic Symptoms in Patients from Lyme Disease–endemic Region. Emg. Inf. Dis. 2012;18(5).

After B. henselae was confirmed as the primary cause of cat-scratch disease in the early 1990s, several reports described an association between the newly identified bacterium and rheumatic disease manifestations, variously described as rheumatoid, reactive, or chronic progressive polyarthritis. One study, however, failed to isolate B. henselae from synovial fluid of 20 patients with chronic arthritis. Because epidemiologic evidence supports an association between rheumatic symptoms and cat-scratch disease and because arthritis is a primary disease manifestation of Borellia burgdorferi infection (Lyme disease), we explored whether antibodies against and bacteremia with Bartonella spp. can be detected in patients examined for arthropathy or chronic myalgia. Our primary objective was to determine the serologic and molecular prevalence of Bartonella spp. bacteremia in patients referred to a clinical rheumatologist. We also compared self-reported symptoms, health history, and demographic factors with Bartonella spp. bacteremia as determined by an enrichment blood culture platform combined with PCR amplification and DNA sequencing, when possible, to determine the Bartonella species and strain.

We identified unexpectedly high serologic and molecular prevalence for B. henselae, B. koehlerae, and B. vinsonii subsp. berkhoffii in patients who had been examined by a rheumatologist, of whom more than half reported a prior diagnosis of Lyme disease, bartonellosis, or babesiosis. However, the diagnostic criterion upon which these infections were based was not available for review because all prior diagnoses were self-reported. Overall, 185 (62.5%) of 296 patients had antibodies to B. henselae, B. koehlerae, or B. vinsonii subsp. berkhoffii, and 122 (41.1%) were positive for Bartonella spp. according to PCR. In most instances, DNA sequencing of the amplified product facilitated identification of the infecting species. The prevalence of antibodies against Bartonella spp. (93 [67.4%]) and bacteremia [57 [1.3%]) among 138 patients with a prior diagnosis of Lyme disease did not differ from that of the overall study population.

Because our analysis was restricted to patients selected by a rheumatologist practicing in a Lyme disease–endemic region, extrapolations to other regions or other rheumatology practices might not be applicable. Also, because the survey was self-administered, objective confirmation of symptoms, conditions, and diagnoses was not always possible; therefore, responses might have been subject to respondent bias. Similarly, because responses associated with symptoms, conditions, and exposures might have occurred over a protracted time, survey responses might also be subject to recall bias.

Despite these study limitations, B. henselae infections seemed to be more common in patients who reported blurred vision, numbness in the extremities, and previous consultation with a neurologist before referral to the rheumatologist.

Although no symptoms were statistically associated with B. koehlerae infection, patients infected with B. koehlerae were more likely to have previously consulted an infectious disease physician. Of the 54 B. koehlerae patients with a positive PCR result, 54% reported a prior diagnosis of Lyme disease (n = 25), bartonellosis (n = 3), or babesiosis (n = 1). Fatigue, insomnia, memory loss, and joint and muscle pain were frequent complaints among those with a positive PCR result for B. koehlerae, but these symptoms did not differ in frequency from those in patients with negative PCR.

Although the pathogenic relevance of the high Bartonella spp. seroprevalence and bacteremia in this patient population are unclear, these results justify additional prospective studies involving more narrowly defined patient and control populations.

It is becoming increasingly clear that no single diagnostic strategy will confirm infection with a Bartonella sp. in immunocompetent patients. Before the current study, we primarily used BAPGM [Bartonella α Proteobacteria growth medium] enrichment blood cultures and PCR to test symptomatic veterinarians, veterinary technicians, and wildlife biologists, who seem to be at occupational risk for Bartonella sp. bacteremia because of animal contact and frequent arthropod exposure.

Cats are the primary reservoir hosts for B. henselae and B. koehlerae, whereas canids, including dogs, coyotes and foxes, are the primary reservoir hosts for B. vinsonii subsp. berkhoffii. Although infrequent when compared with cat transmission of B. henselae resulting in classical cat-scratch disease, dogs have been implicated in the transmission of B. vinsonii subsp. berkhoffii and B. henselae to humans.

The predominant symptoms reported among occupationally at-risk patient populations have included severe fatigue, neurologic and neurocognitive abnormalities, arthralgia, and myalgia.


Disclaimer: E.B.B., in conjunction with Sushama Sontakke and North Carolina State University, holds US Patent No. 7,115,385, Media and Methods for Cultivation of Microorganisms, which was issued October 3, 2006. E.B.B. is chief scientific officer for Galaxy Diagnostics, a newly formed company that provides diagnostic testing for the detection of Bartonella species infection in animals and human patients. R.G. Maggi has lead research efforts to optimize the BAPGM platform and is the scientific technical advisor for Galaxy Diagnostics. R. Mozayeni was the attending physician for the patients described in this study and has recently joined Galaxy Diagnostics as the chief medical officer. All other authors have no potential conflicts.

RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: Bartonella Bacteremia

Post by RitaA » Fri 20 Apr 2012 10:14

http://wwwnc.cdc.gov/eid/article/18/5/1 ... rticle.htm
Volume 18, Number 5—May 2012

Research

Bartonella spp. Bacteremia and Rheumatic Symptoms in Patients from Lyme Disease–endemic Region

State University, Raleigh, North Carolina, USA (R.G. Maggi, E.L. Pultorak, B.C. Hegarty, J.M. Bradley, M. Correa, E.B. Breitschwerdt); Translational Medicine Group, PC, North Bethesda, Maryland, USA (B.R. Mozayeni)

Abstract

Bartonella spp. infection has been reported in association with an expanding spectrum of symptoms and lesions. Among 296 patients examined by a rheumatologist, prevalence of antibodies against Bartonella henselae, B. koehlerae, or B. vinsonii subsp. berkhoffii (185 [62%]) and Bartonella spp. bacteremia (122 [41.1%]) was high. Conditions diagnosed before referral included Lyme disease (46.6%), arthralgia/arthritis (20.6%), chronic fatigue (19.6%), and fibromyalgia (6.1%). B. henselae bacteremia was significantly associated with prior referral to a neurologist, most often for blurred vision, subcortical neurologic deficits, or numbness in the extremities, whereas B. koehlerae bacteremia was associated with examination by an infectious disease physician. This cross-sectional study cannot establish a causal link between Bartonella spp. infection and the high frequency of neurologic symptoms, myalgia, joint pain, or progressive arthropathy in this population; however, the contribution of Bartonella spp. infection, if any, to these symptoms should be systematically investigated.



The genus Bartonella comprises at least 26 species or subspecies of vector-transmitted bacteria, each of which has evolved to cause chronic bacteremia in >1 mammalian reservoir hosts (1–4). Among these, bartonellae of 14 species or subspecies have been implicated in zoonotic diseases (5,6), including cat-scratch disease, which is caused by B. henselae transmission during a cat bite or scratch and characterized by acute onset of self-limiting fever and regional lymphadenopathy (7–9). Recent observations, however, are causing a paradigm shift from the assumption that infection with a Bartonella sp. consistently induces an acute, self-limiting illness to the realization that subsets of infected, immunocompetent patients can become chronically bacteremic (10–15).

After B. henselae was confirmed as the primary cause of cat-scratch disease in the early 1990s, several reports described an association between the newly identified bacterium and rheumatic disease manifestations, variously described as rheumatoid, reactive, or chronic progressive polyarthritis (16–20). One study, however, failed to isolate B. henselae from synovial fluid of 20 patients with chronic arthritis (21). Because epidemiologic evidence supports an association between rheumatic symptoms and cat-scratch disease and because arthritis is a primary disease manifestation of Borellia burgdorferi infection (Lyme disease), we explored whether antibodies against and bacteremia with Bartonella spp. can be detected in patients examined for arthropathy or chronic myalgia. Our primary objective was to determine the serologic and molecular prevalence of Bartonella spp. bacteremia in patients referred to a clinical rheumatologist. We also compared self-reported symptoms, health history, and demographic factors with Bartonella spp. bacteremia as determined by an enrichment blood culture platform combined with PCR amplification and DNA sequencing, when possible, to determine the Bartonella species and strain. This study was conducted in conjunction with North Carolina State University Institutional Review Board approval (IRB# 164–08–05).

Materials and Methods

Study Population

For this cross-sectional study, we enrolled only patients examined by a rheumatologist in the Maryland–Washington, DC, USA, area from August 25, 2008, through April 1, 2009. Because Bartonella spp. are known to primarily infect cells within the vascular system, including erythrocytes, endothelial cells, and potentially circulating and tissue macrophages (1,5,6), selection was biased by patients who had historical, physical examination, or laboratory evidence of small vessel disease, including a subset of patients with a prior diagnosis of Lyme disease or chronic post–Lyme syndrome. We also included patients with chronic joint pain, prior documentation of synovial vascular inflammation, or a diagnosis of rheumatoid arthritis.

A standardized 5-page questionnaire was mailed to each participant for self-report. The questionnaire collected information about demographics, animal/arthropod exposure, history of visiting a medical specialist, outdoor activity, self-reported clinical symptoms, and concurrent conditions. Questionnaires were returned to the Intracelluar Pathogens Research Laboratory at North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina, USA, where results were entered into an electronic database.

Sample Collection

From each patient, the attending rheumatologist aseptically obtained anticoagulated blood samples (in EDTA tubes) and serum samples and shipped them overnight to the laboratory. Patient variations included timing of sample collection relative to onset of illness, duration of illness, current illness severity, and prior or recent use of antimicrobial drugs. The samples were then processed in a limited-access laboratory.

Sample Processing
Immunofluorescence Antibody Assay

To determine the antibody titer to each Bartonella species or subspecies, we used B. henselae, B. koehlerae, and B. vinsonii subsp. berkhoffii (genotypes I, II, and III) antigens in a traditional immunofluorescence antibody (IFA) assay with fluorescein conjugated goat anti-human IgG (Pierce Antibody; Thermo Fisher Scientific, Rockford, IL, USA) (10,12,22). To obtain intracellular whole bacterial antigens for IFA testing, we passed isolates of B. henselae (strain Houston-1, ATCC #49882); B. koehlerae (NCSU FO-1–09); and B. vinsonii subsp. berkhoffii genotypes I (NCSU isolate 93-CO-1, ATCC #51672), II (NCSU isolate 95-CO-2), and III (NCSU isolate 06-CO1) from agar-grown cultures into Bartonella-permissive tissue culture cell lines: AAE12 (an embryonic Amblyomma americanum tick cell line) for B. henselae, DH82 (a canine monocytoid cell line) for B. koehlerae, and Vero (a mammalian fibroblast cell line) for the B. vinsonii genotypes. Heavily infected cell cultures were spotted onto 30-well Teflon coated slides (Cel-Line; Thermo Fisher Scientific), air dried, acetone fixed, frozen, and stored. Serum samples were diluted in a phosphate-buffered saline solution containing normal goat serum, Tween-20, and powdered nonfat dry milk to block nonspecific antigen binding sites and then incubated on antigen slides. All available patient serum was screened at dilutions from 1:16 to 1:64. Samples reactive at a 1:64 dilution were further tested with 2-fold dilutions to 1:8192. As in previous studies, we defined a seroreactive antibody response against a specific Bartonella sp. antigen as a threshold titer of 64 (10–15,23,24).

Bartonella α Proteobacteria Growth Medium Enrichment Culture

Each sample was tested by PCR amplification of Bartonella spp. DNA before and after enrichment of blood and serum in Bartonella α Proteobacteria growth medium (BAPGM) (10–14,23–26). The BAPGM platform incorporates 4 PCR steps, representing independent components of the testing process for each sample, as follows: step 1) PCR amplifications of Bartonella spp. after DNA extraction from whole blood and serum; steps 2 and 3) PCR after whole blood culture in BAPGM for 7 and 14 days; and step 4) PCR of DNA extracted from subculture isolates (if obtained after subinoculation from the BAPGM flask at 7 and 14 days onto plates containing trypticase soy agar with 10% sheep whole blood, which are incubated for 4 weeks). To avoid DNA carryover, we performed PCR sample preparation, DNA extraction, and PCR amplification and analysis in 3 separate rooms with a unidirectional work flow. All samples were processed in a biosafety cabinet with HEPA (high-efficiency particulate air) filtration in a limited-access laboratory.

Methods used to amplify Bartonella DNA from blood, serum, and BAPGM liquid culture and subculture samples included conventional PCR with Bartonella genus primers targeting the 16S-23S intergenic spacer region (ITS) and a second PCR with B. koehlerae ITS species-specific primers, as described (13,25–29). Amplification of the B. koehlerae ITS region was performed by using oligonucleotides Bkoehl-1s: 5′-CTT CTA AAA TAT CGC TTC TAA AAA TTG GCA TGC-3′ and Bkoehl1125as: 5′-GCC TTT TTT GGT GAC AAG CAC TTT TCT TAA G-3′ as forward and reverse primers, respectively. Amplification was performed in a 25-µL final volume reaction containing 12.5 µL of Tak-Ex Premix (Fisher Scientific), 0.1 µL of 100 µM of each forward and reverse primer (IDT; DNA Technology, Coralville, IA, USA), 7.3 µL of molecular grade water, and 5 µL of DNA from each sample tested.

Conventional PCR was performed in an Eppendorf Mastercycler EPgradient (Hauppauge, NY, USA) under the following conditions: 1 cycle at 95°C for 2 s, followed by 55 cycles with DNA denaturing at 94°C for 15 s, annealing at 64°C for 15 s, and extension at 72°C for 18 s. The PCR was completed by a final cycle at 72°C for 30 s. As previously described for the Bartonella ITS genus and B. koehlerae–specific PCRs, all products were analyzed by using 2% agarose gel electrophoresis and ethidium bromide under UV light, after which amplicon products were submitted to a commercial laboratory (Eton Bioscience Inc., Research Triangle Park, NC, USA) for DNA sequencing to identify the species and ITS strain type (13,15,28,30).

To check for potential contamination during processing, we simultaneously processed a noninoculated BAPGM culture flask in the biosafety hood in an identical manner for each batch of patient blood and serum samples tested. For PCR, negative controls were prepared by using 5 µL of DNA from the blood of a healthy dog. All controls remained negative throughout the course of the study.

Statistical Analysis

Descriptive statistics were obtained for all demographic variables, self-reported clinical symptoms and concurrent conditions, previous specialist consultation, and self-reported exposures. The χ2 test was used to assess associations between self-reported clinical symptoms and previous specialist consultation separately with PCR results for B. henselae; B. koehlerae; and B. vinsonii subsp. berkhoffii genotypes I, II, and III. The Fisher exact test was used when expected cell value was <5. For the initial analysis, a liberal α value (α<0.10) was selected. The effect of each significant variable on the outcome variables was adjusted in separate multivariate logistic regression models controlling for age, sex, and health status. The models were repeated for different possible outcomes: PCR results for B. henselae or PCR results for B. koehlerae. Variables maintaining p<0.05 were considered significant. For some comparisons of potential interest, we were unable to estimate associations with the outcome(s) of interest because of low numbers (e.g., B. vinsonii subsp. berkhoffii genotypes I, II and III). Statistical analyses were performed by using SAS/STAT for Windows version 9.2 (SAS Institute Inc., Cary, NC, USA).

Results

Patient Characteristics

The age range of the 296 patients was 3–90 years; median ages were 46 years for women and 36 years for men (Table 1). Women made up ≈70% of the study population. Most (68.2%) patients reported that they felt ill, whether chronically or infrequently, and 27.7% considered themselves to be generally healthy. The most common animal exposure reported was dog (n = 252; 85.1%), followed by cat (n = 202; 68.2%) and horse (n = 86; 29.0%). Most patients reported having been bitten or scratched by an animal (n = 202; 68.2%) or exposed to ticks (n = 229; 77.4%) and biting flies (n = 160; 54.0%). Hiking was the predominant outdoor activity reported (52.0%). Most (273 [92.2%]) patients reported having had a condition diagnosed before visiting the rheumatologist. Previously diagnosed conditions included Lyme disease (46.6%), arthralgia/arthritis or osteoarthritis/rheumatoid arthritis (20.6%), chronic fatigue (19.6%), and fibromyalgia (6.1%) (Figure 1).

Serologic and BAPGM Findings

Of the 296 patients, 185 (62.5%) were seroreactive to >1 Bartonella sp. antigens and 122 (41.1%) were infected with B. henselae, B. koehlerae, B. vinsonii subsp. berkhoffii, or Bartonella spp. Of the 122 patients with Bartonella spp. infection, PCR results were positive but DNA sequencing was unsuccessful or did not enable species identification for 29 (23.7%). After subculture, 6 isolates were obtained from 5 samples: 3 B. henselae isolates, 2 B. koehlerae isolates, and 1 Bartonella sp. isolate that was not fully characterized. Of the Bartonella-infected patients, 120 (98.4%) had a positive PCR result after DNA extraction from blood, serum, or enrichment culture (Figure 2), and 2 (1.6%) had a positive PCR result only after subculture isolation.

For B. henselae, 67 (22.6%) patients were seroreactive and 40 (13.5%) had positive PCR results. Of these 40 patients, only 7 (17.5%) were concurrently B. henselae seroreactive, whereas 33 (82.5%) patients who had a positive PCR result were not seroreactive to B. henselae antigens. There was no association between B. henselae antibodies and bacteremia (p = 0.37).

For B. koehlerae, 89 (30.1%) patients were seroreactive and 54 (18.2%) had positive PCR results. Of these 54 patients, 24 (44.4%) were seroreactive to B. koehlerae by IFA assay, whereas 29 (53.6%) were not seroreactive to B. koehlerae antigens. One patient with a positive B. koehlerae PCR result did not have a concurrent IFA test result (serum not submitted). There was an association between B. koehlerae seroreactivity and bacteremia (p = 0.008); seroreactive patients were more likely to be infected (odds ratio [OR] 2.25 [1.22–4.15]).

For B. vinsonii subsp. berkhoffii, 148 (50.0%) patients were seroreactive by IFA testing to at least 1 of 3 genotypes, and 10 (3.4%) had a positive PCR. Of these 10 patients, 3 were infected with genotype I, 6 were infected with genotype II, and for 1 patient the genotype could not be defined on the basis of readable DNA sequence. Seroreactivity to genotypes I, II, and III was found for 77 (26.0%), 102 (34.5%), and 82 (27.7%) patients, respectively. There was no association between B. vinsonii subsp. berkhoffii seroreactivity and bacteremia. Combined PCR and IFA assay results are summarized in Table 2. Of the patients with a positive PCR, 65% reported a prior diagnosis of Lyme disease (n = 138), bartonellosis (n = 29), or babesiosis (n = 14). Among the 138 patients with a prior diagnosis of Lyme disease, the prevalence of Bartonella spp. antibodies and bacteremia were 93 (67.4%) and 57 (41.3%), respectively.

Factors Associated with Bartonella spp.

PCRs indicated the following: B. henselae positivity was associated (p<0.05) with blurred vision and numbness (Table 3), patients who had visited a neurologist were more likely than those who had not to be B. henselae positive, older median age was significantly associated with B. koehlerae positivity, and patients who reported paralysis were more likely to be positive for B. vinsonii subsp. berkhoffii. No associations were found for self-reported exposures (e.g., insect or animal exposure) and positive PCR for B. henselae, B. koehlerae, or B. vinsonii subsp. berkhoffii. No associations were found for B. henselae, B koehlerae, or B vinsonii subsp. berkhoffii positivity and seroreactivity.

Logistic Regression Analysis

To identify factors associated with PCR positivity for B. henselae or B. koehlerae, we adjusted the models for 3 biological confounders: age, sex, and health status (Table 4). We identified the following factors as associated with B. henselae–positive PCR result: blurred vision (adjusted OR [aOR] 2.37, 95% CI 1.13–4.98), numbness (aOR 2.74, 95% CI 1.26–5.96), and previous consultation with a neurologist (aOR 2.76, 95% CI 1.33–5.73). No self-reported symptoms were significantly associated with PCR positivity for B. koehlerae. However, patients who had visited an infectious disease physician were more likely to have a. B. koehlerae–positive PCR result (aOR 1.98, 95% CI 1.05–3.75).

Discussion

We identified unexpectedly high serologic and molecular prevalence for B. henselae, B. koehlerae, and B. vinsonii subsp. berkhoffii in patients who had been examined by a rheumatologist, of whom more than half reported a prior diagnosis of Lyme disease, bartonellosis, or babesiosis. However, the diagnostic criterion upon which these infections were based was not available for review because all prior diagnoses were self-reported. Overall, 185 (62.5%) of 296 patients had antibodies to B. henselae, B. koehlerae, or B. vinsonii subsp. berkhoffii, and 122 (41.1%) were positive for Bartonella spp. according to PCR. In most instances, DNA sequencing of the amplified product facilitated identification of the infecting species. The prevalence of antibodies against Bartonella spp. (93 [67.4%]) and bacteremia [57 [1.3%]) among 138 patients with a prior diagnosis of Lyme disease did not differ from that of the overall study population. Because our analysis was restricted to patients selected by a rheumatologist practicing in a Lyme disease–endemic region, extrapolations to other regions or other rheumatology practices might not be applicable. Also, because the survey was self-administered, objective confirmation of symptoms, conditions, and diagnoses was not always possible; therefore, responses might have been subject to respondent bias. Similarly, because responses associated with symptoms, conditions, and exposures might have occurred over a protracted time, survey responses might also be subject to recall bias.


Despite these study limitations, B. henselae infections seemed to be more common in patients who reported blurred vision, numbness in the extremities, and previous consultation with a neurologist before referral to the rheumatologist. In a case series of 14 patients, the following were reported by 50% of patients infected with a Bartonella species, specifically B. henselae, B. vinsonii subsp. berkhoffii, or both: memory loss, numbness or a loss of sensation, balance problems, and headaches (10). Another 6 B. henselae–bacteremic patients reported seizures, ataxia, memory loss, and/or tremors; 1 of these patients was co-infected with B. vinsonii subsp. berkhoffii, and another was positive for B. henselae by PCR after enrichment of cerebrospinal fluid in BAPGM (23). An enrichment culture approach also identified an association between intravascular infection with B. vinsonii subsp. berkhoffii genotype II and B. henselae and neurologic symptoms in a veterinarian and his daughter (12). Symptoms in the father included progressive weight loss, muscle weakness, and lack of coordination; symptoms in the daughter were headaches, muscle pain, and insomnia. For each patient, after repeated courses of antimicrobial drugs, blood cultures became negative, antibody titers decreased to nondetectable levels, and all neurologic symptoms resolved.

Although no symptoms were statistically associated with B. koehlerae infection, patients infected with B. koehlerae were more likely to have previously consulted an infectious disease physician. Of the 54 B. koehlerae patients with a positive PCR result, 54% reported a prior diagnosis of Lyme disease (n = 25), bartonellosis (n = 3), or babesiosis (n = 1). Fatigue, insomnia, memory loss, and joint and muscle pain were frequent complaints among those with a positive PCR result for B. koehlerae, but these symptoms did not differ in frequency from those in patients with negative PCR. Similar symptoms were previously reported in a small case series involving B. koehlerae–bacteremic patients (13). Peripheral visual deficits, sensory loss, and hallucinations resolved in a young woman after antimicrobial drug treatment for B. koehlerae infection (30). Because of the small number of patients with positive PCR results for B. vinsonii subsp. berkhoffii, we restricted the multivariate analysis to those with positive results for B. henselae and B. koehlerae. Because limited sample size affected our ability to conduct multivariate analysis to control for potential confounders for B. vinsonii subsp. berkhoffii positivity, the χ2 associations with B. vinsonii subsp. berkhoffii positivity should be interpreted with caution.

Although the pathogenic relevance of the high Bartonella spp. seroprevalence and bacteremia in this patient population are unclear, these results justify additional prospective studies involving more narrowly defined patient and control populations. Of the 92 patients infected with B. koehlerae, B. henselae, or B. vinsonii subsp. berkhoffi, 69 (75%) had at least 1 discordant IFA assay result for Bartonella spp. antigen seroreactivity and only 34 (30.6%) had a concordant species-specific PCR and IFA result. Also, consistent with previous study findings (15), the PCRs depicted in Figure 2 illustrate an increased likelihood of positivity if blood, serum, and enrichment blood cultures are independently tested. According to these and previous results (7,18,31,32), a subset of Bartonella spp.–bacteremic patients could be anergic and might not produce a detectable IFA response, or alternatively, the substantial antigenic variation among various Bartonella strains might result in false-negative IFA assay results for some patients. In a study on Bartonella serology conducted by the Centers for Disease Control and Prevention, IFA cross-reactivity among Bartonella species occurred in 94% of patients with suspected cat-scratch disease (33). Despite the lack of concordance between serologic results and BAPGM enrichment PCR results, most (185 [62.5%]) patients in our study were seroreactive to Bartonella spp., suggesting prior exposure to >1 Bartonella spp. Because serologic cross-reactivity to Chlamydia spp. and Coxiella burnettii antigens has been reported, exposure to these or other organisms might have contributed to the high seroprevalence. In a previous study involving 32 healthy volunteers and patients at high risk for Bartonella spp. bacteremia, seroprevalence rates for B. henselae, B. koehlerae and B. vinsonii subsp. berkhoffii genotypes I and II were 3.1%, 0%, 0,%, and 50%, respectively, for the healthy population compared with 15.6%, 9.2%, 19.8%, and 28.1%, respectively, for the high-risk population (15). Although in that study and the study reported here, the same test antigens and identical IFA assays were used and the same research technologist interpreted the results, the overall seroprevalence in the study reported here was higher than that among high-risk patients with extensive arthropod or animal contact (49.5%) and differed substantially from serologic results from healthy volunteers (15). However, in the study reported here, a large portion of the population (34.5%) was also seroreactive to B. vinsonii berkhoffii genotype II. Immunophenotypic properties giving rise to seroreactivity to this particular antigen among healthy control and patient populations have not been clarified but could be related to polyclonal B-cell activation, commonly found in patients with rheumatologic or chronic inflammatory diseases.

It is becoming increasingly clear that no single diagnostic strategy will confirm infection with a Bartonella sp. in immunocompetent patients. Before the current study, we primarily used BAPGM enrichment blood cultures and PCR to test symptomatic veterinarians, veterinary technicians, and wildlife biologists, who seem to be at occupational risk for Bartonella sp. bacteremia because of animal contact and frequent arthropod exposure (10–15,23). Cats are the primary reservoir hosts for B. henselae and B. koehlerae, whereas canids, including dogs, coyotes and foxes, are the primary reservoir hosts for B. vinsonii subsp. berkhoffii (4,6,29,34). Although infrequent when compared with cat transmission of B. henselae resulting in classical cat-scratch disease, dogs have been implicated in the transmission of B. vinsonii subsp. berkhoffii and B. henselae to humans (35,36). The predominant symptoms reported among occupationally at-risk patient populations have included severe fatigue, neurologic and neurocognitive abnormalities, arthralgia, and myalgia (10–13,23). In the study reported here, dog (85%) and cat (68%) contact were reported by most respondents; however, no associations were found between infection with a Bartonella sp. and contact with a specific animal. Similarly, exposure to mosquitoes, ticks, fleas, and biting flies were all reported by >50% of the study population. The results of this study support documentation of Bartonella spp. bacteremia in patients seen by a rheumatologist in a Lyme disease–endemic area and provides the basis for future studies to ascertain the prevalence of Bartonella spp. in patients with rheumatic and neurologic symptoms.

Dr Maggi is a research assistant professor in the Department of Clinical Sciences at North Carolina State University College of Veterinary Medicine. His research has focused on the development of novel or improved molecular diagnostic and culture methods for detection of Bartonella spp. infections in animals and humans.

Acknowledgments

This study was supported in part by the state of North Carolina, a grant from the American College of Veterinary Internal Medicine Foundation, and a monetary donation from Bayer Animal Health.

E.B.B., in conjunction with Sushama Sontakke and North Carolina State University, holds US Patent No. 7,115,385, Media and Methods for Cultivation of Microorganisms, which was issued October 3, 2006. E.B.B. is chief scientific officer for Galaxy Diagnostics, a newly formed company that provides diagnostic testing for the detection of Bartonella species infection in animals and human patients. R.G. Maggi has lead research efforts to optimize the BAPGM platform and is the scientific technical advisor for Galaxy Diagnostics. R. Mozayeni was the attending physician for the patients described in this study and has recently joined Galaxy Diagnostics as the chief medical officer. All other authors have no potential conflicts.

References

Dehio C. Interactions of Bartonella henselae with vascular endothelial cells. Curr Opin Microbiol. 1999;2:78–82. DOIPubMed
Kordick DL, Breitschwerdt EB. Persistent infection of pets within a household with three Bartonella species. Emerg Infect Dis. 1998;4:325–8. DOIPubMed
Kosoy MY, Regnery RL, Tzianabos T, Marston EL, Jones DC, Green D, Distribution, diversity, and host specificity of Bartonella in rodents from the southeastern United States. Am J Trop Med Hyg. 1997;57:578–88.PubMed
Abbott RC, Chomel BB, Kasten RW, Floyd-Hawkins KA, Kikuchi Y, Koehler JE, Experimental and natural infection with Bartonella henselae in domestic cats. Comp Immunol Microbiol Infect Dis. 1997;20:41–51. DOIPubMed
Boulouis HJ, Chang CC, Henn JB, Kasten RW, Chomel BB. Factors associated with the rapid emergence of zoonotic Bartonella infections. Vet Res. 2005;36:383–410. DOIPubMed
Chomel BB, Boulouis HJ, Maruyama S, Breitschwerdt EB. Bartonella spp. in pets and effect on human health. Emerg Infect Dis. 2006;12:389–94. DOIPubMed
Jendro MC, Weber G, Brabant T, Zeidler H, Wollenhaupt J. Reactive arthritis after cat bite: a rare manifestation of cat scratch disease—case report and overview [in German]. Z Rheumatol. 1998;57:159–63. DOIPubMed
Chomel BB, Kasten RW, Sykes JE, Boulouis HJ, Breitschwerdt EB. Clinical impact of persistent Bartonella bacteremia in humans and animals. Ann N Y Acad Sci. 2003;990:267–78. DOIPubMed
Rolain JM, Brouqui P, Koehler JE, Maguina C, Dolan MJ, Raoult D. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother. 2004;48:1921–33. DOIPubMed
Breitschwerdt EB, Maggi RG, Duncan AW, Nicholson WL, Hegarty BC, Woods CW. Bartonella species in blood of immunocompetent persons with animal and arthropod contact. Emerg Infect Dis. 2007;13:938–41.PubMed
Breitschwerdt EB, Maggi RG, Farmer P, Mascarelli PE. Molecular evidence of perinatal transmission of Bartonella vinsonii subsp. berkhoffii and Bartonella henselae to a child. J Clin Microbiol. 2010;48:2289–93. DOIPubMed
Breitschwerdt EB, Maggi RG, Lantos PM, Woods CW, Hegarty BC, Bradley JM. Bartonella vinsonii subsp. berkhoffii and Bartonella henselae bacteremia in a father and daughter with neurological disease. Parasites & Vectors. 2010;3:29. DOIPubMed
Breitschwerdt EB, Maggi RG, Mozayeni BR, Hegarty BC, Bradley JM, Mascarelli PE. PCR amplification of Bartonella koehlerae from human blood and enrichment blood cultures. Parasites & Vectors. 2010;3:76. DOIPubMed
Breitschwerdt EB, Maggi RG, Varanat M, Linder KE, Weinberg G. Isolation of Bartonella vinsonii subsp. berkhoffii genotype II from a boy with epithelioid hemangioendothelioma and a dog with hemangiopericytoma. J Clin Microbiol. 2009;47:1957–60. DOIPubMed
Maggi RG, Mascarelli PE, Pultorak EL, Hegarty BC, Bradley JM, Mozayeni BR, Bartonella spp. bacteremia in high-risk immunocompetent patient. Diagn Microbiol Infect Dis. 2011;71:430–7. DOIPubMed
Al-Matar MJ, Petty RE, Cabral DA, Tucker LB, Peyvandi B, Prendiville J, Rheumatic manifestations of Bartonella infection in 2 children. J Rheumatol. 2002;29:184–6.PubMed
Giladi M, Maman E, Paran D, Bickels J, Comaneshter D, Avidor B, Cat-scratch disease–associated arthropathy. Arthritis Rheum. 2005;52:3611–7. DOIPubMed
Hayem F, Chacar S, Hayem G. Bartonella henselae infection mimicking systemic onset juvenile chronic arthritis in a 2½-year-old girl. J Rheumatol. 1996;23:1263–5.PubMed
Maman E, Bickels J, Ephros M, Paran D, Comaneshter D, Metzkor-Cotter E, Musculoskeletal manifestations of cat scratch disease. Clin Infect Dis. 2007;45:1535–40. DOIPubMed
Tsukahara M, Tsuneoka H, Tateishi H, Fujita K, Uchida M. Bartonella infection associated with systemic juvenile rheumatoid arthritis. Clin Infect Dis. 2001;32:E22–3. DOIPubMed
Dillon B, Cagney M, Manolios N, Iredell JR. Failure to detect Bartonella henselae infection in synovial fluid from sufferers of chronic arthritis. Rheumatol Int. 2000;19:219–22. DOIPubMed
Breitschwerdt EB, Suksawat J, Chomel B, Hegarty BC. The immunologic response of dogs to Bartonella vinsonii subspecies berkhoffii antigens: as assessed by Western immunoblot analysis. J Vet Diagn Invest. 2003;15:349–54. DOIPubMed
Breitschwerdt EB, Maggi RG, Nicholson WL, Cherry NA, Woods CW. Bartonella sp. bacteremia in patients with neurological and neurocognitive dysfunction. J Clin Microbiol. 2008;46:2856–61. DOIPubMed
Diniz PP, Maggi RG, Schwartz DS, Cadenas MB, Bradley JM, Hegarty B, Canine bartonellosis: serological and molecular prevalence in Brazil and evidence of co-infection with Bartonella henselae and Bartonella vinsonii subsp. berkhoffii. Vet Res. 2007;38:697–710. DOIPubMed
Duncan AW, Maggi RG, Breitschwerdt EB. A combined approach for the enhanced detection and isolation of Bartonella species in dog blood samples: pre-enrichment liquid culture followed by PCR and subculture onto agar plates. J Microbiol Methods. 2007;69:273–81. DOIPubMed
Maggi RG, Duncan AW, Breitschwerdt EB. Novel chemically modified liquid medium that will support the growth of seven Bartonella species. J Clin Microbiol. 2005;43:2651–5. DOIPubMed
Cadenas MB, Bradley J, Maggi RG, Takara M, Hegarty BC, Breitschwerdt EB. Molecular characterization of Bartonella vinsonii subsp. berkhoffii genotype III. J Clin Microbiol. 2008;46:1858–60. DOIPubMed
Maggi RG, Breitschwerdt EB. Potential limitations of the 16S–23S rRNA intergenic region for molecular detection of Bartonella species. J Clin Microbiol. 2005;43:1171–6. DOIPubMed
Maggi RG, Chomel B, Hegarty BC, Henn J, Breitschwerdt EB. A Bartonella vinsonii berkhoffii typing scheme based upon 16S–23S ITS and Pap31 sequences from dog, coyote, gray fox, and human isolates. Mol Cell Probes. 2006;20:128–34. DOIPubMed
Breitschwerdt EB, Mascarelli PE, Schweickert LA, Maggi RG, Hegarty BC, Bradley JM, Hallucinations, sensory neuropathy, and peripheral visual deficits in a young woman infected with Bartonella koehlerae. J Clin Microbiol. 2011;49:3415–7. DOIPubMed
Diniz PP, Wood M, Maggi RG, Sontakke S, Stepnik M, Breitschwerdt EB. Co-isolation of Bartonella henselae and Bartonella vinsonii subsp. berkhoffii from blood, joint and subcutaneous seroma fluids from two naturally infected dogs. Vet Microbiol. 2009;138:368–72. DOIPubMed
Jones SL, Maggi R, Shuler J, Alward A, Breitschwerdt EB. Detection of Bartonella henselae in the blood of 2 adult horses. J Vet Intern Med. 2008;22:495–8. DOIPubMed
Dalton MJ, Robinson LE, Cooper J, Regnery RL, Olson JG, Childs JE. Use of Bartonella antigens for serologic diagnosis of cat-scratch disease at a national referral center. Arch Intern Med. 1995;155:1670–6. DOIPubMed
Breitschwerdt EB, Kordick DL. Bartonella infection in animals: carriership, reservoir potential, pathogenicity, and zoonotic potential for human infection. Clin Microbiol Rev. 2000;13:428–38. DOIPubMed
Keret D, Giladi M, Kletter Y, Wientroub S. Cat-scratch disease osteomyelitis from a dog scratch. J Bone Joint Surg Br. 1998;80:766–7. DOIPubMed
Tsukahara M, Tsuneoka H, Iino H, Ohno K, Murano I. Bartonella henselae infection from a dog. Lancet. 1998;352:1682. DOIPubMed

Figures

Figure 1. . . Bartonella spp. PCR results for the 15 most frequently reported previous diagnoses. OA, osteoarthritis; RA, rheumatoid arthritis.
Figure 2. . . Bartonella PCR amplification results from blood, serum, and enrichment blood culture with the Bartonella α Proteobacteria growth medium. Of 296 patients, 120 had positive PCR results in...

Tables

Table 1. Characteristics and Bartonella spp. PCR results for 296 patients examined by a rheumatologist, Maryland–Washington, DC, USA, August 25, 2008–April 1, 2009
Table 2. Test results for Bartonella spp. in 296 patients examined by a rheumatologist, Maryland–Washington, DC, USA, August 25, 2008–April 1, 2009
Table 3. Factors associated with Bartonella spp. positivity by PCR, among 296 patients examined by a rheumatologist, Maryland–Washington, DC, USA, August 25, 2008–April 1, 2009
Table 4. Factors associated with positive PCR result for Bartonella henselae and B. koehlerae among 296 patients examined by a rheumatologist, Maryland–Washington, DC, USA, August 25, 2008–April 1, 2009
Suggested citation for this article: Maggi RG, Mozayeni BR, Pultorak EL, Hegarty BC, Bradley JM, Correa M, et al. Bartonella spp. bacteremia and rheumatic symptoms in patients from Lyme disease–endemic region. Emerg Infect Dis [serial on the Internet]. 2012 May [date cited]. http://dx.doi.org/10.3201/eid1805.111366

DOI: 10.3201/eid1805.111366

RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: Bartonella Bacteremia

Post by RitaA » Mon 23 Apr 2012 9:07

Bartonella seems to be getting a lot of attention these days:

http://www.ncbi.nlm.nih.gov/pubmed/22229763
FEMS Microbiol Rev. 2012 May;36(3):563-99. doi: 10.1111/j.1574-6976.2012.00324.x. Epub 2012 Feb 7.

Persistence of Bartonella spp. stealth pathogens: from subclinical infections to vasoproliferative tumor formation.

Pulliainen AT, Dehio C.

Source

Institute of Biomedicine, University of Turku, Turku, Finland.

Abstract

Bartonella spp. are facultative intracellular bacteria that typically cause a long-lasting intraerythrocytic bacteremia in their mammalian reservoir hosts, thereby favoring transmission by blood-sucking arthropods. In most cases, natural reservoir host infections are subclinical and the relapsing intraerythrocytic bacteremia may last weeks, months, or even years. In this review, we will follow the infection cycle of Bartonella spp. in a reservoir host, which typically starts with an intradermal inoculation of bacteria that are superficially scratched into the skin from arthropod feces and terminates with the pathogen exit by the blood-sucking arthropod. The current knowledge of bacterial countermeasures against mammalian immune response will be presented for each critical step of the pathogenesis. The prevailing models of the still-enigmatic primary niche and the anatomical location where bacteria reside, persist, and are periodically seeded into the bloodstream to cause the typical relapsing Bartonella spp. bacteremia will also be critically discussed. The review will end up with a discussion of the ability of Bartonella spp., namely Bartonella henselae, Bartonella quintana, and Bartonella bacilliformis, to induce tumor-like vascular deformations in humans having compromised immune response such as in patients with AIDS.

© 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

PMID:
22229763
[PubMed - in process]

slmo
Posts: 8
Joined: Tue 10 Apr 2012 17:31

Re: Bartonella Bacteremia

Post by slmo » Sun 29 Apr 2012 12:05

Thank you for postng this information and data about Bartonella. I came to this forum tonight looking for something about Bartonella; all of my symptoms are consistent with the ones listed here. Doc prescribed me Doxy yesterday because my symptoms are clinically severe. I was dagnosed with Bartonella in 2007 after a cat bite. When I got the Lyme diagnosis in 2009, they did not test for any co-infections. Now years later I cannot feel my fingers or feet. My thoughts are that the double exposure has thrown my body for a loop. Does anyone else have experience to share with persistent Bartonella?

RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: Bartonella Bacteremia

Post by RitaA » Wed 27 Jun 2012 23:10

slmo,

I'm sorry to see you didn't get any responses to your post above. It's possible that no one here has been diagnosed with Bartonella and/or they aren't sure if Lyme disease (and possibly Babesiosis) might have been responsible for some (or all) of their symptoms. I have read elsewhere that Bartonella and Babesia infections are being diagnosed more frequently, so we're bound to hear more from both patients and researchers in the coming years. I'm posting these links in case you and/or others might be interested:

http://www.cvm.ncsu.edu/docs/personnel/ ... dt_ed.html
Research Area

Research Interests: Infectious diseases and immunology.

Dr. Breitschwerdt's research emphasis has been on vector-transmitted, intracellular pathogens. Since 1984, he has supervised a biosafety level P-3 research laboratory and co-supervised the Tick-transmitted Diagnostic Laboratory.
http://www.bayeranimalhealthsymposium.c ... erdt.shtml
Bartonellosis: A hidden epidemic

Edward B. Breitschwerdt, DVM, DACVIM
Center for Comparative Medicine and Translational Research and the Department of Clinical Sciences
College of Veterinary Medicine
North Carolina State University
Raleigh, N.C.

Introduction

Bartonella species are fastidious gram-negative bacteria that are highly adapted to a mammalian reservoir host, within which the bacteria usually cause a long-lasting intra-erythrocytic bacteremia.1-3 These facts are of particular importance to veterinarians and physicians as an increasing number of animal reservoir hosts have been identified for various Bartonella species, including many "pocket-pet" rodents.2 Before 1990 there were only two named Bartonella species; now there are at least 26 named and numerous unnamed or candidatus species.

Fleas play an important role in the transmission of B. henselae, B. clarridgeae, and most likely B. koehlerae among cats.1 In addition to fleas, an increasing number of arthropod vectors, including biting flies, keds, lice, sandflies, and ticks have been implicated in the transmission of Bartonella. Considering the diversity of species and subspecies, the large number of reservoir hosts, and the spectrum of arthropod vectors, the clinical and diagnostic challenges posed by Bartonella may be much more complex than currently appreciated in human and veterinary medicine.

In the natural reservoir host, such as a cat or rodent, chronic bacteremia with a Bartonella species can frequently be detected by blood culture or PCR in outwardly healthy animals.1-3 In contrast, the diagnostic detection of a Bartonella spp. in a nonreservoir-adapted host, such as a dog, horse, or human, can be extremely difficult.2,4 Most—but not all—diseases caused by Bartonella spp. occur in accidental hosts, and these organisms are being increasingly implicated as a cause of zoonotic infections.

[snip]

Cat scratch disease (CSD) in people

For over a century, regional lymphadenopathy has been associated with cat scratches.1 Several studies have identified seroreactivity to B. henselae antigens and Bartonella DNA (amplified using PCR) in people with suspected CSD.2 Subsequently, Bartonella species have been cultured from all but two cats owned by a group of 14 patients with cat scratch disease, indicating that bacteremia is a frequent occurrence in cats that transmit B. henselae to people.2

With the advent of specific diagnostic techniques, such as culture, serology, and PCR, there has been a dramatic increase in reports describing patients with "atypical" manifestations of CSD. Osteomyelitis, granulomatous hepatitis, and granulomatous splenitis have been increasingly recognized in children infected with B. henselae who frequently lack the classical lymphadenopathy of CSD. As evidenced by reports over the past four years, the spectrum of human disease associated with the genus Bartonella continues to expand, requiring periodic reassessment as new information becomes available.4-8

Some patients deny the possibility of a cat scratch or bite wound, or indicate no contact with cats. Transmission from environmental sources, arthropod vectors, perinatally, by blood transfusion, needle stick, or other animal hosts is probable in these cases.

[snip]

Therapy

To date, an optimal protocol has not been established for the treatment of Bartonella infections in cats, dogs, or people.2 Regardless of the antibiotic used for treatment, a long duration of antibiotic administration (e.g., six weeks) may be necessary to eliminate the infection. Fluoroquinolones alone or in combination with amoxicillin have elicited a positive therapeutic response in dogs, which is accompanied by a progressive decrease in B. vinsonii antibody titers. Newer macrolides, or semi-synthetic derivatives of erythromycin, obtain high intracellular concentrations. However, B. henselae rapidly develops resistance to azithromycin, so these antibiotics should not be used as a sole treatment.2 Doxycycline alone may or may not be effective for treatment of B. vinsonii subsp. berkhoffii, and data from cats experimentally or naturally infected with B. henselae or B. clarridgeae indicate that a high dose of doxycycline (10 mg/kg every 12 hours) for four to six weeks may be necessary to eliminate Bartonella infection in dogs, cats, or other animal species.2 With treatment, serum antibody titers decrease rapidly (three to six months) and are generally no longer detectable in dogs that recover following antimicrobial therapy. Therefore, if antibodies are detectable pre-treatment, post-treatment serology may be a useful adjunct to BAPGM/PCR to determine if therapeutic elimination of Bartonella infections has been achieved.

Prevention and public health considerations

Increasingly, veterinarians play an important role in advising the public as to the epidemiological and zoonotic implications associated with vector-borne pathogens. Minimizing or eliminating flea and tick exposure is perhaps of greater veterinary and public health importance today than during any time in history. When rigorous flea and tick control measures are instituted, it is highly probable that transmission of Bartonella species will be greatly reduced or eliminated.

Veterinary professionals appear to have an occupational risk of infection because of extensive contact with a spectrum of animal species and frequent exposure to Bartonella spp. Therefore, these individuals should exercise increased precautions to avoid arthropod bites, arthropod feces (i.e., fleas and lice), animal bites or scratches, and direct contact with bodily fluids from sick animals. A substantial number of diagnostic biological samples collected on a daily basis in veterinary practices could contain viable bacteria.2,4-8 The increasing number of defined Bartonella spp. in conjunction with the high level of bacteremia found in reservoir-adapted hosts, which represent the veterinary patient population, ensures that all veterinary professionals will experience frequent and repeated exposure to animals harboring these bacteria. Consequently, personal protective equipment, frequent hand washing, and avoiding cuts and needle sticks have become more important as our knowledge of this genus has improved and various modes of transmission have been defined.

Physicians should be educated as to the large number of Bartonella spp. in nature, the extensive spectrum of animal reservoir hosts, the diversity of confirmed and potential arthropod vectors, current limitations associated with diagnosis and treatment efficacy, and the ecological and evolving medical complexity of these highly evolved bacteria.

References

1. Chomel BB, Boulouis HJ, Breitschwerdt EB, et al. Ecological fitness and strategies of adaptation of Bartonella species to their hosts and vectors. Vet Res 2009;40:29.

2. Breitschwerdt EB, RG Maggi, BB Chomel, et al. Bartonellosis: An emerging infectious disease of zoonotic importance to animals and human beings. J Vet Emerg Crit Care (San Antonio) 2010;20:8-30.

3. Chomel BB, Kasten RW, Williams C, et al. Bartonella endocarditis: a pathology shared by animal reservoirs and patients. Ann N Y Acad Sci 2009;1166:120-126.

4. Breitschwerdt EB, Maggi RG, Nicholson WL, et al. Bartonella sp. bacteremia in patients with neurological and neurocognitive dysfunction. J Clin Microbiol 2008;46:2856-2861.

5. Breitschwerdt EB, Maggi RG, Lantos PM, et al. Bartonella vinsonii subsp. berkhoffii and Bartonella henselae bacteremia in a father and daughter with neurological disease. Parasit Vectors 2010;3:29.

6. Breitschwerdt EB, Maggi RG, Farmer P, et al. Molecular evidence of perinatal transmission of Bartonella vinsonii subsp. berkhoffii and Bartonella henselae to a child. J Clin Microbiol 2010;48:2289-2293.

7. Breitschwerdt EB, Maggi RG, Mozayeni BR, Bradley JM, Hegarty BC, Mascarelli PE. Isolation or PCR amplification of Bartonella koehlerae from human blood. Parasit Vectors 2010; 3: 76.

8. Oliveira AM, RG Maggi, CW Woods, et al. Putative needle stick transmission of Bartonella vinsonii subsp. berkhoffii to a veterinarian. J Vet Intern Med: 2010; 24:1229-1232.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2546763/
Clin Microbiol. 2008 September; 46(9): 2856–2861.

Published online 2008 July 16. doi: 10.1128/JCM.00832-08

PMCID: PMC2546763

Bartonella sp. Bacteremia in Patients with Neurological and Neurocognitive Dysfunction

E. B. Breitschwerdt,1,* R. G. Maggi,1 W. L. Nicholson,2 N. A. Cherry,1 and C. W. Woods3
Intracellular Pathogens Research Laboratory, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina,1 Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta, Georgia,2 Duke University Medical Center, Durham, North Carolina3
*Corresponding author. Mailing address: College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough St., Raleigh, NC 27606. Phone: (919) 513-8277. Fax: (919) 513-6226. E-mail: ed_breitschwerdt@ncsu.edu

Abstract

We detected infection with a Bartonella species (B. henselae or B. vinsonii subsp. berkhoffii) in blood samples from six immunocompetent patients who presented with a chronic neurological or neurocognitive syndrome including seizures, ataxia, memory loss, and/or tremors. Each of these patients had substantial animal contact or recent arthropod exposure as a potential risk factor for Bartonella infection. Additional studies should be performed to clarify the potential role of Bartonella spp. as a cause of chronic neurological and neurocognitive dysfunction.

[the full article is available here]
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165616/
J Clin Microbiol. 2011 September; 49(9): 3415–3417.
doi: 10.1128/JCM.00833-11
PMCID: PMC3165616

Hallucinations, Sensory Neuropathy, and Peripheral Visual Deficits in a Young Woman Infected with Bartonella koehlerae

Edward B. Breitschwerdt,1,* Patricia E. Mascarelli,1 Lori A. Schweickert,2 Ricardo G. Maggi,1 Barbara C. Hegarty,1 Julie M. Bradley,1 and Christopher W. Woods3
1Intracellular Pathogens Research Laboratory, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina
23C Family Services, Cary, North Carolina
3Duke University School of Medicine, Durham, North Carolina
*Corresponding author. Mailing address: North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606., Phone: (919) 513-8277. Fax: (919) 513-6336. E-mail: ed_breitschwerdt@ncsu.edu .

Abstract

A young woman experiencing depression, anxiety, mood swings, severe headaches, muscle spasms, interphalangeal joint stiffness, decreased peripheral vision, diminished tactile sensation, and hallucinations was persistently Bartonella koehlerae seroreactive and bacteremic. Following antibiotic treatment, B. koehlerae antibodies and DNA were not detected and all symptoms resolved.

[snip]

[the rest of the article is available here]

With the advent of B. henselae serology, PCR, and improved enrichment culture techniques, case studies are suggesting an important and expanding role for Bartonella sp. infection in patients with memory loss, expressive aphasia, word substitution errors, and impaired repetition (3, 4, 10). In our patient, there was a decrease in hallucination frequency following the initial course of antibiotics and total resolution of the hallucinations and visual field deficits following the third course of antibiotics while on a stable dose of antipsychotic medication. We conclude that this constellation of symptoms should raise the index of clinical suspicion for Bartonella infection.

User avatar
inmacdonald
Posts: 978
Joined: Fri 13 Jan 2012 22:32

Re: Bartonella Bacteremia

Post by inmacdonald » Sat 30 Jun 2012 16:44

Persistence of Bartonella in the Endothelium - a Mechanism

http://www.pnas.org/content/109/24/9581.abstract



Bacterial effector binds host cell adenylyl cyclase to potentiate Gαs-dependent cAMP production


Abstract

Subversion of host organism cAMP signaling is an efficient and widespread mechanism of microbial pathogenesis. Bartonella effector protein A (BepA) of vasculotumorigenic Bartonella henselae protects the infected human endothelial cells against apoptotic stimuli by elevation of cellular cAMP levels by an as yet unknown mechanism. Here, adenylyl cyclase (AC) and the α-subunit of the AC-stimulating G protein (Gαs) were identified as potential cellular target proteins for BepA by gel-free proteomics. Results of the proteomics screen were evaluated for physical and functional interaction by: (i) a heterologous in vivo coexpression system, where human AC activity was reconstituted under the regulation of Gαs and BepA in Escherichia coli; (ii) in vitro AC assays with membrane-anchored full-length human AC and recombinant BepA and Gαs; (iii) surface plasmon resonance experiments; and (iv) an in vivo fluorescence bimolecular complementation-analysis. The data demonstrate that BepA directly binds host cell AC to potentiate the Gαs-dependent cAMP production. As opposed to the known microbial mechanisms, such as ADP ribosylation of G protein α-subunits by cholera and pertussis toxins, the fundamentally different BepA-mediated elevation of host cell cAMP concentration appears subtle and is dependent on the stimulus of a G protein-coupled receptor-released Gαs. We propose that this mechanism contributes to the persistence of Bartonella henselae in the chronically infected vascular endothelium.


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