You talking about the Babesia/Bartonella Symptom Questionnaire at the top of this thread? If so, I was given this list by one of my LLMD's during an office visit. Months later, I later saw this same list published in Dr. K. Singleton's book, "The Lyme Disease Solution." Doc S was not the doctor who gave me this list by the way.
I posted a separate thread about a year ago which contains just the questionnaire. It's called the "Bartonella/Babesia Symptom Questionnaires." That particular post used to have a sticky on it but it was unstickied with a bunch of other threads after a few members complained of their being too many stickies at the top of the Medical Forum.
This article is called, "The Role of Bartonella spp. in Veterinary and Human Medicine With Special Emphasis on Pathogenicity Mechanisms," by V.A. J. Kempf, and F. Kramer. It was published in December, 2008 in EJCAP.
It contains some photos photos of Bartonella rashes and has a great chart listing different strains of bartonella, the reservoir and vectors for each strain, and the human diseases that the strains cause.
Fuzzy
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Macrolides are produced by Streptomyces erythreus. Their chemical structures contain large lactone rings linked through glycoside bonds with amino sugars.
Macrolides are inhibitors of protein synthesis. They are effective against Gram-positive bacteria and most Gram-negative bacteria, Neissera, Legionella, and Haemophilus, but not Enterobacteriaceae. The most important macrolides are:
*
Erythromycin *
Oleandomycin
question-
effective against "most" gram negative bacteria?
What KIND of gram negative bacteria is bartonella specifically? (Neissera, Legionella, Haemophilus, OR Enterobacteriaceae??
I have a BAD case of bart, and am trying to beat the bart load down w/ some biaxin before rifampin, but am wondering how effective biaxin is for bart?
I don't care what doctors said what, I am curious to know what kind of gram negative bacteria bartonella specifically is, in order to effectively choose antibiotics.
anyone?
THANKS
-D
-------------------- "Experience is not what happens to you; it is what you do with what happens to you."
I don't know about Biaxin and I haven't tried Rifampin yet. I've had some success using Bactrim, but have found this antibiotic difficult because I have the MTHFR C677T genetic variant, which makes handling drugs which affect folate absorption a challenge.
I am seeing alot of results with Factive. It's still early days with this therapy, so I can't speak to whether it will deal with my Bart infection completely.
I'm not a microbiologist and don't have a scientific background, but my understanding is that Bartonella is a proteobacterium. It's also a gram negative bacterium (bacillus). I think this classification stands for all spp. (species) in the class of Bartonella genus or family. This includes Bartonella Henselae, Bartonella Quintana, etc.
Fuzzy
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I forgot to include this for you, D. This info was linked awhile ago in this thread, but I'll paste it here again. I hope it helps.
The article is titled, "Recommendations for Treatment of Human Infections Caused by Bartonella Species," by J. M. Rolain,1 P. Brouqui,1,2 J. E. Koehler,3 C. Maguina,4 M. J. Dolan,5 and D. Raoult1,2*
Members of the genus Bartonella are facultative intracellular bacteria belonging to the alpha 2 subgroup of the class Proteobacteria and are phylogenetically closely related to Brucella species (15, 73). Until 1993, only three diseases were known to be caused by Bartonella species: Carrion's disease (Bartonella bacilliformis), trench fever (Bartonella quintana), and cat scratch disease (CSD; Bartonella henselae). The genus now comprises B. bacilliformis, species of the former genera Rochalimea and Grahamella (14, 18), and additional, recently described species (Table 1). In mammals, each Bartonella species is highly adapted to its reservoir host; the bacteria can persist in the bloodstream of the host as the result of intraerythrocytic parasitism (49). Intraerythrocytic localization of B. henselae has been demonstrated in cat erythrocytes (88), and B. bacilliformis bacilli have been observed within erythrocytes during the acute phase of Carrion's disease (Oroya fever) (88). Bartonellae also have a tropism for endothelial cells, and intracellular B. henselae can be identified in endothelial cells infected in vitro (28), although intraendothelial cell bacilli have not been identified in vivo.
Bartonella species cause long-recognized diseases, such as Carrion's disease, trench fever, and CSD, and more recently recognized diseases, such as bacillary angiomatosis (BA), peliosis hepatis (PH), chronic bacteremia, endocarditis, chronic lymphadenopathy, and neurological disorders (Table 2) (73). A remarkable feature of the genus Bartonella is the ability of a single species to cause either acute or chronic infection and either vascular proliferative or suppurative manifestations.
The pathological response to infection with Bartonella spp. varies substantially with the status of the host immune system. Indeed, infection with the same Bartonella species (e.g., B. henselae) can result in a focal suppurative reaction (CSD in immunocompetent patients), a multifocal angioproliferative response (BA in immunocompromised patients), endovascular multiplication of the bacteria (endocarditis), or an exaggerated inflammatory response without evidence of bacteria in patient tissues (meningoencephalitis) (86).
Some of the diseases due to Bartonella species can resolve spontaneously without treatment, but in other cases, the disease is fatal without antibiotic treatment and/or surgery. The clinical situations are so different that a single treatment for all Bartonella-related diseases has not been identified, and the approach to treatment must be adapted to each species and clinical situation (49). Moreover, the database of clinical studies with a standard case definition, culture confirmation, rigidly defined disease outcomes, and patients with similar host defenses is very limited. Thus, case reports with a very limited number of subjects often serve to dictate therapy. The objective of this minireview is to summarize the antibiotic treatment recommendations for the different infections caused by Bartonella species. We have compiled the in vitro antibiotic susceptibility data and our knowledge of the in vivo efficacies of antibiotics for each clinical manifestation, and finally, we have summarized and ranked our treatment recommendations according to the Infectious Diseases Society of America (IDSA) practice guidelines (see Table 5) (51).
ANTIBIOTIC SUSCEPTIBILITIES OF BARTONELLA SPECIES
Culture of Bartonella spp. Because Bartonella spp. are facultative intracellular organisms, isolation can be performed in either cell cultures or axenic media with blood-enriched agar plates (63) (Fig. 1 and 2). However, Bartonella bacteria are very fastidious, and primary isolation is difficult, with detection of colonies only after 1 to 4 weeks of incubation on blood agar plates (63). The growth of subcultured isolates on blood agar plates is more rapid, usually yielding colonies after 3 to 5 days. Cell coculture systems have been reported to be more sensitive and allow more rapid growth of bartonellae than blood agar plates (63). Since 1992, several studies have reported on the isolation of B. henselae from the blood and lymph nodes of patients with CSD, with confirmation by serology, PCR, or culture (9, 71). However, isolation of B. henselae from the lymph nodes of CSD patients is very rare compared to the more frequent detection of B. henselae DNA in these patients by PCR assays (63, 109). At present, there is no optimal procedure for the isolation of Bartonella species; rather, several techniques and agars (e.g., cocultivation with eukaryotic cells, in addition to plating onto rabbit blood and chocolate agars) should be combined in order to isolate strains.
In vitro susceptibilities of Bartonella species to antibiotics. The results of susceptibility testing with Bartonella spp. are summarized in Table 3. Evaluation of susceptibilities to antibiotics has been performed either in the presence of eukaryotic cells or without cells, i.e., in axenic media. Use of these different methods of culture for the determination of the bacteriostatic activities of antibiotics yielded similar results. Determination of antibiotic susceptibility in axenic media has been carried out either with solid media enriched with 5 to 10% sheep or horse blood or with liquid media (74, 97). It should be noted that the conditions required to grow Bartonella during susceptibility testing do not meet the standardized criteria established by NCCLS. Bacteria of the genus Bartonella are susceptible to many antibiotics when they are grown axenically, including penicillin and cephalosporin compounds, aminoglycosides, chloramphenicol, tetracyclines, macrolide compounds, rifampin, fluoroquinolones, and co-trimoxazole (74, 79). However, the in vitro and the in vivo antibiotic susceptibilities of Bartonella do not correlate well for a number of antibiotics; for instance, penicillin has no in vivo efficacy, despite the very low MICs observed in vitro.
In vitro antibiotic susceptibilities of Bartonella species cocultivated with eukaryotic cells have also been examined. As with agar-based susceptibilities, these studies demonstrated that Bartonella spp. are susceptible to many antibiotics in vitro (46). However, all of these antibiotics (48) had only bacteriostatic activity (47, 48). It was recently demonstrated in vitro that aminoglycosides alone are bactericidal against Bartonella species grown either in liquid medium (91) or in endothelial cells (78). With a recently established erythrocyte coculture model, it was found that most of the antibiotics tested (i.e., doxycycline, fluoroquinolone compounds, and beta-lactams) were not bactericidal against Bartonella (90). Gentamicin was bactericidal at 4 �g/ml, as was rifampin. At this concentration, gentamicin was shown to enter erythrocytes slowly and to reach a peak level of 0.26 �g/ml after 24 h. However, when the ability of gentamicin to kill extraerythrocytic B. quintana at the concentration of 0.26 �g/ml achieved in the erythrocyte was tested, it was found that gentamicin was not bactericidal, even after 96 h of incubation (90). We hypothesize that erythrocytes may be a reservoir for B. quintana and that the bactericidal activity of gentamicin that was observed occurs mainly when the bacteria emerge from the erythrocytes and are found extracellularly.
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^ for anyone interested.
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Tracy9
Frequent Contributor (1K+ posts)
Member # 7521
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Thanks for bumping this up, it's a GREAT thread, and now that I am finally experiencing the hell of Bart treatment, I appreciate all of Fuzzy's and everyone else's efforts.
I know several of us right now are going through the torturous Rifampin treatment.
I have a question; I have experienced all the horrors of Bart mainly since starting to treat it. Does the Rifampin bring it out of hiding? Is it toxins dying off?
I feel I should know the answer, but what exactly IS it that makes us feel so much worse when we suddenly start treating? I never had all the symptoms of Bart until I swallowed the darned Rifampin...then it was a textbook list of symptoms hitting me!
13 years Lyme & Co.; Small Fiber Neuropathy; Myasthenia Gravis, Adrenal Insufficiency. On chemo for 2 1/2 years as experimental treatment for MG. Posts: 4480 | From Northeastern Connecticut | Registered: Jun 2005
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In my personal experience, I have found the literature pertaining to Bartonella infections to be frustratingly sparse in terms of what we can expect as patients during treatment. We can read about herxheimer reactions and/or drug reactions with plenty of other infections, such as MRSA, Mycoplasmas, Syphillis, and even Borrelia; however, the information about what to expect as far as herxheimer reactions during Bartonella treatment is hard to come by.
I guess our best resources will be our own LLMD's who have seen the progression of this disease, it's growth cycles, responses to treatment, first hand in their patients. And then, our next best resources will be talking with patients who've been through it.
Fuzzy
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BARTONELLA Over 20,000 cases of disease caused by the Bartonella family of bacteria occur each year in the United States. The most commonly known Bartonella infectious disease is ``cat scratch fever.'' Although most cases are due to flea bites from infested, infected animals; cat or dog bites or scratches may also directly cause the illness in humans.
Studies in recent years have found Bartonella and Bartonella-like microorganisms, which live inside cells, in some species of ticks. Scientists suspect that ticks may be transmitting Bartonella to humans in some cases. Further studies are needed.
Reported symptoms from suspected tick-borne Bartonella henselae may include unusual streaked rashes often recurring on the body, visual problems, fatigue with agitation, poor sleep, joint and muscle pain and stiffness, low grade fevers, sweats, headaches, recurring sore throat, lymph node enlargement, lower abdominal pain, ringing in the ears, anxiety, panic disorder, irritability, rage, seizure disorder, tremors, and other neurological problems.
Diagnosis is made clinically; antibody titers and PCR analysis may be helpful but are not always sensitive. Prescribed treatment is often quinolone and tetracycline.
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Excellent article by Dr. Edward B. Breitschwerdt, et. al., "A Groundhog, a Novel Bartonella Sequence, and My Father's Death," from CDC's publication, Emerging Infectious Diseases, Volume 15, Number 12-December 2009.
A Groundhog, a Novel Bartonella Sequence, and My Father's Death
Edward B. Breitschwerdt, Ricardo G. Maggi, Maria Belen Cadenas, and Pedro Paulo Vissotto de Paiva Diniz Author affiliation: North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA
During the summer of 2007, migratory joint pain developed in my (E.B.B.) 86-year-old father, previously an ironworker, farmer, and World War II veteran. Because of occasional tick attachments, a Borrelia burgdorferi ELISA was performed; antibodies were not detected, and no treatment was instituted. In the fall, subtle memory loss developed, and he fell twice a few weeks apart. Dad jokingly blamed the falls and the memory loss on "old timer's disease." Subsequently, episodes of subtle confusion and more frequent memory loss generated family concern as to what the future might hold. On December 15, he broke his left femur during a fall while climbing 2 stairs to enter our home. Despite having successfully climbed those stairs thousands of times in the past, he would never climb those or any other stairs again.
Retrospectively obvious, a pattern of insidious illness characterized by joint pain, memory loss, and incoordination, not recognizable by my father or other family members, had begun before that summer. Medically stable historical problems included coronary artery disease, atherosclerosis, carotid artery occlusion, hypertension, and atrial fibrillation. During the previous year, a normocytic, normochromic, nonregenerative anemia persisted. Despite normal serum iron, total iron binding capacity, ferritin, and vitamin B12 values, anemia was attributed to intestinal blood loss. When examined in May 2007, before anesthesia for endoscopy, mood and affect were appropriate, recent and remote memory were intact, insight and judgment were good. A hiatal hernia, mild antral gastritis, and duodenitis were visualized.
Initial Hospitalization
When my father was hospitalized December 15, 2007, with a broken femur, a resting pill roll tremor and cogwheel rigidity were suggestive of Parkinson disease. Preoperative neurologic consultation identified severe confusion, inattention, and an inability to answer questions. Short-term memory and problem-solving abilities were decreased. There was mild ptosis of the right eye, normal cranial nerves, mild asterixis, and hand weakness. Laboratory abnormalities included anemia, hypercreatinemia, an elevated aspartate aminotransferase level, and hyperglobulinemia. Due to the severity of the femoral fracture, the femoral head was excised and replaced with a bipolar femoral prosthesis.
Postoperatively, poor mentation was considered a sequela of general anesthesia and peri-operative analgesics. For more than a week, dementia persisted. He did not recognize family members and had near constant hallucinogenic activities, including agitation, tying knots, sawing motions, and constantly pulling covers, bed clothes, and fluid lines. Severe hematuria developed after he pulled an inflated Foley catheter from his urethra. Concurrent gastrointestinal bleeding of undetermined cause necessitated multiple blood transfusions. Other complications included difficulty swallowing and paralytic ileus. Repeat abdominal radiographs, in conjunction with stool softeners and laxatives, failed to alleviate gastrointestinal complications. Eventually, he refused food and became severely bloated. Endoscopy performed on December 26 identified severe necrotizing esophagitis, multiple plaques, and a stricture attributed to Candida albicans and herpes zoster. C. albicans esophagitis is known to accompany HIV infection, leukemia, or an unidentified source of immune suppression (1,2). Shingles, caused by herpes zoster, occurred during the previous Thanksgiving and can be associated with immunosuppression, stress, or an aging immune system (3,4). Mentation and gastrointestinal abnormalities improved after starting treatment with fluconazole, acyclovir, and symptomatic medications for erosive esophagitis. However, confusion, lack of orientation, hyponatremia, hypokalemia, and hyperglycemia remained problematic until discharge to a physical therapy center on December 31.
Second Hospitalization
During the next week, strength and mental capacities improved rapidly and discharge to the home environment was scheduled for January 9. On that morning and while driving to Maryland to build entry ramps, I was informed by cell phone that my father fell out of a chair and became nonverbal and that a stroke was suspected. For me, the roller coaster illness ultimately leading to his death would take an unbelievable turn of events. Upon his transfer to the neurology service, encephalopathy, asterixis, Parkinsonian-type tremor, hypoactive reflexes, pinpoint and minimally reactive pupils, and cogwheel rigidity were found. Verbal communication was absent, but he would grimace with pain whenever extremities were manipulated. An urgent computed tomography scan did not identify intracranial abnormalities.
When I was a boy, my father used the expression "something is fishy in Denmark" to imply that something was astray. Based upon historical events, I suspected something was being missed. Laboratory findings included anemia (hemocrit 34%), a normal leukogram (leukocytes 9,100 cells/μL, 2% band neutrophils), mild hypokalemia, hypoalbuminemia, hyperglycemia, increased serum alkaline phosphatase level, erythrocyte sedimentation rate of 79, and hypergammaglobulinemia. Thoracic radiographs identified mild bilateral pleural effusion. Because an undefined infectious source of immunosuppression seemed plausible, and fever (maximum temperature 38.6�C) occurred 24 hours after neurologic decompensation an infectious etiology was pursued. Nasal methicillin-resistant Staphylococcus aureus, blood, urine, and cerebrospinal fluid (CSF) cultures were negative. CSF results, including those for special stains, were unremarkable. Serologic results for Treponema pallidum, Borrelia burgdorferi, Rickettsia rickettsii, Bartonella henselae, Bartonella quintana, and HIV were negative. Results of CSF herpes simplex PCR and a test for T. pallidum antibodies were negative.
On January 11, results of magnetic resonance imaging and magnetic resonance angiography were interpreted as a left posterior stroke with no active bleeding. Initial treatment included intravenous acyclovir, fluconazole, vancomycin, ceftriaxone, ampicillin, and dexamethasone.
Translational Research and the Practice of Medicine
Because I direct the Intracellular Pathogens Research Laboratory (IPRL) at the North Carolina State University College of Veterinary Medicine, aseptically obtained blood and CSF samples were kindly provided for testing. Results of PCR (5,6) specific for Anaplasma, Ehrlichia, and Rickettsia species were negative. Bartonella 16S-23S intergenic spacer primers (7) repeatedly generated amplicons of different sizes from blood and CSF, respectively. Compared with GenBank sequences, the blood amplicon was most similar (434/465bp) to Candidatus Bartonella volans (strain FSq-1, EU294521) isolated from a southern flying squirrel (Glaucomys volans) and Candidatus Bartonella durdenii (391/422bp) amplified from Orchopeas howardi (GenBank accession no. DQ 336386), a flea found on eastern US gray squirrels (Scinrus carolinensis), and a Bartonella sp. (446/492bp, EF125214) identified in ground squirrels (Spermophilus danricus) in the People's Republic of China. The novel rodent Bartonella sequence obtained from my father's blood had an 18-bp insert at positions 2047 or 334 in EU294521 and DQ336386, respectively. Previously, our laboratory had never worked with rodent Bartonella species and had never amplified a 300-bp internal transcribed spacer region amplicon from >3,000 animal or human blood samples. After several unsuccessful cloning attempts, the CSF amplicon was most similar (393/394 bp) to B. henselae (NC-005956). Blood and CSF, cultured by using Bartonella α Proteobacteria growth medium (BAPGM) (8), did not result in the growth of a Bartonella species.
Clinicians and Scientists Working Together
After Bartonella PCR results became available, treatment with piperacillin and tazobactam were continued for 3 weeks until discharge. Levetiracetam was added to the patient's treatment because a generalized seizure occurred shortly after antimicrobial drugs were given. On January 18, severe dependent edema of the right elbow resulted in fluid leakage through intact skin. For 3 weeks, Dad remained semicomatose, disoriented, agitated, and encephalopathic. Hallucinations continued, accompanied by frequent involuntary motor movements. Diabetes mellitus and a large decubital ulcer on the right heel developed. During the fourth week, mentation improved, and he could rise and stand for brief periods. On January 28, he was discharged to a rehabilitation facility, with instructions to receive doxycycline and rifampin 2�/d for 13 days. Blood samples, obtained aseptically before discharge, were again submitted to the IPRL. After BAPGM pre-enrichment and subculture, B. vinsonii subsp. berkhoffii genotype II was isolated, and sequential serologic testing identified a rising titer to B. vinsonii subsp. berkhoffii but did not detect B. henselae antibodies (Table). After a brief, emotionally traumatic stay at the rehabilitation facility, Dad returned home to be cared for by 4 sons, his wife of 60 years, and other family members. Each week a different son slept by his bed, which was relocated to the family living room.
Home Again at Last
During the next 3 weeks, there was substantial and progressive improvement in physical capabilities and a return of normal mental capabilities, including exceptional short- and long-term memory. Appetite normalized, and despite severe atrophy, muscle strength increased so he could stand, walk with assistance, and, although a daily struggle, access the bathroom. A February 10 blood sample obtained while he was receiving oral antimicrobial drugs was Bartonella PCR negative, and no bacteria were isolated in BAPGM. During this precious 3 weeks, our father joked, laughed, and vividly recalled wartime friends and other experiences. On March 1, 2008, he opened Christmas presents with our family. I should have been there.
Third and Final Hospitalization
On March 4, ≈2 weeks after the course of oral antibiotics was completed, agitation and disorientation returned, and mental status deteriorated. Within 24 hours, Dad was hospitalized, where fine motor tremors of the right hand and wrist, asymmetric edema involving the right leg, and edema of the penis and scrotum were noted. He was afebrile and nonverbal and could not follow simple commands. Hematocrit was 30.2%, platelet count 557,000 cells/μL, and leukocyte count 7,800 cells/μL with a normal differential count. Serum biochemical abnormalities included hyperglycemia (glucose 218 mg/dL), hyperglobulinemia (3.6 g/dL), and increased alkaline phosphatase activity (169 IU/L). Urinalysis abnormalities included proteinuria with occasional hyaline casts.
Lorazepam was administered to control the agitation and restlessness. The warfarin dose was increased and heparinization initiated for a potential cerebrovascular accident. Due to the prior documentation of Bartonella infection, intravenous doxycycline, rifampin, and gentamicin were administered, and total parenteral nutrition was instituted. Again, shortly after initiation of antimicrobial drugs, a seizure occurred. Bartonella spp. were not amplified or isolated from a 1-mL blood sample obtained 4 days after initiation of treatment with antimicrobial drugs. During the next 3 weeks, while intravenous antimicrobial drugs were administered, our father again remained encephalopathic, with frequent hallucinations, severe agitation, and near-constant mental confusion. On March 14, intravenous methylprednisolone for potential immune-mediated vasculitis elicited no improvement in mental status. Similar to the previous treatment course, improvement in mental status, coherent communication, and renewed ability to recognize family members occurred during the fourth hospitalization week.
A Battle Lost
On April 4, Dad was discharged to our home and oral antimicrobial drugs (doxycycline and rifampin) were dispensed. Despite all efforts by medical professionals, members of our family, and our tough 86-year-old father, protracted illness and prolonged hospitalizations had resulted in mental and physical debilitation, severe muscle wasting, and profound weakness. More important, he had lost his desire to live. After discharge, there was minimal neurologic improvement. Before the availability of April 4 IPRL test results, he began to refuse all medications. The identical rodent Bartonella DNA sequence was again amplified from his blood, but no bacteria were isolated.
Four weeks later my father died, on Friday, May 2, at 5 pm, around quitting time for an old iron worker. My mother and youngest brother were at his side. After his death, blood culture results from another sample obtained by the hospice nurse on April 28, 2008, became available. B. vinsonii subsp. berkhoffii genotype II was amplified and sequenced from the enrichment BAPGM blood culture. As direct extraction of DNA from blood was negative, growth of viable bacteria in liquid culture was implicated (8,9).
Groundhogs, Fleas, and the Genus Bartonella
Following our father's death, I recalled a small, 0.5-cm, raised, firm lesion within his right eyebrow that developed during the summer of 2007 and would spontaneously hurt or burn, causing him to rub or squeeze the lesion. The mass disappeared after he began taking antimicrobial drugs in 2008. Retrospectively, I suspected a rodent flea bite above the eye had transmitted a novel Bartonella species, which we sequenced from his blood after each hospitalization. All known Bartonella spp. have preferential animal reservoir hosts, and each uses arthropods or animal bites and scratches as the primary modes of transmission (10-12). Dad would occasionally capture mice, rats, skunks, and groundhogs in the barns. Groundhogs were transported in the car trunk to a distant location for release, potentially leaving behind fleas. Therefore, 3 Candidatus Bartonella spp. isolates were provided by Dr. William Nicholson, a colleague at the Centers for Disease Control and Prevention in Atlanta. After sequencing, the 16S-23S intergenic spacer region of a ground squirrel (Candidatus Bartonella durdenii), a flying squirrel (Candidatus Bartonella volans), and a groundhog (Candidatus Bartonella monaxi) isolate, the most similar GenBank sequence was Candidatus Bartonella volans. There was no perfect match with these 3 isolates. However, sequences from Dad's blood clustered with a squirrel Bartonella subgroup. This observation supports the presence of a novel Bartonella species on the eastern shore of Maryland, an as yet undefined animal reservoir, and an unknown arthropod vector.
Regardless of the mode(s) of transmission, repeated molecular documentation of a novel rodent Bartonella sp. and B. vinsonii subsp. berkhoffii supports the unexpected failure of 2 intensive courses of intravenous and oral antimicrobial drugs to eliminate these fastidious, intravascular bacteria. During the first two hospitalization periods, there was similar and progressive improvement in neurologic signs and mental capabilities that began during the fourth week of antimicrobial drug administration. Pre-enrichment BAPGM growth of B. vinsonii subsp. berkhoffii from blood obtained 4 days before death supports persistence of viable organisms. Recently, antimicrobial drug resistance genes have been characterized in B. bacilliformis, B. henselae, and B. quintana by in vitro serial passage (13-15). Retrospectively, the relapse in encephalopathic signs might have been avoided if antimicrobial drugs were continued for a longer interval after discharge from hospital 2, and blood cultures were optimally obtained and sequentially tested to confirm therapeutic elimination.
Elimination of Bartonella spp. by antimicrobial drugs in immunocompetent patients may be more difficult to achieve than is currently appreciated (16). Although co-infection with B. henselae and B. vinsonii subsp. berkhoffii has been previously reported, DNA of 3 Bartonella spp. was detected in our father. Based on repeatable PCR testing, a small quantity of B. henselae DNA was in the January CSF sample. Because PCR amplicon contamination was never detected in any negative control, laboratory error is considered unlikely. Although the BAPGM enrichment approach has improved molecular detection and isolation of some Bartonella spp. from human patient samples (9,16-18), a rodent Bartonella sp. isolate was not obtained. Unfortunately, 8 weeks can be required from inoculation of BAPGM until a subculture agar plate isolate is characterized by DNA sequencing. Therefore, IPRL test results were often not available to Dad's physicians in a timely manner.
Age, Bartonella spp., and Immune Suppression?
Suspicion of an undetermined source of immune suppression and recent tick exposures were primary factors motivating testing in the IPRL. Previously, B. vinsonii subsp. berkhoffii was shown to induce immunosuppression in experimentally infected dogs (19,20). In retrospect, occult infection with Bartonella spp. may have contributed to shingles at Thanksgiving and necrotizing C. albicans esophagitis after hospitalization for the fractured femur. Recently, B. quintana lipopolysaccharide was found to have antiinflammatory properties (21). Immune suppressive factors may facilitate persistent intravascular Bartonella infection without inducing obvious infection indicators, such as fever, tachycardia, leukocytosis, and CSF pleocytosis. Fever was documented once and mild neutrophilia for 3 of 48 blood counts. Thrombocytosis, previously associated with B. henselae (22), was documented 14 times.
Ecologic Complexity of Bartonella spp.
Because of my father's long-standing atherosclerosis and because BAPGM will grow a spectrum of seemingly difficult to isolate bacteria (8,23), pre-enrichment blood cultures and Bartonella internal transcribed spacer region PCR had been performed in September 2005 and August 2006 (Table). Bartonella spp. were not amplified or isolated, which suggests infection occurred after the summer of 2006. Transmission of B. henselae, B. vinsonii subsp. berkhoffii, and B. alsatica can occur as a result of a scratch from a cat, a dog, or a wild rabbit, respectively (17,24-26). Cats are the primary reservoir for B. henselae, whereas dogs and coyotes are the only reported reservoir hosts for B. vinsonii subsp. berkhoffii genotype II in North America (27). Recently, B. vinsonii subsp. berkhoffii genotype II was isolated by BAPGM blood culture from a cat with recurrent osteomyelitis (E.B. Breitschwerdt, unpub. data), which suggests that a bacteremic cat might facilitate transmission of this subspecies. My parents had an old (≈21 years of age) exclusively outdoor barn cat that would occasionally scratch. The cat could not be tested because it died in 2007. B. henselae and B. clarridgeae have been transmitted experimentally by transfusion to cats (24). Because B. vinsonii subsp. berkhoffii seroconversion occurred during hospitalization, transfusion-associated transmission is also possible. The exact timing and mode of transmission of B. henselae, B. vinsonii subsp. berkhoffii, and the rodent Bartonella sp. to our father cannot be established. However, his illness serves to illustrate the medical and ecologic complexity of this genus.
Occult Infection and Chronic Illness
Reconstructing the history of a chronic illness is always difficult and remains an unexacting science due to known, unknown, and undetermined factors that influence disease expression over time. Experimental studies that used rodent models have emphasized the ability of Bartonella spp. to invade erythrocytes and vascular endothelial cells (28). In vitro studies indicate that B. henselae can infect macrophages, microgial cells, dendritic cells, and CD34+ progenitor cells (29). B. henselae and B. vinsonii subsp. berkhoffii have been amplified from dog lymph node aspiration samples (30). Thus in a given patient, Bartonella organisms likely infect a substantial number of cellular targets. B. henselae infection induces chronic arthritis in a subset of cat scratch disease (CSD) patients, and atypical CSD manifestations are more likely to develop in elderly patients (31,32). In the context of arthritis, B. henselae and B. vinsonii subsp. berkhoffii were repeatedly isolated from joint fluid from a dog in which repeated antimicrobial drug therapy was not successful (33). Although a spectrum of acute and generally self-limiting neurologic manifestations have been historically described in CSD patients, B. henselae and B. vinsonii subsp. berkhoffii were only recently isolated from patients with chronic neurologic and neurocognitive abnormalities (16).
We propose that the initial arthritic signs, short-term memory loss, and incoordination were premonitory signs of Bartonella spp. infection, and that persistent infection contributed to localized edema, nonregenerative anemia, thrombocytosis, hyperglobulinemia, and a protracted debilitating illness accompanied by hallucinations, agitation, seizures, and death. Agitation, disorientation, and combative behavior have been reported in association with CSD and physicians have implicated Bartonella spp. as contributors to agitation and treatment-resistant depression (34,35). Memory loss and a spectrum of neurocognitive complaints have also been reported in immunocompetent persons infected with B. vinsonii subsp. berkhoffii and B. henselae (9,16,17).
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Link to Dr. Breitschwerdt's lab website. Currently they are in the protocol validation stage for human testing. Once the validation testing is complete, they will begin human testing for Bartonella.
Galaxy Diagnostics provides an advanced testing methodology for the enhanced detection of hard-to-detect, vector-borne bacteria called Bartonella. Popularly known as Cat Scratch Disease (CSD), Trench Fever, Carrion's Disease, and Orroyo's Fever, Bartonella infection has been identified as an important source of emerging infectious disease in animal and humans. Recent medical evidence has linked Bartonella infection to serious chronic disease processes in immuno-competent patients, as well as to acute infections in immuno-suppressed patients.
Our Bartonella test combines state-of-the-art DNA detection with a patented enrichment culture developed by research scientists at the North Carolina State University College of Veterinary Medicine in response to the serious false negative rates of conventional testing. Our results are highly accurate and significantly more effective than any other available method for detecting active Bartonella spp. infection.
Galaxy's Bartonella Enrichment Culture+PCR platform offers a new standard of patient care in the diagnosis of Bartonella infection. We also offer optimized serology and conventional PCR testing to test for evidence of past/current infection.
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Bacteria transmitted by fleas-and potentially ticks-can be passed to human babies by the mother, causing chronic infections and raising the possibility of bacterially induced birth defects, a scientist has discovered.
Dr. Ed Breitschwerdt, professor of internal medicine in the Department of Clinical Sciences, is among the world's leading experts on Bartonella, a bacteria that is maintained in nature by fleas, ticks and other biting insects, but which can be transmitted by infected cats and dogs as well.
The most commonly known Bartonella-related illness is cat scratch disease, caused by B. henselae, a strain of Bartonella that can be carried in a cat's blood for months to years.
Cat scratch disease was thought to be a self-limiting, or ``one-time'' infection; however, Breitschwerdt's previous work discovered cases of children and adults with chronic, blood-borne Bartonella infections-from strains of the bacteria that are most often transmitted to cats (B. henselae) and dogs (B. vinsonii subsp. berkhoffii) by fleas and other insects.
In his most recent case study, Breitschwerdt's research group tested blood and tissue samples taken over a period of years from a mother, father and son who had suffered chronic illnesses for over a decade. Autopsy samples from their daughter-the son's twin who died shortly after birth-contained DNA evidence of B. henselae and B. vinsonii subsp. berkhoffi infection, which was also found in the other members of the family.
Both parents had suffered recurring neurological symptoms including headaches and memory loss, as well as shortness of breath, muscle weakness and fatigue before the children were born. In addition, their 10-year-old son was chronically ill from birth and their daughter died due to a heart defect at nine days of age.
Results of the parents' medical histories and the microbiological tests indicated that the parents had been exposed to Bartonella prior to the birth of the twins, and finding the same bacteria in both children, one shortly after birth and the other 10 years later, indicates that they may have become infected while in utero.
``This is yet more evidence that Bartonella bacteria cause chronic intravascular infections in people with otherwise normal immune systems, infections that can span a decade or more,'' Breitschwerdt says. ``Also this new evidence supports the potential of trans-placental infection and raises the possibility that maternal infection with these bacteria might also cause birth defects.''
Breitschwerdt's research appears online in the April 14, 2010 Journal of Clinical Microbiology .
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I'm a little hesitant to post this one ... don't want to unncessarily frighten some folks who've had this. But, I think some of the information in the article is very helpful regarding treatment.
Of particular importance is their conclusion. "Effective antibiotic therapy for Bartonella endocarditis should include an aminoglycoside.
Investigative article on the "Outcome and Treatment of Bacterial Endocarditis."
richedie
Frequent Contributor (1K+ posts)
Member # 14689
posted
The thing that really scares me when I see this is that my pain never moves or changes! WHY? My left arm always hurts like heck....and always in the same spots. Not the right arm....just the left.
-------------------- Mepron/Zith/Ceftin Doxy/Biaxin/Flagyl pulse. Artemisinin with Doxy/Biaxin. Period of Levaquin and Ceftin. Then Levaquin, Bactrim and Biaxin. Bactrim/Augmentin/Rifampin. Mepron/Biaxin/Artemisinin/Cat's Claw Rifampin/Bactrim/Alinia Plaquenil/Biaxin Posts: 1949 | From Pennsylvania | Registered: Feb 2008
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Biotechnology scientist Donna Needham works with blood samples. Dr. Edward Breitschwerdt and Ricardo Maggi of NCSU founded Galaxy Diagnostics to cultivate the Bartonella bacteria.
BY SARAH AVERY - Staff Writer
A bacterial infection typically spread by fleas, lice and biting flies could be more prevalent than many think, and may have been transmitted from a mother to her children at birth, scientists from N.C. State University say.
Dr. Edward Breitschwerdt, an infectious disease veterinarian and one of the world's leading researchers of bacteria called Bartonella, has for the first time documented evidence that the pathogen may have been passed between family members.
Although more studies are needed to back up his findings, Breitschwerdt and colleagues describe the case of a mother and father who began battling chronic aches, fatigues and other symptoms soon after they were married. When their twins were born in 1998, the daughter died after nine days from a heart defect, and the son developed chronic health problems.
Using tissue from the daughter's autopsy and blood from the surviving family members, Breitschwerdt's team discovered that the entire family was infected with the same species of Bartonella bacteria, despite having no shared exposures to flea or lice infestations. Bartonella is known to causes such illnesses as trench fever and cat scratch disease, and it is increasingly suspected of triggering a variety of aches and inflammations that doctors have been unable to diagnose.
"I think we have stumbled across something that is of monumental medical importance," said Breitschwerdt, whose findings were published recently in the Journal of Clinical Microbiology.
Proving the mother-child transmission could be difficult, however. Little funding is available for such research because the bacteria are still not considered a major source of human disease.
Dr. Michael Kosoy, who heads the Bartonella laboratory for the Centers for Disease Control and Prevention in Fort Collins, Colo., said scientists are only beginning to build evidence that Bartonella infections may be more common than previously thought.
"Bartonella are circulated around the world in many animals, but there are different Bartonella species, and the question is how can they be transmitted to humans?" Kosoy said, noting that most known cases have been transmitted from biting insects. He said the NCSU findings about the potential family transmission are compelling but inconclusive.
Dozens of strains
At least 26 strains of Bartonella have been named worldwide, and the list is growing. The most notorious Bartonella infection is cat scratch disease, a fever illness passed to humans from flea-infected cats. Fleas are the primary hosts, and they spread the bacteria in their feces.
Other Bartonella strains spread more serious diseases. Kosoy is studying how often heart inflammation is caused by a Bartonella that thrives among rat fleas in Thailand. He has already established that about 25 percent of unexplained fever illnesses among a group of patients there was caused by Bartonella .
"This is not limited to cat scratch," Kosoy said. "That's just the tip of the iceberg."
Breitschwerdt said he thinks the bacteria may be the hidden cause behind a host of chronic symptoms - muscle aches, neurological problems, fatigue, arthritis - that defy diagnosis.
About two years ago, Breitschwerdt began testing blood samples from a doctor in Maryland, who was curious whether Bartonella infections might be causing problems for some of his patients.
"There are lab tests showing inflammation," but no discernible cause, said Dr. Robert Mozayeni, a Yale-educated rheumatologist who practices in Rockville, Md.
Mozayeni contacted Breitschwerdt and his NCSU colleague, Ricardo Maggi, who together developed a more sensitive test for Bartonella. Routine blood tests fail to detect Bartonella because they search for antibodies that the body is slow to produce.
Instead, Breitschwerdt and Maggi figured out how to cultivate the bacteria in the laboratory from blood samples of infected people. They founded a company called Galaxy Diagnostics to handle the laboratory volume.
Of Mozayeni's mystery patients tested at the lab, nearly 20 percent had Bartonella infections.
"I suspect this is going to be one of the causes of rheumatoid arthritis and a few other things, but it's too speculative right now to say," Mozayeni said.
Human testing
More studies are needed, and Mozayeni has joined Breitschwerdt and Maggi in the diagnostic company to oversee human testing.
"Certainly, the prevalence of Bartonella infection in people with chronic illness is higher than I would have ever guessed, but we still don't know what that means," Breitschwerdt said.
Among the biggest unknowns is how to treat people who have been infected. The effectiveness of antibiotics depends on which strain of Bartonella is at work, and with so many strains, treatments can be hit or miss.
Breitschwerdt said the family in his most recent study declined to comment about their experience. He said they were having difficulty finding a doctor.
"It is very difficult to find a physician who wants to see someone with a chronic illness that is poorly defined," he said, adding that many such patients often think they have Lyme disease, a tick-borne bacterial infection with similar symptoms - and stigma. "With an unexplained illness, it becomes problematic."
mojo
Frequent Contributor (1K+ posts)
Member # 9309
posted
Tracy - Rifampin can be a difficult drug to take but I think it's very effective for Bart. I couldn't take it because it sent my Liver Enzymes sky high.
Make sure to get your Liver Enzymes checked regularly.
My sister took it for 8 months or so and she was very ill the entire time (but liver was OK). She was not herself - very cranky and always felt sick. It really did a lot for her, though.
It also treats Lyme so that could be another reason people herx hard.
I wish I could go back on this one!
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Tracy9
Frequent Contributor (1K+ posts)
Member # 7521
posted
I've been very lucky; my liver enzymes have been fine. Is it the Bart coming out that makes us so sick, toxins dying off, or what? The Rifampin seems to be doing a good job, whatever it is.
Also I am on JUST Rifampin. Several people have said you have to be on something else with it but my LLD says no, Rifampin alone is fine.
13 years Lyme & Co.; Small Fiber Neuropathy; Myasthenia Gravis, Adrenal Insufficiency. On chemo for 2 1/2 years as experimental treatment for MG. Posts: 4480 | From Northeastern Connecticut | Registered: Jun 2005
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Tracy9
Frequent Contributor (1K+ posts)
Member # 7521
Published Fri, May 21, 2010 05:10 AM Modified Fri, May 21, 2010 07:54 AM
The pain of Bartonella
A bacterial infection typically spread by fleas, lice and biting flies could be more prevalent than many think, and may have been transmitted from a mother to her children at birth, scientists from N.C. State University say.
Dr. Edward Breitschwerdt, an infectious disease veterinarian and one of the world's leading researchers of bacteria called Bartonella, has for the first time documented evidence that the pathogen may have been passed between family members.
Although more studies are needed to back up his findings, Breitschwerdt and colleagues describe the case of a mother and father who began battling chronic aches, fatigues and other symptoms soon after they were married. When their twins were born in 1998, the daughter died after nine days from a heart defect, and the son developed chronic health problems.
Using tissue from the daughter's autopsy and blood from the surviving family members, Breitschwerdt's team discovered that the entire family was infected with the same species of Bartonella bacteria, despite having no shared exposures to flea or lice infestations. Bartonella is known to causes such illnesses as trench fever and cat scratch disease, and it is increasingly suspected of triggering a variety of aches and inflammations that doctors have been unable to diagnose.
"I think we have stumbled across something that is of monumental medical importance," said Breitschwerdt, whose findings were published recently in the Journal of Clinical Microbiology.
Proving the mother-child transmission could be difficult, however. Little funding is available for such research because the bacteria are still not considered a major source of human disease.
Dr. Michael Kosoy, who heads the Bartonella laboratory for the Centers for Disease Control and Prevention in Fort Collins, Colo., said scientists are only beginning to build evidence that Bartonella infections may be more common than previously thought.
"Bartonella are circulated around the world in many animals, but there are different Bartonella species, and the question is how can they be transmitted to humans?" Kosoy said, noting that most known cases have been transmitted from biting insects. He said the NCSU findings about the potential family transmission are compelling but inconclusive.
Dozens of strains
At least 26 strains of Bartonella have been named worldwide, and the list is growing. The most notorious Bartonella infection is cat scratch disease, a fever illness passed to humans from flea-infected cats. Fleas are the primary hosts, and they spread the bacteria in their feces.
Other Bartonella strains spread more serious diseases. Kosoy is studying how often heart inflammation is caused by a Bartonella that thrives among rat fleas in Thailand. He has already established that about 25 percent of unexplained fever illnesses among a group of patients there was caused by Bartonella .
"This is not limited to cat scratch," Kosoy said. "That's just the tip of the iceberg."
Breitschwerdt said he thinks the bacteria may be the hidden cause behind a host of chronic symptoms - muscle aches, neurological problems, fatigue, arthritis - that defy diagnosis.
About two years ago, Breitschwerdt began testing blood samples from a doctor in Maryland, who was curious whether Bartonella infections might be causing problems for some of his patients.
"There are lab tests showing inflammation," but no discernible cause, said Dr. Robert Mozayeni, a Yale-educated rheumatologist who practices in Rockville, Md.
Mozayeni contacted Breitschwerdt and his NCSU colleague, Ricardo Maggi, who together developed a more sensitive test for Bartonella. Routine blood tests fail to detect Bartonella because they search for antibodies that the body is slow to produce.
Instead, Breitschwerdt and Maggi figured out how to cultivate the bacteria in the laboratory from blood samples of infected people. They founded a company called Galaxy Diagnostics to handle the laboratory volume.
Of Mozayeni's mystery patients tested at the lab, nearly 20 percent had Bartonella infections.
"I suspect this is going to be one of the causes of rheumatoid arthritis and a few other things, but it's too speculative right now to say," Mozayeni said.
Human testing
More studies are needed, and Mozayeni has joined Breitschwerdt and Maggi in the diagnostic company to oversee human testing.
"Certainly, the prevalence of Bartonella infection in people with chronic illness is higher than I would have ever guessed, but we still don't know what that means," Breitschwerdt said.
Among the biggest unknowns is how to treat people who have been infected. The effectiveness of antibiotics depends on which strain of Bartonella is at work, and with so many strains, treatments can be hit or miss.
Breitschwerdt said the family in his most recent study declined to comment about their experience. He said they were having difficulty finding a doctor.
"It is very difficult to find a physician who wants to see someone with a chronic illness that is poorly defined," he said, adding that many such patients often think they have Lyme disease, a tick-borne bacterial infection with similar symptoms - and stigma. "With an unexplained illness, it becomes problematic."
13 years Lyme & Co.; Small Fiber Neuropathy; Myasthenia Gravis, Adrenal Insufficiency. On chemo for 2 1/2 years as experimental treatment for MG. Posts: 4480 | From Northeastern Connecticut | Registered: Jun 2005
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Bartonella vinsonii subsp. berkhoffii and Bartonella henselae bacteremia in a father and daughter with neurological disease
Edward B Breitschwerdt1 , Ricardo G Maggi1 , Paul M Lantos2 , Christopher W Woods2 , Barbara C Hegarty1 and Julie M Bradley1
1 Intracellular Pathogens Research Laboratory, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough St., Raleigh, NC, USA 2 Duke University Medical Center, 2301 Erwin Rd, Durham, NC, USA author email corresponding author email
Received: 4 February 2010 Accepted: 8 April 2010 Published: 8 April 2010 � 2010 Breitschwerdt et al; licensee BioMed Central Ltd.
Abstract
Background Bartonella vinsonii subsp. berkhoffii is an important, emerging, intravascular bacterial pathogen that has been recently isolated from immunocompetent patients with endocarditis, arthritis, neurological disease and vasoproliferative neoplasia. Vector transmission is suspected among dogs and wild canines, which are the primary reservoir hosts. This investigation was initiated to determine if pets and family members were infected with one or more Bartonella species.
Methods PCR and enrichment blood culture in Bartonella alpha Proteobacteria growth medium (BAPGM) was used to determine infection status. Antibody titers to B. vinsonii subsp. berkhoffii genotypes I-III and B. henselae were determined using a previously described indirect fluorescent antibody test. Two patients were tested sequentially for over a year to assess the response to antibiotic treatment.
Results Intravascular infection with B. vinsonii subsp. berkhoffii genotype II and Bartonella henselae (Houston 1 strain) were confirmed in a veterinarian and his daughter by enrichment blood culture, followed by PCR and DNA sequencing. Symptoms included progressive weight loss, muscle weakness, lack of coordination (the father) and headaches, muscle pain and insomnia (the daughter). B. vinsonii subsp. berkhoffii genotype II was also sequenced from a cerebrospinal fluid BAPGM enrichment culture and from a periodontal swab sample. After repeated courses of antibiotics, post-treatment blood cultures were negative, there was a decremental decrease in antibody titers to non-detectable levels and symptoms resolved in both patients.
Conclusions B. vinsonii subsp. berkhoffii and B. henselae are zoonotic pathogens that can be isolated from the blood of immunocompetent family members with arthralgias, fatigue and neurological symptoms. Therapeutic elimination of Bartonella spp. infections can be challenging, and follow-up testing is recommended. An increasing number of arthropod vectors, including biting flies, fleas, keds, lice, sandflies and ticks have been confirmed or are suspected as the primary mode of transmission of Bartonella species among animal populations and may also pose a risk to human beings.
Background
When a genus of bacteria is discovered or, in the case of Bartonella, rediscovered; numerous clinical, microbiological and pathological concepts related to disease causation and microbial pathogenesis are sequentially redefined. Subsequently, the medical relevance of the genus undergoes continued maturation; as knowledge of the organism, the host immune response, diagnostic test sensitivity and specificity, treatment efficacy and epidemiology expand. Since the early 1990s, this paradigm of discovery and ongoing biological and medical redefinition has clearly been applicable to the genus Bartonella. Prior to 1990, only two pathogenic Bartonella species, B. bacilliformis and B. quintana, were known to exist. Since 1990, greater than 22 Bartonella species have been described, of which at least half have been implicated or confirmed as human pathogens [1,2].
Bartonella vinsonii subsp. berkhoffii was initially isolated from a dog with endocarditis in 1993 [3]. Subsequently, four genotypes of B. vinsonii subsp. berkhoffii were described, based upon analysis of blood samples from coyotes, dogs and foxes [4]. To date, genotype II has been the most frequently isolated genotype sequenced from dog and human blood samples [5-8]. Previously, B. vinsonii subsp. berkhoffii genotype II was documented in a healthy dog on 8 of 10 culture attempts spanning a 16-month period, thereby supporting the potential for persistent intravascular infection in pet dogs [9]. Although tick transmission of B. vinsonii subsp. berkhoffii has been suggested, the mode(s) of transmission among canines has not been determined [10]. In contrast to the canine reservoir for B. vinsonii subsp. berkhoffii, domestic and wild felids represent the primary reservoir in nature for Bartonella henselae, an organism transmitted among cats by fleas (Ctenocephalides felis); a factor that contributes to a worldwide distribution for this Bartonella sp. [1,2]. Similar to dogs, outwardly healthy cats can remain bacteremic with B. henselae for months to years [11,12]. However, despite what seems to be exceptional evolutionary adaptation of B. vinsonii subsp. berkhoffii in canines and B. henselae in felines, both of these two bacterial species can be pathogenic in both cats and dogs.
In this study, intravascular infection with B. vinsonii subsp. berkhoffii genotype II and B. henselae were foundin a veterinarian and his daughter. The father presented with progressive weight loss, muscle weakness and lack of coordination; his daughter had developed headaches, muscle pain and insomnia. Both individuals were being evaluated by a neurologist at the time of initial testing for evidence of Bartonella infection. Multiple courses of antibiotics were administered before the patients' clinical status improved and before microbiological, molecular and serological evidence of infection diminished or was negative.
Patients, pets and methods
In October, 2007, the primary author was contacted by the father of a family residing in North Carolina, who requested Bartonella testing as a component of an IRB approved study (North Carolina State University Institutional Review Board, IRB#s 4925-03 and 164-08-05). For all family members and pets (Institutional Animal Care and Use Protocol 07-014-0) tested in this study, a previously described approach that combines PCR detection of Bartonella spp. DNA and enrichment culture of blood and serum samples in Bartonella alpha Proteobacteria growth medium (BAPGM) was used [8]. The three part BAPGM diagnostic platform incorporates PCR amplification of Bartonella spp. following direct DNA extraction from patient blood and serum samples, PCR amplification following enrichment culture in BAPGM for 7 to 14 days, and PCR from isolates obtained following BAPGM subculture inoculation onto trypticase soy agar with 10% rabbit blood. Agar plates are incubated for 4 weeks and checked weekly for evidence of bacterial growth. To assess for potential laboratory contamination, an un-inoculated BAPGM culture flask was processed simultaneously and in an identical manner with each batch of patient blood and serum samples tested. Specifically, while establishing cultures using a batch of samples in the biosafety hood, the top was removed from the BAPGM un-inoculated control flask until all patient samples had been processed. Methods used for testing sample cultures, including DNA extraction, PCR amplification targeting the Bartonella 16S-23S intergenic spacer region (ITS), and sequencing procedures were performed using previously described methods [5-8]. Following the standard operating procedures in the Intracellular Pathogens Research Laboratory, sample preparation including BAPGM cultures and agar plate sub-inoculation, DNA extraction, PCR preparation and PCR amplification and analysis were performed in separate laboratory rooms to avoid culture as well as DNA contamination. In addition, negative and positive Bartonella DNA test control samples, consisting of bacteria-free blood DNA and DNA spiked with B. henselae genomic DNA at 0.5 genome copies per microliter, respectively, were used for each batch of DNA tested. For all results reported in this study, PCR products consistent in size with a Bartonella spp. (400-600 bp amplicon size) were sequenced to confirm the species and ITS strain. Sequences were aligned and compared with GenBank sequences using AlignX software (Vector NTI Suite 6.0, InforMax, Inc.).
Serology was performed using modifications of a previously described indirect fluorescent antibody test [13]. Bartonella vinsonii subsp. berkhoffii and B. henselae antibodies were determined following traditional immunofluorescence antibody assay (IFA) practices with fluorescein conjugated goat anti-human IgG. Bartonella vinsonii subsp. berkhoffii genotypes I, II and III and B. henselae (Houston I strain) were passed from agar grown cultures of each organism into DH82 (a continuous canine histiocytic cell line) cultures to obtain antigens that would seemingly be expressed by an intracellular bacteria localized to erythrocytes or endothelial cells within the vasculature. Heavily infected cell cultures were spotted onto 30-well Teflon coated slides (Cel-Line/Thermo Scientific), air dried, acetone fixed and stored frozen. Serum samples were diluted in phosphate buffered saline (PBS) solution containing normal goat serum, Tween-20 and powdered nonfat dry milk to block non-specific antigen binding sites. Patient sera were screened at dilutions of 1:16 to 1:64. All sera that remained reactive at a titer of 1:64 were further tested with twofold dilutions out to a final dilution of 1:8192.
Results
Father The father was a 50-year-old veterinarian whose symptoms began in 2006 with arthralgias and fatigue, which became progressively severe over ensuing 18 months. He described pain and stiffness of the joints, muscles, and neck that were most severe in the morning but improved throughout the day. He did not have fevers, but he suffered from profound fatigue. He had also experienced an 80-pound weight loss, though this was partially intentional. Beginning in September 2007, and of greatest concern to the patient, was progressive difficulty maintaining his balance while standing or ambulating. His history was notable for extensive occupational and domestic animal exposure. International travel was minimal. He was initially evaluated by a neurologist, and because of his exposure to zoonotic pathogens he was referred for infectious disease evaluation. He had not received any empiric courses of antibiotics.
On physical examination, the patient had a blood pressure of 141/88 mm Hg, a pulse of 98 beats/min, and a temperature of 37�C. He was in no acute distress and had a normal sensorium. Notable abnormal findings included a positive Romberg sign and difficulty with heel-toe walking. Cranial nerves, muscle strength, sensation, and deep tendon reflexes were normal and symmetrical, and his funduscopic examination was normal. There was no lymphadenopathy, no organomegaly, and no rash. Lumbar puncture revealed normal cerebrospinal fluid indices and opening pressure. Magnetic resonance imaging of the brain was notable for an increase in signal intensity throughout the pons and upper medulla lateralizing to the left of the midline (Figure 1).
[click on link for remainder of article]
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Int J Med Sci 2009; 6:131-132 �Ivyspring International Publisher
Ocular Bartonellosis
Massimo Accorinti
Institute of Ophthalmology, University ``La Sapienza'' of Rome (Italy) How to cite this article: Accorinti M. Ocular Bartonellosis. Int J Med Sci 2009; 6:131-132. Available from http://www.medsci.org/v06p0131.htm
Bartonella henselae is a gram negative aerobic bacillus and is the etiologic agent of cat-scratch disease. The infection is present around the world and may affect patients of all ages, including immunocompetent individuals. Humans are usually infected through a cat's scratch or bite, but a bite by cat fleas may also be the origin of infection. More common in children and young adults, it usually presents with a wide range of systemic and ocular symptoms. Other Bartonella species have been described as causing ocular lesions, as shown in Table 1.
Systemic signs and symptoms usually precede ocular involvement and are constituted by the appearance, 3 to 10 days after inoculation of bartonella by scratch or bite, of an erythematous papule on the skin on the site of inoculation. Seven to 14 days after the exposure a follicular conjunctivitis may appear. Fourteen to 21 days after the inoculation regional lymphoadenopathy may occur which is usually associated with myalgias, fatigue and low-grade fever. The association of conjunctivits and regional lymphoadenopathy is well known as Parinaud's oculoglandular syndrome (POGS).
Ocular signs
The most frequent ocular manifestation is neuroretinitis which is usually unilateral. If neuroretinitis is bilateral, it is quite asymmetric. Rarely, posterior pole involvement may be characterized by the presence of a focal inflammatory mass, either of the retina or of the optic disk. Central or paracentral scotoma or physiologic blind spot enlargement are the main alterations of the visual field, while fluorescein angiography usually presents a diffuse leakage from the optic nerve head along with the retinal vessels. Sometimes vascular occlusion with intraretinal haemorrhages and cotton-wool spots are present at the posterior pole. Anterior uveitis, intermediate uveitis and orbital abscess may also be observed in bartonellosis. In HIV-seropositive patients, some cases of bacillary angiomatosis and subretinal neovascular granuloma have been reported.
Diagnosis and Differential diagnosis
Enzyme immunoassay and Western Blot, along with PCR analysis, are usually used for diagnosis, although past history of contact with cats should lead to suspect the proper diagnosis. Serologic tests show a specificity and sensitivity of 90% in immunocompetent patients and only 70% in immunodeficient subjects.
Parinaud's syndrome is a clinical entity that may be due to numerous infections, including tularaemia, sporotrichosis, tuberculosis, syphilis, mononucleosis, coccidioidomycosis, while neuroretinitis with macular star may be observed in vascular disorders, toxoplasmosis, syphilis, tuberculosis, Lyme disease, and viral infection.
Table 1
[The Table didn't copy well -- please see link for the table which includes information on Bartonella pathogens and the eye]
Cat scratch disease is usually a self-limited disease in immunocompetent patients. Bartonella henselae is sensitive to many antibiotics in vitro, but only aminoglycosides have bactericidal activity. In immunocompetent patients doxycicline 200 mg/day is usually administered because of its property to cross the blood-brain and blood-ocular barrier. Caution should be made if administered to children, because it may cause dental changes. Ciprofloxacin (1,5 gr/day), gentamicin (3-5 mg/kg/day), erythromycin (2 gr/day), trimethoprim-sulphamethoxazole (Bactrim � 2 tablets/day) are good alternatives and, like doxycicline, are usually given for 14 to 28 days. Azythromicin may also be given to patients affected by cat scratch disease at 500 mg/day for 3 to 5 days. Immunodeficient patients need a more prolonged course of treatment, usually up to 4 months.
Ocular lesions are treated with antibiotics and with topical steroids for conjunctival lesion, topical steroids and mydriatics for anterior segment involvement and with peribulbar (sub-tenon) steroid injection and/or systemic steroids for retinal and optic nerve involvement. In this last case it is important to start steroid therapy after at least 48 hours from starting specific antibiotic treatment, especially if given locally in a depot preparation.
Bartonella henselae is a gram negative aerobic bacillus and is the etiologic agent of cat-scratch disease. The infection is present around the world and may affect patients of all ages, including immunocompetent individuals. Humans are usually infected through a cat's scratch or bite, but a bite by cat fleas may also be the origin of infection. More common in children and young adults, it usually presents with a wide range of systemic and ocular symptoms. Other Bartonella species have been described as causing ocular lesions, as shown in Table 1.
Systemic signs and symptoms usually precede ocular involvement and are constituted by the appearance, 3 to 10 days after inoculation of bartonella by scratch or bite, of an erythematous papule on the skin on the site of inoculation. Seven to 14 days after the exposure a follicular conjunctivitis may appear. Fourteen to 21 days after the inoculation regional lymphoadenopathy may occur which is usually associated with myalgias, fatigue and low-grade fever. The association of conjunctivits and regional lymphoadenopathy is well known as Parinaud's oculoglandular syndrome (POGS).
Ocular signs
The most frequent ocular manifestation is neuroretinitis which is usually unilateral. If neuroretinitis is bilateral, it is quite asymmetric. Rarely, posterior pole involvement may be characterized by the presence of a focal inflammatory mass, either of the retina or of the optic disk. Central or paracentral scotoma or physiologic blind spot enlargement are the main alterations of the visual field, while fluorescein angiography usually presents a diffuse leakage from the optic nerve head along with the retinal vessels. Sometimes vascular occlusion with intraretinal haemorrhages and cotton-wool spots are present at the posterior pole. Anterior uveitis, intermediate uveitis and orbital abscess may also be observed in bartonellosis. In HIV-seropositive patients, some cases of bacillary angiomatosis and subretinal neovascular granuloma have been reported.
[click on link for remainder of article]
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Candidatus Bartonella mayotimonensis and Endocarditis
Eleanor Y. Lin,1 Constantine Tsigrelis, Larry M. Baddour, Hubert Lepidi, Jean-Marc Rolain, Robin Patel, and Didier Raoult Author affiliations: Mayo Clinic, Rochester, Minnesota, USA (E.Y. Lin, C. Tsigrelis, L.M. Baddour, R. Patel); and Universit� de la M�diterran�e, Marseille, France (H. Lepidi, J.M. Rolain, D. Raoult)
Abstract We describe a new Bartonella species for which we propose the name Candidatus Bartonella mayotimonensis. It was isolated from native aortic valve tissue of a person with infective endocarditis. The new species was identified by using PCR amplification and sequencing of 5 genes (16S rRNA gene, ftsZ, rpoB, gltA, and internal transcribed spacer region).
Bartonella species are small, fastidious, gram-negative, intracellular bacteria that cause culture-negative infective endocarditis. Six species have been documented to cause endocarditis in humans: B. quintana (1), B. henselae (2), B. elizabethae (3), B. vinsonii subsp. berkhoffii (4), B. koehlerae (5), and B. alsatica (6). We report a case of culture-negative endocarditis caused by a new Bartonella species, for which we propose the name Candidatus Bartonella mayotimonensis.
The Patient
A 59-year-old man was initially hospitalized at Sartori Memorial Hospital (Cedar Falls, IA, USA) from April 14 through 19, 2008, for progressive shortness of breath, weight loss, fatigue, and altered mental status. He was then transferred to the Mayo Clinic (Rochester, MN, USA). Physical examination identified a new diastolic heart murmur. He was afebrile and did not have peripheral stigmata of endocarditis. Two sets of blood cultures obtained before antimicrobial drug therapy showed negative results for all bacteria tested after 5 days of incubation. A transesophageal echocardiogram showed a bicuspid aortic valve, mobile components on the left cusp of the aortic valve suggesting vegetations, and a 5.3-cm ascending aortic aneurysm. Empiric antimicrobial drug therapy, including vancomycin and ceftriaxone, was initiated. Subsequently, acute renal dysfunction, possibly secondary to vancomycin exposure, developed in the patient.
The patient lived alone on a farm in Iowa, USA, and had not had recent exposure to animals. However, he had observed murine fecal droppings in his house and mice on the farm. He had had a house cat for 18 years until its death a few years before his hospitalization and had intermittent contact with cats when he visited his daughter.
Serum immunoglobulin G titers were positive for B. henselae and B. quintana (>1,024). Oral doxycycline and rifampin were prescribed for treatment of presumed Bartonella endocarditis.
Gentamicin was not administered because of development of the acute renal dysfunction. Two weeks later, he underwent aortic valve and aortic root replacement.
Results of gram staining, acid-fast staining, fungal staining, anaerobic bacterial culture, aerobic bacterial culture, mycobacterial culture, and fungal culture on resected aortic valve tissue were negative for Bartonella species.
Conclusions
We isolated a new Bartonella species and propose that it be named Candidatus Bartonella mayotimonensis to recognize the contributing institutions (Mayo Clinic and H�pital de la Timone, Marseille, France). This is the seventh Bartonella species documented to cause infective endocarditis in humans.
The reservoir of Candidatus B. mayotimonensis has yet to be determined. Different Bartonella species have been isolated from a variety of mammals, and each species is highly adapted to its reservoir host (11,12). The domestic cat is the primary mammalian reservoir for B. henselae (13). Other Bartonella species have been found in mammalian hosts, including rats (B. elizabethae), dogs and coyotes (B. vinsonii subsp. berkhoffii), cats (B. koehlerae), humans (B. bacilliformis and B. quintana), moles (B. talpae), voles (B. vinsonii subsp. vinsonii), cows (B. bovis [weissii]), deer (B. schoenbuchensis), and rabbits (B. alsatica) (3-6,12,14,15). Our patient had direct exposure to mice on his farm and also had intermittent contact with cats while visiting his daughter. Additional investigations are needed to determine the reservoir(s) and vector(s) for this novel bacterium.
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J Neurol Neurosurg Psychiatry doi:10.1136/jnnp.2009.191940 Letter
Neuralgic amyotrophy associated with Bartonella henselae infection
Cari J Stek1, Jeroen J J van Eijk2, Bart C Jacobs4, Roelien H Enting3, Herman G Sprenger1, Nens van Alfen2, Sander van Assen1
1Department of Internal Medicine, Division of Infectious Diseases, University Medical Centre, Groningen, The Netherlands 2Department of Neurology and Clinical Neurophysiology, Donders Institute for Brain Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 3Department of Neurology, University Medical Centre, Groningen, The Netherlands 4Department of Neurology and Immunology, Erasmus Medical Centre, Rotterdam, The Netherlands Correspondence to Dr J J J van Eijk, 935 Department of Neurology, Donders Institute for Brain Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; [email protected] Contributors CJS and JJJvE contributed equally.
Received 17 August 2009 Revised 8 February 2010 Accepted 25 February 2010 Published Online First 14 August 2010
We report three patients with a brachial plexus neuropathy diagnosed as neuralgic amyotrophy (NA) preceded by a proven Bartonella henselae infection.
Neuralgic amyotrophy is a disabling disease involving the brachial plexus, with attacks of severe shoulder and arm pain followed by weakness and sensory involvement.1
Several observations support the hypothesis of an immune-mediated genesis. First, brachial plexus biopsies of NA patients in the (sub)acute stage show inflammatory changes.2 3 Second, antiganglioside antibodies are reported to be associated with NA.1 4 Third, several immune-triggering events, most frequently infections (50%), are known to precede NA.1-4 Various micro-organisms preceding NA have been reported (see table 1) but not yet B henselae.
B henselae is a Gram-negative, intracellular bacterium causing cat-scratch disease (CSD), which usually presents with fever, malaise and regional lymphadenopathy.
Occasionally, neurological complications occur, most frequently neuroretinitis and encephalopathy, but also peripheral nervous system disorders.5 These complications occur 1-3 weeks from the onset of lymphadenopathy, without any signs of direct infection of the nervous system, suggesting an immune-mediated genesis.
Infections can induce auto-immune reactions by several mechanisms. Molecular mimicry could be the underlying pathophysiological mechanism in NA, comparable with Guillain-Barr� syndrome, for example.
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nefferdun
Frequent Contributor (1K+ posts)
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Would someone please condense the information in all of these links and posts to relevant facts that might help us brain dead people?
I must be missing something but I am just too fried to look for it.
-------------------- old joke: idiopathic means the patient is pathological and the the doctor is an idiot Posts: 4676 | From western Montana | Registered: Apr 2009
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Germ that causes cat scratch disease not necessarily mild
September 20, 2010 By: Edie Lau For The VIN News Service
The pathogen best known for causing cat scratch disease is responsible for a host of serious illnesses in humans that may be misdiagnosed due to lack of awareness in the medical community.
Researchers studying the Bartonella genus of bacteria say veterinarians and veterinary staff, along with others who work with animals -- including groomers, trainers and shelter and rescue organization personnel -- are at particular risk of infection owing to their frequent exposure to animals and animal parasites such as fleas.
``I think it's more common than we think in the veterinary community,'' said Dr. Bruno Chomel, a DVM and professor in the Center for Vectorborne Diseases at the University of California, Davis.
The scope and significance of Bartonella infection among humans in veterinary circles and at large is just beginning to be understood.
Twenty years ago, only two Bartonella species were known. One, B. henselae, was identified as the agent behind cat scratch disease, a condition believed to be transmitted by a cat scratch or bite that causes swelling of the lymph nodes along with fever, headache, fatigue and/or poor appetite. Conventional wisdom said -- and says still -- that ``cat scratch fever'' is nothing to worry about for most people: Except in those with immune system deficiencies such as AIDS, the infection goes away on its own or with a short course of antibiotics. Bartonella became synonymous with mild illness.
But researchers say the picture is more complicated than that. Today, the number of Bartonella species identified is 26 and counting. Species exist that co-evolved with dogs, cattle, squirrels and ground hogs. Arthropods including fleas, lice and possibly ticks transmit the germ to mammals.
Those who study Bartonella characterize it as a ``stealth pathogen'' because of its ability to evade detection even at levels that cause illness. The bacterium has been found to invade and colonize a variety of cell types -- not only blood cells such as erythrocytes and macrophages but vascular endothelial cells and dendritic cells of the nervous system, as well.
This enables the microbe to disperse throughout the body and manifest in a wide range of debilitating conditions, including neuromuscular problems and endocarditis, a serious infection in the valves of the heart. Complicating diagnosis, many symptoms are non-specific. They include fatigue, headache, memory loss, insomnia, muscle pain and joint pain.
Ignorance in the medical community of the disease and its many possible forms has profound effects on those who come down with a clinical infection.
Dr. Kathy Tater, a veterinary dermatologist in Massachusetts, is a case in point. Tater said she visited nearly 20 health-care providers in different institutions over the course of a year before she was diagnosed with Bartonella -- and that was only because through her own reading, she found a laboratory with a sensitive test designed specifically to detect the elusive pathogen.
``What I found was that most physicians have not heard of Bartonella. They have heard of cat scratch disease, but that is not the same as knowing about Bartonella infections,'' said Tater, who is recovering. ``They were not aware that other strains of Bartonella existed, and they were not aware of how to test a person for Bartonella.''
Her story is familiar to Dr. Edward Breitschwerdt. A veterinary internist who directs the Intracellular Pathogens Research Laboratory at North Carolina State University College of Veterinary Medicine, Breitschwerdt has looked at hundreds of cases of suspected human Bartonella infections. Commonly, patients see a variety of specialists -- cardiologists, neurologists, rheumatologists, internists, infectious-disease experts and the like -- on their journey to a Bartonella diagnosis, Breitschwerdt has found.
As a veterinarian, he became by accident the go-to guy for people such as Tater. Breitschwerdt's focus was developing better detection tools for infections in dogs, in which Bartonella similarly is hard to find. The approach he hit upon is to first ``enrich'' the test sample of blood by culturing it in insect growth media rather than mammalian growth media, the standard culture for bacteria. Through this step, the population of bacteria builds up, making the microbes easier to find.
As Breitschwerdt lectured at veterinary conferences about the new diagnostic approach for dogs, a curious thing happened. Veterinarians would come up afterward and say that they'd been sick. They wondered whether they might be infected by this stealth pathogen.
``If there were 100 veterinarians in the audience, there might be three or four who would come up to me,'' Breitschwerdt said. ``They raised the question. I did not.''
That ushered Breitschwerdt into the human world of Bartonella infection. He began accepting human samples for analysis. ``After we developed this novel approach and had a fair amount of data that said it seemed to be working in people,'' he said, ``I tried to find a veterinary or human diagnostics company that would be willing to work with us or at least license the technology from the university.''
But the test isn't simple or cheap, and the idea of devoting significant resources to a pathogen that isn't widely recognized as important was a hard sell, he said. No one bit.
Breitschwerdt and others ultimately started their own company, Galaxy Diagnostics, to handle the work.
As word spread of Breitschwerdt's expertise, human samples flowed in from people in veterinary medicine and beyond. He estimates that he's tested 700 patients over the past three years. ``Overall, we're running about 31 percent positive. That's very high,'' he noted. ``Very high for an organism that is not supposed to be in the blood of immunocompetent people.''
Breitschwerdt began doing studies on human subjects. One subject was Dr. John Barnes, a small-animal and exotics practitioner in Uvalde, Texas.
Barnes, 54, was diagnosed with multiple sclerosis (MS) in 2005. Up to that point, he was a healthy man who jogged regularly and ran up and down bleachers at the local high school for exercise.
One day, shortly after a bout of 103-degree fever and vomiting that he attributed to food poisoning, Barnes was jogging around a track. On the third lap, his left leg stopped cooperating, causing him to stumble. A week or so later, Barnes began tripping again while jogging, this time on the second lap.
Thus began his journey through the medical system. One physician suspected a herpes virus. Another thought it might be Guillain-Barre, a rare neurological syndrome in which the body's immune system attacks part of the peripheral nervous system. Following an MRI and spinal tap, Barnes was told he had MS and that he would likely end up in a wheelchair.
Barnes was not so sure. ``I wasn't trying to balk at the diagnosis but because I had this huge fever (five months earlier) in December when all of this started, I thought maybe I had something else,'' he said. ``It sounded more inflammatory and (like an) infection.''
By chance, while conferring with a colleague at Texas A&M University about an oncology case, Barnes mentioned his condition. The colleague knew Breitschwerdt was doing a study involving veterinarians and veterinary technicians. She recommended Barnes get in touch with him.
It turned out that Barnes had an infection of B. henselae, the same species of Bartonella that causes cat scratch disease. His case and that of five other similarly infected patients was published in a study that appeared in the Journal of Clinical Microbiology in September 2008.
Whether the Bartonella infection had anything to do with his neurological symptoms or was mere coincidence was a point of debate and discussion among various doctors. ``I have so many ologists, I don't know what I'm doing,'' Barnes commented wryly.
His condition worsened in the meanwhile. He fell frequently, once breaking a rib.
Finally in August 2007, he was prescribed two antibiotics to combat the Bartonella: doxycycline and rifampin. Within a month, he said his toes, which had had a cadaverous gray tone, ``started pinking up.''
A couple months later, he noticed his fatigue lifting. By the following summer, he could stand on one leg, cross the other over his standing knee and look at the bottom of his foot -- a position he had not been able to assume in three years.
His odyssey didn't end there, unfortunately. Barnes stopped taking the antibiotics after a year. Breitschwerdt continued to monitor his blood. At first, Barnes was negative for Bartonella. But six months later, the bacteria reappeared.
Barnes went back on antibiotics. In February this year, he sent another blood sample to Breitschwerdt. The <i>B. hensalae</i> showed up still, and this time, not one strain, but two.
Was it the result of a new exposure or something that had been in hiding? The answer may never be clear.
Barnes said that as far as he knows, in 26 years as a clinician, he has never had a patient with a Bartonella infection. But he has spent plenty of time among animals and in the outdoors. ``My dad was a vet,'' he said. ``I was always catching frogs and toads (as a boy). So I think I'm exposed to all this junk.''
Despite the ongoing infection, Barnes said he is doing much better -- on the order of 60 to 70 percent improved, in his estimation. That tells him that while he truly may have MS, there's a relationship between his MS and Bartonella.
``I'm not saying I have just Bartonella or just MS,'' he said. ``But what if, of all the 400,000 people with MS right now, what if 2 percent of them are Bartonella-induced? People get their panties in a wad if I say that Bartonella causes MS. But (the diagnosis of Bartonella infection) helped me. I should be in a wheelchair right now.''
For Breitschwerdt, solving the mysteries of Bartonella has turned personal. In 2007, his 86-year-old father came down with a Bartonella infection that eluded medical professionals until Breitschwerdt ran the samples himself the following year. The researcher gave a moving account of the experience in the article ``A Groundhog, a Novel Bartonella Sequence, and My Father's Death,'' published in the U.S. Centers for Disease Control and Prevention journal Emerging Infectious Diseases.
Dr. Michael Kosoy, chief of the Bartonella Laboratory at the CDC in Fort Collins, Colo., said the pathogen's potential public health impact is taken more seriously in Europe and Asia, where Bartonella is appreciated as a cause of endocarditis and other serious ailments. In this country, by contrast, its importance is ``very, very much unrecognized,'' Kosoy said.
How the CDC Bartonella lab is supported illustrates the point: Kosoy said that although his lab is part of the Division of Vector Borne Diseases, most of its funding comes from the Global Diseases Detection Division. In other words, the CDC sees Bartonella infection more as a risk abroad than here.
Assuming that ever was true, conditions rapidly are changing. Kosoy said Bartonella species specific to rats in Asia and in Australia recently turned up in the California seaport cities of Los Angeles and Oakland. ``They travel with ships around the world,'' Kosoy said.
Lack of recognition of Bartonella's possible role in illness isn't absolute, of course. A few physicians are very aware of the pathogenic potential of the germ. One is Dr. B. Robert Mozayeni, a rheumatologist in North Bethesda, Md., whose quest to help patients with rheumatic conditions often confused with Lyme disease -- a tick-borne illness -- led him to Bartonella.
``In some studies of ticks, there was a significant prevalence of Bartonella,'' Mozayeni explained. ``Also, a significant percentage of cats carry Bartonella.'' From taking their medical histories, Mozayeni said he has learned that a significant fraction of his patients contracted their illness from their cats.
Further research led Mozayeni to Breitschwerdt. Now the two work together: Mozayeni is chief medical officer in Breitschwerdt's startup company, Galaxy Diagnostics.
To date, Mozayeni has evaluated some 400 patients with known or suspected Bartonella infections, some coming from as far away as Nevada, Idaho, Florida, and even other countries, such as Brazil and the Netherlands.
In his experience, Bartonella-infected patients respond with notable consistency to treatment. ``The consistency with the way they responded (positively) made me more convinced that this was a causative microbe, not just an incidental finding,'' Mozayeni said.
As a biomedical researcher trained at Yale University and the National Institutes of Health, Mozayeni called the Bartonella work ``the most exciting translational medicine I've seen --where we've gone from bench to bedside. I see such huge positive impacts on my patients' lives every day,'' he said. ``... The results have been nothing but spectacular. Most patients have gone from chronic disabled to revitalized, active people because we've been able to lock on this microbe.''
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Leading Off: Bartonellosis: Clinical and diagnostic challenges Apr 1, 2010 By: Edward B. Breitschwerdt, DVM, DACVIM
Edward B. Breitschwerdt
Prior to 1990, only two pathogenic Bartonella species, Bartonella bacilliformis and Bartonella quintana, were known to infect people, whereas bartonellosis was not yet known as a disease in pet or domestic animals.
Since 1990, more than 22 Bartonella species have been described, of which at least half have been implicated or confirmed as animal or human pathogens.
When a genus of bacteria is discovered or, in the case of Bartonella, rediscovered, numerous clinical, microbiological, and pathological concepts related to disease causation and microbial pathogenesis are sequentially redefined. Subsequently, the medical relevance of the genus undergoes continued maturation as knowledge of the organism, the host immune response, diagnostic test sensitivity and specificity, treatment efficacy, and epidemiology expand.
Since the early 1990s, this paradigm of discovery, rediscovery, and ongoing biological and medical redefinition has clearly been applicable to the genus Bartonella. This rapidly expanding body of clinically relevant information has been summarized in three recent reviews.1-3
A UNIQUE PATHOGEN
On an evolutionary basis, these highly fastidious, gram-negative bacteria have become adapted to one or more mammalian reservoir hosts (e.g. cattle, deer, elk, sheep, cats, squirrels, groundhogs, kangaroos, dogs, rats, rabbits), within which Bartonella species usually cause a long-lasting endotheliotropic infection, accompanied by a relapsing intraerythrocytic bacteremia. Also, an increasing number of arthropods, including biting flies, fleas, keds, lice, sand flies, and ticks, are confirmed or suspected vectors for Bartonella species transmission among various animal populations.
In the context of intravascular pathogens, Bartonella species may prove to be unique, as these bacteria can induce intraerythrocytic infection and vascular endothelial infection and, experimentally, can achieve intracellular localization within monocytes, macrophages, dendritic cells, and CD 34+ progenitor cells. In the reservoir-adapted host and perhaps in the accidentally infected patient, Bartonella bacteremia may be chronic, potentially spanning months to years in duration.
Although incompletely studied, these bacteria also appear to induce immune suppression through a variety of mechanisms. Collectively, these factors appear to contribute to a diverse spectrum of disease manifestations in people and dogs, including arthritis, endocarditis, epistaxis, granulomatous inflammation, lymphadenopathy, meningoencephalitis, osteomyelitis, panniculitis, and vasoproliferative lesions.1-5
A DIAGNOSTIC CHALLENGE
For the diagnostician, confirming infection with a Bartonella species remains extremely challenging. Bacterial isolation, serology, and PCR amplification of Bartonella species DNA directly from patient samples each have substantial diagnostic limitations. Enrichment culture of blood, cerebrospinal fluid, joint fluid, or various pathological effusions by using Bartonella alpha Proteobacteria Growth Medium (BAPGM--Galaxy Diagnostics) before PCR is performed is often required to document active infection with a Bartonella species.2,4,6,7
Studies from our laboratory have shown that about half of infected dogs will not have detectable antibodies to Bartonella species test antigens.2,6,8 Although unproven, it appears that chronic intravascular infection with a Bartonella species may induce a degree of immunological anergy, resulting in undetectable levels of organism-specific antibodies in some chronically infected patients.
A CONTINUING PURSUIT
Although numerous and important advances have increased our understanding of bartonellosis, there is a substantial need to better characterize various modes of transmission, the duration of infection, deleterious effects on immune function, cellular pathogenesis, optimal treatment regimens, and risk factors for zoonotic Bartonella species infections. Our research to date indicates that veterinary professionals are at risk for occupational exposure to numerous Bartonella species carried by pet and wild animals.2,9,10 In the context of public health, veterinarians should continue to eliminate and control arthropod vectors on animals; avoid bites, scratches, and contact with animal saliva; and exercise caution when obtaining and handling blood and other diagnostic samples.
Editors' note: Dr. Breitschwerdt is the chief scientific officer for Galaxy Diagnostics, which provides the BAPGM test.
Dr. Breitschwerdt is professor of medicine and infectious diseases at North Carolina State University College of Veterinary Medicine and an adjunct professor of medicine at Duke University Medical Center.
REFERENCES
1. Guptill L. Bartonellosis. Vet Microbiol 2010;140(3-4):347-359.
2. Breitschwerdt EB, Maggi RG, Chomel BB, et al. Bartonellosis: an emerging infectious disease of zoonotic importance to animals and human beings. J Vet Emerg Crit Care 2010;20(1):8-30.
3. Chomel BB, Kasten RW. Bartonellosis, an increasingly recognized zoonosis. J Appl Microbiol 2010 Jan 22. [Epub ahead of print]
4. Diniz PPVP, Wood M, Maggi RG, et al. Co-isolation of Bartonella henselae and Bartonella vinsonii subsp. berkhoffi from blood, joint and subcutaneous seroma fluids from two naturally infected dogs. Vet Microbiol 2009;138:368-372.
5. Breitschwerdt EB, Maggi RG. Comparative medical features of canine and human bartonellosis. Clin Microbiol Infect 2009 Apr 30 [Epub ahead of print].
6. Cherry NA, Diniz PPVP, Maggi RG, et al. Isolation or molecular detection of Bartonella henselae and Bartonella vinsonii subsp. berkhoffi from dogs with idiopathic cavitary effusions. J Vet Intern Med 2009;23(1):186-189.
7. Varanat M, Travis A, Lee W, et al. Recurrent osteomyelitis in a cat due to infection with Bartonella vinsonii subsp. berkhoffi genotype II. J Vet Intern Med 2009;23(6):1273-1277.
8. Duncan AW, Marr HS, Birkenheuer AJ, et al. Bartonella DNA in the blood and lymph nodes of Golden Retrievers with lymphoma and in healthy controls. J Vet Intern Med 2008;22:89-95.
9. Breitschwerdt EB, Maggi RG, Duncan AW, et al. Bartonella species in blood of immunocompetent persons with animal and arthropod contact. Emerg Infect Dis 2007;13(6):938-941.
10. Breitschwerdt EB, Maggi RG, Nicholson WL, et al. Bartonella sp. bacteremia in patients with neurological and neurocognitive dysfunction. J Clin Microbiol 2008;46(9):2856-2861.
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Bartonellosis: An emerging and potentially hidden epidemic?
Bartonella species, their animal hosts, potential vectors, and sequelae of infection are being identified at a snowballing rate. A new diagnostic test may help DVMs and MDs come together to better understand these infections in their patients.
Mar 1, 2010 By: Edward B. Breitschwerdt, DVM, DACVIM
Veterinarians and physicians should talk to each other more frequently than we have in the past. Of all known organisms, 61% are zoonotic,1,2 and of the emerging pathogens, the vast majority are zoonotic organisms. My research at the Intracellular Pathogens Research Laboratory at the North Carolina State University College of Veterinary Medicine focuses on vector-transmitted organisms, of which 22% are zoonotic.1,3 In recent years, the genus Bartonella has been the major focus of our vector-borne research efforts.
BARTONELLA SPECIES COMPLEXITIES
The organism that causes cat scratch disease in people was identified as a Bartonella species in 1992. As researchers have continued to study these bacteria, we've learned that the intraerythrocytic component of the infection with a Bartonella species has been somewhat overemphasized. My research laboratory and others have demonstrated that Bartonella species are endotheliotropic bacteria that use a specialized invasion process to enter endothelial cells and can move about the body by infecting macrophages, with localization in a variety of tissues.3
Knowing more about Agrobacterium species and the pathogenic mechanisms it uses to induce tumors in plants will probably benefit physicians and veterinarians in better understanding what Bartonella species are doing to promote vasculoproliferative disorders in our patients.4 Researchers have learned that Bartonella species are the first bacteria identified to have an ability to invade CD34+ progenitor cells in bone marrow.5 This may be why we find Bartonella organisms in cats in only a low percentage (3%) of their erythrocytes.
The genus Bartonella is also unusual because it appears that no other infectious agent is transmitted by more vectors. We now know that sand flies, human body lice, cat fleas, rodent fleas, and probably many other flea species are capable of transmitting certain Bartonella species. And cattle, deer, elk, and sheep all have their own Bartonella species that appear to be transmitted by biting flies or keds (wingless flies).6
Our laboratory wondered whether ticks could transmit Bartonella species. Currently, the answers appear to be yes and maybe.7 Good case-based evidence exists in the human and veterinary medical literature that suggests ticks may transmit Bartonella species. And in many laboratories around the world, PCR testing reveals Bartonella species DNA in ticks, particularly in Ixodes species ticks. Researchers in France have nearly demonstrated Ixodes ricinus transmission of Bartonella henselae.8 Interestingly, Bartonella henselae is prevalent in I. ricinus ticks in southern Germany and in France.9 However, although tick transmission of Bartonella species is possible, it hasn't yet been definitively proven for ticks in North America.
IS A HIDDEN EPIDEMIC POSSIBLE?
In my opinion, a hidden epidemic is possible if several conditions are met.
First, you start with an unknown bacterial genus, which was the situation for Bartonella in North America and much of the world until the human immunodeficiency virus (HIV) epidemic of the late 1980s and 1990s.
Second, the organism must behave as a stealth pathogen that is capable of hiding in the host, as is true for Bartonella species.10
Third, a large number of diverse animal reservoir hosts for the organism are maintained in nature--and that too is the case for the genus Bartonella. Several mammals--grey squirrels, flying squirrels, groundhogs--have their own genetically distinct Bartonella species that have coevolved in those animals and have a high prevalence in their respective hosts in nature.
Finally, the organism creatively facilitates its transmission, not only through vectors, but by direct transmission through bites and scratches, which has been reasonably well-established for dogs and cats and for rabbits in Europe.11
AN UNDER-RECOGNIZED ZOONOSIS
In my opinion, physicians and veterinarians need to come together regarding bartonellosis, because it appears to be an important and under-recognized zoonosis. Depending on their immune competence, people with bartonellosis exhibit tremendous differences in disease expression. And with regard to immunocompetence, we have to consider not only people with severe immunosuppressive illnesses such as infection with HIV, but also pregnant women, children, geriatric people, transplant recipients, and patients treated with immunosuppressive drugs.
Furthermore, diagnostic test sensitivity for documenting infection with this genus of bacteria is extremely poor, and based upon recent experience in our laboratory, patient response to treatment is frequently incomplete.
Endocarditis can be induced by a spectrum of Bartonella species in dogs and human patients and is the best example of documented disease causation for this genus. Historically, Bartonella species have been a cause of culture-negative endocarditis in people and dogs because the diagnostic methods that microbiology laboratories used were not adequate to isolate these bacteria.
Now, by using specialized techniques, a spectrum of Bartonella species are being identified in research and diagnostic laboratories in different parts of the world--in heart valves or in blood cultures from people and dogs with endocarditis.12 And what's important for physicians and veterinarians to recognize is that some of these Bartonella species are found in cats, dogs, rats, ground squirrels, and rabbits. In 1992, two Bartonella species were known to exist, and in 2009, over 26 named or candidatus species exist.
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TX vet co-infected with Bart and two Mycoplasma from sheep!
Journal of Clinical Microbiology doi:10.1128/JCM.01029-10 Copyright (c) 2010, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
Human co-infection with Bartonella henselae and two hemotropic mycoplasma variants resembling Mycoplasma ovis.
Jane E. Sykes*, LeAnn L Lindsay, Ricardo G. Maggi, and Edward B. Breitschwerdt
Department of Medicine & Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA (J. Sykes and L. Lindsay) and Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606 (E. Breitschwerdt and R. Maggi) Correspondence should be addressed to email: [email protected]
Abstract Two variants of an organism resembling the ovine hemoplasma, Mycoplasma ovis, were detected using PCR in blood samples from a veterinarian in Texas. Coinfection with similar variants has been described in sheep. This represents the first report of human infection with this organism. The veterinarian was co-infected with Bartonella henselae.
* * * * * * * Ovine means sheep.
Here's a bit of general info about Mycoplasma found on The Free Dictionary by Farlex:
The genus Mycoplasma are among the smallest of bacterial organisms. The cell varies from a spherical or pear shape to that of a slender branched filament. Mycoplasma species are gram-negative and do not require oxygen. They are colonial microorganisms that lack cell walls.
Mycoplasma spp are parasites of joints and the mucous membranes lining the respiratory, genital, or digestive tracts of cud-chewing animals, carnivores, rodents, and humans. Toxic by-products excreted by the bacteria accumulate in the host's tissues, causing damage. One species causes a widespread but rarely fatal pneumonia in humans.
FuzzySlippers, thanks for this informative Bartonella thread! Smile
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Bartonellosis: An Emerging Disease You Should Know About
Bartonellosis, also known as the `cat scratch disease,' is currently under study to better understand its potential to damage the health of both humans and animals.
Among the new findings about the Bartonella bacteria:
It can cause illness in people and dogs
In the last 20 years, over two dozen new strains of the pathogen have been identified
It is not a self-limiting disease, meaning it does not always run its course without medical intervention
The disease affects not only immunocompromised people, but also people with healthy immune systems . . .
Bartonella Vectors and Hosts
Currently, the following insects are known to be capable of transmitting certain species of the Bartonella bacteria:
Cat fleas Human body lice Rodent fleas Sand flies It is suspected many other flea species can also be transmitters, as well as both the biting flies and wingless flies (known as 'keds') that feed on cattle, deer, elk and sheep.
It also appears likely ticks can transmit species of Bartonella, in particular the common Ixodes species of ticks.
A list of known hosts of Bartonella bacteria includes:
Pocket pets (rodents, rabbits)
Domesticated dogs and cats (including feral cats -- one to two out of every three tested in North Carolina showed positive for the bacteria)
Deer, elk, sheep
Grey squirrels, flying squirrels, groundhogs
Cows (over 80 percent of beef cattle in North Carolina were discovered to have a species of Bartonella in their blood)
KangaroosSymptoms of Bartonellosis
Interestingly, many of the symptoms of the disease are the same for both people and dogs. Unfortunately, many Bartonellosis symptoms are also seen in a wide variety of more common and better understood diseases. This makes accurate diagnosis of Bartonellosis less likely.
The disease impacts microcirculation, causing neurological symptoms including:
Severe pain Numbness Weakness Palpitations Acne on the upper face and forehead Rashes Folliculitis on the upper arms Red stretch marks The first dog Dr. Breitschwerdt (DVM at North Carolina State) tested that was positive for Bartonellosis was a three year-old Labrador retriever.
The dog had been on a year-long course of increasing doses of immunosuppressant drugs due to misdiagnosis of the disease. During that year, the lab went on to develop Bartonella-related seizures, arthritis, vasculitis (inflammation of the blood vessels), epistaxis (nose bleeds), and aortic and mitral valve endocarditis.
Similar situations have been documented with human patients at the Mayo Clinic and Duke University Medical Center. Misdiagnosis and subsequent treatment with immunosuppressant drugs resulted in development of Bartonellosis-related endocarditis. (Endocarditis is inflammation of the heart's inner lining, usually also involving the heart valves.)
In fact, about 80 percent of people and the same percentage of dogs with Bartonellosis develop endocarditis selectively involving the aortic valve.
Dr. Breitschwerdt also suggests that doctors should check for Bartonellosis as a potential cause of unexplained nosebleeds in children.
Diagnosis
Bartonella infection is proving extremely difficult to diagnose in many situations.
The bacteria is able to hide in endothelial tissues (tissues composed of the endothelial cells that line the entire circulatory system), thus the description of it as a 'stealth' pathogen. Dr. Wendy Walker's story is just one of many harrowing tales of missed diagnoses and years of suffering with chronic, debilitating disease.
When the disease was discovered in 1992, only two species of bacteria were known. Today, 26 have been identified.
The usual tests to detect infection -- including cultures, bacterial DNA tests, and antibody testing - don't pick up every incidence of infection. Dr. Breitschwerdt's laboratory has developed a special test which, when combined with other tests, is more effective at detecting the presence of different Bartonella bacteria species.
Treatment
The current treatment protocol for both humans and dogs is a six-month course of antibiotics.
According to Dr. Bobak Robert Mozayeni, a physician and leading expert on Bartonella who practices in Rockville, MD, 95 percent of patients uniformly respond to treatment, without damage to kidneys or the liver according to results of monthly lab work he runs.
Dr. Moyazeni is uncertain about the potential for relapse: "In dogs, there is a 15 percent relapse rate even after six months of treatment, but we need to do formal studies to answer these questions (on the human side)," he says. "But because it's so new, it's hard to get anyone's attention."
[click on link for remainder of article]
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Surviving bartonellosis Veterinarian talks about long-term medical odyssey with disease
Dec 1, 2010 By: Daniel R. Verdon DVM NEWSMAGAZINE
National Report-- Her medical battle with bartonellosis lasted for years. Ironically, it took a horse throwing her, fracturing her shoulder, for physicians to make an accurate diagnosis.
Veterinarian Wendy Walker of Olney, Md. can't pinpoint when she contracted Bartonella, but it has changed her life in ways few could imagine.
Her infection resulted in a kind of cascade of medical problems that tested our human medical and diagnostic system, and resulted in revolving door of specialists, surgeons and doctors all stymied by her chronic condition.
"Bartonella can result in just such a horrible disease. It is such an invasive bug," she tells DVM Newsmagazine.
The symptoms for Walker started as fibromyalgia. "No one could put a finger on what my problem was."
She then lost the use of her right arm. Consults with orthopedic and neurosurgeons hatched a short-lived plan to fuse her neck. Before surgery, she was told by a prominent neurosurgeon, "I don't know what you have, but it is not a surgical fix."
Trigger point injections (30 at a time) was the only way she could use her ailing arm. Her myofacial pain could only be characterized as "horrible."
"Nobody really knew what was going on. I was tested for rheumatoid arthritis, lupus and others. She even tested for cat-scratch disease, but at that time, the tests came back negative.
In the ensuing years, Walker went through four arthroscopic knee surgeries. In 2007, her horse threw her and seriously fractured her shoulder. The fracture was so bad she had to resign her presidency of the Maryland Veterinary Medical Association. Within 24 hours, her knee blew up to the size of a basketball. "It was more painful than the fracture of my arm," she recalls. "They tapped it, and fluid shot across the room. They said, 'you have Lyme disease.' " They were wrong, but the resulting injuries meant three more knee surgeries and a shoulder surgery.
Finally, Walker found herself sitting in Dr. Bobak Robert Mozayeni's office. She had a diagnosis. Walker had pseudogout, a condition that attacks the joint with the formation of calcium crystals. And the Bartonella infection was setting her up for multiple other conditions including the pseudogout. Five orthopedic doctors missed the diagnosis, and it was even outlined in a pathology report, she later found out.
Walker underwent three months of antibiotic therapy, including rifampin (a drug used to treat tuberculosis). The rafampin alone cost $800 a month. And the costs kept piling up. "Insurance companies will fight the costs," she adds.
"Half the trick to treating Bartonella is appropriate treatment. It's a disease that attacks your vascular system. The bug hides out in the endothelial tissues, and it is very difficult to treat sometimes," Walker says.
In the spring of last year, during a veterinary meeting in Colorado, Walker simply blacked out. She suffered from global transient amnesia. Two more episodes occurred, and a brain scan revealed a vasculitis in her brain. Again, it was consistent with bartonellosis.
Walker recounts her story as a way to help sick veterinarians move through the right medical channels.
And while her disease has changed her life, she says pets will remain an important part of it.
"I got into this profession because I love animals, but I think veterinarians need to know about the risks too."
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Bartonella: Quantifying new risks to veterinarians, patients Dec 1, 2010 By: Daniel R. Verdon DVM NEWSMAGAZINE
National Report-- Bartonellosis: It's no longer considered a self-limiting disease, and for some people chronic infection can be as debilitating and hard to diagnose as Lyme disease.
While new human medical and veterinary research is quickly debunking traditional beliefs about these infectious bacteria, expert Dr. Edward Breitschwerdt, of North Carolina State University's College of Veterinary Medicine, wants veterinarians to sit up and take notice. The health risks appear to be very real, and they are heightened by frequent contact with sick animals.
"Going from not knowing a genus of bacteria existed in the 90s to now realizing that cats, dogs, cows, deer, squirrels, voles, moles and kangaroos in Australia are all running around with their own Bartonella species in their blood changes the dynamics of the human-animal bond. And it creates some caution that we didn't have to worry about five years or 10 years ago when we didn't know this information."
Breitschwerdt has spent much of his professional career studying vector-borne infectious diseases. And while cat-scratch disease was recognized nearly 100 years ago, the bacteria that causes this and other Bartonella-related disease manifestations and the routes by which humans become infected needs much more research. What is known is that Bartonella henselae, B. clarridgeiae, B. koehlerae can be transmitted by infected fleas and the inoculation of flea feces. The infected nail beds and saliva of cats are routes of transmission following a bite or scratch," Breitschwerdt says. And persistent intravascular infection in some individuals can result in a cascade of medical conditions like arthritis, endocarditis, encephalitis and others (Tables 1 and 2).
"In the last 2.5 years, we published eight research manuscripts involving human infection. If you spent the time to read all eight, you would be very concerned."
Just last month, a scientific report was published in the Journal of Veterinary Internal Medicine chronicling potential transmission of Bartonella vinsonii subsp. berkhoffii, for which dogs, foxes and coyotes are the reservoir hosts, from an accidental needle stick.
The science challenges two long-standing myths:
> Cat-scratch disease is always self limiting -- in other words, the problem (and the infection) just goes away with time. > And Bartonella causes chronic bacteremia in immunocompromised people but does not cause persistent bacteremia in immunocompetent people.
The science is so new that most physicians aren't aware of the threat to some patients, especially those who handle animals frequently.
In fact, in a paper recently published by Breitschwerdt, et al. titled "PCR amplification of Bartonella koehlerae from human blood and enrichment blood cultures", the study concludes that B. koehlerae bacteremia is more common in immunocompetent people than previously suspected. New studies, the authors suggest, are needed to determine if B. koehlerae is a cause or cofactor in the development of arthritis, peripheral neuropathies or tacyarrhythmias in patients."
So how serious is the threat? No one really knows.
In the past 20 years, researchers have identified 26 species of this bacteria. Some pose health concerns to people, dogs and, increasingly recognized, cats. While evolution has helped cats deal with Bartonella and "they can carry those organisms for years without becoming outwardly sick," they can develop disease.
"What we do know is that there has been a microbiological revolution in the discovery of numerous species in the genus Bartonella. These bacteria reside in the blood of healthy and sick animals that are seen by veterinarians every day. The problem for veterinarians, other animal-health professionals and for individuals with intimate animal contact or frequent arthropod exposure is that our understanding of the transmission of these bacteria is very incomplete," he says.
The recognition of this safety risk has spurred more study on these vector-transmitted diseases.
In fact, Breitschwerdt's team at NCSU started testing people to determine if they could find Bartonella in human blood samples after newly developed techniques improved the detection in cat and dog blood samples. "Although unintentionally biased, the study population became people who were attending national, local, regional and international meetings where Breitschwerdt lectured - thus, they were veterinarians, technicians, a veterinarian's wife or husband who might have been holding the animal that had been hit by a car at night. Someone might receive a bite or scratch while holding this painful and fractious animal, while another person was trying to get a catheter in and sedate the animal.
"What became rapidly clear, as we tested sick veterinarians, was the fact that a rather high percentage of people -- up to 50 percent depending on the population that we looked at -- were actually infected with one or more Bartonella species." The researchers also tested 30 healthy individuals who did not have extensive animal contact or arthropod exposure, and they never found Bartonella in the blood.
"The only thing we can definitively say at this point is ... veterinarians or others who do have extensive animal contact and arthropod exposure are more likely to have these bacteria in their blood."
Treatment with antibiotics is generally effective. The problem, Breitschwerdt says, it's just not on the radar of most physicians or veterinarians as a cause of disease in people or pets.
"This is one of the areas where a lot of work needs to be done. We need to better understand what types of disease Bartonella might be able to cause and determine how Bartonella causes disease."
Case in point? Dr. Michael Lappin's laboratory at Colorado State University and others from around the world have PCR amplified DNA of various Bartonella species from saliva. "We don't know for sure whether saliva is infectious at this point in time... but I do think that contact with saliva should be limited until we have a better understanding of the transmission dynamics," he adds.
Problem list keeps getting longer It is known that dogs and people develop very similar pathology (Tables 1 and 2), and the list keeps growing: thrombocytopenia, immune-mediated hemolytic anemia, encephalitis and arthritis.
The best characterized examples of disease in dogs or humans is endocarditis. In fact, it's the number one cause of blood-culture negative endocarditis. Immunocompromised people or those on immunosuppressive drugs can develop an unusual vasoproliferative lesion, called bacillary angiomatosis. This rare pathological entity has been reported in the literature in a dog that was immunosuprressed and was later confirmed to be infected with B. vinsonii subsp. berkhoffi.
"One thing I have said in lectures is that the dog is a wonderful naturally occurring model to help us understand human bartonellosis. And the human is a wonderful naturally occurring model to better understand canine bartonellosis." Bartonellosis is an excellent example of the importance of "One Medicine and One Health," he adds.
And while Breitschwerdt's affiliation with a testing service called Galaxy Diagnostics hopes to improve data on the numbers of confirmed cases of animal and human infections throughout the United States, the problem, Breitschwerdt says, is the lack of funding for Bartonella research. Currently, the National Institutes of Health has only two funded Bartonella research grants throughout the United States.
"I think both the bacteria and the diseases that these bacteria cause are very much under-appreciated. During the past few years, I certainly have invested a fair amount of my life trying to convince people that there is a problem. I also realize that it takes a lot of medically relevant information from a lot of laboratories and research centers before our medical infrastructure sits up and takes notice of a potentially important cause of chronic disease."
But, Breitschwerdt wants veterinarians and team members to have a clear understanding of the risks associated with these bacteria to help with an early diagnosis and needed advancements in treatment strategies.
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Could your veterinary job destroy your life? By Steve Bennaka, Associate Editor
A young mother, athlete, and veterinary practice manager suffered through extreme fatigue and muscle pain for three years before she discovered her life would never be the same. Could the same thing happen to you simply because of where you work?
Tracy Vargas is not the mom she used to be. She simply doesn't have the energy. Her joints hurt, she gets frequent headaches, and she finds herself short of breath with the slightest physical activity. Often, it's difficult just to get out of bed.
For Vargas, practice manager at Town and Country Animal Clinic in Olney, Md., life hasn't been the same since she contracted bartonellosis more than three years ago. Her three sons, ages 11, 7, and 5, do their best to put on a brave face and be understanding on the days when Vargas just can't do the things she'd like to do.
``It's heartbreaking as a mom,'' Vargas says. ``I hate the days that I'm short on patience due to the constant pain and fear that looms over me every day. I sometimes watch them sleep and I cry, praying that the air comes to my lungs and the chest tightness goes away. And then there are those dreaded days when I have to say, `Sorry, boys, find something quiet to do because Mommy's having a rough day.' That makes me feel like a failure.''
Until May, Vargas didn't even know what was wrong with her body--and neither did anyone else. After countless visits to her physician, she was diagnosed with everything from fibromyalgia to a pulmonary embolism. It wasn't until talking to Town and Country's practice owner, Dr. Wendy Walker, that she began to wonder if she could find answers through veterinary testing.
Dr. Walker had experienced similar symptoms, so the pair sent blood samples to Dr. Edward Breitschwerdt, DACVIM, who's researching the Bartonella species through his role as professor of medicine and infectious diseases at North Carolina State University College of Veterinary Medicine in Raleigh, N.C. Sure enough, Dr. Breitschwerdt identified the infection in both women's blood. They finally had an answer--though one nobody likes to hear: They had contracted bartonellosis, a debilitating zoonotic disease that stems from the Bartonellabacteria found in many pets' blood and most commonly transmitted to people when cat bites or scratches are contaminated with flea excrement.
``This has destroyed my life on every level,'' Vargas says.
From running to rest Vargas' running shoes sit in her closet, largely unused these days. They used to travel all over her neighborhood miles at a time, rain or shine five days a week. Vargas would stride through the crisp morning air almost effortlessly, reveling in the challenge and pushing herself harder each run. Had she known what her life would become, she might have taken a few extra seconds each day to cherish this exercise and reflect on the amazing effort her body could produce.
Once the muscle pains and headaches kicked in, Vargas' fitness regimen came to an abrupt halt. She became short of breath just walking, let alone trying to shave a few seconds off her mile time. So she shifted her energy into a different venture: managing the disease that has changed her life in a way that so few people understand.
Even her physician was stumped. ``A lot of physicians aren't aware of it,'' Vargas says. ``You say bartonellosis and their faces just scrunch up. That's scary to me. Many people get sick, and their doctors tell them they don't know what's wrong. This is something that the public needs to be aware of.''
To manage the disease, Vargas is seeing an internist who also uses holistic care. Her treatment consists mainly of taking vitamins and supplements to build up her immune system, which was so taxed for three years while she fought the infection. ``It's sad to say, but he's the only doctor I've talked to who is not only familiar with zoonotic disease but believed in it and was educated on how to treat it,'' Vargas says.
And while some of her symptoms have decreased in intensity, she knows the recovery process won't be speedy. ``I don't know if I can ever get back to 100 percent, but I'm determined to get as close as possible,'' Vargas says. ``If there's anyone who can get there, it's me.''
Mystery cause
Perhaps the most unsettling part of Vargas' ordeal is that she still doesn't know how she became infected. The bacteria could have entered her system through a scratch or bite at the veterinary clinic, or it could have happened at home--Vargas has three cats and two dogs. No single incident sticks out in her mind, but if there's one good thing to come out of the diagnosis, it's that she and her co-workers are now much more aware of the disease.
``I have to admit, I really wasn't educated on bartonellosis,'' Vargas says. ``I didn't know much about it, and I certainly didn't think of it as a threat.''
The team at Town and Country now focuses more on hand washing and treating scratches they get from pets, and employees use even more caution when handling fractious animals. They also take the opportunity to educate clients on the disease, armed with the knowledge of just how much it has affected their friend and co-worker. ``They've watched me suffer for three years--they know what it can do,'' Vargas says. ``It's kind of hard not to be affected by it.''
Working toward normalcy
Perhaps one day, scientists will find a cure for bartonellosis. For now, Vargas works toward getting back to normal--as normal as her diagnosis allows her to be, anyway. ``It's hard to look at yourself in the mirror and say, `You're not a bad mom, you just have limits you didn't have before,''' Vargas says.
The running shoes will once again see the light of day, though it may take some time. Vargas can finally walk reasonable distances without losing her breath, and she hopes to begin running again by next summer. She now works four days a week--some from home--and may eventually return to her six-day-a-week schedule as the disease allows. Until then, she'll continue to lean on her understanding family while she progresses with her recovery.
``I'm very lucky--I have a supportive family that is there when I need it,'' Vargas says. ``I want to be an independent person, but I just can't be.''
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Scratching the surface The human medical field knows little about bartonellosis, but one physician is trying to make inroads
Dec 1, 2010 By: Alicia Karapetian DVM NEWSMAGAZINE
National Report -- Pain. Numbness. Weakness. Palpitations. These symptoms can be indicative of a variety of conditions, but sometimes the accurate diagnosis is bartonellosis, a chronic infection veterinarians have an elevated risk of contracting.
Bartonellosis manifests in humans as cat-scratch disease due to a strain seen in and passed from felines. Human medicine has much to learn about the condition, says Bobak Robert Mozayeni, MD, a leading expert on Bartonella.
"We are about to enter an era that awareness of chronic infection and its role in human disease is just beginning to emerge," he says. Those with Bartonella can often be misdiagnosed as having chronic Lyme disease, which similarly manifests, though the two are distinct.
Bartonella affects the microcirculation, and, in turn, can cause neurological symptoms. Mozayeni says patients tend to have both central and peripheral nervous system neurological issues, such as palpitations, severe pain, numbness and weakness. Often, adult patients will have acne on their upper face and forehead or get rashes, folliculitis on their upper arms and red stretch marks.
Since no large-scale research or clinical trial has been conducted related to Bartonella infections, many doctors don't diagnose it. As a result, patients as far away as California come to Mozayeni's Rockville, Md., practice for a consultation. "I've diagnosed and treated almost 200 patients and tested 500," he says. "A couple hundred have been through or are in treatment. Even when you develop experience like this, it's not enough to convince other doctors."
Mozayeni has many patients who are DVMs because of his work in this area. Veterinarians are at higher risk of contracting the disease because of their exposure from animals. "From my point of view, it's a pleasure to work with DVMs as patients," he says. "They get it; understand it; know what needs to be done with no medical legal paranoia. They have a vested interest in getting well, understand antibiotics and the potential side effects."
Some of the advice on treatment coming from his colleagues, however, is disconcerting, he says. Some of his other patients have had doctors halting treatment due to potential side effects. But Mozayeni contends that the treatment not only works, but he hasn't seen damage to patients' kidneys and livers. "Ninety-five percent of patients respond to treatment, and all in the same way," he says. "None of the antibiotics we have used have created liver or kidney trouble in any of several hundred patients I've treated. We check the lab work once a month, and typically all we see is a white-count lowering, which is likely attributed to the infection being treated."
Most patients receive a six-month course of antibiotic treatment, though Mozayeni is uncertain about the potential for relapse. "In dogs, there is a 15 percent relapse rate even after six months of treatment, but we need to do formal studies to answer these questions (on the human side)," he says. "But because it's so new, it's hard to get anyone's attention."
Mozayeni says the lack of awareness stems from a long-standing attitude that Bartonella is a veterinary disease and not a human one, but now that more and more cases are emerging, heads are starting to turn. "This is how translational medicine goes. There's a lone voice heard," he says. "What you have to count on is the open-mindedness of your colleagues, and that's not a common thing."
Nevertheless, Mozayeni hopes his work will grab enough attention that a large-scale clinical trial can take place to answer many questions about the condition itself and treatment. But, he concedes, "Generally speaking, most physicians are late adopters for major thought change."
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Leading Off: Bartonellosis: Clinical and diagnostic challenges Apr 1, 2010 By: Edward B. Breitschwerdt, DVM, DACVIM VETERINARY MEDICINE
Edward B. Breitschwerdt
Prior to 1990, only two pathogenic Bartonella species, Bartonella bacilliformis and Bartonella quintana, were known to infect people, whereas bartonellosis was not yet known as a disease in pet or domestic animals. Since 1990, more than 22 Bartonella species have been described, of which at least half have been implicated or confirmed as animal or human pathogens.
When a genus of bacteria is discovered or, in the case of Bartonella, rediscovered, numerous clinical, microbiological, and pathological concepts related to disease causation and microbial pathogenesis are sequentially redefined.
Subsequently, the medical relevance of the genus undergoes continued maturation as knowledge of the organism, the host immune response, diagnostic test sensitivity and specificity, treatment efficacy, and epidemiology expand. Since the early 1990s, this paradigm of discovery, rediscovery, and ongoing biological and medical redefinition has clearly been applicable to the genus Bartonella. This rapidly expanding body of clinically relevant information has been summarized in three recent reviews.1-3
A UNIQUE PATHOGEN
On an evolutionary basis, these highly fastidious, gram-negative bacteria have become adapted to one or more mammalian reservoir hosts (e.g. cattle, deer, elk, sheep, cats, squirrels, groundhogs, kangaroos, dogs, rats, rabbits), within which Bartonella species usually cause a long-lasting endotheliotropic infection, accompanied by a relapsing intraerythrocytic bacteremia. Also, an increasing number of arthropods, including biting flies, fleas, keds, lice, sand flies, and ticks, are confirmed or suspected vectors for Bartonella species transmission among various animal populations.
In the context of intravascular pathogens, Bartonella species may prove to be unique, as these bacteria can induce intraerythrocytic infection and vascular endothelial infection and, experimentally, can achieve intracellular localization within monocytes, macrophages, dendritic cells, and CD 34+ progenitor cells. In the reservoir-adapted host and perhaps in the accidentally infected patient, Bartonella bacteremia may be chronic, potentially spanning months to years in duration. Although incompletely studied, these bacteria also appear to induce immune suppression through a variety of mechanisms.
Collectively, these factors appear to contribute to a diverse spectrum of disease manifestations in people and dogs, including arthritis, endocarditis, epistaxis, granulomatous inflammation, lymphadenopathy, meningoencephalitis, osteomyelitis, panniculitis, and vasoproliferative lesions.1-5
A DIAGNOSTIC CHALLENGE
For the diagnostician, confirming infection with a Bartonella species remains extremely challenging. Bacterial isolation, serology, and PCR amplification of Bartonella species DNA directly from patient samples each have substantial diagnostic limitations. Enrichment culture of blood, cerebrospinal fluid, joint fluid, or various pathological effusions by using Bartonella alpha Proteobacteria Growth Medium (BAPGM--Galaxy Diagnostics) before PCR is performed is often required to document active infection with a Bartonella species.2,4,6,7
Studies from our laboratory have shown that about half of infected dogs will not have detectable antibodies to Bartonella species test antigens.2,6,8 Although unproven, it appears that chronic intravascular infection with a Bartonella species may induce a degree of immunological anergy, resulting in undetectable levels of organism-specific antibodies in some chronically infected patients.
A CONTINUING PURSUIT
Although numerous and important advances have increased our understanding of bartonellosis, there is a substantial need to better characterize various modes of transmission, the duration of infection, deleterious effects on immune function, cellular pathogenesis, optimal treatment regimens, and risk factors for zoonotic Bartonella species infections. Our research to date indicates that veterinary professionals are at risk for occupational exposure to numerous Bartonella species carried by pet and wild animals.2,9,10 In the context of public health, veterinarians should continue to eliminate and control arthropod vectors on animals; avoid bites, scratches, and contact with animal saliva; and exercise caution when obtaining and handling blood and other diagnostic samples.
Editors' note: Dr. Breitschwerdt is the chief scientific officer for Galaxy Diagnostics, which provides the BAPGM test.
Dr. Breitschwerdt is professor of medicine and infectious diseases at North Carolina State University College of Veterinary Medicine and an adjunct professor of medicine at Duke University Medical Center.
REFERENCES
1. Guptill L. Bartonellosis. Vet Microbiol 2010;140(3-4):347-359.
2. Breitschwerdt EB, Maggi RG, Chomel BB, et al. Bartonellosis: an emerging infectious disease of zoonotic importance to animals and human beings. J Vet Emerg Crit Care 2010;20(1):8-30.
3. Chomel BB, Kasten RW. Bartonellosis, an increasingly recognized zoonosis. J Appl Microbiol 2010 Jan 22. [Epub ahead of print]
4. Diniz PPVP, Wood M, Maggi RG, et al. Co-isolation of Bartonella henselae and Bartonella vinsonii subsp. berkhoffi from blood, joint and subcutaneous seroma fluids from two naturally infected dogs. Vet Microbiol 2009;138:368-372.
5. Breitschwerdt EB, Maggi RG. Comparative medical features of canine and human bartonellosis. Clin Microbiol Infect 2009 Apr 30 [Epub ahead of print].
6. Cherry NA, Diniz PPVP, Maggi RG, et al. Isolation or molecular detection of Bartonella henselae and Bartonella vinsonii subsp. berkhoffi from dogs with idiopathic cavitary effusions. J Vet Intern Med 2009;23(1):186-189.
7. Varanat M, Travis A, Lee W, et al. Recurrent osteomyelitis in a cat due to infection with Bartonella vinsonii subsp. berkhoffi genotype II. J Vet Intern Med 2009;23(6):1273-1277.
8. Duncan AW, Marr HS, Birkenheuer AJ, et al. Bartonella DNA in the blood and lymph nodes of Golden Retrievers with lymphoma and in healthy controls. J Vet Intern Med 2008;22:89-95.
9. Breitschwerdt EB, Maggi RG, Duncan AW, et al. Bartonella species in blood of immunocompetent persons with animal and arthropod contact. Emerg Infect Dis 2007;13(6):938-941.
10. Breitschwerdt EB, Maggi RG, Nicholson WL, et al. Bartonella sp. bacteremia in patients with neurological and neurocognitive dysfunction. J Clin Microbiol 2008;46(9):2856-2861.
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Beyond Cat Scratch Disease: Widening Spectrum of Bartonella henselae Infection
Todd A. Florin, MDa,b, Theoklis E. Zaoutis, MD, MSCEb,c,d,e, Lisa B. Zaoutis, MDa,b a Divisions of General Pediatrics c Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania b Departments of Pediatrics d Epidemiology e Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
ABSTRACT
Bartonella henselae was discovered a quarter of a century ago as the causative agent of cat scratch disease, a clinical entity described in the literature for more than half a century. As diagnostic techniques improve, our knowledge of the spectrum of clinical disease resulting from infection with Bartonella is expanding. This review summarizes current knowledge regarding the microbiology, clinical manifestations, diagnostic techniques, and treatment of B henselae infection.
Cat scratch disease (CSD) has been reported in the literature for more than half a century as a syndrome of regional lymphadenopathy and fever. However, it has been only a quarter of a century since Bartonella henselae was identified as the etiologic agent. As diagnostic techniques have improved, Bartonella has been found to be responsible for a broad range of clinical syndromes, particularly prolonged fever of unknown origin (FUO), hepatosplenic disease, encephalopathy, and ocular disease. Although other Bartonella species can cause human disease, this review will focus on those caused by B henselae.
HISTORICAL CONTEXT
The clinical syndrome of CSD was first reported in 1950 by Debr� et al1, although Parinaud2 described similar symptoms in the context of oculoglandular syndrome in 1889. Despite numerous reports and studies of CSD, the causative agent eluded detection until 1983. At that time, Wear et al3 discovered a small, pleomorphic Gram-negative bacillus by using a Warthin-Starry silver stain in infected lymph nodes of patients with CSD. It was not until 5 years later that this organism was successfully isolated and cultured.4 In 1991, Brenner et al5 named the CSD bacillus Afipia felis, after the Armed Forces Institute of Pathology, where the organism was discovered. In 1992, Rochalimaea henselae was isolated from HIV-infected patients with bacillary angiomatosis, peliosis hepatis, and fever syndromes. In that report, Regnery et al6 noted that the majority of their patients with clinically suspected CSD had high serum titers to the R henselae antigen. Additional studies in the 1990s refuted the role of A felis in CSD, in favor of Rochalimaea species.7,8 In 1993, the genera Bartonella and Rochalimaea were united, with Bartonella having nomenclatural precedence over Rochalimaea.9 Thus, B henselae is currently recognized as the causative agent of CSD. Since that time, the most significant study of patients with B henselae infection has been undertaken by Hugh Carithers,10 who saw and reported >1200 cases of CSD in pediatric private practice.
MICROBIOLOGIC FEATURES AND PATHOGENESIS
The genus Bartonella includes 19 distinct species, of which at least 6 are responsible for human disease (B henselae, Bartonella bacilliformis, Bartonella quintana, Bartonella elizabethae, Bartonella vinsonii, Bartonella koehlerae). These species are small, fastidious, intracellular Gram-negative bacilli that are aerobic and oxidase-negative. The organisms are most easily visualized by using a Warthin-Starry silver impregnation stain (see Fig 1) or a Brown-Hopps tissue Gram-stain. Two main genogroups of B henselae have been identified in humans and cats: Houston-1 and Marseille (also known as genotype II).11 These 2 genogroups are further subdivided into 4 variants: Marseille, CAL-1, Houston-1, and ZF-1.12 In infected patients, the organisms are found most commonly in vessel walls, in macrophages lining the sinuses of lymph nodes, in nodal germinal centers, in nonnecrotic areas of inflammation, and in areas of expanding and suppurating necrosis.13,14 Electron microscopy of lymph node tissues of patients with CSD confirms that the bacilli have an affinity for the vascular endothelium, with organisms seen in clumps in vessel walls, intracellularly and free in necrotic debris.15 The response to infection with B henselae depends on the immune status of the infected host. In immunocompetent individuals, the response is granulomatous and suppurative, as compared with a vasoproliferative response in immunocompromised patients.14 Early in the course of infection in an immunocompetent patient, lymphoid hyperplasia, arteriolar proliferation, and widened arteriolar walls are seen in biopsied lymph nodes. This progresses to granulomatous disease, with central areas of necrosis and multinucleated giant cells. Bartonella infection causes an interferon--mediated T helper 1 cell response, resulting in macrophage recruitment and stimulation, ultimately producing granulomatous disease.18 Late in the disease, stellate microabscesses form with suppuration of affected lymph nodes.14 In individuals with an intact immune system, infection generally remains within the lymphatics, with a symptomatic immune response that lasts 2 to 4 months.19
Immunodeficient patients are at risk for bacillary angiomatosis, which manifests as cutaneous angiogenic lesions. These lesions consist of vascular proliferation composed of endothelial cells and a mixed inflammatory cell infiltrate. The mechanism by which B henselae induces angiogenesis is not fully understood. One hypothesis is that Bartonella modulates host or target cell cytokines and growth factors, which lead to angiogenesis. When Bartonella adheres to or is phagocytosed by macrophages, these cells secrete vascular endothelial growth factor (VEGF). It is thought that Bartonella adhesin A is crucial for the secretion of VEGF and other proangiogenic cytokines.20 VEGF is thought to act as an endothelial cell inducer, leading to proliferation of endothelial cells and angiogenesis.19 Another hypothesis involves Bartonella directly triggering proliferation and apoptosis of endothelial cells, resulting in increased angiogenesis.21
. . . .
TABLE 1 Clinical Manifestations of B henselae Infection
More Common Typical CSD (fever and localized lymphadenopathy only) Prolonged fever/FUO Hepatosplenic disease
Really like your check list. "NDPH" can be a "symptom" for Lyme Disease and Co-infections with Bartonella.
My child had a series of misdiagnoses, the last one before Lyme, BLO and WA1 was NDPH. I was tyring to find out about NDPH when another Lyme mom found me online and told me that NDPH was a symptom for Lyme and Bartonella. She called it.
NDPH = New Daily Peristant Headache.
Child's symptoms did fit NDPH syndrome EXCEPT for the lower GI problems (concurrent diarhea and constipation) and abd pain in left upper quadrant. The GI problems were constant and unrelenting as was the headache and neuro problems.
Posts: 124 | From Maryland, USA | Registered: Jan 2010
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Really like your check list. "NDPH" can be a "symptom" for Lyme Disease and Co-infections with Bartonella.
My child had a series of misdiagnoses, the last one before Lyme, BLO and WA1 was NDPH. I was tyring to find out about NDPH when another Lyme mom found me online and told me that NDPH was a symptom for Lyme and Bartonella. She called it.
NDPH = New Daily Peristant Headache.
Child's symptoms did fit NDPH syndrome EXCEPT for the lower GI problems (concurrent diarhea and constipation) and abd pain in left upper quadrant. The GI problems were constant and unrelenting as was the headache and neuro problems.
Posts: 124 | From Maryland, USA | Registered: Jan 2010
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Hopefully the link above will take you to the translated version of the article which speaks to studies that reveal that the Bartonella bacteria are able to adapt to different hosts.
Excerpt:
Ella Barton Fink is the Darwin Among the bacteria
11. February 2011, 19:46
For the first time researchers have demonstrated that bacteria acquire new properties can trigger an adaptive radiation.
The example of the pathogen Bartonella an international research team was able to show that bacteria can adapt by acquiring a molecular "needle" to inject bacterial proteins into host cells much more efficiently to new host organisms such as humans. The findings are of fundamental importance for understanding the evolution of novel pathogens.
The term "adaptive radiation" describes the rapid emergence of a variety of species from a founder population as a result of specific adaptation to different ecological niches.
This fundamental process of evolution is critical to the emergence of biodiversity. Adaptive radiations occur whenever an organism either an adaptive trait (evolutionary key innovation ") re-acquires the help he can quickly adapt to new niches, or if an organism with an existing adaptive feature in a foreign environment with unoccupied niches hits ("ecological opportunity")."
[click on link for remainder of text and photo of Bartonella pathogen]
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Background Bartonella cat scratch disease is classically a febrile illness, in conjunction with lymphadenopathy and cat exposure.
Objective To report 2 atypical cases of cat scratch disease with only blurred vision and headache.
Design Case reports.
Setting University hospital.
Patients Two young adults with unilateral blurred vision, retro-orbital headache, and a positive Bartonella henselae serologic result, without fever or lymphadenopathy.
Main Outcome Measures Funduscopic examination and B henselae serologic findings.
Results Both patients had optic disc swelling and a macular star on funduscopic examination, suggestive of infection. Infection was confirmed by positive serologic results.
Conclusion Cat scratch disease should be considered in the differential diagnosis for patients presenting with blurred vision and headache, even in the absence of fever, lymphadenopathy, or both.
Author Affiliations: Departments of Neurology (Ms Gan and Drs Mandell, Otis, and Perloff) and Ophthalmology (Dr Holmuhamedova), Boston University School of Medicine, Boston University Medical Center, Boston; and Geriatric Research & Educational Clinical Center, Edith Nourse Rogers Memorial VA Medical Center, Bedford (Dr Mandell), Massachusetts. Dr Perloff is now with the New York University Pain Management Center, Langone Medical Center, New York.
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Simultaneous Gastrointestinal Infections in Children and Adolescents
A SPECIAL ARTICLE
Martin D. Fried, Division of Pediatric Gastroenterology and Nutrition, Jersey Shore University Medical Center, Neptune, NJ. Martin E. Adelson and Eli Mordechai, Medical Diagnostic Laboratories, Mount Laurel, NJ.
"DISCUSSION
Bartonella spp. were the most common pathogen detected in our patient population reporting abdominal pain. Previous pediatric reports have associated one of the members of the Bartonella genus, Bartonella henselae, with a vasculitis rash, abdominal pain, heartburn, gastritis and duodenitis (5).
B. henselae has also been associated with cat scratch fever, lymphadenopathy, splenitis, and fevers of unknown origin. Only 5% of patients with cat scratch disease exhibit skin rashes.
When present, the rash may present as violaceous in color and is associated with new blood vessel formation. Described as neovascularization, this rash may be observed near the armpits, on the breasts, buttocks, inner thighs, back of the knee, groin, and/or gluteal area. Neovascularization resembles the stretch marks, or striae distensae, seen in those patients who are obese, on steroid medications, or who gain weight rapidly.
Bartonella-induced rashes differ from striae distensae, however, by exhibiting hard nodularity and persistence, which does not fade over time. Other rashes associated with Bartonella infections include erythema nodosum, thrombocytopenia purpura, erythema annulaire, and granulomatous skin lesions. The GI biopsies showed chronic inflammation with the presence of lymphocytes and plasma cells. Interleukins 2, 6, and 10, which are elicited by Bartonella infections, may account for the chronic inflammation.
Interleukin-6, a multipotent cytokine, is associated with the formation of new blood vessels and may account for the observed neovascularization.
Borrelia burgdorferi has been shown to be associated with gastritis, duodenitis, and colitis in children. B. burgdorferi infections have also been detected inchildren and were observed in the GI tract by Diertele stain of the spirochetes in the stomach, duodenum, and colon and by PCR of gastrointestinal biopsies (6-8).
Helicobacter pylori is a known irritant to the stomach lining that predisposes individuals to gastric and duodenal ulcers. In pediatrics, abdominal pain, vomiting, and hematemesis are the most frequent presentations of H. pylori infection.
In symptomatic patients, gastric biopsies are often inflamed due to H. pylori, and these organisms can be directly visualized by microscopy in the crypts and at the apex of affected tissue. Successful eradication of the organism requires two antibiotics for at least two weeks with concurrent use of a proton pump inhibitor medication (9).
Intracellular Mycoplasma infections are rarely detected in the blood. Due to their low abundancy, Mycoplasma infections have been demonstrated to worsen the symptoms of other infections such as Bartonella and Lyme Disease and have also been associated with Chronic Fatigue Syndrome, rheumatoid arthritis, and Gulf War Syndrome (10,11).
Mycoplasma fermentans stimulates proinflammatory cytokines Interleukin 1 and Interleukin 6 and tumor necrosis factor alpha which explains the inflammation associated with this infection. The chronicity of Mycoplasma infections may be attributed to the organism's surface antigenic variation, inability to suppress the host cell's immune response, intracellular localization, and slow growth rate.
CONCLUSION
Bartonella spp, Borrelia burgdorferi, Helicobacter pylori, and Mycoplasma fermentans were detected as single or multiple infections in the gastrointestinal tract of symptomatic patients. The association of these human pathogens with chronic gastritis, duodenitis and/or colitis warrants further evaluation.
When gastrointestinal coinfections occur, the clinical presentation may include overlapping symptoms contributed by each infecting organism and the clinician should consider the presence of all possible gastrointestinal pathogens and their possible relation to the endoscopic and biopsy findings and the formation of gastritis, duodenitis and ulcer disease before treating the patient (12)."
[click on link for full article]
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Michael C. Chappell, MD, J. Michael Jumper, MD, H. Richard McDonald, MD, Emmett T. Cunningham Jr., MD, PhD, MPH, San Francisco 3/21/2011
Bartonella species are increasingly recognized as a cause of uveitis. Analysis of intraocular fluids can confirm the diagnosis.
Although neuroretinitis has been recognized as a distinct clinical entity for more than 120 years, it wasn't until the 1990s that the syndrome was definitively linked to Bartonella infection.1 There are currently 21 known species of Bartonella, eight of which have been identified as causing human diseases--including cat scratch disease; Carrion's disease; trench fever; endocarditis; bacteremia; myocarditis; bacillary angiomatosis; and various ocular diseases.2,3,4 Bartonella species are facultative, pleomorphic, Gram-negative rods.
Clinical signs and symptoms of infection vary widely depending on both the specific tissue infected and the immune status of the host.2 Bartonella henselae is the most common ocular pathogen, although B. quintana, B. grahamii and B. elizabethae infections each have been reported to infect the eye.3,5,6,7 The natural reservoir of B. henselae is cats and more than 90 percent of cases of cat scratch disease are associated with a history of contact with cats younger than one year of age.8,9
The disease is transmitted primarily by arthropod vectors, most notably flees, and within mammals resides principally within endothelial and red blood cells. This review focuses on the clinical manifestations, diagnosis and treatment of uveitis associated with Bartonella infections.
Ocular Manifestations
Clinically, cat scratch disease (CSD) is the most common presentation of B. henselae infection. Five to 10 percent of patients with CSD develop ocular involvement, most commonly either Parinaud's Oculoglandular Syndrome (POGS; See Figure 1), which affects 5 percent, or neuroretinitis (See Figure 2), which occurs in 1 to 2 percent of symptomatic patients.10,11 POGS is characterized by tender regional lymphadenopathy of the preauricular, submandibular, or cervical lymph nodes associated with infection of the conjunctiva, eyelid or adjacent skin surface.
Usual complaints include unilateral eye redness, foreign body sensation and epiphora. Discharge may be serous or purulent (See Figure 1) and can be copious in some patients.12 Neuroretinitis as described by Theodor Leber and later by Donald Gass is defined as acute unilateral visual loss associated with an exudative optic neuritis with transudation into the macula forming a partial or complete macular star (See Figure 2).13 Optic disc edema typically precedes the formation of a macular star by two to four weeks.14 Associated findings in patients with neuroretinitis may include peripapillary serous retinal detachment, focal retinitis or choroiditis, multifocal retinitis or choroiditis, and vasculitis--which may be occlusive.3,10 Bilateral Bartonella-associated neuroretinitis has been reported, but is rare and should prompt consideration of malignant hypertension, pseudotumor cerebri or bilateral diabetic papillopathy.15
One patient with Bartonella-associated neuroretinitis was reported to have developed acutely elevated intraocular pressure, so-called Inflammatory Ocular Hypertension Syndrome, accompanied by neovascularization of the retina.16,17
Bartonella-Associated Uveitis
Bartonella-associated uveitis can be unilateral or bilateral; anterior, intermediate, or posterior; granulomatous or nongranulomatous; and with differing degrees of posterior segment signs. Though there may be a history of contact with cats, such an exposure history is not required to make the diagnosis.12
The first published description of Bartonella-associated uveitis was a case of nongranulomatous anterior uveitis without posterior segment findings.18 Since then, a number of posterior segment complications have been described. Most common, perhaps, are retinal infiltrates, which are typically superficial, round, and 100 to 300 �m in size. They are usually multiple and often occur in the setting of neuroretinitis.13,21,22
These spots usually clear with no residual scarring in two to three weeks.13,19,20 In addition to multifocal retinitis, there have also been descriptions of focal choroiditis in patients with CSD, and areas of both retinitis and choroiditis may be associated with an adjacent or overlying exudative retinal detachment and/or retinal vascular occlusion.13,19,20
Bartonella infections have also been associated with diffuse choroiditis, focal retinal vasculitis and peripapillary angiomatosis.20,22-24 Most patients with Bartonella-associated neuroretinitis or retinochoroiditis show some degree of vitreous or anterior segment inflammation. Intraocular inflammation can also occur in the absence of focal retinochoroiditis or optic disc involvement, however.25,26
Evidence on HLA-B27
Many Gram-negative bacteria (Klebsiella, Salmonella, Proteus, Yersinia, Shigella and Campylobacter) have been implicated in the development of HLA-B27-associated diseases such as uveitis, reactive arthritis and ankylosing spondylitis.33 There is also emerging evidence of a potential association between Bartonella intraocular infections/uveitis and HLA-B27 antigen expression.
Michel Drancourt and associates described a 40-year-old HLA-B27 positive woman with a 10-year history of poorly controlled nongranulomatous uveitis whose inflammation was controlled only after a Bartonella diagnosis was made and appropriate antibiotic therapy was instituted.34
In an analysis done by Frank Kerkhoff and Aniki Rothova, six of 19 patients with positive enzyme immunoassays for B. henselae were also HLA-B27 positive. This number was significantly higher than the rate of HLA-B27 positivity in a control group of 25 patients with uveitis and no serologic evidence for B. henselae infection.33
Moreover, HLA-B27 positive patients may be at risk for more severe ocular Bartonella infections. Five of the six patients with both serologic evidence of Bartonella infection and HLA-B27 antigen expression described in this study had what Drs. Kerkhoff and Rothova characterized as severe posterior segment involvement.
Four of these patients had a history of previous uveitis restricted to the anterior segment, and only later developed a more severe posterior uveitis when they converted to having B. henselae-positive serology.33 It is currently unknown how such bacterial colonization or infection with B. henselae (and other Gram-negative bacteria) triggers or worsens HLA-associated disease, but there are theories of localized changes related to the interactions between the bacteria and immune cells in HLA-B27-positive patients.33
Treatment
Doxycycline, 100 mg orally b.i.d., is usually prescribed for two to four weeks in immunocompetent patients and up to four months in the immunocompromised.4 Treatment can also be continued for longer periods in immunocompromised patients to help prevent recurrence of ocular disease.36 Doxycycline augments the free radicals used by polymorphonuclear cells to kill phagocitized cells, which are suppressed by Bartonella infections.19
Doxycycline is preferred to erythromycin for its better intraocular and central nervous system penetration, but doxycycline should not be given to young children, in whom tooth discoloration is a possibility. For severe disease or in patients with central nervous system involvement, these same antibiotics can also be given intravenously, or together with rifampin, 300 mg orally b.i.d.36 Patients with severe optic nerve or macular inflammation may benefit from corticosteroids in addition to antimicrobial treatment.22
Bartonella species are well-recognized ocular pathogens. B. henselae is most frequently implicated, with POGS and neuroretinitis being the most common manifestations. Associated findings in patients with neuroretinitis include peripapillary serous retinal detachment, focal retinitis, focal choroiditis, vasculitis and vascular occlusion. More recent studies suggest that infection by diverse Bartonella species may be associated with uveitis and that the inflammation may be granulomatous or non-granulomatous; anterior, intermediate, posterior, or diffuse; and with or without neuroretinitis or peripapillary serous retinal detachment.
Both serologic and intraocular fluid tests are now available to diagnose Bartonella-associated uveitis, but when and how to use these tests remains a subject of debate. Short-term treatment with oral doxycycline is usually adequate to control the ocular manifestations in immunocompetent patients, but longer treatment with multiple agents may be necessary in patients with HIV/AIDS.
[click on link for full article with photos]
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posted
I have posted my treatment and results for Bart on several different threads but thought I would post it here also since you are asking for studies or info on Bart.
I tried 18 months of various abx combos for LD and got to about 80%.
Although my bart testing was negative, I had sore soles, which is a hallmark of bart, and talked my family doc into prescribing tindamax (500 mg) and cipro (250 mg) twice daily.
6 months of tindamax and cipro got me to 100% about 1 year ago. I am not taking any abxs right now and have not had a relapse...yet.
Bartonella Brain Fog Fever Foot/heel pain Ice pick headaches Photophobia Tachycardia Bowel problems IBS/IBD Swollen Glands OCD behavior Anxiety Endocarditis Retinitis Peripheral Neuropathy Rapid relapse off abx Immediate illness following tick bite Subcutaneous nodules Swollen Joints Swollen lymph nodes Psychiatric problems Shin pain No response to previous abx Plantar and costal margin pain (plantar=soles of feet costal margin = The lower edge of the chest (thorax) formed by the bottom edge of the rib cage) Rapid mood shifts Development of these symptoms during Babesia Treatment
Posts: 503 | From Maryland | Registered: Oct 2007
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posted
This is a very good dissertation by S. Billeter, under the direction of Bartonella specialist Edward B. Breitschwerdt.
This paper places particular emphasis on the transmission of various forms of Bartonella via Ticks; however, it also emphasizes transmission through the sandfly, the louse, the flea, keds and biting flies.
Bartonella species are gram-negative bacteria that reside within the alphaproteobacteria class. These bacteria infect red blood cells and can invade endothelial cells, CD34+ progenitor cells, and dendritic cells of their hosts, leading to persistent blood-borne infections (Dehio, 2004; Boulouis et al., 2005; M�ndle et al., 2005; Vermi et al., 2006).
Several Bartonella species have been identified as zoonotic or potentially zoonotic agents including: B. henselae Regnery et al., B. clarridgeiae Lawson and Collins, B. alsatica Heller et al., B. koehlerae Droz et al., B. quintana Schmincke, B. elizabethae Daly et al., B. grahamii Birtles et al., B. vinsonii subsp. arupensis Welch et al., B. vinsonii subsp. berkhoffii Kordick et al. , and ``B. washoensis'' Regnery et al., and ``B. rochalimae'' Eremeeva et al. (Boulouis et al., 2005; Raoult et al., 2006; Chomel et al., 2006).
As scientists, physicians, and veterinarians learn more about the medical importance of the genus Bartonella, there has been renewed focus on known and suspected arthropod vectors. Due to the ability of various Bartonella spp. to reside within erythrocytes of a diverse number of mammalian hosts, there is substantial opportunity for the potential uptake of these blood-borne bacteria by a variety of arthropod vectors.
Recently, Bartonella DNA has been detected in blood samples obtained from loggerhead sea turtles (Caretta caretta Linnaeus), suggesting the possibility of persistent blood-borne infection . . . . [click on link for remainder of article]
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lightfoot
Frequent Contributor (5K+ posts)
Member # 2536
posted
Thanks for an amazing thread!!!
-------------------- Healing Smiles.....lightfoot Posts: 7228 | From CO | Registered: May 2002
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EnrichmentPCRTM testing platform is the most sensitive diagnostic test available for the detection of active Bartonella species infection.
Bartonella species are difficult or, in many cases, impossible to, detect using traditional detection methods, including microbiological diagnosis by bacterial isolation, serological testing for antibodies, and conventional or real-time PCR (polymerase chain reaction). Bartonella are highly fastidious (difficult to isolate) and exhibit characteristically slow growth in cell culture or on a blood agar plate. The bacteria are also intracellular with unique immune-evasive properties which contribute to the low sensitivity of serological tests for the detection of antibodies.
Despite the exceptional sensitivity of conventional or real-time PCR, extremely low level infections can be missed. This problem can been solved with the pre-enrichment growth of bacteria following inoculation of prepared samples (blood, prepared tissue, and other fluids) into a liquid-based insect tissue culture growth medium - Bartonella Alpha Proteobacteria Growth Medium (BAPGM, pronounced bap-gee-em). This medium supports the growth of many Bartonella species and facilitates the detection and isolation of Bartonella spp. in 7 days rather than 7 weeks. BAPGM provides the ideal growth environment for these fastidious, insect-borne pathogens.
BAPGM was envisioned, refined and patented by research scientists at the North Carolina State University College of Veterinary Medicine's Vector Borne Disease Diagnostics Laboratory as a result of ongoing efforts to enhance the growth of these highly fastidious bacteria from animal and human patient samples. Conventional PCR testing is largely ineffective at detecting the presence of Bartonella spp. infection, especially in immunocompetent patients. NCSU-CVM research scientists were able to overcome the low detectability problem by combining a BAPGM enrichment culture step with a highly sensitive PCR testing.
As Bartonella species have a dividing time of approximately 24 hours, a diagnostic sample that contains one bacterium will contain only 2 after 24 hours, 4 after 48 hours, 8 after 72 hours, etc. On a practical basis, this means that time (at least 7-10 days) is required to increase the number of bacteria in the patient's BAPGM culture to a level in which there is enough DNA to be detected by PCR. Our research indicates that use of the BAPGM pre-enrichment culture increases the diagnostic sensitivity of Bartonella species detection by more than 400% when compared to direct extraction and PCR amplification from a patient blood sample.
Below is a short list of references regarding the analytic validity and clinical utility of the combined use of BAPGM enrichment media with PCR for the detection of Bartonella bacteria. Additional information can be found on PubMed and WebMD.
[click on link for more information]
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Fleas Collected from Norway Rats in Downtown Los Angeles Carry Human Pathogen
ScienceDaily (Nov. 16, 2011) -- Most fleas collected from rats trapped in downtown Los Angeles, California carried microbes from the genus Bartonella, many of which are human pathogens, according to a paper in the November Applied and Environmental Microbiology.
The research team limited their investigation to fleas of the species Xenopsylla cheopis, because they are known both to infest Rattus norvegicus, the Norway rat, which is a major pest in high density urban areas, as well as to bite humans, says first author Sarah Billeter of the Centers for Disease Control and Prevention, Fort Collins, CO.
Bartonella species are gram-negative bacteria that infect red blood cells and endothelial cells of the host. More than half are thought to cause some clinical disease in humans. B. rochalimae, found in 72 percent of the collected fleas, was first isolated from the blood of a patient who became ill after returning to the United States from a vacation in Peru, says Billeter.
"She complained of fever, insomnia, nausea, headache, and mild cough. Upon examination at the hospital, she was found to have recurrent fever, splenomegaly, and anemia." B. rochalimae has also been identified as a cause of infectious endocarditis in a dog from San Francisco, says Billeter.
The remaining fleas harbored sequences most closely related to B. tribocorum, a bacterium that has been detected in rodents "from various parts of the world," including France, says Billeter, and was isolated from the blood of a febrile Thai patient. "At this point, it remains unclear whether B. tribocorum is a human pathogen," says Billeter.
"From a public health standpoint, however, it is important to determine whether R. norvegicus are reservoirs for zoonotic Bartonella spp. due to their close contact with humans and their pets." The question of whether X. cheopis can actually spread such pathogens to humans also warrants further investigation, says Billeter.
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lyme in Putnam
Frequent Contributor (1K+ posts)
Member # 11561
posted
Found this old thread. Anyone have evidence of bartonella causing hyponatremia. On rifampin since october and my salt has been dropping a point a week since then. Dropped 3 points ths week and llmd wants me to stay on and raise sodium tablet. Seeing my nephrologist Tuesday, if thinks rifampin causing it, will take me off. I've googled, searched, anyone have documented link between bartonella and hyponatremia. Almost at hospital level, hospitalized twice last year with this. On 6000 mg salt a day and lasix to retain what I have and it's still dropping. Thanks.
-------------------- He took u to it, He'll you through Posts: 2837 | From NE. | Registered: Apr 2007
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Research by Intracellular Pathogens Research Lab Advances Understanding of Bartonella--the 'stealth pathogen' The following article by the Veterinary Information Network (VIN) News Service profiles the ongoing Bartonella research being conducted by the Intracellular Pathogens Research Laboratory (IPRL) within the CVM Center for Comparative Medicine and Translational Research. Directed by Dr. Ed Breitschwerdt, the work of the IRPL is an example of the ``One Medicine'' concept and the importance of the connections between animal and human health and veterinary and human medicine.
By: Edie Lau For The VIN News Service The pathogen best known for causing cat scratch disease is responsible for a host of serious illnesses in humans that may be misdiagnosed due to lack of awareness in the medical community.
Researchers studying the Bartonella genus of bacteria say veterinarians and veterinary staff, along with others who work with animals -- including groomers, trainers and shelter and rescue organization personnel -- are at particular risk of infection owing to their frequent exposure to animals and animal parasites such as fleas.
``I think it's more common than we think in the veterinary community,'' said Dr. Bruno Chomel, a DVM and professor in the Center for Vectorborne Diseases at the University of California, Davis.
The scope and significance of Bartonella infection among humans in veterinary circles and at large is just beginning to be understood.
Twenty years ago, only two Bartonella species were known. One, B. henselae, was identified as the agent behind cat scratch disease, a condition believed to be transmitted by a cat scratch or bite that causes swelling of the lymph nodes along with fever, headache, fatigue and/or poor appetite. Conventional wisdom said -- and says still -- that ``cat scratch fever'' is nothing to worry about for most people: Except in those with immune system deficiencies such as AIDS, the infection goes away on its own or with a short course of antibiotics. Bartonella became synonymous with mild illness.
But researchers say the picture is more complicated than that. Today, the number of Bartonella species identified is 26 and counting. Species exist that co-evolved with dogs, cattle, squirrels and ground hogs. Arthropods including fleas, lice and possibly ticks transmit the germ to mammals.
Those who study Bartonella characterize it as a ``stealth pathogen'' because of its ability to evade detection even at levels that cause illness. The bacterium has been found to invade and colonize a variety of cell types -- not only blood cells such as erythrocytes and macrophages but vascular endothelial cells and dendritic cells of the nervous system, as well.
This enables the microbe to disperse throughout the body and manifest in a wide range of debilitating conditions, including neuromuscular problems and endocarditis, a serious infection in the valves of the heart. Complicating diagnosis, many symptoms are non-specific. They include fatigue, headache, memory loss, insomnia, muscle pain and joint pain.
Ignorance in the medical community of the disease and its many possible forms has profound effects on those who come down with a clinical infection.
Dr. Kathy Tater, a veterinary dermatologist in Massachusetts, is a case in point. Tater said she visited nearly 20 health-care providers in different institutions over the course of a year before she was diagnosed with Bartonella -- and that was only because through her own reading, she found a laboratory with a sensitive test designed specifically to detect the elusive pathogen.
``What I found was that most physicians have not heard of Bartonella. They have heard of cat scratch disease, but that is not the same as knowing about Bartonella infections,'' said Tater, who is recovering. ``They were not aware that other strains of Bartonella existed, and they were not aware of how to test a person for Bartonella.''
Her story is familiar to Dr. Edward Breitschwerdt. A veterinary internist who directs the Intracellular Pathogens Research Laboratory at North Carolina State University College of Veterinary Medicine, Breitschwerdt has looked at hundreds of cases of suspected human Bartonella infections. Commonly, patients see a variety of specialists -- cardiologists, neurologists, rheumatologists, internists, infectious-disease experts and the like -- on their journey to a Bartonella diagnosis, Breitschwerdt has found.
As a veterinarian, he became by accident the go-to guy for people such as Tater. Breitschwerdt's focus was developing better detection tools for infections in dogs, in which Bartonella similarly is hard to find. The approach he hit upon is to first ``enrich'' the test sample of blood by culturing it in insect growth media rather than mammalian growth media, the standard culture for bacteria. Through this step, the population of bacteria builds up, making the microbes easier to find.
As Breitschwerdt lectured at veterinary conferences about the new diagnostic approach for dogs, a curious thing happened. Veterinarians would come up afterward and say that they'd been sick. They wondered whether they might be infected by this stealth pathogen.
``If there were 100 veterinarians in the audience, there might be three or four who would come up to me,'' Breitschwerdt said. ``They raised the question. I did not.''
That ushered Breitschwerdt into the human world of Bartonella infection. He began accepting human samples for analysis. ``After we developed this novel approach and had a fair amount of data that said it seemed to be working in people,'' he said, ``I tried to find a veterinary or human diagnostics company that would be willing to work with us or at least license the technology from the university.''
But the test isn't simple or cheap, and the idea of devoting significant resources to a pathogen that isn't widely recognized as important was a hard sell, he said. No one bit.
Breitschwerdt and others ultimately started their own company, Galaxy Diagnostics, to handle the work.
As word spread of Breitschwerdt's expertise, human samples flowed in from people in veterinary medicine and beyond. He estimates that he's tested 700 patients over the past three years. ``Overall, we're running about 31 percent positive. That's very high,'' he noted. ``Very high for an organism that is not supposed to be in the blood of immunocompetent people.''
Breitschwerdt began doing studies on human subjects. One subject was Dr. John Barnes, a small-animal and exotics practitioner in Uvalde, Texas.
Barnes, 54, was diagnosed with multiple sclerosis (MS) in 2005. Up to that point, he was a healthy man who jogged regularly and ran up and down bleachers at the local high school for exercise.
One day, shortly after a bout of 103-degree fever and vomiting that he attributed to food poisoning, Barnes was jogging around a track. On the third lap, his left leg stopped cooperating, causing him to stumble. A week or so later, Barnes began tripping again while jogging, this time on the second lap.
Thus began his journey through the medical system. One physician suspected a herpes virus. Another thought it might be Guillain-Barre, a rare neurological syndrome in which the body's immune system attacks part of the peripheral nervous system. Following an MRI and spinal tap, Barnes was told he had MS and that he would likely end up in a wheelchair.
Barnes was not so sure. ``I wasn't trying to balk at the diagnosis but because I had this huge fever (five months earlier) in December when all of this started, I thought maybe I had something else,'' he said. ``It sounded more inflammatory and (like an) infection.''
By chance, while conferring with a colleague at Texas A&M University about an oncology case, Barnes mentioned his condition. The colleague knew Breitschwerdt was doing a study involving veterinarians and veterinary technicians. She recommended Barnes get in touch with him.
It turned out that Barnes had an infection of B. henselae, the same species of Bartonella that causes cat scratch disease. His case and that of five other similarly infected patients was published in a study that appeared in the Journal of Clinical Microbiology in September 2008.
Whether the Bartonella infection had anything to do with his neurological symptoms or was mere coincidence was a point of debate and discussion among various doctors. ``I have so many ologists, I don't know what I'm doing,'' Barnes commented wryly.
His condition worsened in the meanwhile. He fell frequently, once breaking a rib.
Finally in August 2007, he was prescribed two antibiotics to combat the Bartonella: doxycycline and rifampin. Within a month, he said his toes, which had had a cadaverous gray tone, ``started pinking up.''
A couple months later, he noticed his fatigue lifting. By the following summer, he could stand on one leg, cross the other over his standing knee and look at the bottom of his foot -- a position he had not been able to assume in three years.
His odyssey didn't end there, unfortunately. Barnes stopped taking the antibiotics after a year. Breitschwerdt continued to monitor his blood. At first, Barnes was negative for Bartonella. But six months later, the bacteria reappeared.
Barnes went back on antibiotics. In February this year, he sent another blood sample to Breitschwerdt. The B. hensalae showed up still, and this time, not one strain, but two.
Was it the result of a new exposure or something that had been in hiding? The answer may never be clear.
Barnes said that as far as he knows, in 26 years as a clinician, he has never had a patient with a Bartonella infection. But he has spent plenty of time among animals and in the outdoors. ``My dad was a vet,'' he said. ``I was always catching frogs and toads (as a boy). So I think I'm exposed to all this junk.''
Despite the ongoing infection, Barnes said he is doing much better -- on the order of 60 to 70 percent improved, in his estimation. That tells him that while he truly may have MS, there's a relationship between his MS and Bartonella.
``I'm not saying I have just Bartonella or just MS,'' he said. ``But what if, of all the 400,000 people with MS right now, what if 2 percent of them are Bartonella-induced? People get their panties in a wad if I say that Bartonella causes MS. But (the diagnosis of Bartonella infection) helped me. I should be in a wheelchair right now.''
For Breitschwerdt, solving the mysteries of Bartonella has turned personal. In 2007, his 86-year-old father came down with a Bartonella infection that eluded medical professionals until Breitschwerdt ran the samples himself the following year. The researcher gave a moving account of the experience in the article ``A Groundhog, a Novel Bartonella Sequence, and My Father's Death,'' published in the U.S. Centers for Disease Control and Prevention journal Emerging Infectious Diseases.
Dr. Michael Kosoy, chief of the Bartonella Laboratory at the CDC in Fort Collins, Colo., said the pathogen's potential public health impact is taken more seriously in Europe and Asia, where Bartonella is appreciated as a cause of endocarditis and other serious ailments. In this country, by contrast, its importance is ``very, very much unrecognized,'' Kosoy said.
How the CDC Bartonella lab is supported illustrates the point: Kosoy said that although his lab is part of the Division of Vector Borne Diseases, most of its funding comes from the Global Diseases Detection Division. In other words, the CDC sees Bartonella infection more as a risk abroad than here.
Assuming that ever was true, conditions rapidly are changing. Kosoy said Bartonella species specific to rats in Asia and in Australia recently turned up in the California seaport cities of Los Angeles and Oakland. ``They travel with ships around the world,'' Kosoy said.
Lack of recognition of Bartonella's possible role in illness isn't absolute, of course. A few physicians are very aware of the pathogenic potential of the germ. One is Dr. B. Robert Mozayeni, a rheumatologist in North Bethesda, Md., whose quest to help patients with rheumatic conditions often confused with Lyme disease -- a tick-borne illness -- led him to Bartonella.
``In some studies of ticks, there was a significant prevalence of Bartonella,'' Mozayeni explained. ``Also, a significant percentage of cats carry Bartonella.'' From taking their medical histories, Mozayeni said he has learned that a significant fraction of his patients contracted their illness from their cats.
Further research led Mozayeni to Breitschwerdt. Now the two work together: Mozayeni is chief medical officer in Breitschwerdt's startup company, Galaxy Diagnostics.
To date, Mozayeni has evaluated some 400 patients with known or suspected Bartonella infections, some coming from as far away as Nevada, Idaho, Florida, and even other countries, such as Brazil and the Netherlands.
In his experience, Bartonella-infected patients respond with notable consistency to treatment. ``The consistency with the way they responded (positively) made me more convinced that this was a causative microbe, not just an incidental finding,'' Mozayeni said.
As a biomedical researcher trained at Yale University and the National Institutes of Health, Mozayeni called the Bartonella work ``the most exciting translational medicine I've seen --where we've gone from bench to bedside. I see such huge positive impacts on my patients' lives every day,'' he said. ``... The results have been nothing but spectacular. Most patients have gone from chronic disabled to revitalized, active people because we've been able to lock on this microbe.''
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Bartonella spp. bacteremia in high-risk immunocompetent patients.
Ricardo G Maggi, Patricia E Mascarelli, Elizabeth L Pultorak, Barbara C Hegarty, Julie M Bradley, B Robert Mozayeni and Edward B Breitschwerdt Diagn Microbiol Infect Dis () (2011) PMID 21996096 Serum and blood samples from 192 patients, who reported animal exposure (100.0%) and recent animal bites or scratches (88.0%), were screened for antibodies by indirect immunofluorescence assays and for bacteremia using the BAPGM (Bartonella alpha Proteobacteria growth medium) platform. Predominant symptoms included fatigue (79.2%), sleeplessness (64.1%), joint pain (64.1%), and muscle pain (63.0%). Bartonella spp. seroreactivity or bacteremia was documented in 49.5% (n = 95) and 23.9% (n = 46) of the patients, respectively; however, indirect immunofluorescence antibodies were not detected in 30.4% (n = 14) of bacteremic patients. Regarding components of the BAPGM platform, Bartonella DNA was amplified from 7.5% of blood (n = 21), 8.7% of serum (n = 25), and 10.3% of enrichment culture samples (n = 29). Polymerase chain reaction (PCR) on only extracted blood would not have detected Bartonella infection in 34.7% (16/46) of bacteremic patients. Serology, in conjunction with blood, serum, and BAPGM enrichment culture PCR, facilitates the diagnosis of Bartonella spp. bacteremia in immunocompetent patients. Copyright � 2011 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.diagmicrobio.2011.09.001
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Veterinary team members, you're at risk for the disease simply because you work with animals. But how much do you really know about bartonellosis?
Nov 26, 2010 By: Steve Bennaka
What is it?
Bartonellosis is a condition caused by infection with Bartonella bacteria. Various strains of the bacteria can cause ailments including cat-scratch disease, endocarditis, and neuroretinitis. In the past 20 years, researchers have identified 26 species of Bartonella, although not all are thought to infect people. Symptoms in people include pain and fatigue (see the symptoms below). Those with bartonellosis are often misdiagnosed as suffering from chronic Lyme disease.
How is it transmitted?
Cat scratches and bites contaminated with flea excrement or bites and accidental needle sticks contaminated with Bartonella-infected cat blood are common routes of transmission. At this time, researchers are unsure whether cat saliva is infectious. The Bartonella species that commonly infect dogs have only been reported to infect people in rare circumstances, and ticks possibly infected those individuals.
Who is at risk?
Pet owners, veterinarians, veterinary team members, and others who work with animals regularly are at the highest risk for bartonellosis infection. In fact, of the veterinary professionals whom Dr. Edward Breitschwerdt's team tested, up to 50 percent were infected with one or more Bartonella species. And while it's commonly thought that Bartonella only causes chronic bacteremia in immunocompromised people, Dr. Breitschwerdt's team has found that even healthy people can become ill.
How is it treated?
Once diagnosed, bartonellosis is typically treated with antibiotics. Ninety-five percent of patients respond to treatment, according to Bobak Robert Mozayeni, MD, a leading expert on Bartonella.
What precautions can you take?
Most people become infected with Bartonella from wounds that get contaminated with flea excrement. One of the best ways to ward off bartonellosis is to recommend that your clients--especially cat owners--use a monthly parasite prevention that protects against fleas.
Take commonsense precautions, such as avoiding being bitten or scratched by patients and promptly washing any bites or scratches you receive. Also try to avoid contact with blood and other bodily fluids from cats and dogs.
10 symptoms of bartonellosis in people 1. Fever 2. Fatigue 3. Headache 4. Poor appetite 5. Unusual, streaked rash 6. Gastritis 7. Palpitations 8. Severe pain 9. Numbness 10. Acne on upper face and forehead
Sources: California Lyme Disease Association; Bobak Robert Mozayeni, MD
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quote:Bartonella spp. are facultative intracellular pathogens that employ a unique stealth infection strategy comprising immune evasion and modulation, intimate interaction with nucleated cells, and intraerythrocytic persistence.
Infections with Bartonella are ubiquitous among mammals, and many species can infect humans either as their natural host or incidentally as zoonotic pathogens. Upon inoculation into a naive host, the bartonellae first colonize a primary niche that is widely accepted to involve the manipulation of nucleated host cells, e.g., in the microvasculature.
Consistently, in vitro research showed that Bartonella harbors an ample arsenal of virulence factors to modulate the response of such cells, gain entrance, and establish an intracellular niche. Subsequently, the bacteria are seeded into the bloodstream where they invade erythrocytes and give rise to a typically asymptomatic intraerythrocytic bacteremia.
While this course of infection is characteristic for natural hosts, zoonotic infections or the infection of immunocompromised patients may alter the path of Bartonella and result in considerable morbidity.
For instance I think lyme might be every 4 weeks and babessia every week. Some people are able to see a flare of symptoms for the lyme and babesia at the above rates.
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canefan17
Frequent Contributor (5K+ posts)
Member # 22149
posted
Some believe Bart can reproduce as fast as every 20 minutes!!
Buhner has a book coming out soon that has some extensive research done on Bartonella reproduction cycles.
But without a doubt it reproduces super fast (at the very least daily in my case)
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posted
What treatment is there for children with bartonella? My son has a positive test for babs, and is being treated with Mepron/Zithromax. He is negative to bart., but has obvious bart streaks accross his lower back.
Doc says no levaquin for kids. She may put him on A-Bart next month. How about Rifampin? Can you use that for children?
Posts: 418 | From NJ | Registered: Sep 2007
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posted
Oh, I forgot to ask...what exactly is meant by sole pain in feet? I have wondered whether I have seronegative bart., due to symptoms, including foot pain. But, my foot pain is in the bones/tendons of my feet, not the skin. I am confused when people mention sole pain, because I think of this almost as surface pain on the soles of the feet. Is that what is meant by it?
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posted
New article on bartonella, very well done, by the folks from Galaxy Diagnostics. On the CDC site too! Wow.
Pls check the data tables too. _______________________
Volume 18, Number 5--May 2012 Research
Bartonella spp. Bacteremia and Rheumatic Symptoms in Patients from Lyme Disease-endemic Region Ricardo G. Maggi, B. Robert Mozayeni, Elizabeth L. Pultorak, Barbara C. Hegarty, Julie M. Bradley, Maria Correa, and Edward B. Breitschwerdt Author affiliations: North Carolina 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)
-------------------- My biofilm film: www.whyamistillsick.com 2004 Mycoplasma Pneumonia 2006 Positive after 2 years of hell 2006-08 Marshall Protocol. Killed many bug species 2009 - Beating candida, doing better Lahey Clinic in Mass: what a racquet! Posts: 830 | From Mass. | Registered: Aug 2006
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Bartonella spp. Bacteremia and Rheumatic Symptoms in Patients from Lyme Disease-endemic Region
Ricardo G. Maggi, B. Robert Mozayeni, Elizabeth L. Pultorak, Barbara C. Hegarty, Julie M. Bradley, Maria Correa, and Edward B. Breitschwerdt Author affiliations: North Carolina 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).
. . . . . . 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.
[click on link for entire article]
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Bartonella infection associated with rheumatoid illnesses in humans
April 23, 2012
A bacterium historically associated with cat scratch fever and transmitted predominately by fleas may also play a role in human rheumatoid illnesses such as arthritis, according to new research from North Carolina State University.
Bartonella is a bacterium that is maintained in nature by fleas, ticks and other biting insects. It can be transmitted to humans both by these parasites as well as by bites or scratches from infected cats and dogs. The most commonly known Bartonella-related illness is cat scratch disease, caused by B. henselae, a species of Bartonella that can be carried in a cat's blood for months to years.
In collaboration with Dr. Robert Mozayeni, a rheumatologist based in Maryland, and Dr. Ricardo Maggi, a research assistant professor at NC State, Dr. Ed Breitschwerdt, professor of internal medicine at NC State's College of Veterinary Medicine and adjunct professor of medicine at Duke University, tested blood samples from 296 patients for evidence of Bartonella infection. The patients had previously been diagnosed with conditions ranging from Lyme disease to arthritis to chronic fatigue. Since rheumatic symptoms have sometimes been reported following cat scratch disease, the researchers wanted to see if these patients tested positive for B. henselae.
Of the 296 patients, 62 percent had Bartonella antibodies, which supported prior exposure to these bacteria. Bacterial DNA was found in 41 percent of patient samples, allowing investigators to narrow the species of Bartonella present, with B. henselae, B. kohlerae and B. vinsonii subsp. berkhoffii the most prevalent. The study appears in Emerging Infectious Diseases.
"Based upon this one study we can't definitively say that a subset of rheumatoid illnesses have an infectious origin," Breitschwerdt says. "However, our results thus far do implicate Bartonella as a factor in at least some cases. If the link between Bartonella and rheumatoid illnesses is valid, it may also open up more directed treatment options for patients with rheumatoid illnesses."
More information: "Bartonella spp. Bacteremia and Rheumatic Symptoms in Patients from Lyme Disease-endemic Region" Ricardo G. Maggi, et al. Online ahead of print in Emerging Infectious Diseases.
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. Provided by North Carolina State University
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Persistence of Bartonella spp. stealth pathogens: from subclinical infections to vasoproliferative tumor formation
Arto T. Pulliainen1, Christoph Dehio2,* Article first published online: 7 FEB 2012
DOI: 10.1111/j.1574-6976.2012.00324.x
� 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd.
FEMS Microbiology Reviews Special Issue: Intracellular Pathogens and Persistence
Volume 36, Issue 3, pages 563-599, May 2012
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.
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Bartonella vinsonii subsp. berkhoffii and Bartonella henselae as potential causes of proliferative vascular diseases in animals
Christiane Beerlage, Mrudula Varanat, Keith Linder, Ricardo G. Maggi, Jim Cooley, Volkhard A. J. Kempf and Edward B. Breitschwerdt
Abstract
Bartonella species are highly fastidious, vector borne, zoonotic bacteria that cause persistent intraerythrocytic bacteremia and endotheliotropic infection in reservoir and incidental hosts. Based upon prior in vitro research, three Bartonella sp., B. bacilliformis, B. henselae, and B. quintana can induce proliferation of endothelial cells, and each species has been associated with in vivo formation of vasoproliferative tumors in human patients. In this study, we report the molecular detection of B. vinsonii subsp. berkhoffii, B. henselae, B. koehlerae, or DNA of two of these Bartonella species simultaneously in vasoproliferative hemangiopericytomas from a dog, a horse, and a red wolf and in systemic reactive angioendotheliomatosis lesions from cats and a steer. In addition, we provide documentation that B. vinsonii subsp. berkhoffii infections induce activation of hypoxia inducible factor-1 and production of vascular endothelial growth factor, thereby providing mechanistic evidence as to how these bacteria could contribute to the development of vasoproliferative lesions. Based upon these results, we suggest that a fourth species, B. vinsonii subsp. berkhoffii, should be added to the list of bartonellae that can induce vasoproliferative lesions and that infection with one or more Bartonella sp. may contribute to the pathogenesis of systemic reactive angioendotheliomatosis and hemangiopericytomas in animals.
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Intruders below the Radar: Molecular Pathogenesis of Bartonella spp.
Alexander Harms and Christoph Dehio
Focal Area Infection Biology, Biozentrum, University of Basel, Basel, Switzerland
SUMMARY
Summary: Bartonella spp. are facultative intracellular pathogens that employ a unique stealth infection strategy comprising immune evasion and modulation, intimate interaction with nucleated cells, and intraerythrocytic persistence. Infections with Bartonella are ubiquitous among mammals, and many species can infect humans either as their natural host or incidentally as zoonotic pathogens.
Upon inoculation into a naive host, the bartonellae first colonize a primary niche that is widely accepted to involve the manipulation of nucleated host cells, e.g., in the microvasculature. Consistently, in vitro research showed that Bartonella harbors an ample arsenal of virulence factors to modulate the response of such cells, gain entrance, and establish an intracellular niche.
Subsequently, the bacteria are seeded into the bloodstream where they invade erythrocytes and give rise to a typically asymptomatic intraerythrocytic bacteremia. While this course of infection is characteristic for natural hosts, zoonotic infections or the infection of immunocompromised patients may alter the path of Bartonella and result in considerable morbidity.
In this review we compile current knowledge on the molecular processes underlying both the infection strategy and pathogenesis of Bartonella and discuss their connection to the clinical presentation of human patients, which ranges from minor complaints to life-threatening disease.
Many Gram-negative bacteria (Klebsiella, Salmonella, Proteus, Yersinia, Shigella and Campylobacter) have been implicated in the development of HLA-B27-associated diseases such as uveitis, reactive arthritis and ankylosing spondylitis.33 There is also emerging evidence of a potential association between Bartonella intraocular infections/uveitis and HLA-B27 antigen expression. Michel Drancourt and associates described a 40-year-old HLA-B27 positive woman with a 10-year history of poorly controlled nongranulomatous uveitis whose inflammation was controlled only after a Bartonella diagnosis was made and appropriate antibiotic therapy was instituted.34 In an analysis done by Frank Kerkhoff and Aniki Rothova, six of 19 patients with positive enzyme immunoassays for B. henselae were also HLA-B27 positive. This number was significantly higher than the rate of HLA-B27 positivity in a control group of 25 patients with uveitis and no serologic evidence for B. henselae infection.33
Moreover, HLA-B27 positive patients may be at risk for more severe ocular Bartonella infections. Five of the six patients with both serologic evidence of Bartonella infection and HLA-B27 antigen expression described in this study had what Drs. Kerkhoff and Rothova characterized as severe posterior segment involvement.
Four of these patients had a history of previous uveitis restricted to the anterior segment, and only later developed a more severe posterior uveitis when they converted to having B. henselae-positive serology.33 It is currently unknown how such bacterial colonization or infection with B. henselae (and other Gram-negative bacteria) triggers or worsens HLA-associated disease, but there are theories of localized changes related to the interactions between the bacteria and immune cells in HLA-B27-positive patients.33
Diagnosis
The diagnosis of CSD has historically been made clinically, but the development of biomolecular laboratory techniques such as sensitive and specific serologic tests and polymerase chain reaction analyses are now used to aid in the identification of B. henselae infection in most patients. In the United States, there are two types of serologic tests currently used for the diagnosis of CSD. In 1992, the Centers for Disease Control and Prevention began offering an indirect fluorescent assay specific for antibodies directed against B. henselae.
This test has a sensitivity and specificity above 90 percent, but it does not differentiate between IgM and IgG antibodies.8 The other commercially available serologic test is an enzyme-linked immunoassay for both IgG and IgM anti-B. henselae antibodies. These ELISA tests are currently available at multiple laboratories and have variable sensitivity and specificity.35 With both IFA and ELISA, IgM tests are more accurate in the first eight weeks of CSD symptoms, while the IgG tests can remain accurate for longer periods of time or can be found in patients without any evidence of ocular or systemic CSD.25,35 Most of these tests have cross-reactivity to B. quintana, and some have cross-reactivity to other Bartonella species as well. PCR-based techniques have also been created.
These tests are very sensitive and can differentiate between Bartonella species, but they are not yet widely available and thus far have mostly been used in research institutions. Culture of Bartonella species is possible, but it is difficult and infrequently used for diagnostic or therapeutic purposes.
Though serologic markers of Bartonella infection were linked to ocular CSD in the late 1990s, the prevalence and full spectrum of Bartonella-associated uveitic disease was difficult to ascertain because of limited numbers of patients in the original case reports.11,19 These issues were partly addressed by Michel Drancourt and colleagues, who evaluated a population of 1,520 cases of previously idiopathic uveitis.12 Using both serology (IFA) confirmed with Western blot analysis and PCR analysis of intraocular fluids, the investigators found that 21 of 78 fastidious bacteria responsible for the uveitis were Bartonella species (B. henselae 9, B. quintana 7, B. grahamii 4, other Bartonella species1). Eighteen of these 21 patients were identified serologically, and three were identified using intraocular specimens. Of the 21 patients, 10 had bilateral disease. The uveitis was granulomatous in 11 cases (See Figure 3), nongranulomatous in 10 cases, posterior in 11 cases, anterior in eight cases and intermediate in two cases.
When and how to test for Bartonella infection in patients with uveitis remains the subject of debate. Most agree that serologic testing for B. henselae exposure is indicated for patients presenting with well-recognized complications of CSD, including signs of POGS, neuroretinitis or focal retinitis or choroiditis of the type described in patients with known B. henselae infection. While a single positive IgG supports the diagnosis of bartonellosis in patients with characteristic clinical features, either a positive IgM or a fourfold change in IgG titers provides the most compelling evidence for association in patients with an atypical presentation, particularly since 3 to 5 percent of the general population has positive B. henselae titers.25
It is less clear when to perform testing for exposure to other Bartonella species. Because uveitis caused by Bartonella species other than B. henselae appears to be uncommon, and, since the reported clinical presentations in such patients have been fairly non-descript, such testing is typically reserved for those patients with systemic signs or symptoms suggesting infection by a specific Bartonella species. Where available, broad PCR-based screening of aqueous or vitreous for bacterial and viral DNA, including Bartonella species, may be considered in patients with chronic uveitis refractory to treatment. We do not typically test for B. henselae infection in patients with HLA-B27-associated anterior uveitis, or for HLA-B27 positivity in patients with ocular complications of CSD, both because the degree of correlation appears to be limited and because a positive result would not alter management.
Treatment
Doxycycline, 100 mg orally b.i.d., is usually prescribed for two to four weeks in immunocompetent patients and up to four months in the immunocompromised.4 Treatment can also be continued for longer periods in immunocompromised patients to help prevent recurrence of ocular disease.36
Doxycycline augments the free radicals used by polymorphonuclear cells to kill phagocitized cells, which are suppressed by Bartonella infections.19 Doxycycline is preferred to erythromycin for its better intraocular and central nervous system penetration, but doxycycline should not be given to young children, in whom tooth discoloration is a possibility.
For severe disease or in patients with central nervous system involvement, these same antibiotics can also be given intravenously, or together with rifampin, 300 mg orally b.i.d.36 Patients with severe optic nerve or macular inflammation may benefit from corticosteroids in addition to antimicrobial treatment.22
Bartonella species are well-recognized ocular pathogens. B. henselae is most frequently implicated, with POGS and neuroretinitis being the most common manifestations. Associated findings in patients with neuroretinitis include peripapillary serous retinal detachment, focal retinitis, focal choroiditis, vasculitis and vascular occlusion. More recent studies suggest that infection by diverse Bartonella species may be associated with uveitis and that the inflammation may be granulomatous or non-granulomatous; anterior, intermediate, posterior, or diffuse; and with or without neuroretinitis or peripapillary serous retinal detachment.
Both serologic and intraocular fluid tests are now available to diagnose Bartonella-associated uveitis, but when and how to use these tests remains a subject of debate. Short-term treatment with oral doxycycline is usually adequate to control the ocular manifestations in immunocompetent patients, but longer treatment with multiple agents may be necessary in patients with HIV/AIDS.
Dr. Chappell is a resident in ophthalmology at California Pacific Medical Center in San Francisco. Dr. Jumper is the Retina Service chief at CPMC and in private practice at the West Coast Retina Medical Group. Dr. McDonald is an attending at CPMC and in private practice at the West Coast Retina Medical Group. Dr. Cunningham is director of the Uveitis Service at CPMC, an adjunct clinical professor of ophthalmology at Stanford University School of Medicine, Stanford, Calif., and in private practice at West Coast Retina Medical Group. Address correspondence to Dr. Cunningham at West Coast Retina Medical Group, Lobby 2, Ste. 130, 185 Berry St., San Francisco, CA 94107. Phone: (415) 972-4600; fax: (415) 975-0999; e-mail: [email protected]. This work was supported in part by the Pacific Vision Foundation and by the San Francisco Retina Foundation.
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