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We report a Bartonella henselae infection in a 40-y-old patient who presented with fever, weight loss, night sweats, elevated lactate dehydrogenase and multinodular splenomegaly with multiple abdominal lymphadenopathies. Splenic cat-scratch disease is an exceptional diagnosis in adults and can easily be mistaken for a splenic lymphoma, thereby leading to an unnecessary splenectomy.
Bartonella henselae is an emerging pathogen capable of causing severe disease. We report a case of severe protracted illness in an otherwise healthy police dog handler. The patient recovered slowly after antibiotic treatment. This case report emphasizes the importance of considering B. henselae infections in patients with fever of unknown origin.
PURPOSE: To present endophthalmitis-like massive vitreous opacity as a manifestation of cat-scratch disease. METHODS: Report of a case. RESULTS: A 47-year-old man developed massive vitreous opacity and total retinal detachment in his right eye after a four-month period of uveitis, which was controlled with oral prednisolone. During the diagnostic vitrectomy, a massive fluffy white opacity adhering to the detached retina was shaved using a vitreous cutter. Further surgical procedures to reattach the retina were not pursued because of the poor state of the infected retina. Pathological examination of the vitreous aspirates revealed pleomorphic bacilli. The serological testing done at referral revealed an IgG titer positive for Bartonella henselae and culture of the vitreous proved the infection a month later. With a mixture of oral sulfamethoxazole (1600 mg daily) and trimethoprim (320 mg daily), the intraocular inflammation subsided. CONCLUSION: Rapid progression of massive vitreous opacity with total retinal detachment, mimicking endophthalmitis, can occur in cat-scratch disease.
Contemporary Bartonella quintana infections have emerged in diverse regions of the world, predominantly involving socially disadvantaged persons. Available data suggest that the human body louse Pediculus humanus is the vector for transmission of B. quintana. Descriptions of the clinical manifestations associated with contemporary B. quintana infections have varied considerably and include asymptomatic infection, a relapsing febrile illness, headache, leg pain, "culture-negative" endocarditis, and, in human immunodeficiency virus-infected persons, bacillary angiomatosis. Laboratory diagnosis is most convincing when B. quintana is isolated in blood culture, but growth often takes 20-40 days; problems exist with both sensitivity and specificity of serological assays. On the basis of available information, use of doxycycline, erythromycin, or azithromycin to treat B. quintana infections is recommended. Treatment of uncomplicated B. quintana bacteremia for 4-6 weeks and treatment of B. quintana endocarditis (in a person who does not undergo valve surgery) for 4-6 months are recommended, with the addition of a bactericidal agent (such as a third-generation cephalosporin or an aminoglycoside) during the initial 2-3 weeks of therapy for endocarditis.
A 45-year-old man presented with progressively worsening vitreitis of 1 week's duration. Treatment for cat-scratch disease 3 years prior to presentation and persistent vitreitis led to vitrectomy, and analysis of the vitrectomy specimen revealed inflammatory cells and necrotic debris; polymerase-chain-reaction analysis of the vitreous fluid sample, done by use of a novel heminested protocol, demonstrated the presence of Bartonella henselae DNA. Treatment with doxycycline led to improvement in the intraocular inflammation but resulted in a poor visual outcome.
Whipple's disease is a systemic infection sometimes associated with cardiac manifestations. Recently, there has been an increase in the number of reported cases of Whipple's endocarditis. The purpose of our study was to describe this entity. Data from 35 well-described cases of Whipple's endocarditis were collected and compared with those of blood culture-positive endocarditis, Q fever endocarditis, and Bartonella endocarditis. Some patients with generalized Whipple's disease presented with cardiac involvement, among other symptoms. Others presented with a nonspecific, blood culture-negative endocarditis with no associated symptoms. In comparison with cases of endocarditis due to other causes, congestive heart failure, fever, and previous valvular disease were less frequently observed in the cases of Whipple's endocarditis. Without examination of the excised valves, the diagnosis of infective endocarditis could not have been confirmed in most cases. Treatment is not well established. Whipple's endocarditis is a specific entity involving minor inflammatory reactions and negative blood cultures, and its incidence is probably underestimated.
We describe 2 adult patients (1 of whom was infected with human immunodeficiency virus) with osteomyelitis due to Bartonella henselae. Diagnosis was established on the basis of direct identification of the microorganism in one case and seroconversion in the other. Both patients recovered completely within 3 months.
Bartonella henselae causes severe disease in immunocompromised individuals. B. henselae was isolated from 12 human immunodeficiency virus (HIV)-infected individuals with bacillary angiomatosis and/or peliosis hepatis and from their 15 cat contacts. Specific associations between the 2 B. henselae genotypes, individual pulsed-field gel electrophoresis (PFGE) patterns, and different clinical syndromes and pathogenicity were investigated. The role of cat contacts as the source of human infection was also examined. Three of the 4 patients with B. henselae genotype I infection, but none of the 8 patients with genotype II infection, had hepatosplenic vascular proliferative lesions (P=.018). Four of 5 human-cat pairs had closely-related PFGE patterns and concordant results by 16S rDNA typing, which strongly suggests that human infection was caused by the cat contact. These results corroborate the major role of cats in the transmission of B. henselae to humans and suggest that B. henselae genotypes may induce different pathological features in HIV-infected patients.
Chronic asymptomatic bacteremia caused by Bartonella quintana occurs in homeless people, but its pathophysiology is unknown. We investigated homeless people with bacteremia to determine whether the persistence of B. quintana is associated with a specific immune profile. Homeless people without B. quintana infection exhibited an inflammatory profile--levels of circulating markers of leukocyte activation (soluble interleukin [IL]-2 receptor and neopterin) and cytokines released by mononuclear cells (tumor necrosis factor, IL-1beta, IL-6, and IL-10) were significantly higher than levels in healthy control subjects. In contrast, homeless people with B. quintana bacteremia exhibited specific increases in IL-10 secretion by mononuclear cells. This overproduction of IL-10 was associated with an attenuated inflammatory profile. The depressed inflammatory response was specific of bacteremia, because patients with specific antibodies and without bacteremia had responses similar to those of homeless people. The overproduction of IL-10 and attenuated inflammatory response may account for the persistence of B. quintana in homeless people.
Few data are available on the seroprevalence of antibodies to Bartonella henselae among children. We retrospectively evaluated the presence of immunoglobulin G and M class antibodies to B. henselae in 508 children living in central Italy who were apparently free of any features suggesting B. henselae infection. We found that B. henselae infection is common among children in central Italy, occurs early in life, is in most cases asymptomatic, and resolves spontaneously.
Bacteria of the genus Bartonella are transmitted by ectoparasites (lice, fleas, ticks) and have mammalian reservoirs in which they cause chronic, asymptomatic bacteremia. Humans are the reservoir of B. quintana, the louse-borne agent of trench fever. We detected DNA of B. quintana in the dental pulp of a person who died 4000 years ago.
BACKGROUND: Bartonella quintana, the etiological agent of bacillary angiomatosis (BA), causes endothelial cell proliferation. Erythromycin has dramatic effects on BA, and the effects are largely unexplained by the compound's bacteriostatic properties. Our aim here was to evaluate the possibility that erythromycin alters angiogenesis. METHODS: The effect of erythromycin on B. quintana-induced endothelial cell proliferation was studied using a wild-type strain and an erythromycin-resistant B. quintana mutant. The latter was generated by serial subcultures on blood agar plates. RESULTS: We show that erythromycin significantly inhibits the proliferation of dermal microvascular endothelial cells induced either by wild-type B. quintana or by our erythromycin-resistant mutant. Doxycycline and gentamycin failed to exert such an effect. Finally, we found that the resistant strain harbored a 27-bp insertion in the highly conserved region of the gene encoding the ribosomal protein L4; this insertion may explain the existence of the resistance to erythromycin. CONCLUSION: The data presented here indicate that erythromycin profoundly down-modulates endothelial cell proliferation irrespective of its bacteriostatic effects and suggest that this may be a key component of the efficacy of the compound in the treatment of patients with BA.
Bartonella henselae was recovered from the conjunctival scraping of a 38-year-old woman who presented with a 2-week history of tender preauricular lymphadenopathy and a 1-day history of a red left eye. Dry adherent colonies were observed on agar plates at 21 days of incubation, and the isolate was identified through conventional and molecular tests. Polymerase chain reaction (PCR) amplification of a specific region of the 16S rRNA gene and confirmation by a separate PCR reaction with hybridization of the product with a B. henselae-specific probe confirmed the isolate as B. henselae. This is the first reported isolation of the causative agent of cat scratch disease from ocular tissue in a patient with Parinaud's oculoglandular syndrome.
Infections with Bartonella (Rochalimaea) henselae can result in a variety of clinical entities, including bacillary angiomatosis in immunocompromised hosts. The fastidious nature of this bacterium has so far prevented the culture of many clinical isolates. We report the recovery of the first European B. henselae isolate associated with bacillary angiomatosis. The isolate was cultured in a frozen skin biopsy specimen from a human immunodeficiency virus (HIV)-infected patient and was characterized by means of biochemical, bacteriologic, immunologic, and molecular biological methods including pulsed-field gel electrophoresis. This strain was compared with two B. henselae strains isolated in the United States to determine the relationship between the isolates. We found that it was phenotypically and genotypically indiscernible from B. henselae Houston-1, a blood culture isolate from an HIV-infected patient in Houston. These data suggest that one B. henselae clone is associated with human infections in Europe and the United States.
A 17-kDa, immunodominant antigen of Bartonella henselae Houston-1 has previously been cloned, sequenced, and characterized. This clone (H13) contains the 17-kDa antigen gene plus a partial open reading frame, designated ORF1, which is 459 nucleotides long and is directly upstream of the 17-kDa gene. Comparison of the deduced partial amino acid sequence of ORF1 with that of other known genes in GenBank revealed significant identity with several other bacterial virulence genes, including VirB4 of the Agrobacterium tumefaciens virB operon (56/149 amino acids). An overlapping clone, pGB3, was recovered and shown to contain a 3.0-kb region upstream of the 17-kDa gene. Sequence analysis revealed three ORFs upstream of the gene. The deduced amino acid sequence of each ORF was compared with sequences in GenBank, and identity was found with VirB2, VirB3, and VirB4 of A. tumefaciens. In vitro transcription/translation and SDS-PAGE demonstrated that three proteins of 9 kDa, 10 kDa, and 92 kDa, corresponding to the predicted molecular weight of 10.9 kDa, 11.7 kDa, and 89.9 kDa of VirB2, VirB3, and VirB4, respectively, could be expressed from these coding regions. These results indicate that virulence-associated genes and their overall chromosomal arrangement are relatively well conserved between B. henselae and other gram-negative bacteria such as A. tumefaciens.
A Bartonella henselae genomic A library was screened with antiserum generated in mice against live B. henselae. One of the immunoreactive clones expressed a 17-kDa antigen that was characterized previously as an immunodominant protein of B. henselae. Sequence analysis of the recombinant clone, pBHIM-2, revealed that the open reading frame (ORF) encoding the 17-kDa antigen was situated between homologs of virB4 and virB6, two genes that belong to the virB operon. The virB operon has been associated with the transfer of oncogenic T-DNA in Agrobacterium tumefaciens and with secretion of the pertussis toxin in Bordetella pertussis. Downstream of the virB6 gene within pBHIM-2 was a partial open reading frame that was homologous to the virB8 gene. Rescreening of the library by plaque hybridization using probes specific to the 5' and 3' ends of the pBHIM-2 insert resulted in the isolation of recombinant clones containing additional virB genes. Assembly of the sequences obtained from the recombinant clones revealed that eight of the open reading frames encode homologs of the VirB proteins. The homology and colinearity with the virB genes suggest that the gene encoding the 17-kDa antigen is expressed within the virB locus of B. henselae.
A library of Bartonella henselae DNA was screened with antibody raised to the bacteriophage particle associated with this organism. A clone was isolated that expresses a 36-kD protein (termed PapA for particle-associated protein) when examined by immunoblot analysis using antibody raised to the particle. Southern blot hybridization indicates that the gene is present on the bacterial chromosome and packaged into the 14-kb particle-associated DNA. A papA-specific probe hybridized to multiple bands of B. henselae genomic DNA digested with several different restriction endonucleases. Thus, the gene is present in multiple copies on the genome or in different arrangements within a given population of B. henselae cells. The gene coding for PapA has been sequenced and codes for a 326-amino-acid protein with a deduced molecular weight of 36,161 daltons. The deduced protein shows 33.3% identity over a 108-amino-acid sequence with the P-min gene product of Escherichia coli. P-min is partially located within the invertible P region of the excisable element e14, found on the E. coli chromosome. Taken together, these results suggest that papA is present on a mobile genetic element of the B. henselae genome and is also packaged into the bacteriophage particle.
We describe aortic valve endocarditis caused by Bartonella quintana in a 31-year-old man. The diagnosis was made on the basis of polymerase chain reaction amplification of the B quintana citrate synthase gene from cardiac valve tissue, the compatibility of histochemical stains of cardiac valve tissue, and serologic studies.