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Cat-scratch disease: epidemiology, aetiology and treatment.

Cat-scratch disease (CSD) is a clinical syndrome that usually presents as a self-limiting lymphadenopathy associated with a cat scratch or bite. Commonly affecting children and young adults, it has a worldwide distribution. In temperate climates, higher rates are reported in the autumn and winter, which can be attributed to the seasonal breeding of the domestic cat. The organism responsible was identified in 1983, having eluded detection for 50 years. Initially, Afipia felis was thought to be the cause; however, subsequent study failed to confirm a link. During the 1990s, it was demonstrated conclusively that Rochalimaea henselae, later reclassified as Bartonella henselae, was the cause of CSD. B. henselae has been isolated from bacteraemic cats, with transmission among cats thought to be via the cat flea. Although other Bartonella species are transmitted by arthropod vectors, it is unlikely that the cat flea is involved directly in human infection, but plays a role in amplifying the reservoir. B. henselae is difficult to culture, and either serology or the polymerase chain reaction are considered to be the best methods of detection. Genetic variation occurs amongst B. henselae strains, perhaps explaining the inconsistency of some diagnostic techniques. A separate serogroup (Marseilles) has been reported in a seronegative patient with CSD, and B. clarridgeiae has the potential to cause the disease. Atypical presentation is seen in up to 25% of cases, and manifests itself as ocular involvement, encephalopathy, granulomatous hepatitis, hepatosplenic infection, endocarditis and osteomyelitis. The majority of CSD cases resolve spontaneously and do not require antibiotic treatment. In complicated CSD, treatment with trimethoprim-sulphamethoxazole, ciprofloxacin or azithromycin is recommended, with gentamicin being reserved for the severely ill patient.

Animals↗

Bacillary angiomatosis in HIV-infected patients--an epidemiological and clinical study.

BACKGROUND: No data were available on the epidemiological and clinical characteristics of bacillary angiomatosis (BA) in Germany. OBJECTIVE: To determine epidemiological and clinical data on HIV-associated BA. METHODS: A chart review of all BA cases between 1990 and 1998 was performed in 23 German AIDS treatment units. RESULTS: A total of 21 cases of BA was diagnosed. During this period, the participating HIV centers treated about 17,000 HIV-infected patients. As a result, a BA prevalence of 1.2 cases/1,000 patients can be assumed. 19 BA were localized in the skin; in 5 cases bones and in 4 cases the liver were involved. Out of 20 patients who received antibiotic therapy, 13 had complete remission. The median time of duration up to complete remission was 32 days (9-82). During the follow-up of the 20 patients, 7 relapses were observed. CONCLUSION: BA is a rare HIV-associated disease with a prevalence of 1,2 cases/1,000 patients in the presented study.

Adult↗

Unusual trafficking pattern of Bartonella henselae -containing vacuoles in macrophages and endothelial cells.

Bartonella henselae, the agent of cat-scratch disease and vasculoproliferative disorders in humans, is a fastidious facultative intracellular pathogen, whose interaction with macrophages and endothelial cells (ECs) is crucial in the pathogenesis of these diseases. However, little is known about the subcellular compartment in which B. henselae resides. Two hours after infection of murine macrophages and human ECs, the majority of B. henselae-containing vacuoles (BCVs) lack typical endocytic marker proteins, fail to acidify, and do not fuse with lysosomes, suggesting that B. henselae resides in a non-endocytic compartment. In contrast to human umbilical vein endothelial cells, bacterial death and lysosomal fusion with BCVs is apparent in J774A.1 macrophages at 24 h. This phenomenon of delayed lysosomal fusion requires bacterial viability, and is confined to the BCV itself. Using magnetic selection, we enriched for transposon-mutagenized B. henselae trapped in lysosomes of macrophages 2 h after infection. Genes affected appear to be relevant to the intracellular lifestyle in macrophages and ECs and include some previously implicated in Bartonella pathogenicity. We conclude that B. henselae has a specific capacity to actively avoid the host endocytic pathway after entry of macrophages and ECs, from within a specialized non-endocytic membrane-bound vacuole.

Animals↗

Bartonella henselae bacteraemia in domestic cats from Auckland.

Bartonella henselae causes most cases of cat scratch disease, a self-limited localised lymphadenopathy illness of humans. Bartonella henselae also causes disseminated cutaneous and visceral disease in immunocompromised people. Cat blood (1-5 ml) collected from cats in the Auckland area was processed and plated on to 5% sheep blood brain heart infusion agar and incubated at 35 degrees C in 5% CO2 for 14 days. Bartonella henselae was identified by colony morphology, Gram's stain, twitching motility, biochemical tests and molecular methods. Eight of 48 cats (17%) had Bartonella bacteraemia. Species-specific probes and biochemical profiles identified all isolates as B. henselae. Infected cats pose a risk to humans they lick, scratch or bite. People should be made aware of the risk cats pose.

Journal Article↗

Detection and identification of Ehrlichia, Borrelia burgdorferi sensu lato, and Bartonella species in Dutch Ixodes ricinus ticks.

A sensitive and specific PCR hybridization assay was developed for the simultaneous detection and identification of Ehrlichia and Borrelia burgdorferi sensu lato. In separate assays the 16S rRNA gene of Ehrlichia species and the 23S-5S rRNA spacer region of B. burgdorferi sensu lato were amplified and labeled by PCR. These PCR products were used in a reverse line blot hybridization assay in which oligonucleotide probes are covalently linked to a membrane in parallel lines. Hybridization of the samples with the oligonucleotide probes on this membrane enabled the simultaneous detection and identification of Ehrlichia, B. burgdorferi, and Bartonella species in 40 different samples. The application of the assay to DNA extracts from 121 Ixodes ricinus ticks collected from roe deer demonstrated that 45% of these ticks carried Ehrlichia DNA. More than half of these positive ticks carried species with 16S rRNA gene sequences closely related to those of E. phagocytophila and the human granulocytic ehrlichiosis agent. The majority of the other positive ticks were infected with a newly identified Ehrlichia-like species. In addition, 13% of the ticks were infected with one or more B. burgdorferi genospecies. In more than 70% of the ticks 16S rRNA gene sequences for Bartonella species or other species closely related to Bartonella were found. In five of the ticks both Ehrlichia and B. burgdorferi species were detected.

Animals↗

A heat-stable component of Bartonella henselae upregulates intercellular adhesion molecule-1 expression on vascular endothelial cells.

Bartonella henselae upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVECs). The induction level of ICAM-1 depended on the inoculation bacterial dose. ICAM-1 expression began increasing 4 h after infection and reached a sustained peak beginning at 12 h after B. henselae infection; this time course was similar to that of lipopolysaccharide (LPS) of Escherichia coli. The stimulatory effect was abolished when live B. henselae were separated from HUVECs by a filter membrane. The nonpiliated strain, which is unable to invade endothelial cells, induced ICAM-1 expression to the same extent as the piliated strain. Inactivation of B. henselae by ultraviolet (UV) irradiation, heat (56 degrees C, 30 min), or sonication did not alter its stimulatory activity. Polymyxin B, which strongly inhibited the effect of LPS, did not exert any influence on the stimulatory activity of B. henselae. Furthermore, the effect of sonicated B. henselae was not inhibited even by boiling, which was also the case with LPS. Our data suggest that some heat-stable component of B. henselae binds to the endothelial cell surface, inducing ICAM-1 expression. Though the participation of LPS could not be completely ruled out, we suppose that some unidentified heat-stable proteins, lipids, or polysaccharides may be the stimulatory factor(s). The ability of B. henselae to enhance the expression of adhesion molecules on endothelial cells may be an important mechanism in the pathogenesis of B. henselae infection.

Animals↗

Ocular manifestation of systemic infections.

Patients with various systemic infections can often be diagnosed on the basis of their presenting ocular signs and symptoms. Recognition of the ocular manifestations of systemic infections will expedite diagnosis and allow rapid institution of appropriate therapy thereby reducing morbidity and mortality. Recent literature discussing ophthalmologic findings in the following diseases are reviewed: Whipple's disease, endogenous endophthalmitis, cat-scratch disease, toxoplasmosis, and hepatitis C.

Bartonella henselae↗

Ocular manifestations of cat-scratch disease.

Bartonella henselae has only recently been isolated, characterized, and found to be the principal cause of cat-scratch disease (CSD). The availability of specific serologic investigations has allowed the recognition of a spectrum of ocular CSD syndromes that previously were ill defined and considered idiopathic. The primary inoculation complex causing regional lymphadenopathy is represented in the eye by Parinaud's oculoglandular syndrome; B. henselae is the most common cause. Leber's neuroretinitis has been identified for 80 years, and new data suggest that it is commonly a manifestation of CSD; the extent of the association remains to be determined. CSD optic neuritis is also described. The vitreoretinal manifestations include anterior uveitis, vitritis, pars planitis, focal retinal vasculitis, a characteristic retinal white spot syndrome, Bartonella retinitis, branch retinal arteriolar or venular occlusions, focal choroiditis, serous retinal detachments, and peripapillary angiomatous lesions. The pattern of ocular disease in AIDS-associated B. henselae infections is poorly delineated; unusual manifestations include conjunctival and retinal bacillary angiomatosis. The benefit of antimicrobial therapy for CSD in immunocompetent individuals has been difficult to establish, partly because most infections are self limited. Empirically, azithromycin, ciprofloxacin, rifampin, parenteral gentamicin, or trimethoprim-sulfamethoxazole provide the best therapeutic choices to minimize damage to the eye.

Anti-Bacterial Agents↗

Bone infection in cat-scratch disease: a review of the literature.

OBJECTIVE: To describe the main features of bone infection associated with Cat-scratch disease (CSD). METHODS: We searched for articles indexed in the international literature databases by using the following key words: "Bartonella", "bone", "cat-scratch", "osteomyelitis" and "osteolytic". RESULTS: Cases of 47 patients were reviewed. The median age was 9 years, with an equal sex distribution. Bone pain and fever were the main symptoms. The presence of fever and increased age were more common in patients with bone infection than classically reported in uncomplicated (i.e. nodal) CSD. The vertebral column and pelvic girdle were the most common sites of infection. Radiological examination typically confirmed bone osteolysis. All patients recovered without complications or chronic infection, although they received a various combination antibiotic regimen and duration therapy. The mechanism by which infection might spread to the bone is via the haematogenous route, accounting for most of the disseminated cases and via the lymphatic route, for those with regional limited extension. CONCLUSIONS: Bone infection is rare but should be considered when bone pain and fever are present in a patient with nodal CSD. The prognosis is good, whatever treatment is given. Thus bone biopsy should be recommended only in a difficult diagnostic setting, when other bacteria or malignant disease are suspected.

Adolescent↗

[The epidemiology of trench fever: a pilot study in homeless people in Marseilles].

Trench fever, cause by Bartonella quintana, disappeared decades ago. Between 1992 and 1994 about 20 cases were reported in industrialized countries [6, 7]. Some of these cases were associated with HIV infection [5], but most affected the homeless. The epidemiology of B. quintana is unknown in Europe, but infection and transmission are favoured by poor housing and hygiene. This paper describes the results of a seroprevalence survey among the homeless living in Marseille. The eight major non-profit organizations caring for the homeless in the city participated for the four winter months. Four of these organizations also provide health care. Each subject who came to be housed for more than one day were asked to complete a questionnaire and give a small blood sample by micropuncture. They were clearly informed about the aims of the research and were allowed to refuse participation freely. All blood samples were tested by the WHO collaborative center for ricketssiae using a previously tested and validated immunofluorescence technique. The subjects were scored positive if the IgG titer was above 1/100. Two hundred and twenty one subjects agreed to participate in the study. Most were of French origin (51.4%) and 40% under 40 years old. The seroprevalence was 1.8% (IC 95%: 0.05-3.55). None of the four positive subjects presented symptoms and clinical examination was normal. All four were over 40 years old; two were of French origin, 1 from Algeria and 1 from the Comoro Islands. One had an IgG titer above 1/3, 200, possibly reflecting recent contamination and/or severe infection. Statistical analysis revealed no significant association between seropositivity and housing or hygiene conditions. No socio-demographic data are available about the homeless in Marseille and indeed, there is no list of such individuals. It is therefore not possible to estimate the representativity of our sample. Nevertheless, we show that the homeless include infected individuals. Physicians who care for such subjects should prescribe B. quintana serological investigations, and organizations that take in these people should implement preventive action and health education programs. Any such policy must be designed so as to be acceptable to homeless people. This work should also encourage public health professionals to investigate more extensively infectious diseases among the homeless.

Adolescent↗

Bartonella henselae endocarditis in an immunocompetent adult.

We describe a case of aggressive Bartonella henselae endocarditis in an immunocompetent man who owned a cat. Aortic valve replacement was required, and his infection was diagnosed by histology, serology, and polymerase chain reaction analysis. The manifestations of his disease included mediastinal lymphadenopathy, glomerulonephritis, myocarditis, and a petechial rash; the unusual finding of a positive titer of c-antineutrophil cytoplasmic antibodies was noted. Serological titers were markedly elevated for > 1 year despite clinical improvement.

Adult↗

Cat-scratch disease with paravertebral mass and osteomyelitis.

The case of a 9-year-old girl with cat-scratch disease (CSD) complicated by development of a paravertebral mass and osteomyelitis is presented. Following multiple scratches and inguinal lymphadenopathy, she developed back pain, and imaging demonstrated a paravertebral mass with evidence of osteomyelitis involving vertebra T9. The diagnosis was made on the basis of detection of Bartonella henselae by use of molecular techniques on an aspirate from the vertebral column and supportive serology for infection with B. henselae. Eleven other cases of this unusual manifestation associated with CSD have been reported in the literature and are reviewed. The patient was treated with gentamicin, followed by rifampicin and trimethoprim-sulfamethoxazole, orally and made a favorable recovery over 7 months. This is comparable with other case reports, regardless of the choice of antibiotic therapy. CSD in immunocompetent hosts is not always self-limiting, and tissues beyond the lymph nodes can be involved.

Bartonella henselae↗

The MutT motif family of nucleotide phosphohydrolases in man and human pathogens (review).

Human cells express at least eight members of the MutT motif protein (or nudix hydrolase) family. These enzymes are believed to eliminate toxic nucleotide derivatives from the cell and regulate the levels of important signalling nucleotides and their metabolites. Six have been fully or partially characterized: i) hMTH1 is a nucleoside triphosphatase which restricts AT-->CG transversions by specifically degrading the oxidized nucleotide 8-oxo-dGTP; ii) hAPAH1 preferentially degrades the signalling dinucleotide Ap4A; iii) DIPP is unusual in hydrolysing two seemingly unrelated signalling substrate groups - the dinucleotides Ap6A and Ap5A, and the diphosphoinositol polyphosphates; iv) DIPP2 is closely related to DIPP; v) hYSAH1 is an NDP-sugar hydrolase which prefers ADP-ribose, and vi) hGFG is a protein of unknown function encoded by the antisense transcript of the basic fibroblast growth factor gene. Although not yet associated with known hereditary or acquired disorders, the functional loss of any one of these hydrolases would be expected to be detrimental to cellular function. Furthermore, the ialA invasion gene of Bartonella bacilliformis and other invasive pathogens encodes a MutT motif Ap4A hydrolase while poxviruses express two MutT motif proteins, at least one of which is essential for infectivity. This protein family, therefore, occupies a position of some importance in controlling human health and disease.

Amino Acid Sequence↗