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[Bacterial zoonoses: emerging concepts].

Bacterial zoonoses are evolving with changes in society, climate and lifestyles. A hierarchy of non food-borne zoonoses was recently proposed in France, and includes characteristics such as severity criteria and bioterrorism potential. The creation of specific networks and reference centers has provided the means to monitor the emergence (or re-emergence) of zoonoses such as brucellosis and Q fever. Molecular tools have facilitated the detection of bacteria that are transmitted by arthropod vectors (ticks, fleas, etc.) and that cause diseases such as Lyme borreliosis, bartonellosis and ehrlichiosis.

Animals↗

Emerging bacterial zoonotic and vector-borne diseases. Ecological and epidemiological factors.

Among the etiologic agents of emerging infectious diseases are several bacterial organisms that naturally reside in animal and arthropod hosts. The most compelling emerging bacterial zoonotic and vector-borne diseases in the United States are Lyme disease; a Southern erythema migrans-like illness; human monocytic ehrlichiosis; human granulocytic ehrlichiosis; a novel cat flea-associated typhus group rickettsiosis; bartonelloses of immunocompetent and immunocompromised persons, particularly with AIDS; and sylvatic plague. Some of these antimicrobial-treatable infections are life threatening. During the acute stage of illness when antimicrobial agents are most effective, the flulike clinical signs and symptoms and available laboratory tests frequently do not point to a particular diagnosis. Epidemiological factors determined by the ecology of the bacteria are often the most useful diagnostic clues. The recognition of these evolving problems emphasizes the need for development of better laboratory diagnostic methods, for surveillance for and tracking of disease, and for continued research into factors contributing to transmission of the organisms. The continual appearance of previously unidentified bacterial infections requires prospective national strategies for timely recognition of the syndrome, identification of the agent, establishment of criteria and methods for diagnosis, optimization of the treatment regimen, and determination of successful approaches to prevention and control.

Animals↗

Longitudinal monitoring of the dynamics of infections due to Bartonella species in UK woodland rodents.

Blood samples were repeatedly collected from 12 sympatric woodland rodents over a 12-month period and DNA extracts from each were incorporated into a bartonella-specific PCR targeting a fragment of the 16S/23S rRNA intergenic spacer region (ISR). The composition of each amplicon was analysed using restriction enzyme analysis (REA) and base sequence comparison. Bartonella DNA was detected in 70 of 109 samples. Eleven samples contained DNA derived from more than one strain. Sequence analysis of 62 samples found 12 sequence variants (ISR genotypes) that were provisionally assigned to 5 different species, 2 of which were newly recognized. Up to five different species were detected in each animal. On about two-thirds of occasions, a species detected I month was not there the next, but never was a genotype superseded by another of the same species. However, a genotype could be re-encountered months later in the same animal, even if interim samples contained other genotypes. Our results suggest that although most animals are bacteraemic most of the time, specific infections are often superseded and that a complex and dynamic epidemiology of bartonella bacteraemias exists in woodland rodents.

Animals↗

The role of the host immune response in pathogenesis of Bartonella henselae.

Bartonella henselae can infect humans resulting in a wide range of disease syndromes including cat-scratch disease, fever with bacteremia, endocarditis, bacillary angiomatosis, and bacillary peliosis hepatis, among others. The nature and severity of the clinical presentation correlates well with the status of the hosts' immune system. Individuals with impaired immune function, including HIV infection, progress to systemic infections more often. Patients with intact immune function who become infected with B. henselae usually get cat-scratch disease, a disease that usually involves lymphadenopathy resulting from a strong cellular immune response to the bacterium. However, immunocompromised patients often progress to bacillary angiomatosis or bacillary peliosis hepatis. The reduced ability of the hosts immune response to control bacterial infection apparently results in a bacteremia of longer duration, and in some patients the presence of angiogenic lesions that are unique among bacterial infections to Bartonella. Recently, the role of immune effector cells that produce angiogenic cytokines upon stimulation with B. henselae has been proposed. Here, the current status of the role of the immune response in both controlling infection and in B. henselae-triggered immunopathogenesis is presented.

Animals↗

Bartonella bacilliformis GroEL: effect on growth of human vascular endothelial cells in infected cocultures.

Bartonella are the only bacteria known to induce angioproliferative lesions of the human vasculature and liver during infection. Previous work from our lab suggests that GroEL participates in the mitogenic response observed in HUVEC cultures supplemented with the soluble fraction of Bartonella bacilliformis. Work in this study shows that exposure to high concentrations of the fraction is actually cytotoxic for HUVECs. To analyze this phenomenon, live B. bacilliformis-HUVEC cocultures were employed to study the effect of excess bacterial GroEL on the host cell during active infection. Four B. bacilliformis strains were generated to produce varying levels of GroEL. HUVEC cocultures with LSS100, a strain that synthesizes markedly greater quantities of GroEL relative to others, significantly accelerates apoptosis of the cocultured HUVECs relative to other strains. Acceleration of apoptosis can be inhibited by Z-VAD-FMK, a pan-caspase inhibitor. Time course data show that, at 18 h of infection, both LSS100 and control strains significantly inhibit spontaneous apoptosis of cocultured HUVECs, as previously reported for other Bartonella species. However, by 48 h, LSS100 significantly increases apoptosis of the host cell. We hypothesize that intracellular Bartonella GroEL functions as an Hsp60 analogue, a eukaryotic orthologue known to accelerate pro-caspase 3 activation by enhancing its vulnerability to upstream activator caspases. These data suggest another strategy whereby Bartonella may regulate host cell growth.

Apoptosis↗

[Cat-scratch disease and disease caused by Bartonella (Rochalimaea)].

The aetiology of cat scratch disease remains controversial since both Afipia felis and Bartonella (Rochalimaea) henselae have been isolated from diseased lymph nodes. Bartonella henselae, Bartonella (Rochalimaea) quintana and Bartonella (Rochalimaea) elizabethae cause endocarditis and Bartonella bacilliformis cause septicemia (Oroya's fever) in non-immunocompromized patients, and Bartonella henselae and Bartonella quintana cause fever, bacillary angiomatosis, and visceral peliosis in human immunodeficiency virus-infected patients. Bartonella quintana is the historical agent of trench fever and we recently isolated it from chronic adenopathy. The diagnosis of Afipia felis and Bartonella infections relies upon the isolation of the bacterium from blood, node tissue after inoculation of cell cultures systems and molecular identification, and upon the serology. In vitro both species are sensitive to aminoglycosides, and we recommend aminoglycosides be included in antibiotic regimens for treating cat scratch disease and Bartonella infections.

Anti-Bacterial Agents↗

Fatal meningitis and encephalitis due to Bartonella henselae bacteria.

Bacterial infection due to Bartonella henselae commonly develops in children and young adults following cat/dog contacts and/or cat/dog scratches. Regional lymphadenopathy is its most common clinical expression. However, encephalitis and Parinaud's syndrome (oculoglandular syndrome) have also been reported as has systemic illness. A review of the international literature in all languages revealed no fatal complications in immunocompetent hosts. A four-year-old white child with no underlying illness began to have seizure-like activity. She was taken to a local hospital and subsequently transferred to a medical center. The child was treated aggressively for seizures and fever of unknown origin. However, her condition rapidly declined and she died without a specific diagnosis. At autopsy there was marked cerebral edema with no gross evidence of acute meningitis. Microscopic exams revealed multiple granulomatous lesions as well as a meningitis and encephalitis. A variety of cultures and stains were negative for acid fast and fungal organisms. Warthin-Starry stains of involved tissue including brain and liver revealed pleomorphic rod shaped bacilli consistent with Barronella henselae. Analysis of brain tissue with polymerase chain reaction (PCR) and Southern blot for the deoxyribonucleic acid (DNA) was definitive for DNA of Bartonella henselae bacteria.

Bartonella Infections↗

Evidence of rodent-associated Bartonella and Rickettsia infections among intravenous drug users from Central and East Harlem, New York City.

We tested serum samples collected in 1997 and 1998 from a cohort of 204 injection drug users (IDUs) recruited from Central and East Harlem, New York City, New York, for antibodies reactive with seven rickettsial or Bartonella spp. antigens. Rodent-associated Bartonella elizabethae and Rickettsia akari were the primary etiologic agents of interest. The testing panel also included Bartonella henselae, Bartonella quintana, Rickettsia prowazekii, Rickettsia rickettsii, and Rickettsia typhi. The highest prevalence of seroreactive serum samples (46%) was found with B. elizabethae antigens; 10% of the samples reacted with B. henselae antigens, while 2% reacted with B. quintana antigens. Reactivity to the latter two antigens was likely due to cross-reactivity with B. elizabethae antigens in most instances. Among the spotted fever group rickettsiae, 18 (9%) samples reacted with R. akari, including 10 samples (5%) that also reacted with R. rickettsii. Cross-adsorption studies demonstrated that most of the spotted fever group rickettsiae antibodies were due to R. akari infections. Among the typhus group rickettsiae, 5 samples reacted weakly to R. prowazekii antigens, and no samples reacted with R. typhi antigens. These findings suggest that Harlem IDUs are commonly exposed to two rodent-associated zoonotic agents. Further study of IDU populations may help elucidate transmission cycles of these agents in inner cities where higher levels of transmission occur.

Adolescent↗

Predominant T helper 2 immune responses against Bartonella henselae in naturally infected cats.

This study was conducted to explicate the mechanism of long-term bacteremia in Bartonella henselae-infected cats by the examining host immune responses. Blood samples were collected from three naturally infected cats and the IgG antibody titers and the cytokine responses in peripheral blood mononuclear cells (PBMC) were examined by quantitative reverse transcriptase-polymerase chain reactions (RT-PCR). Relapsing bacteremia was found in two of the three cats during the examination period. The quantitative RT-PCR analyses demonstrated that increases of the mRNA expressions in interleukin-4 (IL-4) but not in gamma-interferon (IFN-gamma) were observed in PBMC from these infected cats after the bacteremia had peaked, showing that the T helper 2 (Th2) responses were specifically induced in the cats. Furthermore, the specific antibody titer increased, resulting in a decrease in the number of B. henselae to undetectable levels in these cats. However, the number of bacteria increased again in two of these cats at 90 and 45 days after the previous bacteremia, respectively. These results suggest that B. henselae predominantly induced IL-4 production from PBMC and resulted in stimulation of the humoral immune responses, including the secretion of specific antibodies in the cats. Furthermore, the specific antibody may play a role in eliminating the bacteria from cats partially but not completely, because relapsing bacteremia was found in these two cats.

Animals↗

[Bacillary angiomatosis of the liver, a suspected ultrasound diagnosis?].

Infections with Bartonella henselae or Bartonella quintana present with vasoproliferative lesions in skin and parenchymatous organs in immunocompromised patients. A case report of a 38-year-old patient with HIV infection and hepatitis B surface antigen status is described. The dominant clinical symptoms in our patient were fever and icterus. Ultrasonography of the abdomen showed a picture similar to that of liver cirrhosis. Irregular (echorich) nodes with hyper-vascularization were suspected to be hepatocellular carcinoma. Ultrasound guided puncture of one of these lesions and histological examination revealed the diagnosis of bartonella infection. Under antibiotic treatment with clarithromycin and doxycycline the fever and the hyperbilirubinemia decreased. The sonographically detectable lesions reduced in size. Vasoproliferative lesions in immunodeficient patients caused by bartonella infection show a characteristic slightly hyperechogenic irregular pattern at ultrasound. Typically, circumscribed hypervascularization might be shown by color Doppler imaging. Liver cirrhosis and diffuse tumor infiltration should be excluded.

AIDS-Related Opportunistic Infections↗

Current knowledge of Bartonella species.

Bartonella species are now considered emerging pathogens. Of the 11 currently recognized species, four have been implicated in human disease, although only two have been encountered in Europe. Bartonella quintana infections are now being diagnosed among the urban homeless and deprived, manifesting as trench fever, and Bartonella henselae has been shown to be the causative agent of cat scratch disease. Both species also cause a variety of HIV-associated infections, including bacillary anglomatosis. However, perhaps the most significant presentation of bartonellae infection is culture-negative endocarditis. The epidemiologies of Bartonella infections are poorly understood; most Bartonella henselae infections are probably acquired from infected cats, either directly by contact with a cat or indirectly via fleas. No animal reservoir has been implicated for Bartonella quintana; however, infection can be transmitted via the human body louse. Diagnosis of Bartonella infections can be made using histological or microbiological methods. The demonstration of specific antibodies may be useful in some instances, although certainly not in all. Cultivation of Bartonella is difficult, as the bacteria are extremely fastidious. Polymerase chain reaction-based or immunological methods for the detection of bartonella in infected tissues have proven useful. Clinical relapse is often associated with Bartonella infections despite a wide range of prescribed regimens. Only aminoglycosides display in vitro bactericidal activity against intracellular Bartonella species; therefore, they are recommended for treatment of Bartonella infections.

AIDS-Related Opportunistic Infections↗