Bartonella spp. are haemotropic gram-negative bacteria within the family Bartonellaceae that are mainly transmitted by vectors. A characteristic feature of these bacteria is their adherence to and invasion of erythrocytes, causing a long lasting intra-erythrocytic bacteraemia and endotheliotropic infection.
The widespread occurrence and diversity of these bacteria has been increasingly recognised and resulted in expansion of the genus Bartonella to more than 35 currently described species and over 15 Candidatus species (Breitschwerdt, 2017). Many Bartonella species appear to be well-adapted to extended survival in mammalian reservoir hosts often without causing symptomatic disease.
While cats are considered to be the main mammalian reservoir for important zoonotic Bartonella species (Bartonella henselae, Bartonella clarridgeiae and Bartonella koehlerae), the role of dogs as a reservoir is less clear. Current evidence indicates that canids – including coyotes, dogs and grey foxes – potentially serve as reservoir hosts for Bartonella vinsonii subsp. berkhoffii. Furthermore, the presence of Bartonella rochalimae in dogs, grey and red foxes, raccoons and coyotes, as well as fleas collected on grey foxes, indicates that carnivores may function as natural reservoirs of this zoonotic Bartonella species, with fleas being suspected as the main vector.
Species known to infect dogs are B. vinsonii subsp. berkhoffii, B. henselae, which also seem to be the most likely species to be associated with clinical disease in dogs. Infections with B. clarridgeiae, Bartonella washoensis, Bartonella elizabethae, B. koehlerae and Bartonella quintana have also been reported.
Several Bartonella species have been identified as zoonotic pathogens including B. henselae and B. vinsonii subsp. berkhoffii.
For a comprehensive overview on Bartonella species and their reservoirs see Breitschwerdt (2017).
Bartonella spp. have a widespread, global distribution with species varying among countries. Seroprevalences are also varying depending on species and country.
For cat populations several studies show the prevalence of Bartonella henselae to vary considerably between different geographies, with low prevalence rates detected in cold climates whereas higher prevalence rates were found in warm and humid climates.
For dogs and infections with Bartonella vinsonii subsp. berkhoffii, a world-wide distribution is supposed. The epidemiologic situation seems quite distinct between tropical areas, where several studies have shown a high prevalence of antibodies – especially in stray dogs – and more temperate regions, where very low prevalence rates have been detected in domestic dogs, kept as pets.
Fleas play a major role in the transmission of Bartonella spp., particularly in felines (Bartonella henselae). Due to their ubiquitous nature and spread through animal transport, fleas pose a worldwide Bartonella infection risk for cats and dogs.
However other arthropod vectors for Bartonella transmission have been identified including keds, lice, sand flies, ticks and, potentially, mites and spiders, with different vectors reported for different Bartonella spp. Confirmed vectors are e.g. the cat flea (Ctenocephalides felis) not only for B. henselae but also for Bartonella clarridgeiae and Bartonella koehlerae, the rat flea (Xenopsylla cheopis) for Bartonella elizabethae, the sand fly (Lutzomyia verrucarum) for Bartonella bacilliformis, and the human louse (Pediculus humanus humanus respectively Pediculus humanus corporis) for Bartonella quintana. For Bartonella vinsonii subsp. berkhoffii, Rhipicephalus sanguineus has been suggested as a likely vector.
Besides transmission via blood-feeding arthropods, blood transfusion and mechanical transmission of Bartonella spp. by biting and scratching also poses a risk for human infection as well known for the cat scratch disease.
Bartonella spp. infect erythrocytes, endothelial cells and macrophages, often leading to persistent blood-borne infections. Immune system avoidance via intracellular location, frequent genetic rearrangements, and alteration of outer membrane proteins, is also considered important for the maintenance of infection. Location within erythrocytes and also vascular endothelial cells is believed to protect Bartonellae from antimicrobial agents.
Because bartonellosis is characterized by persistent intravascular infection, subsets of animal and human patients develop endocarditis, myocarditis or various other forms of vascular pathology.
Bartonella henselae, Bartonella vinsonii subsp. berkhoffii and Bartonella koehlerae appear to be the medically most important species infecting cats, dogs, horses and potentially humans. In dogs, B. vinsonii subsp. berkhoffii causes chronic infections by establishing intracellular infection in erythrocytes and endothelial cells, thereby escaping the acquired humoral and cell-mediated immune defences of the host. It is suspected that infection with B. vinsonii subsp. berkhoffii induces a degree of chronic immunosuppression that could predispose dogs to infections with other pathogenic agents, which might influence the pathogenesis of these other diseases, resulting in a wide array of clinical manifestations in naturally-infected dogs.
Bartonella infections can be diagnosed by detection of serum antibodies, immunohistochemical analysis of tissue biopsies (lymph nodes, skin, liver, or other affected organs), molecular detection of Bartonella DNA by PCR assays or using a combination of Bartonella alpha Proteobacteria growth medium, followed by PCR. In recent years, DNA amplification after blood culture pre-enrichment became the gold standard for diagnosis of Bartonella infection.
Serology is a common method for the laboratory diagnosis of Bartonella infections, using indirect immunofluorescence techniques. Serological tests such as IFAT (indirect fluorescence antibody test) can be used for the diagnosis of present or previous infection. However, dogs naturally infected with Bartonella may to a certain extent remain seronegative and with chronic intracellular infection antibody titres decline to non-diagnostic levels. Also cross-reactions between different species, as well as different genera have been observed. However, serology can be used as a screening test to detect past exposure in populations with the IFAT considered the gold standard test for serological diagnosis.
Detection of Bartonella spp. by culture on agar plates is also possible, but time-consuming and during chronic infection the pathogen is hard to isolate from blood because of the low bacteraemia. Further, some species like Bartonella vinsonii subsp. berkhoffii may be difficult to culture.
A chemically-modified liquid culture medium (Bartonella/alpha-Proteobacteria growth media, BAPGM), supporting the growth of several Bartonella species, has been developed. The combination of BAPGM culture with PCR assay was developed for diagnostic use, to characterise and quantify Bartonella infection in blood samples and became the gold standard for diagnosis of Bartonella infection.
Depending on the Bartonella spp., a wide range of clinical and pathologic abnormalities can develop in dogs. Similar to those observed in humans clinical manifestation can range from asymptomatic infection, to severe disease and sudden death, with a large variation in duration of illness.
In dogs, Bartonella vinsonii subsp. berkhoffii has been identified as an important cause of endocarditis and has been associated with cardiac arrhythmias, myocarditis, granulomatous rhinitis, anterior uveitis and chorioretinitis.
Clinical signs related to Bartonella infection in dogs are:
- uveitis, choroiditis
- weight loss
Clinically, many disease manifestations also have been attributed to Bartonella spp. infections in cats. However, it is very difficult to prove disease associations in cats in the field because of the high prevalence rates in non-clinical carriers. Endocarditis has been reported in cats, cows, and humans, infected with a spectrum of reservoir-adapted Bartonella spp., and cardiac arrhythmias secondary to myocarditis can be detected in cats without echocardiographic evidence of endocarditis. Additionally, uveitis may be a manifestation of natural Bartonella infection in cats.
Treatment & Prevention
Treatment of bartonellosis is very difficult, requiring long term antibiotic treatment often with a combination of antibiotics. Treatment should be performed with an antibiotic capable of crossing lipid membranes and reaching high intracellular concentrations, such as azithromycin, doxycycline, and enrofloxacin. Macrolides, like azithromycin are effective, but Bartonella henselae isolates are known to rapidly develop resistance, so that single therapy with these substances might not be recommended any longer. Instead, combinations of e.g. fluoroquinolones with doxycycline might be used. Treatment of several weeks' duration may be needed to eliminate Bartonella spp. infections.
As the Bartonella spp. possess a zoonotic potential, prevention of pathogen transmission is essential especially in form of ectoparasite control especially in cats as a major reservoir. Dogs should equally be protected from flea and tick infestations by the regular use of ectoparasiticides in the form of collars, spot-on or spray-on formulations in order to prevent pathogen transmission and disease in the canine host itself. Vaccines against the relevant species of dogs and cats like B. henselae and B. vinsonii subsp. berkhoffii are not available.
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