The number of Bartonella species identified as zoonotic pathogens has increased considerably over the last decades. Pets have been recognized as a notable reservoir of Bartonella spp. whereas cats are known to act as the main reservoir for human infection with regard to Bartonella henselae, Bartonella clarridgeiae and Bartonella koehlerae.

Important diseases caused by Bartonella species in humans are Oroya fever (also known as Carrións disease, caused by B. bacilliformis), Trench fever, a louse-borne disease caused by Bartonella quintana and the cat-scratch disease (CSD) mainly caused by B. henselae with the domestic cat as the natural reservoir. 

In dogs infected with Bartonella spp. similar disease manifestations like in human patients have been observed and thus dogs are representing epidemiological sentinels for human exposure. However, the role of dogs as source of human infection is less clear than it is for cats.

Pathogen

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.

The widespread occurrence and diversity of these bacteria has been increasingly recognized and thus resulted in expansion of the genus Bartonella to 24 currently described species or subspecies. Many Bartonella species appear to be well-adapted to extended survival in mammalian reservoir hosts without causing clinical symptoms.

While cats are considered the main mammalian reservoir for important zoonotic Bartonella spp. (B. henselae, B. clarridgeiae and B. koehlerae.), the role of dogs as an important reservoir seems less clear. Current evidence indicates that canids, including coyotes, dogs and grey foxes, potentially serve as reservoir hosts for B. vinsonii subsp. berkhoffii. Furthermore, the presence of B. rochalimae (previously described as B. clarridgeiae-like) in dogs, grey and red foxes, raccoons and coyotes, as well as fleas collected on grey foxes, indicates that wild carnivores may function as natural reservoir of this zoonotic Bartonella species too with fleas being the main vector.

It is not completely clear, if Bartonellae are primary pathogens of dogs, or opportunistic pathogens. Species known to infect dogs are B.vinsonii subsp. berkhoffii, B. henselae, which seem to be the most likely species to be associated with clinical disease. Further B. clarridgeiae, B .washoensis, B. elizabethae, B. koehlerae and B. quintana have been reported.

Several Bartonella species have been identified as zoonotic pathogens including B. henselae and B. vinsonii subsp. berkhoffii.

Other examples of reservoir hosts include cattle, which appear to be the mammalian reservoir for B. bovis, human beings for B. Quintana and B. bacilliformis and California ground squirrels for candidatus B. washoensis.

Distribution

Bartonella spp. have a widespread, global distribution which varying species present among countries from North and South America, Europe, Africa, Asia and Australia. Seroprevalences are also very different depending on the Bartonella species and the country.

Several studies designed to determine the importance of cats as a reservoir for B. henselae showed that prevalence of infection varies considerably among cat populations. Low prevalence rates were detected in cold climates whereas high rates were found in warm and humid climates.

Among the 2 16S rDNA genotypes of B. henselae, type Marseille, was detected in cat populations in the western United States, western Europe (France, Germany, Italy, the Netherlands, United Kingdom), and Australia, whereas type Houston-1 was dominant in Asia (Japan and the Philippines). 

Concerning the infection of dogs with B. 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 northern regions, where very low rates of prevalence have been detected in domestic dogs, kept as pets.

Pathogenesis and transmission

Fleas play a major role in the transmission of Bartonella, particularly in felines (B. henselae). Due to their ubiquitous nature and spread through animal transport, fleas pose a worldwide risk for cats and dogs to become infected with Bartonella spp. But also other potential vectors for Bartonella transmission, such as ticks and biting flies, have been identified.

Due to the fact, that dogs which are seropositive to B. vinsonii subsp. berkhoffii are often seropositive to Ehrlichia canis and/or Babesia canis at the same time, the transmitting tick vector, Rhipicephalus sanguineus, has been suggested as a likely vector also for Bartonella.

Different arthropod vectors have been reported for different Bartonella spp. Confirmed vectors are the cat flea (Ctenocephalides felis) for B. henselae, B. clarridgeiae, B. koehlerae , the sand fly (Lutzomyia verrucarum) for B. bacilliformis, the human louse (Pediculus humanus humanus) for B. quintana and the rat flea (Xenopsylla cheopis) for B. elizabethae.

Further suspected vectors for Bartonella comprise different species of fleas, sandflies, mites, biting flies and flies.

Besides transmission via blood-feeding arthropods, 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. Location within erythrocytes and also within vascular endothelial cells is believed to protect Bartonellas from antimicrobial agents.. Immune system avoidance via intracellular location, frequent genetic rearrangements, and alteration of outer membrane proteins, is also considered important.

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 defenses of the host. Following experimental inoculation of SPF dogs with culture grown B. vinsonii subsp. berkhoffii, there was sustained suppression of peripheral blood CD8+ lymphocytes, accompanied by an altered cell surface phenotype and an increase in CD4+ lymphocytes in the peripheral lymph nodes. Therefore, infection with B. vinsonii subsp. berkhoffii might induce a degree of chronic immunosuppression that could predispose dogs to infections with other pathogenic agents, resulting in a wide array of clinical manifestations in naturally-infected dogs.

Co-infection

Dogs can be co-infected with other pathogens like Ehrlichia, Babesia or Rickettsia spp..

A frequent co-infection with other tick-borne pathogens transmitted by R. sanguineus has been observed in dogs, coupled with a markedly increased risk of B. vinsonii subsp. berkhoffii infection with tick infestations. Thus, R. sanguineus is assumed as a likely vector of B. vinsonii subsp. berkhoffii, but this supposition has not yet been proven.

Also Bartonella spp DNA has been found in other tick species like Ixodes pacificus or Ixodes ricinus. The finding of co-infection in ticks with different tick-borne pathogens like with Borrelia spp., Babesia spp. or Bartonella spp. is not uncommon.

In dogs, co-infection with Bartonella spp. are supposed to influence the pathogenesis of other diseases and due to the chronic immunosuppressive effects of Bartonella infections dogs may be predisposed to secondary infections.

Clinical signs

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 of Bartonella infection can range from asymptomatic infection, to severe disease and sudden death. There is also a large variation in duration of illness.

In dogs, B. 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:

Endocarditis

Myocarditis

Anemia

Hepatitis

Polyarthritis

Uveitis, choroiditis

Weight loss

Epistaxis

Diagnosis

Diagnosis of Bartonella infections can be confirmed by detection of serum antibodies, by immunohistochemical analysis of tissue biopsies (lymph nodes, skin, liver, or other affected organs), by molecular detection of Bartonella DNA by PCR assays or by using a combination of Bartonella alpha Proteobacteria growth medium followed by PCR. The latter is suggested to be the most sensitive method of detecting Bartonella infection in dogs.

One common method for the laboratory diagnosis of Bartonella infections is serology, using indirect immunofluorescence techniques. Serological tests such as IFAT (indirect immunofluorescence assay test can be used for the diagnosis of infection, present or previous. However, to a certain extend dogs naturally infected with Bartonella may remain seronegative. Cross-reactions between the different species, and also between genera such as Coxiella and Chlamydia have also been observed and with chronic intracellular infection antibody titers decline to non-diagnostic levels. However, serology can be used as a screening test to detect past exposure in populations. The IFAT (immunofluorescent antibody test) is 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 the blood because of the low bacteremia. Further, some spp. may be difficult to culture like B. vinsoniii subsp. berkhoffii.

Recently, a novel 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.

Microscopic examination of stained blood smears is only effective to visualize B. bacilliformis, a solely human pathogen in South America. Other Bartonella sp. cannot be visualized on blood smears. When isolated on an agar plate, colonies are described as silvery-white shining, with a rough or smooth, mucoid appearance.

Treatment

There is no consistent treatment protocol for B. vinsonii subsp. berkhoffii infection in dogs.

Antibiotic treatment should be performed with an antibiotic capable of crossing lipid membranes and reaching high intracellular concentrations, as azithromycin, doxycycline, and enrofloxacin. Macrolides, like azithromycinare effective, but B. henselae isolates rapidly develop resistance. Treatment of several weeks duration may be needed to eliminate Bartonella infections.

Prevention

Dogs should be protected from flea and tick infestations by the regular use of acaricides in the form of spot on or spray on formulations or by using impregnated collars.

Vaccines against B. henselae and B. vinsonii subsp. berkhoffii is not available.

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