Canine Bartonellosis

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DEFINITIONAn infection caused by various Bartonella species or subspecies in domestic dogs causing a wide spectrum of clinical signs from subclinical infection to severe clinical manifestations, including granulomatous hepatitis, granulomatous lymphadenitis, and most commonly endocarditis. Infection in dogs appears to be more common in tropical environments (up to 65% of dogs in these areas are seropositive) than in temperate or cold climates (< 5%).1 Canine bartonellosis is suspected to be a vector-borne infection, but the true vectors have yet to be identified. However, ticks could be involved for some of the Bartonella species that infect dogs.^2,3

SIGNALMENTSpecies. Bartonella vinsonii subspecies berkhoffii infection has been reported mainly in dogs and some wild canids, such as coyotes in California.^1,3,4 Domestic cats are the main reservoir for B. henselae. However, this Bartonella species has been diagnosed in a few clinical cases in dogs and a recent study has shown seropositivity for this bacterium in a high percentage of dogs.⁵ Similarly, cats are the main reservoir for B. clarridgeiae, but this species has also been isolated from domestic dogs and associated with endocarditis and liver disease.¹

Finally, a few clinical cases in dogs were caused by species usually found in rodents (B. washoensis and B. elizabethae).¹

Breed Predilection. Seropositivity was mainly observed in herding dogs and dogs living in rural areas;^2,6 toy breeds were less commonly affected.⁶ Endocarditis isprimarily reported in large to medium-sized breeds.⁷

Age and Range. Unknown (not enough data available). Endocarditis is usually seen in middle-aged dogs (median age, 8.5 years in a case series).⁷

Gender. No predilection.

CAUSES / PATHOPHYSIOLOGYBartonella are fastidious, Gram-negative organisms that have a specific tropism for red blood cells and endothelial cells and are usually transmitted by insect vectors.^1,3 Endocarditis is probably the result of chronic Bartonella infection in dogs and is characterized by a preferential localization on the aortic valve.⁷ Bartonellae stimulate several cellular functions of endothelial cells, resulting in cell invasion, proinflammatory activation, suppression of apoptosis, and stimulation of proliferation, which may culminate in vasoproliferative tumor growth.⁸

RISK FACTORSFor B. vinsonii subspecies berkhoffii, several risk factors have been associated with seropositivity in dogs. Dogs living in rural environments (especially on farms) and that were allowed to roam outdoors as well as those presenting with heavy tick and/or flea infestations were more likely to have antibodies against B. vinsonii berkhoffii (odds ratio [OR] 14 and 5.6, respectively).² Seropositivity to tick-borne pathogens (mainly Ehrlichia species, Anaplasma phagocytophilum, Babesia canis) was more commonly seen in dogs seropositive for Bartonella.^2,9 In another study, when compared with sporting breeds, herding dogs were more likely to be seropositive for Bartonella species (OR, 2.23; 95% confidence interval (CI), 1.11 to 4.48), whereas toy breeds were less likely to have antibodies against Bartonella species (OR, 0.26; CI, 0.08 to 0.80).⁶

CLINICAL SIGNSIn dogs, infection with Bartonella species is known to cause endocarditis, but it has also been commonly associated with arrhythmias, myocarditis, peliosis hepatis, granulomatous lymphadenitis, granulomatous rhinitis, and granulomatous and lymphocytic hepatitis.^3,10-13 In addition, the clinical spectrum of Bartonella species infection has expanded on the basis of serologic evidence, and may include such clinical signs as anterior uveitis, choroiditis, cutaneous vasculitis, meningoencephalitis, spleno-megaly, polyarthritis, lameness, nasal discharge, or epistaxis.^6,14 Thrombo­cytopenia, immune-mediated hemolytic anemia, neutrophilic leukocytosis, and eosinophilia are the most commonly detected hematologic abnormalities in dogs seropositive for B. vinsonii berkhoffii.¹⁴ While these clinical and laboratory abnormalities have been reported, any one of them alone would not be sufficient to indicate the need for Bartonella testing.

Diagnosis

CLINICAL DIAGNOSISClinical diagnosis is problematic, as the clinical spectrum of Bartonella infection in dogs is just being established. Bartonella infection should be suspected in cases of endocarditis or cardiac abnormalities (arrhythmias, myocarditis), especially when the aortic valve is affected. It also should be suspected in dogs with prolonged or intermittent fever, lethargy, or unexplained lameness or in unexplained granulomatous disease. Similarly, a diagnostic test for Bartonella infection should be considered when there is clinical or epidemiologic suspicion of a tick-borne infection. Thrombo­cytopenia, anemia, neutrophilic leukocytosis, and eosinophilia are the most commonly detected hematologic abnormalities in dogs seropositive for B. vinsonii berkhoffii.¹⁴

DIFFERENTIAL DIAGNOSISIn cases of endocarditis, blood culture should be done to exclude any conventional bacterial endocarditis (caused by bacteria, such as Streptococcus or Staphylococcus).

In cases of vegetative endocarditis, especially on the aortic valve, suspicion of Bartonella infection should be high. Among other causes of culture-negative endocarditis, Coxiella burnetii (Q fever) infection should be considered.

Because of the broad spectrum of clinical signs, bartonellosis can be confused with several tick-borne infections, such as Lyme disease, ehrlichiosis, anaplasmosis, or babesiosis. Therefore, Bartonella serologic testing should be included in any "tick-borne diseases" panel.

SEROLOGIC TESTINGIn dogs, individual serologic testing mainly consists of indirect immunofluorescent antibody testing against B. vinsonii berkhoffii. However, in dogs with a high clinical suspicion for infection, testing against other Bartonella species that have been recently isolated or detected by PCR in dogs, especially B. henselae and B. clarridgeiae, should be done. Serologic testing is good for initial screening of infected dogs. A titer 1:64 or greater is usually considered indicative of exposure to the agent. In suspected clinical cases, testing two samples at 2-week intervals is strongly suggested to evaluate the kinetics of the infection. As in humans, Bartonella endocarditis cases are usually characterized by high titers (>1:512) and cross-reactivity with several Bartonella antigens occurs.⁷ Due to this cross-reactivity, isolation or PCR is necessary to confirm the infecting Bartonella species.

BLOOD CULTURECulturing Bartonella from blood is very difficult, even when dogs have endocarditis.^1,3 Isolation is done using lysis-centrifugation tubes (Wampole Isostat 1.5) or EDTA tubes (plastic tubes are the most convenient). Whole anticoagulated blood is plated, usually after freezing to induce red blood cell lysis, onto fresh rabbit blood agar and incubated for at least 4 weeks at 35ºC with 5% carbon dioxide. The isolate is then identified using PCR techniques and partial sequencing. Such testing can only be done in a few diagnostic laboratories across the country.^1,3(See Aids & Resources.)

EXTRACTION OF DNAExtraction of DNA from tissue samples with PCR testing is also a common method of diagnosis and has been more successful than culture in dogs. Frozen tissues or fresh biopsies can be easily tested. PCR extraction from paraffin-embedded tissues is more cumbersome, but possible. Testing should be done in laboratories familiar with these fastidious organisms, and laboratories should be contacted for specific instructions for sample collection and submission.

Treatment

Studies have not yet been done to determine the efficacy of antibiotics in Bartonella infection in dogs. The use of antibiotics that achieve high intracellular concentrations, such as doxycycline, fluoroquinolones, or azithromycin, would be required to eliminate intracellular infection. Based on data from other species, it is likely that antibiotics, such as doxycycline or tetracycline, could reduce the level of bacteremia during chronic infections. Treatment should continue for 4 to 6 weeks. Because azithromycin reaches high intracellular antimicrobial concentrations, it is suggested as a first-line antibiotic for treatment of Bartonella infections in dogs.¹⁴ However, if lesions of endocarditis are already well-established, antibiotic therapy may not be effective.

Follow-Up

PATIENT MONITORING

Patients should be monitored for negative blood culture (may be very difficult) and decreased antibody titers after treatment.¹⁴

PREVENTIONCanine Bartonella infections are likely to be vector-borne. A tick vector is strongly suspected for B. vinsonii berkhoffii³; therefore, prevention of tick infestation should be one of the main control measures in the clinical setting. Use of tick repellents and cleaning of the dog after a walk in high-risk terrain should be done systematically to prevent Bartonella as well as other tick-borne infections. Flea control measures are also important, as dogs may become infected with B. henselae, possibly when exposed to cat fleas, which are known to transmit the infection among cats.

COMPLICATIONSSevere cardiac insufficiency and respiratory distress caused by fulminant cardiogenic pulmonary edema may occur in dogs with major vegetative lesions on cardiac valves caused by Bartonella infection.¹⁵

In General

RELATIVE COST OF TREATMENTDepends on severity of clinical signs. Patients with endocarditis seen in emergency rooms for fulminant pulmonary edema can incur thousands of dollars in medical expenses ($$$). The antibiotic treatment of dogs diagnosed with a Bartonella infection usually runs in the $300 to $600 range ($$).

PROGNOSISIt is difficult to establish a clear prognosis for dogs with Bartonella infection, as the clinical spectrum of the infection in dogs is just being recognized. The prognosis is usually poor for most dogs with endocarditis,^7,15 but one dog was documented to have survived over 3 years after the initial diagnosis.¹¹

FUTURE CONSIDERATIONSCurrent clinical research is focused on identifying clinical entities associated with Bartonella infection in dogs and establishing the prevalence of infection in various dog populations. Furthermore, Bartonella species other than B. vinsonii berkhoffii that infect dogs are being identified. Research is still greatly needed to determine which antibiotic, and at what dose, would most effectively control Bartonella infection in dogs. Finally, research is needed to confirm the role of ticks in the transmission of infection.