Bartonellosis In Canine and Feline

 Bartonellosis In Canine and Feline: Causes, Symptoms and Treatment

Overview

An intracellular bacterial infection can affect both cats and dogs, and it’s caused by various bacterial species. 

These are small, adaptable, picky intracellular bacteria with a preference for silver staining that appear as Gram-negative rods or bacilli. They are considered emerging pathogens transmitted by vectors such as fleas and ticks. These bacteria have adapted to reservoir hosts and can establish long-lasting infections within red blood cells.

In cats, these bacteria typically do not cause noticeable symptoms and are often found as a reservoir. 

In contrast, dogs are experiencing an emerging clinical syndrome associated with these bacteria. The occurrence of cases follows a seasonal pattern, with more reported between July and January.

In humans, the syndrome caused by these bacteria can vary but cat scratch disease is the most common manifestation. 

This infection is found worldwide, but it rarely leads to fatalities. 

Causes of  Bartonellosis In Canine and Feline

• Dogs are more susceptible to Bartonella infections when they are exposed to fleas and ticks in rural environments. 
• The Bartonella species known to cause clinical problems in both dogs and cats: Bartonella henselae, B. clarridgeiae, B. koehlerae, B. quintana, B. vinsonii ssp. berkhoffii, B. rochalimae, and B. elizabethae.
• In humans, the disease is typically associated with contact with cats, especially kittens infested with fleas. Over 90% of human cases are linked to such cat exposure.

Pathogenesis of  Bartonellosis In Canine and Feline

• Bartonella is a meticulous, blood-loving, and gram-negative rod-shaped bacterium.
• Bartonella enter and reproduce inside red blood cells (RBCs).
• At least one Bartonella species, and potentially others, produces a factor that triggers the proliferation of vascular endothelial cells, a characteristic feature seen in human conditions such as bacillary angiomatosis, bacillary splenic peliosis, and peliosis hepatis.
• B. henselae, for instance, consists of two primary genetically distinct types, each with at least two subgroups. Genetic variation can even occur during the course of an infection, making the development of vaccines very challenging.

Cats:

• Cats can become infected with five different Bartonella species, namely B. henselae, B. clarridgeiae, B. koehlerae, B. quintana, and B. bovis, most of which have the potential to infect humans (zoonotic). 
• B. clarridgeiae is found in about 10% of cats with bacteremia.
• Mixed infections involving both B. henselae (which contains at least two subgroups) and B. clarridgeiae can occur.
• Transmission of Bartonella typically requires the presence of infected cat fleas (Ctenocephalides felis felis). 
• Infectious agents can be found in flea dirt and are capable of causing infection when injected intradermally. B. henselae can survive for up to 3 days in flea dirt.
• Transmission can also take place through blood transfusion, even if administered subcutaneously or intradermally.
• Transmission between cats does not occur in the absence of fleas.
• Bacteremia caused by B. henselae and B. clarridgeiae tends to be chronic and recurrent, often lasting for years.
•  Bartonella organisms have been observed within RBCs, in the bloodstream, and in various tissues (including vascular endothelial cells), but they may also exist in other parts of the body.

Dogs:

• Dogs can be infected with four different Bartonella species: B. vinsonii subsp. berkhoffii, B. henselae, B. clarridgeiae, and B. elizabethae.
• Ticks and fleas may serve as vectors for transmitting B. vinsonii subsp. berkhoffii to dogs.
• In experimental settings, B. vinsonii subsp. berkhoffii causes no clinical symptoms but does induce mild immunosuppression and persistent bacteremias, which can last up to 247 days.
• Natural cases in dogs are rare and are typically associated with diseases caused by B. henselae (such as peliosis hepatis) and B. vinsonii subsp. berkhoffii (leading to endocarditis, granulomatous rhinitis, and granulomatous lymphadenitis).

Symptoms (History & Physical Examination) of  Bartonellosis In Canine and Feline

History

Cats:

• The highest occurrence of seroprevalence is associated with B. henselae and is observed worldwide.
• Seroprevalence reaches its peak in warm, humid climates, among older cats, and those with the most exposure to fleas.
• In the United States, the prevalence of bacteremia in cats ranges from 5% to 40%, with the highest rates found in regions characterized by warm and humid conditions.
• It seems that the presence of fleas is a crucial factor for the transmission of B. henselae from cats to humans, although the direct transmission to humans via flea bites remains speculative.
• Until recently, it was not believed that B. henselae caused disease in cats.

Dogs:

• The seroprevalence of B. henselae in the United States is approximately 3% to 9%.
• There is a high seroprevalence of B. vinsonii subsp. berkhoffii in coyotes, ranging from about 25% to 75%. This suggests that coyotes might serve as the reservoir host for this particular species.
• Endocarditis cases in dogs can vary but often manifest with symptoms like weight loss, syncope (fainting), collapse, and sudden death.
• Hepatic disease in dogs can lead to symptoms such as depression, weight loss, and vomiting.

Physical examination 

Cats:

• Clinical signs are rarely observed in natural cases.
• Some suggest that uveitis may be caused by Bartonella, but one study found that healthy cats were more likely to test positive for Bartonella than cats with uveitis.
• When B. henselae is intradermally inoculated in cats, they develop an abscess at the inoculation site, along with lymph node enlargement, periodic fever, and mild neurological symptoms like nystagmus, whole-body tremors, focal motor seizures, and behavioral changes.
• Histological findings include peripheral lymph node enlargement, splenic follicular hyperplasia, lymphocytic cholangitis/pericholangitis, lymphocytic hepatitis, lymphoplasmacytic myocarditis, and interstitial lymphocytic nephritis.
• Endocarditis has been associated with two cats infected with B. henselae.
• So far, there is no proven link between Bartonella infection and conditions like anemia, gingivostomatitis, neurological disorders, or uveitis in cats.
• Cats with rhinosinusitis do not seem to have any support for a pathogenic role played by Bartonella.
• Bartonella DNA could not be detected in the tissues of cats with plasmacytic pododermatitis or peliosis hepatis.

Dogs:

• B. vinsonii subsp. berkhoffii has been associated with conditions like endocarditis, cardiac arrhythmias, granulomatous rhinitis, and granulomatous lymphadenopathy.
• Ocular signs such as uveitis and chorioretinitis have been linked to Bartonella infections.
• In some cases, B. henselae has been identified by PCR in the liver of a dog with peliosis hepatis, and another dog with granulomatous hepatitis.

Humans:

• In humans, an erythematous papule typically appears at the site of inoculation (e.g., scratch or bite), followed by painful unilateral regional lymphadenopathy within 3–10 days, which occurs in over 90% of cases.
• Common symptoms include mild fever, occasional chills, anorexia, myalgia, and nausea.
• Atypical manifestations, which are more common in immunosuppressed patients (up to 25% of cases), may include encephalopathy (1–7% of cases), palpebral conjunctivitis (3–5% of cases), meningitis, osteolytic lesions, granulomatous hepatitis, and pneumonia.

Diagnosis of  Bartonellosis In Canine and Feline

1- From History and Physical Examination

2- Diagnostic Procedures

CBC/Biochemistry/Urinalysis:

• Hematological findings may include anemia, low platelet count (thrombocytopenia), and an increase in eosinophils (eosinophilia).
• Biochemically, there may be higher levels of globulins, signs indicating liver dysfunction, and the possibility of low blood sugar (hypoglycemia).

Other Laboratory Tests:

• Serological testing involves methods like indirect fluorescent antibody, ELISA, and western immunoblot.
• A fourfold increase in antibody levels over a 2–3-week period is indicative of an infection.
• These tests generally have good specificity but may have limited sensitivity, especially in acutely ill animals with high levels of bacteria in their bloodstream, as detectable antibodies may be lacking.
• Polymerase chain reaction (PCR) can be used to amplify bacterial DNA in blood, bodily fluids, or fresh/fresh-frozen tissue. This is particularly useful in cases with negative culture results and serology.
• Culturing Bartonella alpha proteobacteria using Bartonella alpha proteobacteria growth medium (BAPGM) can be done with samples like blood, cerebrospinal fluid, joint fluid, effusions, or tissue biopsies. This culture method is enriched and requires 14–30 days, and it’s crucial to obtain the culture before starting antibiotic treatment. Combining BAPGM culture with PCR can enhance diagnostic sensitivity.

Pathological Findings:

• When examining lymph nodes histopathologically, the findings often show non-specific inflammatory reactions, including granulomas, micro-abscesses, and tissue necrosis.
• The Warthin–Starry silver stain can be used to identify bacilli in lesions.
• Immunohistochemistry, either alone or in combination with PCR, can help identify the presence of bacteria in tissues.

3- Differential Diagnosis

• Bacterial infections that cause endocarditis.
• When dealing with hepatic dysfunction, it’s important to distinguish it from other potential causes by eliminating alternative factors for dysfunction and confirming the presence of Bartonella organisms associated with the condition.
• Other infections transmitted by ticks (such as Ehrlichia and Babesia) should also be considered. 

Treatment of  Bartonellosis In Canine and Feline

General 

Cats:

• The effectiveness of antibiotics in treating cats is significantly less compared to humans.
• Treatment should be reserved for cats displaying clinical signs of the disease.
• If treatment is administered, it’s necessary to conduct follow-up blood cultures (taken three weeks after discontinuing antimicrobial therapy) to confirm the success of treatment.

Dogs:

• If dogs exhibit clinical symptoms and test positive in serological tests, they should receive antibiotic treatment.

 Humans:

• Supportive care, such as bed rest and the application of heat to swollen lymph nodes, is recommended.
• Treatment options include doxycycline, erythromycin, and rifampin.
• In immunocompetent individuals, treatment typically lasts for 2 weeks, while in immunocompromised individuals, it may extend to 6 weeks.

Medications:

• For cats, options include doxycycline, amoxicillin-clavulanate, fluoroquinolones, and azithromycin.
• In the case of dogs, a recommended initial choice is a combination of fluoroquinolone and doxycycline. 
• Other options encompass amoxicillin, gentamicin or amikacin, rifampin, erythromycin, and azithromycin.
• Macrolides are not advisable as the primary treatment due to the rapid development of resistance.

Some Notes:

• Due to documented resistance in naturally occurring infections in humans, fluoroquinolones are no longer recommended.
• Doxycycline may result in esophagitis and stricture; higher doses appear to be more effective in eliminating the infection in cats.
• In cases of hepatic or biliary dysfunction, reduce the dosage of azithromycin.
• Vigorous flea treatment is essential for cats.
•  In humans, it is important to clean any cat scratches or bites.
• Take precautions to prevent cats from coming into contact with open wounds.
• Individuals with compromised immune systems should steer clear of young cats.
• Enrofloxacin can lead to retinal degeneration and blindness in some cats when administered at doses exceeding 5 mg/kg.