Feline bartonellosis

Edit October 6, 2015



The Bartonella species infection in cats guidelines that the present article is updating were published in J Feline Med Surg 2013; 15: 563-569; the update has been compiled by Fulvio Marsilio.





The ABCD guidelines on Bartonella species infection in cats (Pennisi et al., 20130) lists various species and subspecies of Bartonella, which are confirmed or potential human pathogens (Tab. 1). B rochalimae should now be included, for which reservoir hosts may be raccoons, coyotes, red foxes and cats. The vectors are fleas, and persons may be accidental hosts.


The important role of fleas in the transmission of B henselae and B clarridgeiae among cats has been demonstrated. Using a quantitative molecular approach, B henselae DNA was detected in both fleas and their faeces for the entire 12-day life span of the arthropod, starting at 24 hours after the blood meal (Bouhsira et al., 2013). The possible role of several bat fly species (Nycteribiidae) as bartonella vectors has been studied. It remains a subject of debate, but a reservoir function should be considered in addition to pathogenic, parasitic, or mutualistic interactions (Morse et al., 2012).


The role of Bartonella as a pathogen after natural transmission is still unclear; however, B henselae was found associated with pyogranulomatous myocarditis and diaphragmatic myositis in cats (Fig. 1; Varanat et al., 2012).


For rapid laboratory diagnosis, a real-time PCR and pyrosequencing-based algorithm was described that allowed rapid differentiation of at least 11 medically relevant Bartonella spp within five hours from receipt of the specimens (Buss et al., 2012).



Bacterial properties


Bartonella are small (2 by 0.5  μm), vector-transmitted Gram-negative intracellular bacteria that are well adapted to one or more mammalian reservoir hosts. Until now, over 22 Bartonella species have been described, but their role as pathogens of humans and domestic animals is the subject of ongoing investigations (Tab. 1).


Bartonella spp.Primary reservoirVectorAccidental host
B. bacilliformisHumanLutzomia verrucarumNone
B. quintanaHumanPediculus humanusCat, dog, monkey
B. elizabethaeRattus norvegicusXenopsylla cheopisHuman, dog
B. grahamiiSeveral species of wild miceRodent fleasHuman
B. henselaeCatCtenocephalides felis felisHuman, dog
B. clarridgeiaeCatC. felisHuman, dog
B. koehleraeCatC. felisHuman
B. vinsonii subsp. berkhoffiiCoyote, dogTicks?Human
B. vinsonii subsp. arupensisPeromyscus leucopusTicks? Fleas?Human
B. washoensisSpermophilus beecheyiiFleas?Human, dog
B. asiaticaRabbitFleas?Human
Table 1: Species and subspecies of Bartonella that are confirmed or potential human pathogens (after Chomel et al., 2006). Zoonotic species are indicated with an asterisk (*).



The most common species in both cats and humans is B henselae, which causes cat scratch disease in the latter, as well as other potentially fatal disorders affecting immunocompromised people.


Cats naturally infected with Bartonella usually do not show clinical signs. Given the long lasting association of B henselae and domestic cats, there have been adaptations between host and bacterium to facilitate co-existence and minimise pathogenic effects on the mammalian host (Guptill, 2010).





Bartonella spp. have a worldwide distribution with highest prevalences in areas where conditions are most favourable for arthropod vectors, mainly fleas. In Europe, many studies have been carried out, and the antibody prevalence in cats ranged from 8 to 53% (Tab. 2).



CountryNumber of catsPrevalence (%)Reference
The Netherlands163 (stray)52Bergmans et al., 1997 8
Austria9633Allerberger et al., 1995 9
Switzerland7288Glaus et al., 1997 10
Germany71315Haimerl et al., 1999 11
24537.1Morgenthal et al., 2012 12
France6436Chomel et al., 1995 13
9453Heller et al., 1997 14
17941Gurfield et al., 2001 15
Spain68023.8Ayllon et al., 2012 16
Italy54038Fabbi et al., 2004 17
1300 (stray)23.1Brunetti et al., 2012 18
Scotland7815.3Bennett et al, 2011 19
Table 2: Antibody prevalence of Bartonella infection in the feline population in European countries



Epidemiological evidence and experimental studies have demonstrated the important role for fleas in the transmission of B henselae and ʼ among cats. Three other species, B koehlarae, B bovis and B quintana have been isolated from cat blood, but the modes of transmission and the reservoir potential of these species in felids have not been established. In addition, B vinsonii subsp. berkhoffii DNA was detected in the blood of a cat (Varanat et al., 2009).





B henselae is naturally transmitted among cats by the flea Ctenocephalides felis felis, or by flea faeces. In the infected cat, Bartonella inhabits red blood cells, which are ingested by the flea and survive in its gut. Contaminated flea faeces deposited on the skin end up under the cat’s claws due to grooming. A cat scratch is the common mode of transmission of the organism to other animals, including humans (Chomel et al., 1996).


B henselae was experimentally transmitted among cats by transferring fleas fed on naturally infected cats to SPF cats, and by intradermal inoculation of excrement
collected from fleas fed on B henselae-infected cats (Chomel et al., 1996). This has demonstrated that both the vector and the cat - through scratches - may transmit the organism. Infection is amplified in the flea hindgut, and B henselae can persist in the environment in flea faeces for at least nine days (Finkelstein et al., 2002). Blood transfusion also represents a risk: cats have been experimentally infected with B henselae and B clarridgeiae by intravenous or intramuscular inoculation with infected cat blood (Abbott et al., 1997).


B henselae transmission did not occur when infected cats lived together with uninfected cats in a flea-free environment. Transmission consequently does not occur through bites, scratches in the absence of fleas, grooming, or sharing of litter boxes and food dishes. Furthermore, transmission could not be demonstrated between bacteraemic female cats and uninfected males during mating, or to the kittens of infected females either during gestation or in the neonatal period, again in flea-free environments (Guptill et al., 1997).


Ticks may also act as vectors for transmission among cats, human beings, dogs, and other mammalian hosts: transstadial transmission of B henselae was demonstrated in Ixodes ricinus (Cottè et al., 2008).


Chronic bacteraemia mainly occurs in cats under the age of 2 years (Guptill et al., 2004). Young experimentally infected cats maintained relapsing B henselae or B clarridgeiae bacteraemia for as long as 454 days (Kordick et al., 1999). Immune system avoidance due to its intracellular location, frequent genetic rearrangements and alteration of outer membrane proteins are considered important for the maintenance of persistent bacteraemia. The location within erythrocytes and vascular endothelial cells is believed to protect Bartonellae also from antimicrobial agents. Cats can be re-infected by different strains of Bartonella (Guptill, 2010).



Clinical signs


Cats naturally infected with Bartonella spp. usually do not show clinical signs. Both experimental and natural infection studies have tried to establish an association between clinical signs and infection, but a link has not been unequivocally proven. Exposure to infected fleas does not result in clinical signs (Chomel et al., 1996; Bradbury & Lappin, 2009). In some cases of experimental inoculation, a self-limiting febrile disease, transient mild anaemia, localized or generalized lymphadenopathy, mild neurologic signs and reproductive failure have been reported (Kordick et al., 1999). In these animals, pyogranulomatous inflammation was seen in the lung, liver, spleen, kidney, heart (Fig. 1) and lymphoid tissue at necropsy (Guptill et al., 1997; Kordick et al., 1999).



Fig. 1. Gross and histological findings in two cats from North Carolina shelter that had died after a litter of flea-infested kittens was introduced to the shelter. (a) Coalescent granulomas distributed throughout the myocardium (b) Pyogranulomatous myocarditis in an 8-month-old castrated male cat, which had been co-housed with the flea-infested kittens. Macrophages, with a rare multinucleated giant cell (arrow) are particularly numerous at the upper left of the image. Hematoxylin/eosin stain. Inset: cluster of short bacilli in an inflammatory focus are immunoreactive (brown) for B. henselae- specific monoclonal antibody. Reproduced with permission from Varanat et al., 2012

Fig. 1. Gross and histological findings in two cats from North Carolina shelter that had died after a litter of flea-infested kittens was introduced to the shelter.
(a) Coalescent granulomas distributed throughout the myocardium (b) Pyogranulomatous myocarditis in an 8-month-old castrated male cat, which had been co-housed with the flea-infested kittens. Macrophages, with a rare multinucleated giant cell (arrow) are particularly numerous at the upper left of the image. Hematoxylin/eosin stain. Inset: cluster of short bacilli in an inflammatory focus are immunoreactive (brown) for B henselae- specific monoclonal antibody. Reproduced with permission from Varanat et al., 2012


The role of Bartonella to cause clinical signs is even more unclear after natural infection. Studies based on antibody detection are of limited value, because antibody only proves exposure, but not necessarily an active infection. Moreover, there is cross reactivity between different Bartonella species that may or may not cause clinical signs. Because of the high percentage of infected healthy cats in endemic areas, an association between clinical signs and B henselae infection is not easy to demonstrate.
It has been suggested that Bartonella infection could play a role in chronic gingivostomatitis, (Ueno et al., 1996; Glaus et al., 1997), but the prevalence of antibodies or organisms was not higher in diseased cats than in control populations (Quimby et al., 2008; Dowers et al., 2010; Pennisi et al., 2010; Belgard et al., 2010, Namekata et al, 2010).
Cats positive for both FIV and Bartonella antibodies had an increased risk of lymphadenopathy (Ueno et al., 1996). An association between Bartonella antibodies and urinary tract disease or haematuria has been suggested (Glaus et al., 1997; Breitschwerdt et al., 2005). Pearce et al. (2006) did not find any difference in antibody prevalence between healthy cats and cats with seizures or other neurological conditions. A non-controlled retrospective study reported Bartonella DNA and antibodies in cerebrospinal fluid from cats with CNS disease (Leibovitz et al., 2008).
No difference in Bartonella prevalence was found between healthy cats and cats affected by uveitis (Fontenelle et al., 2008), but some had reported evidence of Bartonella spp. exposure in cats with uveitis responsive to drugs considered effective against Bartonella (Lappin & Black, 1999; Ketring et al., 2004). No difference in Bartonella prevalence was found in cats affected by anaemia (Ishak et al., 2007) or fever (Lappin et al., 2009). A study based on serology and culture did not find an association between Bartonella infection and chronic rhinosinusitis (Berryessa et al., 2008). There was also no link between Bartonella infection and pancreatitis, because cats with normal fPLI values and cats with elevated values did not show any difference in Bartonella prevalence (Bayliss et al., 2009).


Since 1993, many Bartonella species have been associated with endocarditis in humans and dogs (Breitschwerdt et al., 1995; La Scola & Raoult, 1999; Mc Donald et al., 2004). Some research groups have looked for Bartonella in cats with this rare condition. Aortic and fatal mitral valve B henselae-associated endocarditis was reported in two cats in the USA (Chomel et al., 2003; Chomel et al., 2009). Also, B henselae anterior mitral valve leaflet vegetative endocarditis associated with a grade III/IV systolic heart murmur and signs of aortic embolization (lethargy and weakness in the hind limbs, weak femoral pulses, pelvic pain, increased serum creatine kinase activity) was successfully treated in a cat (Perez et al., 2010), suggesting that Bartonella species may be a cause of blood culture-negative endocarditis, as previously suspected (Malik et al., 1999). Lameness and pain during limp palpation were observed in a cat affected by recurrent osteomyelitis and polyarthritis associated with B vinsonii subsp. berkhoffii infection and bacteraemia (Varanat et al., 2009).
In conclusion, most cats naturally infected by B henselae do not show clinical signs. However, other Bartonella species, for which cats are accidental hosts, may have pathogenic properties.



Clinical signs in humans


B henselae is the causative agent of cat scratch disease. This is a self- limiting regional lymphadenopathy developing after a primary papular lesion and lasting for a few weeks to several months (Boulouis et al., 2005). Abscessation of the lymph node and systemic signs are occasionally reported. Atypical forms and an expanding spectrum of clinical conditions are being associated with B henselae infection (Boulouis et al., 2005), such as neuroretinitis, uveitis (Fonollosa et al., 2011) and endocarditis (Tsuneoka et al, 2010). An unusual CSD case has been reported in a veterinarian affected by persistent fever and back pain after an accidental needle puncture (Lin et al., 2011).
Bacillary angiomatosis (Lange et al., 2008) is one of the most common clinical manifestation in immunocompromised individuals that may be fatal if untreated, whereas immunocompetent persons may experience subclinical Bartonella infection (Massei et al., 2004).





Passive immunity


Data concerning passive immunity are lacking.



Active immune response


The antibody response to B henselae has been investigated for the identification of vaccine candidates. The kinetics in response to B henselae antigens in chronically infected experimental cats is highly variable in degree and duration (Chomel et al., 1996; Kordick et al., 1999; Yamamoto et al., 2002). The extent of serologic cross-reactivity to other Bartonella species needs to be clarified.
 Reinfection by a different strain of B henselae is possible, as supported by the isolation of unrelated bacterial clones from the same cat at different times (Arvand et al., 2008). Antibodies are therefore considered not protective, and Bartonella spp.-seropositive cats may be infected (Fabbi et al., 2004).





Bartonella laboratory testing is required for feline blood donors, for pet cats belonging to immune-suppressed persons, or when a human Bartonella-related disease is diagnosed in a cat’s home.
Isolation of the bacterium is the gold standard, but because of the high prevalence of infection in healthy cats in endemic areas, a positive culture is not confirmatory, and other compatible diagnoses must be ruled out.
The disease is therefore diagnosed on the basis of exclusion, and by assessing the response to therapy. The ex juvantibus-inference about disease causation from the observed response to a treatment may apply to uveitis, endocarditis and multifocal CNS disease, which are compatible with feline bartonellosis.
PCR may be used in blood, aqueous humour, cerebrospinal fluid or tissues, and several gene targets have been studied.
Serology (IFAT or ELISA) is more useful for exclusion than for confirmation, because of the low positive predictive value (39-46%) compared to the good negative predictive value (87-97%; Chomel et al., 1995, Gurfield et al., 2001, Fabbi et al., 2004, Guptill et al., 2004).
Repeated blood cultures are required or PCR performed on more than one kind of biological sample (blood, lymph node, oral swab; Pennisi et al., 2010).





Treatment is recommended for cats living with immunosuppressed persons or in the rare cases where Bartonella have actually caused disease, e.g endocarditis. Current therapeutic strategies in cats (Tab. 3) are based on in vitro studies and human bartonellosis.



DrugDose  DurationReference 
Doxycycline10 mg/kg, PO, q12e24 h2 to 4 weeksLappin and
Black, 1999
Azithromycin10 mg/kg PO q24h (48h)for 7 days followed by every other day for 6-12 weeksKetring et al., 2004; Varanat et al., 2009
Marbofloxacin5 mg/kg PO q246 weeksPerez et al., 2010
Amoxicillin- clavulanate62.5 mg PO q122 monthsVaranat et al., 2009
(with azithromycin)
Table 3: Suggested treatment for Bartonellosis in cats



Data from controlled efficacy studies in cats are lacking. A cat affected by recurrent osteomyelitis and polyarthritis associated with B vinsonii subsp. berkhoffii genotype II infection and bacteraemia recovered after therapy with azithromycin (10 mg/Kg PO q48h for three months) and amoxicilline-clavulanate (62.5 mg PO q12 for two months; Varanat et al., 2009).

After natural or experimental infection with B henselae or B clarridgeiae, healthy cats have been treated to eliminate bacteraemia (Greene et al., 1996, Regnery et al., 1996, Kordick et al., 1997), and many drugs have been evaluated: doxycycline, amoxicillin, amoxicillin-clavulanate, enrofloxacin, erythromycin, rifampin. Based on these results, clearance of bacteraemia cannot be guaranteed and, in the case of failure, there is the risk to induce antimicrobial resistance. Treatment of healthy carriers therefore cannot be considered an effective measure for eliminating the zoonotic risk; it is sometimes requested, in human cases of CSD or other Bartonella-related disease in a family member.





According to all transmission studies, a strict flea (and tick) control is the only successful preventive measure. There is no vaccine available against Bartonella infection.



Zoonotic aspects


Cats are the main reservoir for B henselae, the agent of cat scratch disease and other human diseases mainly observed in immunosuppressed persons. Recognised risk factors for bacteraemia in cats are young age, infestation with fleas, outdoor lifestyle and a multicat environment (Chomel et al., 1995, Foley et al., 1998, Gurfield et al., 2001, Guptill et al., 2004, Boulouis et al., 2005).


Fig. 2. Immunohistochemical identification of B. henselae in a case of cat scratch disease. Courtesy of Dharam Ramnani, Webpathology.com

Fig. 2. Immunohistochemical identification of B henselae in a case of cat scratch disease. Courtesy of Dharam Ramnani, Webpathology.com


There is no benefit from testing cats or people, except in cases of immunosuppressed persons in the home. Infection does not always lead to clinical signs in healthy persons and many have antibodies (Massei et al., 2004; Mc Gill et al., 2005). Owner education about Bartonella transmission is essential to reduce the zoonotic risk; it is crucial to allow immune-suppressed persons to keep their pet cat or to adopt a new one.



Key points to minimise the zoonotic risk (Kaplan et al., 2002; Brunt et al., 2006):


• Immune-suppressed owners should preferably adopt cats older than 1 year, flea-free, in good health, not from shelters or multicat households, and without contact with cats of unknown health status
• A strict flea control should be exercised
• Rough play should be avoided, and the cat's claws kept trimmed
• Any wound should promptly be cleaned with soap and water, and medical advice sought
• Cats should be kept indoors to avoid exposure to fleas and other possible vectors, but also to prevent other zoonotic risks.


Control in Specific Situations

Strict flea and tick control is the only effective preventive measure.




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