GUIDELINE for Feline bartonellosis

The Bartonella species infection in cats guidelines were first published in the J Feline Med Surg 2013, 15: 563-569 by Maria Grazia Pennisi et al. This update was authored by Maria Grazia Pennisi, Fulvio Marsilio and ABCD colleagues.

Key points

• Bartonella infect humans and domestic animals and some species and subspecies are confirmed or suspected pathogens.
• Bartonella have a worldwide distribution with higher prevalences in areas where most favourable conditions for arthropod vectors (particularly fleas) exist.
• Bartonella (B.) henselae is the causative agent of cat scratch disease (CSD) in humans, a self-limiting regional lymphadenopathy.
• Cats are the main reservoir hosts of henselae and accidental hosts of other species.
• The primary role of fleas in the transmission of henselae among cats has been demonstrated.
• Most cats naturally infected by henselae do not show clinical signs, but some individuals can develop life-threatening cardiovascular diseases and possibly other pathologies associated with generalized lymphadenopathy.
• Other Bartonella can have pathogenic properties in cats, as seen in dogs and humans.
• Antibodies are not protective and antibody-positive cats can be re-infected.
• Bartonellosis is diagnosed in symptomatic Bartonella-positive cats based on exclusion of other compatible diagnoses, and by assessing the response to antibiotic therapy.
• No benefit derives from testing healthy cats and humans, except in cases of immunosuppressed people in the home.
• Strict flea and tick control is the only effective preventive measure.

Agent properties

Bartonella are small (2.0 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 (Table 1).

The most common species in both cats and humans is B. henselae, which causes cat scratch disease (CSD) in the latter, as well as other potentially fatal disorders affecting immunocompromised people. Cats can be co-infected by different Bartonella spp. at the same time (Diniz et al., 2022).

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). However, some cases of severe disease due to osteomyelitis, endocarditis and myocarditis have been described (Chomel et al., 2003, 2009; Perez et al., 2010; Varanat et al., 2012; Joseph et al., 2018; Hui et al., 2022; Colella et al., 2023; Fingerhood et al., 2024). Moreover, B. vinsonii subsp. berkhoffii DNA was detected in the blood and effusions of cats and associated with osteomyelitis and pericarditis (Varanat et al., 2009; Wheatley et al., 2023).

Table 1: Species and subspecies of Bartonella that are confirmed or potential human pathogens (Chomel et al., 2006, 2016; Molia et al., 2016)

Bartonella spp.	Primary reservoir	Vector	Accidental host
B. bacilliformis	Humans	Lutzomia verrucarum	None
B. quintana	Humans	Pediculus humanus	Cat, dog, monkey
B. elizabethae	Rattus norvegicus	Xenopsylla cheopis	Humans, dog
B. grahamii	Several species of wild mice	Rodent fleas	Humans
B. henselae	Cat	Ctenocephalides felis felis	Humans, dog
B. clarridgeiae	Cat	C. felis	Humans, dog
B. koehlerae subsp. koehlerae	Cat, lion	C. felis	Humans
B. koehlerae subsp. boulouisii	Mountain lion	Fleas?	Unknown
B. koehlerae subsp. bothieri	Bobcat, cheetah	Fleas?	Unknown
B. vinsonii subsp. berkhoffii	Coyote, dog	Ticks?	Humans, cat
B. vinsonii subsp. arupensis	Peromyscus leucopus	Ticks? Fleas?	Humans
B. washoensis	Spermophilus beecheyii	Fleas?	Humans, dog
B. asiatica	Rabbit	Fleas?	Humans
B. rochalimae	Wild carnivores	Fleas	Humans

Epidemiology

Prevalence

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 3.6 to 53% (Table 2).

Table 2: Antibody prevalences of Bartonella infection in the feline populations sampled in European countries

Country	Number of cats	Prevalence (%)	Reference
The Netherlands	163 (stray)	52	Bergmans et al., 1997
Austria	96	33	Allerberger et al., 1995
Switzerland	728	8	Glaus et al., 1997
Germany	713	15	Haimerl et al., 1999
	245	37.1	Morgenthal et al., 2012
	50	46	Schäfer et al., 2023
France	64	36	Chomel et al., 1995
	94	53	Heller et al., 1997
	179	41	Gurfield et al., 2001
Spain	680	23.8	Ayllon et al., 2012
	118	78	Álvarez-Fernández et al., 2021
	88	36.3	Peris et al., 2024
Italy	540	38	Fabbi et al., 2004
	55	3.6	Zobba et al., 2009
	1300 (stray)	23.1	Brunetti et al., 2013
	197	45.7	Persichetti et al., 2018
	167	18.0	Morelli et al., 2019
	95	29.47	Ebani et al., 2021
Scotland	78	15.3	Bennett et al., 2011
Greece	452	35.4	Kokkinaki et al., 2022

The DNA of Bartonella spp. is often detected in the blood of both healthy and sick cats (Zarea et al., 2023) (table 1). Mazurek et al. (2020) reported the occurrence of Bartonella spp. in blood by PCR testing of 672 cats randomly selected from the largest clinics in eastern Poland and showed a prevalence of 40.5%. Interestingly, only B. henselae DNA was detected.

In Turkey, Muz et al. (2021) conducted a study on the prevalence of protozoan and microbial pathogens in owned sick cats presented to veterinary clinics, and demonstrated B. henselae DNA in 40.1% of 167 blood samples. In contrast, Ceylan et al. (2024) detected Bartonella spp. DNA in the blood of only 2.4% of apparently healthy cats admitted to a veterinary teaching hospital in Turkey.

Razgūnaitė et al. (2021) reported Bartonella spp. DNA in 4.9% of Lithuanian cat blood samples (8/163) and 29.4% (30/102) of fleas collected from the same cats. B. henselae and B. clarridgeiae were identified in the cats and fleas, with B. henselae found to be more common than B. clarridgeiae. In Spain (in Zaragoza), B. henselae DNA was amplified from blood samples in 9.3% of stray cats sampled as a part of a trap-neuter-release programme (Villanueva-Saz et al., 2023). In Croatia, Stepanić et al. (2024) found that B. henselae is prevalent throughout the country and isolated the bacterium from the blood in 16% of cat blood samples tested.

Transmission

Epidemiological evidence and experimental studies have demonstrated the important role of fleas in the transmission of B. henselae and B. clarridgeiae between cats. B. henselae is naturally transmitted among cats by the flea Ctenocephalides felis felis, or by flea faeces.

Bartonella 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 – can transmit the organism. B. henselae is amplified in the flea hindgut and can persist in the environment in flea faeces for at least nine days (Finkelstein et al., 2002). Using a quantitative real-time PCR, 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).

Bartonella 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). Outdoor lifestyle and lack of ectoparasite prevention and control are risk factors for feline B. henselae infection (Mazurek et al., 2020).

Blood transfusion 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).

The modes of transmission and the reservoir potential in felids of three other species isolated from cat blood, i.e. B. koehlerae, B. bovis and B. quintana, have not been established (Chomel et al., 2004; Breitschwerdt, 2008).

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).

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).

Persichetti et al. (2016) evaluated PCR positivity to vector-borne pathogens in cats and their ectoparasites and they sequenced B. clarridgeiae in PCR products amplified from DNA extracted from two ticks (one Ixodes ventalloi and one Rhipicephalus sanguineus specimen) but not in the blood of the two cats carrying each of them. Similarly, Regier et al. (2017) found B. henselae in Ixodes ricinus ticks collected from one PCR-negative cat that was, however, positive for anti-B. henselae antibodies. Whether this observation implies a role for ticks in the transmission of both Bartonella spp. to cats needs to be resolved.

Mazurek et al. (2019) reported the frequency of the occurrence of Bartonella spp. DNA in dogs from households where cats with clinical bartonellosis were kept. The presence of DNA with 99–100% nucleotide sequence identity with the sequence of the Bartonella DNA isolated from cats was demonstrated in the body of 10% of tested dogs. The results indicated that cats serve as a Bartonella reservoir for dogs, and dogs can play the same role with regard to humans.

Pathogenesis

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 following grooming. A cat scratch is the common mode of transmission of the organism to other animals, including humans (Chomel et al., 1996). 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 (Diniz et al., 2022). The location within erythrocytes and vascular endothelial cells is believed to protect Bartonellae from antimicrobial agents. Cats can be re-infected by different strains of Bartonella (Guptill, 2010; Diniz et al., 2022).

In some experimentally infected cats, pyogranulomatous inflammation was seen in the lung, liver, spleen, kidney, heart and lymphoid tissue at necropsy (Guptill et al., 1997; Kordick et al., 1999).  Interestingly, pyogranulomatous inflammation in myocardium (Fig. 2)  and diaphragm was found in some spontaneous cases diagnosed in kittens where other compatible causative pathogens had been excluded (e.g. FCoV and Toxoplasma) (Varanat et al., 2012; Fingerhood et al., 2024).

Immunity

Passive immunity

Data concerning passive immunity are lacking.

Active immunity

 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. Re-infection 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 can be infected (Fabbi et al., 2004).

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. Neither did exposure to infected fleas result in clinical signs (Chomel et al., 1996; Bradbury and Lappin, 2009). In some cases of experimental inoculation, a self-limiting febrile disease, transient mild anaemia, localised or generalized lymphadenopathy, mild neurologic signs and reproductive failure have been reported (Kordick et al., 1999). However, the role of Bartonella in causing clinical signs in cats after spontaneous transmission is still not completely clear.

Studies based on antibody detection have limited value because antibodies indicate exposure, not necessarily active infection. Moreover, there is cross-reactivity between different Bartonella species, which 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 anti-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. However, an uncontrolled retrospective study reported Bartonella DNA in cerebrospinal fluid and confirmed specific antibody production in the CNS of cats with CNS disease (Leibovitz et al., 2008).  Castel et al. (2019) reported co-infection with B. henselae and Sarcocystis sp. in a 6-year-old male neutered domestic longhair cat with chronic waxing and waning neurologic mild signs and presenting an acute progressive multifocal neuromuscular syndrome and chorioretinitis. Determining the contribution of each agent and the influence of the co-infection to the pathogenesis of the neuromuscular and ocular lesions was not possible, but treatment with fluoroquinolones, trimethoprim sulfadiazine and pyrimethamine was directed at both organisms. After an initial worsening of clinical signs, a progressive improvement followed by full recovery was observed. As Sarcocystis sp. clinical infection in cats has been associated with immunosuppression, the authors hypothesised that relapsing B. henselae bacteraemia might have decreased the cat’s immune competence and caused a normally quiescent protozoal infection to induce intermittent clinical signs (Castel et al., 2019). Based on these data, Bartonella spp. infection should be considered when other compatible diagnoses of CNS disease have been excluded in symptomatic cats.

No difference in Bartonella antibody prevalence was found between healthy cats and cats affected by uveitis (Fontenelle et al., 2008), but there have been some reports of Bartonella spp. exposure in cats with uveitis that were responsive to drugs considered effective against Bartonella (Lappin and Black, 1999; Ketring et al., 2004). No difference in Bartonella PCR prevalence was found in cats affected by anaemia compared to control cats (Ishak et al., 2007). Prevalence of anti-Bartonella antibodies was lower in cats with fever compared to afebrile controls, but the former had a higher blood DNA positivity approaching statistical significance (Lappin et al., 2009). Moreover, a unique, identical B. henselae genotype was cultured from blood of three kittens and it was recognised as the causative agent of their cyclic relapsing fever associated with anaemia and neutropenia by excluding other infections and observing a clinical cure with azythromycin treatment (Breitschwerdt et al., 2015).

A study based on serology and culture did not find an association between Bartonella infection and chronic rhinosinusitis (Berryessa et al., 2008). Neither was any association found between Bartonella infection and pancreatitis, because cats with normal fPLI values and cats with elevated fPLI 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 and Raoult, 1999; Mc Donald et al., 2004) and some research groups have looked for Bartonella in cats with endocarditis, which is uncommon  in cats. Aortic and fatal mitral valve B. henselae-associated endocarditis was reported in two cats in the USA (Chomel et al., 2003, 2009). Also, B. henselae anterior mitral valve leaflet vegetative endocarditis associated with a grade III to 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 might be a cause of blood culture-negative endocarditis, as previously suspected (Malik et al., 1999). Colella et al. (2023) reported B. henselae mitral valve endocarditis associated with multi-resistant Enterococcus faecalis bacteraemia in a cat with prolonged prednisone therapy to treat presumed infiltrative enteropathy. Pyogranulomatous myocarditis (Fig. 2) caused by B. henselae was diagnosed at post-mortem examination in two kittens from the same shelter that died acutely (Varanat et al., 2012). One of the two kittens had received corticosteroids one week before death to treat fever and diarrhoea and these signs resolved within 2 days (Varanat et al., 2012).  Joseph et al. (2018) described a clinical case of congestive heart failure with acute onset in a 3-year-old cat from a household fostering stray cats. Echocardiography and electrocardiography respectively evidenced ventricular asymmetrical myocardial thickening with a diffusely mottled hypoechoic echotexture and a left bundle branch block. After a positive blood PCR test for B. henselae, azythromycin treatment was given for a month and a complete resolution of clinical, ultrasound and electrocardiographic abnormalities was documented (Joseph et al., 2018).

Fingerhood et al. (2024) considered B. henselae as the most likely cause of multifocal pyogranulomatous lesions detected in a 2-month-old kitten euthanised because of its severe clinical condition associated with tri-cavitary effusions. A negative reverse-transcriptase PCR test for FCoV from the pleural effusion and a negative FeLV rapid antigen test had been obtained before euthanasia. The post-mortem examination of the kitten revealed pyogranulomas on the serosal surface of the gastrointestinal tract, the diaphragm, the epicardium, myocardium, endocardium, and pancreas. Immunohistochemical assays for FCoV and Toxoplasma were performed in the intestine but were negative. Silver impregnation of myocardium fixed tissue showed small aggregates of argyrophil bacteria within a myocardial inflammatory lesion. Indirect immunofluorescence for B. henselae was performed and found positive from multiple organs. Finally, B. henselae DNA was amplified in heart and colon samples (Fingerhood et al., 2024).

Bartonella vinsonii subspecies berkhoffii DNA was amplified from the pericardial effusion of a cat with recurrent pericardial and pleural effusions (Wheatley et al., 2023). Eosinophilic pericardial effusion and eosinophilic pericarditis were diagnosed by cytological and histological investigations in this cat.  Culture of the pleural transudate was negative for aerobic and anaerobic bacteria, while peripheral blood culture and sequencing revealed the DNA of an apicomplexan protozoon (90% homology with Colpodella species) of unknown clinical relevance (Wheatley et al., 2023). Aggressive osteomyelitis causing an incomplete fracture of the radial metaphysis was associated with B. henselae bacteraemia in a young cat with generalised peripheral and abdominal lymphadenopathy (Hui et al., 2022). The cat was treated with a combination of doxycycline and pradofloxacin for 6 weeks and clinical and radiographic improvement was documented. A negative blood culture was also obtained as well as evidence of seroreversion one year later (Hui et al., 2022).

Lameness and pain during limb palpation were observed in a cat affected by pyogranulomatous multifocal osteomyelitis, and polyarthritis progressively affecting limbs, that was 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, but some individuals can develop acute life-threatening cardiovascular diseases and possibly other chronic pathologies associated with generalised lymphadenopathy and pyogranulomatous inflammation in affected tissues. Moreover, other Bartonella species, for which cats are accidental hosts, can have pathogenic properties.

Diagnosis

Laboratory changes

Hyperproteinaemia and hyperglobulinaemia have been reported in cats with various forms of bartonellosis (Chomel et al., 2003; Varanat et al., 2009; Josephet al., 2018; Castel et al., 2019). Mature neutrophilia and mild elevation of serum alkaline phosphatase were found in cats with osteomyelitis due to bartonellosis by B. henselae (Hui et al., 2022). Reactive lymphoid hyperplasia was cytologically diagnosed from lymph nodes and splenic hypoechoic nodules observed in this cat at ultrasound abdominal evaluation (Hui et al., 2022). In kittens with recurring acute-onset, fever associated with B. henselae anaemia and neutropenia were the unique clinicopathological abnormalities detected during the febrile episodes (Breitschwerdt et al., 2015). In a kitten with tricavitary effusion (modified transudate), complete blood count changes included an inflammatory leukogram with a left shift, toxic neutrophils and nonregenerative anaemia (Fingerhood et al., 2024). The serum biochemical abnormalities were low values of globulins, sodium, potassium, chlorine, phosphorus, and glucose (Fingerhood et al., 2024).

Diagnostic imaging

Endocardial and myocardial changes and effusions are visible by echocardiography. They include aortic and mitral valve changes (Chomel et al., 2003, 2009; Perez et al., 2010), and ventricular asymmetrical myocardial thickening with a diffusely mottled hypoechoic echotexture (Joseph et al., 2018). The clinical cure is confirmed by the normalisation of both cardiac structure and function observed by echocardiography (Perez et al., 2010; Joseph et al., 2018).

Cortical lysis with a moderate periosteal reaction was seen at the proximal metaphysis of the radius in radiographic and computed tomography investigations in a cat with osteomyelitis caused by B. henselae (Hui et al., 2022). Abdominal ultrasound evaluation of this cat revealed multifocal lymphadenopathy and hypoechoic splenic nodules (Hui et al., 2022).

Electrocardiography (ECG) investigations

Electrocardiography performed in a cat with acute cardiac disease associated with a positive blood PCR test for B. henselae showed a left bundle branch block that disappeared after a 30-day course of azithromycin therapy (Joseph et al., 2018).

Detection of the infectious agents

Apart from in cats suspected of bartonellosis, Bartonella laboratory testing is required in healthy cats to be used as feline blood donors, in pet cats belonging to immunosuppressed persons, or when a human Bartonella-related disease is diagnosed in a person that lives with cats or has contact with cats.

Direct detection

Cultivation of the bacterium is the gold standard method of diagnosing Bartonella infection and a combinational approach with pre-enrichment culture and PCR increases sensitivity (Breitschwerdt et al., 2007). Sensitivity can also be increased by repeated blood cultures or PCR performed on several biological samples (blood, lymph node, oral swab, tissues) (Pennisi et al., 2010; Drummond et al., 2018). For rapid laboratory diagnosis, a real-time PCR and pyrosequencing-based algorithm was described that allowed rapid differentiations of at least 11 medically relevant Bartonella spp. within five hours from receipt of the specimens (Buss et al., 2012). Parra et al. (2017) proposed a real time PCR for Bartonella spp. detection to improve PCR sensitivity and to identify species not previously described. Moreover, in order to detect and classify new Bartonella species from fleas a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDITOF-MS) has been proposed (El Hamzaoui et al., 2018).

Because of the high prevalence of infection in healthy cats in endemic areas, a positive culture or PCR are not confirmatory of disease in cats with compatible signs, and other compatible diagnoses must be ruled out. The disease is therefore confirmed based on exclusion, and by assessing the response to therapy. This ‘ex juvantibus’-inference—determining disease causation based on the observed response to treatment—can apply to uveitis, endocarditis, myocarditis, pericarditis, cavitary effusions, and multifocal CNS disease, which are all compatible with feline bartonellosis. However, apart from blood, more appropriate biological samples according to the clinical presentation should be submitted for PCR and cultivation (e.g. effusion, aqueous humour) before assessing the response to therapy.

Indirect detection

Serology (IFAT or ELISA) is more useful for exclusion than for confirmation, because of the low positive predictive value (39-46%) compared to the high negative predictive value (87-97%; Chomel et al., 1995; Gurfield et al., 2001; Fabbi et al., 2004; Guptill et al., 2004; Breitschwerdt et al., 2015). However, a very high antibody level was detected in a cat with endocardial bartonellosis (Chomel et al., 2009).

Treatment

Treatment is recommended for cats living with immunosuppressed persons or in rare cases where Bartonella has actually caused disease, e.g. endocarditis or myocarditis. Data from controlled efficacy studies in cats are lacking. Current therapeutic strategies in cats are based on in vitro-studies, experimental infections and human bartonellosis. High doses of doxycycline (10-15 mg/kg q12h PO) combined with quinolones (pradofloxacin 5-7.5 mg/kg q12h PO), alone or in combination with amoxicillin, have been used as first-line treatments in cats (Hui et al., 2022; Diniz et al., 2022; Lappin and Fitzgerald, 2024). The two or three different antibiotics are, however, started at least five days apart to avoid a potential shock-like reaction caused by the sudden release of bacterial endotoxins and antigens during the first days of antibiotic therapy (Diniz et al., 2022). The suggested duration of treatment is six weeks but can be longer, and should be evaluated for an individual case (Hui et al., 2022; Diniz et al., 2022; Lappin and Fitzgerald, 2024).

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 treatment failure, there is the risk of inducing antimicrobial resistance. Treatment of healthy carriers therefore cannot be considered an effective measure for eliminating the zoonotic risk; apart from in cats living with immunosuppressed people, it is sometimes requested in human cases of CSD or other Bartonella-related disease in a family member.

Prognosis

Prognosis is poor when diagnosis is delayed, particularly in cases of myocarditis and endocarditis (Chomel et al., 2003, 2009). However, cats with valvular endocarditis and myocarditis can be cured when they are promptly treated with antibiotics and receive intensive supportive care (Perez et al., 2010; Joseph et al., 2018). Prognosis is good in treated cats with osteomyelitis (Varanat et al., 2009; Hui et al., 2022) and neurologic disorders (Castel et al., 2019).

Prevention

According to all transmission studies, strict flea (and tick) control is the only successful preventive measure (Greco et al., 2019). There is no vaccine available against Bartonella infection.

Disease control in specific situations

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

Zoonotic risk

Cats are the main reservoir for B. henselae, the agent of CSD and other human diseases mainly observed in immunosuppressed persons (Fig. 3).

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).

Sepúlveda-García et al. (2023) studied in households with cats the risk of infection with Bartonella spp. in cats and their owners and estimated the risk factors for Bartonella spp. positivity. Cats younger than one year, non-neutered, sampled at home, and with improper application of tick/flea control products showed a higher risk for Bartonella spp. DNA presence in blood samples. Humans with occupational exposure involving animal contact were more likely to exhibit B. henselae antibody seropositivity in blood. Bartonella spp. DNA was present in at least one cat from 20.4% of the households sampled, but Bartonella DNA was not detected in owners’ blood, inferring that there was a low risk of recent human infection in the studied population.

Clinical signs in humans

CSD in humans 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), endocarditis (Tsuneoka et al., 2010) and encephalopathy (Samarkos et al., 2018). 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., 2009) is one of the most common clinical manifestations in immunocompromised individuals that may be fatal if untreated, whereas immunocompetent persons may experience subclinical Bartonella infection (Massei et al., 2004). There is no benefit of testing asymptomatic 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 immunosuppressed people to keep their pet cat or to adopt a new one.

Interestingly, Dong and colleagues reported the concurrent Coronavirus disease 2019 (COVID-19) and a severe recurrence of bartonellosis caused by B. henselae, which had been clinically cured one month before (Dong et al., 2024).

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

• Immunosuppressed 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.
• Strict flea and tick control should be exercised.
• Rough play should be avoided, and the cat’s claws should be regularly trimmed.
• Any wound should be promptly cleaned with soap and water, and medical advice should be sought.
• Cats should be kept indoors to avoid exposure to fleas and other possible vectors and to prevent other zoonotic risks.

Acknowledgement

ABCD Europe gratefully acknowledges the support of Boehringer Ingelheim (the founding sponsor of the ABCD), MSD Animal Health, Vétoquinol, Virbac and IDEXX.

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