Chronic Bartonellosis in Cats: What are the potential implications?

Practical relevance: Bartonellae are small, vector-transmitted Gram-negative intracellular bacteria that are well adapted to one or more mammalian reservoir hosts. Cats are the natural reservoir for Bartonella henselae, which is a (re-)emerging bacterial pathogen. It can cause cat scratch disease in humans and, in immunocompromised people, may lead to severe systemic diseases, such as bacillary angiomatosis. Cats bacteraemic with B henselae constitute the main reservoir from which humans become infected. Most cats naturally infected with B henselae show no clinical signs themselves, but other Bartonella species for which cats are accidental hosts appear to have more pathogenicity. Global importance: Several studies have reported a prevalence of previous or current Bartonella species infection in cats of up to 36%. B henselae is common in cats worldwide, and bacteraemia can be documented by blood culture in about a quarter of healthy cats. The distribution of B henselae to various parts of the world has largely occurred through humans migrating with their pet cats. The pathogen is mainly transmitted from cat to cat by fleas, and the majority of infected cats derive from areas with high flea exposure. No significant difference in B henselae prevalence has been determined between male and female cats. In studies on both naturally and experimentally infected cats, chronic bacteraemia has mainly been found in cats under the age of 2 years, while those over 2 years of age are rarely chronically bacteraemic. Evidence base: This article reviews published studies and case reports on bartonellosis to explore the clinical significance of the infection in cats and its impact on humans. The article also discusses possible treatment options for cats and means of minimising the zoonotic potential.     

Infection and re-infection of domestic cats with various Bartonella species or types: B. henselae type I is protective against heterologous challenge with B. henselae type II

Four Bartonella species have been isolated from domestic cats, of which two serotypes/genotypes of Bartonella henselae and possibly B. clarridgeiae are human pathogens, causing cat scratch disease (CSD).Our objectives were to evaluate infection and potential cross-protection during re-infection in domestic cats with various Bartonella species or types.Thirty-six cats were primarily inoculated with B. henselae type I (n=16), B. henselae type II (n=10), B. clarridgeiae (n=6) or B. koehlerae (n=4). They were challenged with B. henselae type I (n=15), B. henselae type II (n=13) or B. clarridgeiae (n=8).All 36 cats became bacteremic (1.25x10(2)-1.44x10(6)CFU/ml) and bacteremia lasted from 37 to 582 days. Duration of bacteremia for cats inoculated with B. henselae type I was shorter than for cats inoculated with either B. henselae type II (P=0.025) or B. clarridgeiae (P=0.011).After challenge, 26 cats became bacteremic. Among the nine cats primarily inoculated with B. henselae type I and challenged with B. henselae type II, six cats stayed abacteremic. The three bacteremic cats had a transient low-level bacteremia. No bacteremia was observed in three cats primarily inoculated with B. henselae type I and challenged with another strain of B. henselae type I. Bacteremia levels in the 26 cats were significantly lower than for primary inoculation (P=0.022) and its duration was shorter (P=0.012). Among the eight cats challenged with B. clarridgeiae, duration of bacteremia in the four cats primarily inoculated with B. henselae type I was shorter than in the four cats primarily inoculated with B. henselae type II (P=0.01). Bartonella clarridgeiae inoculated cats were more likely to have relapses for both primary and secondary infections.This is the first demonstration of cross-protection, evidenced by absence of bacteremia, in cats primarily infected with B. henselae type I and challenged with B. henselae type II, whereas no cross-protection was previously shown for cats primarily infected with B. henselae type II and challenged with B. henselae type I. Such results are of major importance for future feline Bartonella vaccine development.     

Prevalence of Bartonella henselae antibodies in serum of cats with and without clinical signs of central nervous system disease

Bartonella henselae is occasionally associated with neurological dysfunction in people and some experimentally infected cats. The purpose of this study was to determine whether B henselae seroprevalence or titer magnitude varies among cats with neurological disease, cats with non-neurological diseases, and healthy cats while controlling for age and flea exposure. There was no difference in B henselae seroprevalence rates between cats with seizures and cats with other neurological diseases. Cats with non-neurological disease and healthy cats were more likely than cats with neurological disease to be seropositive. While the median B henselae antibody titer was greater in cats with seizures than in cats with other neurological disease, the median B henselae antibody titer was also greater in healthy cats than cats with seizures. The results suggest that titer magnitude cannot be used alone to document clinical disease associated with B henselae infection and that presence of B henselae antibodies in serum of cats with neurological disease does not prove the clinical signs are related to B henselae.     

Prevalence of Bartonella infection in domestic cats in Denmark

Whole blood and serum from 93 cats (44 pets and 49 shelter/stray cats) from Denmark were tested for the presence of feline Bartonella species by culture and for the presence of Bartonella antibodies by serology. Bartonella henselae was isolated from 21 (22.6%) cats. Bacteremia prevalence was not statistically different between shelter/stray cats (13/49, 26.5%) and pet cats (8/44, 18.2%), but varied widely by geographical origin of the cats, even after stratification for cat origin or age (p < 0.001). All isolates but one were B. henselae type II. The only cat bacteremic with B. henselae type I was not co-infected with B. henselae type II. None of the cats was harboring either B. clarridgeiae or B. koehlerae. Almost half (42/92, 45.6%) of the cats were seropositive for B. henselae and antibody prevalence was similar in shelter/stray cats (23/49, 46.9%) and pet cats (19/43, 44.2%). This is the first report of isolation of B. henselae from domestic cats in Denmark. This study also indicates that domestic cats, including pet cats, constitute a large Bartonella reservoir in Denmark.     

Genomic diversity of Bartonella henselae isolates from domestic cats from Japan, the USA and France by pulsed-field gel electrophoresis

The genomic DNA diversity of 27 Bartonella henselae and three B. clarridgeiae isolates from 18 domestic cats from Japan, the USA and France was investigated by pulsed-field gel electrophoresis (PFGE) with NotI, AscI and SmaI restriction enzymes. A great diversity of genomic patterns was found for all B. henselae, but none for B. clarridgeiae isolates. The DNA size of B. henselae and B. clarridgeiae isolates were 1.7-2.9 and 1.7Mbp, respectively. All 13 Japanese cat isolates were identified as B. henselae type I. Furthermore, three of the four Japanese cats harbored genetically different B. henselae type I isolates, suggesting for the first time co-infection with various type I isolates.One French cat and one American cat were co-infected with B. henselae and B. clarridgeiae. B. henselae type I and type II were mainly grouped in two different clusters by PFGE using SmaI endonuclease in the dendrogram.     

Experimental infection of specific pathogen free (SPF) cats with two different strains of bartonella henselae type I: a comparative study

Domestic cats are the reservoir of Bartonella henselae, the main causative agent of cat scratch disease. We compared B. henselae type I infection characteristics in 6 SPF cats infected with a feline strain (4.8 x 10(7) colony-forming units (CFU)/mL) and in 6 SPF cats infected with the reference Houston I strain (6.6 x 10(6) CFU/mL to 9.6 x 10(7) /mL). All the cats inoculated with the feline strain, but none of the cats inoculated with B. henselae Houston I, developed a fever within 2-12 days (mean: 5.8 days) post inoculation (PI), which lasted for 1-2 weeks. However, all 12 cats became bacteremic. The duration of bacteremia was significantly longer in the cats inoculated with the feline strain (mean: 237 days) than in the cats inoculated with Houston I strain (mean: 60 days) (p < 0.01). Five (83%) cats inoculated with the feline strain and none of the six cats inoculated with B. henselae Houston I had relapsing bacteremia (p = 0.02). IgG antibodies were detected by IFA within 1-2 weeks for both strains, but peaked later (week 10 versus week 3 PI) for the feline strain. By ELISA, using antigens of each B. henselae strain, all 12 cats developed Bartonella specific IgM and IgG antibodies, but the cats infected with B. henselae Houston I antigen yielded significantly lower optical density values (p < 0.05). By SDS-PAGE, PFGE and Western blotting, protein profile differences (84 to 89% homology) were observed between the two strains. If a feline vaccine is to be developed in order to prevent human infection, the choice of the vaccine strain will be critical, since major differences were identified even between strains belonging to the same sero/genotype.     

Bartonella henselae bacteraemia in domestic cats from Auckland

Bartonella henselae causes most cases of cat scratch disease, a self-limited localised lymphadenopathy illness of humans. Bartonella henselae also causes disseminated cutaneous and visceral disease in immunocompromised people. Cat blood (1-5 ml) collected from cats in the Auckland area was processed and plated on to 5% sheep blood brain heart infusion agar and incubated at 35 degrees C in 5% CO2 for 14 days. Bartonella henselae was identified by colony morphology, Gram's stain, twitching motility, biochemical tests and molecular methods. Eight of 48 cats (17%) had Bartonella bacteraemia. Species-specific probes and biochemical profiles identified all isolates as B. henselae. Infected cats pose a risk to humans they lick, scratch or bite. People should be made aware of the risk cats pose.     

A serological investigation of Bartonella henselae infection in cats in Turkey

Bartonella henselae is the causative agent of cat scratch disease (CSD) in humans. Cats are the main reservoir of this bacterium and may infect humans through scratches and bites. The purpose of this study was to determine the B. henselae seroprevalence in cats in Turkey. A total of 298 cats blood samples were collected from six different provinces of Turkey. Sera were tested for the presence of anti-B. henselae IgG antibodies by indirect fluorescent antibody test (IFA). The seroprevalence of B. henselae was 27.9% (83/298) for the cats examined in this study. The seroprevalence of cats by province was significantly higher in Bursa (41.3%), Adana (33.9%), Aydin (27.5%) and Burdur (32.3%) than in Kayseri (17.9%) and Istanbul (12.5%). Statistically significant differences were not observed between cat sexes and living conditions of cats. The results revealed that B. henselae is an important zoonotic pathogen in Turkey.     

Evaluation and use of a nested polymerase chain reaction assay in cats experimentally infected with Bartonella henselae genotype I and Bartonella henselae genotype II.

Cats have been shown to be infected with Bartonella henselae genotype I, B. henselae genotype II, and B. clarridgeiae. Feline bartonellosis infections and the strains involved in these infections are important in both veterinary and human medicine. Nucleic acid amplification methods such as polymerase chain reaction (PCR) are being used in both research and diagnostics as tools for understanding many infectious diseases. Bartonella bacteremia in cats is detected by blood culture; however, because of the limitations of culture (delayed turnaround time and sensitivity limits), PCR may be a more efficient method for identifying infected cats. Three distinct PCR assays that could differentiate among B. henselae genotype I, B. henselae genotype II. and B. clarridgeiae were developed and used to detect as few as 3.2 organisms. Fourteen cats experimentally infected with B. henselae genotype I and B. henselae genotype II were followed by bacterial culture and PCR through the course of infection, including periods of primary and relapsing bacteremia. The PCR assay was positive in 11 of the 14 cats for periods of 1-9 weeks after culture became negative. Of the 223 blood specimens that were culture negative, the PCR assay was positive in 38 (17%) of the specimens. Two of the 14 cats developed relapsing bacteremia. The 2 B. henselae genotypes were amplified in the cats and the bacteremic phase of these infections as determined by PCR lasted for a longer period than previously determined by culture. Using laboratory assays such as PCR to understand the strains involved in feline bartonellosis and the course of the infection is important in the understanding of these zoonotic agents.     

Bartonella henselae infection in splenectomized domestic cats previously infected with hemotropic Mycoplasma species

Cat scratch disease is caused by Bartonella henselae and the domestic cat represents its main reservoir. In immunocompromised patients, infection with B. henselae is characterized by more severe clinical forms than in non-immunocompromised individuals. The objective of the present study was to investigate the characteristics of B. henselae (Houston-I strain) infection in four splenectomized and three non-splenectomized cats, five of which were chronically infected with 'Candidatus Mycoplasma haemominutum'. No major clinical signs were observed in either group of cats. Cats in both splenectomized and non-splenectomized groups became bacteremic within a week post-inoculation. Although bacteremia was on average 10 days longer in the splenectomized cats, that difference was not statistically significant (P=0.72). In both groups, the level of bacteremia peaked within the same time frame; however, the level of bacteremia was about 10-fold higher in the splenectomized cats (P=0.007). Such a difference could be associated with a reduced immune response to the infection, especially a reduced ability to phagocytize Bartonella organisms in the splenectomized cats. Concurrent infection with 'Candidatus M. haemominutum' did not appear to alter the course of infection.     

Extracellular Bartonella henselae and artifactual intraerythrocytic pseudoinclusions in experimentally infected cats

Blood, spleen and liver of specific pathogen-free (SPF) cats and SPF cats experimentally infected with Bartonella henselae were examined. Using immunohistochemical labeling, no intracellular B. henselae were observed in tissues of any cats, but extracellular B. henselae were detected in tissues of infected cats. Pseudoinclusions were detected in erythrocytes of all cats using electron microscopy.     

Isolation of Bartonella henselae from a serologically negative cat in Bloemfontein, South Africa

Sera collected from apparently healthy 6-12-month-old cats (n = 31) presented to the Society for the Prevention of Cruelty to Animals Veterinary Clinic in Bloemfontein for neutering were tested for antibodies reactive to Bartonella henselae (Houston-1 strain) by indirect fluorescent antibody testing. Whole blood collected from the cats was used in isolation experiments and subsequent identification of Bartonella species was based on comparison of the nucleotide base sequence of polymerase chain reaction-amplified citrate synthase gene fragments. While none of the cats had antibodies reactive with B. henselae at titres > or =1/64, an organism with a partial citrate synthase gene sequence identical to that of B. henselae (Houston-1) was isolated from 1 cat.     

Epidemiology of Bartonella infection in domestic cats in France

Blood samples were collected between February and June 1996 from a convenience sample of 436 domestic French cats living in Paris and its environs and were tested for Bartonella bacteremia and seropositivity. Seventy-two cats (16.5%) were Bartonella bacteremic, of which 36 cats (50%) were infected with Bartonella henselae type II (B.h. II) only, 15 cats (21%) were infected with Bartonella clarridgeiae (B.c.) only, and 11 cats (15%) were infected with B. henselae type I (B.h. I) only. Eight cats (11%) were co-infected with B. henselae and B. clarridgeiae (B.h. II/B.c.: five cats; B.h. I/B.c.: three cats). Two cats (2.8%) were concurrently bacteremic with B. henselae types I and II. Risk factors associated with bacteremia included ownership for <6months (prevalence ratio (PR)=1.80; 95% confidence interval (CI)=1.13-2.85), adoption from the pound or found as a stray (PR=1.67, 95% CI=1.05-2.65), and cohabitation with one or more cats (PR=1.60, 95% CI=1.01-2.53). Bartonella antibodies to either B. henselae or B. clarridgeiae were detected in 179 cats (41.1%). Risk factors associated with seroposivity paralleled those for bacteremia, except for lack of association with time of ownership. Prevalence ratios of bacteremic or seropositive cats increased with the number of cats per household (p=0.02). The lack of antibodies to B. henselae or B. clarridgeiae was highly predictive of the absence of bacteremia (predictive value of a negative test=97.3%). Multiple logistic regression analysis indicated that bacteremia, after adjustment for age and flea infestation, and positive serology, after adjustment for age, were associated with origin of adoption and number of cats in the household. Flea infestation was associated with positive serology.     

猫巴尔通体病和猫抓病研究进展

巴尔通体是一种人兽共患病的病原,其传播情况比较复杂.牛、犬、人、啮齿类动物和野生动物都是其宿主,蝇、跳蚤、虱子、蛉等节肢动物都是其储存宿主.猫可以感染5种巴尔通体,包括Bartonella henselae、B.bovis、B.clarridgeae、B.koehlerae和B.quintana.研究表明,猫抓病主要是...     

Prevalence of Bartonella species causing bacteraemia in domesticated and companion animals in the United Kingdom

Between October 1999 and February 2000, 691 blood samples examined routinely for either haematological or virological assessment were screened by culture for the presence of Bartonella species. They came from 615 animals: 360 cats, 211 dogs, 27 horses, 16 cattle and a gorilla. The samples were incubated for long periods on 10 per cent horse blood agar at 37 degrees C in an atmosphere containing 5 per cent carbon dioxide. Isolates were obtained from 35 samples from 34 (9.4 per cent) of the cats, but not from any of the other animals. Comparison of citrate synthase gene sequences from the isolates indicated that they were all Bartonella henselae. Analysis of 16S rRNA gene fragments indicated that 30 of the cats were infected solely with B henselae genotype II, two were infected solely with B henselae genotype I and two were infected with both genotypes.     

Immune response of neonatal specific pathogen-free cats to experimental infection with Bartonella henselae

The purpose of this study was to determine whether neonatal cats develop and maintain a persistent bacteremia for longer than do adult cats with a normal mature immune system, and whether neonatal cats are susceptible to infection with Bartonella henselae by oral inoculation. Neonatal specific pathogen-free (SPF) cats were inoculated with B. henselae intradermally (n = 4) or orally (n = 5) or with 0.9% NaCl (n = 2). Blood was collected periodically through 16 weeks post-inoculation (PI) for serology, bacteriology and complete blood count. Cats inoculated orally or intradermally at 3-5 days of age were bacteremic through 12-16 weeks PI, similar to what is documented for adult cats inoculated intradermally or intravenously. One cat inoculated at age 2 weeks was bacteremic through 10 weeks PI; the other was not bacteremic. Intradermally inoculated neonatal cats produced serum IgG antibodies to B. henselae but orally inoculated neonatal cats did not. Infected cats with and without serum IgG antibodies to B. henselae became blood-culture negative simultaneously, suggesting that IgG is not required to clear bacteremia.     

Experimental infection of domestic cats with passaged genotype I Bartonella henselae

The influence of in vitro passage on Bartonella henselae pathogenesis in cats has not been thoroughly evaluated. Our objective was to examine the bacterial kinetics and humoral immune responses in cats experimentally infected with three different in vitro passages of B. henselae F1, a genotype I strain of feline origin. The F1 strain was in vitro passaged 20 and 40 times, and each was inoculated into a group of 5 cats. The kinetics of bacteremia and the feline humoral immune response to bacterial antigens were compared to a previous study involving a group of six cats inoculated with the original F1 strain. Among the three groups of cats, the kinetics of bacteremia profiles and the humoral immune responses to B. henselae lysates were similar. The influence of passage on bacterial membrane proteins was examined. In vitro passage altered the expression of 4/17 (23.5%) bacterial membrane proteins and 6/15 (40%) bacterial membrane antigens. An association between poor seroreactivity to three lysate antigens (15-, 18- and 45kDa), prolonged bacteremia and decreased serum bactericidal activity was noted. Our data show that in vitro passage of B. henselae did not alter the kinetics of bacteremia, including the occurrence of relapsing bacteremia, in experimentally infected cats. This suggests that highly passaged strains may not be suitable for future vaccination studies. Furthermore, in vitro passage results in phenotypic and antigenic changes in the bacterial membrane protein profile, which warrants caution in the interpretation of studies involving passaged B. henselae strains.     

Serological survey of vector-borne zoonotic pathogens in pet cats and cats from animal shelters and feral colonies

Although cats and their arthropod parasites can sometimes be important sources of zoonotic diseases in humans, the extent of exposure among various cat populations to many potential zoonotic agents remains incompletely described. In this study, 170 domestic cats living in private homes, feral cat colonies, and animal shelters from California and Wisconsin were evaluated by serology to determine the levels of exposure to a group of zoonotic vector-borne pathogens. Serological positive test results were observed in 17.2% of cats for Rickettsia rickettsii, 14.9% for R akari, 4.9% for R typhi, 11.1% for R felis, and 14.7% for Bartonella henselae. Although vector-borne disease exposure has been documented previously in cats, the evaluation of multiple pathogens and diverse cat populations simultaneously performed here contributes to our understanding of feline exposure to these zoonotic pathogens.     

A review of bacterial pathogens in Ctenocephalides felis in New Zealand

The cat flea, Ctenocephalides felis, is the recognised vector of Bartonella henselae, B. clarridgeiae and Rickettsia felis. Although these Gram-negative bacteria were only described in the last decade, they are already known to cause a variety of diseases in people, particularly children and the immunosuppressed. Such diseases include cat-scratch disease, bacillary angiomatosis, endocarditis, bacteraemia, encephalopathy, neuroretinitis, osteomyelitis and peliosis hepatis. Although most infections in cats and dogs appear to be subclinical, recent studies have provided growing evidence that the bartonellas can also cause serious problems in pets, including hepatitis, endocarditis, central nervous system (CNS) signs, lymphadenopathy, uveitis, cataracts and reproductive failure. In 2004, DNA of B. henselae, B. clarridgeiae and R. felis was demonstrated in cat fleas from New Zealand and pets and their owners in the country are thus at risk of infection. While flea control programmes have traditionally been advocated by veterinarians to prevent pruritis and tapeworms in pets, they should now also be recommended to prevent infections with the new flea-borne bacterial pathogens. To raise awareness of the organisms amongst veterinarians and animal health workers, this review describes: the biology of the organisms; clinical and laboratory features of infections in cats, dogs and people; diagnosis; and possible treatments and control of infections with these organisms.     

Occurrence of Bartonella henselae types I and II in Central Italian domestic cats

Serological and molecular surveys were conducted to determine the occurrence of Bartonella henselae in domestic cats in Central Italy. Samples from 234 pet cats were tested for B. henselae antibodies by indirect immunofluorescence with 78 (33.3%) positive. A PCR assay specific for the Bartonella 16S rRNA gene was carried out on DNA samples extracted from blood of the 234 cats; 26 (11.1%) of the seropositive cats were positive. Two PCR protocols, which discriminate genotypes I and II of B. henselae, were performed on all DNA samples. Sixteen (6.8%) cats were infected by genotype I, 6 (2.5%) by genotype II, and two males (0.8%) by both genotypes. Two female (0.8%) cats which were Bartonella sp. PCR positive, gave negative results with the types I and II PCR. This protocol facilitates the direct and rapid detection of Bartonella DNA in feline blood samples, and differentiates B. henselae genotypes.