R och alim aea and G rah am ella. Due to the broad host. tonella species are distinct from H aem obarton ella

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1 Feline Health Topics for veterinarians December Volume 12, Number 4 Beyond Cat Scratch Disease: Evolving implications of Bartonella Infection in the Cat Edward Breitschwerdt, D.V.M. and Dorsey Kordick, B.S. E lec to n m ic r o g r a p h o f felin e e r th r o c y te co n ta in in g B a r to n ella. P h o to fro m C o n su lta tio n s in F e lin e In tern a l M e d ic in e 3 co u rtesy o f W. B. S a u n d e rs Infection with B a rto n ella species has recently focused the attention of the medical community on these important opportunistic pathogens which are of primary concern to immunocompromised people. The genus B arton ella consists of 11 species, includ- Inside this issu e... Beyond Cat Scratch D isease page 1 Research Briefs page 7 ing those previously classified in the genera R och alim aea and G rah am ella. Due to the broad host range, it is likely that additional species will be identified in the future. Although haemotropic, B a r tonella species are distinct from H aem obarton ella species which were recently found to be more closely related to mycoplasma (Rikihisa and others 1997). This discussion will be limited to B hen selae and B cla rrid g eia e, bacteria that have been frequently cultured from healthy domestic cats and have been associated with a variety of human disease processes. Although B cla rrid g eia e was recently implicated with human infection, B h en sela e is the most frequently identified cause of cat scratch disease and has become an important opportunistic pathogen in immunocompromised individuals (Schwartzman 1992, Kordick and others 1995, Kordick and others 1997a). Veterinary practitioners, cat breeders, cat owners and physicians all share an interest in these recently identified bacteria for which the cat appears to be the primary reservoir. In addition to the concern about possible contact transmission among closely housed cats in catteries, breeders are interested in the potential for transmission via semen, in utero, aerosols, lactogenically or the likelihood of transmission during contact with inanimate objects such as the show table. Veterinarians should be aware of the potential for iatrogenic transmission via blood transfusion, as well as diagnostic methods, treatment options and preventative strategies. We all must be increasingly cognisant of the issues related to public

2 Feline Health Topics 2 health. Cats, subclinically infected with B hen selae and/or B cla rrid g eia e, have been found throughout the United States, England, France, The Netherlands, Israel, Japan and Australia. Human serological data, derived from several other countries, indicates frequent exposure to Bartonella organisms, presumably by way of infected cats. The prevalence of bacteraemia, documented by blood culture, indicates that between 20 per cent and 40 per cent of healthy cats in the United States are infected with B henselae or B cla rrid g eia e (Keohler and others 1994, Chomel and others 1995, Kordick and others 1995). In France, Heller and others (1996) isolated B henselae or B cla rrid g eia e from 50/94 (53 per cent) of stray cats. Thirty-five of the 50 isolates were B henselae, 15/50 were B cla rrid g eia e. Cats may be coinfected with both B henselae and B cla rrid g eia e (Kordick and Breitschwerdt, unpublished). B hen selae and B cla rrid g eia e seem to be highly host-adapted for cats, as no other mammalian reservoir for these organisms has been found. Following infection, cats become asymptomatic carriers. Naturally-exposed cats and those experimentally challenged with infected blood inoculum or infected fleas can experience long periods of bacteraemia interspersed with abacteraemic inter- The ultim ate purp ose of the C ornell Feline H ealth Center is to im prove the health of cats everyw here by d evelop in g m ethods to p revent or cure feline d iseases, and by provid in g continuing education to veterinarians and cat ow ners. A ll contributions are tax-deductible. D ir e c t o r : Jam es R. Richards, D.V.M. A d m in is t r a t o r : Iva H eim S e c re t a rie s : G w en d o ly n M.Frost K athleen M. M ospan P am ela E. Sackett Sheryl A. Thom as 1997 b y Cornell U niversity on behalf of the C ornell Feline H ealth Center, C ollege of Veterinary M edicine, Ithaca, N Y Phone: (607) Fax: (607) All rights reserved. Perm ission to reprint selected portions m ust be obtained in writing. Cornell U niversity is an equal opportunity, affirmative action educator and em ployer. Printed on recycled paper. vals. No predictive cycle of bacteraemia has been determined (Fig 1). We have documented bacteraemia for periods of up to 21 months in naturally-infected cats and for up to 19 months in experimentallyinfected cats individually housed in an ectoparasitefree environment (Kordick and others 1997). Based upon our repeated inability to culture the organism from blood, some naturally-exposed cats appear to spontaneously eliminate Bartonella infection, although latent infection which is below the level of detection by blood culture is possible. In contrast, cats experimentally-infected with laboratory-cultivated bartonella became abacteraemic after only two to three months of infection (Regnery and others 1996, Abbott and others 1997), presumably associated with the phenomenon of attenuated virulence of cultivated bacteria. Regardless of the mechanism, route of administration and source of infectious inocula must be considered when comparing the outcomes of experimental infection studies. When results from blood culture studies and serosurveys are reviewed, incidence of Bartonella infection appears to correlate with temperate regions in which flea infestation is common (Baneth and others 1995, Jameson and others 1995). These observations, in addition to the presumption that all B arto n ella species utilise arthropod vectors for dissemination to other hosts, led to a recent survey that verified transmission of B hen selae by Ctenocephcilides fe lis, the cat flea. However, the actual route of transmission remains unclear; flea regurgitation, selfinoculation with infectious flea faeces, or ingestion of infected fleas are all considered potential means by which infection could be transferred between fleas and cats. C fe lis is prevalent in the United Kingdom and throughout much of the world. In view of the fact that nine day-old flea faeces contain viable Bartonella organisms (Higgins and others 1996), flea faeces may play an important role in the transmission of B hen selae and presumably B cla rrid g eia e between cats and people. Either receiving infectious inoculum through a scratch from a claw containing flea faeces or direct contamination of an open wound

3 3 with Bartonella-infected flea faeces in the environment could potentially result in transmission. Based upon current research, cats may serve as a biological and a mechanical vector for the transmission of Bartonella to people. Tick exposure has been implicated in a few cases of B hen selae infection in people; however, definitive studies assessing the potential of ticks to carry and transmit these bacteria have not been reported. Clearly, rigorous flea and tick control will not only decrease the opportunity for Bartonella transmission but will also provide other health benefits to cats. Collation of retrospective data from numerous cases of Bartonella infection involving people most frequently indicates a temporally associated scratch from a cat. Cat bites, kissing cats, and contact with cat urine have been infrequently associated with human infection. However, since we have observed B hen selae within feline erythrocytes (Kordick and Breitschwerdt 1995) stomatitis or haematuria could conceivably result in infectious saliva or urine. B a r tonella hen selae DNA has been detected in the saliva of a bacteremic cat using a species specific polymerase chain reaction (PCR) assay (Demers and others 1995). Although not detected in urine derived from bacteraemic cats, B hen selae and B cla rrid g eia e could be cultured from experimentally-inoculated cat urine after 48 hours of incubation (Kordick and Breitschwerdt, unpublished). Only one research group has examined the possibility of vertical transmission from queen to kittens. Abbott and others (1997) identified both bacteraemic and abacteraemic kittens derived from an experimentally-infected bacteraemic queen, but the investigators were unable to rule out vectorial transmission since fleas were present on the kittens. The same group found that four kittens from another experimentally-infected queen were seroreactive but culture negative and became seronegative within six weeks of birth, leading one to suspect that maternal rather than filial antibodies were detected. To our knowledge, evidence for sexually transmitted Bartonella infection between toms and queens has only been examined in one breeding pair (Abbott and others 1997). A naturally-infected, chronically bacteraemic queen was housed with an SPF tom for six months. During this time the status of bacteraemia with Bartonella fluctuated in the queen, however, despite sexual contact between the cats, blood cultures performed on the tom were continuously negative and seroconversion was not evidenced. The converse situation, placing an infected tom with a naive queen has not been explored, nor has seminal fluid been examined for the presence of Bartonella. The utility of testing cats for Bartonella infection before breeding appears to be limited to those cats that might be concurrently exposed to fleas. During an investigation into the prevalence and persistence of Bartonella bacteraemia in cats, we observed several households containing bacteraemic cats living with abacteraemic, seronegative cats. Cats were continuously exposed to identical environmental factors and shared sleeping areas, food dishes and litter boxes, yet transfer of infection was not detected. In most cases, both fleas and ticks were at least occasionally present. The inability to transfer infection could be due to immunity from previous exposure, innate resistance to Bartonella infection, or inefficient transmission. During a controlled study, Chomel and others (1996) assessed the infection status of Bartonellanaive kittens housed with bacteraemic kittens for 21 months. Casual contact between bacteraemic and abacteraemic cats did not result in transmission of Bartonella. Based upon these observations, we feel it is unlikely that cats in the showring would be infected by fomites or close cage contact. Similarly, if measures to control ectoparasite populations are employed, transmission among cats in catteries should not easily occur. Currently, there is no evidence that retroviralinfected cats have an increased incidence of opportu- (continued on next page)

4 Feline Health Topics 4 nistic infection with Bartonella species (Chomel and others 1995, Kordick and Breitschwerdt, unpublished). These findings support the hypothesis that unlike the transmission of FIV infection, cat fighting is probably not a significant mode of cat-to-cat transmission of Bartonella. When compared to healthy cat populations, serosurveys have not revealed an increased prevalence of bartonella antibodies in retroviral-infected cats, however, use of this parameter to assess exposure may be negatively biased given the immune-compromised condition of the subjects. Functional B- and T-cell alterations may be responsible for lower than expected numbers of seroreactive cats in this health category or coinfection may result in exaggerated disease. Clearly, the pathogenic features of coinfection with Bartonella and retroviruses in cats need to be addressed in future studies, since concurrent infection with HIV seems to enhance the morbidity associated with Bartonella infections in people. The pathogenic potential of Bartonella species in cats appears to be low, however, future studies may reveal that strain virulence is responsible for episodes of clinical disease. Following experimental challenge with infected blood or bacterial cultures, brief febrile episodes are sometimes observed. Aside from transient, mild anaemia, detected in some experimentally-infected cats shortly after challenge and mild eosinophilia in chronically-infected cats, no other significant haematological or biochemical abnormalities have been observed and these irregularities have not been notable in naturally-infected cats. Abbott and others (1997) documented normal CD4 and CDS lymphocyte counts in cats experimentallyinfected with laboratory-cultivated B henselae. Although unable to substantiate causation due to Bartonella, we have observed self-limiting neurological deficits consisting of temporary disorientation and postural reaction deficits in two cats experimentally-infected and one cat naturally-infected with B henselae. These signs were transitory and lasted one to two days without recurrence during several months of follow-up examination. Cataractous lens lesions were observed in some experimentally-infected SPF cats that were chronically bacteremic with blood containing B henselae or B clarridgeiae (Kordick and Breitschwerdt, unpublished). Uveitis was not observed, however, only four ophthalmic examinations were performed during a 19 month evaluation period. Non-specific inflammatory lesions have been observed during post mortem examination of cats infected with Bartonella. Neutrophilic infiltrates in the liver and spleen, multifocal myocarditis, focal pyogranulomatous nephritis and hepatic abscesses were described in acutely infected cats following D ays P ost-inoculatio n D ays P ost-inoculation Graphs depicting Bartonella colony and seroreactivity in cats experimentally inoculated with Bartonella infected cat blood. Courtesy of W. B. Saunders

5 5 experimental infection with laboratory cultivated bacteria (Guptill and others 1997). Multifocal lymphocytic cholangitis or pericholangitis and focal accumulations of lymphocytes and plasma cells in the myocardium were present in tissues obtained from chronically bacteraemic cats that received infected blood as inoculum (Kordick and Breitschwerdt, unpublished). Considering the high frequency and long duration of Bartonella infection in cats, the role of these organisms in chronic disease processes deserves additional study. Unlike haemobartonellosis, examination of peripheral blood films does not provide an accurate means to identify bacteraemic cats. Blood culture is the preferred method for establishing a diagnosis of Bartonella bacteraemia. Blood isolation of Bartonella species from cats can be accomplished using the pediatric Isolator system (Oxoid, UK). Approximately 1.5ml of aseptically obtained blood is placed in the Isolator tube, which if necessary may remain at room temperature for up to 24 hours prior to processing. Isolator tubes contain a chemical mixture that facilitates the lysing of cells which enhances recovery of Bartonella. Alternatively, blood can be drawn in the presence of EDTA and frozen to lyse the cells. Thawed samples should be streaked onto chocolate or blood agar plates and incubated at 35 C with 5% CO,. Although growth of Bartonella can often be detected within 10 to 14 days, some strains may require several weeks of incubation. Since we have observed apparently relapsing periods of bacteraemia in both naturally-and experimentally-infected cats, repeat cultures of negative animals performed at later timepoints may reveal previously undiagnosed infection. Serological testing to detect Bartonella-specific immunoglobulins by indirect immunofluorescent antibody (IFA ) or by enzym e-linked immunosorbent assay (ELISA) methods is available for both cats and people. Due to several immunoreactive surface antigens shared by the various species, a species-specific diagnosis is not yet possible serologically. Immunoglobulin kinetics remain unclear. However, Chomel and others (1995) explored the relationship between IFA serology results and blood culture findings. In their study serologic testing had a positive predictive value of 46.4% and negative predictive value of 89.7%. Although some seronegative cats are bacteremic, given the high negative predictive value we would recommend seronegative cats as safe for immunocompromised owners. Since Bartonella infection is easily established in cats following blood transfusion, a substantial concern for iatrogenic transmission exists. Although healthy cats can presumably tolerate varying levels of Bartonella bacteraemia without discernible deleterious effects, the subpopulation of cats receiving therapeutic transfusions are in a tenuous state of health. Burdening the organ systems of debilitated animals with Bartonella may further alter fragile physiological conditions potentially resulting in unexplained deterioration or death. Therefore, we urge screening prospective blood donors by blood culture and serological testing. Cats that are culture-positive or culture-negative with a high antibody titre are not advocated for use as donors. The optimal antimicrobial treatment regimen for eradication of Bartonella infections in cats is unknown. Enrofloxacin (22.7 mg q 12h PO), doxycycline (25 mg q 12h PO), and amoxycillin ( mg q 12h PO) have been reported effective in some cases (Kordick and others 1997b; Regnery and others 1996, Green and others 1996). In these studies, the duration of treatment ranged from one to four weeks. Several factors, including Bartonella species, strain or level of bacteremia may affect the success of treatment. Given the occult nature of feline Bartonella infections, relying on a clinical response to treatment is not possible. Follow-up blood cultures should be performed two to four weeks after completion of antimicrobial treatment and periodically thereafter to monitor bacteraemia status. Conflicting reports exist concerning the potential for reinfection. (continued on next page)

6 Feline Health Topics 6 Despite concerns about the utility of treatment if cats can become reinfected or concerns related to the possible development of drug resistant strains of Bartonella or other bacteria if treatment is initiated without definitive diagnosis of infection, treatment of an infected cat owned by an immunocompromised person is advised. In order to decrease the opportunity for re-exposure following treatment, cats should be kept indoors, away from other cats and appropriate flea and tick control implemented. Although several investigators are pursuing the development of a vaccine, no product is commercially available for cats or people. Since human infection with B henselae is most frequently incidental when scratched, common sense should be exercised with regard to rough play and scratch or bite wounds should be thoroughly cleansed. Obviously, people with decreased immune function are at higher risk for opportunistic infection if exposed to Bartonella species. As the psychological benefits of pet ownership are extensive, removal or euthanasia of an infected animal are not recommended. Although the typical presentation of a cat scratch disease in immunocompetent people is characterised by regional lymphadenopathy accompanied by fatigue and occasionally fever, hepatosplenic involvement, ophthalmic disease and encephalopathy due to Bartonella infection are being increasingly recognised as atypical manifestations of classical CSD. Among immunocompromised patients, bacillary angiomatosis pulses, bacillary peliosis, endocarditis, osteomyelitis and AIDS-related dementia are frequent consequences of Bartonella infection. Severity of disease in people is highly variable but usually correlates with immune status. The occupational risk for exposure to Bartonella was examined by Noah and others (1997) in a group of veterinarians attending a regional meeting. The seroreacti vity of veterinarians to Bartonella species was 8.1% compared with 6.8% of non-veterinarian attendees. Although results of their study were not suggestive of an increased risk, several confounding factors were proposed. A more realistic comparison might be with a study by Zangwill and others (1993), which reported a 3.6% seroreactivity rate in a blood donor control population. In a study from Japan (Arashima and others 1994), CSD was reported in 19 of 102 veterinarians and four of 45 veterinary technicians as compared to three of 555 people in the general population. Despite the evolving implications of Bartonella infection in cats, prudence should be exercised when considering the fate of an infected cat. Bartonella infection in cats does not appear to be easily transmitted from cat to cat except by an arthropod vector or as a result of blood transfusion. Transmission to human beings is presumably highly inefficient, since rarely does an infected cat cause multiple cases of CSD. Despite the substantive amount of information that is accumulating about acute and chronic Bartonella infection in cats, much remains to be learned regarding transmission, pathogenic potential and clinical manifestations in cats and people.b References Abbott RC, Chomel BB, Kasten RW, Floyd-H aw kins KA, Kikuchi Y, Koehler JE, Pedersen NC (1997) Experim ental and natural infection with Bartonella henselae in domestic cats. Comparative Immunology and Microbiology o f Infectious Diseases 20, pp A rashim a Y, Kum asaka K, Kawano K, Ikeda T, M unem ura T, Asano R, Hokari S, Takagi A (1994) A study on wounds caused by cats as basic materials of cat scratch disease. Kansenshogaku Zasshi 68, pp Baneth G, Kordick DL, Hegarty BC, Breitschwerdt EB (1995) Com parative seroreactivity to Bartonella henselae and Bartonella quintana among cats from Israel and N orth Carolina. Veterinary M icrobiology 50, pp Chomel BB, Abbott RC, Kasten RW, Floyd-Hawkins KA, Kass PH, Glaser CA, Pedersen NC. Koehler JE (1995) Bartonella henselae prevalence in domestic cats in California: risk factors and association between bacterem ia and antibody titers. Journal o f Clinical M icrobiology 34, pp Chom el B, Kasten RW, Floyd-H aw kins K, Chi B, Yam am oto K, Roberts- Wilson J, Gurfield AN, Abbott RC, Pedersen NC, Koehler JE (1996) Experim ental transm ission of Bartonella henselae by the cat flea. Journal o f Clinical M icrobiology 34, pp Dem ers DM, Bass JW, V incent JM, Person DA, N oyes DK, Staege CM,

7 7 Sam laska CP, Lockwood NH, Regnery RL, Anderson BE (1995) Catscratch disease in Hawaii: etiology and seroepidemiology. Journal o f Pediatrics 127, pp Greene CE, M cderm ott M, Jam eson PH, Atkins CL, M arks AM (1996) Bartonella henselae infection in cats: evaluation during primary infection, treatm ent and rechallenge infection. Journal o f Clinical M icrobiology 34, pp Guptill L, Slater L, Wu CC, Lin T, Glickm an L, W elch D, HogenEsch H (1997) Experimental infection of young SPF cats with Bartonella henselae. Journal o f Infectious Diseases 176, pp H eller R, Artois M, Xem ar V, DeBriel D, G ehin H, Jaulhac B, M onteil H, Piem ont Y (1996) Epidem iology o f Bartonella clarridgeiae, a new species of im portance in cats. Presented at the 1st International Conference on Emerging Zoonoses, Jerusalem, Israel, November Higgins JA, Radulovic S, Jaworski DC, Azad AF (1996) Acquisition of the cat scratch disease agent Bartonella henselae by cat fleas (Siphonaptera: Pulicidae). Journal o f M edical Entomology 331, pp Jam eson P, Greene C, Regnery R, Dryden M, M arks A, Brown J, Cooper J, Glaus B, Greene R (1995) Seroprevalence of Rochalimaea henselae in pet cats throughout regions o f N orth America. Journal o f Infectious Disease 112, pp Koehler JE, Glaser CA, Tappero JW (1994) Rochalimaea henselae infection: a new zoonosis with the dom estic cat as reservoir. Journal o f the American Medical Association 271, pp Kordick DL, Breitschwerdt EB (1995) Intraerythrocytic presence of Bartonella henselae. Journal o f Clinical M icrobiology 33, pp Kordick DL, W ilson KH, Sexton DJ. Hadfield TL, Berkhoff HA, Breitschwerdt EB (1995) Prolonged Bartonella bacteraemia in cats associated w ith cat scratch disease patients. Journal o f Clinical M icrobiology 33, pp Kordick DL, Breitschwerdt EB (1997) Relapsing bacterem ia following blood transm ission o f Bartonella henselae to cats. American Journal o f Veterinary Research 58, pp Kordick DL, Hilyard EJ, Hadfield TL, Wilson KH, Steigerwalt AG, Brenner DJ, Breitschwerdt EB (1997a) Bartonella clarridgeiae, a newly recognized zoonotic pathogen causing inoculation papule, fever and lym phadenopathy (cat scratch disease). Journal o f Clinical M icrobiology 35, pp Kordick DL, Papich MG, Breitschwerdt EB (1997b) Efficacy of enrofloxacin or doxycycline for treatm ent of Bartonella henselae or Bartonella clarridgeiae infection in cats. Antimicrobial Agents and Chemotherapy, in press Noah DL, K ram er CM, Verbsky MP, Rooney JA, Smith KA, Childs JE (1997) Survey of veterinary professionals and other veterinary conference attendees for antibodies to Bartonella henselae and B quintata. Journal o f the American Veterinary Medical Association 210, pp Regnery RL, Rooney JA, Johnson AM, Nesby SL. M anzewitsch P, Beaver K, Olsen JG (1996) Experim entally induced Bartonella henselae infections followed by challenge exposure and antimicrobial therapy in cats. American Journal o f Veterinary Research 57, pp Rikihisa Y. Kawahara M, W en B, Kociba G, Fuerst P, Kawamori F, Suto C. Shibata S, Futohashi M (1997) W estern im m unoblot analysis of Haemobartonella muris and com parison of 16S rrna gene sequence of H muris, H felis and eperythrozoon suis. Journal o f Clinical M icrobiology 35, pp Schwartem an WA (1992) Infections due to Rochalimaea: the expanding clinical spectrum. Clinical Infectious Diseases 15, pp Zangwill KM, Ham ilton DH, Perkins BA, Regnery RL, Plikaytis BD, Hadler JL. Cartter ML, W enger JD (1993) Cat scratch disease in Connect! cut: epidem iology, risk factors and evaluation o f a new diagnostic test. New England Journal o f Medicine 329, pp 8-13 Edward Breitschwerdt is a Professor o f Medicine and Infectious Disease, College o f Veterinary Medicine at North Carolina State University, Raleigh, N.C. This article was reprinted with permission from the Journal o f the Feline Advisory Bureau Newsletter 35:86-89, Research Briefs E sophagostom y Tubes as a M ethod of N u tritional M an agem en t in C ats - A R etrospective Study (Authors: P.B. Levine, L.J. Smallwood, and J.L. Buback) The use of esophagostomy tubes in 60 feline patients was evaluated retrospectively. Indications for tube replacement, complications associated with placement and management, duration of treatment and change in patient body weight were evaluated. Hepatic disease was the most common indication for tube placement. A minor complication associated with the surgical technique for tube placement was observed in three cases. Inflammation or infection of the tube site, swelling of the head, or vomition of the tube were observed complications during management of 19 cases. Vomiting occurred and was a complicating factor in nine cases. The average duration of tube placement was 23 days, and most patients maintained or gained weight while (continued on next page)

8 Feline Health Topics 8 being fed through their esophagostomy tubes. (Resource: J Am er Anim Hosp Assn 33: ) Duration of Im m unity in Cats Vaccinated with an Inactivated Feline Panleukopenia, H erpesvirus, and C alicivirus Vaccine (Authors: F.W. Scott and C. Geissinger) Duration of immunity, based on antibody titers, was evaluated in a group of specific pathogen free cats vaccinated as kittens with an inactivated triple vaccine (feline panleukopenia, feline herpesvirus, and feline calicivirus). Vaccination of 15 kittens at 8 and 12 weeks of age with two doses of this inactivated vaccine resulted in high antibody titers against FPV for at least 6 years. FHV and FCV antibody titers were low positive after vaccination, but gradually declined over the 6 years. All vaccinated cats had positive FHV antibody titers for at least 3 years after vaccination, and positive FCV antibody titers for at least 4 years. Negative FHV titers were first determined in some vaccinated cats at 4 years after vaccination, and at 5 years for FCV. All 17 unvaccinated contact control cats had negative antibody titers against the three viruses throughout the 6-year study. (Resource: Feline Pract 25: 12) C o m p a ra tiv e G en e-m a p p in g in T he Dom estic Cat (Authors: S.J. Obrien, S.J. Cevario, J.S. Martenson, et al.) The genetic map of the domestic cat has been developed as a model for studying both feline analogues of human genetic disease and comparative genome organization of mammals. We present here the results of syntenic mapping of 35 genes based upon concordant occurrence of feline gene homologues with feline chromosomes and previously mapped loci in a panel of 41 rodent x cat somatic cell hybrids. These somatic cell hybrids retain rodent chromosomes and segregate feline chromosomes, but in different combinations in each hybrid cell line. Thirty-three of the 35 new locus assignm ents extend and reaffirm conserved chromosome segment homologies between the human and cat genom es previously recognized by comparative mapping and zoo-fish. These results demonstrate the extensive syntenic conservation between the human and feline genomes and extend the feline gene map to include 105 assigned loci. (Resource: J Hered 88: ) Photocopies of the above articles are available by making your request via mail to the Flower- Sprecher Library, College of Veterinary Medicine, Ithaca, NY 14853; or by telephone at (607) ; or by fax at (607) V J x C o rn ell F eline H ea lth C e n te r C o rn ell U n iv e r sity C o lle g e o f V e te r in a r y M ed icin e Ithaca, N e w Y ork