Cat Scratch Disease: Has Identification of The Causative Agent Been Solved?

Cat Scratch Disease (CSD) was first recognized more than 60 years ago. The majority of human cases, most frequently affecting children and young adults, have a history of recent traumatic exposure to cats, including bites and scratches. While cats do not appear to be clinically affected,   humans,   immunocompromised  or immunocompetent, tend to show a variety of clinical manifestations, including systemic and cutaneous angiomatosis, prolonged or relapsing fever with bacteremia, and central nervous system disorders. Typically, a papule develops within three to five days after feline contact at the site of the injury. Within ten to fourteen days, the lymph nodes of the draining site proximal to the lesion become markedly enlarged and inflamed. The patients may also exhibit fever, malaise, weight loss, myalgia, headache, conjunctivitis, skin eruptions and arthralgia. A substantial proportion of the patients develop suppurative lymphadenitis, necessitating the drainage of the lymph nodes. Rarely, although reported in the literature, encephalitis and neuroretinitis occurs. The disease tends to be self-limiting, but the lymphadenitis may persist for several months. Surgical excision of the affected lymph nodes is usually not required and treatment with aminoglycosides and 3rd generation cephalosporins(cefotaxime) may be helpful. In the United States the incidence of CSD has been estimated at 9.3 cases per 100,000 population each year.

Various viral, bacterial and chlamydial agents have been proposed to be the etiological agent of CSD and diagnosis has been extremely difficult until recent years. In the past, the diagnosis has depended upon several criteria: a compatible clinical picture, primarily with unilateral regional lymphadenitis; documentation of exposure through feline contact or wounds; papule formation at the site of injury; the exclusion of other common etiologies of lymphadenopathies; characteristic histopathologic lesions including microabscesses and granulomas from lymph node biopsies; and a positive reaction to the CSD skin test. This skin test relies upon the intradermal inoculation of diluted and autoclaved pus derived from patients known to have the disease.

In 1983, lymph node biopsies prepared with Warthin-Stany silver stain enabled visualization of pleomorphic organisms. In 1988, a specific bacillus was cultured from the lymph nodes of CSD patients. This motile, gram-negative rod was later named Afipiafelis in honor of the Armed Forces Institute of Pathology (AFIP), where most of the work was performed. This is the organism currently reported to be the etiologic agent of CSD in Veterinary Clinics of North America, Small Animal Practice. Unfortunately, the demonstration and isolation of this potential causative agent from CSD lesions has been inconsistent.  Information then emerged suggesting that Rochalimaeahenselae was a more common cause and isolate from lymph nodes of patients. Like A. felis,R. henselae is a Proteobacteria(alpha-2 subclass) and is visualized with Warthin-Stany stain. However, this bacterium belongs to the Rickettsial order and is not closely related to A. felis. When an indirect fluorescent-antibody (IFA) test for R. henselae was used, 88% of patients with suspected CSD had markedly elevated serum tilers of the respective antibody. Polymerase chain reaction (PCR) amplification of DNA from five CSD skin test antigen preparations had yielded sequences   which   were   consistent   with Rochalimaeasp., not withA felis. In 1994, Minet al. applied an immunocytochemical labeling technique to lymph node biopsies from patients with the clinical diagnosis of CSD to assess whether the organisms demonstrated by the Warthin-Stany stain might be R. henselae. Their results confirmed that the bacilli detected with stain were also identified by antibodies to R. henselae.

Rochalimaea henselae has been renamed Bartonella henselae, and as of last year, definitive identification of Bartonella organisms to the species level had been done with time-consuming molecular biologic techniques. Therefore in 1995, the development of the diagnostic tool called repetitive element PCR (re-PCR) allowed it to become the most novel and rapid method now used to distinguish between the Bartonella species by genonuc DNA fingerprinting.

While the causative agent has now been specifically identified and diagnosed, additional aspects of CSD must now be addressed. Although fleas or ticks on the cat have been speculated to play a role in cat-to-cat infection and transmission, the exact pathogenetic mechanism for cats to become infected with B. henselae and transmit infection to people is unknown. With further research and experimentation, a vaccination for cats or humans may be available for preventing further outbreaks of this disease.

- by F.ClaireGaskell, Class of 1997

- edited by Tsang Long Lin,DVM,PhD

References:

Lappin, M.R. Feline Zoonotic Diseases. Veterinary Clinics of North America, Small Animal Practice. 1993; 23:1, 57-78.

Schellekens, J.R  Cat Scratch Disease. Veterinary Quarterly. April 1994; 16 Suppi:!, 11S-12S.

Zangwill,K.M., Hamilton,D.H.,Perkins, B.A., Regnery, RL.,Plikaytis, B.D.,Hadler,J.L., Cartter, M.L.,Wenger,J.D. Cat Scratch Disease in Connecticut - Epidemiology, Risk Factors, and Evaluation of a New Diagnostic Test. The New England Journal of Medicine. July 1993; 6:3, 8-13.

Margileth, A.M. Cat Scratch Diseae - From Feline Affection to Human Infection. The New England Journal of Medicine. July 1993; 329:1, 53-54.

Margileth, A.M. Cat Scratch Disease: No Longer a Diagnostic Dilemma. Seminars in Veterinary Medicine and Surgery (Small Animal). August lf991; 6:3, 199-202.

Min,K.W., Reed,J.A., Welch,D.F., Slater, L.N.Morphologically Variable Bacilli of Cat Scratch    Disease    are    identified    by Immunocytochemical Labeling with Antibodies to Rochalimaea henselae. American Journal of Clinical Pathology. 1994; 101:5,607-610.

Rodriguez-Barradas, M.C.,Hamill, R.J., Houston,E.D.,Georghiou, P.R, Clarridge, J.E., Regnery,   RL.,   Koehler,   J.E.   Genomic Fingerprinting of Bartonella Species by Repetitive Element PCR for Distinguishing Species and Isolates. Journal of Clinical Microbiology. May 1995; 33:5, 1089-1093.