Vol. 17, No. 22
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Monday, June 1, 1998
A. Provided by Marguerite-Hawkins, Epidemiology and Disease Control Program, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene.
From May 21, 1998 through May 27, 1998, 5 outbreaks have been reported to the Maryland Department of Health and Mental Hygiene. They are as follows: 3 food-related gastroenteritis, 1 presumed viral gastroenteritis and 1 outbreak of hemolysis in dialysis patients.
B. The Johns Hopkins Hospital. Information provided by Dr. Edward Weir, Dept. of Pathology.
Patient History: The patient is a 4 year old otherwise healthy female who presented to her pediatrician with a four day history of fever, headache, and malaise. Physical examination was notable for a temperature of 38.2oC and a 1.2 cm pustule on the right forearm. In addition, the patient had mildly tender lymphadenopathy of the right cervical and axillary regions. A lymph node biopsy showed follicular hyperplasia and central, stellate necrosis surrounded by a layer of palisading histiocytes. A Warthin-Starry silver stain demonstrated pleomorphic extracellular bacillary organisms within the necrotic debris. The child's mother reports a history of a cat bite at a neighbor's house approximately two weeks prior to presentation.
Organism: The clinical history combined with the histopathologic findings in the above case are consistent with a diagnosis of cat scratch disease (CSD). The organism responsible for CSD is Bartonella henselae. Reorganization of the Bartonella genus, based on 16S rRNA analysis, has resulted in the transfer of the Rochalimaea organisms into the Bartonella genus. Bartonella now consists of eight species, four of which are pathogenic in man: B. bacilliformis, B. quintana, B. henselae, and B. elizabethae. The bacteria are small (0.5 x 1.0um), gram-negative, aerobic bacilli with fastidious growth requirements. Although the organisms can grow on enriched blood agar, prolonged incubation (1 to 6 wks.) in a humid, 37oC atmosphere supplemented with CO2 is required for their initial recovery. Motility varies with species; B. bacilliformis possesses polar flagella whereas B. henselae and B. quintana display twitching motility due to the presence of pili. Members of the Bartonella genus are found in a variety of animal reservoirs, typically without the presence of disease, and are often transmitted via insect vectors.
Clinical Disease: CSD is a benign, self-limited infection most frequently (80%) diagnosed in children. The infection typically (90% of cases) begins as a cutaneous papule or pustule that usually develops within a week of contact with an animal, usually a cat and occasionally a dog. The organism is transmitted via an animal bite, scratch, or possible contact with animal fleas. Regional lymphadenopathy develops in 1 to 7 weeks. About one third of patients have fever, and about one sixth develop suppuration of the lymph nodes. Lymph node histology consists of a mixture of nonspecific inflammatory reactions including granulomas and stellate necrosis. Bacilli may be demonstrable by Warthin-Starry staining and less effectively by tissue Gram staining. Atypical CSD usually presents as Parinaud's oculoglandular syndrome characterized by granulomatous conjunctivitis followed by preauricular and cervical lymphadenopathy, manifestations of primary ocular inoculation. Rarely, CSD will progress to involve the central nervous system. Children who develop encephalitis, encephalopathy, or radiculitis usually experience sudden onset of neurologic symptoms, often accompanied by fever. This generally occurs within one to six weeks of the onset of adenopathy. The spinal fluid is typically normal, but may show minimal pleocytosis or elevation of protein. In spite of possible CNS involvement, spontaneous resolution of the disease usually occurs in 3 to 6 months.
Laboratory Diagnosis: Methods of direct examination of the organism, including Warthin-Starry silver staining and immunohistochemical labeling techniques applied to fixed tissue, carry poor specificity and only moderate sensitivity. However, if CSD is clinically suspected, culture protocols designed to yield slowly growing organisms may result in recovery of Bartonella species. For example, B. henselae has been successfully isolated from homogenized lymph node and skin specimens by direct plating on freshly prepared heart infusion agar containing 10% defibrinated rabbit or horse blood. Other necessary conditions include a humid atmosphere and 35 to 37oC incubation for 3 to 4 weeks. Colonies of B. henselae are usually irregular, raised, white, rough, and dry in appearance. The Gram stain of a colony reveals small, gram-negative, slightly curved rods. In a wet mount, there is twitching motility of cells. These features plus a lengthy incubation and negative catalase and oxidase reactions are sufficient for presumptive identification of B. henselae. More definitive diagnosis is based on the characteristic presentation and serologic evidence of a recent infection. Persons with CSD develop IgM antibodies that can be measured early in the course of disease and IgG antibodies whose levels rise somewhat later and then decline over time. Human antibody responses to Bartonella species have been measured by a variety of techniques. Results of immunofluorescence tests and EIA for B. henselae have demonstrated a good correlation with each other at high levels of sensitivity and specificity. Skin testing for CSD antigens (prepared from pus of suppurative lymph nodes), which is not commercially available or standardized, has fallen out of favor because it carries the potential risk of transmitting occult infection.
Treatment: Antimicrobial susceptibility testing can be performed by incorporation of antimicrobial agents into either blood or chocolate agars or into Haemophilus test medium by using a broth microdilution technique. Generally, isolates of B. henselae are susceptible in vitro to most antibacterial agents tested, including beta-lactams, tetracyclines, macrolides, aminoglycosides, vancomycin, rifampin, chloramphenicol, and co-trimoxazole, but resistant to nalidixic acid. Growing clinical experience with B. henselae in the setting of HIV infection suggests that therapy with beta-lactams may be suboptimal and supports the use of tetracyclines, erythromycin, or chloramphenicol.
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