Objective. —To determine the frequency and temporal changes in application of seven accepted methodological standards for the evaluation of diagnostic tests. Data Sources. —A search of the MEDLINE database yielded 1302 articles about diagnostic test studies, during a 16-year secular interval, 1978 through 1993, in four prominent general medical journals. Study Selection. —In the 112 eligible studies, the test was intended for clinical use, indexes of accuracy (sensitivity and specificity or likelihood ratios) were provided, and more than 10 patients were enrolled. Data Extraction. —Although each study was critically reviewed by one primary observer, a subset was independently evaluated for interrater consistency. Data Synthesis. —The percentage of studies that fulfilled criteria for each of the seven methodological standards are as follows: (1) specify spectrum of evaluated patients, 27%; (2) report test indexes for clinical subgroups, 8%; (3) avoid workup bias, 46%; (4) avoid review bias, 38%; (5) provide numerical precision for test indexes, 11%; (6) report frequency and management of indeterminate results when calculating test indexes, 22%; and (7) specify test reproducibility, 23%. Secular increases were found for six of the seven standards in ranges of use from 14% to 31% during 1978-1981 to 1990-1993. Nevertheless, only one standard, avoidance of workup bias, was fulfilled by more than 50% of studies in the most recent secular interval. Conclusions. —These results indicate that most diagnostic tests are still inadequately appraised. The routine demand for methodological standards could raise the quality of diagnostic test information, and the careful predissemination evaluation of diagnostic tests could eliminate useless tests before they receive widespread application. (JAMA. 1995;274:645-651)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=389496&pdfFileName=jama_274_8_042.pdf

Use of methodological standards in diagnostic test research. Getting better but still not good

Bartonella henselae is an emerging bacterial pathogen, causing cat scratch disease and bacillary angiomatosis. Cats bacteremic with B. henselae constitute a large reservoir from which humans become infected. Prevention of human infection depends on elucidation of the natural history and means of feline infection. We studied 47 cattery cats in a private home for 12 months to determine the longitudinal prevalence of B. henselae bacteremia, the prevalence of B. henselae in the fleas infesting these cats, and whether B. henselae is transmitted experimentally to cats via fleas. Vector-mediated transmission of B.henselae isolates was evaluated by removing fleas from the naturally bacteremic, flea-infested cattery cats and transferring these fleas to specific-pathogen-free (SPF) kittens housed in a controlled, arthropod-free University Animal Facility. B. henselae bacteremia was detected in 89% of the 47 naturally infected cattery cats. A total of 132 fleas were removed from cats whose blood was simultaneously cultured during different seasons and were tested individually for the presence of B. henselae DNA by PCR. B. henselae DNA was detected in 34% of 132 fleas, with seasonal variation, but without an association between the presence or the level of bacteremia in the corresponding cat. Cat fleas removed from bacteremic cattery cats transmitted B. henselae to five SPF kittens in two separate experiments; however, control SPF kittens housed with highly bacteremic kittens in the absence of fleas did not become infected. These data demonstrate that the cat flea readily transmits B. henselae to cats. Control of feline infestation with this arthropod vector may provide an important strategy for the prevention of infection of both humans and cats.

Experimental transmission of Bartonella henselae by the cat flea.

Members of the genus Bartonella (formerly Rochalimaea) were virtually unknown to modern-day clinicians and microbiologists until they were associated with opportunistic infections in AIDS patients about 6 years ago. Since that time, Bartonella species have been associated with cat scratch disease, bacillary angiomatosis, and a variety of other disease syndromes. Clinical presentation of infection with Bartonella ranges from a relatively mild lymphadenopathy with few other symptoms, seen in cat scratch disease, to life-threatening systemic disease in the immunocompromised patient. In some individuals, infection manifests as lesions that exhibit proliferation of endothelial cells and neovascularization, a pathogenic process unique to this genus of bacteria. As the spectrum of disease attributed to Bartonella is further defined, the need for reliable laboratory methods to diagnose infections caused by these unique organisms also increases. A brief summary of the clinical presentations associated with Bartonella infections is presented, and the current status of laboratory diagnosis and identification of these organisms is reviewed.

Bartonella spp. as emerging human pathogens.

Background Although cat scratch disease is commonly diagnosed in patients who have unexplained regional lymphadenopathy after encounters with cats, its epidemiology and the risk factors for disease are not clearly defined, and there is no generally accepted diagnostic test. Methods We conducted a physician survey to identify cases of cat scratch disease occurring over a 13-month period in cat owners in Connecticut. We interviewed both the patients (or their parents) and controls matched for age who owned cats. Serum from the patients was tested for antibodies to Rochalimaea henselae with a new, indirect fluorescent-antibody test. Results We identified 60 patients with cat scratch disease and 56 age-matched, cat-owning control subjects. Patients were more likely than controls to have at least one pet kitten 12 months old or younger (odds ratio, 15), to have been scratched or bitten by a kitten (odds ratio, 27), and to have had at least one kitten with fleas (odds ratio, 29). A conditional logistic-regressi...

https://www.nejm.org/doi/pdf/10.1056/NEJM199307013290102

Cat Scratch Disease in Connecticut -- Epidemiology, Risk Factors, and Evaluation of a New Diagnostic Test

Objective. —To determine the reservoir and vector(s) forRochalimaea henselae, a causative agent of bacillary angiomatosis (BA) and cat scratch disease, and to estimate the percentage of domestic cats withR henselaebacteremia in the Greater San Francisco Bay Region of Northern California. Design. —Hospital-based survey of patients diagnosed with BA who also had significant exposure to at least one pet cat, as well as a convenience sampling of pet or impounded cats for prevalence ofRochalimaeabacteremia. Setting. —Community and university hospitals and clinics; veterinary clinics treating privately owned or impounded cats. Patients. —Patients with or without human immunodeficiency virus infection, with biopsy-confirmed BA, who had prolonged exposure to pet cats prior to developing BA. Main Outcome Measures. —Cultures and laboratory studies were performed on blood drawn from pet cats associated with patients with BA. TheRochalimaeaspecies infecting pet cats and fleas and causing the BA lesions in human contacts of these cats was identified by culture, polymerase chain reaction—restriction fragment length polymorphism analysis, and DNA sequencing. The presence ofR henselaebacteremia in pet cats was documented, and predictor variables for culture positivity were evaluated. Results. —Four patients diagnosed with BA who had prolonged contact with seven pet cats were identified. TheRochalimaeaspecies causing BA lesions in these patients was determined to beR henselae. The seven pet cats were found to be bacteremic withR henselae; this bacterium was also detected in fleas taken from an infected cat by both direct culture and polymerase chain reaction. Blood samples were cultured from pet and impounded cats (N=61) in the Greater San Francisco Bay Region, andR henselaewas isolated from 41% (25/61) of these cats. Conclusion. —We have documented that the domestic cat serves as a major persistent reservoir forR henselae, with prolonged, asymptomatic bacteremia from which humans, especially the immunocompromised, may acquire potentially serious infections. Antibiotic treatment of infected cats and control of flea infestation are potential strategies for decreasing human exposure toR henselae. (JAMA. 1994;271:531-535)

Rochalimaea henselae Infection A New Zoonosis With the Domestic Cat as Reservoir

Objective. To assess the serologic response to Afipia and Bartonella, previously named Rochalimaea, in patients with cat scratch disease (CSD) and a healthy control group. Design. Prospective, controlled trial. Setting. Referral clinic and hospitalized patients in a university medical center. Participants. Eighty patients with CSD and 57 healthy control subjects of similar age. Main Outcome Measures. The immune responses to Afipia felis and Bartonella henselae were evaluated by a newly developed enzyme-linked immunosorbent assay (ELISA) in patients with CSD and healthy control subjects. Responses to B henselae were also measured by indirect fluorescent antibody (IFA) tests. Antibody levels to Bartonella quintana were measured by ELISA and IFA in a limited number of patients and control subjects. Results. Of the 80 patients with clinical CSD, 56 had positive results of CSD skin tests. ELISA antibody levels to A felis did not differ between patients and control subjects, but immunoglobulin M (IgM) and IgG ELISA antibodies to B henselae and B quintana were significantly higher in patients than in control subjects. IFA responses to B henselae and B quintana were also significantly higher in patients than in control subjects. Conclusion. Patients with CSD had significant serologic responses to B henselae and B quintana but not to A felis, suggesting that the causative agent of CSD is antigenically related to the Bartonella genus and not to Afipia. The Bartonella IgM ELISA and IFA assay were both sensitive and specific and may be used to establish the diagnosis of CSD.

Russell L. Regnery

Papers

Cat Scratch Disease in Connecticut -- Epidemiology, Risk Factors, and Evaluation of a New Diagnostic Test

Serologic responses to Bartonella and Afipia antigens in patients with cat scratch disease.

Case 22-1992--pathogenesis of cat scratch disease.