sábado, 9 de noviembre de 2013

Tropheryma whipplei Endocarditis - Vol. 19 No. 11 - November 2013 - Emerging Infectious Disease journal - CDC

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Tropheryma whipplei Endocarditis - Vol. 19 No. 11 - November 2013 - Emerging Infectious Disease journal - CDC

Attributed to the Sappho Painter Odysseus Escaping from the Cave of Polyphemos (detail) (c. 2500 years ago) Attic black-figured column-krater, ceramic. Courtesy of the Michael C. Carlos Museum of Emory University, Atlanta, Georgia, USA. Photo by Bruce M. White, 2004

Volume 19, Number 11—November 2013


Tropheryma whipplei Endocarditis

Florence Fenollar, Marie Célard, Jean-Christophe Lagier, Hubert Lepidi, Pierre-Edouard Fournier, and Didier RaoultComments to Author 
Author affiliations: Aix-Marseille Université, Marseille, France (F. Fenollar, J.-C. Lagier, H. Lepidi, P.-E. Fournier, D. Raoult); Assistance Publique Hopitaux de Marseille, Marseille (F. Fenollar, J.-C. Lagier, P.-E. Fournier, D. Raoult); Groupement Hospitalier Est, Bron, France (M. Célard)
Suggested citation for this article


Tropheryma whipplei endocarditis differs from classic Whipple disease, which primarily affects the gastrointestinal system. We diagnosed 28 cases of T. whipplei endocarditis in Marseille, France, and compared them with cases reported in the literature. Specimens were analyzed mostly by molecular and histologic techniques. Duke criteria were ineffective for diagnosis before heart valve analysis. The disease occurred in men 40–80 years of age, of whom 21 (75%) had arthralgia (75%); 9 (32%) had valvular disease and 11 (39%) had fever. Clinical manifestations were predominantly cardiologic. Treatment with doxycycline and hydroxychloroquine for at least 12 months was successful. The cases we diagnosed differed from those reported from Germany, in which arthralgias were less common and previous valve lesions more common. A strong geographic specificity for this disease is found mainly in eastern-central France, Switzerland, and Germany. T. whipplei endocarditis is an emerging clinical entity observed in middle-aged and older men with arthralgia.
Whipple disease was first described in 1907 (1). This chronic infection is characterized by histologic indication of gastrointestinal involvement, determined by a positive periodic acid–Schiff (PAS) reaction in macrophages from a small bowel biopsy sample (2). It is caused by Tropheryma whipplei and encompasses asymptomatic carriage of the organism to a wide spectrum of clinical pathologic conditions, including acute and chronic infections (1,2).
In 1997, T. whipplei was first implicated as an agent of blood culture–negative endocarditis in 1 patient by use of broad-range PCR amplification and direct sequencing of 16S rRNA applied to heart valves from patients in Switzerland (3). Two years later, 4 additional cases were reported in Switzerland (4). In 2000, the first strain of T. whipplei was obtained from the aortic valve of a patient with blood culture–negative endocarditis (5).
Blood culture–negative endocarditis accounts for 2.5%–31.0% of all cases of endocarditis. The incidence rate of T. whipplei endocarditis among blood culture–negative endocarditis cases has not been established; however, at our center (Assistance Publique Hôpitaux de Marseille, Marseille, France), this incidence rate was estimated to be 2.6% (6). In Germany, the reported incidence rate for T. whipplei endocarditis is 6.3%: T. whipplei was the fourth most frequent pathogen found among 255 cases of endocarditis with an etiologic diagnosis and was the most common pathogen associated with blood culture–negative endocarditis. This incidence rate exceeds rates of infections caused by Bartonella quintana; Coxiella burnetii; and members of the Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella spp. group (7). Smaller studies found incidence rates of 3.5% in Denmark (8), 4.3% in Switzerland (9), 7.1% in the Czech Republic (10), 2.8% in Spain (11), and none in Algeria (12). We describe 28 cases of T. whipplei endocarditis and compare them with cases reported in the literature.

Materials and Methods

Patient Recruitment and Case Definitions
Our center in Marseille, France, has become a referral center for patients with T. whipplei infections and blood culture–negative endocarditis (2,5,6). We receive samples from France and other countries. Each sample is accompanied by a questionnaire, completed by the physician, covering clinico-epidemiologic, biological, and therapeutic data for each patient. We analyzed data from October 2001 through April 2013. Diagnosis of T. whipplei endocarditis was confirmed by positive results from PAS staining and/or specific immunohistochemical analysis and 2 positive results from specific PCRs of a heart valve specimen in addition to lack of histologic lesions in small bowel biopsy samples or lack of clinical involvement of the gastrointestinal tract.

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