Intrafamilial Circulation of Tropheryma whipplei, France

Florence Fenollar, Alpha K. Keita, Sylvain Buffet, and Didier Raoult

Author affiliations: Université de la Méditerranée, Marseille, France

Abstract

Tropheryma whipplei, which causes Whipple disease, has been detected in 4% of fecal samples from the general adult population of France. To identify T. whipplei within families, we conducted serologic and molecular studies, including genotyping, on saliva, feces, and serum from 74 relatives of 13 patients with classic Whipple disease, 5 with localized chronic T. whipplei infection, and 3 carriers. Seroprevalence was determined by Western blot and compared with 300 persons from the general population. We detected T. whipplei in 24 (38%) of 64 fecal samples and 7 (10%) of 70 saliva samples from relatives but found no difference between persons related by genetics and marriage. The same circulating genotype occurred significantly more often in families than in other persons. Seroprevalence was higher among relatives (23 [77%] of 30) than in the general population (143 [48%] of 300). The high prevalence of T. whipplei within families suggests intrafamilial circulation.

Whipple disease, a rare sporadic disease, was first considered a metabolic disease (1) and later suspected to be an infectious disease caused by a rare bacterium, Tropheryma whipplei (2). However, the causative bacterium is common (3–5), and the well-known and classic form of Whipple disease (characterized by periodic acid–Schiff-stained bacilli in infected small-bowel macrophages) represents only 1 rare clinical form of infection caused by T. whipplei (6,7). In the absence of intestinal lesions, T. whipplei is involved in subacute or chronic infections, such as endocarditis (8), encephalitis (2), uveitis (9,10), adenopathy (2), and osteoarticular infections (2,11). Recently, T. whipplei was reported to cause acute infections, such as pneumonia (12,13), gastroenteritis (14,15), and bacteremia (16). Asymptomatic carriers have been identified for whom T. whipplei prevalence varied widely by geography or occupation (17–19). In Europe, the prevalence of T. whipplei in fecal samples from the general healthy adult population is ≈1%–11% (2,3). T. whipplei has been detected in sewage and is more prevalent in fecal samples of sewer workers (12%–26%) than in the general population (4%) (20,21). In a study in 2 rural Senegalese villages, 44% of children 2–10 years of age carried T. whipplei in their feces (4).

T. whipplei genotyping has shown high genetic diversity unrelated to pathogenicity, but this diversity varies geographically between Europe and Africa (4,22). Some clones circulate in particular communities, suggesting interhuman transmissibility (4,14). Moreover, the chronic carriage of T. whipplei in saliva and feces suggests that the bacterium might be transmissible within the same family. This question was raised to one of us (D.R.) by a person who had chronic carriage of T. whipplei in his saliva (20) and was concerned about his family. The development of T. whipplei serologic assays has enabled delineation between patients with Whipple disease who lack or have weak immune responses against T. whipplei and asymptomatic carriers who show strong immune response to the bacterium (23–25).

To identify T. whipplei within families, during 2003–2011 we conducted molecular and serologic investigations on samples from the families of patients who had chronic T. whipplei infection and were asymptomatic carriers. We also studied T. whipplei seroprevalence in the population of France, which enabled us to compare the prevalence with that of the families.