**1. Introduction**

*Tropheryma whipplei*, formerly *Tropheryma whipplei, i*s an intracellular gram-positive Actinobacteria ubiquitous in the environment that is involved in a large variety of clinical forms [1, 2]. The initial name was proposed by Relman *et al.* in 1992, and comes from the Greek *trophe,* nourishment, and *eryma*, barrier, due to the malabsorption it causes, and from the surname of George Hoyt Whipple [3]. In 2001, the name of the bacterium was slightly modified to conform to the proper spelling of Dr. George H. Whipple's name [4].

Dr. Whipple was the first who reported, in 1907, a "hitherto undescribed disease" he named "intestinal lipodystrophy" in a 36-year-old man with malabsortion, weight loss, diarrhea, migratory polyarthritis, cough and mesenteric lymphadenopathy [5]. Now, we refer to this disease as Whipple's disease. Although this disease was first described at the beginning of the last century, the hypothesis of its bacterial origin goes back to the late 40's and was supported with use of periodic acid-Schiff (PAS) staining and the success of the first antibiotic treatment [6, 7]. Subsequently, the presence of the microorganism was confirmed by electron microscopy (rod-shaped organism), polymerase chain reaction (PCR) of the 16S rRNA and finally by culture [1, 3, 8–12]. The isolation and later sequencing of its genome made possible to define its antibiotic susceptibility [13–16].

Until recently, *T. whipplei* was known to be only the causative agent of Whipple's disease, now called by some authors "classical Whipple disease", a rare chronic multisystemic infection [5]. Incidence of Whipple's disease was reported in approximately 1 per 1.000.000, although it remains unclear and epidemiological estimates varies among different studies [17–19]. Classical form of Whipple's disease usually involves the gastrointestinal tract, joints and central nervous system with malabsorption, diarrhea, abdominal pain and/or weight loss and arthralgia as prominent manifestations. Cardiac, ocular or other organs involvement has been also reported in patients with Whipple's disease [20–29]. The knowledge of the genome of *T. whipplei* has allowed developing specific and sensible tools that have let to involve this microorganism in a broad spectrum of clinical conditions [13, 14]. Therefore, *T. whipplei* can produce acute localized forms of infection such as pneumonia [30, 31], bacteremia [32], acute diarrhea [33, 34], uveitis [35, 36]; sub-acute forms such as adenitis [37] and chronic forms as uveitis [38], and, overall, endocarditis [39, 40].

*T. whipplei* has also been detected in asymptomatic carriers based, mainly, on stools and saliva analysis with very different prevalence among populations [41–52]. The carriage of *T. whipplei* varies considerably across studies and subjects. Many factors are involved in those differences such as the geographical region, exposure or the age of the studied subjects. The prevalence of asymptomatic carriers of *T. whipplei* in Africa and Asia is higher than in Europe and it is also higher in children than in adults [49–51, 53]. Actinobacteria are environmental microorganisms that can be found in freshwater, soil or seawater sediments, this fact could explain the high prevalence of *T. whipplei* in people expose to sewage and sewage plant workers [2, 41, 47, 54, 55]. People in contact with patients with Whipple's disease, as patients' relatives or carriers, or those with poor hygiene conditions such as homeless, also presents higher prevalences [56–59]. Differences between the targets used for the PCR and the samples used have been also observed and could explain these reported differences [52, 60]. Li *et al.* assessed that genomic variants of *T. whipplei* are associated with neither the organotropism of the bacteria nor the geographical residence of the individuals [61], however later studies show that different genotypes are more frequent in some populations [34, 56, 58, 62]. Therefore, despite Whipple's disease is rare, the high number of healthy carriers, the ubiquitous presence of the bacteria in the environment [41, 47, 57, 59] and the possibility of interhuman transmission [49, 56–59, 63, 64] make *T. whipplei* a common bacterium in humans.
