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We obtained fecal samples from migrant children12 years of age throughout hotspots in Greece and tested them for Tropheryma whipplei by using a quantitative PCR assay. We identified 6 genotypes of T. whipplei, 4 of which are newly described. Our findings suggest a high prevalence of T. whipplei in these regions.

We examined fecal specimens of patients with diarrhea from 3 continents for Tropheryma whipplei and enteropathogens. T. whipplei was most common in South Africa, followed by Singapore and Germany. Its presence was associated with the presence of other pathogens. An independent causative role in diarrhea appears unlikely.

This bacterium may be an etiologic agent of gastroenteritis., Tropheryma whipplei, which causes Whipple disease, is found in human feces and may cause gastroenteritis. To show that T. whipplei causes gastroenteritis, PCRs for T. whipplei were conducted with feces from children 2–4 years of age. Western blotting was performed for samples from children with diarrhea who had positive or negative results for T. whipplei. T. whipplei was found in samples from 36 (15%) of 241 children with gastroenteritis and associated with other diarrheal pathogens in 13 (33%) of 36. No positive specimen was detected for controls of the same age (0/47; p = 0.008). Bacterial loads in case-patients were as high as those in patients with Whipple disease and significantly higher than those in adult asymptomatic carriers (p = 0.002). High incidence in patients and evidence of clonal circulation suggests that some cases of gastroenteritis are caused or exacerbated by T. whipplei, which may be co-transmitted with other intestinal pathogens.

This bacterium may be an etiologic agent of pneumonia., Tropheryma whipplei is the etiologic pathogenic agent of Whipple disease (WD), characterized by various clinical signs, such as diarrhea, weight loss, lymphadenopathy, and polyarthritis. PCR-based methods for diagnosis of WD have been developed. T. whipplei has been identified in saliva and stool samples from patients with WD and from healthy persons. T. whipplei DNA has also been found in bronchoalveolar lavage (BAL) samples of a child with pneumonia. We detected DNA of T. whipplei in 6 (3%) of 210 BAL samples collected in intensive care units by using 16S rDNA and specific quantitative PCR. We identified 4 novel genotypes of T. whipplei. In 1 case, T. whipplei was the only bacterium; in 4 others, it was associated with buccal flora. We suggest that T. whipplei should be investigated as an etiologic agent of pneumonia.

To the Editor: The clinical spectrum of Whipple disease has widely expanded since its etiologic agent, Tropheryma whipplei, was isolated in 2000 (1). Systematic 16S rDNA sequencing unexpectedly identified T. whipplei in patients for whom blood cultures were negative for endocarditis, spondylitis, and uveitis (2). Features common to these conditions and to Whipple disease include long-standing, unexplained arthralgia and deterioration of the patient’s condition after treatment with immunosuppressive drugs (2). We report an unexpected case of postoperative panendophthalmitis identified by systematic 16S rDNA sequencing of a vitreous sample in a patient who had unexplained arthralgia and had been given topical corticosteroids after cataract surgery. A 78-year-old woman in France underwent left eye phacoemulsification with intraocular lens implantation in May 2005 and retinal surgery followed by local corticoid application in April 2006. She had experienced cortisone-resistant polyarthralgia for 2 years before the first surgery. In July 2006, she showed decreased visual acuity (20/1,000) and a painful, red eye. Chronic postoperative endophthalmitis was suspected, and the patient underwent anterior chamber paracentesis (ACP). Parameters included 0.614 × 109 eosinophils/L in the blood and an erythrocyte sedimentation rate of 70 mm in the first hour. Sequencing of 16S rDNA of the ACP specimen showed 99.9% similarity with that of T. whipplei (GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"AJ551273","term_id":"29292527","term_text":"AJ551273"}}AJ551273). A specific PCR confirmed this result in the ocular sample and detected T. whipplei in saliva and stool samples, whereas blood and cerebrospinal fluid were negative for the organism by PCR. Duodenal biopsy specimens were negative by periodic acid–Schiff staining, specific immunohistochemical analysis, and PCR. The patient was treated with topical corticosteroids, cycloplegic drugs, doxycycline (200 mg/d), hydroxychloroquine (200 mg 3×/d), and sulfamethoxazole/trimethoprim (1,600 mg and 320 mg 3×/d) (2). She was hospitalized for 7 days in the ophthalmology department and for 4 days in the infectious disease department. At 8-month follow-up, visual acuity had improved (20/50) despite intraocular inflammation with a Tyndall effect, moderate capsular opacification, decreased vitreitis, macular edema, and retinal macular abnormalities shown by optical coherence tomography. T. whipplei DNA was again not detected by PCR in saliva and stool samples at 8-month follow-up, and the patient remained free of symptoms at 16-month follow-up when treatment was stopped. Diagnosis of Whipple disease uveitis was confirmed by detection of T. whipplei DNA in the ocular sample by 2 laboratories that used 2 molecular targets and negative controls. T. whipplei was identified by 16S rDNA sequencing and by detection of T. whipplei–specific repeat sequences. Further investigations detected T. whipplei in saliva and stool samples. Uveitis was the initial manifestation of Whipple disease, although patient evaluation showed a 2-year history of idiopathic, corticoresistant polyarthralgia described as a hallmark of Whipple disease (2). Initial unexplained eosinophilia in blood was observed, as in several confirmed cases of Whipple disease (2). Uveitis has been reported in Whipple disease (2), but

High prevalence within families might reflect a specific immune condition., 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.

To the Editor: Tropheryma whipplei causes Whipple disease, a rare multisystemic disorder that affects mainly middle-aged white men and is most widely distributedin Europe and North America (1). In the general population of France, T. whipplei DNA was found in 2%–4% of stool samples and T. whipplei–specific antibodies were found in 51% of serum samples (2). Still, the prevalence of classic Whipple disease, which causes arthralgia, diarrhea, and weight loss, remains extremely low (1). Whipple disease has 4 known manifestations: 1) classic Whipple disease; 2) focused chronic infections, mainly endocarditis; 3) acute infections, such as gastroenteritis, bacteremia, and pneumonia; and 4) asymptomatic T. whipplei carriage in healthy persons (1–5). T. whipplei is thought to be transmitted through oral and oro–fecal routes by human-to-human contact (2,6). The pathogen was cultivated in 2000, and 2 genomes were sequenced (reference strains Twist and TW08/27) (7,8). These events made possible a genotyping system based on 4 highly variable genetic sequences found by genome comparison (TW133, ProS, SecA, Pro184) (9). Since 2007, we have applied this system to patient samples positive for T. whipplei from central Europe and sub-Saharan Africa (2,3,9,10). The system showed a higher discriminatory power than previous typing methods and improved the genotyping resolution of T. whipplei, promoting better understanding of its epidemiology on the molecular level (9). Since 2003, we have subcultured strain Twist every 3 weeks. In 2007 and 2012, we compared sequences for the subcultured strains with that for the 2003 strain. We found that the spacer sequence remained stable over the ≈10-year period. This finding suggests a high intrastrain genetic stability and highlights the value of the typing system, which is stable. Thus, a change in genotype in a patient with Whipple disease must be interpreted as an infection with a different strain and cannot be attributed to mutation of the original strain. To date, 191 samples positive for T. whipplei collected from patients from central Europe (France, Germany, Switzerland, Austria, and Italy) have been typed, revealing a genetic diversity by identifying 72 different T. whipplei genotypes: 1–23, 25–45, 58–60, 76–77, 82–102, and 111–116. The discriminatory power was high (Hunter-Gaston discriminatory index 0.9298) for all samples from Europe. No connection between clinical manifestations and T. whipplei genotypes has been described. Reasons might be found either in an unknown link between genomics in T. whipplei and clinical outcome or might be because the typing system cannot identify possible virulence factors. Genotypes 1 and 3 are predominant (1,3), accounting for 35.1% of all tested T. whipplei samples from Europe. Genotype 3 is the most common T. whipplei genotype in Europe (19.9% of all samples) and could be considered epidemic in and specific to France, Switzerland, and Italy. This genotype was proposed to be responsible for small outbreaks caused by clonal strains, such as gastroenteritis among young children or the strain carried by homeless persons in Marseille, France (3,6), but it has not been described in Germany or Austria (Figure). Figure Geographic distribution of the 2 most common genotypes of Tropheryma whipplei in central Europe. Numbers in circles indicate number of cases with corresponding genotype; circles without a number indicate single cases. Cities are either the residence of ... Genotype 1 is found throughout central Europe and is the second most common genotype (15.2% of all samples) (Figure). Predominance of this genotype in Germany is high (46.2%, n = 13) and Austria (80%, n = 5). Infection with this genotype seems to be endemic in the population of the area, although no outbreaks have been reported. Of 191samples, a total of 55 (28.8%) showed a unique genotype consistent with the high genetic variability in T. whipplei specimens. Phylogenetic analysis and clustering of these singletons showed no correlation between clusters and geographic origin of samples. Of the 191 samples, a total of 66 (34.6%) were from Marseille and represented 40 different genotypes. This finding underscores the broad heterogeneity in T. whipplei. Twelve (18.5%) of the 66 tested samples were genotype 3, which might be linked to the local outbreak among homeless persons mentioned above. Genotype 1, which is endemic to France, was found in only 2 (3.1%) persons in Marseille. The fact that Marseille is a metropolitan area with a high migration rate could play a role in the vast diversity of T. whipplei genotypes found there Questions regarding the epidemiologic character of Whipple disease remain unanswered, such as why the bacterium is highly prevalent but the disease is not. Persons with the putative immunological defect probably responsible for classic Whipple disease (1) have the highest bacterial load in their stools. But these persons are unlikely to come into direct contact with one another. Thus, propagation of this bacterium on a large scale might be relatively limited, which could explain the high genetic diversity in the bacterial specimens assessed so far. Two predominant genotypes seem to break out of this pattern: genotypes 1 and 3. Genotype 3 could be considered a genotype that causes small epidemics, whereas genotype 1 could be considered a genotype endemic to central Europe. Reasons for the success of these 2 genotypes remain unknown, but improvement of genotyping methods could provide the answers.

To the Editor: Language is about comprehension; provided the parties in a discussion can understand each other, variations in pronunciation of individual words may be tolerated or disregarded. In modern English, numerous examples of variant pronunciations exist that cause no problems of comprehension (e.g., either, tomato, laboratory, fertile). These arise from several causes; regional practice is likely the most important factor, but the speaker's education and social background, personal preferences, and even etymologic theories also play a part. It would be futile and, some would feel, undesirable to attempt to impose uniformity by prescribing approved pronunciations if communication is not endangered. Moreover, both language and pronunciation are subject to constant change. The same is not true regarding the spelling of organisms' names. Although we accept variation in pronunciation, we should not accept variation in the spelling of binomial names. Common spelling variants and the citation frequency (PubMed) of 4 organisms, Acinetobacter baumannii, Coccidioides immitis (the fungal causal agent of coccidioidomycosis), Coxiella burnetii (the causal agent of Q fever), and Tropheryma whipplei (the causal agent of Whipple disease), are detailed in the Table. Common spelling mistakes occur with double letters (e.g., nn, ii), as well as complicated strings of consecutive vowels (e.g., Coccidioides). However, a defense to such criticism is that various authors have adopted the spelling of a previous taxonomic description that has become outdated, e.g., C. burneti (previous) and C. burnetii (current). Historic change in the spelling of these names is the primary reason they are published and cited in PubMed with different spellings. However, even disregarding historic taxonomic variants, ≈14.8% of Tropheryma whipplei, 14.3% of Acinetobacter baumannii, 12.3% of Coxiella burnetii, and 1.9% of Coccidioides citations are spelled incorrectly in PubMed. These relatively large percentages may mean that relevant literature is overlooked in searches. Table Common spellings of binomial names of organisms* Authors should be aware that previous taxonomic spelling of binomial names exist and check their historic evolution in the List of Prokaryotic Names with Standing in Nomenclature (http://www.bacterio.cict.fr). Authors should cite previous spelling when such a change has been recent and they may wish to include previous spellings in literature searches. Additionally, the most current and formally accepted spelling must be used when preparing a manuscript for publication. The origins of incorrect and variant spellings of binomial names may lie in an array of sources, including original mispronunciation with subsequent incorrect phonetic transcription. Written language is rarely a phonetic transcript of vocal acoustics, however, it interfaces with several factors that prevent us from spelling words the way they sound. Orthography, which promotes the practice of writing words with the proper letters according to standard usage and conventionally correct spelling, is further complicated by the use of Greek or Latin words, each with their own linguistic peculiarities. Although we may not be able to standardize phonetic pronunciation of binomial names locally, nationally, or internationally, we should be constantly conscious of their spelling. As authors and peer reviewers, we should strive to achieve uniformity in written media to promote enhanced communication with our peers in infectious diseases.