Tropheryma whippelii
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The Bug



What is it?

Tropheryma whipelii is a gram-positive, filamentous, aerobic, 1-2 micron by 0.2 micron, soil dwelling actinomycete (Tropheryma whippeligen.nov. sp.nov.). It is an argyrophilic rod shaped organism.

In 1992 Relman proposed the name in homage to George Hoyt Whipple, who described the disease for the first time in 1907. The name Tropheryma was derived from Greek trophi (nourishment) and eryma (barriers) because of the malabsorption syndrome this bacteria causes.

In 1949, Black-Schaffer first described the characteristic histological changes on which the diagnosis of Whipple disease has since been based. He found that foamy macrophages in the lamina propria of the intestinal mucosa of affected patients contained large amounts of PAS positive, diastase resistant material. Electron microscopy of affected tissue shows characteristic rod shaped bacilli that are both intracellular and extracellular. PAS positive macrophages and characteristic bacilli have also been found in non-intestinal tissues including liver, lung, heart, brain, lymph nodes, and synovium.

It has been possible to detect Tw before the recurrence of the symptoms in some treated asymptomatic patients and this may predict relapse of the disease. Attempts to culture Tropheryma whippelii have been unsuccessful, but recent studies have shown that the specific identification of this pathogen does not require culture but can be accomplished by molecular analysis of the bacterial 16s ribosomal RNA gene isolated from infected tissue.

PCR permits the identification of a specific 16s ribosomal RNA gene of Tw in affected tissues. PCR can also demonstrate Tw in tissues that show no evidence of disease histologically. Tw has also been identified in peripheral blood and pleural effusion cells.

Electron microscopy has demonstrated that the organism (Tw) has a unique membrane external to its cell wall, resulting in a triple wall appearance.

The classification of Tw as an actinobacterium is of interest because many bacteria within that classification are common soil or water saprophytes, and others are commensal organisms that colonize the mucosa in humans and animals. The mucosal commensal anctinobacteria can cause invasive disease in humans when normal anatomical barriers are breached or when the host's immune defense mechanisms are compromised.

Preliminary passage of Tw obtained from two patients with “culture negative” endocarditits associated with Whipple's disease was reported in human macrophages deactivated with a combination of interleukin-4 and interleukin-10. Positve PAS, identically amplified sequences of the 16s RNA gene, electron microscopy and positive immunoflourescence staining of the isolate in infected HEL cells confirmed that the passage isolates were Tropheryma whippelii.


Where is it found?

In a study reported in Lancet on October 1999, researchers found that a third of a random sample of healthy people had Tropheryma whippelii DNA in their saliva, which suggests that Tw can be an oral commensal organism. This finding is consistent with reports that Tw DNA was recorded in 25 of 38 waste-water samples obtained from different sewage treatment plants in southern Germany, providing the first evidence that Tw occurs in the environment within a polimicrobial community. In 105 patients with no clinical signs of Whipple's disease who underwent elective gastro-surgery, Tw was found in 13.3 % of either their biopsy specimens or gastric juice samples.

Researchers suggest that Tropheryma whippelii, generally regarded as a mysterious and remote organism, is another environmental commensal organism which is ubiquitous and rarely pathogenetic.


How is it transmitted?

The mode of contamination and of dissemination of Tropheryma whippelii are still unanswered questions. It remains unclear as to whether Tw is a rare member of the normal human microbial flora and whether or not it might be associated with other human diseases. It is suggested that Tw infection is common but rarely causes illness. There is no evidence for human to human transmission.


What diseases does it cause?

Tropheryma whippelii infection is linked to Whipple's disease and is found consistently in infected tissues of patients with the disease. The prominent deposition of fat within intestinal mucosa and mesenteric lymph nodes made George Hoyt Whipple propose initially the name of “intestinal lipodystrophy”. Nowdays the disease is generally known as Whipple's disease, in the homage of the doctor, who for the first time described this not well understood disease in a missionary in 1907. The symtoms of this disease are malabsorption, weight loss, arthralgia, fevers, and abdominal pain. Any organ system can be affected, including the heart, lungs, skin, joints, and central nervous system. This disease can be fatal if not adequately treated with antibiotics. Fatality is most often related to a relapse in the nervous system, months or years after successful treatment with antibiotics.


Who/what is at risk of infection?

Tropheryma whippelii is considered an actinobacterium, one of a group of bacteria that are common soil or water saprofites, or commensal mucosal organisms.

It is not known how widespread exposure to this bacillus really is. However, many reports of disease occur in patients who work in trades where they have frequent contact with soil such as agriculture and construction. The rarity, the sporadic nature of the infection, and its association with HLA-B27, strongly suggests the presence of genetically determined susceptibility factors in those individiuals diagnosed with the disease. In addition, most, if not all patients, have immune defects characterized by deficiency in the production of interleukin-12 (IL-12) associated with a reduced capability to produce IFN-gamma. A similar, but not identical, genetically determined immune abnormality has previously been reported in patients with chronic mycobacterial infection. These defects may create difficulties in the patient's ability to handle intracellular infection with Tropheryma whippelii, thus putting these patients in the category of individuals at the highest risk for disease.

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Copyright 1999-2007 Department of Microbiology, Mount Sinai Hospital, Toronto, Canada. All rights reserved.