The Bug
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.
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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.
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.
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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.
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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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