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Lengthy treatment needed to treat Whipple's disease

Published April 27, 2008

The actor who played George Whipple the fretful grocer died last fall, and I was reminded not of
his Charmin toilet paper commercials, but of Whipple's disease.
The disease is not named for George Whipple, television icon, but for Dr. George Whipple,
professor at Johns Hopkins University.
In 1907, Dr. Whipple described a chronic illness characterized by diarrhea, anemia, malnutrition,
weight loss and arthritis. He thought the mysterious illness might be an unusual metabolic
disorder.
He was wrong, but that did not prevent him from later winning a Nobel Prize for his work on
pernicious anemia.
Decades later, Dr. Whipple's disease was found to be an infection. It wasn't until 2000, however,
that the causative agent of the infection finally was identified and grown in the laboratory. That
agent is a bacterium called Tropheryma whipplei. Its DNA was sequenced five years ago, but
many questions still remain about this elusive bacterium, the mysterious illness it causes, and
how best to treat it.
A hundred years after Dr. Whipple described his original case - which was fatal - patients with
Dr. Whipple's disease continue to be scarce. There are no accurate estimates of its prevalence in
the general population or the overall death rate from the infection. Usually, deaths are due to a
failure to diagnose and treat the disease. Men seem to get the disease eight times as often as
women, and most of those men are middle-aged and white. There also may be a genetic
susceptibility to Dr. Whipple's disease.
Although Dr. Whipple's disease typically presents with major gastrointestinal symptoms, the
infection also may spread from the intestines to affect the heart, liver, eyes and the central
nervous system. Heart murmurs may result in some cases, and symptoms of CNS infection may
include headaches, meningitis, seizures and dementia.
Dr. Whipple's disease and its grab-bag of crippling symptoms are caused by a crippled bacterium
that needs to be carried from the intestines to other organs by the patient's own white cells
(macrophages and monocytes). T. whipplei seems to live out its pathogenic life within the safety
and comfort of patient's cells because it lacks so many necessary genes for an independent
lifestyle. In fact, T. whipplei can only be grown in human cell cultures in the lab. It seems to be a
true parasite in constant need of a reluctant, but protective host.

So where does T. whipplei come from and how does it infect people? No one is certain, but there
are some clues.
It has been found in sewage treatment plants. Farmers and other rural workers are more likely to
contract Dr. Whipple's disease than people in other occupations. This suggests T. whipplei may
lurk in soil or rural water supplies. How it gets from the environment to the intestines is still
unclear.
Once Dr. Whipple's disease was understood to be an infection, antibiotics became the gold
standard of treatment. A few years ago, treatment would be two weeks of penicillin and
streptomycin, followed by an oral course of trimethoprim-sulphamethoxazole for one year! The
lengthy treatment is necessary because the slow-growing bacteria are safely tucked away inside
cells in the intestine. It's hard to build up killing concentrations of antibiotics in such places so
disease relapse is common.
Relapse is serious because Dr. Whipple's disease has a potentially fatal outcome due to cardiac
failure, CNS damage, physical wasting or septic shock.
Because Dr. Whipple's disease is rare, hard to diagnose and harder still to treat, the most effective
treatments and appropriate patient follow-ups have been a matter of guesswork. The man who
first grew T. whipplei in the lab and sequenced its DNA (Didier Raoult at the Universite de la
Mediterrantee, France) made some new recommendations based on recent laboratory research
and clinical trials. His treatment suggestions still call for a yearlong ordeal of antibiotic therapy,
but some ineffective drug combinations could be replaced with a better drug (sulfadiazine) for
CNS symptoms.
Dr. George Whipple died in 1976 at age 97, having lived long enough to witness the growing
suspicion that the illness he described in 1907 was actually an infection. He would certainly be
surprised to know his "Whipple's bacillus" now has been analyzed down to its last DNA
nucleotide, yet the bug and the disease still retain many mysteries.

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Dr. Edward McSweegan has a Ph.D. in microbiology and lives in Crofton. He works on and
writes about infectious disease issues. He may be contacted at mcsweegan@nasw.org