Helicobacter pylori…

Medical Wisdom Challenged by a Cocktail

bacteria clinging to the tissues s that nagging, burning of his biopsy specimens. He feeling in your stomach worked diligently with his Icaused by stress, excess associate, the Australian acid, eating spicy food, or physician Barry Marshall, in maybe your insensitive boss? culturing what they saw under the microscope, but to no Back in 1981, Barry Marshall avail. However during the didn’t think so. His discovery Easter weekend of 1982, they regarding the true cause of inadvertently left their duodenal and gastric ulcers cultures incubating for five has changed the way we think days; and to their surprise Jay Hardy, CLS, SM (ASCP) about this disease forever. In they discovered the colonies fact, Marshall believed in his cause so strongly that, to

Jay Hardy is the founder and prove his theory, he drank a CEO of Hardy Diagnostics. bacterial cocktail that made He began his career in him violently ill. But he microbiology as a Medical proved his case; to the benefit Technologist in Santa of millions of people who Barbara, California. suffer from ulcers. In 1980, he began manufacturing culture media It was known as far back as for the local hospitals. 1875 by German scientists Today, Hardy Diagnostics is that a spiral-shaped bacterium the third largest media manufacturer in the U.S. inhabited the lining of the human stomach. However, To ensure rapid and reliable because this organism was turn around time, Hardy impossible to culture at the Diagnostics maintains six time, it was quickly forgotten. distribution centers, and produces over 2,700 products used in clinical and Fast forward to 1979. It was industrial microbiology an Australian pathologist, laboratories throughout the Robin Warren, who noticed world. that many of his gastric ulcer Barry Marshall, MD. patients had a mysterious growing upon their return been the way it was taught. So from the holiday. I never thought that medical research would be interesting, When they described their but as I did my internship ... I discovery and challenged the realized there were a lot of thought that ulcers were people who had things wrong caused by stress and spicy with them that you couldn't do food, they were met with H. pylori shown attached to the anything about particularly." skepticism and criticism from gastric mucosa. the medical community. A leading microbiologist at After all, it was well known Medical dogma can be that time said about Marshall: that no bacteria could ever stubborn, and it wasn’t until "The vast majority of the survive the strong acid twelve years later, in 1994 medical profession, not only environment of the stomach. that the National Institutes of in Australia but worldwide, Several research groups Health in America published considered Barry to be a confirmed the Warren and an opinion stating that most quack and really were Marshall hypothesis and recurrent duodenal and gastric extremely dismissive for a identified the bacteria as ulcers were caused by H. number of years." Campylobacter pyloridis, now pylori and recommended that known as Helicobacter pylori. antibiotics be included in the A gastroenterologist who was treatment regimen. Their an early convert said THE BACTERIAL genius and persistence was regarding Marshall: "He was COCKTAIL finally rewarded when Warren changing the world and the and Marshall were awarded world wasn't seeing it." Frustrated by not being taken the Nobel Prize in Medicine Marshall himself underplays seriously by his colleagues, in 2005 for their work on H. the underdog image. "I used Marshall drank a cocktail pylori. to have a pretty good consisting of a beaker full of following. Robin Hood and H. pylori in a broth solution. his merry men - we used to He became seriously ill think of it as guerilla warfare. several days later with nausea There were a lot of people and vomiting. An endoscopy who didn't believe what we ten days after inoculation said but they couldn't keep us revealed inflammatory signs quiet. I was very thick- of gastritis and the presence of skinned." H. pylori. These results proved that H. pylori was the Why all the resistance to this causative agent of gastric Electron micrograph of H. pylori. seemingly logical germ theory ulcers and not just a of gastric ulcer disease? The bystander. Marshall and Marshall describes his interest pharmaceutical industry held Warren went on to show that in research with this story: the biggest vested interest in antibiotics could be an "When I was in medical ulcers. At the time, Tagamet effective in the treatment of school I was given the and Zantac were two of its this infectious disease. impression that everything biggest all-time profit earners. had already been discovered in medicine. It must have or make other drastic lifestyle only in persons who have changes to address the ulcers and not dyspepsia purported cause of their (stomach upset without an disease ulcer). It is difficult to kill the H. pylori because the place In this environment, the where they live in the lining possibility that the ailment of the stomach helps protect was directly caused by a them from antibiotics. These drugs did not cure single microorganism that Amoxicillin and ulcers; they merely controlled could be completely Clarithromycin are commonly the release of stomach acid, eliminated with a two-week used for this purpose. meaning that patients often course of antibiotics was a Metronidazole may be needed lifelong therapy. The real threat to the status quo. substituted if the patient is notion that common garden allergic to penicillin. varieties of antibiotics (many As for treatment of H. pylori, Levofloxacin or Bismuth of which were out of patent Marshall noticed that many of compounds may also be used and so did not hold the lure of his patients became cured, at in stubborn or antibiotic vast profits) might cure ulcers least temporarily, after a resistant cases. To be sure the was, unsurprisingly, not high course of Pepto-Bismol. He infection is cleared, at least on the industry's list of confirmed that the bismuth in two effective antibiotics plus priorities. this popular remedy was the either an acid-lowering agent toxic agent to this tenacious (proton-pump inhibitor or bacterium. Later, several histamine H2 receptor antibiotics and an acid blocker) or bismuth suppressing agent were added subsalicylate (Pepto-Bismol) to the treatment regimen. are taken.

It is now known that H. pylori

Helicobacter pylori is a gram is the most common cause of negative, flagellated, helix shaped, ulcers of the stomach and microaerophilic organism. It is a duodenum, accounting for up slow growing organism that can be to 90% of duodenal ulcers and cultured on Chocolate or Brucella up to 80% of gastric ulcers. with Sheep Blood Agar in the same microaerophilic atmosphere as Infected persons also have a Campylobacter. 2- to 6-fold increased risk of developing mucosa-associated Volumes had been published lymphoid tissue (MALT) lymphoma, and gastric cancer detailing the alleged compared with uninfected psychological causes of This is known as the persons. gastric ailments, and ulcers commonly applied “triple remained a frequently cited therapy”; or sometimes example of psychosomatic TREATMENT “quadruple therapy” when illness. Patients were bismuth is added. These At the present time, the CDC routinely advised to seek medicines are all taken at the guidelines recommend that H. psychiatric counseling, find same time, either 2 to 4 times less demanding employment pylori infection be treated a day (depending on the Medium shows a positive (purple) from the acidic contents of the regimen) for 1-2 weeks. reaction as a result of urea lumen towards the more degradation creating an alkaline shift in the medium. neutral pH environment of the DIAGNOSIS epithelial cell surface. The Urea Breath Test (UBT) “glue” that holds it in place Diagnosis of H. pylori H. pylori infection can be are called “adhesins” which infections can be made by detected in the exhaled breath bind to membrane-associated three methods: using this special test. This lipids and carbohydrates and test is positive only if the help it adhere to epithelial Endoscopy person has a current infection. cells. Small samples of the lining of Sensitivity and specificity of the stomach are taken through this test ranges from 94-98%. Urease breaks down urea a tube that is passed through (which is normally secreted the mouth into the stomach. Serologic test (IgG into the stomach) to carbon The histology test, considered antibody) dioxide and ammonia (which the gold standard of A serologic blood test shows neutralizes gastric acid). The diagnostic tests for H. pylori, if a person has ever been survival of H. pylori in the can be performed on the tissue infected. This test remains acidic stomach is dependent sample. positive for years after on urease, and it would infection and also for several eventually die without the months after H. pylori has enzyme. The ammonia that is been successfully treated. produced is toxic to the Sensitivity and specificity of epithelial cells, and, along this test ranges from 80-95% with the other products depending on the type of damages those cells; thus assay used. causing the inflammation that is so familiar to those Immunohistochemical stain of a suffering from gastric ulcers. gastric biopsy specimen. PATHOGENISIS

CONCLUSION The culture test, can be So how do these bacteria survive the harsh environment performed using a Urea Agar As a result of Barry medium formulated for biopsy of the stomach? To colonize the stomach, H. pylori must Marshall’s dogged specimens, such as Hardy persistence, millions of people Diagnostics’ Rapid Urea survive the acidic pH of the lumen and burrow into the now have relief from this Medium (Cat. no. Z54). painful disease. This story mucus to reach its niche, close to the stomach's epithelial cell also serves as a reminder that layer. The bacterium has the conventional wisdom of flagella and moves through the day which we hold on to the stomach lumen and drills so tightly may become into the mucoid lining of the tomorrow’s folly; often to the stomach. To avoid being embarrassment of the medical carried into the lumen, H. industry. pylori senses the pH gradient

within the mucus layer by H. pylori is a strong producer of Jay Hardy, CLS, SM (ASCP) urease. Above, Hardy’s Rapid Urea chemotaxis and swims away Santa Maria, CA