Helicobacter pylori Case File

Helicobacter pylori Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 10

A 48-year-old man presents for the evaluation of a 2-month history of upper abdominal pain associated with nausea. It is made worse when he drinks coffee, soda, or alcohol. He has taken multiple over-the-counter antacid medications that provide temporary relief. He admits to a 20-pack-year smoking history and drinking one or two alcoholic beverages a week but denies significant use of nonsteroidal anti-inflammatory drugs (NSAIDs). His general physical examination and vital signs are normal. His abdominal examination is notable for epigastric tenderness without the presence of masses, rebound tenderness, or guarding. A rectal examination reveals his stool to be heme positive. A complete blood count (CBC) shows a mild hypochromic, microcytic anemia. He is referred to a gastroenterologist for an upper GI endoscopy, which shows diffuse gastritis and a gastric ulcer.

◆ What organism is most likely to be visualized on histologic evaluation of a gastric biopsy specimen?

◆ Besides microscopic evaluation, what other clinical test may provide a rapid detection of this organism?

◆ What two factors facilitate this organism’s ability to colonize the stomach?

ANSWERS TO CASE 10: Helicobacter pylori

Summary: A 48-year-old man has diffuse gastritis and a gastric ulcer on endoscopic examination.

◆ Organism on histologic evaluation of a gastric biopsy: The organism likely to be visualized on biopsy specimen is Helicobacter pylori.

◆ Other clinical test for rapid detection of this organism: The urease test.

◆ Factors facilitating this organism’s ability to colonize the stomach: Blockage of acid production by a bacterial acid-inhibitory protein and neutralization of acid by ammonia produced by urease activity.

CLINICAL CORRELATION

Helicobacter pylori has been implicated in the development of multiple GI diseases, including gastritis, ulcers, and gastric cancers. Humans are the primary reservoir of the infection and human-to-human transfer, via fecal-oral contact, is likely to be an important mode of transfer. Helicobacter pylori is a curved gram-negative bacillus with motility facilitated by corkscrew motion and polar flagella. Culture of this organism requires a complex medium and microaerophilic environment. Helicobacter pylori that colonize the stomach produce urease, an enzyme that has many effects. Urease activity produces ammonia, which neutralizes gastric acid. This, along with a specific acidinhibitory protein that directly blocks gastric acid production, facilitates the colonization of the acidic stomach environment. Urease by-products also cause local tissue damage and stimulate an inflammatory response. Urease activity is enhanced by the presence of a heat shock protein, HspB, which exists on the surface of H. pylori. The identification of urease activity in a gastric biopsy sample is highly specific for the presence of an active H. pylori infection, making it the basis for a widely used clinical test for the rapid detection of H. pylori infections.

APPROACH TO SUSPECTED Helicobacter pylori INFECTION

Objectives

1. Be able to describe the characteristics of Helicobacter bacteria.
2. Understand the role of H. pylori in causing gastric ulcers.

Definitions

Urease: Helicobacter pylori uses this enzyme to convert urea into ammonia and carbon dioxide. This chemical reaction is the basis of the rapid urea breath test for diagnosis of H. pylori. The increased ammonia produced by this reaction neutralizes gastric acid, which allows the organism to survive the normally harsh gastric environment and damages the gastric mucosa.

Type B gastritis: Type B gastritis is gastritis of the antrum caused by H. pylori infection (compare with Type A of the fundus, caused by autoimmune disorders).

Corkscrew motility: Helicobacter pylori is highly motile because of 5–6 polar flagella.

Microaerophilic organisms: Organisms that require reduced oxygen concentration (5%) to grow optimally (include: H. pylori and Campylobacter jejuni).

Upper endoscopy: Visual examination of the mucosa of the esophagus, stomach, and duodenum using a flexible fiberoptic system introduced through the mouth.

DISCUSSION

Characteristics of Helicobacter pylori Impacting Transmission

Helicobacter pylori is a curved gram-negative bacilli that requires microaerophilic environments to grow. Discovered in 1983, the organism was originally classified under the Campylobacter genus, but eventually was reclassified under a new and separate genus, Helicobacter, as understanding of the organism has evolved. Urease production is the most important enzyme that distinguishes H. pylori from Campylobacter species and other various Helicobacter species, and allows the organism to survive the harsh gastric environment. Helicobacter pylori also has oxidase, catalase, mucinase, phospholipase enzymes, and vacuolating cytotoxin, which aid in the virulence and pathogenesis of the organism. Infections of H. pylori are ubiquitous, worldwide, and extremely common in developing nations and among lower socioeconomic groups. Humans are the primary reservoir, and no animal reservoir has been identified at the present time. The primary mode of transmission is person to person (usually by the fecal-oral route), and the infection commonly is clustered in families or among close contacts. Some speculation has been made that contaminated water or food sources may be a reservoir, but at the present time there are no data to support this.

Diagnosis

Helicobacter pylori has been clearly associated with Type B gastritis, gastric ulcers, gastric adenocarcinoma of the body and antrum, and gastric mucosaassociated lymphoid tissue (MALT) B-cell lymphomas. Diagnosis of H. pylori should be considered in patients with symptoms of these diseases. The most rapid test to detect H. pylori is the urease test or urea breath test that detects by-products of the urease reaction cleaving urea into ammonia and carbon dioxide; however, the invasiveness of biopsy or the expense of breath detection instruments limits the use of these assays. Microscopy is both extremely sensitive and specific for diagnosis of H. pylori in gastric biopsy specimens when stained with Warthin-Starry silver stain, hematoxylin-eosin, or Gram stain. Antigen detection in stool samples via a commercial polyclonal enzyme immunoassay is highly sensitive and specific, while also inexpensive and easy to perform. Serology is another preferred diagnostic test, whereby H. pylori stimulates a humoral immune response (IgM early in infection; IgG and IgA later in infection and persisting), but it cannot distinguish between past and present infections. Culture is a more challenging and time-consuming way to diagnose H. pylori, because it must be grown in a microaerophilic atmosphere on an enriched medium containing charcoal, blood, and hemin.

Treatment and Prevention

Because H. pylori is primarily transmitted person to person via fecal-oral route, the best prevention is improving hygiene by frequent hand washing, especially before meals. In symptomatic patients who are positive for infection with H. pylori, combination therapy is needed. This therapy includes (1) acid suppression, usually with a proton pump inhibitor, (2) one or more antibiotics, and (3) occasional additive therapy with bismuth.

COMPREHENSION QUESTIONS

[10.1] A 45-year-old man presents to the hospital vomiting blood. He is diagnosed with a perforated peptic ulcer. The causative agent discovered by gastric biopsy is a spiral gram-negative bacillus. What other long-term complications could this organism cause if not treated?

A. Skin ulcers

B. Esophageal varices

C. Gastric MALT lymphomas

D. Colon cancer

[10.2] Which of the following is an important distinguishing characteristic of H. pylori as compared to Campylobacter species?

A. Oxidase production

B. Catalase production

C. Urease production

D. Curved shape

E. Polar flagellum

[10.3] A 58-year-old man presents to the clinic with decreased appetite, nausea, vomiting, and upper abdominal pain. If the causative agent is a curved gram-negative rod with urease production, what treatment should be given to this patient?

A. Proton pump inhibitor and antibiotic

B. Proton pump inhibitor, antibiotic, and bismuth

C. Over-the-counter antacids and antibiotics

D. Nonsteroidal anti-inflammatory drugs (NSAIDs)

Answers

[10.1] C. Helicobacter pylori is the causative agent that can cause Type B gastritis, peptic ulcers, gastric adenocarcinoma, and gastric MALT B cell lymphomas.

[10.2] C. Both Campylobacter species and H. pylori have a curved shape, are oxidase and catalase positive, with polar flagellum. Urease production is the distinguishing factor of H. pylori, and it is the basis of the rapid urease breath test that diagnoses H. pylori infection.

[10.3] B. The combination therapy of proton pump inhibitor, antibiotic, and bismuth is required to eradicate an infection with H. pylori.

MICROBIOLOGY PEARLS ❖ Helicobacter pylori are characterized as being curved gram-negative bacilli and microaerophilic, and by having multiple polar flagella and urease activity. ❖ Clinical manifestations include Type B gastritis, gastric ulcers, gastric adenocarcinoma, gastric MALT lymphomas conjunctivitis, or gastroenteritis. ❖ It is transmitted via the fecal-oral route. ❖ Antimicrobial treatment includes acid suppression, antibiotics, and adjunctive treatments (i.e., bismuth).

REFERENCES

Johnson AG, Hawley LB, Lukasewycz OA, Jiegler RJ. Microbiology and Immunobiology, 4th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2002. 

Levinson W, Jawetz E. Medical Microbiology and Immunology, 7th ed. New York: McGraw-Hill, 2002. 

Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005:291–295. 

Passaro D, Chosy EJ, Parssonet J. Helicobacter pylori: Consensus and controversy. Clin Infect Dis 2002;35:298–304. 

Weingart V, Rüssmann H, Koletzko S, et al. Sensitivity of a novel stool antigen test for detection of Helicobacter pylori in adult outpatients before and after eradiacation therapy. J Clin Microbiol 2004. 42:1319–21. 

Youngerman-Cole S. Digestive disorders health centre: Helicobacter pylori tests. http://www.webmd.com/digestive-disorders/Helicobacter-pylori-Tests. Last updated January 12, 2006.

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