Helicobacter Pylori (H. pylori) Infection

Helicobacter pylori (H. pylori or, as it is sometimes termed, stomach bacteria) is a spiral-shaped gram-negative bacterium that can cause chronic inflammation of the inner lining of the stomach (gastritis) and in the duodenum (first part of the small bowel) in humans. This bacterium also is considered a common cause of ulcers worldwide; as many as 90% of people with ulcers are infected with H. pylori. However, many people have these organisms residing in (colonizing or mucosa-associated) their stomach and upper digestive tract and have few or no symptoms. LPS (lipopolysaccharide) is part of the H. pylori outer membrane and can be toxic when the bacteria die and lyse.

H. pylori bacteria may cause a stomach infection in some individuals. H. pylori infections start with a person acquiring the bacterium from another person (via either the fecal-oral or oral-oral route). Although the majority of individuals who have these bacteria in their gastrointestinal (GI) tracts have few if any symptoms (see symptoms), most people develop stomach inflammation (gastritis) from the body's response to the bacterium itself and to a cytotoxin-associated substance termed Vac-A, a chemical that the bacterium produces.

Researchers also suggest that stomach acid stimulates the bacterium to grow and produce the cytotoxin, and increases invasion of the lining of the stomach by the bacteria, resulting in inflammation, and peptic ulcer formation (peptic ulcer disease). Other investigators have shown that these bacteria and their products cause alterations in the cells of the stomach lining that when altered are associated with stomach and other cancers, although these are infrequently seen diseases.

The frequency of people infected may somehow be related to race. About 60% of Hispanics and about 54% of African Americans have detectable organisms as compared to about 20% to 29% of White Americans. In developing countries, children are very commonly infected.

There is a consensus among doctors that individuals should be treated if they are infected with H. pylori and have ulcers. The goal of treatment is to eradicate the bacterium, heal ulcers if they are present, and prevent the ulcers' return. Patients with MALT lymphoma of the stomach also should be treated. MALT lymphoma is rare, but the tumor often quickly regresses upon successful eradication of H. pylori.

There currently is no formal recommendation to treat patients infected with H. pylori without ulcers or MALT lymphoma. Since antibiotic combinations can have side effects, and stomach cancers are infrequent in the United States, some healthcare professionals feel that the risks of treatment to eradicate H. pylori in patients without symptoms or ulcers may not justify the unproven benefits of treatment to prevent stomach cancer. On the other hand, H. pylori infection is known to cause atrophic gastritis (chronic inflammation of the stomach leading to atrophy of the inner lining of the stomach). Some doctors believe that atrophic gastritis can lead to cell changes (intestinal metaplasia) that can be precursors to stomach cancer. Studies have also shown that the eradication of H. pylori may reverse atrophic gastritis. Thus, some doctors are recommending the treatment of ulcer- and symptom-free patients infected with H. pylori.

Many physicians believe that dyspepsia (non-ulcer symptoms associated with meals) may be associated with infection with H. pylori. Although it is not clear if H. pylori cause dyspepsia, many doctors will test patients with dyspepsia for infection with H. pylori and treat them if the infection is present.

Scientists studying the genetics of H. pylori have found different strains (types) of the bacterium. Some strains of H. pylori appear to be more prone to cause ulcers and stomach cancer. A meta-analysis of H. pylori eradication treatment seems to reduce gastric cancer risk. Further research in this area may help doctors intelligently select those patients who need treatment. Vaccination against H. pylori is unlikely to be available soon.

Most individuals with Helicobacter pylori infections have few or no symptoms. Some may experience a few symptoms from mild gastritis episodes, for example:

• Minor belching
• Bloating
• Nausea
• Vomiting
• Abdominal discomfort

Often, these symptoms simply go away. However, those individuals who have more serious infection experience signs and symptoms of stomach and duodenal ulcers or severe gastritis which include:

• Abdominal pain and/or discomfort that usually does not wax and wane
• Nausea and vomiting sometimes with blood that is red, or the color is like coffee grounds or like vomitus
• Dark or tar-like stools (black color of feces due to bleeding ulcers)
• Fatigue
• Low red blood cell counts due to bleeding
• The full feeling after consuming a small amount of food
• A decreased appetite that is more constant

Other symptoms may include:

• Diarrhea
• Heartburn
• Bad breath (halitosis)

Persons with symptoms of black, tarry stools, and fatigue should seek immediate medical help or go to an emergency department to be evaluated for intestinal bleeding.

Yes, H. pylori are contagious. However, sometimes there is a gray area between the terms contagious and colonized. Contagious usually implies that a disease-causing agent is transferred from person to person, while colonization usually implies an agent that simply populates an organ but does not cause disease, even when transferred from person to person. The gray area occurs when many people have the agent that causes disease in some of them, but not in many others.

Some microbiologists consider such organisms as adapting to their human hosts by slowly changing from infecting humans to colonizing them. Although this is speculation, it seems to fit the ongoing situation with H. pylori. However, others think the bacteria become infecting agents when H. pylori’s genetic makeup is triggered by the surrounding GI environment to produce and release enough toxic chemicals to cause the GI tract to become inflamed.

Many individuals can be treated by their primary care doctors; however, some people may need specialists like infectious disease specialists, gastroenterologists, and possibly a surgeon to help manage and/or treat the person with H. pylori infection.

Accurate and simple tests for the detection of H. pylori infection are available (H. pylori infection tests). They include blood antibody tests, urea breath tests, stool antigen tests, and endoscopic biopsies.

• Blood tests for the presence of antibodies to H. pylori can be performed easily and rapidly. However, blood antibodies can persist for years after the complete eradication of H. pylori with antibiotics. Therefore, blood antibody tests (immunoglobulin G or IgG and/or IgA) may be good for diagnosing infection, but they are not good for determining if antibiotics have successfully eradicated the bacterium.
• The urea breath test (UBT) is a safe, easy, and accurate test for the presence of H. pylori in the stomach. The breath test relies on the ability of H. pylori to break down the naturally occurring chemical, urea, into carbon dioxide, which is absorbed from the stomach and eliminated from the body in the breath. Ten to 20 minutes after swallowing a capsule containing urea labeled with either a minute amount of radioactive carbon or heavy but not radioactive carbon, a breath sample is collected and analyzed for labeled carbon dioxide. The presence of labeled carbon dioxide in the breath (a positive test) means that there is an active infection. The test becomes negative (there is no radioactive carbon dioxide in the breath) shortly after the eradication of the bacterium from the stomach with antibiotics. Individuals who are concerned about even minute amounts of radioactivity can be tested with urea labeled with heavy, nonradioactive carbon.
• Endoscopy is an accurate test for diagnosing H. pylori as well as the inflammation and ulcers that it causes. For endoscopy, the doctor inserts a flexible viewing tube (endoscope) through the mouth, down the esophagus, and into the stomach and duodenum. During endoscopy, small tissue samples (biopsies) from the stomach lining can be removed. A biopsy specimen is placed on a special slide containing urea (for example, CLO test slides). If the urea is broken down by H. pylori in the biopsy, there is a change in color around the biopsy on the slide. This means that there is an infection with H. pylori in the stomach. Endoscopy also allows the determination of the severity of gastritis with biopsies as well as the presence of ulcers, MALT lymphoma, and cancer.
• Biopsies also may be cultured in the bacteriology laboratory for the presence of H. pylori; however, this is done infrequently since other simpler tests are available.
• Stool sample: A recently-developed test for H. pylori is a test in which the presence of the bacterium can be diagnosed from a sample of stool. The test uses an antibody to H. pylori to determine if H. pylori antigen is present in the stool. If it is, it means that H. pylori are infecting the stomach. Like the urea breath test, in addition to diagnosing infection with H. pylori, the stool test can be used to determine if eradication has been effective soon after treatment.

In 2012, the FDA approved the urea breath test to be done in children aged 3 years to 17 years old.

Chronic infection with H. pylori weakens the natural defenses of the lining of the stomach to the ulcerating action of acid. Medications that neutralize stomach acid (antacids) and medications that decrease the secretion of acid in the stomach (H2-blockers and proton pump inhibitors or PPIs) have been used effectively for many years to treat ulcers.

• H2-blockers
  • famotidine (Pepcid, Zantac 360)
  • cimetidine (Tagamet)
  • nizatidine (Axid)
• PPIs
  • omeprazole (Prilosec)
  • lansoprazole (Prevacid)
  • rabeprazole (Aciphex)
  • pantoprazole (Protonix)
  • esomeprazole (Nexium)

Treating H. pylori with acid-reducing antacids, H2-blockers, and PPIs, however, does not eradicate H. pylori from the stomach, and ulcers frequently return promptly after these medications are discontinued. Hence, antacids, H2-blockers, or PPIs have to be taken daily for many years to prevent the return of the ulcers and the complications of ulcers such as bleeding, perforation, and obstruction of the stomach. Even such long-term treatments can fail.

Eradication of H. pylori, however, usually prevents the return of ulcers and ulcer complications even after appropriate medications such as PPIs are stopped. Eradication of H. pylori also is important in the treatment of the rare condition known as MALT lymphoma of the stomach.

Treatment of H. pylori to prevent stomach cancer is controversial and discussed in this article.

H. pylori are difficult to eradicate (cure) from the stomach because it is capable of developing resistance to commonly used antibiotics (antibiotic-resistant H. pylori). Therefore, two or more antibiotics usually are given together with a PPI and/or bismuth-containing compounds to eradicate the bacterium. (Bismuth and PPIs have anti-H. pylori effects.)

Examples of combinations of medications that are effective include:

• a PPI, amoxicillin (Amoxil), and clarithromycin (Biaxin)
• a PPI, metronidazole (Flagyl), tetracycline, and bismuth subsalicylate (Pepto-Bismol, Bismuth)

These combinations of medications can be expected to cure 70% to 90% of infections. However, studies have shown that resistance of H. pylori (failure of antibiotics to eradicate the bacterium) to clarithromycin is common among patients who have prior exposure to clarithromycin or other chemically similar macrolide antibiotics (such as erythromycin).

Similarly, H. pylori's resistance to metronidazole is common among patients who have had prior exposure to metronidazole. In these patients, doctors have to find other combinations of antibiotics to treat H. pylori. Antibiotic resistance is another reason why antibiotics should be used carefully and judiciously for the right reasons, and the indiscriminate use of antibiotics for improper reasons should be discouraged.

First-line regimens for Helicobacter pylori eradication or cure are taken from the guidelines developed by the American College of Gastroenterology as follows:

1. Standard dose of a *PPI (proton pump inhibitor) *b.i.d. (esomeprazole is *q.d.),clarithromycin 500 mg b.i.d., amoxicillin 1,000 mg b.i.d. for 10-14 days
2. Standard dose PPI b.i.d., clarithromycin 500 mg b.i.d. metronidazole 500 mg b.i.d. for 10-14 days
3. Bismuth subsalicylate 525 mg p.o. q.i.d. metronidazole 250 mg * p.o. *q.i.d., tetracycline 500 mg p.o. q.i.d., ranitidine 150 mg p.o. b.i.d. or standard dose PPI q.d. to b.i.d. for 10-14 days
4. PPI + amoxicillin 1 g b.i.d., for 5 days, followed by PPI, clarithromycin 500 mg, tinidazole 500 mg b.i.d. for 5 days (used mainly in other countries)

*PPI = proton pump inhibitor; pcn = penicillin; p.o. = orally; q.d. = daily; b.i.d. = twice daily; t.i.d. = three times daily; q.i.d. = four times daily.

A recent investigation reported that triple therapy of either levofloxacin (Levaquin) or rifabutin in combination with amoxicillin and esomeprazole yielded cure rates of 90% and 88.6%. The treatments lasted 10 to 12 days respectively (10 days of levofloxacin 20=50 mg b.i.d. or rifabutin 150 mg q.d. for 12 days. Amoxicillin dose was 1 gm, esomeprazole was 40 mg, both b.i.d.).

Some doctors may want to confirm eradication of H. pylori after treatment with a urea breath test or a stool antigen test, particularly if there have been serious complications of the infection such as perforation or bleeding in the stomach or duodenum. Endoscopic biopsies to determine eradication of the bacterium are not necessary, and blood tests are not good for determining eradication since it takes many months or years for the antibodies to H. pylori to decrease. The best tests for determining eradication are the breath and stool tests discussed previously. Patients who fail to eradicate H. pylori with treatment are retreated, often with a different combination of medications. Also, a meta-analysis study of patients started on low-dose aspirin showed less than 20% were tested for H. pylori; this is concerning because low-dose aspirin roughly doubles the risk factors for getting an upper GI bleed in individuals with H. pylori infection.

There are many claims about natural treatments and cures for H. pylori infection. None of these have been scientifically proven to cure H. pylori infection; however, they include:

• Mastic gum
• Broccoli
• Matuka tea
• Manuka honey
• Coconut oil

Discuss all-natural herbs and supplements with your doctor before taking them.

Nutritionists and health care professionals suggest avoiding spicy foods, coffee, carbonated drinks, and pickled foods as these may increase the symptoms associated with the infection.

Many infections are mild and produce few if any, symptoms. The prognosis of these infections is excellent. Patients with more serious symptoms who are treated appropriately usually have a good prognosis although up to 20% may have a reoccurrence of the infection. Those with ulcers who have effective eradication of their infection heal their ulcers well (with usually minor scarring in the tissue).

Untreated and severe infections have a more guarded prognosis because extensive damage can occur with bleeding, scarring, anemia, and hypotension (low blood pressure) occurring. Some patients with these symptoms will die if not treated quickly. About 1% of people with the infection go on to develop gastric cancer. Researchers have suggested that it may be possible to use special inhibitors that will block the bacteria from adhering to the lining of the stomach's gastric tissue.

With at least 50% of the world population having detectable H. pylori in their stomachs, it seems likely that with no vaccine available, it will be very difficult or impossible for people to have no exposure to these bacteria. The chance of the organisms causing the symptomatic infection is low, but certainly not absent. Currently, suggestions have been made to prevent ulcers, but the effectiveness of these recommendations is unknown.

The following is a list of recommendations to help prevent ulcers:

1. Reduce or stop the intake of alcohol.
2. Stop smoking.
3. For pain control, use acetaminophen (Tylenol and others) instead of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs).
4. Avoid caffeine in coffee and many "power" drinks.
5. Check for GI symptoms and treat them immediately during or after radiation therapy.
6. Identify and reduce or avoid stress.
7. Wash hands with uncontaminated water to avoid contracting the bacterium.
8. If infected with H. pylori, antimicrobial treatment may prevent ulcer formation and extension of the disease.

Currently, there is no commercially available vaccine to prevent either the infection or colonization of the stomach by H pylori. However, research is ongoing, and the NIH is funding vaccine studies in conjunction with vaccine makers (For example, Helicovax to prevent H. pylori colonization of human GI tracts by EpiVax, Inc.). Moreover, some nutritionists suggest that a diet high in fruits and vegetables, and low in sugar may help reduce or stop H. pylori infection. In many individuals, the immune response to infection is ineffective and leads to life-long infection.