Helicobacter Pylori - Key Facts

Helicobacter Pylori - Key Facts

Anil Kumar, PhD
Apr 20 2021 12:35

What is Helicobacter Pylori?

H. Pylori is bacteria in the gut that convert urea into ammonia to survive the harsh acidic conditions in the stomach (1).

It is a spiral bacterium that lives on the stomach lining. High mobility and its ability to produce ammonia allows it to survive in the highly acidic conditions of the stomach.

Shaped as road of 2-4 micrometers in length and 0.5-1 micrometers in width, its uniquely identifying features are 2-6 rod-like flagella. They are about 3 micrometers in length, with a distinctive bulb at the head.

There are several species of Helicobacter. However, Helicobacter pylori is specific to the human stomach. Different Helicobacter species have also been found in cats, dogs and other animals where they are known to cause ulcers.

H. pylori strongly adapts to our unique stomach environments allowing it to stay throughout our lives. This is one reason why infections acquired during childhood continue in adults.

The pH of stomach lining varies between 4 and 6.5. But the bacterium prefers to grow around a pH of 5.5. It survives the fluctuations in stomach acidity by converting urea in the stomach into ammonia and bicarbonates. And by quickly moving away from high acidic regions.

This unique ability to digest urea is a hallmark of H. pylori, and is frequently used for confirming the bacterial infection.

How prevalent is H. pylori? 

Prevalence (approximate data from 2013-14) (2):

  • US and Canada: 30-35%
  • Mexica: 50%
  • Western Europe: 30-70%
  • Eastern Europe: 40-80%
  • India and China: 60%
  • Turkey: 80%
  • Ethiopia: 65%

Prevalence in younger generation is lower, e.g., in China the numbers were 30% in children compared to almost 60% in adults (2).

For past several decades, there is a steady decline in cases due to better hygiene & other unknown reasons. As an example, in The Netherlands, cases declined from 48% in 1940s to 16% in 1980s (2).

In developing countries, the infections often start in children and continue as they grow into adults, causing acidity, ulcers and stomach cancers. However, in developed countries most cases are observed among adults. First and second-generation immigrants from developing countries have higher rates compared to natives, likely from infections acquired during childhood.

Transmission of H. pylori:

  • How H. pylori transmits is not completely understood; however, with high probability, children acquire it during early childhood.
  • Most likely medium of transmission among people is either oral through saliva or fecal or both.
  • The bacterium has been detected in saliva, vomit, gastric reflux and feces.
  • There are no data to support infection from dentists, nurses, clinic visits for sexually-transmitted-disease or gastroenterologists (3).

What are the risk factors and who is at risk of H. pylori infection?

  • Family members: 75% of spouses and parents of children and half of siblings have been found to be in positive for those infected (4).
  • Age: About one-third of children and adults under 30 years of age have been found infected but the numbers increase to almost two-third among the 55-65 age groups (5).
  • Race: Risk of infection among African Americans and Hispanic groups is twice that among Europeans (6).
  • Living conditions: Risk increases among those sharing beds and living in crowded homes. That's because close proximity increases the oral or fecal transmission of the pylori bacteria. Those in rural communities seem to have higher prevalence than in urban communities (7).
  • Others: Risk has been found to be higher in US for those in lower socio-economic backgrounds, poor living conditions. People recently immigrated from regions with higher prevalence (e.g., developing or tropical countries) also tend to be at higher risk.
  • No difference was found between genders. The impact of smoking and alcohol is also not clearly understood (7).
  • There might be some genetic component that is not yet fully understood. Studies of identical twins growing apart often show similar infections (8).

Risk increases with additional common symptoms of:

  • Fevers
  • Weight loss
  • Anemia
  • Gastrointestinal bleeding
  • Difficult in swallowing (dysphagia)
  • Family history of abnormal and excessive tissue growth (neoplasm)
  • Indigestion (dyspepsia)

What are the implications of infection?

  • Helicobacter pylori is a known carcinogen (9). Although extremely rare, studies have shown that it can cause cancer of the duodenum (end of stomach that connects to the small intestine ).
  • Infections are often asymptotic but in serious cases, they can cause high acidity, ulcers, and acid reflex which can be very difficult to diagnose.
  • Infection generally has no immediate implications unless it results in common symptoms of gastric ulcer or other annoying side effects.
  • There are no clear data to indicate H. pylori increases the risk of GERD or heart burn (1).
  • The risk of developing gastric cancer due to H. pylori in US and Europe is relatively small (1-2% cases). However, the bacterial infection increases the risk ten-fold and treatment seem to have no change in this risk (1).

What are the various testing methods for H. pylori?

There are different kinds of H. pylori test:

  • Urea breath test (10): when the bacteria convert carbon-labeled urea into ammonia & CO2. These can be detected through a breath test. The test is highly reliable, at about 95% sensitivity and specificity (true positive and true negative rates, respectively). The cost is much higher at 4-5 times of fecal antigen test.
  • Fecal antigen test: an ELISA test that checks for the presence of bacteria in stool. It has approx. 95% sensitivity and specificity.
  • Blood antibody test: checks for IgG antibodies in the blood, from current or past infections. It does not depend on medication or antibiotics. It is an efficient way to check large groups for population-based studies.

H. pylori antibody test: What are the advantages and limitations?

  • Advantage: Simple and easy test with a finger prick sample that can be collected at home and mailed to the lab from home. It does not depend on medication (e.g., PPIs) or antibiotics.
  • Limitation: can't tell whether it's currently active or a past infection. Therefore a positive case might require another stool or urea breath test for confirmation.
  • Things to Keep in Mind:

  • An IgG antibody test checks for immune response against the infection. However, very recent infections might not have produced enough antibodies to detect. And very old infections might have very little antibodies left in the blood. Some people may not even produce enough antibodies.
  • For taking the stool test, one should not be taking acid reducing medications (PPIs or proton-pump inhibitors such as Nexium, Prilosec, Omeprazole, Esomeprazole, Protonix) for at least two weeks. And they should not be on antibiotics for at least 4 weeks. The blood antibody test has no such requirement.

What’s the treatment for H. pylori infection?

  • A triple therapy of PPI (Omeprazole, Esomeprazole, Nexium or Prilosec) and antibiotics (amoxycillin and levofloxacin or clarithromycin or bismuth-containing quadruple regimen) for 7-14 days is a prescribed testing methodology (11).
  • Probiotics have shown to help with better outcomes in treatment (12).
  • Mayo Clinic recommends all treatment regimens should be taken for 14 days, and eradication testing should be performed in all patients (13).
  • The reinfection rate is relatively low, at around 1-3%, mainly in cases where the bacteria is not fully removed from the body. But reinfection rates vary by regions, with some countries showing much higher rates of reinfection.

What are the known virulence factors for H. pylori?

Definition: Just as our body develops immunity against bacteria and viruses over time, these pathogens have clever defense mechanisms to counteract and overcome our body's defense mechanisms. They carry 'virulence' genes that are capable of producing molecules that allow them to enter the body, hide without detection, and then multiply and grow to cause infections (14). In that sense, 'virulence factors' are genes that allow the bacterial 'wolfs' to wrap themselves in the 'sheep's clothing' of our body's cells (15).

Some of these protein molecules are more dangerous than others. For H. pylori, certain strains or variations of the bacteria are more infectious. Few of them are listed here (1):

  • cagA: this gene produces protein CagA (also called cytotoxin-associated gene A) and is found more often than others genes. About 50-70% of all strains in US and Europe are cagA. Its presence causes more severe infection, stronger gastritis (acidity), higher inflammation and greater risk of stomach ulcer and gastric cancer.
  • vacA: vacuolating toxin A—which causes holes-like features in the cells—about half of strains carry vacA. This gene increases the risk of damage to the lining of the stomach. VacA carrying strains also have much higher adaptability. This allows a more persistent infection, observed as a constant growing and shrinking duodenal ulcer.
  • babA: blood-group antigen binding adhesion, is known to increase the risk of peptic ulcer and gastric cancer. It is often a more severe disease and long-term infection.
  • dupA: duodenal-ulcer promoting gene A. It is associated with ulcer in the duodenum (the part of stomach connecting with small intestine). But known for reduced risk of damage to lining of the stomach.
  • iceA: induced-by-contact-with-epithelium A, a gene causing higher inflammation. In some instances it even causes peptic ulcer.
  • oipA: outer-membrane inflammatory protein A gene, is often linked to cagA. It is known to cause duodenal ulcer and gastric cancer.
  • virB and virD are part of the cagA pathogenicity island (PAI—the gene clusters of pathogens responsible for causing the disease). They increase the risk of peptic ulcer and gastric cancer.

Key Moment: 2005 Nobel Prize

To Barry J. Marshall and J. Robin Warren for their discovery of “the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease".

helicobacter-pylori-key-facts

Source: The Nobel Prize: https://www.nobelprize.org/prizes/medicine/2005/press-release/

References: