Stool Antigen Testing:critical factors to consider

Background and Clinical Significance

•  H. pylori is a spiral-shaped Gram negative bacterium that infects about 3 billion people worldwide 
•  Most people are infected as children
• Colonizes the stomach and duodenum indefinitely 
•  Infection increases linearly with age > 40% age over 60 years
•  HP has been classified as group I carcinogen for gastric carcinoma by the World Health Organization 
•  HP-infected individual has 2-8 times higher risk of gastric carcinoma than the general population 
•  Stomach cancer causes about 800,000 deaths worldwide per year

 Common in East Asia and Eastern Europe World Cancer Report 2014. World Health Organization

Mode of transmission:

•  fecal-oral 
•  person to person 
• contaminated water 
•  contaminated food 
•  zoonotic – (domestic cats, primates, sheep)

Clinical Outcomes of Helicobacter pylori infections

• Greater than  80% of people infected will be asymptomatic 
•  15 - 20%  will suffer from chronic gastritis, gastric ulcer or duodenal ulcer
• Less than 1% of people will develop gastric cancer

Source: Dr. Hagmeyer
https://drhagmeyer.com/the-damaging-effects-of-h-pylori/

The prevalence rates of Helicobacter pylori (H. pylori) infection in the US

60% of Hispanics, 54% of African Americans, and  20% Caucasians are affected.

•  New Mexico 15-20% 
• New York 15-20% S
• outh Carolina ≥20% 
• Puerto Rico ≥20% 
• llinois 15-20% 

Sonnenberg et al. (2010). A National Study of Helicobactor pylori Infection in Gastric Biopsy Specimens

 

Prevalence of H. pylori in Africa and East Asia

Why Stool Antigen Testing?

•  Simple 
• Cost-effective 
• High Sensitivity and Specificity 

 Purpose

• Diagnose an active infection
•  Confirm eradication of H. pylori after treatment
• Eradication reduces risk of gastric cancer

 Pit falls

•  False negative result in patients who are taking PPIs antibiotics or bismuth 
•  Inadequate sample volume 
•  False positive result in patients with acute upper gastrointestinal bleeding 
•  H. pylori antigen testing appears to be more accurate at detecting eradication when performed 4 - 8 weeks

 Data Interpretation

 Why cut-off value?

•  H pylori is genetically highly diverse
•  Several strains, variation in virulence factors depending on geographic location

CagA gene differs between isolates from East Asia versus Europe and North America iceA1 found in Asian countries; iceA2 found in Western countries Particular variants of vacA, such as vacA s1/m1 restricted to East Asia. (Shiota et al., 2013)

• Cut-off values for EIA testing set by manufacturers not representative of samples

 Other Factors to Consider

• Country of origin/birth Geographic location and prevalence of H. pylori 
• Age 
• Frequency of travel
• Travel destination

Robin Warren (left) Barry Marshal(right). Won the Nobel prize in physiology in 2005 for their discovery of H. pylori in 1981. 

To treat or not to treat: Helicobacter pylori: Friend or foe?

• Antibiotic Resistance Adverse effects- anaphylaxis Clostridium difficile infection
•  Treatment tops $32 billion in the US 
• Protection from gastroesophageal reflux disease and esophageal adenocarcinoma 
• H. pylori has been colonizing the human stomach for more than 58,000 years 
• What if you alter the colonization of the fecal microbiome? 
• Inverse relationship between H. pylori infection and asthma, allergies (Malnick et al., 2014) Possible protection from Multiple Sclerosis (Mohebi et al., 2013) 

References

 1. Nishikawa, H. et al. Impact of structural polymorphism for the Helicobacter pylori CagA oncoprotein on binding to polarity-regulating kinase PAR1b. Sci. Rep. 6, 30031; doi: 10.1038/srep30031 (2016).
 2. Suzuki R, Shiota S, Yamaoka Y. Molecular epidemiology, population genetics, and pathogenic role of Helicobacter pylori. Infection, Genetics and Evolution. 2012;12(2):203-213. doi:10.1016/j.meegid.2011.12.002
  3. Ranjbar R, Khamesipour F, Jonaidi‐Jafari N, Rahimi E. Helicobacter pylori isolated from Iranian drinking water: vacA, cagA, iceA, oipA and babA2genotype status and antimicrobial resistance properties. FEBS Open Bio. 2016;6(5):433-441. doi:10.1002/2211-5463.12054
4. Yamaoka Y. Mechanisms of disease: Helicobacter pylori virulence factors. Nature reviews Gastroenterology & hepatology. 2010;7(11):629-641. doi:10.1038/nrgastro.2010.154.
 5. SHIOTA S, SUZUKI R, YAMAOKA Y. The significance of virulence factors in Helicobacter pylori. Journal of digestive diseases. 2013;14(7):341-349. doi:10.1111/1751-2980.12054.
6. Mégraud F, Lehours P. Helicobacter pylori Detection and Antimicrobial Susceptibility Testing. Clinical Microbiology Reviews. 2007;20(2):280-322. doi:10.1128/CMR.00033-06.
7. Syam AF, Rani AA, Abdullah M, et al. Accuracy of Helicobacter pylori stool antigen for the detection of Helicobacter pylori infection in dyspeptic patients. World
8. Journal of Gastroenterology : WJG. 2005;11(3):386-388. doi:10.3748/wjg.v11.i3.386.
9. Shimoyama T. Stool antigen tests for the management of Helicobacter pylori infection. World Journal of Gastroenterology : WJG. 2013;19(45):8188-8191. doi:10.3748/wjg.v19.i45.8188.  10.Kodama M, Murakami K, Okimoto T, et al. Influence of proton pump inhibitor treatment on Helicobacter pylori stool antigen test. World Journal of Gastroenterology : WJG. 2012;18(1):44-48. doi:10.3748/wjg.v18.i1.44.
11. Wang Y-K, Kuo F-C, Liu C-J, et al. Diagnosis of Helicobacter pylori infection: Current options and developments. World Journal of Gastroenterology : WJG. 2015;21(40):11221-11235. doi:10.3748/wjg.v21.i40.11221.
12. Malnick SDH, Melzer E, Attali M, Duek G, Yahav J. Helicobacter pylori: Friend or foe? World Journal of Gastroenterology : WJG. 2014;20(27):8979-8985. doi:10.3748/wjg.v20.i27.8979.
 13. Mohebi N, Mamarabadi M, Moghaddasi M. Relation of Helicobacter Pylori Infection and Multiple Sclerosis in Iranian Patients. Neurology International. 2013;5(2):e10. doi:10.4081/ni.2013.e10.
 14. Tveit AH, Bruce MG, Bruden DL, et al. Alaska Sentinel Surveillance Study of Helicobacter pylori Isolates from Alaska Native Persons from 2000 to 2008. Journal of Clinical Microbiology. 2011;49(10):3638-3643. doi:10.1128/JCM.01067-11.
 15. Stewart VR, Wild CP. World Cancer Report 2014. In: Stewart VR, Wild CP. Cancer by organ site. Geneva, Switzerland: IARC Publications; 2014.