Helicobacter pylori (H. pylori) is a ubiquitous, microaerophilic, gram-negative, bacillus. It affects more than 50% of the population worldwide and is one of the widely prevalent common chronic bacterial infections. Drs. Barry Marshall and Robin Warren first isolated H. pylori in the year 1983. The prevalence of H. pylori is variable between 19 and 88% and depends on various factors such as geographical location, patient's age, sanitation, and socioeconomic status. Patients often acquire H. pylori infections during childhood, and if untreated, persist throughout life.
H. pylori have strong associations with many non-neoplastic (peptic ulcer disease, chronic atrophic gastritis) and neoplastic (adenocarcinoma of the stomach, gastric lymphoma arising from mucosa-associated lymphoid tissue or MALT) conditions of the gastrointestinal (GI) tract. Due to this strong association with malignant conditions, the World Health Organization (WHO) categorized H. pylori as a class I (definite) carcinogen in 1994. Early diagnosis of H. pylori and successful eradication cures chronic gastritis and can reduce the progression to the long-term complications. H. pylori gastritis is also implicated in non-ulcer dyspepsia. Many hematologic disorders such as unexplained iron deficiency anemia and immune thrombocytopenic purpura in adults also have links with H. pylori, but the exact pathogenic mechanisms are unclear.
Tests for H pylori include both invasive and non-invasive methods. Each method has its advantages and limitations. The selection of a test or combination of tests depends on many factors such as the clinical contexts, cost of the testing, availability, and their sensitivities and specificities. The gold standard investigation for confirmation of H. pylori is esophagogastroduodenoscopy (EGD) with histopathological examination of the biopsy. Further testing methods such as immunohistochemical staining, rapid urease test, bacterial culture and, PCR increase the diagnostic yield of EGD. EGD also offers the advantage of evaluation of the long-term complications associated with H. pylori. EGD is recommended in the evaluation of dyspepsia in patients over 60 years of life and also in the presence of alarm symptoms such as significant weight loss, gastrointestinal bleeding, abdominal mass, iron deficiency anemia and difficulty in swallowing. However, EGD is invasive and expensive, limiting its utility as the first investigation of choice in young (less than 60 years of life) patients with dyspepsia and without alarm symptoms. Also, an EGD evaluation may be falsely negative in patients who have a patchy distribution of the disease. The popular non-invasive methods include urea breath test (UBT), H. pylori stool antigen test (SAT), and serological tests.
Reliable non-invasive methods include UBT and SAT. UBT is the most accurate testing among the non-invasive tests. SAT is cheaper but slightly less accurate than the UBT. SAT involves stool collection, which may not be preferred by some patients. H. pylori IgG serology is not recommended in places with lower prevalence rates of less than 30%. With the lower prevalence of H. pylori, the pretest probability of diagnosing a true infection is lower. Also, the antibodies against H. pylori persist for an indefinite period and does not differentiate past from present infections. For the same reason, serological methods are not useful for evaluation of eradication after completion of treatment. However, serological testing for H. pylori is useful for epidemiological studies and for screening larger populations in places with a higher prevalence rate. Antigen-specific serological tests in whole blood, saliva are not recommended due to their lower predictive value.
UBT is useful for both the initial diagnosis of H. pylori (test-and-treat strategy) and also in the evaluation of post-treatment status. Urease is not present in mammalian cells, and hence its presence indicates urease containing microbes. H. pylori utilize urease to breakdown urea into ammonia and carbon dioxide (CO2). The ammonia is utilized by H. pylori in the neutralization of gastric acidity and helps in its colonization. Bacteria other than H. pylori are usually not present in the stomach with few exceptions such as in patients with achlorhydria. UBT exploits this ability of urease, which is abundantly present in H. pylori to promptly hydrolyze urea into ammonia and carbon dioxide (CO2). This CO2 enters the bloodstream and is later exhaled via the lungs. By using urea as a substrate with a labeled carbon (C) isotope, the exhaled CO2 with the labeled C, can be measured and quantified for the diagnosis of H. pylori. Testing commonly uses two isotopes of carbon for UBT - 14C (a radioactive isotope) and 13C (naturally occurring, stable non-radioactive isotope). The performance of both UBTs is almost similar, with sensitivities above 95% and specificities above 93%.