REVIEW Diagnostic methods for Helicobacter pylori infection: ideals, options, and limitations Parisa Sabbagh 1 & Mousa Mohammadnia-Afrouzi 1,2 & Mostafa Javanian 1 & Arefeh Babazadeh 1 & Veerendra Koppolu 3 & VeneelaKrishna Rekha Vasigala 4 & Hamid Reza Nouri 2 & Soheil Ebrahimpour 1 Received: 10 October 2018 /Accepted: 26 October 2018 /Published online: 9 November 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Helicobacter pylori (H. pylori) resides in the stomach, colonizes gastric epithelium, and causes several digestive system diseases. Several diagnostic methods utilizing invasive or non-invasive techniques with varying levels of sensitivity and specificity are developed to detect H. pylori infection. Selection of one or more diagnostic tests will depend on the clinical conditions, the experience of the clinician, cost, sensitivity, and specificity. Invasive methods require endoscopy with biopsies of gastric tissues for the histology, culture, and rapid urease test. Among non-invasive tests, urea breath test and fecal antigen tests are a quick diagnostic procedure with comparable accuracy to biopsy-based techniques and are methods of choice in the test and treatment setting. Other techniques such as serological methods to detect immunoglobulin G antibodies to H. pylori can show high accuracy as other non-invasive and invasive biopsies, but do not differentiate between current or past H. pylori infections. Polymerase chain reaction (PCR) is an emerging option that can be categorized as invasive and non-invasive tests. PCR method is beneficial to detect H. pylori from gastric biopsies without the need for the cultures. There is no other chronic gastrointestinal infection such as H. pylori with a set of comparable diagnostic methodologies. Despite the availability of multiple diagnostic methods, it remains unclear on the choice of any one method as the gold standard for detecting H. pylori infection, especially in epidemiological studies. In this work, we review the principal diagnostic methods used to detect H. pylori infection and their advantages and disadvantages, and applications in clinical practice. Keywords Helicobacter pylori . Characteristics of infection . Diagnosis . Invasive tests . Non-invasive tests Introduction Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes in gastric epithelium [1–5]. First, this bacterium was misrecognized as Pseudomonas spp. even though [6], during a clinical research project, Barry Marshall and Robin Warren discovered [7] it as Campylobacter pyloridis, which was later changed to H. pylori [8, 9]. H. pylori represent one of the most common bacterial in- fection in humans, which infected about half of the world’ s population [10, 11]. Often, H. pylori infection occurs in child- hood and continue throughout life when proper treatment is not provided [11]. In this regard, some studies suggested that the infected mothers are the major source of this infection of their kids, through contact with the contaminated stomach juice from the mother’ s mouth [12]. Research indicates that H. pylori spread from East Africa about 58,000 years ago and subsequently developed into many strains with varying degrees of pathogenicity [13]. Generally, the prevalence of the bacterium infection varies according to age, region, race, and socioeconomic statuses. The prevalence of H. pylori infection in the developing coun- tries is 50.8%, whereas the prevalence is 34.7% in the devel- oped countries [14]. Many documents show that humans are * Soheil Ebrahimpour drsoheil1503@yahoo.com 1 Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran 2 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran 3 Scientist Biopharmaceutical Development Medimmune, Gaithersburg, MD 20878, USA 4 Rangaraya Medical College, NTR University of Health Sciences, Kakinada, India European Journal of Clinical Microbiology & Infectious Diseases (2019) 38:55–66 https://doi.org/10.1007/s10096-018-3414-4