Strengths and weakness of endoscopic and noninvasive tests for the detection of
Abstract
Helicobacter pylori (H. pylori) is a Gram-negative bacterium that infects approximately 50% of the world population, and currently, no treatment is satisfactory for its management. Understanding the pathophysiology and pathogenesis mechanisms of H. pylori has increased over the years. Proper adherence and colonization of H. pylori induce genetic alterations, express numerous virulence factors, and trigger diverse adaptive mechanisms, making possible the colonization of an organ with a highly acidic lumen. The mode for the transmission of infection can be oral-oral or fecal-oral. Various effector proteins or toxins are released by the organism for successful colonization and infection. For the virulence and pathogenicity of H. pylori, the virulence factors, host, and environmental factors interplay a very important role. Virulence factors for H. pylori enhanced the pathogenicity of cytotoxin-associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory proteins, and gamma-glutamyl transpeptidase. The host immune system through Th1-polarized response plays a crucial role in the course of infection. The most common symptoms in H. pylori-positive individuals are peptic ulcers, gastric adenocarcinomas, and mucosa-associated lymphoid tissue lymphomas, whereas some positive individuals remain asymptomatic. Detection of H. pylori infection can be through invasive and noninvasive diagnostic methods. We critically reflect on the infection of H. pylori and the virulence and pathogenesis mechanisms of H. pylori.
Keywords
- pathogenesis
- virulence factor
- colonization
- transmission
- diagnosis
1. Introduction
![](http://cdnintech.com/media/chapter/83199/1718141272-78148737/media/F1.png)
Figure 1.
Representation of characteristics of
2. Clinical manifestations and diagnosis
The discovery of
Tests | Mechanism | Strengths | Weaknesses |
---|---|---|---|
Culture | Can be kept in a transport medium, like Portagerm pylori or Stuart’s transport medium up to 24 h at 4°C. The commonly used media include Pylori agar, Skirrow agar, Columbia blood agar, Brucella agar, Brain heart infusion or Trypticase soy agar, supplemented with sheep or horse blood. | Allows testing of antibiotic susceptibilities | Poor availability in some countries |
Molecular-based | Several target genes like UreA, glmM, UreC, 16S rRNA, 23S rRNA, HSP60, and VacA genes detected for the detection of | Detects infection and can assess susceptibility/resistance for all six commonly used antibiotics. Stool can be used. It gives Rapid results (days) | not to be covered by insurance |
Histology | Accuracy of histology, such as the site, size and number of biopsies, the staining methods, proton pump inhibitor (PPI), antibiotics of the examining pathologist. | Can be used for the testing of infection and evaluate for eradication. Provides additional information such as degree of inflammation and associated pathology | Accurate results require interested pathologist and use of special stain, preferably immunohistochemical |
Rapid urease | Convert the urea test reagent to ammonia, resulting in increase of pH and color change during pH monitor | It is a Rapid, Inexpensive. Good sensitivity and specificity | Requires prior cessation of antibiotics, bismuth. products, or proton pump inhibitors to reduce risk of false negative results |
Serology | Detection of Specific anti- | Widely available, Least expensive. Does not require medication modifications prior to testing | Does not reliably delineate between active and previous infection. Cannot confirm eradication |
Stool antigen | assesses the presence of bacterial antigens in stool. | High sensitivity and specificity. Can be used to test for active infection and evaluate for eradication | Stool sample needed, patient aversion. Requires prior cessation of antibiotics, bismuth products, or proton pump inhibitors to reduce risk of false negative results |
Urea breath | Enzyme splits urea into ammonia and CO2Patients ingest urea labeled with either 13C or 14C, and the labeled urea comes into contact with the mucosa and diffuses through the mucus towards the | High sensitivity and specificity Can be used to test for active infection and evaluate for eradication | Resources and trained personnel needed to reliably reproduce test Requires prior cessation of antibiotics, bismuth products, or proton pump inhibitors to reduce risk of false negative results |
Table 1.
First-generation immigrants from high-prevalence countries and potential high-risk populations were targeted for testing. Once the presence of the infection has been diagnosed and documented outreach to family members is suggested because transmission from person to person occurs within families [40]. Testing and treating of
The diagnostic strategy utilized clinical indication as well as the local availability and costs of the different tests followed by patient preferences [35]. The presence of the infection gives rise to a serum immune response. Recently, the most commonly used diagnostic test was serology [38]. By Medicare serology is generally neither recommended currently. Tests for the detection of
A meta-analysis reported that testing for antibodies from urine samples might be a good diagnostic option [54, 55]. For the confirmation of the accuracy of this method, further studies are necessary. Through the discovery of specific serological markers for the diagnosis of
3. Pathogenesis
3.1 Colonization
A special mechanism is required by
Apart from them, various transition metals are crucial for living organisms, as they serve as cofactors for enzymatic reactions that enhanced the rate of reaction which carries out genetic material replication, transcription, attenuation of oxidative stress, and cellular energy production [54]. In bacteria for survival and successful infection, these metals are crucial [62]. Nickel is an essential metal for
3.2 Cytotoxin-associated gene product (CagA)
Cytotoxin-associated gene product (CagA) is one of the most important and studied virulence factors of
Transport of CagA protein from gastric mucosal surface to endothelial cells for the tyrosine phosphorylation, carried out by T4SS which directly induces an immune response [75, 77]. The specific interaction between the
Virulence factors | Functions | References |
---|---|---|
Arginase | Prevents bacterial killing & T-cell proliferation, Stimulate apoptosis, Impairing of immune responses, Help the | [80] |
Heat shock proteins | Enhancing adherence to epithelial surfaces, engaged in urease activation, apoptosis and autophagy Control, To maintain the structure and properties of the effector proteins, Protection of cell from reactive oxygen species (ROS),Promotes the production and release of IL-8, TNF-α, and COX-2 | [81, 82] |
Superoxide dismutase (SOD) | Protection of cell from reactive oxygen species (ROS), colonization enhancement, Inhibiting the production of cytokines, Stimulating the activation of macrophage | [83] |
γ-glutamyl-transferase | Facilitating the apoptosis and necrosis, Inducing the release of pro-inflammatory proteins and release of ROS, Stimulate DNA damage | [84] |
Lipopolysaccharide | Triggering of signaling pathways, Induction of several inflammatory responses, Induce immune responses, Disrupts the mucus secretion | [85] |
Cholesteryl α-glucosyltransferase (αCgT) | Shield | [86] |
Phospholipase | Activating the signaling pathways (e.g. ERK1/2)and Trigger chronic inflammation, Enhancing the bacterial colonization, Involved in the degradation of lipids and damage to mucus layer | [87, 88] |
Table 2.
Important virulence factors in
3.2.1 Non-CagA virulence factors
Impairing gastric homeostasis is the main capacity by other various virulence factors. Vacuolating cytotoxins (VacA) protein and its genes are presents in almost all the strains, promotes pathogenicity of
The virulence factor promotes gastritis, ulcer, and prolonged infection lead to the cancer development [17, 92]. Duodenal ulcer-promoting gene (DupA) gives a higher acid resistance to the bacterium which promote increase in the production of IL-8 in the gastric mucosa [95]. DupA belongs to the T4SS which integrate conjugative element (ICEHptfs4). VirB4 ATPase homolog is encoded by
3.3 Treatment
No universal regimen for the treatment of
![](http://cdnintech.com/media/chapter/83199/1718141272-78148737/media/F2.png)
Figure 2.
Treatment regimens of
Probiotics are ―live microorganisms that, when administered in adequate amounts, confer health benefits on the host and they favorably alter the balance in intestinal microflora [107]. Probiotics prevent the adhesion of pathogens by competing for the binding site on intestinal epithelial cells, reducing the colonization of pathogens and thereby preventing the onset of infection. The probiotic's clinical benefits are widely accepted such as diarrhea, antibiotic-associated diarrhea, functional digestive involvements, inflammatory bowel disease, cardiovascular diseases, allergic reactions, and cancer [104, 107]. Anti -
![](http://cdnintech.com/media/chapter/83199/1718141272-78148737/media/F3.png)
Figure 3.
Mechanism of probiotics against
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