Helicobacter Pylori: The Silent Stomach Invader in MENA

Quick facts

• pylori infection is a significant public health concern in the MENA region due to its strong association with various gastroduodenal diseases, including chronic gastritis, peptic ulcers, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma.
• The MENA region exhibits a higher prevalence of pylori infection than the global average, attributed to socioeconomic factors, genetic susceptibility, and shortcomings in diagnostic and treatment strategies. Additionally, the lack of standardized regional screening guidelines highlights the urgent need for robust studies to determine its accurate prevalence rates.
• Antibiotic resistance is a major concern, with high rates of resistance to metronidazole and clarithromycin, especially in regions with poor sanitation, such as MENA.
• Emerging vaccine methods utilizing antigen-based strategies, vector-based vaccines, nano-delivery systems, and parenteral vaccines hold promise to address the high prevalence in the MENA regions.

Uncovering the facts behind the bacteria

Helicobacter Pylori (H. pylori) infection is a widespread bacterium that has effectively colonized the Middle East and North Africa (MENA) regions. In general, the prevalence of H. pylori infection ranges from around 7% to 50% in young children and up to 36% to 94% in adults in the MENA region. Countries such as Yemen exhibit an exceptionally high prevalence of nearly 80% of H. pylori infection cases. Additionally, Africa as a developing region carries a disproportionately high burden of infectious diseases compared to other continents. It accounts for around 70% of the global prevalence of H. pylori infections, with the highest rates observed among young children.

1. pylori is a gram-negative, microaerophilic bacterium with a distinctive helical shape and multiple polar-sheathed flagella that facilitate motility and tissue invasion. In the MENA region, inadequate hygiene, poor sanitation, contaminated water, and dietary habits, such as consuming unpasteurized dairy and undercooked meats, significantly increase the risk of H. pylori transmission. Contributing factors like age, lack of standardized diagnostic methods, limited education, and antibiotic resistance have exacerbated infection rates over the past decade.

Diagnosing H. pylori can be done using various methods that differ in invasiveness and timing relative to treatment. The choice depends on infection prevalence, patient age, and cost. Invasive endoscopy with biopsies can result in inaccurate findings due to uneven colonization and is not suitable for large-scale studies. For broader population screening, serodiagnosis, particularly enzyme-linked immunosorbent assay (ELISA), is favored for its efficiency in detecting antibodies. Despite numerous local and regional comparative studies of these methods, there are still no established local consensus guidelines in the MENA region.

Helicobacter Pylori Unmet needs

There is a lack of well-designed epidemiological studies on the prevalence of various H. pylori genotypes in the MENA region, highlighting the epidemiological gaps. Existing research underscores the urgent need for concerted efforts to validate affordable, non-invasive, and accurate diagnostic methods. Moreover, the MENA region faces a significant challenge with the prevalence of antibiotic-resistant H. pylori strains, complicating the selection of effective treatment regimens. Additionally, inadequate testing for antibiotic sensitivity leads to treatment failures and hinders the accurate diagnosis of ongoing infections. Thus, the lack of standardized protocols for H. pylori testing contributes not only to inconsistencies in testing procedures and result interpretation but also impacts the accuracy of diagnosis. Thus, it is essential to develop standardized guidelines and diagnostic protocols tailored to the MENA region, incorporating adjusted thresholds for interpreting test outcomes. This approach ensures a thorough assessment of test sensitivity and specificity across different diagnostic methods.

Helicobacter Pylori Treatment challenges

Numerous studies indicate that H. pylori infection is the leading bacterial cause of both malignant and non-malignant gastroduodenal diseases and is implicated in extra-gastroduodenal conditions. The International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) classify H. pylori as a definitive carcinogen for stomach cancer. However, the precise mechanisms by which H. pylori contributes to the development of gastric cancer are not fully understood. Although it is a significant risk factor, the interplay between the infection, host, and environmental factors also influences the incidence of gastric cancer in this region.

The bacterium’s main virulence genes, including cagA, vacA (subtypes s1 and m1/m2), and iceA, are associated with severe gastroduodenal diseases in the MENA region.  Studies suggest vacA gene is widely found, with the s1 and m1 alleles being more frequently present in the northern areas of the MENA region as opposed to the southern parts, likely due to the diverse genetic makeup of H. pylori strains in these regions. The cagA gene is also commonly seen, showing a high prevalence in non-Semitic populations. Conversely, the iceA gene is notably prevalent among patients with dyspepsia in Saudi Arabia, where the iceA1 subtype is the most common.

Furthermore, the current approach to treating H. pylori infections is therapeutic rather than preventive, focusing on eradicating the bacteria to heal associated peptic ulcers, making the increased prevalence of antibiotic resistance a global challenge. Clarithromycin-based triple therapy, which includes a proton pump inhibitor (PPI), clarithromycin, and either amoxicillin or metronidazole for 14 days, is no longer recommended as a first-line treatment in many MENA regions due to rising clarithromycin resistance. Instead, bismuth quadruple therapy (a PPI, bismuth, tetracycline, and a nitroimidazole for 10–14 days) is preferred as a first-line treatment, especially in areas with high clarithromycin resistance or for patients with prior macrolide exposure. Additionally, concomitant therapy, which involves a PPI, clarithromycin, amoxicillin, and nitroimidazole for 10–14 days, is another promising first-line option, demonstrating similar or improved efficacy. Therefore, physicians in the MENA region should take into account local antibiotic resistance patterns and the patient’s history of antibiotic use when selecting the most appropriate first-line treatment for H. pylori infection.

Emerging Helicobacter Pylori vaccine approaches

The approval of an effective H. pylori vaccine has the potential to transform the reduction of the global burden of this infection and curb the spread of resistant strains. Several promising vaccine strategies are under development, including the use of H. pylori antigens like urease, CagA, and VacA in combination with immune adjuvants or inactivating whole-cell H. pylori vaccines that aim to enhance mucosal immunity and reduce bacterial colonization in the stomach. Vector vaccines using Bacillus subtilis spores to express H. pylori urease subunits A and B, administered orally, which have also shown success in boosting IgA levels and further decreasing stomach colonization in mice. Furthermore, nano-delivery systems with chitosan polymers as immune adjuvants for H. pylori vaccines exhibit potential, as do parenteral vaccines employing E. coli heat-labile toxin among others.

Currently, the only H. pylori vaccine to complete Phase III clinical trials so far is a recombinant subunit vaccine using urease subunit B (UreB) as the antigen, which demonstrated sound prophylactic effects. Despite these promising advances, the progress toward an effective vaccine has been slow, necessitating further research. Therefore, H. pylori vaccines represent a promising frontier in infection management, with ongoing research poised to alleviate global health burdens associated with antibiotic resistance and persistent infection risks.