- The hpAfrica2 strain of Helicobacter pylori is a distinct phylogenetic population of this gram-negative, spiral-shaped bacterium, identified through multi-locus sequence typing (MLST).
- It is one of the three African H. pylori populations, alongside hpAfrica1 and hpNEAfrica, and is considered unique due to its deep phylogenetic divergence from other global populations.
- Predominantly found in South Africa, hpAfrica2 is believed to have co-evolved with human populations in Africa for tens of thousands of years, potentially predating the out-of-Africa migration.
- Its limited geographic distribution and genetic isolation make it a critical strain for studying H. pylori evolution, human migration, and the bacterium’s role in gastric diseases. Unlike hpAfrica1, which is more widespread across West and South Africa, hpAfrica2 is less common and primarily associated with specific ethnic groups, such as the Khoisan populations in South Africa, reflecting ancient human-bacterial co-evolution.
- Genetically, hpAfrica2 exhibits distinct characteristics that set it apart from other H. pylori populations. It forms a separate clade in phylogenetic analyses, indicating significant divergence from hpAfrica1, hpEurope, and hpEastAsia strains. A key feature of hpAfrica2 is its frequent possession of an intact cag pathogenicity island (cagPAI) in many isolates, which encodes the cagA gene and a type IV secretion system (T4SS) responsible for injecting CagA into host gastric epithelial cells. This contributes to increased inflammation and a higher risk of severe gastric diseases, such as peptic ulcers and gastric cancer. However, some hpAfrica2 isolates may have non-functional cagA due to mutations, similar to certain hpAfrica1 strains. The vacA gene in hpAfrica2 typically presents as the s1m1 allele, which is highly toxic and associated with severe pathology, though s2m2 and s1m2 alleles are also observed in South African isolates. Notably, hpAfrica2 strains often possess a full-length dupA gene (duodenal ulcer-promoting gene), with 16 of 22 isolates in one study showing this feature, unlike the truncated or absent dupA in many hpAfrica1 strains. This suggests a stronger association with duodenal ulcer risk in hpAfrica2-infected individuals.
- In terms of pathogenicity, hpAfrica2 is linked to a range of gastric diseases, but its clinical impact is less severe compared to hpAfrica1 in regions like Nigeria. In South Africa, where hpAfrica2 is prevalent, it is associated with gastritis and peptic ulcers, with lower rates of gastric erosions (4%) and ulcers (9.3%) compared to hpAfrica1’s 43.6% and 15.4% in Nigeria. The lower disease severity may be influenced by mixed infections with hpAfrica1 or host factors, such as immune modulation by co-infections (e.g., helminths) or dietary antioxidants, which are thought to contribute to the “African enigma.” This enigma refers to the paradoxically low gastric cancer rates in Africa despite high H. pylori prevalence (>70%). In South Africa, hpAfrica2’s role in gastric cancer is minimal, potentially due to genetic variations, such as non-functional cagA in some isolates, or environmental factors reducing carcinogenic progression. The strain’s interaction with the host immune system, often eliciting a Th2-biased response (IgG1 subclass), may further mitigate severe outcomes compared to Western populations.
- Antibiotic resistance in hpAfrica2 strains mirrors the challenges seen with hpAfrica1, though data specific to hpAfrica2 is less extensive. In South Africa, H. pylori isolates, including hpAfrica2, show high resistance to metronidazole (up to 75.8%, often linked to RdxA mutations), amoxicillin (72.6%), clarithromycin (29.2%), tetracycline (48.7%), and fluoroquinolones (17.4%). Clarithromycin resistance, driven by mutations like A2143G, is particularly concerning, suggesting that clarithromycin-based therapies may be ineffective in regions where hpAfrica2 is prevalent. The high resistance rates underscore the need for region-specific treatment guidelines, such as bismuth quadruple or concomitant therapies, and highlight the challenge of limited antimicrobial susceptibility testing in Africa. hpAfrica2’s resistance profile, combined with its genetic distinctiveness, makes it a valuable strain for studying the evolution of antibiotic resistance in H. pylori.
- In research, hpAfrica2 is significant for its insights into H. pylori’s evolutionary history and its implications for human migration. Its deep divergence suggests it may represent an ancient lineage of H. pylori, potentially linked to early human populations in Africa, such as the Khoisan. This makes hpAfrica2 a key strain for tracing human migration patterns and understanding bacterial adaptation to host populations. Comparative genomic studies with hpAfrica1 and non-African strains (e.g., hpEurope, hpEastAsia) reveal hpAfrica2’s unique genetic adaptations, such as its dupA prevalence and cagPAI functionality, which help elucidate differences in disease outcomes. The African enigma, where hpAfrica2’s high prevalence contrasts with low gastric cancer rates, is a focal point of investigation, with factors like host immunity, co-infections, and under-reporting of cancer cases considered. Overall, hpAfrica2’s genetic isolation, virulence profile, and regional significance make it a critical strain for advancing our understanding of H. pylori pathogenesis and developing targeted therapeutic strategies in Africa.
