- The hpAfrica1 strain of Helicobacter pylori is a major phylogenetic population of this gram-negative, spiral-shaped bacterium, identified through multi-locus sequence typing (MLST). It is predominantly found in African populations and holds significant research value due to its association with human migration patterns and diverse disease outcomes.
- Originating in Africa, hpAfrica1 reflects the bacterium’s co-evolution with humans over approximately 120,000 years. It is primarily distributed in West and South Africa, with subtypes such as hspWestAfrica (e.g., Nigeria) and hspSouthAfrica (e.g., South Africa), and is also detected in African diaspora populations, like in the Dominican Republic, due to historical migrations such as the slave trade. Some European and Middle Eastern strains show hpAfrica1 ancestry, likely from admixture events.
- The strain’s genetic diversity, with unique allele combinations, allows it to form distinct clades in phylogenetic analyses, separate from other populations like hpAfrica2 or hpEurope.
- In terms of virulence, hpAfrica1 strains are characterized by key factors that influence their pathogenicity.
- Most are cagA-positive, carrying the cag pathogenicity island (cagPAI), which encodes a type IV secretion system to inject CagA into host cells, increasing inflammation and the risk of ulcers or gastric cancer. However, some isolates, such as N2-85C2 and N1-103A1C1, lack the cagPAI, resulting in reduced virulence.
- In South Africa, certain isolates (e.g., SA-289A1, SA-330C) are cagA-positive by PCR but do not express functional CagA due to frameshift mutations or stop codons, highlighting variability.
- The vacA gene, another critical virulence factor, typically presents as the s1m1 allele in hpAfrica1, which is highly toxic and linked to severe gastric disease.
- In Nigeria, 82.9% of isolates have s1m1, compared to 62.3% in South Africa, where s2m2 (15.6%) and s1m2 (7.8%) are less common.
- The dupA gene, associated with duodenal ulcers, is often truncated or absent in hpAfrica1, unlike in hpAfrica2, and some strains possess unique integrating conjugative elements like ICEHptfs4, indicating specific genetic adaptations.
- Clinically, hpAfrica1 is linked to gastritis, peptic ulcer disease, and, to a lesser extent, gastric cancer, though outcomes vary by region.
- In Nigeria, hpAfrica1 strains are associated with higher rates of gastric erosions (43.6%) and ulcers (15.4%) compared to South Africa (4% and 9.3%, respectively). Despite its high prevalence in Africa (>70%), gastric cancer rates remain low, contributing to the “African enigma.” This paradox may stem from immune modulation by co-infections (e.g., helminths promoting Th2-biased responses), dietary antioxidants, or strain-specific factors like non-functional cagA.
- Nigerian strains, often cagA-positive and vacA s1m1, correlate with more severe pathologies, including rare gastric cancer cases (2.6%, unverified by histopathology), while South African strains show milder outcomes, possibly due to mixed infections with hpAfrica2 or genetic variations. No significant association exists between cagA functionality or phylogenetic profile and ulcer/erosion diagnoses in South Africa, underscoring regional differences.
- Antibiotic resistance is a major challenge with hpAfrica1 strains, particularly in Africa.
- Resistance rates are high for metronidazole (75.8%, linked to RdxA mutations), amoxicillin (72.6%, unusually high globally), clarithromycin (29.2%, with A2143G mutations in North Africa), tetracycline (48.7%), and fluoroquinolones (17.4%, with D87I mutations).
- In Senegal, hpAfrica1 isolates show 85% metronidazole resistance but only 1% clarithromycin resistance, reflecting regional variability. These high resistance rates, especially to clarithromycin (>15–20%), suggest that clarithromycin-based therapies should be abandoned in some African regions, with bismuth quadruple or concomitant therapies preferred.
- The lack of standardized antimicrobial susceptibility testing in Africa further complicates treatment, often requiring samples to be sent to better-equipped facilities.
- In research, hpAfrica1 is valuable for studying human migration and H. pylori pathogenesis. Its genetic diversity serves as a marker for tracing out-of-Africa migrations, with its presence in the Dominican Republic reflecting colonial slave trade patterns.
- Comparative genomics with hpEurope and hpEastAsia strains helps elucidate virulence differences, particularly why hpAfrica1 is less associated with gastric cancer than hpEastAsia. Admixture events in European and Middle Eastern strains show elevated hpAfrica1 ancestry, possibly due to selection against deleterious mutations in non-African strains.
- The African enigma, where high hpAfrica1 prevalence contrasts with low gastric cancer rates, is a focal point of study, with factors like host immunity, diet, and under-reporting of cancer cases considered. Overall, hpAfrica1’s genetic and clinical variability makes it a critical strain for understanding H. pylori’s global impact and developing region-specific treatment strategies.
