Fernando, Neluka Suhasini; (2001) Investigations into the variation of strains of Helicobacter pylori and the host response to infection from different geographical locations. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Most patients colonized by H. pylori remain asymptomatic. Many patients complain of dyspepsia, but any association with H. pylori colonization remains controversial. About 20% of colonized individuals develop duodenal or gastric ulcers and some develop gastric cancer. Urease, lipopolysaccharide, vacuolating cytotoxin (VacA) and cytotoxin associated protein (CagA) are potential virulence factors, but their role in different geographical populations is unclear. Therefore this study aimed to determine: H.pylori genotypes found in different parts of the world; the host immune response to selected antigens; the socio-economic conditions in the study areas; and to correlate bacterial, host and environmental, differences with the clinical status of the patient. Techniques included ELISA; SDS-PAGE; Westernblotting; Isoelectric focusing; PCR; and Southern blotting. H. pylori prevalence in Sri Lanka, believed to be low, was found to be high, similar to other developing countries. Initial infection occurred in early childhood, whilst active disease developed in later childhood. Serology and antigen detection methods failed to reveal the true prevalence. Strains from different geographical regions were diverse, with all vacA alleles represented. The s1 allele normally predominated. Overall, the genotype was not related to disease, but in Italian children there was a significant association. In Sri Lanka and Italy, the commonest genotype was s1am1, with greater heterogeneity in Sri Lanka. In Zambia s1b was the commonest subtype. In Iran s2 and s1 occurred at equal frequency, with s1c observed most commonly. H.pylori strains of similar genotype were associated with different clinical and histological presentations. Serology showed that urban upbringing, Ascaris infection and low CD4+ count were inversely related to H. pylori sero-positivity. Antibodies to lipopolysaccharide and a 35kDa protein were the only serological markers associated with pathology. In conclusion, H.pylori-associated states results from a combination of bacterial, host and environmental factor merit further investigation.

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