Antibody response patterns to <i>Helicobacter pylori</i> infection in a rural Ugandan population cohort

Abstract Background Helicobacter pylori ( H. pylori ) establishes life-long infection in humans in the absence of treatment and has been associated with a variety of gastrointestinal conditions including peptic ulcer and gastric cancer. Antibody responses to H. pylori antigens are found to be associated with disease risk, however, data from Africa are scarce. Methods To assess the seroprevalence of H. pylori and characterise antibody response patterns, we measured serum IgG antibody levels to 14 antigens among 7,211 individuals in a rural Ugandan population cohort. Multivariate-adjusted linear regression models were fitted to investigate the influence of age, sex, and co-infection on antibody seroreactivity levels. Results H. pylori seroprevalence was 95% in our study population, with 94% of individuals seropositive in childhood (<15 years). In H. pylori positive individuals, we found a markedly high seroprevalence (~99%) and antibody levels to the high-risk antigens CagA and VacA, in addition to Cagδ. HSV-2 co-infection was significantly associated with higher IgG levels of CagA and VacA (OR=1.10, 95% C. I=1.05-1.16). HIV infection was associated with lowered IgG levels to CagA (OR=0.86, 95% C.I.=0.80-0.93), and HPV infection was associated with increased IgG levels to VacA (OR=1.16, 95% C.I.=1.11-1.21). Conclusions H. pylori in this population is ubiquitous from childhood, with a high prevalence and high seroreactivity levels of high-risk antigens, suggesting chronic active inflammatory responses in individuals that are indicative of risk of disease. Further investigation is warranted to fully understand the relationship between host, immunogenicity, and clinical outcomes to better stratify by risk and improve treatment. Key Messages Antibody responses to H. pylori antigens are found to be associated with risk of gastric cancer, however, despite the high seroprevalence in African populations, data from Africa are scarce. This is the first study of antibody response patterns and their determinants from an African population. Our study shows a population where H. pylori is ubiquitous from childhood, and seroprevalence of virulent antigens is distinctively high suggesting an increased of disease compared to other populations. We observe inter-individual variation in virulent antibody responses partly influenced by co-infection. We highlight crucial insights into antibody-based biomarkers of disease risk and reinforce the need for population-based H. pylori screening and treatment programmes for gastric cancer control.