Background
In sub-Saharan Africa, the future burden of gastric cancer is projected to be up to six times higher than estimates reported in 2022, largely due to demographic changes. Helicobacter pylori (HP) is classified as a Group 1 carcinogen for non-cardia gastric cancer. Gastric atrophy (GA) is a precancerous condition widely used as a surrogate marker of gastric cancer risk. Characterizing the epidemiology of HP infection and GA is therefore essential for informing preventive strategies in anticipation of the rising gastric cancer burden, particularly in settings with limited cancer surveillance infrastructure.
 
Objectives
The International Agency for Research on Cancer (IARC) initiated a series of global epidemiological studies, the Epidemiological iNvestigatIon of Gastric MAlignancies (ENIGMA) studies, to characterize regional patterns of HP infection and gastric cancer using a standardized framework. The ENIGMA Uganda study represents a key African site within this global network, to investigate the epidemiology of HP infection and GA in Africa.
 
Methods
This population-based study included 700 individuals aged 1–69 years, equally stratified by sex and 5-year age groups. Participants were randomly selected from the General Population Cohort (GPC),  a cohort established in 1989 to monitor HIV epidemiology in rural southwestern Uganda. Participants completed a structured questionnaire to assess risk factors related to HP infection and GA (including sociodemographic characteristics, lifestyle factors, and health status), underwent anthropometric measurements, and provided blood, urine and stool samples. Anti-HP IgG antibodies were measured using enzyme-linked immunosorbent assays (ELISA). Plasma pepsinogen I (PG I) and pepsinogen II (PG II) concentrations were also measured by ELISA to define GA serologically( PG I ≤ 70 µg/L and a PG I/PG II ratio < 3).
 
Results
The age-standardized HP seroprevalence was 75.6% (crude estimate: 76.9%, 537/698). Crude age-specific seroprevalence increased with age, peaking in the 10–19-year age group (86.9%), and declined thereafter. Among men aged >40 years, HP seroprevalence was significantly lower than among younger men (68.0% vs. 82.0%) and was also lower than among women in the same age group (77.9%). HP seropositivity was associated with father's education among children under 12 years of age, and with pesticide exposure among individuals aged 12–39 years. Serologically defined GA was uncommon, with an overall prevalence of 3.3% among individuals aged ≥40 years (10/301; 95% CI: 1.8%-6.0%), and was concentrated in those aged ≥65 years (11.9%, 7/59, 95% CI: 0.5%-22.9%).  Among participants aged ≥40 years, those who consumed chili occasionally (but not daily) had significantly higher odds of serologically defined GA compared with those who never consumed chili (OR 7.4, 95% CI: 1.7–51.7).
 
Conclusions/Implications for practice or policy
In Uganda, HP infection is acquired early in life and is highly prevalent, whereas serologically defined gastric atrophy remains uncommon, representing a distinct epidemiological pattern (also observed in Zambia) that contrasts markedly with patterns reported in other countries. This discrepancy warrants further investigation to elucidate the progression from HP infection to gastric atrophy and ultimately gastric cancer in Uganda, to better understand the country’s future gastric cancer burden, and to inform prevention strategies.