BackgroundAlthough micronutrient supplementation can reduce morbidity and mortality due to diarrhoea, nutritional influences on intestinal host defence are poorly understood. We tested the hypothesis that micronutrient supplementation can enhance barrier function of the gut.MethodsWe carried out two sub-studies nested within a randomised, double-blind placebo-controlled trial of daily micronutrient supplementation in an urban community in Lusaka, Zambia. In the first sub-study, gastric pH was measured in 203 participants. In the second sub-study, mucosal permeability, lipopolysaccharide (LPS) and anti-LPS antibodies, and serum soluble tumour necrosis factor receptor p55 (sTNFR55) concentrations were measured in 87 participants. Up to three stool samples were also analysed microbiologically for detection of asymptomatic intestinal infection. Gastric histology was subsequently analysed in a third subset (n = 37) to assist in interpretation of the pH data. Informed consent was obtained from all participants after a three-stage information and consent process.ResultsHypochlorhydria (fasting gastric pH > 4.0) was present in 75 (37%) of participants. In multivariate analysis, HIV infection (OR 4.1; 95%CI 2.2-7.8; P < 0.001) was associated with hypochlorhydria, but taking anti-retroviral treatment (OR 0.16; 0.04-0.67; P = 0.01) and allocation to micronutrient supplementation (OR 0.53; 0.28-0.99; P < 0.05) were protective. Hypochlorhydria was associated with increased risk of salmonellosis. Mild (grade 1) gastric atrophy was found in 5 participants, irrespective of Helicobacter pylori or HIV status. Intestinal permeability, LPS concentrations in serum, anti-LPS IgG, and sTNFR55 concentrations did not differ significantly between micronutrient and placebo groups. Anti-LPS IgM was reduced in the micronutrient recipients (P <0.05).ConclusionsWe found evidence of a specific effect of HIV on gastric pH which was readily reversed by anti-retroviral therapy and not mediated by gastric atrophy. Micronutrients had a modest impact on gastric pH and one marker of bacterial translocation.Trial RegistrationCurrent Controlled Trials ISRCTN31173864

Background Gastric cancer is a leading cause of cancer deaths worldwide but there are few data from Africa. We have recently observed a trend towards diagnosis in younger patients. Objective To test the hypothesis that HIV may have altered risk factors for acquisition of gastric cancer, in a case-control study in the University Teaching Hospital, Lusaka, Zambia. Methods Cases (n=52) with confirmed gastric adenocarcinoma and controls (n=94) undergoing endoscopy but with no macroscopic gastric pathology. Established risk factors and HIV status were compared. Results HIV status did not differ significantly in cases and controls (Odds Ratio 1·03; 95% CI 0·2–4·3; P=1·00) and seroprevalence in cases was similar to the Zambian population. Smoking, regular alcohol intake, and gastric atrophy were all associated with cancer in univariate and multivariate analysis. H. pylori serology was positive in 84% of patients studied and cagA serology in 66%; neither serological marker was associated with cancer. Atrophy, assessed serologically, was common in cases (57%) and controls (30%). In controls, both smoking and alcohol use were associated with atrophy, and intestinal metaplasia was present in 17% but was not associated with atrophy. Conclusions HIV was not associated with gastric cancer and does not explain the apparent change in age distribution in Zambia. Atrophy was common and was not essential for the development of intestinal metaplasia, suggesting that gastric carcinogenesis in Africa does not always follow the Correa pathway.

Background and aimsThere a shortage of robust information about profiles of gastrointestinal disease in sub-Saharan Africa. The endoscopy unit of the University Teaching Hospital in Lusaka has been running without interruption since 1977 and this 38-year record is largely intact. We report an analysis of endoscopic findings over this period.MethodsWritten endoscopy records from 29th September 1977 to 16th December 2014 were recovered, computerised, coded by two experienced endoscopists and analysed. Temporal trends were analysed using tables, graphs, and unconditional logistic regression, with age, sex of patient, decade, and endoscopist as independent variables to adjust for inter-observer variation.ResultsSixteen thousand nine hundred fifty-three records were identified and analysed. Diagnosis of gastric ulcer rose by 22 %, and that of duodenal ulcer fell by 14 % per decade. Endoscopically diagnosed oesophageal cancer increased by 32 % per decade, but gastric cancer rose only in patients under 60 years of age (21 % per decade). Oesophageal varices were the commonest finding in patients presenting with haematemesis, increasing by 14 % per decade in that patient group. Two HIV-related diagnoses, oesophageal candidiasis and Kaposi’s sarcoma, rose from almost zero to very high levels in the 1990s but fell substantially after 2005 when anti-retroviral therapy became widely available.ConclusionsThis useful dataset suggests that there are important trends in some endoscopic findings over four decades. These trends are not explained by inter-observer variation. Reasons for the divergent trends in incidence of peptic ulceration and apparent trends in diagnosis of upper gastrointestinal cancers merit further exploration.