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Aim: To identify risk factors associated with esophageal cancer in Zambia and association between dietary intake and urinary 8-iso prostaglandin F2α (8-isoPGF2α)., Methods: We conducted a prospective, case control study at the University Teaching Hospital. Subjects included both individuals admitted to the hospital and those presenting for an outpatient upper endoscopy. Esophageal cancer cases were compared to age and sex-matched controls. Cases were defined as patients with biopsy proven esophageal cancer; controls were defined as subjects without endoscopic evidence of esophageal cancer. Clinical and dietary data were collected using a standard questionnaire, developed a priori. Blood was collected for human immunodeficiency virus (HIV) serology. Urine was collected, and 8-isoPGF2α was measured primarily by enzyme-linked immunosorbent assay and expressed as a ratio to creatinine., Results: Forty five controls (mean age 54.2 ± 15.3, 31 male) and 27 cases (mean age 54.6 ± 16.4, 17 males) were studied. Body mass index was lower in cases (median 16.8) than controls (median 23.2), P = 0.01. Histopathologically, 25/27 (93%) were squamous cell carcinoma and 2/27 (7%) adenocarcinoma. More cases smoked cigarettes (OR = 11.24, 95%CI: 1.37-92.4, P = 0.02) but alcohol consumption and HIV seropositivity did not differ significantly (P = 0.14 for both). Fruit, vegetables and fish consumption did not differ significantly between groups (P = 0.11, 0.12, and 0.10, respectively). Mean isoprostane level was significantly higher in cases (0.03 ng/mg creatinine) than controls (0.01 ng/mg creatinine) (OR = 2.35, 95%CI: 1.19-4.65, P = 0.014)., Conclusion: Smoking and isoprostane levels were significantly associated with esophageal cancer in Zambians, but diet, HIV status, and alcohol consumption were not.

Background: Complex biomedical research can lead to disquiet in communities with limited exposure to scientific discussions, leading to rumours or to high drop-out rates. We set out to test an intervention designed to address apprehensions commonly encountered in a community where literacy is uncommon, and where complex biomedical research has been conducted for over a decade. We aimed to determine if it could improve the validity of consent., Methods: Data were collected using focus group discussions, key informant interviews and observations. We designed an intervention that exposed participants to a detailed demonstration of laboratory processes. Each group was interviewed twice in a day, before and after exposure to the intervention in order to assess changes in their views., Results: Factors that motivated people to participate in invasive biomedical research included a desire to stay healthy because of the screening during the recruitment process, regular advice from doctors, free medical services, and trust in the researchers. Inhibiting factors were limited knowledge about samples taken from their bodies during endoscopic procedures, the impact of endoscopy on the function of internal organs, and concerns about the use of biomedical samples. The belief that blood can be used for Satanic practices also created insecurities about drawing of blood samples. Further inhibiting factors included a fear of being labelled as HIV positive if known to consult heath workers repeatedly, and gender inequality. Concerns about the use and storage of blood and tissue samples were overcome by a laboratory exposure intervention., Conclusion: Selecting a group of members from target community and engaging them in a laboratory exposure intervention could be a useful tool for enhancing specific aspects of consent for biomedical research. Further work is needed to determine the extent to which improved understanding permeates beyond the immediate group participating in the intervention.

Background: Hepatitis E virus (HEV) infection causes major epidemics of infectious hepatitis, with high mortality rates in pregnant women. Recent reports indicate that HEV coinfections with human immunodeficiency virus (HIV) may have a more protracted course. However, the impact of HEV infections in communities heavily affected by HIV remains poorly studied. We set out to examine age-related seroprevalence in a community where we have previously carried out studies on environmental enteropathy., Methods: Blood samples from 194 children and 106 adults were examined for immunoglobulin G and immunoglobulin M antibodies for HEV. HEV data were correlated with HIV status and morphometric analysis of small intestinal biopsies., Results: Seroprevalence rose throughout childhood, from 8% in children aged 1-4 years, to 36% in children aged 10-14 years. In adults, the overall prevalence was 42%, with 28% in HIV-seronegative adults and 71% in HIV-seropositive adults (odds ratio, 6.2; 95% confidence interval, 2.2-18; P = .0001). In adults, villous height and crypt depth measurements showed that HEV seropositivity was associated with worse enteropathy (P = .05 and P = .005, respectively)., Conclusions: HEV infection is common in Zambia. In adults it is strongly associated with HIV status, and also with environmental enteropathy.

There is an urgent need to identify ways of enhancing the mucosal immune response to oral vaccines. Rotavirus vaccine protection is much lower in Africa and Asia than in industrialized countries, and no oral vaccine has efficacy approaching the best systemic vaccines. All-trans retinoic acid (ATRA) up-regulates expression of α4β7 integrin and CCR9 on lymphocytes in laboratory animals, increasing their gut tropism. The aim of this study was to establish the feasibility of using ATRA as an oral adjuvant for oral typhoid vaccination. In order to establish that standard doses of oral ATRA can achieve serum concentrations greater than 10 nmol/l, we measured ATRA, 9-cis and 13-cis retinoic acid in serum of 14 male volunteers before and 3 h after 10 mg ATRA. We then evaluated the effect of 10 mg ATRA given 1 h before, and for 7 days following, oral typhoid vaccine in eight men, and in 24 men given various control interventions. We measured immunoglobulin (Ig)A directed against lipopolysaccharide (LPS)and protein preparations of vaccine antigens in whole gut lavage fluid (WGLF) and both IgA and IgG in serum, 1 day prior to vaccination and on day 14. Median [interquartile range (IQR)] C(max) was 26·2 (11·7-39·5) nmol/l, with no evidence of cumulation over 8 days. No adverse events were observed. Specific IgA responses to LPS (P = 0·02) and protein (P = 0·04) were enhanced in WGLF, but no effect was seen on IgA or IgG in serum. ATRA was well absorbed, well tolerated and may be a promising candidate oral adjuvant., (© 2013 British Society for Immunology.)

Background: Gastric cancer is a leading cause of cancer deaths worldwide but there are few data from Africa. We recently observed a trend towards diagnosis in younger patients., Objective: To test the hypothesis that HIV might have altered risk factors for acquisition of gastric cancer, in a case-control study in the University Teaching Hospital, Lusaka, Zambia., Methods: Patients (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 between cases and controls (odds ratio 1.03; 95% CI 0.2 - 4.3; p=1.00) and seroprevalence in cases was similar to that of the Zambian population. Smoking, regular alcohol intake, and gastric atrophy were all associated with cancer in univariate and multivariate analysis. Helicobacter pylori serology was positive in 84% of patients studied and cagA serology in 66%; neither serological marker was associated with cancer. Atrophy was common in cases (57%) and controls (30%) and associated with both smoking and alcohol use. Intestinal metaplasia was present in 17% of the controls, but was not associated with atrophy., Conclusions: HIV was not associated with gastric cancer and does not explain the apparent younger age distribution. Atrophy was common and was not essential for the development of intestinal metaplasia, suggesting that gastric carcinogenesis in Africa does not always follow the pathway from atrophy to intestinal metaplasia to gastric carcinoma (the so-called Correa pathway).