Serological response to Epstein-Barr virus early antigen is associated with gastric cancer and human immunodeficiency virus infection in Zambian adults: a case-control study.

INTRODUCTION: Gastric cancer is one of the major causes of cancer related deaths, but data from sub-Saharan Africa are very scanty. The cancer genome atlas (TCGA) initiative confirmed Epstein-Barr virus (EBV) related cancer as a distinct subtype, and we set out to look for serological evidence of its role in a sub-Saharan African patient group. METHODS: We used stored serum samples obtained from a gastric cancer case-control study conducted between 2010 and 2012 in Lusaka, Zambia. A total of 147 patients were included with 51 gastric adenocarcinoma cases and 96 age and sex matched controls. The presence of antibodies to EBV nuclear antigen-1 (EBNA-1) and early antigen (EA) was determined using commercially available ELISA kits. Data were analysed in STATA Stata Corp, College Station TX. RESULTS: Over 90% of all the samples analysed were positive for antibodies to EBNA-1. The presence of antibodies to EBV EA was significantly higher in gastric cancer cases than in controls, (OR 4.38; 95% CI 1.53-13.06, P = 0.0027), with an attributable risk of 23%. HIV infection was also associated with EBV EA seroprevalence (OR 10.97; 95% CI 2.26 -13.06, P = 0.001) but not EBNA-1 (OR 0.81; 95% CI 0.10 -38.75, P = 0.596). There was no association of EBV infection with age below 45 years, Helicobacter pylori infection, intestinal metaplasia, gastric atrophy or inflammation. CONCLUSION: We therefore conclude that EBV exposure is common among Zambian adults and that EBV EA seropositivity is associated with gastric cancer and HIV infection, but not premalignant lesions.Funding: wellcome Trust through SACORE, grant number WT087537MA

Esophageal squamous cell cancer in a highly endemic region

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

Alcohol reduction outcomes following brief counseling among adults with HIV in Zambia: A sequential mixed methods study

Data from sub-Saharan Africa on the impact of alcohol on the HIV epidemic in sub-Saharan Africa is limited. In this region, it is not well understood how people with HIV (PLWHA) respond to alcohol reduction counseling while they are linked to HIV clinical care. We conducted an explanatory sequential mixed-methods study to understand patterns of alcohol use among adults (18+ years) within a prospective HIV cohort at two urban public-sector clinics in Zambia. At antiretroviral therapy (ART) start and one year later, we measured alcohol use with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and those reporting any alcohol use were provided brief counseling. We conducted focus groups at 1 year with participants who had any alcohol use and 20 in-depth interviews among the subgroup with unhealthy use pre-ART and who either reduced or did not reduce their use by 1 year to moderate levels or abstinence. Focus group Discussions (FGDs) (n = 2) were also held with HIV clinic staff. Qualitative data were analyzed using thematic analysis. The data obtained from 693 participants was analyzed (median age 34 years, 45% men), it revealed that unhealthy alcohol use (AUDIT-C >3 for men; >2 for women) was reported among 280 (40.4%) at baseline and 205 (29.6%) at 1 year on ART. Reduction from unhealthy to moderate use or abstinence was more common with older age, female, non-smoking, and at Clinic B (all P<0.05). Qualitative data revealed ineffective alcohol support at clinics, social pressures in the community to consume alcohol, and unaddressed drivers of alcohol use including poverty, poor health status, depression, and HIV stigma. Healthcare workers reported a lack of training in alcohol screening and treatment, which led to mixed messages provided to patients ('reduce to safe levels' versus 'abstain'). In summary, interventions to reduce unhealthy alcohol use are needed within HIV clinics in Zambia as a substantial population have persistent unhealthy use despite current HIV clinical care. A better understanding is needed regarding the implementation challenges related to screening for unhealthy alcohol use integrated with HIV services

Development of a diarrhoea severity scoring scale in a passive health facility-based surveillance system

Background Diarrhoeal disease remains a leading cause of death among children mostly in low and middle- income countries. Factors contributing to disease severity are complex and there is currently no consensus on a scoring tool for use in community-based studies. Methods Data were collected during a passive surveillance system in an outpatient health facility in Lusaka, Zambia from March 2019 to July 2019. Diarrhea episodes were assessed for severity using an in-house severity scoring tool (CIDRZ) and previously published scores (Vesikari, Clark, CODA, and DHAKA). The CIDRZ score was constructed using fieldworker-reported clinical signs and exploratory factor analysis. We used precision-recall curves measuring severe diarrhoea (i.e., requiring intravenous rehydration or referred for hospital admission) to determine the best performing scores. Then, we used Cronbach's alpha to assess the scale's internal consistency. Finally, we used Cohen's kappa to assess agreement between the scores. Results Of 110 diarrhea episodes, 3 (3%) required intravenous rehydration or were referred for hospital admission. The precision-recall area under the curve of each score as a predictor of severe diarrhoea requiring intravenous rehydration or hospital admission was 0.26 for Vesikari, 0.18 for CODA, 0.24 for Clark, 0.59 for DHAKA, and 0.59 for CIDRZ. The CIDRZ scale had substantial reliability and performed similarly to the DHAKA score. Conclusions Diarrhoea severity scores focused on characteristics specific to dehydration status may better predict severe diarrhea among children in Lusaka. Aetiology-specific scoring tools may not be appropriate for use in community healthcare settings. Validation studies for the CIDRZ score in diverse settings and with larger sample sizes are warranted

Biomass Smoke Exposure Is Associated With Gastric Cancer and Probably Mediated Via Oxidative Stress and DNA Damage: A Case-Control Study.

PURPOSE: We investigated the association between gastric cancer and environmental and dietary exposures. In addition, we explored probable mechanistic pathways for the influence of biomass smoke on gastric carcinogenesis. PATIENTS AND METHODS: The study was conducted in Lusaka, Zambia. Questionnaires were used to collect data on risk factors, whereas enzyme-linked immunosorbent assays and high-performance liquid chromatography were used to measure biologic exposures. Study data were analyzed using contingency tables and logistic regression. RESULTS: We enrolled 72 patients with gastric adenocarcinoma and 244 controls. Gastric cancer was positively associated with rural residence (odds ratio [OR], 2.9; 95% CI, 1.5 to 5.3), poverty (OR, 4.2; 95% CI, 1.9 to 9.1), and daily consumption of processed meat (OR, 6.4; 95% CI, 1.3 to 32) and negatively associated with consumption of green vegetables (OR, 0.2; 95% CI, 0.1 to 0.5). Gastric cancer was also associated with biomass smoke exposure (OR, 3.5; 95% CI, 1.9 to 6.2; P < .0001), an association that was stronger for intestinal-type cancers (OR, 3.6; 95% CI, 1.5 to 9.1; P = .003). Exposure to biomass smoke in controls was associated with higher urinary levels of 8-isoprostane (P < .0001), 8-hydroxydeoxyguanosine (P = .029), and 1-hydroxypyrene (P = .041). Gastric cancer was not associated with biochemical measures of current exposure to aflatoxins or ochratoxins. CONCLUSION: In Zambia, exposure to biomass smoke, daily consumption of processed meat, and poverty are risk factors for gastric cancer, whereas daily consumption of green vegetables is protective against gastric cancer. Exposure to biomass smoke was associated with evidence of oxidative stress and DNA damage, suggesting mechanistic plausibility for the observed association, and the association was restricted to intestinal-type gastric cancer

Pancreatic cancer: Patterns in a low- to middle- income Ppopulation, Zambia

Introduction: In 2007, the Cancer Disease Hospital (CDH) was opened as the national referral center for patients diagnosed with cancer in Zambia. Since inception of the CDH, there has been no systematic analysis of the disease burden and implication on healthcare delivery with regards to pancreatic cancer. There are limited studies describing patterns of pancreatic cancer in a native African population. Data suggest African-Americans have a higher incidence and poorer prognosis of pancreatic cancer than non-African Americans.Objective: Our aim is to describe the demographic features (age, gender) of pancreatic cancer using the Cancer Disease Hospital (CDH) data base in a native African population and compare with the African-American cohort using the  Surveillance, Epidemiology End Results (SEER) Program database.Methods: This was a retrospective study of patients diagnosed with pancreatic  cancer at the CDH in Zambia, Southern Africa between 2007 and 2014. We entered the term “pancreatic cancer” into the CDH database, extracted patient medical records numbers, and manually located the records for review. From each chart we extracted: age, gender, geographic origin, ethnicity, clinical features at presentations, location of tumor, stage at diagnosis and treatment. Data collection tool and master code sheet created a priori were used. Data was analyzed using statistical analysis software (SAS). Descriptive statistics including means, medians as well as frequency distributions and crosstabulations were used. SEER database was used to compare subjects  between Zambia and USA. Groups were compared using Chi-square tests and Wilcoxon Signed Rank test. Ap-value less than 0.05 was used as the level of significance.Results: Thirty-eight charts were identified in the CDH dataset, of which 27 were included in final analysis and 11 excluded (5 non-pancreatic cancer diagnosis, 6 not manually located). The mean age of diagnosis was 55.7 years in the native African population, compared to 66.7 years for the African-Americans in the SEER  database, p &lt; 0.0001. There were 63.0% males (CDH) compared to 48.1% (SEER), p=0.121. Further review of the CDH database revealed that the most common presenting symptom was abdominal pain (52.6%), mode of diagnosis surgical (83%, missing 3), histopathology adenocarcinoma (86%, missing 6), location head of pancreas (83%, missing 9) and stage 4 at diagnosis (100%, missing 3).Conclusion: Pancreatic cancer occurs at a younger age in Zambians when compared to the African American, USApopulation. There is no statistically significant difference in sex presentation between Zambian and USAblack population

Alcohol reduction outcomes following brief counseling among adults with HIV in Zambia: A sequential mixed methods study.

Data from sub-Saharan Africa on the impact of alcohol on the HIV epidemic in sub-Saharan Africa is limited. In this region, it is not well understood how people with HIV (PLWHA) respond to alcohol reduction counseling while they are linked to HIV clinical care. We conducted an explanatory sequential mixed-methods study to understand patterns of alcohol use among adults (18+ years) within a prospective HIV cohort at two urban public-sector clinics in Zambia. At antiretroviral therapy (ART) start and one year later, we measured alcohol use with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and those reporting any alcohol use were provided brief counseling. We conducted focus groups at 1 year with participants who had any alcohol use and 20 in-depth interviews among the subgroup with unhealthy use pre-ART and who either reduced or did not reduce their use by 1 year to moderate levels or abstinence. Focus group Discussions (FGDs) (n = 2) were also held with HIV clinic staff. Qualitative data were analyzed using thematic analysis. The data obtained from 693 participants was analyzed (median age 34 years, 45% men), it revealed that unhealthy alcohol use (AUDIT-C >3 for men; >2 for women) was reported among 280 (40.4%) at baseline and 205 (29.6%) at 1 year on ART. Reduction from unhealthy to moderate use or abstinence was more common with older age, female, non-smoking, and at Clinic B (all P<0.05). Qualitative data revealed ineffective alcohol support at clinics, social pressures in the community to consume alcohol, and unaddressed drivers of alcohol use including poverty, poor health status, depression, and HIV stigma. Healthcare workers reported a lack of training in alcohol screening and treatment, which led to mixed messages provided to patients ('reduce to safe levels' versus 'abstain'). In summary, interventions to reduce unhealthy alcohol use are needed within HIV clinics in Zambia as a substantial population have persistent unhealthy use despite current HIV clinical care. A better understanding is needed regarding the implementation challenges related to screening for unhealthy alcohol use integrated with HIV services