Short term micronutrient-antioxidant supplementation has no impact on a serological marker of gastric atrophy in Zambian adults: retrospective analysis of a randomised controlled trial

BACKGROUND: Gastric cancer is a major contributor to cancer deaths in Zambia but, as elsewhere, no preventive strategies have been identified. We set out to investigate the possibility of reducing gastric atrophy, a premalignant lesion, using micronutrient-antioxidant supplementation. METHODS: We analysed 215 archival samples from a randomised controlled trial of micronutrient-antioxidant supplementation carried out from 2003 to 2006. Participants were randomised to receive either the supplement or placebo and had been taking the allocated intervention for a mean of 18 (range 14–27) months when the samples used in this study were taken. We used low pepsinogen 1 to 2 (PEP1:2) ratio as a surrogate marker of gastric atrophy. A PEP 1:2 ratio of less than three was considered low. HIV serology, age, nutritional status, smoking, alcohol intake and gastric pH were also analysed. Ethical approval was obtained from the University of Zambia Biomedical Research Ethics Committee (011-04-12). The randomized trial was registered (ISRCTN31173864). RESULTS: The overall prevalence of low PEP 1:2 ratio was 15/215 (7%) and it did not differ between the placebo (8/103, 7.8%) and micronutrient groups (7/112, 6.3%; HR 1.24; 95% CI 0.47-3.3; P = 0.79). The presence of low PEP 1:2 ratio was not influenced by HIV infection (HR 1.07; 95% CI 0.37-3.2; P =0.89) or nutritional status but it inversely correlated with gastric pH (Spearman’s rho = -0.34; P = 0.0001). Age above 40 years was associated with atrophy, but neither alcohol nor smoking had any influence. CONCLUSION: Short term micronutrient supplementation does not have any impact on PEP 1:2 ratio, a serological marker of gastric atrophy. PEP 1:2 ratio inversely correlates with gastric pH

Evaluation of the burden of unsuspected pulmonary tuberculosis and co-morbidity with non-communicable diseases in sputum producing adult inpatients

A high burden of tuberculosis (TB) occurs in sub-Saharan African countries and many cases of active TB and drug-resistant TB remain undiagnosed. Tertiary care hospitals provide an opportunity to study TB co-morbidity with non-communicable and other communicable diseases (NCDs/CDs). We evaluated the burden of undiagnosed pulmonary TB and multi-drug resistant TB in adult inpatients, regardless of their primary admission diagnosis, in a tertiary referral centre. In this prospective study, newly admitted adult inpatients able to produce sputum at the University Teaching Hospital, Lusaka, Zambia, were screened for pulmonary TB using fluorescent smear microscopy and automated liquid culture. The burden of pulmonary TB, unsuspected TB, TB co-morbidity with NCDs and CDs was determined. Sputum was analysed from 900 inpatients (70.6% HIV infected) 277 (30.8%) non-TB suspects, 286 (31.8%) TB suspects and 337 (37.4%) were already receiving TB treatment. 202/900 (22.4%) of patients had culture confirmed TB. TB co-morbidity was detected in 20/275 (7.3%) NCD patients, significantly associated with diabetes (P = 0.006, OR 6.571, 95%CI: 1.706-25.3). 27/202 (13.4%) TB cases were unsuspected. There were 18 confirmed cases of MDR-TB, 5 of which were unsuspected. A large burden of unsuspected pulmonary TB co-morbidity exists in inpatients with NCDs and other CDs. Pro-active sputum screening of all inpatients in tertiary referral centres in high TB endemic countries is recommended. The scale of the problem of undiagnosed MDR-TB in inpatients requires further study

Improving validity of informed consent for biomedical research in Zambia using a laboratory exposure intervention.

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

FGD Study participants.

<p>FGD Study participants.</p

Codes, categories and themes.

<p>Codes, categories and themes.</p

Questions.

<p>Questions.</p

Assessment of the Xpert MTB/RIF Assay for Diagnosis of Tuberculosis with Gastric Lavage Aspirates in Children in Sub-Saharan Africa: A Prospective Descriptive Study

Background: Rapid and accurate diagnosis of pulmonary tuberculosis in children remains challenging because of difficulties in obtaining sputum samples and the paucibacillary nature of the disease. The Xpert MTB/RIF assay is useful for rapid diagnosis of childhood tuberculosis with sputum and nasopharyngeal samples. We assessed this assay for the detection of tuberculosis and multidrug resistant (MDR) tuberculosis with gastric lavage aspirate (GLA) samples in children admitted to hospital. Methods: We did a prospective study to assess the sensitivity and specificity of the Xpert MTB/RIF assay with GLA samples for the detection of pulmonary tuberculosis and MDR tuberculosis in new paediatric inpatient admissions at the University Teaching Hospital, Lusaka, Zambia. Children aged 15 years or younger were recruited between June, 2011, and May, 2012. GLA and sputum were analysed by standard smear-microscopy, mycobacterial growth indicator tube (MGIT) culture, MGIT drug-susceptibility testing, and the Xpert MTB/RIF assay. Sensitivity of the Xpert MTB/RIF assay was assessed with the Pearson χ2 or Fishers exact test. Findings: Of 930 children, 142 produced sputum and GLA was obtained from 788 non-sputum producers. Culture-positive tuberculosis was identified in 58 (6·2%) of 930 children: ten from sputum producers and 48 from GLA of non-sputum producers. The sensitivity and specificity of the Xpert MTB/RIF assay were similar: sensitivity was 68·8% (95% CI 53·6-80·9) for GLA versus 90·0% (54·1-99·5; p=0·1649) for sputum samples; specificity was 99·3% (98·3-99·8) for GLA and 98·5% (94·1-99·7; p=0·2871) for sputum samples. The Xpert MTB/RIF assay detected an extra 28 tuberculosis cases compared with smear microscopy and was significantly more sensitive than smear microscopy for both sputum (90·0% [54·1-99·5] vs 30·0% [8·1-64·6], p=0·01) and GLA (68·8% [53·6-80·9] vs 25·0% [14·1-40·0], p<0·0001). The assay load did not differ significantly by sample type (p=0·791). 22 children were infected with HIV and tuberculosis and significant differences in assay performance could not be detected when stratifying by HIV status for either sample type. The Xpert MTB/RIF assay detected rifampicin resistance in three GLA samples: two confirmed as MDR tuberculosis and one false positive. Interpretation: Analyses of GLA samples with the Xpert MTB/RIF assay is a sensitive and specific method for rapid diagnosis of pulmonary tuberculosis in children who cannot produce sputum. The single site nature of our study invites caution. Funding: European Commission, European Developing Countries Clinical Trials Partnership, and UBS Optimus Foundation. © 2013 Elsevier Ltd

Study population demographics.

<p>IQR – interquartile range; TB – tuberculosis; PTB – pulmonary TB; EPTB - extrapulmonary TB; CNS – central nervous system.</p>a<p>Pearson chi-squared test.</p>b<p>Admission diagnosis could not be gathered from 14 admissions.</p

Burden of pulmonary TB and admission diagnosis co-morbidities with HIV, NCDs and CDs.

<p>Data are n TB positive/n tested (%) [95% CI], Odds Ratios (ORs) and associated confidence intervals (CIs) from binary logistic regression analysis.</p>a<p>Multivariate analysis was controlled for the effects of Age and HIV.</p>b<p>Age was analysed as a continuous variable but is displayed as grouped to illustrate the distribution.</p>c<p>Three TB culture negative patients were represented in multiple NCD diagnosis categories.</p>d<p>Two TB culture negative patients were represented in multiple CD diagnosis categories.</p

TB prevalence in different patient groups stratified by HIV status (HIV status was available for 858/900 study participants).

<p>TB prevalence in different patient groups stratified by HIV status (HIV status was available for 858/900 study participants).</p