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Summary Background The contribution of alcohol to the large burden of oesophageal squamous cell carcinoma (ESCC) in east Africa remains uncertain and difficult to assess owing to complex consumption patterns of traditional and commercial drinks. We aimed to assess whether alcohol drinking, overall and at specific intake levels, contributes to ESCC risk in east Africa. Methods We did a hospital-based case-control study in Kenya, Tanzania, and Malawi, which included comprehensive assessment of a variety of locally consumed alcohol that we used to classify drinkers as exclusively low alcohol-by-volume (ABV

People Living with HIV (PLHIV) are at an increased risk of pneumococcal pneumonia than HIV-uninfected adults, but the reasons for this are still not well understood. We investigated whether alveolar macrophages (AM) mediated control of pneumococcal infection is impaired in PLHIV compared to HIV-uninfected adults. We assessed anti-bactericidal activity against

The lung is the site most commonly affected by infectious and non-infectious complications of HIV infection [1], even in individuals on effective antiretroviral therapy (ART). HIV infection is associated with lymphocytic alveolitis [2], a condition characterised by the influx of CD8+ T-cells into the alveolar space. This is thought to occur in response to HIV antigens and forms part of the host response to the presence of HIV in the lung [2, 3]. Excessive influx of inflammatory cells in the lung probably leads to tissue damage, disruption of immune cell homeostasis, impaired gas exchange [4] and predisposition to HIV-associated lung complications., Disruption of lung cytokine networks during chronic HIV infection is incompletely restored in individuals on antiretroviral therapy http://ow.ly/klkF30gTtwf

HIV-infected adults are at an increased risk to lower respiratory tract infections (LRTIs). CD8+CD161++TCRvα7.2+ T cells are an innate-like T cell subset that are thought to play an important role in early defense against pathogens in the respiratory tract. HIV infection leads to irreversible depletion of these cells in peripheral blood, however, its impact on this subset in the human airway is still unclear. Here, we show presence of CD103 expressing CD8+CD161++TCRvα7.2+ T cells in the airway that exhibited a distinct cytokine functional profile compared to their CD103- airway counterparts and those from peripheral blood. These CD103 expressing airway CD8+CD161++TCRvα7.2+ T cells were selectively depleted in untreated HIV-infected adults compared to healthy controls. Their frequency was positively correlated with frequency of airway CD4+ T cells. Furthermore, the frequency of airway CD8+CD161++TCRvα7.2+ T cells was also inversely correlated with HIV plasma viral load, while suppressive antiretroviral therapy (ART) resulted in restoration of airway CD8+CD161++TCRvα7.2+ T cells. Our findings show that CD103 expressing airway CD8+CD161++TCRvα7.2+ T cells are functionally distinct and are preferentially depleted during untreated asymptomatic HIV infection. Depletion of CD103 expressing airway CD8+CD161++TCRvα7.2+ T cells, at a major portal of pathogen entry, could partly contribute to the increased propensity for opportunistic LRTIs observed in untreated HIV-infected adults.

Background: HIV infection is associated with increased risk to lower respiratory tract infections (LRTI). However, the impact of HIV infection on immune cell populations in the lung is not well defined. We sought to comprehensively characterise the impact of HIV infection on immune cell populations in the lung. Methods: Twenty HIV-uninfected controls and 17 HIV-1 infected ART-naïve adults were recruited from Queen Elizabeth Central Hospital, Malawi. Immunophenotyping of lymphocyte and myeloid cell populations was done on bronchoalveolar lavage fluid and peripheral blood cells. Results: We found that the numbers of CD8 + T cells, B cells and gamma delta T cells were higher in BAL fluid of HIV-infected adults compared to HIV-uninfected controls (all p+ T cells in HIV-infected adults compared to HIV-uninfected controls (p=0.7065). Intermediate monocytes were the predominant monocyte subset in BAL fluid (HIV-, 63%; HIV+ 81%), while the numbers of classical monocytes was lower in HIV-infected individuals compared to HIV-uninfected adults (1 × 10 5 vs. 2.8 × 10 5 cells/100ml of BAL fluid, p=0.0001). The proportions of alveolar macrophages and myeloid dendritic cells was lower in HIV-infected adults compared to HIV-uninfected controls (all p Conclusions: Chronic HIV infection is associated with broad alteration of immune cell populations in the lung, but does not lead to massive depletion of alveolar CD4 + T cells. Disruption of alveolar immune cell homeostasis likely explains in part the susceptibility for LRTIs in HIV-infected adults.

Background: HIV infection is associated with increased risk to lower respiratory tract infections (LRTI). However, the impact of HIV infection on immune cell populations in the lung is not well defined. We sought to comprehensively characterise the impact of HIV infection on immune cell populations in the lung. Methods: Twenty HIV-uninfected controls and 17 HIV-1 infected ART-naïve adults were recruited from Queen Elizabeth Central Hospital, Malawi. Immunophenotyping of lymphocyte and myeloid cell populations was done on bronchoalveolar lavage fluid and peripheral blood cells. Results: We found that the numbers of CD8+ T cells, B cells and gamma delta T cells were higher in BAL fluid of HIV-infected adults compared to HIV-uninfected controls (all p+ T cells in HIV-infected adults compared to HIV-uninfected controls (p=0.7065). Intermediate monocytes were the predominant monocyte subset in BAL fluid (HIV-, 63%; HIV+ 81%), while the numbers of classical monocytes was lower in HIV-infected individuals compared to HIV-uninfected adults (p=0.0006). The proportions of alveolar macrophages and myeloid dendritic cells was lower in HIV-infected adults compared to HIV-uninfected controls (all p Conclusions: Chronic HIV infection is associated with broad alteration of immune cell populations in the lung, but does not lead to massive depletion of alveolar CD4+ T cells. Disruption of alveolar immune cell homeostasis likely explains in part the susceptibility for LRTIs in HIV-infected adults.

Background Untreated human immunodeficiency virus (HIV) disease disrupts B cell populations causing reduced memory and reduced naïve resting B cells leading to increases in specific co-infections and impaired responses to vaccines. To what extent antiretroviral treatment reverses these changes in an African population is uncertain. Methods A cross-sectional study was performed. We recruited HIV-uninfected and HIV-infected Malawian adults both on and off antiretroviral therapy attending the Queen Elizabeth Central hospital in Malawi. Using flow cytometry, we enumerated B cells and characterized memory B cells and compared these measurements by the different recruitment groups. Results Overall 64 participants were recruited - 20 HIV uninfected (HIV-), 30 HIV infected ART naïve (HIV+N) and 14 HIV-infected ART treated (HIV+T). ART treatment had been taken for a median of 33 months (Range 12-60 months). Compared to HIV- the HIV+N adults had low absolute number of naïve resting B cells (111 vs. 180 cells/μl p = 0.008); reduced memory B cells (27 vs. 51 cells/μl p = 0.0008). The HIV+T adults had B-cell numbers similar to HIV- except for memory B cells that remained significantly lower (30 vs. 51 cells/μl p = 0.02). In the HIV+N group we did not find an association between CD4 count and B cell numbers. Conclusions HIV infected Malawian adults have abnormal B-cell numbers. Individuals treated with ART show a return to normal in B-cell numbers but a persistent deficit in the memory subset is noted. This has important implications for long term susceptibility to co-infections and should be evaluated further in a larger cohort study.

Objectives: Bronchoalveolar lavage obtained at bronchoscopy is useful for research on pulmonary defence mechanisms. Bronchoscopy involves some discomfort and risk to subjects. We audited the process of consent, experienced adverse effects and reasons for participation among research bronchoscopy volunteers. Design: 100 consecutive volunteer research subjects attending for bronchoscopy, repeat bronchoscopy or routine recruitment clinic were interviewed. Information was gathered about volunteer motivation, perception of the consent process and adverse effects of bronchoscopy. Suggestions for improvement were requested. Responses were themed by a second investigator prior to data analysis. Results: 81 bronchoscopy-experienced subjects (total of 263 procedures) and 19 new volunteers were interviewed. 19 subjects (21%) reported adverse symptoms during or after bronchoscopy, but no symptoms were of sufficient severity that they would not repeat the procedure. The frequency of symptoms was not related to gender, the quality of the lavage or the HIV status of the subject. 76 subjects (94%) reported that the information given pre-procedure was useful and adequate but 43 (56%) had further questions mostly relating to their own results. The reasons given for research participation were access to health assessment (75 subjects), access to treatment when ill (61 subjects), desire to participate in research (15 subjects) and remuneration (6 subjects). 7 subjects complained that the remuneration was inadequate. Conclusions: The main incentive to participation in research bronchoscopy was access to healthcare. Informed consent and procedure technique were adequate but subjects would value more feedback about individual and project results.

Introduction HIV and Helicobacter pylori are common chronic infections in sub-Saharan Africa. Both conditions can predispose to gastric hypochlorhydria that may be a risk factor for enteric infections and reduced drug absorption. We have investigated to what extent HIV and H. pylori infections are associated with hypochlorhydria in a Malawian cohort of patients undergoing endoscopy. Method 104 sequential symptomatic adults referred for gastroscopy at Queen Elizabeth Central Hospital, Blantyre, Malawi, had blood taken for rapid HIV testing and fasting serum gastrin analysis. Gastric fluid was aspirated for pH testing, and gastric biopsies were taken. Results After 9/104 HIV-infected patients who were already established on antiretroviral therapy were excluded, 17/95 (25.0%) were seropositive for untreated HIV, and 68/95 (71.6%) patients were H. pylori positive by histology. Hypochlorhydria (fasting gastric pH >4.0) was present in 55.8% (53/95) of patients. H. pylori infection was significantly associated with hypochlorhydria (OR 2.91, [1.02–7.75], p = 0.046). While single infection with HIV was not significantly independently associated with hypochlorhydria. H. pylori and HIV co-infection was more strongly associated with hypochlorhydria (OR 6.25, [1.33–29.43], p = 0.020) than either infection alone, suggesting an additive effect of co-infection. HIV infection was associated with higher serum gastrin levels (91.3pM vs. 53.1pM, p = 0.040), while H. pylori infection was not (63.1pM vs. 55.1pM, p = 0.610). Irrespective of H. pylori and HIV status, most patients (>90%) exhibited pangastritis. Only three patients had histological evidence of gastric atrophy, of which only one was HIV-infected. Conclusion H. pylori infection was associated with fasting hypochlorhydria, while HIV was not independently associated. HIV and H. pylori co-infection, however, was more strongly associated with hypochlorhydria than H. pylori infection alone. The mechanism of this apparent additive effect between HIV and H. pylori remains unclear, but appears to be related to chronic pangastritis rather than gastric atrophy, and associated with hypergastrinaemia in HIV-infected individuals. Disclosure of interest None Declared.

Introduction Dyspepsia is a very common symptom world wide. Unless managed effectively it can burden endoscopy services and create high treatment costs. Management algorithms are widely used in developed countries but have not been validated in sub-Saharan Africa. In Malawi, Helicobacter pylori (HP) infection rates are high, endoscopy facilities are scarce and proton pump inhibitors (PPIs) expensive. In addition the region has extremely high rates of oesophageal cancer and HIV. The incidence of gastric cancer is not known. These conditions make dyspepsia management particularly challenging. Queen Elizabeth Central Hospital (QECH) in Blantyre is Malawi9s tertiary hospital, and provides endoscopy services for a large part of the Southern Region. Methods A prospective audit of all patients presenting routinely to the outpatient department or endoscopy unit at QECH with dyspeptic symptoms over a 4-week period between August and September 2010. Patients were interviewed and health records and prescriptions reviewed. Results 105 patients with dyspepsia were identified; 55 already listed for endoscopy. 143 prescriptions for HP eradication were reviewed; 95% of these did not conform to a recognised regimen. Most errors were in dosing or duration but 38% used a H 2 receptor antagonist instead of a PPI and 31% included only one antibiotic. The 55 patients undergoing gastroscopy had all received prior HP eradication therapy. Mean symptom duration was 33.8 months. The clinical diagnosis matched endoscopic findings in only 18%. 9% were found to have peptic ulcer disease and “gastritis” was recorded for 35%. There was one gastric cancer and 10 oesophageal cancers. Seven of these 11 patients had dysphagia and malignancy had been suspected; 4/11 malignancies were not suspected. Only 5.5% of endoscopies were normal. Conclusion Empirical management of dyspepsia in Malawi is poor. HP eradication therapy is given frequently but almost always incorrectly. This is likely to promote antibiotic resistance and make subsequent HP eradication more difficult. Referral criteria for endoscopy are not clear, yet the yield of serious pathology is surprisingly high. The low rate of normal endoscopic findings contrasts with UK practice but may be explained by over-diagnosis of “gastritis”. In light of this audit, guidelines on dyspepsia management were developed and implemented. They emphasise correct medical management in young dyspeptic patients without alarm symptoms and urgent referral for gastroscopy if malignancy is suspected at any age. Urease testing has been piloted. The impact of these changes will be assessed later this year. Competing interests None declared.

Introduction Sustainable endoscopy services could improve management of upper gastrointestinal malignancy and haemorrhage, both common in Malawi. Since 2008 we have committed to improving endoscopy training through an International Health Link (IHL) partnership with Malawi. We aimed to (1) develop a sustainable training “hub” with locally-trained Trainers in Blantyre (2) develop locally-relevant training courses, (3) extend training support to regional hospital “spokes”. Methods We partnered in five training visits to Malawi, funded by the Tropical Health Education Trust and the British Society of Gastroenterology. We ran 14 courses (Basic Skills, Skills Enhancement, Training the Gastroscopy Trainers (TGT) and Endoscopy Nurses) involving 52 delegate-training-episodes (29 local doctors, 12 clinical officers (COs), three expatriate doctors, eight nurses). Outcomes were monitored by JAG-format DOPS and course evaluations. Progress over time towards the three aims was assessed. Results Aim 1) Training models and audit, reporting and assessment tools were introduced in Blantyre. The mean number of delegate-episodes increased from 6.3 during the first four visits, to 20 during the last two visits. During the first four visits the local faculty was four expatriate doctors and one CO, increasing to seven local doctors, five COs, two nurses and one expatriate doctor during the last two visits. In the first four visits, 16/21 delegate-episodes involved only skills learning and 5/21 (24%) were as mentored or local faculty, while in the last two visits, 25/40 involved only skills learning and 15/40 (38%) were as mentored or local faculty. In 2011 we ran and evaluated the first TGT within Malawi. Aim 2) We developed a Basic Skills in Gastroscopy course appropriate to local circumstances, which was delivered, evaluated and modified over each visit, and ultimately delivered by two locally-trained Trainers. Aim 3) The delegates9 region of origin for the first four visits was 18/19 from Blantyre, and for the last two visits was 15/40 Blantyre, 13/40 Lilongwe, 7/40 Zomba, 3/40 Mzuzu and 2/40 Zambia. The origin of UK external faculty increased from 1 to 3 sites, and two new IHLs were established with Lilongwe and Zomba. Conclusion IHL partnerships represent a sustainable means of improving GI endoscopy training. Modified JAG-format courses, assessments and evaluations were useful even in a resource-limited setting. A hub-and-spoke model helped to support other regions. Future training priorities include training in therapy and further development of local trainers. Local reporting tools should allow audit of outcomes across regions. Competing interests None declared.

Background: Air pollution from biomass fuels in Africa is a significant cause of mortality and morbidity both in adults and children. The work describes the nature and quantity of smoke exposure from biomass fuel in Malawian homes. \ud \ud Methods: Markers of indoor air quality were measured in 62 homes (31 rural and 31 urban) over a typical 24 h period. Four different devices were used (one gravimetric device, two photometric devices and a carbon monoxide (HOBO) monitor. Gravimetric samples were analysed for transition metal content. Data on cooking and lighting fuel type together with information on indicators of socioeconomic status were collected by questionnaire. \ud \ud Results: Respirable dust levels in both the urban and rural environment were high with the mean (SD) 24 h average levels being 226 μg/m3 (206 μg/m3). Data from real-time instruments indicated respirable dust concentrations were >250 μg/m3 for >1 h per day in 52% of rural homes and 17% of urban homes. Average carbon monoxide levels were significantly higher in urban compared with rural homes (6.14 ppm vs 1.87 ppm; p