Browsing by Author "Kelly P"

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Anti-microbial peptide gene expression during oral vaccination: analysis of a randomized controlled trial.
(2016-Nov) Simuyandi M; Kapulu M; Kelly P; Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia. m.p.kelly@qmul.ac.uk.; Programme for the Awareness and Elimination of Diarrhoea (PAED), Centre for Infectious Disease Research in Zambia.; Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.; Barts and the London School of Medicine, London, UK. m.p.kelly@qmul.ac.uk.; Biological Sciences Department, School of Natural Sciences, University of Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
We have observed previously that micronutrient supplementation ameliorated suppression of α-defensin expression during diarrhoea. However, how interactions between anti-microbial peptide (AMP) expression and diarrhoeal disease are altered by micronutrient supplementation remain unclear. Using oral vaccination as a model of intestinal infection, we measured changes in AMP expression during multiple micronutrient supplementation. In the first part, volunteers underwent duodenal jejunal biopsy before and at 1, 2, 4 or 7 days after administration of one of three live, attenuated oral vaccines against rotavirus, typhoid and enterotoxigenic Escherichia coli. In the second part, participants were randomized to receive a multiple micronutrient supplement or placebo for 6 weeks before undergoing intestinal biopsy, vaccination against typhoid and rebiopsy after 14 days. Expression of human alpha-defensin (HD)5, HD6, hBD1, hBD2 and LL-37 was measured by quantitative reverse transcription-polymerase chain reaction. Taken together, the bacterial vaccines, but not rotavirus vaccine, reduced HD5 expression (P = 0·02, signed-rank test) and reduced LL-37 expression in seven of the eight individuals whose biopsies had expression prevaccination (P = 0·03). hBD2 was not detected. In the controlled trial, HD5 and HD6 expression after vaccination was lower [median ratio 0·5, interquartile range (IQR) = 0·07-2·2 and 0·58, IQR = 0·13-2·3, respectively] than before vaccination. There was no significant effect detected of micronutrient supplementation on expression of HD5, HD6, hBD1 or LL-37. We conclude that live attenuated bacterial vaccines, but not rotavirus vaccine, can reduce intestinal α-defensins, and typhoid vaccine reduced LL-37 expression. We found no evidence that micronutrient supplementation in the short term had any impact on anti-microbial peptide expression.
Chronic hepatitis B virus monoinfection at a university hospital in Zambia.
(2018-Sep-27) Vinikoor MJ; Sinkala E; Kanunga A; Muchimba M; Nsokolo B; Chilengi R; Wandeler G; Mulenga J; Chisenga T; Bhattacharya D; Saag MS; Foster G; Fried MW; Kelly P; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, United States.; Zambian Ministry of Health, Ndeke House, Lusaka 30205, Zambia.; Zambia National Blood Transfusion Service, Private Bag RW1X Ridgeway, Lusaka 50110, Zambia.; Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90035, United States.; Tropical Gastroenterology and Nutrition Group, School of Medicine, University of Zambia, Lusaka 50110, Zambia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, United States.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern 3012, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka 34681, Zambia.; Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London E1 2AT, United Kingdom.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
AIM: To characterize antiviral therapy eligibility among hepatitis B virus (HBV)-infected adults at a university hospital in Zambia. METHODS: Hepatitis B surface antigen-positive adults ( RESULTS: The median age was 33 years, 71.9% were men, and 30.9% were diagnosed with HBV through a clinically-driven test with the remainder identified CONCLUSION: Approximately one in ten HBV-monoinfected Zambians were eligible for antivirals. Many had indeterminate phenotype and needed clinical follow-up.
Eligibility for hepatitis B antiviral therapy among adults in the general population in Zambia.
(2020) Vinikoor MJ; Sinkala E; Kanunga A; Muchimba M; Zanolini A; Saag M; Pry J; Nsokolo B; Chisenga T; Kelly P; Zambian Ministry of Health, Lusaka, Zambia.; Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.; Department for International Development, Dar Es Salaam, Tanzania.; University of California at Davis, Davis, California, United States of America.; Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: We evaluated antiviral therapy (AVT) eligibility in a population-based sample of adults with chronic hepatitis B virus (HBV) infection in Zambia. MATERIALS AND METHODS: Using a household survey, adults (18+ years) were tested for hepatitis B surface antigen (HBsAg). Sociodemographic correlates of HBsAg-positivity were identified with multivariable regression. HBsAg-positive individuals were referred to a central hospital for physical examination, elastography, and phlebotomy for HBV DNA, hepatitis B e antigen, serum transaminases, platelet count, and HIV-1/2 antibody. We determined the proportion of HBV monoinfected adults eligible for antiviral therapy (AVT) based on European Association for the Study of the Liver (EASL) 2017 guidelines. We also evaluated the performance of two alternative criteria developed for use in sub-Saharan Africa, the World Health Organization (WHO) and Treat-B guidelines. RESULTS: Across 12 urban and 4 rural communities, 4,961 adults (62.9% female) were tested and 182 (3.7%) were HBsAg-positive, 80% of whom attended hospital follow-up. HBsAg-positivity was higher among men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 0.99-1.87) and with decreasing income (AOR, 0.89 per household asset; 95% CI, 0.81-0.98). Trends toward higher HBsAg-positivity were also seen at ages 30-39 years (AOR, 2.11; 95% CI, 0.96-4.63) and among pregnant women (AOR, 1.74; 95% CI, 0.93-3.25). Among HBV monoinfected individuals (i.e., HIV-negative) evaluated for AVT, median age was 31 years, 24.6% were HBeAg-positive, and 27.9% had HBV DNA >2,000 IU/ml. AVT-eligibility was 17.0% by EASL, 10.2% by WHO, and 31.1% by Treat-B. Men had increased odds of eligibility. WHO (area under the receiver operating curve [AUROC], 0.68) and Treat-B criteria (AUROC, 0.76) had modest accuracy. Fourteen percent of HBsAg-positive individuals were HIV coinfection, and most coinfected individuals were taking tenofovir-containing antiretroviral therapy (ART). CONCLUSION: Approximately 1 in 6 HBV monoinfected adults in the general population in Zambia may be AVT-eligible. Men should be a major focus of hepatitis B diagnosis and treatment. Further development and evaluation of HBV treatment criteria for resource-limited settings is needed. In settings with overlapping HIV and HBV epidemics, scale-up of ART has contributed towards hepatitis B elimination.
Hepatosplenic schistosomiasis in Zambian adults is characterized by increased liver stiffness: A nested case-control study.
(2020-Jul) Sinkala E; Vinikoor M; Miyanda Siyunda A; Zyambo K; Besa E; Nsokolo B; Wandeler G; Foster GR; Kelly P; Department of Medicine, University of Alabama at Birmingham, Birmingham, USA.; Institute of Social and Preventive Medicine, University of Bern, Switzerland.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Tropical Gastroenterology & Nutritional Group, Department of Internal Medicine, University of Zambia, Lusaka, Zambia.; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Cirrhosis commonly complicates portal hypertension worldwide but in Zambia hepatosplenic schistosomiasis (HSS) dominates as the cause of portal hypertension. We need easier and non-invasive ways to assess HSS. Transient elastography (TE), a measure of liver stiffness can diagnose liver cirrhosis. TE remains unexplored in HSS patients, who generally have normal liver parenchyma. We aimed to explore liver stiffness in HSS. This nested case control study was conducted at the University Teaching Hospital, Lusaka, Zambia between January 2015 and January 2016. We enrolled 48 adults with HSS and 22 healthy controls. We assessed liver stiffness using TE while plasma hyaluronan was used to assess liver fibrosis. Plasma tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) were used to assess inflammation. The median (interquartile range) liver stiffness was higher in patients, 9.5 kPa (7.8, 12.8) than in controls, 4.7 kPa (4.0, 5.4),
New Window Into Hepatitis B in Africa: Liver Sampling Combined With Single-Cell Omics Enables Deep and Longitudinal Assessment of Intrahepatic Immunity in Zambia.
(2024-Nov-15) Musonda T; Wallace MS; Patel H; Martin OP; Oetheimer C; Mwakamui S; Sinkala E; Nsokolo B; Kanunga A; Lauer G; Chung RT; Wandeler G; Bhattacharya D; Kelly P; Alatrakchi N; Vinikoor MJ; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, University of California Los Angeles, Los Angeles, California, USA.; Blizard Institute, Queen Mary University of London, London, United Kingdom.; Tropical Gastroenterology and Nutrition Group, University of Zambia, Lusaka, Zambia.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Medicine, Levy Mwanawasa University Teaching Hospital, Lusaka, Zambia.; Division of Infectious Diseases, University of Alabama Birmingham, Birmingham, Alabama, USA.; Department of Research, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
In Lusaka, Zambia, we introduced liver fine-needle aspiration biopsy (FNAB) into a research cohort of adults with treatment-naive chronic hepatitis B virus (HBV) infection, with and without human immunodeficiency virus (HIV) coinfection, as well as with acute HBV infection. From 117 enrollment and 47 longitudinal FNABs (at 1-year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single-cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa.
Propranolol Reduces Portal Vein Diameter in Schistosomal Liver Disease with Portal Hypertension: A Prospective Cohort Study.
(2020-Apr) Sinkala E; Vinikoor M; Zyambo K; Besa E; Nsokolo B; Kelly P; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.; Department of Internal Medicine, Tropical Gastroenterology and Nutritional Group, University of Zambia, Lusaka, Zambia.; Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Hepatosplenic schistosomiasis (HSS) complicates portal hypertension, leading to life-threatening variceal bleeding. Variceal bleeding is associated with increased portal vein diameter (PVD). Beta-blockers prevent variceal bleeding. It is unclear whether beta-blockers such as propranolol can reduce PVD in HSS. We aimed to explore the effect of propranolol on PVD in HSS. A longitudinal study was conducted at the University Teaching Hospital, Zambia, as an extension of a clinical trial of rifaximin undertaken to test the hypothesis that rifaximin could reduce bacterial translocation in HSS. We randomized 85 adults to either rifaximin and standard care, or propranolol-based standard care only for 42 days. We then followed up all the patients on propranolol up to day 180. We used ultrasound to measure PVD at baseline and day 180. The primary outcome was reduction in PVD. Beta-blockade and splenic size reduction were secondary outcomes. Portal vein diameter reduced after 180 days of propranolol therapy from median 12 mm (interquartile range (IQR): 11-14) to median 10 mm (IQR: 9-13) (
Rifaximin Reduces Markers of Inflammation and Bacterial 16S rRNA in Zambian Adults with Hepatosplenic Schistosomiasis: A Randomized Control Trial.
(2018-Apr) Sinkala E; Zyambo K; Besa E; Kaonga P; Nsokolo B; Kayamba V; Vinikoor M; Zulu R; Bwalya M; Foster GR; Kelly P; Paediatric Centre of Excellence Laboratory, University Teaching Hospital, Lusaka, Zambia.; Department of Internal Medicine, Tropical Gastroenterology & Nutritional Group, University of Zambia, Lusaka, Zambia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.; Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, United Kingdom.; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Cirrhosis is the dominant cause of portal hypertension globally but may be overshadowed by hepatosplenic schistosomiasis (HSS) in the tropics. In Zambia, schistosomiasis seroprevalence can reach 88% in endemic areas. Bacterial translocation (BT) drives portal hypertension in cirrhosis contributing to mortality but remains unexplored in HSS. Rifaximin, a non-absorbable antibiotic may reduce BT. We aimed to explore the influence of rifaximin on BT, inflammation, and fibrosis in HSS. In this phase II open-label trial (ISRCTN67590499), 186 patients with HSS in Zambia were evaluated and 85 were randomized to standard care with or without rifaximin for 42 days. Changes in markers of inflammation, BT, and fibrosis were the primary outcomes. BT was measured using plasma 16S rRNA, lipopolysaccharide-binding protein, and lipopolysaccharide, whereas hyaluronan was used to measure fibrosis. Tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) assessed inflammation. 16S rRNA reduced from baseline (median 146 copies/µL, interquartile range [IQR] 9, 537) to day 42 in the rifaximin group (median 63 copies/µL, IQR 12, 196),