Browsing by Author "Zyambo K"

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Geospatial Patterns of Progress towards UNAIDS "95-95-95" Targets and Community Vulnerability in Zambia.
(2023-Apr-26) Cuadros DF; Chowdhury T; Milali M; Citron D; Nyimbili S; Vlahakis N; Savory T; Mulenga L; Sivile S; Zyambo K; Bershteyn A; National HIV Program, Ministry of Health, Lusaka, Zambia.; Digital Epidemiology Laboratory, Digital Futures, University of Cincinnati, Cincinnati, OH, USA.; Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.
In sub-Saharan Africa, HIV/AIDS remains a leading cause of death. The UNAIDS established the "95-95-95" targets to improve HIV care continuum outcomes. Using geospatial data from the Zambia Population-based HIV Impact Assessment (ZAMPHIA), this study aims to investigate geospatial patterns in the "95-95-95" indicators and individual-level determinants that impede HIV care continuum in vulnerable communities, providing insights into the factors associated with gaps. This study used data from the 2016 ZAMPHIA to investigate the geospatial distribution and individual-level determinants of engagement across the HIV care continuum in Zambia. Gaussian kernel interpolation and optimized hotspot analysis were used to identify geospatial patterns in the HIV care continuum, while geospatial k-means clustering was used to partition areas into clusters. The study also assessed healthcare availability, access, and social determinants of healthcare utilization. Multiple logistic regression models were used to examine the association between selected sociodemographic and behavioral covariates and the three main outcomes of study. Varied progress towards the "95-95-95" targets were observed in different regions of Zambia. Each "95" displayed a unique geographic pattern, independent of HIV prevalence, resulting in four distinct geographic clusters. Factors associated with gaps in the "95s" include younger age, male sex, and low wealth, with younger individuals having higher odds of not being on ART and having detectable viral loads. Our study revealed significant spatial heterogeneity in the HIV care continuum in Zambia, with different regions exhibiting unique geographic patterns and levels of performance in the "95-95-95" targets, highlighting the need for geospatial tailored interventions to address the specific needs of different subnational regions. These findings underscore the importance of addressing differential regional gaps in HIV diagnosis, enhancing community-level factors, and developing innovative strategies to improve local HIV care continuum outcomes.
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),
Integrating isoniazid preventive therapy into the fast-track HIV treatment model in urban Zambia: A proof-of -concept pilot project.
(2023) Mukumbwa-Mwenechanya M; Mubiana M; Somwe P; Zyambo K; Simwenda M; Zongwe N; Kalunkumya E; Mwango LK; Rabkin M; Mpesela F; Chungu F; Mwanza F; Preko P; Bolton-Moore C; Bosomprah S; Sharma A; Morton K; Kasonde P; Mulenga L; Lingu P; Mulenga PL; ICAP at Columbia University and Departments of Medicine & Epidemiology, New York, New York, United States of America.; ICAP at Columbia University, Mbabane, Eswatini.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Network of Zambian People Living with HIV, Lusaka, Zambia.; Clinton Health Access, Lusaka, Zambia.; ICAP at Columbia University, Lusaka, Zambia.; Columbia University Mailman School of Public Health, New York, New York, United States of America.; Ministry of Health, Lusaka, Zambia.; CIHEB, Lusaka, Zambia.; JSI USAID SAFE, Lusaka, Zambia.; University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; Treatment Advocacy and Literacy Campaign, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Most people living with HIV (PLHIV) established on treatment in Zambia receive multi-month prescribing and dispensing (MMSD) antiretroviral therapy (ART) and are enrolled in less-intensive differentiated service delivery (DSD) models such as Fast Track (FT), where clients collect ART every 3-6 months and make clinical visits every 6 months. In 2019, Zambia introduced Isoniazid Preventive Therapy (IPT) with scheduled visits at 2 weeks and 1, 3, and 6 months. Asynchronous IPT and HIV appointment schedules were inconvenient and not client centered. In response, we piloted integrated MMSD/IPT in FT HIV treatment model. We implemented and evaluated a proof-of-concept project at one purposively selected high-volume facility in Lusaka, Zambia between July 2019 and May 2020. We sensitized stakeholders, adapted training materials, standard operating procedures, and screened adults in FT for TB as per national guidelines. Participants received structured TB/IPT education, 6-month supply of isoniazid and ART, aligned 6th month IPT/MMSD clinic appointment, and phone appointments at 2 weeks and months 1-5 following IPT initiation. We used descriptive statistics to characterize IPT completion rates, phone appointment keeping, side effect frequency and Fisher's exact test to determine variation by participant characteristics. Key lessons learned were synthesized from monthly meeting notes. 1,167 clients were screened with 818 (70.1%) enrolled, two thirds (66%) were female and median age 42 years. 738 (90.2%) completed 6-month IPT course and 66 (8.1%) reported IPT-related side effects. 539 clients (65.9%) attended all 7 telephone appointments. There were insignificant differences of outcomes by age or sex. Lessons learnt included promoting project ownership, client empowerment, securing supply chain, adapting existing processes, and cultivating collaborative structured learning. Integrating multi-month dispensing and telephone follow up of IPT into the FT HIV treatment model is a promising approach to scaling-up TB preventive treatment among PLHIV, although limited by barriers to consistent phone access.
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) (
Retinoic acid elicits a coordinated expression of gut homing markers on T lymphocytes of Zambian men receiving oral Vivotif, but not Rotarix, Dukoral or OPVERO vaccines.
(2018-Jun-27) Mwanza-Lisulo M; Chomba MS; Chama M; Besa EC; Funjika E; Zyambo K; Banda R; Imikendu M; Sianongo S; Hancock REW; Lee A; Chilengi R; Stagg AJ; Namangala B; Kelly PM; Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia; Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK.; Institute of Distance Education, University of Zambia, Lusaka, Zambia.; Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia. Electronic address: mpalamwanza123@gmail.com.; Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia.; Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia; Department of Chemistry, University of Zambia, Lusaka, Zambia.; University of British Columbia, Vancouver, Canada.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK.
All-trans retinoic acid (ATRA) up-regulates, in laboratory animals, the expression of the gut homing markers α4β7 integrin and CCR9 on lymphocytes, increasing their gut tropism. Here, we show that, in healthy adult volunteers, ATRA induced an increase of these gut homing markers on T cells in vivo in a time dependent manner. The coordinated increase of α4β7 and CCR9 by ATRA was seen in 57% (12/21) of volunteers and only when given together with an oral Vivotif vaccine. When this coordinated response to ATRA and Vivotif vaccine was present, it was strongly correlated with the gut immunoglobulin A (IgA) specific response to vaccine LPS (ρ = 0.82; P = 0.02). Using RNA-Seq analysis of whole blood transcription, patients receiving ATRA and Vivotif in conjunction showed transcriptomic changes in immune-related pathways, particularly including interferon α/β signaling pathway, membrane-ECM interactions and immune hubs. These results suggest that exogenous ATRA can be used to manipulate responses to a subclass of oral vaccines, so far limited to a live attenuated Vivotif vaccine.
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),