Browsing by Author "Fenner L"

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Cardiovascular Involvement in Tuberculosis Patients Treated in Southern Africa.
(2025-Jan) Samim D; Muula G; Banholzer N; Chibomba D; Xulu S; Bolton C; Evans D; Perrig L; De Marchi S; Günther G; Egger M; Pilgrim T; Fenner L; Department of Pulmonology and Allergology, Inselspital, University Hospital of Bern, Bern, Switzerland.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, Republic of South Africa.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; University Teaching Hospital, Department of Internal Medicine, Lusaka, Zambia.; Department of Cardiology, Helen Joseph Clinic, Johannesburg, Republic of South Africa.; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.; Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
BACKGROUND: Tuberculosis (TB) is the leading cause of death among people with HIV and a major global health challenge. Subclinical cardiovascular manifestations of TB are poorly documented in high TB and HIV burden countries. OBJECTIVES: The purpose of this study was to quantify the prevalence of cardiovascular involvement in TB patients and investigate changes after completion of anti-TB treatment. METHODS: HIV-positive and HIV-negative patients diagnosed with pulmonary TB between October 2022 and November 2023 were enrolled from 2 tertiary care hospitals in Zambia and South Africa. Standardized transthoracic echocardiography (TTE) was conducted at TB diagnosis and after 6 months of anti-TB treatment. Cross-sectional and longitudinal analyses assessed pericardial effusion, thickening, or calcification, with and without signs of pericardial constriction. RESULTS: A total of 286 TB patients (218 [76%] men, 109 [38%] people with HIV, median age 35 years) underwent TTE at TB diagnosis, of whom 105 participants had a second TTE after completion of treatment. At TB diagnosis, 134 (47%) had pericardial effusions, 86 (30%) thickening, 7 (2%) calcifications, 103 (42%) signs of constriction, and 13 (12%) had definite diagnosis of constriction. After TB treatment, pericardial effusions (47% vs 16%, CONCLUSIONS: Cardiac involvement is frequent in newly diagnosed TB patients. Early pericardial changes may be reversed with anti-TB treatment. Echocardiographic screening facilitates early detection and timely management of cardiovascular involvement in TB patients.
Detection and management of drug-resistant tuberculosis in HIV-infected patients in lower-income countries.
(2014-Nov) Ballif M; Nhandu V; Wood R; Dusingize JC; Carter EJ; Cortes CP; McGowan CC; Diero L; Graber C; Renner L; Hawerlander D; Kiertiburanakul S; Du QT; Sterling TR; Egger M; Fenner L; Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; University of Ghana Medical School, Accra, Ghana.; University of Chile School of Medicine, Santiago, Chile.; Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; United States Agency for International Development Academic Model Providing Access to Healthcare, Eldoret, Kenya.; Centre Intégré de Recherches Biocliniques, Abidjan, Côte d'Ivoire.; Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Children's Hospital, Ho Chi Minh City, Viet Nam.; Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Women's Equity in Access to Care & Treatment, Kigali, Rwanda.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons. OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries. DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs. RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages. CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.
Field evaluation of nanopore targeted next-generation sequencing to predict drug-resistant tuberculosis from native sputum in South Africa and Zambia.
(2025-Mar-12) Schwab TC; Joseph L; Moono A; Göller PC; Motsei M; Muula G; Evans D; Neuenschwander S; Günther G; Bolton C; Keller PM; Ramette A; Egger M; Omar SV; Fenner L; Population Health Sciences, University of Bristol, Bristol, United Kingdom.; Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland.; Institute for Infectious Diseases, University of Bern Institute for Infectious Diseases, Bern, Switzerland.; Department of Medical Science, Faculty of Health Sciences, University of Namibia, Windhoek, Namibia.; Centre for Infectious Disease Epidemiology & Research, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa.; Centre for Tuberculosis, National & WHO Supranational TB Reference Laboratory, a division of the National Health Laboratory Services, National Institute for Communicable Diseases, Johannesburg, South Africa.; Department of Pulmonology and Allergology, Inselspital Universitatsspital Bern, Bern, Switzerland.; Clinical Bacteriology/Mycology, University Hospital Basel, Basel, Switzerland.; Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Rapid and comprehensive drug susceptibility testing (DST) is essential for diagnosing and treating drug-resistant tuberculosis effectively, and next-generation sequencing can be an effective genotypic DST method. We implemented and evaluated the performance of a nanopore targeted sequencing assay, called the Tuberculosis Drug Resistance Test (TBDR, Oxford Nanopore Diagnostics, Ltd., United Kingdom), which predicts drug resistance to 16 TB drugs, at a South African reference laboratory and a district diagnostic laboratory in Zambia. We compared the sequencing success rates between unprocessed and decontaminated sputum samples and determined the diagnostic accuracy against local DST (Xpert MTB/RIF Ultra, Xpert MTB/XDR, and BD BACTEC MGIT phenotypic DST). We prospectively sequenced 236 samples and have 148 samples with sequencing results from unprocessed and decontaminated sputum. We obtained successful sequencing results from 66.4% (94/148) unprocessed sputum samples and 75% (111/148) decontaminated samples. Sequencing success rates at the two sites differed, with 50.7% (36/71) successful sequencing results from unprocessed sputum in Zambia and 75.3% (58/77) in South Africa. Samples with "low" bacterial load, measured by Xpert MTB/RIF Ultra, tended to produce fewer successful sequencing results. TBDR sequencing predicted resistances in 48 samples, detecting resistance for rifampicin (
Seasonal variations in tuberculosis diagnosis among HIV-positive individuals in Southern Africa: analysis of cohort studies at antiretroviral treatment programmes.
(2018-Jan-11) Ballif M; Zürcher K; Reid SE; Boulle A; Fox MP; Prozesky HW; Chimbetete C; Zwahlen M; Egger M; Fenner L; Centre for Infectious Disease Epidemiology and Research (CIDER), School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Departments of Epidemiology and Global Health, Boston University, Boston, USA.; Médecins Sans Frontières, Khayelitsha, South Africa.; Tuberculosis Department Unit, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Institute of Social and Preventive Medicine, University of Bern, Bern, BE, Switzerland.; Division of Infection Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.; Department of Internal Medicine, Health Economics and Epidemiology Research Office, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Division of Infectious Diseases, Department of Medicine, University of Stellenbosch & Tygerberg Academic Hospital, Cape Town, South Africa.; Newlands Clinic, Harare, Zimbabwe.
OBJECTIVES: Seasonal variations in tuberculosis diagnoses have been attributed to seasonal climatic changes and indoor crowding during colder winter months. We investigated trends in pulmonary tuberculosis (PTB) diagnosis at antiretroviral therapy (ART) programmes in Southern Africa. SETTING: Five ART programmes participating in the International Epidemiology Database to Evaluate AIDS in South Africa, Zambia and Zimbabwe. PARTICIPANTS: We analysed data of 331 634 HIV-positive adults (>15 years), who initiated ART between January 2004 and December 2014. PRIMARY OUTCOME MEASURE: We calculated aggregated averages in monthly counts of PTB diagnoses and ART initiations. To account for time trends, we compared deviations of monthly event counts to yearly averages, and calculated correlation coefficients. We used multivariable regressions to assess associations between deviations of monthly ART initiation and PTB diagnosis counts from yearly averages, adjusted for monthly air temperatures and geographical latitude. As controls, we used Kaposi sarcoma and extrapulmonary tuberculosis (EPTB) diagnoses. RESULTS: All programmes showed monthly variations in PTB diagnoses that paralleled fluctuations in ART initiations, with recurrent patterns across 2004-2014. The strongest drops in PTB diagnoses occurred in December, followed by April-May in Zimbabwe and South Africa. This corresponded to holiday seasons, when clinical activities are reduced. We observed little monthly variation in ART initiations and PTB diagnoses in Zambia. Correlation coefficients supported parallel trends in ART initiations and PTB diagnoses (correlation coefficient: 0.28, 95% CI 0.21 to 0.35, P<0.001). Monthly temperatures and latitude did not substantially change regression coefficients between ART initiations and PTB diagnoses. Trends in Kaposi sarcoma and EPTB diagnoses similarly followed changes in ART initiations throughout the year. CONCLUSIONS: Monthly variations in PTB diagnosis at ART programmes in Southern Africa likely occurred regardless of seasonal variations in temperatures or latitude and reflected fluctuations in clinical activities and changes in health-seeking behaviour throughout the year, rather than climatic factors.
The long-term impact of the COVID-19 pandemic on tuberculosis care and infection control measures in anti-retroviral therapy (ART) clinics in low- and middle-income countries: a multiregional site survey in Asia and Africa.
(2025-Mar-24) Ballif M; Banholzer N; Perrig L; Avihingsanon A; Nsonde DM; Obatsa S; Muula G; Komena E; Uemura H; Lelo P; Otaalo B; Huwa J; Gouéssé P; Kumarasamy N; Brazier E; Michael D; Rafael I; Ramdé R; Somia IKA; Yotebieng M; Diero L; Euvrard J; Ezechi O; Fenner L; Centre de Traitement Ambulatoire, Brazzaville, Republic of Congo.; Centre for Reproduction and Population Health Studies, Nigerian Institute of Medical Research, Lagos, Nigeria.; City University of New York, Institute for Implementation Science in Population Health, New York, NY, USA.; Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.; CePReF, Abidjan, Côte d'Ivoire.; Lighthouse Trust, Lilongwe, Malawi.; Centre for Microbiology and Research, Kenya Medical Research Institute, Kisumu, Kenya.; AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland lukas.fenner@unibe.ch.; Faculty of Medicine, Udayana University, Ngoerah Hospital, Bali, Indonesia.; School of Public Health, University of Cape Town, Cape Town, South Africa.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Pediatric Hospital of Kalembelembe, Kinshasa, Democratic Republic of the Congo.; CART Clinical Research Site, Voluntary Health Services, Chennai, India.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.; HIV-NAT / Thai Red Cross AIDS Research Centre and Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.; SolidarMed, Chiure, Mozambique.; PAC-CI program, Abidjan, Côte d'Ivoire.; CHU Sourô Sanou, Bobo-Dioulasso, Burkina Faso.; Department of Medicine, Moi University, AMPATH Program / Moi Teaching and Referral Hospital, Eldoret, Kenya.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Kisesa Observation Cohort study, National Institute for Medical Reseach, Mwanza, Tanzania.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The COVID-19 pandemic challenged healthcare systems, particularly in settings with high infectious disease burden. We examined the postpandemic long-term impacts of COVID-19 on tuberculosis (TB) services at anti-retroviral therapy (ART) clinics in lower-income countries. METHODS: Using standardised online questionnaires, we conducted a cross-sectional site survey among ART clinics providing TB services in Africa and Asia from July to September 2023 (site-level information and number of TB diagnoses and tests). RESULTS: Of 45 participating ART clinics, 32 (71%) were in Africa and 13 (29%) in Asia. During the COVID-19 pandemic (2020-2022), 43 (96%) clinics reported implementing social distancing or separation measures, 39 (87%) personal protections for staff members and 32 (71%) protections for patients. Infection control measures were in place in 45% of the clinics before the pandemic (until 2019), 23% introduced measures during the pandemic and 15% maintained them after the pandemic (after 2022). Service provision was affected during the pandemic in 33 (73%) clinics, including TB services in 22 (49%) clinics. TB service restrictions were addressed by introducing changes in directly observed therapy provision in 8 (18%) clinics, multimonth TB drug dispensing in 23 (51%), telehealth services in 25 (56%) and differentiated service delivery in 19 (42%). These changes were sustained after the pandemic at 4 (9%), 11 (24%), 17 (38%) and 12 (27%) clinics, respectively. Compared with 2018-2019, the number of TB diagnoses decreased sharply in 2020-2021 and improved after the pandemic. CONCLUSIONS: COVID-19 affected TB care services in ART clinics in Africa and Asia. This was paralleled by a reduction in TB diagnoses, which partly resumed after the pandemic. Infection control measures and alternative modes of service delivery were adopted during the pandemic and only partially maintained. Efforts should be made to sustain the lessons learnt during the COVID-19 pandemic, particularly approaches that reduce the risk of transmission of infectious diseases, including TB, in ART clinics.
The Tuberculosis Sentinel Research Network (TB-SRN) of the International epidemiology Databases to Evaluate AIDS (IeDEA): protocol for a prospective cohort study in Africa, Southeast Asia and Latin America.
(2024-Jan-09) Enane LA; Duda SN; Chanyachukul T; Bolton-Moore C; Navuluri N; Messou E; Mbonze N; McDade LR; Figueiredo MC; Ross J; Evans D; Diero L; Akpata R; Zotova N; Freeman A; Pierre MF; Rupasinghe D; Ballif M; Byakwaga H; de Castro N; Tabala M; Sterling TR; Sohn AH; Fenner L; Wools-Kaloustian K; Poda A; Yotebieng M; Huebner R; Marcy O; Duke Global Health Institute, Duke University, Durham, North Carolina, USA.; Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.; Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; The Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA lenane@iu.edu.; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Vanderbilt Institute of Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Mbarara University of Science and Technology Faculty of Medicine, Mbarara, Uganda.; Center for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland.; Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; TREAT Asia/amfAR - The Foundation for AIDS Research, Bangkok, Thailand.; Kinshasa School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.; Université de Bordeaux, Bordeaux, France.; The Kirby Institute, UNSW, Sydney, New South Wales, Australia.; Centre de Prise en Charge de Recherche et de Formation (Aconda-CePReF), Abidjan, Côte d'Ivoire.; Vanderbilt Tuberculosis Center, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; Indiana University Center for Global Health Equity, Indianapolis, Indiana, USA.; The Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti.; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Medicine, Moi University College of Health Sciences, Eldoret, Kenya.; Centre Hospitalier Universitaire Sourô Sanou, Bobo Dioulasso, Burkina Faso.
INTRODUCTION: Tuberculosis (TB) is a leading infectious cause of death globally. It is the most common opportunistic infection in people living with HIV, and the most common cause of their morbidity and mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The TB Sentinel Research Network (TB-SRN) provides a platform for coordinated observational TB research within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS AND ANALYSIS: This prospective, observational cohort study will assess treatment and post-treatment outcomes of pulmonary TB (microbiologically confirmed or clinically diagnosed) among 2600 people aged ≥15 years, with and without HIV coinfection, consecutively enrolled at 16 sites in 11 countries, across 6 of IeDEA's global regions. Data regarding clinical and sociodemographic factors, mental health, health-related quality of life, pulmonary function, and laboratory and radiographic findings will be collected using standardised questionnaires and data collection tools, beginning from the initiation of TB treatment and through 12 months after the end of treatment. Data will be aggregated for proposed analyses. ETHICS AND DISSEMINATION: Ethics approval was obtained at all implementing study sites, including the Vanderbilt University Medical Center Human Research Protections Programme. Participants will provide informed consent; for minors, this includes both adolescent assent and the consent of their parent or primary caregiver. Protections for vulnerable groups are included, in alignment with local standards and considerations at sites. Procedures for requesting use and analysis of TB-SRN data are publicly available. Findings from TB-SRN analyses will be shared with national TB programmes to inform TB programming and policy, and disseminated at regional and global conferences and other venues.