Browsing by Author "Kerkhoff AD"

Now showing 1 - 20 of 27

A mixed methods study on men's and women's tuberculosis care journeys in Lusaka, Zambia-Implications for gender-tailored tuberculosis health promotion and case finding strategies.
(2023) Kerkhoff AD; Mwamba C; Pry JM; Kagujje M; Nyangu S; Mateyo K; Sanjase N; Chilukutu L; Christopoulos KA; Muyoyeta M; Sharma A; Division of Epidemiology, University of California Davis, Davis, California, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of HIV, Infectious Diseases and Global Medicine Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, California, United States of America.; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Men and women with undiagnosed tuberculosis (TB) in high burden countries may have differential factors influencing their healthcare seeking behaviors and access to TB services, which can result in delayed diagnoses and increase TB-related morbidity and mortality. A convergent, parallel, mixed-methods study design was used to explore and evaluate TB care engagement among adults (≥18 years) with newly diagnosed, microbiologically-confirmed TB attending three public health facilities in Lusaka, Zambia. Quantitative structured surveys characterized the TB care pathway (time to initial care-seeking, diagnosis, and treatment initiation) and collected information on factors influencing care engagement. Multinomial multivariable logistic regression was used to determine predicted probabilities of TB health-seeking behaviors and determinants of care engagement. Qualitative in-depth interviews (IDIs; n = 20) were conducted and analyzed using a hybrid approach to identify barriers and facilitators to TB care engagement by gender. Overall, 400 TB patients completed a structured survey, of which 275 (68.8%) and 125 (31.3%) were men and women, respectively. Men were more likely to be unmarried (39.3% and 27.2%), have a higher median daily income (50 and 30 Zambian Kwacha [ZMW]), alcohol use disorder (70.9% [AUDIT-C score ≥4] and 31.2% [AUDIT-C score ≥3]), and a history of smoking (63.3% and 8.8%), while women were more likely to be religious (96.8% and 70.8%) and living with HIV (70.4% and 36.0%). After adjusting for potential confounders, the probability of delayed health-seeking ≥4 weeks after symptom onset did not differ significantly by gender (44.0% and 36.2%, p = 0.14). While the top reasons for delayed healthcare-seeking were largely similar by gender, men were more likely to report initially perceiving their symptoms as not being serious (94.8% and 78.7%, p = 0.032), while women were more likely to report not knowing the symptoms of TB before their diagnosis (89.5% and 74.4%; p = 0.007) and having a prior bad healthcare experience (26.4% and 9.9%; p = 0.036). Notably, women had a higher probability of receiving TB diagnosis ≥2 weeks after initial healthcare seeking (56.5% and 41.0%, p = 0.007). While men and women reported similar acceptability of health-information sources, they emphasized different trusted messengers. Also, men had a higher adjusted probability of stating that no one influenced their health-related decision making (37.9% and 28.3%, p = 0.001). In IDIs, men recommended TB testing sites at convenient community locations, while women endorsed an incentivized, peer-based, case-finding approach. Sensitization and TB testing strategies at bars and churches were highlighted as promising approaches to reach men and women, respectively. This mixed-methods study found important differences between men and women with TB in Zambia. These differences suggest the need for gender-tailored TB health promotion, including addressing harmful alcohol use and smoking among men, and sensitizing HCWs to prolonged delays in TB diagnosis among women, and also using gender-specific approaches as part of community-based, active case-finding strategies to improve TB diagnosis in high burden settings.
A Prospective Evaluation of the Diagnostic Accuracy of the Point-of-Care VISITECT CD4 Advanced Disease Test in 7 Countries.
(2025-Feb-04) Gils T; Hella J; Jacobs BKM; Sossen B; Mukoka M; Muyoyeta M; Nakabugo E; Van Nguyen H; Ubolyam S; Macé A; Vermeulen M; Nyangu S; Sanjase N; Sasamalo M; Dinh HT; Ngo TA; Manosuthi W; Jirajariyavej S; Denkinger CM; Nguyen NV; Avihingsanon A; Nakiyingi L; Székely R; Kerkhoff AD; MacPherson P; Meintjes G; Reither K; Ruhwald M; School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom.; German Centre for Infection Research, Heidelberg University Hospital, Heidelberg, Germany.; Viet Tiep Hospital, Hai Phong, Viet Nam.; Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand.; National Lung Hospital, Ha Noi, Viet Nam.; Taksin Hospital, Bangkok, Thailand.; Global Health Institute, University of Antwerp, Wilrijk, Belgium.; Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; University of Basel, Basel, Switzerland.; Public Health Group, Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.; Ifakara Health Institute, Dar es Salaam, Tanzania.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California, San Francisco, San Francisco, California, USA.; Clinical Research Unit, Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; Department of Pathology, Kamuzu University of Health Sciences, Blantyre, Malawi.; HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre and Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.; Foundation for Innovative New Diagnostics, the Global Alliance for Diagnostics, Geneva, Switzerland.; Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.; Division of Infectious Disease and Tropical Medicine, Heidelberg University Hospital and Faculty of Medicine, Heidelberg University, Heidelberg, Germany.; Infectious Diseases Institute, Makerere University, Kampala, Uganda.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: CD4 measurement is pivotal in the management of advanced human immunodeficiency virus (HIV) disease. VISITECT CD4 Advanced Disease (VISITECT; AccuBio, Ltd) is an instrument-free, point-of-care, semiquantitative test allowing visual identification of CD4 ≤ 200 cells/µL or >200 cells/ µL from finger-prick or venous blood. METHODS: As part of a diagnostic accuracy study of FUJIFILM SILVAMP TB LAM, people with HIV ≥18 years old were prospectively recruited in 7 countries from outpatient departments if a tuberculosis symptom was present, and from inpatient departments. Participants provided venous blood for CD4 measurement using flow cytometry (reference standard) and finger-prick blood for VISITECT (index text), performed at point-of-care. Sensitivity, specificity, and positive and negative predictive values of VISITECT to determine CD4 ≤ 200 cells/ µL were evaluated. RESULTS: Among 1604 participants, the median flow cytometry CD4 was 367 cells/µL (interquartile range, 128-626 cells/µL) and 521 (32.5%) had CD4 ≤ 200 cells/µL. VISITECT sensitivity was 92.7% (483/521; 95% confidence interval [CI], 90.1%-94.7%) and specificity was 61.4% (665/1083; 95% CI, 58.4%-64.3%). For participants with CD4 0-100, 101-200, 201-300, 301-500, and >500 cells/µL, VISITECT misclassified 4.5% (95% CI, 2.5%-7.2%), 12.5 (95% CI, 8.0%-18.2%), 74.1% (95% CI, 67.0%-80.5%), 48.0% (95% CI, 42.5%-53.6%), and 22.6% (95% CI, 19.3%-26.3%), respectively. CONCLUSIONS: VISITECT's sensitivity, but not specificity, met the World Health Organization's minimal sensitivity and specificity threshold of 80% for point-of-care CD4 tests. VISITECT's quality needs to be assessed and its accuracy optimized. VISITECT's utility as CD4 triage test should be investigated. Clinical Trials Registration. NCT04089423.
Clinical and radiographic characteristics of presumptive tuberculosis patients previously treated for tuberculosis in Zambia.
(2022) Mateyo K; Kerkhoff AD; Dunn I; Nteeni MS; Muyoyeta M; Department of Radiology, Levy Mwanawasa University Teaching Hospital, Lusaka, Zambia.; Division of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, California, United States of America.; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Radiology, University of British Columbia, Vancouver, Canada.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Persistent respiratory symptoms and radiographic abnormalities are common among individuals previously treated for tuberculosis (TB) and may contribute to misdiagnosis and incorrect treatment when they seek care. We sought to determine if clinical and radiographic characteristics differed among previously treated, presumptive TB patients according to their current TB disease status. METHODS: Adults (>18 years of age) seeking care at a public health facility in Lusaka, Zambia were systematically evaluated for active TB using symptom screening and chest X-ray. All patients with presumptive TB submitted a sputum sample for microbiological TB testing. Patients who reported a prior history of TB treatment were included in the present analysis. 'Confirmed TB' was defined by the detection of TB using Xpert Ultra and/or liquid culture, while 'possible TB' was defined by the receipt of TB treatment without a positive Xpert Ultra or culture result. We evaluated the positive predictive value (PPV) of clinical symptoms and radiographic features for active TB alone and in combination. RESULTS: Of 740 presumptive TB patients, 144 (19%) had been previously treated for active TB. Of these, 19 (13%) patients had confirmed TB, 14 (10%) had possible TB, and 111 (77%) had no pulmonary TB. Overall, 119 (83%) patients had ≥1 current respiratory symptom-this did not differ according to current TB disease classification (95%, 93%, 79%; p = 0.23). Sixty-one patients (56%) had radiographic abnormalities suggestive of active TB and such findings were more common among patients with confirmed or possible TB compared to those without TB (93%, 71%, vs. 47%; p = 0.002). Most patients (n = 91, 83%) had at least one radiographic abnormality-no difference by current TB classification was observed (93%, 100%, 79%; p = 0.08). The PPV of any current respiratory symptom, active TB radiographic finding, or any radiographic abnormality for TB was 13% (95%CI: 7-21%), 21% (95%CI: 12-34) and 14% (95%CI: 9-23), respectively; combining clinical and radiographic characteristics did not significantly improve the PPV for active TB. CONCLUSIONS: Among presumptive TB patients previously treated for TB, respiratory symptoms and radiographic abnormalities were common and poorly differentiated those with current active TB from those without current active TB. Reliance on clinical and radiographic characteristics alone in this patient population may result in substantial overtreatment and therefore, microbiological investigations should be used to inform TB treatment decisions whenever possible.
Community-wide Screening for Tuberculosis.
(2020-Mar-19) Kerkhoff AD; Muyoyeta M; Cattamanchi A; University of California, San Francisco, San Francisco, CA andrew.kerkhoff@ucsf.edu.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; University of California, San Francisco, San Francisco, CA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Designing community-based strategies to reach non-household contacts of people with tuberculosis in Lusaka, Zambia: a rapid qualitative study among key stakeholders.
(2024) Kerkhoff AD; Foloko M; Kundu-Ng'andu E; Nyirenda H; Jabbie Z; Syulikwa M; Mwamba C; Kagujje M; Muyoyeta M; Sharma A; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, CA, United States.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: In high-burden settings, most tuberculosis (TB) transmission likely occurs outside the home. Our qualitative study in Zambia explored the acceptability and preferences for designing TB active case finding (ACF) strategies to reach non-household contacts of people with TB. METHODS: We conducted 56 in-depth interviews with persons with TB ( RESULTS: All participants felt that TB was an important issue in their community and that new detection strategies were needed. A "social-network strategy" was perceived as acceptable and feasible, where participants noted it was a caring act and could facilitate early diagnosis. For a "venue-based strategy," most participants suspected TB transmission occurred at bars/taverns due to heavy alcohol use and prolonged time spent in crowded spaces; churches and betting halls were also commonly mentioned locations. Nearly all owners/leaders and patrons/attendees of bars, churches, and betting halls expressed acceptance of a venue-based strategy. They also indicated an interest in participating, citing many benefits, including increased TB knowledge/awareness, early diagnosis, convenience, and possibly reduced transmission, and recommended that the strategy incorporate sensitization, consent, volunteerism, and respectful, confidential, private services. For both strategies, most participants preferred the use of and being approached by trained peer TB survivors to facilitate ACF, given their prior TB patient experience and trust among community members. CONCLUSION: Stakeholders found social-network and venue-based TB-ACF strategies highly acceptable, recognizing their potential benefits for individuals and the broader community. Future research should evaluate the feasibility and effectiveness of TB ACF strategies for reaching non-household contacts.
Diagnosed with TB in the era of COVID-19: patient perspectives in Zambia.
(2020-Dec-21) Mwamba C; Kerkhoff AD; Kagujje M; Lungu P; Muyoyeta M; Sharma A; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California, San Francisco, San Francisco, CA, USA.; National Tuberculosis and Leprosy Control Programme, Lusaka.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: Delayed TB diagnosis and treatment perpetuate the high burden of TB-related morbidity and mortality in resource-constrained settings. We explored the potential of COVID-19 to further compromise TB care engagement in Zambia. METHODS: From April to May 2020, we purposefully selected 17 adults newly diagnosed with TB from three public health facilities in Lusaka, Zambia, for in-depth phone interviews. We conducted thematic analyses using a hybrid approach. RESULTS: The majority of participants were highly concerned about the impact of lockdowns on their financial security. Most were not worried about being diagnosed with COVID-19 when seeking care for their illness because they felt unwell prior to the outbreak; however, they were very worried about contracting COVID-19 during clinic visits. COVID-19 was perceived as a greater threat than TB as it is highly transmittable and there is no treatment for it, which provoked fear of social isolation and of death among participants in case they contracted it. Nonetheless, participants reported willingness to continue with TB medication and the clinic visits required to improve their health. CONCLUSION: The COVID-19 pandemic did not appear to deter care-seeking for TB by patients. However, messaging on TB in the era of COVID-19 must encourage timely care-seeking by informing people of infection control measures taken at health facilities.
Diagnostic accuracy of a novel point-of-care urine lipoarabinomannan assay for the detection of tuberculosis among adult outpatients in Zambia: a prospective cross-sectional study.
(2021-Nov) Muyoyeta M; Kerkhoff AD; Chilukutu L; Moreau E; Schumacher SG; Ruhwald M; These authors contributed equally to this work.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, CA, USA.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia Mondemuy@gmail.com.; Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: A novel, rapid, point-of-care urine-based lipoarabinomannan assay (Fujifilm SILVAMP TB LAM ("FujiLAM")) has previously demonstrated substantially higher sensitivity for tuberculosis (TB) compared with the commercially available Determine TB LAM assay using biobanked specimens. However, FujiLAM has not been prospectively evaluated using fresh urine specimens. Therefore, we determined the diagnostic accuracy of FujiLAM among HIV-positive and HIV-negative outpatients with presumptive TB in Zambia. METHODS: Adult (≥18 years old) presumptive TB patients presenting to two outpatient public health facilities in Lusaka were included. All patients submitted sputa samples for smear microscopy, Xpert MTB/RIF and mycobacterial culture, and urine samples for the FujiLAM assay. Microbiologically confirmed TB was defined by the detection of RESULTS: 151 adults with paired sputum microbiological tests and urine FujiLAM results were included; 45% were HIV-positive. Overall, 34 out of 151 (23%) patients had culture-confirmed pulmonary TB. The overall sensitivity and specificity of FujiLAM was 77% (95% CI 59-89%) and 92% (95% CI 86-96%), respectively. FujiLAM's sensitivity among HIV-positive patients was 75% (95% CI 43-95%) compared with 75% (95% CI 51-91%) among HIV-negative patients. The sensitivity of FujiLAM in patients with smear-positive, confirmed pulmonary TB was 87% (95% CI 60-98%) compared with 68% (95% CI 43-87%) among patients with smear-negative, confirmed pulmonary TB. CONCLUSIONS: FujiLAM demonstrated high sensitivity for the detection of TB among both HIV-positive and HIV-negative adults, and also demonstrated good specificity despite the lack of systematic extrapulmonary sampling to inform a comprehensive microbiological reference standard.
Diagnostic yield as an important metric for the evaluation of novel tuberculosis tests: rationale and guidance for future research.
(2024-Jul) Broger T; Marx FM; Theron G; Marais BJ; Nicol MP; Kerkhoff AD; Nathavitharana R; Huerga H; Gupta-Wright A; Kohli M; Nichols BE; Muyoyeta M; Meintjes G; Ruhwald M; Peeling RW; Pai NP; Pollock NR; Pai M; Cattamanchi A; Dowdy DW; Dewan P; Denkinger CM; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Boston Children's Hospital, Boston, MA, USA.; The University of Sydney Infectious Diseases Institute, Sydney, NSW, Australia; Children's Hospital at Westmead, Sydney, NSW, Australia.; Bill & Melinda Gates Foundation, Seattle, WA, USA.; Department of Epidemiology, Epicentre, Paris, France.; McGill International TB Centre, McGill University, Montreal, QC, Canada.; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA; Department of Medicine, Division of Pulmonary Diseases and Critical Care Medicine, University of California Irvine, Irvine, CA, USA.; Department of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany; DSI-NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.; London School of Hygiene & Tropical Medicine, London, UK.; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Department of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany; German Center for Infection Research, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: claudia.denkinger@uni-heidelberg.de.; Department of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Department of Medicine, University of Cape Town, Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; Division of HIV, Infectious Diseases, and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, CA, USA; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.; Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.; Department of Medicine, Centre for Outcomes Research & Evaluation, McGill University, Montreal, QC, Canada.; FIND, Geneva, Switzerland.; Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Better access to tuberculosis testing is a key priority for fighting tuberculosis, the leading cause of infectious disease deaths in people. Despite the roll-out of molecular WHO-recommended rapid diagnostics to replace sputum smear microscopy over the past decade, a large diagnostic gap remains. Of the estimated 10·6 million people who developed tuberculosis globally in 2022, more than 3·1 million were not diagnosed. An exclusive focus on improving tuberculosis test accuracy alone will not be sufficient to close the diagnostic gap for tuberculosis. Diagnostic yield, which we define as the proportion of people in whom a diagnostic test identifies tuberculosis among all people we attempt to test for tuberculosis, is an important metric not adequately explored. Diagnostic yield is particularly relevant for subpopulations unable to produce sputum such as young children, people living with HIV, and people with subclinical tuberculosis. As more accessible non-sputum specimens (eg, urine, oral swabs, saliva, capillary blood, and breath) are being explored for point-of-care tuberculosis testing, the concept of yield will be of growing importance. Using the example of urine lipoarabinomannan testing, we illustrate how even tests with limited sensitivity can diagnose more people with tuberculosis if they enable increased diagnostic yield. Using tongue swab-based molecular tuberculosis testing as another example, we provide definitions and guidance for the design and conduct of pragmatic studies that assess diagnostic yield. Lastly, we show how diagnostic yield and other important test characteristics, such as cost and implementation feasibility, are essential for increased effective population coverage, which is required for optimal clinical care and transmission impact. We are calling for diagnostic yield to be incorporated into tuberculosis test evaluation processes, including the WHO Grading of Recommendations, Assessment, Development, and Evaluations process, providing a crucial real-life implementation metric that complements traditional accuracy measures.
Diagnostic yield of urine lipoarabinomannan and sputum tuberculosis tests in people living with HIV: a systematic review and meta-analysis of individual participant data.
(2023-Jun) Broger T; Koeppel L; Huerga H; Miller P; Gupta-Wright A; Blanc FX; Esmail A; Reeve BWP; Floridia M; Kerkhoff AD; Ciccacci F; Kasaro MP; Thit SS; Bastard M; Ferlazzo G; Yoon C; Van Hoving DJ; Sossen B; García JI; Cummings MJ; Wake RM; Hanson J; Cattamanchi A; Meintjes G; Maartens G; Wood R; Theron G; Dheda K; Olaru ID; Denkinger CM; Population Health Program, Tuberculosis Group, Texas Biomedical Research Institute, San Antonio, TX, USA.; National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.; Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA; Trauma Center, University of California San Francisco, San Francisco, CA, USA; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.; Division of Emergency Medicine, University of Cape Town, Cape Town, South Africa; Division of Emergency Medicine, Stellenbosch University, Cape Town, South Africa.; The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK; Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, Cape Town, South Africa; South African MRC Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South Africa.; Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Irving Medical Center, New York, NY, USA; Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.; Division of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany.; New Zealand Institute for Plant and Food Research, Auckland, New Zealand.; Department of Medicine, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA; Department of Medicine, Division of Pulmonary Diseases and Critical Care Medicine, University of California Irvine, Irvine, CA, USA.; Department of Medicine, University of Cape Town, Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; UniCamillus, International University of Health and Medical Science, Rome, Italy; Community of Sant'Egidio, DREAM programme, Rome, Italy.; Field Epidemiology Department, Epicentre, Paris, France.; Department of Medicine, Médecins Sans Frontières, Paris, France.; Division of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany; Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK.; Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, Cape Town, South Africa; South African MRC Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South Africa.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; UNC Global Projects, LLC Zambia, Lusaka, Zambia.; Institute for Global Health, University College London, London, UK; Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK.; Centre for Healthcare-Associated Infections, Antimicrobial Resistance and Mycoses, National Institute for Communicable Diseases, Johannesburg, South Africa; Institute for Infection and Immunity, St George's University of London, London, UK.; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.; Department of Medicine, University of Medicine 2, Yangon, Myanmar.; Service de Pneumologie, l'institut du thorax, Nantes Université, CHU Nantes, Nantes, France.; Division of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany; German Center for Infection Research, partner site, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: claudia.denkinger@uni-heidelberg.de.; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council Centre for Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily available. We hypothesised that sample availability influences the diagnostic yield of various tuberculosis tests. METHODS: In this systematic review and meta-analysis of individual participant data, we compared the diagnostic yield of point-of-care urine-based lipoarabinomannan tests with that of sputum-based nucleic acid amplification tests (NAATs) and sputum smear microscopy (SSM). We used microbiologically confirmed tuberculosis based on positive culture or NAAT from any body site as the denominator and accounted for sample provision. We searched PubMed, Web of Science, Embase, African Journals Online, and clinicaltrials.gov from database inception to Feb 24, 2022 for randomised controlled trials, cross-sectional studies, and cohort studies that assessed urine lipoarabinomannan point-of-care tests and sputum NAATs for active tuberculosis detection in participants irrespective of tuberculosis symptoms, HIV status, CD4 cell count, or study setting. We excluded studies in which recruitment was not consecutive, systematic, or random; provision of sputum or urine was an inclusion criterion; less than 30 participants were diagnosed with tuberculosis; early research assays without clearly defined cutoffs were tested; and humans were not studied. We extracted study-level data, and authors of eligible studies were invited to contribute deidentified individual participant data. The main outcomes were the tuberculosis diagnostic yields of urine lipoarabinomannan tests, sputum NAATs, and SSM. Diagnostic yields were predicted using Bayesian random-effects and mixed-effects meta-analyses. This study is registered with PROSPERO, CRD42021230337. FINDINGS: We identified 844 records, from which 20 datasets and 10 202 participants (4561 [45%] male participants and 5641 [55%] female participants) were included in the meta-analysis. All studies assessed sputum Xpert (MTB/RIF or Ultra, Cepheid, Sunnyvale, CA, USA) and urine Alere Determine TB LAM (AlereLAM, Abbott, Chicago, IL, USA) in people living with HIV aged 15 years or older. Nearly all (9957 [98%] of 10 202) participants provided urine, and 82% (8360 of 10 202) provided sputum within 2 days. In studies that enrolled unselected inpatients irrespective of tuberculosis symptoms, only 54% (1084 of 1993) of participants provided sputum, whereas 99% (1966 of 1993) provided urine. Diagnostic yield was 41% (95% credible interval [CrI] 15-66) for AlereLAM, 61% (95% Crl 25-88) for Xpert, and 32% (95% Crl 10-55) for SSM. Heterogeneity existed across studies in the diagnostic yield, influenced by CD4 cell count, tuberculosis symptoms, and clinical setting. In predefined subgroup analyses, all tests had higher yields in symptomatic participants, and AlereLAM yield was higher in those with low CD4 counts and inpatients. AlereLAM and Xpert yields were similar among inpatients in studies enrolling unselected participants who were not assessed for tuberculosis symptoms (51% vs 47%). AlereLAM and Xpert together had a yield of 71% in unselected inpatients, supporting the implementation of combined testing strategies. INTERPRETATION: AlereLAM, with its rapid turnaround time and simplicity, should be prioritised to inform tuberculosis therapy among inpatients who are HIV-positive, regardless of symptoms or CD4 cell count. The yield of sputum-based tuberculosis tests is undermined by people living with HIV who cannot produce sputum, whereas nearly all participants are able to provide urine. The strengths of this meta-analysis are its large size, the carefully harmonised denominator, and the use of Bayesian random-effects and mixed-effects models to predict yields; however, data were geographically restricted, clinically diagnosed tuberculosis was not considered in the denominator, and little information exists on strategies for obtaining sputum samples. FUNDING: FIND, the Global Alliance for Diagnostics.
Evaluation of kidney function among people living with HIV initiating antiretroviral therapy in Zambia.
(2022) Pry JM; Vinikoor MJ; Bolton Moore C; Roy M; Mody A; Sikazwe I; Sharma A; Chihota B; Duran-Frigola M; Daultrey H; Mutale J; Kerkhoff AD; Geng EH; Pollock BH; Vera JH; School of Medicine, University of California, Davis, California, United States of America.; School of Medicine University of Alabama, Birmingham, Alabama, United States of America.; Ersilia Open Source Initiative, Cambridge, United Kingdom.; School of Medicine, Washington University, St. Louis, Missouri, United States of America.; School of Medicine, University of California, San Francisco, California, United States of America.; Centre for Infectious Disease Research Zambia (CIDRZ), Lusaka, Zambia.; Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom.
As the response to the HIV epidemic in sub-Saharan Africa continues to mature, a growing number of people living with HIV (PLHIV) are aging and risk for non-communicable diseases increases. Routine laboratory tests of serum creatinine have been conducted to assess HIV treatment (ART) suitability. Here we utilize those measures to assess kidney function impairment among those initiating ART. Identification of non-communicable disease (NCD) risks among those in HIV care creates opportunity to improve public health through care referral and/or NCD/HIV care integration. We estimated glomerular filtration rates (eGFR) using routinely collected serum creatinine measures among a cohort of PLHIV with an HIV care visit at one of 113 Centre for Infectious Disease Research Zambia (CIDRZ) supported sites between January 1, 2011 and December 31, 2017, across seven of the ten provinces in Zambia. We used mixed-effect Poisson regression to assess predictors of eGFR <60ml/min/1.73m2 allowing random effects at the individual and facility level. Additionally, we assessed agreement between four eGFR formulae with unadjusted CKD-EPI as a standard using Scott/Fleiss method across five categories of kidney function. A total of 72,933 observations among 68,534 individuals met the inclusion criteria for analysis. Of the 68,534, the majority were female 41,042 (59.8%), the median age was 34 (interquartile range [IQR]: 28-40), and median CD4 cell count was 292 (IQR: 162-435). The proportion of individuals with an eGFR <60ml/min/1.73m2 was 6.9% (95% CI: 6.7-7.1%) according to the unadjusted CKD-EPI equation. There was variation in agreement across eGFR formulas considered compared to unadjusted CKD-EPI (χ2 p-value <0.001). Estimated GFR less than 60ml/min/1.73m2, per the unadjusted CKD-EPI equation, was significantly associated with age, sex, body mass index, and blood pressure. Using routine serum creatinine measures, we identified a significant proportion of individuals with eGFR indicating moderate or great kidney function impairment among PLHIV initiating ART in Zambia. It is possible that differentiated service delivery models could be developed to address this subset of those in HIV care with increased risk of chronic kidney disease.
Improving measurement of tuberculosis care cascades to enhance people-centred care.
(2023-Dec) Faust L; Naidoo P; Caceres-Cardenas G; Ugarte-Gil C; Muyoyeta M; Kerkhoff AD; Nagarajan K; Satyanarayana S; Rakotosamimanana N; Grandjean Lapierre S; Adejumo OA; Kuye J; Oga-Omenka C; Pai M; Subbaraman R; McGill International TB Centre, Montréal, QC, Canada; Mycobacteriology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montréal, QC, Canada.; Mainland Hospital Yaba, Lagos, Nigeria.; Department of Social and Behavioural Research, ICMR-National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India.; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru; TB Centre, London School of Hygiene & Tropical Medicine, London, UK.; Department of Public Health and Community Medicine and Center for Global Public Health, Tufts University School of Medicine, Boston, MA, USA; Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA, USA. Electronic address: ramnath.subbaraman@tufts.edu.; School of Public Health Sciences, University of Waterloo, Waterloo, ON, Canada.; Mycobacteriology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.; Tuberculosis Department, Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, CA, USA.; National Tuberculosis and Leprosy Control Program, Abuja, Nigeria.; Centre for Operational Research, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France; South-East Asia Office, International Union Against Tuberculosis and Lung Disease (The Union), New Delhi, India.; Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, QC, Canada; McGill International TB Centre, Montréal, QC, Canada.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Care cascades represent the proportion of people reaching milestones in care for a disease and are widely used to track progress towards global targets for HIV and other diseases. Despite recent progress in estimating care cascades for tuberculosis (TB) disease, they have not been routinely applied at national and subnational levels, representing a lost opportunity for public health impact. As researchers who have estimated TB care cascades in high-incidence countries (India, Madagascar, Nigeria, Peru, South Africa, and Zambia), we describe the utility of care cascades and identify measurement challenges, including the lack of population-based disease burden data and electronic data capture, the under-reporting of people with TB navigating fragmented and privatised health systems, the heterogeneity of TB tests, and the lack of post-treatment follow-up. We outline an agenda for rectifying these gaps and argue that improving care cascade measurement is crucial to enhancing people-centred care and achieving the End TB goals.
Intention to receive new vaccines post-COVID-19 pandemic among adults and health workers in Lusaka, Zambia.
(2025-Mar-19) Sharma A; Kerkhoff AD; Haambokoma M; Shamoya B; Sikombe K; Simbeza SS; Zulu N; Geng EH; Eshun-Wilsonova I; Le Tourneau N; Pry JM; Division of Infectious Diseases, School of Medicine, Washington University in St. Louis, Saint Louis, MO, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Division of Epidemiology, School of Medicine, University of California, Davis, California, United States of America. Electronic address: jmpry@ucdavis.edu.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of HIV, Infectious Diseases and Global Medicine Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, California, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: To estimate intention to receive newly introduced adult vaccines among community members and healthcare workers (HCWs) in Lusaka, Zambia in the context of previous COVID-19 vaccine uptake and perceived disease threat and, identify trusted sources of vaccine information. METHODS: We conducted a cross-sectional survey among a random sample of community members and a convenience sample of HCWs from 13 November to 15 December 2023. We evaluated future vaccination intentions by self-reported COVID-19 vaccine uptake, community role, vaccine type (COVID-19 booster, HIV, tuberculosis, malaria, pneumonia, diarrheal disease) and source of information using adjusted, mixed effects Poisson regression and adjusted probability models. RESULTS: We enrolled 395 (79.2 %) community members and 104 (20.8 %) HCWs (N = 499). There was high intention to receive new vaccines among community members (mean score = 83.6 %) and HCWs (mean score = 86.0 %), though intentions varied by vaccine type. Prior COVID-19 vaccine uptake (0, 1, 2+ doses) impacted intentions to receive a novel COVID-19 vaccine among community members (43.3 %, 62.8 %, 79.7 %, respectively) but were not associated with any other vaccine types. Intention to receive a vaccine was strongly associated with perceived disease severity and susceptibility as well as age, sex, education, and household income. Social media as a vaccine information source was associated with lower overall vaccine intention among community members, while health system and community sources were associated with higher overall intention to receive new vaccines. Government was a highly trusted source of vaccine information among all participants. CONCLUSION: Prior COVID-19 vaccination uptake did not predict future non-COVID-19 vaccine intention in Zambia. Perceived threat and select socio-demographic factors were key predictors, suggesting the need for rapid research to design communication strategies and identify trusted sources per target population.
Interrupted time-series analysis of active case-finding for tuberculosis during the COVID-19 pandemic, Zambia.
(2022-Mar-01) Lungu PS; Kerkhoff AD; Muyoyeta M; Kasapo CC; Nyangu S; Kagujje M; Chimzizi R; Nyimbili S; Khunga M; Kasese-Chanda N; Musonda V; Tambatamba B; Kombe CM; Sakulanda C; Sampa K; Silumesii A; Malama K; National Tuberculosis and Leprosy Control Programme, Ministry of Health, Ndeke House, Haile-Selaise Road, PO Box 30205, Lusaka, Zambia.; United States Agency for International Development, Lusaka, Zambia.; Eradicate Tuberculosis Project, United States Agency for International Development, Lusaka, Zambia.; Ministry of Health, Lusaka, Zambia.; Division of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic and the subsequent implementation of tuberculosis response measures on tuberculosis notifications in Zambia. METHODS: We used an interrupted time-series design to compare monthly tuberculosis notifications in Zambia before the pandemic (January 2019 to February 2020), after implementation of national pandemic mitigation measures (April 2020 to June 2020) and after response measures to improve tuberculosis detection (August 2020 to September 2021). The tuberculosis response included enhanced data surveillance, facility-based active case-finding and activities to generate demand for services. We used nationally aggregated, facility-level tuberculosis notification data for the analysis. FINDINGS: Pre-pandemic tuberculosis case notifications rose steadily from 2890 in January 2019 to 3337 in February 2020. After the start of the pandemic and mitigation measures, there was a -22% (95% confidence interval, CI: -24 to -19) immediate decline in notifications in April 2020. Larger immediate declines in notifications were seen among human immunodeficiency virus (HIV)-positive compared with HIV-negative individuals (-36%; 95% CI: -38 to -35; versus -12%; 95% CI: -17 to -6). Following roll-out of tuberculosis response measures in July 2020, notifications immediately increased by 45% (95% CI: 38 to 51) nationally and across all subgroups and provinces. The trend in notifications remained stable through September 2021, with similar numbers to the predicted number had the pandemic not occurred. CONCLUSION: Implementation of a coordinated public health response including active tuberculosis case-finding was associated with reversal of the adverse impact of the pandemic and mitigation measures. The gains were sustained throughout subsequent waves of the pandemic.
Mitigating the effects of COVID-19 on HIV treatment and care in Lusaka, Zambia: a before-after cohort study using mixed effects regression.
(2022-Jan) Pry JM; Sikombe K; Mody A; Iyer S; Mutale J; Vlahakis N; Savory T; Wa Mwanza M; Mweebo K; Mwila A; Mwale C; Mukumbwa-Mwenechanya M; Kerkhoff AD; Sikazwe I; Bolton Moore C; Mwamba D; Geng EH; Herce ME; Department of Infectious Disease, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.; University of California San Francisco, San Francisco, California, USA.; San Francisco General Hospital and Trauma Center, San Francisco, California, USA.; Zambia Ministry of Health, Lusaka, Zambia.; Division of Global HIV & Tuberculosis, Centers for Disease Control and Prevention, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia jmpry@ucdavis.edu.; Institute for Global Health & Infectious Diseases, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.; Department of Public Health Environments and Society, London School of Hygiene & Tropical Medicine, London, UK.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Internal Medicine, Washington University School of Medicine in Saint Louis, St Louis, Missouri, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: The Zambian Ministry of Health (MoH) issued COVID-19 mitigation guidance for HIV care immediately after the first COVID-19 case was confirmed in Zambia on 18 March 2020. The Centre for Infectious Disease Research in Zambia implemented MoH guidance by: 1) extending antiretroviral therapy (ART) refill duration to 6 multi-month dispensation (6MMD) and 2) task-shifting communication and mobilisation of those in HIV care to collect their next ART refill early. We assessed the impact of COVID-19 mitigation guidance on HIV care 3 months before and after guidance implementation. METHODS: We reviewed all ART pharmacy visit data in the national HIV medical record for PLHIV in care having ≥1 visit between 1 January-30 June 2020 at 59 HIV care facilities in Lusaka Province, Zambia. We undertook a before-after evaluation using mixed-effects Poisson regression to examine predictors and marginal probability of early clinic return (pharmacy visit >7 days before next appointment), proportion of late visit (>7 days late for next appointment) and probability of receiving a 6MMD ART refill. RESULTS: A total of 101 371 individuals (64% female, median age 39) with 130 486 pharmacy visits were included in the analysis. We observed a significant increase in the adjusted prevalence ratio (4.63; 95% CI 4.45 to 4.82) of early return before compared with after guidance implementation. Receipt of 6MMD increased from a weekly mean of 47.9% (95% CI 46.6% to 49.2%) before to 73.4% (95% CI 72.0% to 74.9%) after guidance implementation. The proportion of late visits (8-89 days late) was significantly higher before (18.8%, 95% CI17.2%to20.2%) compared with after (15.1%, 95% CI13.8%to16.4%) guidance implementation . CONCLUSIONS: Timely issuance and implementation of COVID-19 mitigation guidance involving task-shifted patient communication and mobilisation alongside 6MMD significantly increased early return to ART clinic, potentially reducing interruptions in HIV care during a global public health emergency.
Mortality estimates by age and sex among persons living with HIV after ART initiation in Zambia using electronic medical records supplemented with tracing a sample of lost patients: A cohort study.
(2020-May) Kerkhoff AD; Sikombe K; Eshun-Wilson I; Sikazwe I; Glidden DV; Pry JM; Somwe P; Beres LK; Simbeza S; Mwamba C; Bukankala C; Hantuba C; Moore CB; Holmes CB; Padian N; Geng EH; Georgetown University, Washington, District of Columbia, United States of America.; Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California, San Francisco, San Francisco, California, United States of America.; University of California, Berkeley, Berkeley, California, United States of America.; Division of Infectious Diseases, Department of Medicine, Washington University, St. Louis, Missouri, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; Johns Hopkins University, Baltimore, Maryland, United States of America.; Center for Dissemination and Implementation, Institute for Public Health, Washington University, St. Louis, Missouri, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Men in sub-Saharan Africa have lower engagement and retention in HIV services compared to women, which may result in differential survival. However, the true magnitude of difference in HIV-related mortality between men and women receiving antiretroviral therapy (ART) is incompletely characterized. METHODS AND FINDINGS: We evaluated HIV-positive adults ≥18 years old newly initiating ART in 4 Zambian provinces (Eastern, Lusaka, Southern, and Western). In addition to mortality data obtained from routine electronic medical records, we intensively traced a random sample of patients lost to follow-up (LTFU) and incorporated tracing outcomes through inverse probability weights. Sex-specific mortality rates and rate differences were determined using Poisson regression. Parametric g-computation was used to estimate adjusted mortality rates by sex and age. The study included 49,129 adults newly initiated on ART between August 2013 and July 2015; overall, the median age among patients was 35 years, the median baseline CD4 count was 262 cells/μl, and 37.2% were men. Men comprised a smaller proportion of individuals starting ART (37.2% versus 62.8%), tended to be older (median age 37 versus 33 years), and tended to have lower CD4 counts (median 220 versus 289 cells/μl) at the time of ART initiation compared to women. The overall rate of mortality among men was 10.3 (95% CI 8.2-12.4) deaths/100 person-years (PYs), compared to 5.5 (95% CI 4.3-6.8) deaths/100 PYs among women (difference +4.7 [95% CI 2.3-7.2] deaths/100 PYs; p < 0.001). Compared to women in the same age groups, men's mortality rates were particularly elevated among those <30 years old (+6.7 deaths/100 PYs difference), those attending rural health centers (+9.4 deaths/100 PYs difference), those who had an initial CD4 count < 100 cells/μl (+9.2 deaths/100 PYs difference), and those who were unmarried (+8.0 deaths/100 PYs difference). After adjustment for potential confounders and mediators including CD4 count, a substantially higher mortality rate was predicted among men <30 years old compared to women of the same age, while women ≥50 years old had a mortality rate similar to that of age-matched men, but considerably higher than that predicted among young women (<30 years old). No clinically significant differences were evident with respect to rates of facility transfer or care disengagement between men and women. The main study limitations were the inability to successfully ascertain outcomes in all patients selected for tracing and missing clinical and laboratory data due to the use of medical records. CONCLUSIONS: In this study, we found that among HIV-positive adults newly initiating ART, mortality among men exceeded mortality among women; disparities were most pronounced among young patients. Older women, however, also experienced high mortality. Specific interventions for men and older women at highest mortality risk are needed to improve HIV treatment outcomes.
Pathways to care and preferences for improving tuberculosis services among tuberculosis patients in Zambia: A discrete choice experiment.
(2021) Kerkhoff AD; Kagujje M; Nyangu S; Mateyo K; Sanjase N; Chilukutu L; Eshun-Wilson I; Geng EH; Havlir DV; Muyoyeta M; University Teaching Hospital, Department of Internal Medicine, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of HIV, Infectious Diseases and Global Medicine Zuckerberg San Francisco General Hospital and Trauma Center University of California, San Francisco, California, United States of America.; Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Delays in the diagnosis of tuberculosis (TB) contribute to a substantial proportion of TB-related mortality, especially among people living with HIV (PLHIV). We sought to characterize the diagnostic journey for HIV-positive and HIV-negative patients with a new TB diagnosis in Zambia, to understand drivers of delay, and characterize their preferences for service characteristics to inform improvements in TB services. METHODS: We assessed consecutive adults with newly microbiologically-confirmed TB at two public health treatment facilities in Lusaka, Zambia. We administered a survey to document critical intervals in the TB care pathway (time to initial care-seeking, diagnosis and treatment initiation), identify bottlenecks and their reasons. We quantified patient preferences for a range of characteristics of health services using a discrete choice experiment (DCE) that assessed 7 attributes (distance, wait times, hours of operation, confidentiality, sex of provider, testing incentive, TB test speed and notification method). RESULTS: Among 401 patients enrolled (median age of 34 years, 68.7% male, 46.6% HIV-positive), 60.9% and 39.1% were from a first-level and tertiary hospital, respectively. The median time from symptom onset to receipt of TB treatment was 5.0 weeks (IQR: 3.6-8.0) and was longer among HIV-positive patients seeking care at a tertiary hospital than HIV-negative patients (6.4 vs. 4.9 weeks, p = 0.002). The time from symptom onset to initial presentation for evaluation accounted for the majority of time until treatment initiation (median 3.0 weeks, IQR: 1.0-5.0)-an important minority of 11.0% of patients delayed care-seeking ≥8 weeks. The DCE found that patients strongly preferred same-day TB test results (relative importance, 37.2%), facilities close to home (18.0%), and facilities with short wait times (16.9%). Patients were willing to travel to a facility up to 7.6 kilometers further away in order to access same-day TB test results. Preferences for improving current TB services did not differ according to HIV status. CONCLUSIONS: Prolonged intervals from TB symptom onset to treatment initiation were common, especially among PLHIV, and were driven by delayed health-seeking. Addressing known barriers to timely diagnosis and incorporating patients' preferences into TB services, including same-day TB test results, may facilitate earlier TB care engagement in high burden settings.
Patient Preferences for Strategies to Improve Tuberculosis Diagnostic Services in Zambia.
(2022-Aug-01) Kerkhoff AD; Chilukutu L; Nyangu S; Kagujje M; Mateyo K; Sanjase N; Eshun-Wilson I; Geng EH; Havlir DV; Muyoyeta M; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California, San Francisco School of Medicine, San Francisco.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia.; Division of Infectious Diseases, Washington University School of Medicine, St Louis, Missouri.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
IMPORTANCE: Delayed engagement in tuberculosis (TB) services is associated with ongoing transmission and poor clinical outcomes. OBJECTIVE: To assess whether patients with TB have differential preferences for strategies to improve the public health reach of TB diagnostic services. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was undertaken in which a discrete choice experiment (DCE) was administered between September 18, 2019, and January 17, 2020, to 401 adults (>18 years of age) with microbiologically confirmed TB in Lusaka, Zambia. The DCE had 7 attributes with 2 to 3 levels per attribute related to TB service enhancements. Latent class analysis was used to identify segments of participants with unique preferences. Multiscenario simulations were used to estimate shares of preferences for different TB service improvement strategies. MAIN OUTCOMES AND MEASURES: The main outcomes were patient preference archetypes and estimated shares of preferences for different strategies to improve TB diagnostic services. Collected data were analyzed between January 3, 2022, to July 2, 2022. RESULTS: Among 326 adults with TB (median [IQR] age, 34 [27-42] years; 217 [66.8%] male; 158 [48.8%] HIV positive), 3 groups with distinct preferences for TB service improvements were identified. Group 1 (192 participants [58.9%]) preferred a facility that offered same-day TB test results, shorter wait times, and financial incentives for testing. Group 2 (83 participants [25.4%]) preferred a facility that provided same-day TB results, had greater privacy, and was closer to home. Group 3 (51 participants [15.6%]) had no strong preferences for service improvements and had negative preferences for receiving telephone-based TB test results. Groups 1 and 2 were more likely to report at least a 4-week delay in seeking health care for their current TB episode compared with group 3 (29 [51.3%] in group 1, 95 [35.8%] in group 2, and 10 [19.6%] in group 3; P < .001). Strategies to improve TB diagnostic services most preferred by all participants were same-day TB test results alone (shares of preference, 69.9%) and combined with a small financial testing incentive (shares of preference, 79.3%), shortened wait times (shares of preference, 76.1%), or greater privacy (shares of preference, 75.0%). However, the most preferred service improvement strategies differed substantially by group. CONCLUSIONS AND RELEVANCE: In this study, patients with TB had heterogenous preferences for TB diagnostic service improvements associated with differential health care-seeking behavior. Tailored strategies that incorporate features most valued by persons with undiagnosed TB, including same-day results, financial incentives, and greater privacy, may optimize reach by overcoming key barriers to timely TB care engagement.
Placing the values and preferences of people most affected by TB at the center of screening and testing: an approach for reaching the unreached.
(2023) Kerkhoff AD; West NS; Del Mar Castro M; Branigan D; Christopher DJ; Denkinger CM; Nhung NV; Theron G; Worodria W; Yu C; Muyoyeta M; Cattamanchi A; Treatment Action Group, New York, NY, USA.; World Alliance for Lung and Intensive Care in Uganda, Kampala, Uganda.; Division of Infectious Diseases and Tropical Medicine, Center of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.; German Center of Infection Research, Partner Site Heidelberg University Hospital, Heidelberg, Germany.; Center for Tuberculosis Research, De La Salle Medical and Health Sciences Institute, City of Dasmarinas, The Philippines.; Division of Pulmonary Diseases and Critical Care Medicine, University of California Irvine, Irvine, CA, USA.; Division of Pulmonology, Mulago National Referral Hospital, Kampala, Uganda.; Division of HIV, Infectious Diseases and Global Medicine Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, CA, USA.; Pulmonary, Critical Care Allergy and Sleep Medicine, University of California San Francisco, San Francisco, USA.; University of Medicine and Pharmacy, Vietnam National University Hanoi, Hanoi, Vietnam.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Department of Pulmonary Medicine, Christian Medical College, Vellore, India.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
To reach the millions of people with tuberculosis (TB) undiagnosed each year, there is an important need to provide people-centered screening and testing services. Despite people-centered care being a key pillar of the WHO END-TB Strategy, there have been few attempts to formally characterize and integrate the preferences of people
Prevalence and interpretation of Xpert
(2022-Mar-21) Chilukutu L; Mwanza W; Kerkhoff AD; Somwe P; Kagujje M; Muyoyeta M; Centre for Infectious Disease Research in Zambia, TB Department, Lusaka Zambia.; Division of HIV, Infectious Diseases and Global Medicine Zuckerberg San Francisco General Hospital and Trauma Center University of California, San Francisco, San Francisco, CA, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The "trace call" results on Xpert® Ultra indicates extremely low TB levels and may be difficult to interpret. The prevalence of trace results among presumptive TB patients in high TB-HIV infection settings is unknown, as is the significance of divergent "trace call" result interpretations. METHODS: Presumptive TB patients attending a public health facility in Lusaka, Zambia, were prospectively enrolled. Participants underwent several TB investigations, including sputum smear microscopy, Ultra testing, and culture. The diagnostic accuracy of Ultra (culture-based reference) and the number of patients recommended for TB treatment was assessed according to several different interpretation criteria for "trace call" results. RESULTS: Among the 740 participants, 78 (10.5%) were Ultra-positive and an additional 37 (5.0%) had a "trace call" result. The prevalence of trace results did not differ according to HIV status (5.3% vs. 4.8%) or prior TB status (5.6% vs. 4.9%). Differing interpretations of trace results had modest effects on Ultra's sensitivity (range 79.3-82.6%) and specificity (range 94.3-99.2%), but increased the number of patients recommended for treatment by up to 44.9%. CONCLUSIONS: Ultra trace results were common in this setting. The interpretation of trace results may substantially impact TB case yield.
Prospective multicentre accuracy evaluation of the FUJIFILM SILVAMP TB LAM test for the diagnosis of tuberculosis in people living with HIV demonstrates lot-to-lot variability.
(2024) Székely R; Sossen B; Mukoka M; Muyoyeta M; Nakabugo E; Hella J; Nguyen HV; Ubolyam S; Chikamatsu K; Macé A; Vermeulen M; Centner CM; Nyangu S; Sanjase N; Sasamalo M; Dinh HT; Ngo TA; Manosuthi W; Jirajariyavej S; Mitarai S; Nguyen NV; Avihingsanon A; Reither K; Nakiyingi L; Kerkhoff AD; MacPherson P; Meintjes G; Denkinger CM; Ruhwald M; Clinical Research Department, London School of Hygiene & Tropical Medicine, London, United Kingdom.; HIV-NAT, Thai Red Cross AIDS Research Centre and Centre of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.; Viet Tiep Hospital, Hai Phong, Viet Nam.; Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand.; National Lung Hospital, Ha Noi, Viet Nam.; Taksin Hospital, Bangkok, Thailand.; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; University of Basel, Basel, Switzerland.; Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan.; Public Health Group, Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; Ifakara Health Institute, Dar es Salaam, Tanzania.; FIND, The Global Alliance for Diagnostics, Geneva, Switzerland.; Department of Pathology, Kamuzu University of Health Sciences, Blantyre, Malawi.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.; Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, CA, United States of America.; Division of Infectious Disease and Tropical Medicine, Heidelberg University Hospital and Faculty of Medicine, Heidelberg University, Heidelberg, Germany.; Infectious Diseases Institute, Makerere University, Kampala, Uganda.; Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; German Centre for Infection Research (DZIF), Partner site Heidelberg University Hospital, Heidelberg, Germany.; Division of Medical Microbiology, University of Cape Town and National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
There is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. This prospective trial in seven high tuberculosis burden countries evaluated the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatients and outpatients living with HIV. Diagnostic performance of FujiLAM was assessed against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard (eMRS), and a composite reference standard including clinical evaluation. Of 1637 participants considered for the analysis, 296 (18%) were tuberculosis positive by eMRS. Median age was 40 years, median CD4 cell count was 369 cells/ul, and 52% were female. Overall FujiLAM sensitivity was 54·4% (95% CI: 48·7-60·0), overall specificity was 85·2% (83·2-87·0) against eMRS. Sensitivity and specificity estimates varied between sites, ranging from 26·5% (95% CI: 17·4%-38·0%) to 73·2% (60·4%-83·0%), and 75·0 (65·0%-82·9%) to 96·5 (92·1%-98·5%), respectively. Post-hoc exploratory analysis identified significant variability in the performance of the six FujiLAM lots used in this study. Lot variability limited interpretation of FujiLAM test performance. Although results with the current version of FujiLAM are too variable for clinical decision-making, the lipoarabinomannan biomarker still holds promise for tuberculosis diagnostics. The trial is registered at clinicaltrials.gov (NCT04089423).