Browsing by Author "Cattamanchi A"

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Community-wide Screening for Tuberculosis.
(2020-Mar-19) Kerkhoff AD; Muyoyeta M; Cattamanchi A
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
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
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.
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
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
Preferences for Tongue Swab versus Sputum Collection for Tuberculosis Testing: A Multi-Country Survey.
(2025-Jul-05) Manoj Kumar K; Borkman A; Kim A; Crowder R; Ajide B; Alí-Francia K; Chirwa M; Kamulegeya L; Le H; Trung VN; Venter R; Bimba J; Christopher DJ; Dalay V; Van Hung N; Muyoyeta M; Nakiyingi L; Van Nhung N; Theron G; Yu C; Zamudio-Fuertes C; Atim J; Kerkhoff AD; Castro Noriega MDM; Nahid P; Denkinger CM; Cattamanchi A; Dorman SE; West N
BACKGROUND: Sputum collection for tuberculosis (TB) diagnosis poses challenges for children, people living with HIV, and those who struggle with sputum production. Tongue swab-based molecular testing offers a promising non-invasive alternative, but person-centered research on acceptability is limited. METHODS: We conducted a pragmatic survey across eight countries (Vietnam, Philippines, South Africa, Nigeria, Zambia, India, Uganda, Peru) among people with presumptive TB attending primary care facilities. Participants provided both tongue swab and sputum samples, then completed a 5-10 minute survey about their collection preferences. RESULTS: From October 2023 to July 2024, 1,297 participants were enrolled (median age 43 years, 45% female, 13% HIV-positive). Overall, 61% (95% CI: 58-64%) preferred tongue swab collection compared to 22% (95% CI: 20-25%) who preferred sputum collection and 17% (95% CI: 15-19%) with no preference. Preference for tongue swab was consistent across demographic and clinical subgroups, with country-level variation ranging from 47% in South Africa to 74% in Zambia and Nigeria. CONCLUSION: Strong preference for tongue swab over sputum collection among individuals with presumptive TB supports this diagnostic innovation's potential to overcome barriers to timely TB testing, particularly for populations struggling with sputum production.
Tongue Swab Xpert MTB/RIF Ultra Testing for Tuberculosis Using a Revised Consensus Protocol: A multi-country diagnostic accuracy study.
(2025-Jul-10) Ajide B; Moe CA; Barrameda J; Chirwa M; Rockman L; de Haas P; de Vos M; Kato-Maeda M; Tasca B; Bimba J; Yu C; Denkinger CM; Kremer K; Nahid P; Cattamanchi A; Theron G; Muyoyeta M
BACKGROUND: Tongue swabs are a promising specimen for tuberculosis (TB) diagnosis. In a previous study using a consensus protocol, tongue swabs tested with Xpert MTB/RIF Ultra (Xpert Ultra, Cepheid, USA) outperformed sputum smear microscopy, but a substantial proportion (6.1%) of results were non-actionable (e.g., invalid/error). We evaluated a revised protocol in four high TB burden countries. METHODS: Participants aged ≥12 years with presumptive TB were enrolled from outpatient clinics in the Philippines, South Africa, Nigeria, and Zambia. Tongue swabs were processed using Sample Reagent (SR, Cepheid, USA) diluted 2:1 with phosphate buffer or phosphate-buffered saline and tested with Xpert Ultra. Diagnostic performance was assessed against a culture-based microbiological reference standard and compared to sputum-based tests. RESULTS: From March to November 2024, 1168 participants were enrolled (median age 37 [IQR 28-48] years; 46.7% female, 21.8% living with HIV, 18.5% culture-confirmed TB). The proportion of nonactionable results was 5.6% overall, but was less than 4% in all countries except South Africa (15.4%). Tongue swab sensitivity was 66.0% (95% CI 59.0-72.5); specificity was 99.6% (95% CI 98.9-99.9). CONCLUSION: The revised protocol yielded low error rates at most sites and moderate sensitivity, supporting tongue swabs as an alternative when sputum is unavailable.
Validating novel diagnostic assays for tuberculosis in the context of existing tools.
(2021-Sep) Kerkhoff AD; Cattamanchi A; Muyoyeta M; Denkinger CM; Dowdy DW