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The CIDRZ Research Repository serves as an open-access archive for peer-reviewed publications, conference papers, and other scholarly outputs from CIDRZ researchers. Our goal is to promote the dissemination of knowledge and support evidence-based public health initiatives.
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Item Associations Between QuantiFERON-TB Gold Plus IFNγ Concentrations and Progression to Symptomatic Tuberculosis in Global High-Burden TB Settings.(2026-Jul) Sunshine, Justine; Shaffer, Michael; Han, Linda L.; Gaikwad, Deepali; Houana, Amelia A.; Gler, Maria T.; Hadinegoro, Sri R.; Hanekom, Willem A.; Lama, Javier R.; Muyoyeta, Monde; Musala, Sissy; Nduba, Videlis; Rolla, Valeria C.; Roy, Tapash ; Sutherland, Jayne S.; Khosa, Celso; Wajja, Anne; Walker, Timothy M.; Cinar, Amy; Schmidt, Alexander C.; Dagnew, Alemnew F.; Frahm, NicoleBACKGROUND: Predictive biomarkers for symptomatic tuberculosis (TB) progression would transform targeted prevention efforts. Although interferon-gamma release assays (IGRAs), including QuantiFERON® TB-Gold Plus (QFT-Plus), have been studied for this purpose, systematic evaluation of the QFT-Plus TB1 and TB2 Interferon-Gamma (IFNγ) concentrations remains limited, particularly in high-burden TB settings. METHODS: Baseline TB1 and TB2 IFNγ concentrations from 5246 participants (ages 15-34 years) in TB-endemic regions were analyzed in relation to subsequent TB outcomes over a median of 525 days follow-up (NCT05190146). Participants were categorized as controls (no TB), suspected TB (no microbiological confirmation), or laboratory-confirmed TB, including a subset meeting a stringent case definition (≥2 positive microbiologic tests). Associations between baseline IFNγ concentrations and progression to symptomatic TB were assessed. RESULTS: In the full cohort (IGRA+/- participants), baseline TB2 IFNγ concentrations were significantly higher compared with controls among participants who developed suspected TB ( CONCLUSIONS: Quantitative IFNγ concentrations from QFT-Plus, particularly TB2, were associated with progression to symptomatic TB, met or exceeded WHO-recommended sensitivity and specificity thresholds for predictive biomarkers, and may support biomarker-based stratification in TB clinical research.Item Defining person-centred treatment support for multidrug-resistant TB: a discrete choice experiment.(2026-Jun) Kagujje, Mary; Mtumbi G; Sikandangwa M; Shatalimi J; Muyoyeta, Monde; Kerkhoff, Andrew D.BACKGROUND: Multidrug-resistant TB (MDR-TB) treatment remains challenging, with significant toxicity and associated hardships that undermine adherence and cure rates. Support packages may improve outcomes, but the features most valued by people with MDR-TB are unknown. METHODS: A discrete choice experiment was performed among adults receiving MDR-TB treatment in Lusaka, Zambia. Five features (3-4 levels each) comprising a support package were evaluated through 12 choice tasks comparing hypothetical packages. RESULTS: Among 99 participants (median age 36 years, 68.9% men, 42.4% HIV-positive), material support was the most valued feature (relative importance [RI] = 45.7%), with transport vouchers plus food assistance being the most preferred option. Visit frequency was also important (RI = 26.7%), with similar preferences for monthly and bimonthly visits. Participants preferred phone calls for visit reminders (RI = 11.8%), health care workers for emotional support (RI = 11.2%), and community-based health care workers or loved ones for treatment observation (RI = 4.7%). Three distinct preference groups were identified - all highly valued material support but varied in their preferences for other support features and their delivery. CONCLUSION: Among people with MDR-TB in Zambia, material support mechanisms and less frequent clinic visits were highly valued. Incorporating patient preferences into treatment programmes could optimise MDR-TB care and improve treatment adherence and outcomes.Item "That is why I trust": a qualitative study on acceptability and feasibility of novel tongue swab diagnostics to assess people presenting with tuberculosis symptoms in Viet Nam and Zambia.(2026-Jun-19) Sales, Alyssa; Le, Hien; Muzazu, Seke; Kunda-Ng'andu, Evelyn; Castro, Maria D. M.; Kerkhoff, Andrew D.; Phan, Ha; Denkinger, Claudia M.; Cattamanchi, Adithya; West, Nora; Muyoyeta, MondeBACKGROUND: Millions of tuberculosis (TB) cases are estimated to be undiagnosed and unreported annually. Sputum has been the primary approach for diagnostic testing, but tongue swabs are being investigated as an alternative to expand testing. To understand potential uptake and implementation, we explored the acceptability, usability, and feasibility of tongue swab-based TB testing from the perspectives of healthcare workers, people undergoing TB screening, and caregivers in Viet Nam and Zambia. METHODS: We interviewed people with symptoms of TB, caregivers of children undergoing TB evaluation, and healthcare workers who collected tongue swabs (n = 76 participants) between September 2023 and February 2024. Interviews were analyzed using framework analysis to elucidate preferences, experiences, and acceptability of tongue swabs vs. sputum. Findings were further organized according to acceptability and feasibility to understand barriers and facilitators to uptake. RESULTS: Most participants preferred tongue swab to sputum collection. The perceived usability and feasibility of tongue swabs were high. Key themes that influenced the acceptability of tongue swabs included ease of use, diagnostic accuracy, diagnostic yield, hygiene, risk of TB transmission during sample collection, time to test result, and trust in healthcare workers and the health system. Across interviews, many participants described tongue swabs as a comfortable and easy way to test for TB, compared to the physical discomfort and difficulty expectorating sputum. Participants described tongue swabs as suitable for everyone, yet perceived diagnostic accuracy was crucial in shaping test preference. CONCLUSION: Tongue swab-based testing for TB is likely to be highly acceptable and feasible if incorporated into TB diagnostic guidelines. Future integration of tongue swabs in facilities and communities should target drivers of acceptability.Item Expanding molecular diagnostic coverage for tuberculosis by combining computer-aided chest radiography and sputum specimen pooling: a modeling study from four high-burden countries.(2024) Codlin, Andrew J.; Vo, Luan N. Q.; Garg, Tushar; Banu, Sayera; Ahmed, Shahriar; John, Stephen; Abdulkarim, Suraj; Muyoyeta, Monde; Sanjase, Nsala; Wingfield, Tom; Iem, Vibol; Squire, Bertie; Creswell, JacobBACKGROUND: In 2022, fewer than half of persons with tuberculosis (TB) had access to molecular diagnostic tests for TB due to their high costs. Studies have found that the use of artificial intelligence (AI) software for chest X-ray (CXR) interpretation and sputum specimen pooling can each reduce the cost of testing. We modeled the combination of both strategies to estimate potential savings in consumables that could be used to expand access to molecular diagnostics. METHODS: We obtained Xpert testing and positivity data segmented into deciles by AI probability scores for TB from the community- and healthcare facility-based active case finding conducted in Bangladesh, Nigeria, Viet Nam, and Zambia. AI scores in the model were based on CAD4TB version 7 (Zambia) and qXR (all other countries). We modeled four ordinal screening and testing approaches involving AI-aided CXR interpretation to indicate individual and pooled testing. Setting a false negative rate of 5%, for each approach we calculated additional and cumulative savings over the baseline of universal Xpert testing, as well as the theoretical expansion in diagnostic coverage. RESULTS: In each country, the optimal screening and testing approach was to use AI to rule out testing in deciles with low AI scores and to guide pooled vs individual testing in persons with moderate and high AI scores, respectively. This approach yielded cumulative savings in Xpert tests over baseline ranging from 50.8% in Zambia to 57.5% in Nigeria and 61.5% in Bangladesh and Viet Nam. Using these savings, diagnostic coverage theoretically could be expanded by 34% to 160% across the different approaches and countries. CONCLUSIONS: Using AI software data generated during CXR interpretation to inform a differentiated pooled testing strategy may optimize TB diagnostic test use, and could extend molecular tests to more people who need them. The optimal AI thresholds and pooled testing strategy varied across countries, which suggests that bespoke screening and testing approaches may be needed for differing populations and settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s44263-024-00081-2.Item Early user perspectives on using computer-aided detection software for interpreting chest X-ray images to enhance access and quality of care for persons with tuberculosis.(2023-Dec-21) Creswell, Jacob; Vo, Luan N. Q.; Qin, Zhi Z.; Muyoyeta, Monde; Tovar, Marco; Wong, Emily B.; Ahmed, Shahriar; Vijayan, Shibu; John, Stephen ; Maniar, Rabia; Rahman, Toufiq; MacPherson, Peter; Banu, Sayera; Codlin, Andrew J.Despite 30 years as a public health emergency, tuberculosis (TB) remains one of the world's deadliest diseases. Most deaths are among persons with TB who are not reached with diagnosis and treatment. Thus, timely screening and accurate detection of TB, particularly using sensitive tools such as chest radiography, is crucial for reducing the global burden of this disease. However, lack of qualified human resources represents a common limiting factor in many high TB-burden countries. Artificial intelligence (AI) has emerged as a powerful complement in many facets of life, including for the interpretation of chest X-ray images. However, while AI may serve as a viable alternative to human radiographers and radiologists, there is a high likelihood that those suffering from TB will not reap the benefits of this technological advance without appropriate, clinically effective use and cost-conscious deployment. The World Health Organization recommended the use of AI for TB screening in 2021, and early adopters of the technology have been using the technology in many ways. In this manuscript, we present a compilation of early user experiences from nine high TB-burden countries focused on practical considerations and best practices related to deployment, threshold and use case selection, and scale-up. While we offer technical and operational guidance on the use of AI for interpreting chest X-ray images for TB detection, our aim remains to maximize the benefit that programs, implementers, and ultimately TB-affected individuals can derive from this innovative technology.Item Standard of care in advanced HIV disease: review of HIV treatment guidelines in sub-Saharan African countries-an extension study of eight countries.(2025-Mar-29) Scheier, Thomas C.; Tufa, Tafese B.; Feldt, Torsten ; Hardy, Yasmine ; Minga, Albert; Moh, Raoul; Damasceno, Albertino; Chambal, Lucia; Ntoumi, Francine; Kades, Carine; Bitunguhari, Leopold; Sebatunzi, Osee R.; Missanga, Marco; Njekwa, Katanekwa; Muyoyeta, Monde; Rangarajan, Sumathy; Meintjes, Graeme; Mertz, Dominik; Eikelboom, John W.; Wasserman, SeanINTRODUCTION: The World Health Organization (WHO) has published guidelines for the management of patients with advanced HIV disease (AHD) but mortality remains high. Adoption of WHO recommendations by national guidelines is poorly documented. We aimed to extend our prior review of six national management guidelines by including additional countries from sub-Saharan Africa. METHODS: We identified guidelines of eight additional countries participating in a multicountry trial of azithromycin prophylaxis for AHD. Data was extracted in five domains including definition of AHD (1 item), screening (6 items), prophylaxis (6 items), supportive care (1 items), and HIV treatment (4 items) and scored agreement of each national guideline with the WHO guidelines. RESULTS: Six of the eight national guidelines had a designated section for AHD. Compared with the WHO guideline, the agreement score for national guidelines was between 7 and 17 out of 18, whereby disagreement is mainly driven by missing information. None of the national guidelines had more than three items not in agreement with the WHO guidelines, and the maximum number of items not addressed by any one guideline was eight. Main areas of disagreement were the targeted population for start of ART in presence of tuberculosis meningitis (1/8 in agreement) and urine lipoarabinomannan screening (2/8 in agreement). The targeted population group for cotrimoxazole prophylaxis and its discontinuation was in line with the WHO recommendations in 3/8 national guidelines. Except one guideline, all documents showed similar overall agreement, irrespectively of publication date. CONCLUSION: National guidelines for the management of people with AHD are broadly in agreement with WHO guidelines. Main areas of disagreement are recommendations regarding urine lipoarabinomannan screening, cotrimoxazole prophylaxis and start of antiretroviral therapy in presence of tuberculosis.Item Tuberculosis care cascade in Zambia - identifying the gaps in order to improve outcomes: a population-based analysis.(2021-Aug-10) Lungu, Patrick; Kerkhoff, Andrew D.; Kasapo, Clara C.; Mzyece, Judith; Nyimbili, Sulani; Chimzizi, Rhehab ; Silumesii, Andrew; Kagujje, Mary; Subbaraman, Ramnath; Muyoyeta, Monde; Malama, KennedyOBJECTIVE: Tuberculosis (TB) remains a leading cause of morbidity and mortality in Zambia, especially for people living with HIV (PLHIV). We undertook a care cascade analysis to quantify gaps in care and align programme improvement measures with areas of need. DESIGN: Retrospective, population-based analysis. SETTING: We derived national-level estimates for each step of the TB care cascade in Zambia. Estimates were informed by WHO incidence estimates, nationally aggregated laboratory and notification registers, and individual-level programme data from four provinces. PARTICIPANTS: Participants included all individuals with active TB disease in Zambia in 2018. We characterised the overall TB cascade and disaggregated by drug susceptibility results and HIV status. RESULTS: In 2018, the total burden of TB in Zambia was estimated to be 72 495 (range, 40 495-111 495) cases. Of these, 43 387 (59.8%) accessed TB testing, 40 176 (55.4%) were diagnosed with TB, 36 431 (50.3%) were started on treatment and 32 700 (45.1%) completed treatment. Among all persons with TB lost at any step along the care cascade (n=39 795), 29 108 (73.1%) were lost prior to accessing diagnostic services, 3211 (8.1%) prior to diagnosis, 3745 (9.4%) prior to initiating treatment and 3731 (9.4%) prior to treatment completion. PLHIV were less likely than HIV-negative individuals to successfully complete the care cascade (42.8% vs 50.2%, p<0.001). Among those with rifampicin-resistant TB, there was substantial attrition at each step of the cascade and only 22.8% were estimated to have successfully completed treatment. CONCLUSIONS: Losses throughout the care cascade resulted in a large proportion of individuals with TB not completing treatment. Ongoing health systems strengthening and patient-centred engagement strategies are needed at every step of the care cascade; however, scale-up of active case finding strategies is particularly critical to ensure individuals with TB in the population reach initial stages of care. Additionally, a renewed focus on PLHIV and individuals with drug-resistant TB is urgently needed to improve TB-related outcomes in Zambia.Item Cross-sectional assessment of tuberculosis and HIV prevalence in 13 correctional facilities in Zambia.(2021-Sep-27) Kagujje, Mary; Somwe, Paul; Hatwiinda, Sisa; Bwalya, Joel; Zgambo, Tamala; Thornicroft, Moomba; Bozzani, Fiammetta M.; Moonga, Clement; Muyoyeta, MondeOBJECTIVE: To determine the prevalence of tuberculosis (TB) and HIV in 13 Zambian correctional facilities. METHODS: Cross-sectional study. SETTING: 13 correctional facilities in seven of the 10 provinces in Zambia. PARTICIPANTS: All incarcerated individuals were eligible for TB and HIV screening and testing. Of the total study population of 9695 individuals, which represent 46.2% of total correctional population at the beginning of the study, 8267 and 8160 were screened for TB and HIV, respectively. INTERVENTIONS: TB and HIV screening and testing was done between July 2018 and February 2019. PRIMARY OUTCOME MEASURES: All forms of TB, bacteriologically confirmed TB, drug-resistant TB, HIV. RESULTS: Prevalence of all forms of TB and bacteriologically confirmed TB was 1599 (1340-1894) per 100 000 population and 1056 (847-1301) per 100 000 population, respectively. Among those with bacteriologically confirmed TB, 4.6% (1.3%-11.4%) had drug-resistant TB.There was no statistically significant difference in the prevalence of all forms of TB, bacteriologically confirmed TB and drug resistant TB between adults and juveniles: (p=0.82), (p=0.23), (p=0.68) respectively. Of the bacteriologically confirmed TB cases, 28.7% were asymptomatic. The prevalence of HIV was 14.3% (13.6%-15.1%). The prevalence of HIV among females was 1.8 times the prevalence of HIV among males (p=0.01). CONCLUSION: Compared with the study in 2011 which screened inmates representing 30% of the country's inmate population, then the prevalence of all forms of TB and HIV in correctional facilities has reduced by about 75% and 37.6%, respectively. However, compared with the general population, the prevalence of all forms of TB and HIV was 3.5 and 1.3 times higher, respectively. TB/HIV programmes in correctional facilities need further strengthening to include aspects of juvenile-specific TB programming and gender responsive HIV programming.Item Evaluating InferVision's Computer-Aided Detection (CAD) algorithm for Tuberculosis (TB) screening, Lusaka, Zambia.(2025) Somwe, Paul; Maimbolwa, Minyoi; Chiyenu, Kanema; Lumpa, Mwansa; Kagujje, Mary; Muyoyeta, MondeThe objective of this study was to evaluate the diagnostic performance of InferRead DR Chest for tuberculosis (TB) screening in a high HIV and TB burden setting. The study assessed the performance of InferRead DR Chest using anonymized chest X-ray images from an active TB case finding study in Lusaka, Zambia, for individuals aged 15 and older. The Xpert MTB/RIF or MTB culture was the composite reference standard. Performance was evaluated using the Area Under the Receiver Operating Characteristic Curve (AUC), and a binary classification point was selected where the sensitivity aligned with the WHO target product profile for TB screening tools. Of the 1,890 chest X-ray images that met the inclusion criteria, 91.5% of participants reported at least one TB symptom. The median age was 38 years (IQR: 29-47), and 1,186 (62.8%) were male. From the study sample, 449 participants (23.8%) reported a history of previous TB, and 704 (37.2%) were HIV positive. Among the analyzed images, 289 (15.3%) were classified as TB positive based on the composite reference standard test results. The overall area under the curve (AUC) was 0.81 (95% CI: 0.78-0.83). Among individuals with a history of previous TB and those who were HIV positive, the AUCs were 0.71 (95% CI: 0.63-0.79) and 0.77 (95% CI: 0.72-0.82), respectively. At a sensitivity of 90.3% (95% CI: 86.3%-93.5%), InferRead DR Chest achieved a specificity of 39.2% (95% CI: 36.8%-41.7%) at TB score cut point of 0.12. InferRead DR Chest had acceptable performance in our population. Additional training and piloting of InferRead DR Chest in this population is recommended.Item Undernotification and underreporting of tuberculosis in Zambia: a national data quality assessment.(2022-Aug-22) Lungu PS; Kabaso ME; Mihova R; Silumesii A; Chisenga T; Kasapo C; Mwaba I; Kerkhoff, Andrew D.; Muyoyeta, Monde; Chimzizi R; Malama KBACKGROUND: Despite national implementation of several high impact interventions and innovations to bolster tuberculosis (TB) detection and improve quality of TB services in Zambia, notifications have been declining since 2004. A countrywide data quality assessment (DQA) of Zambia's National TB and Leprosy Programme (NTLP) was undertaken to quantify the degree to which undernotification and underreporting of TB notifications may be occurring. METHODS: The NTLP conducted a retrospective DQA of health facilities in high burden districts in all ten Zambian provinces. Multiple routine programmatic data sources were triangulated through a multi-step verification process to enumerate the total number of unique TB patients diagnosed between 1st January and 31st August 2019; both bacteriologically confirmed and clinically diagnosed TB patients were included. Undernotification was defined as the number of TB patients identified through the DQA that were not documented in facility treatment registers, while underreporting was defined as the number of notified TB cases not reported to the NTLP. RESULTS: Overall, 265 health facilities across 55 districts were assessed from which 28,402 TB patients were identified; 94.5% of TB patients were ≥ 15 years old, 65.1% were male, 52.0% were HIV-positive, and 89.6% were a new/relapse case. Among all TB cases, 32.8% (95%CI: 32.2-33.3) were unnotified. Undernotification was associated with age ≥ 15 years old (adjusted prevalence odds ratio [aPOR] = 2.4 [95%CI: 2.0-2.9]), HIV-positive status (aPOR = 1.6 [95%CI: 1.5-1.8]), being a new/relapse TB case (aPOR = 17.5 [95%CI: 13.4-22.8]), being a clinically diagnosed TB case (aPOR = 4.2 [95%CI:3.8-4.6]), and being diagnosed at a hospital (range, aPOR = 1.5 [95%CI: 1.3-1.6] to 2.6 [95%CI: 2.3-2.9]). There was substantial heterogeneity in the proportion of unnotified TB cases by province (range, 18.2% to 43.6%). In a sub-analysis among 22,199 TB patients with further data available, 55.9% (95%CI: 55.2-56.6) were notified and reported to the NTLP, 32.8% (95%CI: 32.2-33.4) were unnotified, and 11.3% (95%CI: 10.9-11.7) went unreported to the NTLP. CONCLUSIONS: The findings from Zambia's first countrywide TB programme DQA demonstrate substantial undernotification and underreporting of TB cases across all provinces. This underscores the urgent need to implement a robust and integrated data management system to facilitate timely registration and reporting of all TB patients who are diagnosed and treated.