Publications
Permanent URI for this communityhttps://pubs.cidrz.org/handle/123456789/11558
Welcome to the CIDRZ Research Repository
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.
News
New Research Publications Added
We have recently added new publications on HIV prevention, maternal health, and epidemiology. Browse the latest research in our repository.
Browse
32 results
Search Results
Item Design and feasibility considerations for a phase 3 efficacy trial of the M72/AS01(2026-Jul-11) Dagnew AF; Noble R; Cinar A; Burhan E; Churchyard G; Fairlie L; Hanekom WA; Muyoyeta M; Mwandumba HC; Nduba V; Curran M; Schmidt ACBACKGROUND: M72/AS01 METHODS: We conducted event-driven simulations using lower bound (LB) of the two-sided 95% confidence interval (CI) for VE(D). For IGRA-positive participants, assumptions included 1:1 randomization, 9000 participants/arm, 0.4% TB incidence/year, 55% true VE(D), 5% dropout/year, and two-year enrollment. Enrollment irrespective of baseline IGRA status (mixed IGRA-status population) and IGRA-negative-only scenarios were explored to estimate sample sizes and trial duration. RESULTS: Simulations demonstrated that 110 events rule out a VE(D) 95% CI LB ≤10%, and 185 events rule out ≤25%, assuming ≥90% power and a true VE(D) of 55%. With 18,000 IGRA-positive participants, simulations projected a 90% probability of accruing 110 events within 3.5 to 4 years and 185 within 5.5 to 6 years. In the mixed IGRA-status population, few endpoints occurred among IGRA-negative participants, yielding insufficient power. Standalone VE(D) evaluation in IGRA-negative participants required large sample sizes (approximately 134,800) and prolonged timelines, indicating infeasibility. Accordingly, the selected primary objective of the phase 3 trial was to confirm VE(D) in IGRA-positive HIV-negative participants using LB of 95% CI for VE(D) > 10% after 110 events; secondary objectives include safety and immunogenicity in HIV-negative IGRA-positive; HIV-negative IGRA-negative; and HIV-positive individuals irrespective of IGRA status. CONCLUSIONS: An IGRA-positive-enriched, event-driven phase 3 trial is feasible to confirm VE(D) of M72/AS01Item Multicountry assessment of tongue swabs for tuberculosis using a common protocol for Xpert MTB/RIF Ultra testing: a prospective diagnostic accuracy study.(2026-May-14) de Vos M; Le H; Marcelo D; Ajide B; Alí-Francia KG; Borkman AL; Desravines R; Chang HT; Dowling W; Kamulegeya L; Marconi S; Moe CA; Rockman L; Shuma B; Christopher DJ; Hapeela N; Muyoyeta M; Nakiyingi L; Theron G; Ugarte-Gil C; Hung NV; Luong DV; Yu C; Alland D; Denkinger CM; Ellner J; Dorman SE; Kremer K; Manabe YC; Nahid P; Ruhwald M; Shah M; Penn-Nicholson A; Cattamanchi A; Bimba JSBACKGROUND: Despite advancements in tuberculosis diagnostics, many cases remain unconfirmed because of challenges in conventional sputum-based testing. This study aimed to evaluate the diagnostic accuracy of tongue swab sampling as a non-invasive alternative for tuberculosis diagnosis using Xpert MTB/RIF Ultra (Ultra). METHODS: We conducted a large-scale, multicountry, prospective diagnostic accuracy study of Ultra using tongue swabs in people with presumptive pulmonary tuberculosis. Participants were enrolled consecutively at primary health centres and hospitals across eight countries from June 26, 2023, to Feb 15, 2024, and the study was coordinated by three consortia. Eligible participants were individuals aged 12 years or older or 18 years or older, according to the consortium involved, with presumptive pulmonary tuberculosis or at least one risk factor for tuberculosis and a positive tuberculosis screening test at the select consortia. Standardised tongue swab collection and processing protocols were used in all countries. Sensitivity and specificity with 95% CI values were calculated against sputum liquid or solid culture (primary) and sputum Ultra (secondary) reference standards using Wilson's score method. Fisher's exact tests were used for subgroup comparisons, with p values < 0·05 considered statistically significant. FINDINGS: Among the 1844 participants included in the analysis, 389 tested positive and 1455 tested negative for pulmonary tuberculosis based on the primary sputum culture reference standard. 871 (47·2%) participants were female and 973 (52·7%) were male, with a mean age of 43 years (range 12-90). Among the 1844 participants, 399 (21·7%) were enrolled in Viet Nam, 166 (9·0%) in India, 427 (23·2%) in South Africa, 271 (14·7%) in the Philippines, 138 (7·5%) in Nigeria, 102 (5·5%) in Zambia, 175 (9·5%) in Uganda, and 166 (9·0%) in Peru. Tongue swab Ultra testing showed a sensitivity of 65·6% (95% CI 60·6-70·3) and specificity of 98·5% (95% CI 97·7-99·1) against the culture-based reference standard. Sensitivity estimates varied across collection centres and were higher in individuals without HIV than in those living with HIV (68·4% vs 50·0%; absolute difference 18·4 percentage points [95% CI 3·3-33·4]). When sputum Ultra was used as the reference standard, sensitivity was 75·4% (95% CI 69·0-78·8). Tongue swab Ultra showed higher sensitivity than sputum smear microscopy. Invalid or error result rates were variable and high at certain sites (range 0-16%). INTERPRETATION: Tongue swabs are a promising sample type for rapid diagnostic tests for tuberculosis, with moderate sensitivity and high specificity when Ultra was used as the reference standard. However, further research is needed to optimise protocols for Ultra testing and develop assays tailored to tongue swab specimens. Adoption of tongue swab-based molecular testing could expand tuberculosis diagnostics access, especially for populations unable to produce sputum, thus supporting global tuberculosis elimination goals. FUNDING: National Institute of Allergy and Infectious Diseases, United States Agency for International Development.Item Design and feasibility considerations for a phase 3 efficacy trial of the M72/AS01(2026-May-12) Dagnew AF; Noble R; Cinar A; Burhan E; Churchyard G; Fairlie L; Hanekom WA; Muyoyeta M; Mwandumba HC; Nduba V; Curran M; Schmidt ACBACKGROUND: M72/AS01 METHODS: We conducted event-driven simulations using lower bound (LB) of the two-sided 95% confidence interval (CI) for VE(D). For IGRA-positive participants, assumptions included 1:1 randomization, 9000 participants/arm, 0.4% TB incidence/year, 55% true VE(D), 5% dropout/year, and two-year enrollment. Enrollment irrespective of baseline IGRA status (mixed IGRA-status population) and IGRA-negative-only scenarios were explored to estimate sample sizes and trial duration. RESULTS: Simulations demonstrated that 110 events rule out a VE(D) 95% CI LB ≤10%, and 185 events rule out ≤25%, assuming ≥90% power and a true VE(D) of 55%. With 18,000 IGRA-positive participants, simulations projected a 90% probability of accruing 110 events within 3.5 to 4 years and 185 within 5.5 to 6 years. In the mixed IGRA-status population, few endpoints occurred among IGRA-negative participants, yielding insufficient power. Standalone VE(D) evaluation in IGRA-negative participants required large sample sizes (approximately 134,800) and prolonged timelines, indicating infeasibility. Accordingly, the selected primary objective of the phase 3 trial was to confirm VE(D) in IGRA-positive HIV-negative participants using LB of 95% CI for VE(D) > 10% after 110 events; secondary objectives include safety and immunogenicity in HIV-negative IGRA-positive; HIV-negative IGRA-negative; and HIV-positive individuals irrespective of IGRA status. CONCLUSIONS: An IGRA-positive-enriched, event-driven phase 3 trial is feasible to confirm VE(D) of M72/AS01Item Pulmonary Tuberculosis Detection with MiniDock MTB Using Swab Samples.(2026-Apr-30) Yerlikaya S; Chirwa M; Ajide B; Castro MDM; Ha H; Kato-Maeda M; Kisakye E; Marcelo D; Mochizuki T; Rockman L; Steadman A; Thangakunam B; Bimba JS; Christopher DJ; Muyoyeta M; Phan H; Theron G; Yu C; Kremer K; Phillips PPJ; Nahid P; Denkinger CM; Cattamanchi A; Andama ABACKGROUND: Improved diagnostic tools for tuberculosis that are suitable for use in peripheral health centers are essential for reducing the persistent gap between estimated and notified cases. The diagnostic accuracy and usability of the MiniDock MTB test for detecting pulmonary tuberculosis is unknown. METHODS: We conducted a prospective, cross-sectional study at outpatient centers in India, Nigeria, the Philippines, South Africa, Uganda, Vietnam, and Zambia. Patients 12 years of age or older with presumptive pulmonary tuberculosis were enrolled between September 12, 2024, and March 31, 2025. Assessment with MiniDock MTB was performed with sputum swabs and tongue swabs. Diagnostic accuracy was evaluated against a sputum-culture-based reference and as compared with sputum-smear microscopy and Xpert MTB/RIF Ultra assay. Usability was assessed with a system usability scale and direct observation. RESULTS: A total of 1380 participants were enrolled; 255 (18.5%) had human immunodeficiency virus infection and 226 (16.4%) had culture-confirmed tuberculosis. MiniDock MTB sensitivity was 85.7% (95% confidence interval [CI], 80.4 to 90.0) with sputum and 79.6% (95% CI, 73.8 to 84.7) with tongue swabs; specificity was greater than 97.5% for both. Results of sputum tests with MiniDock MTB closely matched those with Xpert MTB/RIF Ultra for sensitivity (difference, -2.8 percentage points; 95% CI, -6.0 to 0.5). MiniDock MTB had greater sensitivity than smear microscopy for tests of sputum (difference, 24.3 percentage points; 95% CI, 17.9 to 30.7) and tongue swabs (difference, 18.3 percentage points; 95% CI, 12.0 to 24.7). The test showed diagnostic accuracy that was consistent with World Health Organization (WHO) accuracy targets for near-point-of-care tuberculosis diagnostics (≥85% sensitivity for sputum and ≥75% for nonsputum and ≥98% specificity for both). The median score on the system usability scale (range, 0 to 100, with higher scores indicating better perceived usability) was 75 (interquartile range, 65 to 80), which indicated good usability. No adverse events related to the index test were reported. CONCLUSIONS: MiniDock MTB met WHO targets for diagnostic accuracy and usability for tuberculosis detection across diverse clinical settings. (Funded by the National Institutes of Health and others; Rapid Research in Diagnostics Development for TB Network and Assessing Diagnostics at Point-of-Care for Tuberculosis ClinicalTrials.gov numbers, NCT04923958 and NCT05941052.).Item Diagnostic Yield of Tongue Swab- Compared to Sputum-Based Molecular Testing for Tuberculosis in Four High-Burden Countries.(2026-Apr-30) Moe CA; Luswata RK; Barrameda AJ; Le H; Muzazu S; Crowder R; Andama AO; Denkinger CM; Muyoyeta M; Phan H; Cattamanchi A; Yu CBACKGROUND: Tongue swabs are a promising alternative specimen for tuberculosis (TB) diagnosis. Although test specificity exceeds 98%, sensitivity is lower than sputum-based molecular testing. We investigated whether the use of tongue swabs could increase sample availability, resulting in similar diagnostic yield. METHODS: In this cross-sectional study (July 2024-January 2025), we screened consecutive people with presumptive TB at health centers in the Philippines, Vietnam, Uganda, and Zambia. Participants were asked to provide tongue swabs and referred for routine sputum collection. Tongue swabs were tested in research laboratories using the MiniDock MTB Test (Guangzhou Pluslife Biotech Co., Ltd., China); sputum was tested using WHO-recommended molecular testing per national guidelines. We compared diagnostic yield, defined as proportion of positive test results among all participants, between tongue swab- and sputum-based molecular testing with a prespecified 3.0% non-inferiority margin. RESULTS: Of 1639 participants, 851 (51.9%) were female, 415 (25.3%) were diagnosed with HIV, and 132 (8.1%) were children <5 years. All provided tongue swabs, but only 1389 (84.7%) produced sputum. Diagnostic yield was 3.8% (63/1639) for tongue swabs and 4.1% (68/1639) for sputum-based (68/1639, 4.1%) molecular testing. The difference (0.3%, 95% CI -0.6 to +1.2) was within the prespecified non-inferiority margin. Results were consistent across countries and key subgroups (age, sex, and HIV status). CONCLUSIONS: Tongue swab-based molecular testing with MiniDock MTB achieved non-inferior diagnostic yield compared with sputum-based molecular testing. These findings support scale-up of swab-based platforms as a cost-efficient alternative, particularly where sputum collection is challenging or smear microscopy remains the primary diagnostic method.Item Tongue swab Xpert MTB/RIF Ultra testing for TB using a revised consensus protocol.(2026-Apr-27) 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 MBACKGROUNDTongue swabs are a promising specimen type for TB diagnosis. In a previous study, using a consensus protocol, tongue swabs tested with Xpert MTB/RIF Ultra outperformed sputum smear microscopy, but a substantial proportion (6.1%) of results were non-actionable (e.g., invalid/error). We evaluated a revised protocol for tongue swab Xpert Ultra testing in four high-burden countries.METHODSParticipants 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 culture-based microbiological reference standard and compared to sputum tests.RESULTSFrom March to November 2024, 1,168 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 non-actionable tongue swab results was 5.6% overall, but <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).CONCLUSIONThe revised protocol yielded low error rates at most sites and moderate sensitivity, supporting tongue swabs as an alternative specimen for Xpert Ultra testing when sputum is unavailable..Item 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 MBACKGROUND: 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.Item Costs and cost-effectiveness of a comprehensive tuberculosis case finding strategy in Zambia.(2021) Jo Y; Kagujje M; Johnson K; Dowdy D; Hangoma P; Chiliukutu L; Muyoyeta M; Sohn HINTRODUCTION: Active-case finding (ACF) programs have an important role in addressing case detection gaps and halting tuberculosis (TB) transmission. Evidence is limited on the cost-effectiveness of ACF interventions, particularly on how their value is impacted by different operational, epidemiological and patient care-seeking patterns. METHODS: We evaluated the costs and cost-effectiveness of a combined facility and community-based ACF intervention in Zambia that utilized mobile chest X-ray with computer-aided reading/interpretation software and laboratory-based Xpert MTB/RIF testing. Programmatic costs (in 2018 US dollars) were assessed from the health system perspective using prospectively collected cost and operational data. Cost-effectiveness of the ACF intervention was assessed as the incremental cost per TB death averted over a five-year time horizon using a multi-stage Markov state-transition model reflecting patient symptom-associated care-seeking and TB care under ACF compared to passive care. RESULTS: Over 18 months of field operations, the ACF intervention costed $435 to diagnose and initiate treatment for one person with TB. After accounting for patient symptom-associated care-seeking patterns in Zambia, we estimate that this one-time ACF intervention would incrementally diagnose 407 (7,207 versus 6,800) TB patients and avert 502 (611 versus 1,113) TB-associated deaths compared to the status quo (passive case finding), at an incremental cost of $2,284 per death averted over the next five-year period. HIV/TB mortality rate, patient symptom-associated care-seeking probabilities in the absence of ACF, and the costs of ACF patient screening were key drivers of cost-effectiveness. CONCLUSIONS: A one-time comprehensive ACF intervention simultaneously operating in public health clinics and corresponding catchment communities can have important medium-term impact on case-finding and be cost-effective in Zambia. The value of such interventions increases if targeted to populations with high HIV/TB mortality, substantial barriers (both behavioral and physical) to care-seeking exist, and when ACF interventions can optimize screening by achieving operational efficiency.Item Cross-sectional assessment of tuberculosis and HIV prevalence in 13 correctional facilities in Zambia.(2021-Sep-27) Kagujje M; Somwe P; Hatwiinda S; Bwalya J; Zgambo T; Thornicroft M; Bozzani FM; Moonga C; Muyoyeta MOBJECTIVE: 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 Clinical diagnosis of TB: lessons on misdiagnosis and overdiagnosis.(2025-Jun) Singini DS; Sanjase N; Kagujje M; Shatalimi J; Chisanga CP; Lupatali ZD; Phiri D; Tatila T; Olwit W; Kerkhoff AD; Muyoyeta MClinically diagnosed TB patients (n = 335) at two facilities in Lusaka, Zambia were re-evaluated within two weeks of diagnosis. This re-evaluation included sputum Xpert Ultra testing and expert reader interpretation of the chest x-rays (CXRs) used for initial diagnosis. Repeat Xpert Ultra detected TB in just 2.6% (n=6). Of the remaining patients (n=222), expert CXR re-interpretation classified 18.0% as normal; 36.0% as abnormal, consistent with TB; and 46.0% as abnormal, not consistent with TB. These findings suggest that clinical TB is frequently over diagnosed in those without detectable CXR abnormalities and misdiagnosed in those with abnormal CXRs: these abnormalities are likely due to other respiratory conditions. Such misdiagnosis leads to unnecessary treatment, failure to treat the true underlying condition and incorrect estimates of TB burden.