Browsing by Author "Nyangu, Sarah"

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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, Andrew D.; Mwamba, Chanda; Pry, Jake M.; Kagujje, Mary; Nyangu, Sarah; Mateyo, Kondwelani; Sanjase, Nsala; Chilukutu, Lophina ; Christopoulos, Katerina A. ; Muyoyeta, Monde; Sharma, Anjali
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, Tinne; Hella, Jerry; Jacobs, Bart K.M.; Sossen, Bianca; Mukoka, Madalo; Muyoyeta, Monde; Nakabugo, Elizabeth; Nguyen, Hung Van; Ubolyam, Sasiwimol; Macé, Aurélien; Vermeulen, Marcia; Nyangu, Sarah; Sanjase, Nsala; Sasamalo, Mohamed; Dinh, Huong T.; Ngo, The A.; Manosuthi, Weerawat; Jirajariyavej, Supunnee; Denkinger, Claudia M. ; Nguyen, Nhung V.; Avihingsanon, Anchalee; Nakiyingi, Lydia; Székely, Rita; Kerkhoff, Andrew D.; MacPherson, Peter; Meintjes, Graeme; Reither, Klaus; Ruhwald, Morten
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.
Interrupted time-series analysis of active case-finding for tuberculosis during the COVID-19 pandemic, Zambia.
(2022-Mar-01) Lungu, Patrick S.; Kerkhoff, Andrew D.; Muyoyeta, Monde; Kasapo, Clara C.; Nyangu, Sarah; Kagujje, Mary; Chimzizi, Rhehab; Nyimbili, Sulani; Khunga, Morton; Kasese-Chanda, Nancy; Musonda, Victoria ; Tambatamba, Bushimbwa; Kombe, Christopher M.; Sakulanda, Charles ; Sampa, Kizito; Silumesii, Andrew; Malama, Kennedy
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.
Pathways to care and preferences for improving tuberculosis services among tuberculosis patients in Zambia: A discrete choice experiment.
(2021) Kerkhoff, Andrew D.; Kagujje, Mary; Nyangu, Sarah; Mateyo, Kondwelani ; Sanjase, Nsala; Chilukutu, Lophina; Eshun-Wilson, Ingrid; Geng, Elvin H.; Havlir, Diane V.; Muyoyeta, Monde
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, Andrew D.; Chilukutu, Lophina; Nyangu, Sarah; Kagujje, Mary; Mateyo, Kondwelani ; Sanjase, Nsala; Eshun-Wilson, Ingrid; Geng, Elvin H.; Havlir, Diane V.; Muyoyeta, Monde
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.
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, Rita; Sossen, Bianca; Mukoka, Madalo; Muyoyeta, Monde; Nakabugo, Elizabeth; Hella, Jerry; Nguyen, Hung V.; Ubolyam, Sasiwimol; Chikamatsu, Kinuyo; Macé, Aurelien; Vermeulen, Marcia; Centner, Chad M.; Nyangu, Sarah; Sanjase, Nsala; Sasamalo, Mohamed; Dinh, Huong T.; Ngo, The A.; Manosuthi, Weerawat; Jirajariyavej, Supennee; Mitarai, Satoshi; Nguyen, Nhung V.; Avihingsanon, Anchalee; Reither, Klaus; Nakiyingi, Lydia; Kerkhoff, Andrew D.; MacPherson, Peter; Meintjes, Graeme; Denkinger, Claudia M.; Ruhwald, Morten
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).
The accuracy of point-of-care C-Reactive Protein as a screening test for tuberculosis in children.
(2024) Kagujje, Mary; Nyangu, Sarah; Maimbolwa, Minyoi M.; Shuma, Brian; Sanjase, Nsala; Chungu, Chalilwe ; Kerkhoff, Andrew D.; Creswell, Jacob; Muyoyeta, Monde
Systematic screening for TB in children, especially among those at high risk of TB, can promote early diagnosis and treatment of TB. The World Health Organization (WHO) recently recommended C-Reactive Protein as a TB screening tool in adults and adolescents living with HIV (PLHIV). Thus, we aimed to assess the performance of point-of-care (POC) CRP as a screening tool for TB in children. A cross-sectional study was conducted at 2 primary health care facilities in Lusaka, Zambia between September 2020 -August 2021. Consecutive children (aged 5-14 years) presenting for TB services were enrolled irrespective of TB symptoms. All participants were screened for the presence of TB symptoms and signs, asked about TB contact history, and undertook a POC CRP test, chest X-ray, and sputum Xpert MTB/RIF Ultra test. The accuracy of CRP (≥10 mg/L cutoff) was determined using a microbiological reference standard (MRS) and a composite reference standard (CRS). Of 280 children enrolled and with complete results available, the median age was 10 years (IQR 7-12), 56 (20.0%) were HIV positive, 228 (81.4%) had a positive WHO symptom screen for TB, 62 (22.1%) had a close TB contact, and 79 (28.2%) had a positive CRP POC test. Five (1.8%) participants had confirmed TB, 71 (25.4%) had unconfirmed TB, and 204 (72.3%) had unlikely TB. When the MRS was used, the sensitivity of CRP was 80.0% (95%CI: 28.4-99.5%) and the specificity was 72.7% (95%CI: 67.1-77.9%). When the CRS was used, the sensitivity of CRP was 32.0% (95%CI: 23.3% - 42.5%), while the specificity was 74.0% (95%CI: 67.0% - 80.3%). Using the CRS, there were no statistically significant differences in sensitivity and specificity of CRP in the HIV positive and HIV negative individuals. Among children in Zambia, POC CRP had limited utility as a screening tool for TB. There remains a continued urgent need for better tools and strategies to improve TB detection in children.
Urine-Xpert Ultra for the diagnosis of tuberculosis in people living with HIV: a prospective, multicentre, diagnostic accuracy study.
(2024-Dec) Sossen, Bianca; Székely, Rita; Mukoka, Madalo; Muyoyeta, Monde; Nakabugo, Elizabeth; Hella, Jerry; Van Nguyen, Hung; Ubolyam, Sasiwimol; Erkosar, Berra; Vermeulen, Marcia; Centner, Chad M.; Nyangu, Sarah; Sanjase, Nsala; Sasamalo, Mohamed; Dinh, Huong T.; Ngo, The A.; Manosuthi, Weerawat; Jirajariyavej, Supunnee; Nguyen, Nhung V.; Avihingsanon, Anchalee; Kerkhoff, Andrew D.; Denkinger, Claudia M.; Reither, Klaus; Nakiyingi, Lydia; MacPherson, Peter; Meintjes, Graeme; Ruhwald, Morten
BACKGROUND: Diagnostic delays for tuberculosis are common, with high resultant mortality. Urine-Xpert Ultra (Cepheid) could improve time to diagnosis of tuberculosis disease and rifampicin resistance. We previously reported on lot-to-lot variation of the Fujifilm SILVAMP TB LAM. In this prespecified secondary analysis of the same cohort, we aimed to determine the diagnostic yield and accuracy of Urine-Xpert Ultra for tuberculosis in people with HIV, compared with an extended microbiological reference standard (eMRS) and composite reference standard (CRS) and also compared with Determine TB LAM Ag (AlereLAM, Abbott). METHODS: In this prospective, multicentre, diagnostic accuracy study, we recruited consecutive inpatients and outpatients (aged ≥18 years) with HIV from 13 hospitals and clinics in seven countries (Malawi, South Africa, Tanzania, Thailand, Uganda, Viet Nam, and Zambia). Patients with no isoniazid preventive therapy in the past 6 months and fewer than three doses of tuberculosis treatment in the past 60 days were included. Reference and index testing was performed in real time. The primary outcome of this secondary analysis was the diagnostic yield and accuracy of Urine-Xpert Ultra compared with the eMRS and CRS. Diagnostic accuracy was compared with AlereLAM and diagnostic yield was compared with both AlereLAM and Sputum-Xpert Ultra. This study was registered with ClinicalTrials.gov, NCT04089423, and is complete. FINDINGS: Between Dec 13, 2019, and Aug 5, 2021, 3528 potentially eligible individuals were screened and 1731 were enrolled, of whom 1602 (92·5%) were classifiable by the eMRS (median age 40 years [IQR 33-48], 838 [52·3%] of 1602 were female, 764 [47·7%] were male, 937 [58·5%] were outpatients, 665 [41·5%] were inpatients, median CD4 count was 374 cells per μL [IQR 138-630], and 254 [15·9%] had microbiologically confirmed tuberculosis). Against eMRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 32·7% (95% CI 27·2-38·7) and 30·7% (25·4-36·6) and specificities were 98·0% (97·1-98·6) and 90·4% (88·7-91·8), respectively. Against CRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 21·1% (95% CI 17·6-25·1), and 30·5% (26·4-34·9), and specificities were 99·1% (98·3-99·6) and 95·1% (93·5-96·3), respectively. The combination of Sputum-Xpert Ultra with AlereLAM or Urine-Xpert Ultra diagnosed 202 (77·1%) and 204 (77·9%) of 262 eMRS-positive participants, respectively, in incompletely overlapping groups; combining all three tests diagnosed 214 (81·7%) of 262 eMRS-positive participants INTERPRETATION: Urine-Xpert Ultra could offer promising clinical utility in addition to AlereLAM and Sputum-Xpert Ultra. In inpatient settings where both AlereLAM and Urine-Xpert Ultra are possible, both should be offered to support rapid diagnosis and treatment. FUNDING: Global Health Innovative Technology Fund, KfW Development Bank, Commonwealth of Australia represented by the Department of Foreign Affairs and Trade, and the Netherlands Enterprise Agency.