Browsing by Author "Muyoyeta, Monde"

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Active TB case finding in a high burden setting; comparison of community and facility-based strategies in Lusaka, Zambia.
(2020) Kagujje, Mary; Chilukutu, Lophina; Somwe, Paul; Mutale, Jacob; Chiyenu, Kanema; Lumpa, Mwansa; Mwanza, Winfrida; Muyoyeta, Monde
INTRODUCTION: We conducted an implementation science study to increase TB case detection through a combination of interventions at health facility and community levels. We determined the impact of the study in terms of additional cases detected and notification rate and compared the yield of bacteriologically confirmed TB of facility based and community based case finding. METHODOLOGY: Over a period of 18 months, similar case finding activities were conducted at George health facility in Lusaka Zambia and its catchment community, an informal peri-urban settlement. Activities included awareness and demand creation activities, TB screening with digital chest x-ray or symptom screening, sputum evaluation using geneXpert MTB/RIF, TB diagnosis and linkage to treatment. RESULTS: A total of 18,194 individuals were screened of which 9,846 (54.1%) were screened at the facility and 8,348 (45.9%) were screened in the community. The total number of TB cases diagnosed during the intervention period were 1,026, compared to 759 in the pre-intervention period; an additional 267 TB cases were diagnosed. Of the 563 bacteriologically confirmed TB cases diagnosed under the study, 515/563 (91.5%) and 48/563 (8.5%) were identified at the facility and in the community respectively (P<0.0001). The TB notification rate increased from 246 per 100,000 population pre-intervention to 395 per 100,000 population in the last year of the intervention. CONCLUSIONS: Facility active case finding was more effective in detecting TB cases than community active case finding. Strengthening health systems to appropriately identify and evaluate patients for TB needs to be optimised in high burden settings. At a minimum, provider initiated TB symptom screening with completion of the TB screening and diagnostic cascade should be provided at the health facility in high burden settings. Community screening needs to be systematic and targeted at high risk groups and communities with access barriers.
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, Nicole
BACKGROUND: 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.
Comparison of indoor contact time data in Zambia and Western Cape, South Africa suggests targeting of interventions to reduce Mycobacterium tuberculosis transmission should be informed by local data.
(2016-Feb-09) McCreesh, Nicky; Looker, Clare; Dodd, Peter J.; Plumb, Ian D.; Shanaube, Kwame; Muyoyeta, Monde; Godfrey-Faussett P; Corbett, Elizabeth L.; Ayles, Helen; White, Richard G.
BACKGROUND: In high incidence settings, the majority of Mycobacterium tuberculosis (M.tb) transmission occurs outside the household. Little is known about where people's indoor contacts occur outside the household, and how this differs between different settings. We estimate the number of contact hours that occur between adults and adult/youths and children in different building types in urban areas in Western Cape, South Africa, and Zambia. METHODS: Data were collected from 3206 adults using a cross-sectional survey, on buildings visited in a 24-h period, including building function, visit duration, and number of adults/youths and children (5-12 years) present. The mean numbers of contact hours per day by building function were calculated. RESULTS: Adults in Western Cape were more likely to visit workplaces, and less likely to visit shops and churches than adults in Zambia. Adults in Western Cape spent longer per visit in other homes and workplaces than adults in Zambia. More adults/youths were present at visits to shops and churches in Western Cape than in Zambia, and fewer at homes and hairdressers. More children were present at visits to shops in Western Cape than in Zambia, and fewer at schools and hairdressers. Overall numbers of adult/youth indoor contact hours were the same at both sites (35.4 and 37.6 h in Western Cape and Zambia respectively, p = 0.4). Child contact hours were higher in Zambia (16.0 vs 13.7 h, p = 0.03). Adult/youth and child contact hours were highest in workplaces in Western Cape and churches in Zambia. Compared to Zambia, adult contact hours in Western Cape were higher in workplaces (15.2 vs 8.0 h, p = 0.004), and lower in churches (3.7 vs 8.6 h, p = 0.002). Child contact hours were higher in other peoples' homes (2.8 vs 1.6 h, p = 0.03) and workplaces (4.9 vs 2.1 h, p = 0.003), and lower in churches (2.5 vs 6.2, p = 0.004) and schools (0.4 vs 1.5, p = 0.01). CONCLUSIONS: Patterns of indoor contact between adults and adults/youths and children differ between different sites in high M.tb incidence areas. Targeting public buildings with interventions to reduce M.tb transmission (e.g. increasing ventilation or UV irradiation) should be informed by local data.
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, Monde
OBJECTIVE: 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.
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.
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.
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, Monde
The 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.
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, Jacob
BACKGROUND: 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.
Implementation of isoniazid preventive therapy in people living with HIV in Zambia: challenges and lessons.
(2019-Oct-22) Kagujje, Mary; Mubiana, Muhau L.; Mwamba, Eugenia; Muyoyeta, Monde
BACKGROUND: Uptake of Isoniazid Preventive Therapy (IPT) among People Living with HIV in Zambia has continued to be low despite various evidence for its added benefit in reducing TB incidence and mortality when taken with antiretroviral therapy. In 2017, only 18% of People Living with HIV newly enrolled in care were initiated on IPT in Zambia. MAIN TEXT: Various challenges including policy and management level factors, supply chain factors, health worker perceptions about IPT, monitoring and evaluation factors and limited demand creation activities have constrained the scale up of IPT in Zambia. Lessons that have been learnt while addressing the above challenges are shared and they can be applied by government ministries, project managers, public health specialists to strengthen IPT activities in their settings. CONCLUSION: Zambia has both a high burden of TB and HIV and without preventing new cases of TB from reactivation of latent TB infection, it will be difficult to control TB. All stakeholders involved in prevention of TB among PLHIV need to commit to addressing the challenges limiting scale up of IPT.
Integrating HIV care and treatment into tuberculosis clinics in Lusaka, Zambia: results from a before-after quasi-experimental study.
(2018-Oct-26) Herce, Michael E.; Morse, Jill; Luhanga, Dora; Harris, Jennifer; Smith, Helene J.; Besa, Stable; Samungole, Graham; Kancheya, Nzali; Muyoyeta, Monde; Reid, Stewart E.
BACKGROUND: Patients with HIV-associated tuberculosis (TB) often have their TB and HIV managed in separate vertical programs that offer care for each disease with little coordination. Such "siloed" approaches are associated with diagnostic and treatment delays, which contribute to unnecessary morbidity and mortality. To improve TB/HIV care coordination and early ART initiation, we integrated HIV care and treatment into two busy TB clinics in Zambia. We report here the effects of our intervention on outcomes of linkage to HIV care, early ART uptake, and TB treatment success for patients with HIV-associated TB in Lusaka, Zambia. METHODS: We provided integrated HIV treatment and care using a "one-stop shop" model intervention. All new or relapse HIV-positive TB patients were offered immediate HIV program enrolment and ART within 8 weeks of anti-TB therapy (ATT) initiation. We used a quasi-experimental design, review of routine program data, and survival analysis and logistic regression methods to estimate study outcomes before (June 1, 2010-January 31, 2011) and after (August 1, 2011-March 31, 2012) our intervention among 473 patients with HIV-associated TB categorized into pre- (n = 248) and post-intervention (n = 225) cohorts. RESULTS: Patients in the pre- and post-intervention cohorts were mostly male (60.1% and 52.9%, respectively) and young (median age: 33 years). In time-to-event analyses, a significantly higher proportion of patients in the post-intervention cohort linked to HIV care by 4 weeks post-ATT initiation (53.9% vs. 43.4%, p = 0.03), with median time to care linkage being 59 and 25 days in the pre- and post-intervention cohorts, respectively. In Cox proportional hazard modelling, patients receiving the integration intervention started ART by 8 weeks post-ATT at 1.33 times the rate (HR = 1.33, 95% CI: 1.00-1.77) as patients pre-intervention. In logistic regression modelling, patients receiving the intervention were 2.02 times (95% CI: 1.11-3.67) as likely to have a successful TB treatment outcome as patients not receiving the intervention. CONCLUSIONS: Integrating HIV treatment and care services into routine TB clinics using a one-stop shop model increased linkage to HIV care, rates of early ART initiation, and TB treatment success among patients with HIV-associated TB in Lusaka, Zambia.
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, Andrew D.; West, Nora S.; Del Mar Castro, Maria; Branigan, David; Christopher, Devasahayam J.; Denkinger, Claudia M.; Nhung, Nguyen V.; Theron, Grant; Worodria, William; Yu, Charles; Muyoyeta, Monde; Cattamanchi, Adithya
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, Kingsley K.; Borkman, April; Kim, Ashley; Crowder, Rebecca ; Ajide, Bukola; Alí-Francia, Karla; Chirwa, Masuzyo; Kamulegeya, Louis; Le, Hien; Trung, Vu N.; Venter, Rouxjeane; Bimba, John; Christopher, Devasahayam J.; Dalay, Victoria; Van Hung N; Muyoyeta, Monde; Nakiyingi, Lydia; Van Nhung, Nguyen; Theron, Grant; Yu, Charles; Zamudio-Fuertes, Carlos; Atim, Julian; Kerkhoff, Andrew D.; Noriega, Maria D. M. C.; Nahid, Payam; Denkinger, Claudia M.; Cattamanchi, Adithya; Dorman, Susan E.; West, Nora
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.
Protein Dose-Sparing Effect of AS01B Adjuvant in a Randomized Preventive HIV Vaccine Trial of ALVAC-HIV (vCP2438) and Adjuvanted Bivalent Subtype C gp120.
(2024-Aug-16) Chirenje, Zvavahera M.; Laher, Fatima; Dintwe, One; Muyoyeta, Monde; deCamp, Allan C.; He, Zonglin; Grunenberg, Nicole; Laher, Faatima, O.; Seaton, Kelly E.; Polakowski, Laura; Davis, Amanda S. W.; Maganga, Lucas; Baden, Lindsey R.; Mayer, Kenneth; Kalams, Spyros ; Keefer, Michael; Edupuganti, Srilatha; Rodriguez, Benigno; Frank, Ian; Scott, Hyman; Stranix-Chibanda, Lynda; Gurunathan, Sanjay; Koutsoukos, Marguerite; Van Der Meeren, Olivier; DiazGranados, Carlos A.; Paez, Carmen; Andersen-Nissen, Erica; Kublin, James; Corey, Lawrence ; Ferrari, Guido; Tomaras, Georgia; McElrath, Juliana M.
BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled human immunodeficiency virus (HIV) vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at 2 dose levels in healthy HIV-uninfected adults. METHODS: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200 μg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40 μg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses. RESULTS: We enrolled 160 participants, 55% women, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40 μg gp120/AS01B group were higher than in either of the 200 μg gp120 groups. CONCLUSIONS: The 40 μg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses. Clinical Trials Registration . NCT03122223.
Sensitivity and specificity of CRP and symptom screening as tuberculosis screening tools among HIV-positive and negative outpatients at a primary healthcare facility in Lusaka, Zambia: a prospective cross-sectional study.
(2023-Apr-18) Kagujje, Mary; Mwanza, Winnie; Somwe, Paul; Chilukutu, Lophina; Creswell, Jacob; Muyoyeta, Monde
OBJECTIVES: To evaluate the performance of point-of-care C-reactive protein (CRP) as a screening tool for tuberculosis (TB) using a threshold of 10 mg/L in both people living with HIV (PLHIV) and HIV-negative individuals and compare it to symptom screening using a composite reference for bacteriological confirmation of TB. METHODS: Prospective cross-sectional study. SETTING: A primary healthcare facility in Lusaka, Zambia. PARTICIPANTS: Consecutive adults (≥18 years) presenting for routine outpatient healthcare were enrolled. Of the 816 individuals approached to participate in the study, 804 eligible consenting adults were enrolled into the study, of which 783 were included in the analysis. PRIMARY OUTCOME MEASURES: Sensitivity, specificity, positive predictive value and negative predictive value (NPV) of CRP and symptom screening. RESULTS: Overall, sensitivity of WHO-recommended four-symptom screen (W4SS) and CRP were 87.2% (80.0-92.5) and 86.6% (79.6-91.8) while specificity was 30.3% (26.7-34.1) and 34.8% (31.2-38.6), respectively. Among PLHIV, sensitivity of W4SS and CRP was 92.2% (81.1-97.8) and 94.8% (85.6-98.9) while specificity was 37.0% (31.3-43.0) and 27.5% (22.4-33.1), respectively. Among those with CD4≥350, the NPV for CRP was 100% (92.9-100). In the HIV negative, sensitivity of W4SS and CRP was 83.8% (73.4-91.3) and 80.3% (69.5-88.5) while specificity was 25.4% (20.9-30.2) and 40.5% (35.3-45.6), respectively. Parallel use of CRP and W4SS yielded a sensitivity and NPV of 100% (93.8-100) and 100% (91.6-100) among PLHIV and 93.3% (85.1-97.8) and 90.0% (78.2-96.7) among the HIV negatives, respectively. CONCLUSION: Sensitivity and specificity of CRP were similar to symptom screening in HIV-positive outpatients. Independent use of CRP offered limited additional benefit in the HIV negative. CRP can independently accurately rule out TB in PLHIV with CD4≥350. Parallel use of CRP and W4SS improves sensitivity irrespective of HIV status and can accurately rule out TB in PLHIV, irrespective of CD4 count.
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, Sean
INTRODUCTION: 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.
Superimposed Pulmonary Tuberculosis (PTB) in a 26-Year-Old Female with No Underlying Co-Morbidities Recovering from COVID-19-Case Report.
(2023-May-08) Njekwa, Katanekwa; Muyoyeta, Monde; Mulenga, Bavin; Chisenga, Caroline C.; Simuyandi, Michelo; Chilengi, Roma
Tuberculosis before the COVID-19 pandemic is said to have killed more people globally than any other communicable disease and is ranked the 13th cause of death, according to the WHO. Tuberculosis also still remains highly endemic, especially in LIMCs with a high burden of people living with HIV/AIDS, in which it is the leading cause of mortality. Given the risk factors associated with COVID-19, the cross similarities between tuberculosis and COVID-19 symptoms, and the paucity of data on how both diseases impact each other, there is a need to generate more information on COVID-19-TB co-infection. In this case report, we present a young female patient of reproductive age with no underlying comorbidities recovering from COVID-19, who later presented with pulmonary tuberculosis. It describes the series of investigations performed and treatments given during the follow-up. There is a need for more surveillance for possible COVID-19-TB co-infection cases and further research to understand the impact of COVID-19 on tuberculosis and vice versa, especially in LMICs.
"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, Monde
BACKGROUND: 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.
Tongue Swab Xpert MTB/RIF Ultra Testing for Tuberculosis Using a Revised Consensus Protocol: A multi-country diagnostic accuracy study.
(2025-Jul-10) Ajide, Bukola; Moe, Caitlin A.; Barrameda, Jheannie; Chirwa, Masuzyo; Rockman, Loren; de Haas, Petra ; de Vos, Margaretha; Kato-Maeda, Midori; Tasca, Bianca ; Bimba, John; Yu, Charles; Denkinger, Claudia M.; Kremer, Kristin ; Nahid, Payam; Cattamanchi, Adithya ; Theron, Grant; Muyoyeta, Monde
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.
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, Kennedy
OBJECTIVE: 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.
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 K
BACKGROUND: 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.