BMI and incident tuberculosis in close TB contacts [TBN 091]

A longitudinal observational study developed and internally validated a prediction model for progression to active tuberculosis (TB) among close contacts of culture-confirmed pulmonary TB patients in the RePORT-Brazil cohort. The study enrolled participants between June 2015 and June 2019 across four cities in three Brazilian states (Rio de Janeiro, Bahia, and Amazonas) and followed contacts for 24 months. The objective was to identify predictors of progression from exposure or latent infection to active TB disease.

The study included 1,846 close contacts of 619 pulmonary TB index patients, with 86% completing at least 1.5 years of follow-up. Close contacts were defined as individuals exposed to a culture-positive pulmonary TB patient for at least 4 hours per week during the 6 months preceding diagnosis. At baseline, contacts underwent clinical evaluation, chest radiography, interferon-gamma release assay (IGRA) testing, HIV testing, and collection of sociodemographic and clinical data. Contacts were eligible only if they were asymptomatic for TB at enrollment. Follow-up assessments occurred at 6 months in person and every 6 months thereafter by telephone, with clinical evaluation if symptoms developed. Progression to TB was defined by microbiological confirmation or clinical diagnosis. Thirty baseline variables were initially considered. Predictor selection involved empirical review followed by least absolute shrinkage and selection operator (LASSO) regression with 5-fold cross-validation. Cox proportional hazards models were used after variable selection.

Among the 1,846 contacts, 25 (1.4%) developed TB within 24 months. Of these, 13 cases were microbiologically confirmed, 2 had histopathological evidence suggestive of TB, and 10 were clinically diagnosed; 75% had pulmonary TB. Baseline IGRA positivity was more common among progressors than non-progressors (75% vs 36.3%). The final prediction model identified three predictors of progression: tuberculosis preventive therapy (TPT), smoking status, and baseline IGRA positivity. 

Internal validation demonstrated good discrimination with an optimism-corrected AUC of 0.81 (95% CI 0.74-0.88). Contacts who never initiated TPT had substantially higher risk of developing TB than those who completed TPT (adjusted hazard ratio [aHR] 16.55, 95% CI 2.20-124.43). Among IGRA-positive contacts, TPT remained the only retained predictor, with an optimism-corrected AUC of 0.73 (95% CI 0.64-0.79); failure to start TPT was associated with increased TB risk (aHR 14.75, 95% CI 1.95-111.68). In the subgroup of IGRA-positive contacts who did not receive TPT or received it for less than 30 days, lower body mass index (BMI) emerged as an additional predictor. Each 1 kg/m² increase in BMI was associated with a 13% reduction in TB risk (aHR 0.89, 95% CI 0.80-0.99). A BMI threshold of approximately 25 kg/m² was identified, with BMI <25 kg/m² associated with higher risk of progression (aHR 4.14, 95% CI 1.17-14.67). In this high-risk subgroup, TB incidence was 8.4% among those with BMI <25 kg/m² compared with 2.1% among those with BMI ≥25 kg/m².

The study concluded that lack of TPT, baseline IGRA positivity, smoking status, and lower BMI are important predictors of progression to active TB among close contacts of pulmonary TB patients. Completion of TPT appeared to be the strongest protective factor. Major limitations include the small number of TB progressors (25 events), which may have reduced statistical precision and increased uncertainty around effect estimates. Internal validation showed good model performance, but external validation in other populations is needed before broader implementation. 

Source: Arriaga MB, Amorim G, Figueiredo MC, Staats C, Kritski AL, Cordeiro-Santo M, Rolla VC, Rebeiro PF, Andrade BB, Sterling TR. Body mass index and incident tuberculosis in close tuberculosis contacts. Clinical Infectious Diseases. 2026 Jan 15;82(1):e100-9.

Asymptomatic TB in children with household exposure to Mtb [TBN 090]

A study aimed to evaluate both asymptomatic and symptomatic tuberculosis (TB) among young children with household exposure to drug-susceptible TB, using standardized investigations regardless of symptom status. It was a prospective observational cohort study conducted in Worcester, South Africa, between September 2019 and March 2024. Children aged 2 to 60 months with documented household exposure to an adult with TB within the previous 12 months were enrolled. Children with HIV infection or other medical conditions that could alter TB risk were excluded. Participants without prevalent TB at baseline were followed for up to 36 months.

All enrolled children underwent comprehensive baseline TB evaluation irrespective of symptoms. Investigations included symptom screening, interferon-γ release assay (QuantiFERON-TB Gold Plus), induced sputum testing with liquid mycobacterial culture (MGIT) and Xpert MTB/RIF Ultra, chest radiography (CXR), and multiplex respiratory pathogen PCR testing. TB was classified using a modified childhood TB consensus case definition that allowed inclusion of asymptomatic children. Confirmed TB required microbiological confirmation by culture or Xpert Ultra (excluding trace-positive results). Unconfirmed TB required at least two features among TB-compatible symptoms, TB-compatible CXR findings, household TB exposure, or trace-positive Xpert Ultra results. Prevalent TB was defined as meeting TB criteria within 60 days of enrollment.

Among 506 screened child household contacts, 430 (85.0%) were enrolled. Prevalent TB was identified in 154/430 children (35.8%), including 21/430 (4.9%) with Confirmed TB and 133/430 (30.9%) with Unconfirmed TB. Notably, 17/21 (81.0%) children with Confirmed TB were asymptomatic. Overall, 55/154 (35.7%) children with prevalent TB were asymptomatic and 99/154 (64.3%) were symptomatic. Compared with symptomatic TB cases, asymptomatic TB cases were more likely to have microbiologically confirmed disease (30.9% vs 4.0%, P < .001) and a TB-compatible CXR (54.4% vs 15.2%, P < .001). 

TB treatment was initiated in 78/154 (50.6%) children meeting the TB case definition, including all Confirmed TB cases. Treatment was started more frequently in asymptomatic than symptomatic TB cases (80.0% vs 34.3%, P = .01). Among treated children, positive IGRA was associated with asymptomatic TB compared with children without TB (adjusted odds ratio [aOR] 3.23, 95% CI 1.66–6.30), as was male sex (aOR 1.98, 95% CI 1.01–3.87). Compared with symptomatic TB, microbiological confirmation was associated with asymptomatic TB (aOR 3.73, 95% CI 1.08–12.88).

The findings suggest that a substantial proportion of TB among young household-exposed children is asymptomatic, including most microbiologically confirmed cases. Reliance on symptom-based screening alone would likely miss many children with TB. Key limitations include incomplete CXR availability during the COVID-19 pandemic, potential diagnostic uncertainty among Unconfirmed TB cases, and conduct at a single South African site, which may limit generalizability. 

Source: Mulenga H, Shenje J, Mendelsohn SC, Luabeya AK, Tameris M, Tredoux EN, Nemes E, Bilek N, Beyers E, Ivacik-Goncalves D, Andrews JR. Asymptomatic tuberculosis in children with household exposure to Mycobacterium tuberculosis. Clinical Infectious Diseases. 2026 May 15;82(5):e1005-13.

Keterbatasan Penggunaan Gejala sebagai Dasar Klasifikasi Tuberkulosis [TBN 089]

Cara mengategorikan tuberkulosis (TB) telah berkembang seiring waktu, mengikuti perubahan metode utama yang digunakan untuk mendeteksinya. Pada pertengahan abad ke-20, banyak negara, terutama negara maju, menggunakan skrining massal dengan foto rontgen dada yang memungkinkan identifikasi spektrum penyakit TB yang luas, termasuk pada individu tanpa gejala yang jelas. Ketika angka TB menurun di negara-negara berpendapatan tinggi pada paruh kedua abad ke-20, upaya pencegahan dan pelayanan TB global beralih ke negara berpendapatan rendah dan menengah. Dalam konteks ini, keterbatasan sumber daya mendorong fokus pada diagnosis dan pengobatan TB menular yang bergejala, yang pada saat itu dianggap sama dengan TB BTA positif, sehingga memperkuat pandangan bahwa gejala merupakan penentu utama adanya penyakit.

Sebagai respons terhadap meningkatnya perhatian terhadap TB tanpa gejala yang jelas, Organisasi Kesehatan Dunia (WHO) menerbitkan laporan mengenai TB asimtomatik pada tahun 2025. Laporan tersebut memperkenalkan pembedaan antara TB simptomatik (symptomatic TB, sTB) dan TB asimtomatik (asymptomatic TB, aTB), yang semata-mata didasarkan pada ada atau tidaknya gejala TB yang dilaporkan saat skrining.

Gejala TB yang dilaporkan memang berkorelasi dengan tingkat keparahan penyakit. Sebagai contoh, tinjauan terhadap survei prevalensi TB nasional menunjukkan adanya hubungan berkekuatan sedang antara keluhan batuk dan hasil sputum BTA positif. Gejala yang lebih berat dan/atau menetap kemungkinan mencerminkan tingkat keparahan TB yang lebih tinggi dibandingkan gejala ringan, seperti batuk sesekali. Beberapa bukti juga menunjukkan bahwa gejala yang cukup berat hingga mendorong seseorang mencari pelayanan kesehatan dan terdiagnosis secara pasif (petugas kesehatan didatangi pasien) mungkin merupakan indikator keparahan penyakit yang lebih bermakna dibandingkan gejala yang hanya dilaporkan saat skrining aktif (petugas kesehatan mendatani pasien). Namun demikian, adanya hubungan statistik tidak cukup untuk menjadi satu-satunya dasar penggunaan gejala yang dilaporkan oleh pasien sebagai alat klasifikasi penyakit.

Meskipun berkaitan dengan tingkat keparahan penyakit, gejala yang dilaporkan pasien tidak menjadi indikator yang kuat, andal, maupun dapat digeneralisasikan untuk menentukan status penyakit. Status gejala memang menarik sebagai cara mengklasifikasikan tingkat keparahan TB karena biayanya rendah, sederhana, dan mudah diterapkan dalam skala besar. Namun, alternatif yang lebih mumpuni dan objektif untuk mengklasifikasikan status penyakit sebetulnya sering kali sudah tersedia, misalnya kuantifikasi beban kuman Mtb dalam sputum menggunakan diagnostik molekuler atau penilaian luas serta morfologi kerusakan paru pada foto rontgen dada, baik berdasarkan interpretasi radiolog maupun hasil perangkat computer-aided detection (CAD) berbasis akal imitasi.

Laporan WHO juga menimbulkan pertanyaan mengenai optimalisasi pengobatan untuk TB asimtomatik. Pengembangan rejimen yang lebih singkat, lebih mudah ditoleransi, serta pendekatan pengobatan TB yang lebih beragam sesuai kondisi pasien tentu patut disambut baik. Namun, mengingat keterbatasan gejala yang dilaporkan sebagai indikator keparahan penyakit, gejala, terutama gejala ringan, sebaiknya tidak dijadikan kriteria utama dalam menentukan siapa yang layak menerima rejimen yang kurang intensif. Sebaliknya, metode yang lebih objektif kemungkinan dapat memberikan gambaran yang lebih akurat mengenai penentuan manakah individu yang cukup diberi rejimen obat yang lebih ringan. Pendekatan ini juga akan memerlukan pedoman pengobatan yang spesifik untuk berbagai setting dan kelompok risiko, mengingat pelaporan gejala dapat sangat bervariasi antar populasi.

Pengumpulan data mengenai gejala yang dilaporkan saat skrining akan memerlukan perubahan besar pada sistem pengumpulan data di sebagian besar negara, karena saat ini data yang lebih detail umumnya baru dikumpulkan setelah diagnosis ditegakkan. Jika negara memiliki kapasitas untuk mengumpulkan data notifikasi tambahan, penambahan penilaian yang lebih objektif terkait keparahan penyakit akan lebih bermanfaat, seperti kategori semikuantitatif Xpert atau informasi mengenai apakah kasus ditemukan melalui penemuan kasus pasif atau aktif. Perbedaan tersebut kemungkinan lebih mencerminkan tingkat keparahan penyakit dibandingkan hanya berdasar pada gejala yang dilaporkan saat skrining. Pada negara yang memiliki kapasitas memadai, kombinasi indikator mikrobiologis, radiologis, dan klinis akan memberikan gambaran paling komprehensif mengenai tingkat keparahan penyakit.

Saat ini, estimasi insidens TB WHO belum membedakan antara TB asimtomatik dan TB simptomatik. Meskipun survei prevalensi menunjukkan bahwa sekitar setengah dari individu dengan TB prevalen tidak melaporkan adanya gejala, mengukur peran gejala dalam estimasi insidens jauh lebih sulit. Kesulitan ini disebabkan oleh keterbatasan data yang tersedia untuk menghasilkan estimasi yang kuat serta berbagai kelemahan penggunaan data gejala yang dilaporkan sebagai indikator status penyakit. 

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Translation © 2026 Yoseph Samodra. This text is a translated adaptation of portions of: McCreesh N, MacPherson P, Bampi JV, Engel N, Kranzer K, Khan PY. Reported tuberculosis symptoms: an inadequate classifier of disease state. Clinical Infectious Diseases. 2026 Mar 15;82(3):e589-94. Available at: https://doi.org/10.1093/cid/ciaf611.

The original article is licensed under CC BY 4.0: https://creativecommons.org/licenses/by/4.0/. Copyright in the original work remains with the original authors. This translation was prepared by Yoseph Samodra. Translation-related contributions are © Yoseph Samodra. Any translation errors are the translator’s responsibility.

Impact of Diabetes Mellitus in TB Patients on TB Transmission [TBN 088]

A longitudinal analysis evaluated whether diabetes mellitus (DM) in patients with microbiologically confirmed tuberculosis (TB) affects TB transmissibility to household contacts (HHCs) and the risk of TB disease development among exposed contacts. The study was embedded within a prospective cohort conducted between September 2009 and August 2012 across 20 districts in Lima, Peru. The investigators hypothesized that if DM increased infectiousness, household contacts of TB patients with DM would have higher rates of TB infection and might develop disease earlier than contacts of TB patients without DM.

The study systematically enrolled all newly diagnosed TB patients aged 16 years or older presenting to participating health clinics, avoiding convenience sampling. TB diagnoses were confirmed by sputum smear microscopy and mycobacterial culture. Household contacts were visited within 2 weeks of index patient diagnosis and were evaluated for TB symptoms. Baseline TB infection was assessed using the tuberculin skin test (TST), except among contacts with co-prevalent TB, prior TB disease, or a previous positive TST. Follow-up assessments occurred at 6 and 12 months. Index patients were classified as having DM based on self-reported prior diagnosis or use of hypoglycemic medication. Serum fructosamine levels were additionally measured in 1,523 randomly selected smear-positive index patients to assess recent glycemic control. The analysis included 12,767 HHCs of 3,109 microbiologically confirmed TB patients; DM status was available for 3,083 index patients, of whom 173 (5.6%) had DM.

Index TB patients with DM were more likely to be sputum smear-positive than those without DM (80.2% vs 72.5%, P = .03), suggesting potentially greater bacillary burden. However, among 4,259 child HHCs with known baseline infection status, exposure to a DM index patient was not associated with a higher prevalence of TB infection at baseline (adjusted prevalence risk ratio [aPRR] 1.05, 95% CI 0.78-1.42). Results remained similar across multiple sensitivity analyses, including alternative DM definitions based on fructosamine levels, adjustment for Mycobacterium tuberculosis lineage, restriction to older index patients, and stratification by metformin use. Among 4,812 initially uninfected HHCs, exposure to a DM index patient was not associated with increased incident TB infection during follow-up (adjusted cumulative rate ratio [aCRR] 0.85, 95% CI 0.66-1.09), and all sensitivity analyses yielded similar null findings. 

In contrast, among 12,442 HHCs free of TB disease at enrollment, 368 (3.0%) developed incident TB disease over 12 months. Contacts exposed to TB patients with DM had a substantially lower risk of developing incident TB disease than contacts exposed to TB patients without DM (aCRR 0.33, 95% CI 0.13-0.85), representing approximately a two-thirds reduction in risk. This association remained generally consistent across sensitivity analyses, including alternative DM classifications, adjustment for M. tuberculosis lineage and isoniazid preventive therapy use, and restriction to index patients aged 40 years or older. Among the subgroup of contacts exposed to DM index patients, contacts who themselves had DM showed numerically higher rates of incident TB infection (6.7% vs 2.2%) and incident TB disease (3.3% vs 0.8%) than contacts without DM, although neither comparison reached statistical significance.

TB patients with DM were more likely to be smear-positive but did not appear to transmit TB infection more frequently to household contacts. Unexpectedly, household contacts exposed to TB patients with DM had a lower risk of developing incident TB disease during follow-up. As an observational cohort study, the findings are susceptible to residual confounding and cannot establish causality. The apparent protective association for incident TB disease warrants further investigation to determine whether it reflects biological mechanisms, differences in contact patterns, treatment-related factors, or unmeasured confounding.

Source: Huang CC, Tan Q, Becerra MC, Calderon R, Contreras C, Howard NC, Lecca L, Jimenez J, Madden AE, Yataco R, Galea JT. Impact of Diabetes Mellitus in Tuberculosis (TB) Patients on TB Transmission. Clinical Infectious Diseases. 2026 May 15;82(5):829-40.

Diagnostic accuracy of CXR CAD software for detection of TB in household contacts [TBN 087]

A prospective cohort study evaluated digital chest X-ray computer-aided detection (CAD) among adult household contacts of patients with rifampicin-resistant tuberculosis (RR-TB) in Khayelitsha, South Africa. Recruitment occurred from November 2014 to September 2017, with follow-up until May 2021. The objectives were to assess the diagnostic accuracy of three CAD packages for prevalent and incident pulmonary TB, evaluate recommended CAD thresholds, and compare or combine CAD scores with blood-based biomarkers.

Eligible participants were household contacts aged 18 years or older. Pregnant participants, those already on TB treatment, and those without CAD readings were excluded. At baseline, all participants underwent symptom screening, HIV testing, physical examination, digital posterior-anterior CXR, and microbiological testing regardless of symptoms, using spontaneous and induced sputum samples processed by smear microscopy, Xpert MTB/RIF, and MGIT culture. Three CAD tools were evaluated: CAD4TBv7, qXRv3, and Lunitv3, using thresholds of 50, 0.5, and 0.15, respectively. No participants received preventive therapy, consistent with guidelines at the time. A nested subgroup of HIV-uninfected, asymptomatic participants also underwent CRP, ESR, QuantiFERON-Gold, and 3-gene RNA MTB-HR testing.

Among 483 analyzed participants, median age was 33 years, 61% were female, 23% had previous TB, and 28% were people with HIV. Median follow-up was 4.6 years. Prevalent bacteriologically confirmed TB was found in 23 participants (4.7%), and 38 of 460 participants without prevalent TB later developed incident TB (8.3%). CAD tools performed well for prevalent TB, with AUCs of 0.87 to 0.91 for all prevalent cases, but were less accurate for predicting incident TB from baseline CXR, with AUCs of 0.60 to 0.65. At recommended thresholds, sensitivity and specificity for all prevalent TB were 0.70/0.93 for CAD4TBv7, 0.57/0.94 for qXRv3, and 0.87/0.86 for Lunitv3, compared with 0.61/0.87 for human CXR reading. CAD accuracy was better in participants without previous TB. In the biomarker subgroup, CAD outperformed blood biomarkers for asymptomatic prevalent TB, and adding blood biomarkers did not significantly improve detection of prevalent or incident TB.

Overall, CAD-based CXR screening was useful for detecting prevalent TB among adult RR-TB household contacts, including asymptomatic cases, but had limited ability to predict future incident TB. Key limitations include a single high-burden setting, exclusion of children and pregnant participants, incomplete follow-up sputum rescreening, and reduced generalizability to populations receiving preventive therapy.

Source: Macpherson L, Kik SV, Quartagno M, Lakay F, Jaftha M, Yende N, Galant S, Aziz S, Daroowala R, Court R, Taliep A. Diagnostic accuracy of chest X-ray computer-aided detection software for detection of prevalent and incident tuberculosis in household contacts. Clinical Infectious Diseases. 2025 Mar 15;80(3):626-36.

Reducing Household Tuberculosis Transmission [TBN 086]

A pilot cluster-randomized controlled trial used a hybrid type 1 effectiveness-implementation design to evaluate whether a targeted respiratory bundle could reduce acquisition of Mycobacterium tuberculosis (Mtb) infection among household contacts (HHCs) of patients with pulmonary tuberculosis. The study was conducted in Santiago, Chile, between October 2021 and April 2024 across three healthcare districts comprising 44 primary healthcare clinics. Healthcare districts were randomized at the cluster level to either the intervention arm (2 districts, 25 clinics) or control arm (1 district, 19 clinics) to minimize contamination and facilitate real-world implementation.

Eligible index patients had newly diagnosed pulmonary tuberculosis confirmed by culture, acid-fast bacillus smear, or Xpert MTB/RIF Ultra PCR and had received no more than three daily doses of anti-tuberculosis therapy. Household contacts aged >5 years were invited to participate. The intervention consisted of a two-week respiratory bundle: KN95/FFP2 mask use by both patients and household contacts when sharing indoor spaces, sleeping separately for the index patient, improved ventilation through open windows, and educational materials. Controls received routine tuberculosis care. Household contacts underwent symptom screening, chest radiography, and QuantiFERON-TB Gold Plus (QFT) testing at baseline and, if initially QFT-negative, again after 12 weeks. The primary outcome was incident tuberculosis infection, defined by QFT conversion.

A total of 157 index patients and 384 household contacts were included in the analysis. Among household contacts, 32.3% had positive baseline QFT results and 67.7% were QFT-negative. Of the 216 QFT-negative contacts assigned to intervention or control groups, 179 (82.9%) completed 12-week follow-up. QFT conversion occurred in 10.8% (10/93) of controls and 12.8% (11/86) of intervention participants, yielding a risk ratio (RR) of 1.10 (95% CI, 0.71-1.71; P = .68), indicating no significant reduction in new tuberculosis infection with the intervention. In the per-protocol analysis, participants with good adherence to the respiratory bundle at both day 7 and day 14 had a QFT conversion rate of 6.7%, compared with 10.8% in controls (RR 0.69, 95% CI 0.25-1.91; P = .47), although this difference was not statistically significant. Factors independently associated with increased risk of QFT conversion included high sputum bacillary burden in index patients (adjusted RR [adjRR] 12.10, 95% CI 2.52-55.81), drug use by the index patient (adjRR 10.02, 95% CI 2.70-36.33), suboptimal treatment adherence (adjRR 3.56, 95% CI 1.17-10.74), and household contact age below 45 years (adjRR 7.56, 95% CI 1.57-35.37). The intraclass correlation coefficient for QFT conversion within households was 0.085 (95% CI 0.005-0.360).

In this pilot cluster-randomized trial, the respiratory bundle did not significantly reduce incident Mtb infection among household contacts in the intention-to-treat analysis. However, lower infection rates among participants with good adherence suggest that adherence may influence effectiveness and warrants further investigation in larger trials. Important implementation barriers included household overcrowding, limited ability to isolate index patients, family social dynamics around meals, and stigma related to tuberculosis disclosure. As a pilot study, statistical power was limited, and confidence intervals were wide. The study provides moderate-level evidence from a randomized design regarding feasibility and implementation challenges in real-world household tuberculosis prevention.

Source: Ruiz-Tagle C, Seguel R, Villarroel L, Bernales M, Vargas-García S, Pizarro A, Peña C, Neira V, García P, Allel K, Nathavitharana RR. Reducing Household Tuberculosis Transmission: A Pilot Cluster-Randomized Controlled Trial. Clinical Infectious Diseases. 2026 Feb 15;82(2):291-8.

Gendered Patterns of Suboptimal Care Engagement Among TB Patients Who “Successfully” Completed Treatment [TBN 085]

A prospective cohort study examined patterns of care engagement among adults with drug-susceptible pulmonary TB who were programmatically classified as having treatment success. The study used latent class trajectory modeling of medication refill data and was conducted from February 2021 to August 2022 in 21 government healthcare facilities in Buffalo City Metro Health District, Eastern Cape Province, South Africa.

The analysis included 548 of 657 enrolled adults (83.4%) who were classified as cured or treatment completed. Eligible participants were aged 18 years or older, spoke English or isiXhosa, lived in a participating clinic catchment area, and gave informed consent; people with extrapulmonary TB without lung involvement or drug-resistant TB were excluded. Participants completed staff-administered questionnaires on sociodemographic factors, health status, PHQ-9 depression symptoms, AUDIT alcohol use, GAD-7 anxiety symptoms, TB knowledge, attitudes, and beliefs. Refill dates, scheduled visits, treatment start dates, and outcomes were abstracted from medical records. The main outcome was cumulative missed TB medication refill days during treatment, analyzed using latent class trajectory modeling. Level of evidence: prospective observational cohort.

Among those with treatment success, median age was 38 years (IQR, 30 to 47), 67% were men, 78.3% were unemployed, 46.2% were living with HIV, 28.1% had previous TB, and 38.9% screened positive for moderate to severe depression. Three overall engagement trajectories were identified: consistent engagement (84.1%), suboptimal engagement after 2 months (7.7%), and suboptimal engagement from onset (8.2%). By treatment completion, predicted cumulative missed refill days were 9.68 (95% CI, 7.41 to 11.83), 68.42 (95% CI, 60.35 to 76.92), and 55.47 (95% CI, 48.05 to 62.66), respectively. Men had three classes, while women had two; overall suboptimal engagement was higher among men than women (16.9% vs 10.5%). Recent TB within the past 2 years was strongly associated with suboptimal engagement overall (aOR, 4.38; 95% CI, 2.29 to 8.36), among men, and among women. Among men, HIV-negative status was also associated with suboptimal from-initiation engagement (aOR, 2.72; 95% CI, 1.13 to 6.54).

In conclusion, many patients labeled as having TB treatment success still had meaningful refill delays, especially men and those with recent prior TB. Key limitations include use of refill timing as a proxy for adherence, restriction to patients classified as treatment success, and generalizability mainly to similar public-sector TB settings in South Africa.

Source: Medina-Marino A, Arua E, de Vos L, Fiphaza K, Bezuidenhout D, Ngcelwane N, Charalambous S, Daniels J. Hidden in Success: Gendered Patterns of Suboptimal Care Engagement Among Tuberculosis Patients Who “Successfully” Completed Treatment in South Africa. Clinical Infectious Diseases. 2025 Dec 19:ciaf714.

Characterizing Treatment Adherence Trajectories in the endTB Multisite Cohort of DR-TB Patients [TBN 084]

A study analyzed adherence patterns and their relationship with treatment outcomes among patients with multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB) enrolled in the endTB Observational Study, a prospective multicountry cohort conducted between April 2015 and December 2019. The study included patients treated with regimens containing at least bedaquiline and/or delamanid across 12 countries. The objective was to identify distinct adherence trajectories during treatment and assess how these trajectories were associated with unsuccessful treatment outcomes, defined as treatment failure, death, or loss to follow-up.

A total of 1,787 patients were included from an original cohort of 2,803 consenting participants. Eligible patients had started an endTB regimen after enrollment, had at least one month of adherence data, a recorded final treatment outcome, and complete covariate information. Monthly adherence was calculated as the proportion of prescribed treatment days on which all medications were taken as prescribed. Adherence data were collected through directly observed therapy (DOT), self-report, or pill counts, depending on treatment delivery. The investigators applied a joint latent class mixed model consisting of a multinomial logistic model for class membership, a class-specific linear mixed model for adherence trajectories, and a class-specific survival model for time to unsuccessful treatment outcome. The survival model adjusted for age, sex, previous TB treatment, HIV/antiretroviral therapy status, hepatitis C virus (HCV) infection, diabetes, extensive disease, low BMI, fluoroquinolone resistance, baseline regimen drugs, and study site.

The median age was 35 years (IQR 26-45), 36.9% were female, 65.0% had fluoroquinolone resistance, and 65.7% had extensive disease. Median treatment duration was 20 months, and median monthly adherence was 95.9% (IQR 88.8%-100%). Overall, 19.0% of patients experienced an unsuccessful outcome, including 7.6% deaths, 3.3% treatment failures, and 8.1% loss to follow-up. Four adherence trajectory classes were identified: "consistently high" (72.5%), "high to low" (14.3%), "low to high" (7.3%), and "consistently low" (5.9%). Median adherence ranged from 98.0% in the consistently high group to 42.1% in the consistently low group. Unsuccessful outcomes occurred in 74.3% of the consistently low group, 1.5% of the low-to-high group, and 6.8% of the consistently high group. Compared with the consistently high group, the adjusted hazard ratio (aHR) for unsuccessful outcomes was 23.2 (95% CI 15.7-24.3) in the high-to-low group and 43.2 (95% CI 26.2-71.5) in the consistently low group. The low-to-high group did not have a significantly different risk (aHR 0.7, 95% CI 0.1-3.8). Adherence trajectory classification predicted unsuccessful outcomes substantially better than conventional adherence measures, with an AUROC of 0.84 (95% CI 0.82-0.86) versus approximately 0.65 for classifications based on overall adherence rates.

Distinct longitudinal adherence trajectories were strongly associated with MDR/RR-TB treatment outcomes, and trajectory-based classification predicted unsuccessful outcomes more accurately than conventional summary adherence measures. These findings suggest that patterns of adherence over time may be more clinically informative than overall adherence percentages alone. Limitations include exclusion of several study sites because of adherence data quality concerns, reliance on adherence measures that partly used self-report or pill counts, and inclusion only of patients with complete data. As an observational cohort study, residual confounding cannot be excluded. 

Source: Law S, Fulcher I, Ashraf S, Bastard M, Docteur W, Franke MF, Guerra D, Hewison C, Huerga H, Khan M, Khan P. Characterizing Treatment Adherence Trajectories in the endTB Multisite Cohort of Drug-Resistant Tuberculosis Patients: An Application of Group-Based Trajectory Modeling. Clinical Infectious Diseases. 2026 Mar 15;82(3):e571-9.

TPT for Household Contacts at Health Facility and Community Settings in Pakistan [TBN 083]

A study assessed whether adding community-based services to fixed health facilities improved completion of the tuberculosis preventive treatment (TPT) cascade among household contacts of individuals with TB. It was a programmatic cascade analysis within the Zero TB Initiative conducted from January 2018 to March 2021 in Karachi and Peshawar, Pakistan, using 8 health facilities in Karachi, 6 in Peshawar, and community-based mobile X-ray van services that began in May 2019.

Household contacts were first invited to fixed health facilities for evaluation. After 2 phone reminders and a household visit, contacts who did not attend but were reachable were offered community-based screening near the patient’s home. All contacts evaluated at facilities or mobile vans received symptom screening, clinical evaluation, chest radiography, and Xpert MTB/RIF testing using sputum or stool samples when indicated. Contacts in whom TB disease was ruled out were offered TPT regardless of TB infection status. Contacts aged 2 years or older received weekly isoniazid–rifapentine for 12 doses (3HP), while children younger than 2 years received 6 months of daily isoniazid (6H). Completion was defined as at least 11 of 12 3HP doses within 16 weeks or about 160 6H doses within 7 months, assessed using pharmacy records and self-report. The cascade included household contact enumeration, TB evaluation, TB diagnosis, TPT eligibility, TPT initiation, and TPT completion. The program did not capture the number prescribed TPT between eligibility and initiation. Level of evidence: observational programmatic implementation evidence.

Overall, 24,369 of 28,443 household contacts (85.7%) completed clinical evaluation; 20,855 (85.6%) were evaluated at health facilities and 3,514 (14.4%) in community settings. TB was diagnosed in 612 of 24,369 evaluated contacts (2.5%). Among 23,757 TPT-eligible contacts, 14,436 (60.8%) initiated TPT, and 10,879 of those initiating treatment (75.4%) completed it. Adding community-based services increased clinical evaluation by 12.4 percentage points (95% CI, 11.7 to 13.0), treatment completion by 11.6 percentage points (95% CI, 10.6 to 12.7), and overall cascade completion by 5.9 percentage points (95% CI, 5.1 to 6.7). In Karachi, community-based services increased cascade completion by 4.6 percentage points (95% CI, 3.7 to 5.4); in Peshawar, the increase was 10.6 percentage points (95% CI, 8.9 to 12.3).

In conclusion, adding community-based screening and TPT follow-up to fixed facility services improved evaluation, treatment completion, and overall TPT cascade completion among household contacts in two Pakistani cities. Key limitations include the observational programmatic design, reliance partly on self-reported treatment completion, absence of captured data on TPT prescription, and limited generalizability beyond urban Zero TB Initiative settings with mobile X-ray capacity.

Source: Jaswal MR, Martinez L, Brooks M, Farooq S, Safdar N, Shah JA, Islam Z, Nasir K, Fareed U, Manzar S, Maniar R. Tuberculosis-Preventive Treatment for Household Contacts at Health Facility and Community Settings in Pakistan. Clinical Infectious Diseases. 2025 Jun 15;80(6):1290-2.

Preferences for TB Point-of-Care Tests among Tuberculosis-Affected Individuals [TBN 082]

The study aimed to quantify preferences among TB-affected adults for point-of-care (POC) TB tests compared with standard facility-based testing. This survey-based discrete choice experiment (DCE) was conducted from December 2022 to September 2024 in outpatient public health facilities in the Philippines, Vietnam, South Africa, Uganda, and India, with an additional community-based sample from Uganda.

Participants were adults aged 18 years or older with presumptive or confirmed TB. The analysis included 1149 participants who met data quality standards: 207 from India, 210 from the Philippines, 219 from South Africa, 305 from Uganda, and 208 from Vietnam. The DCE tested 5 diagnostic attributes: sample type, sensitivity, cost, location, and time to result. Participants completed 12 randomized choice tasks comparing 2 TB test options and stated whether they would actually use their preferred option. The study population had a median age of 42 years, 50.4% were female, 9.1% were HIV-positive, 13.1% had diabetes, and 32.7% had current or prior TB.

POC testing was preferred over standard-of-care testing when sensitivity was equal, with preference shares of 78.8% (95% CI, 77.9–79.8) for facility-based POC testing, 70.0% (95% CI, 68.5–71.5) for community-based POC testing, and 64.6% (95% CI, 62.7–66.5) for home-based POC testing. Preferences declined when POC sensitivity was lower: at 10% lower sensitivity, preference shares were 58.1%, 50.7%, and 47.8%, respectively; at 20% lower sensitivity, they were 41.9%, 36.3%, and 34.4%. Fifteen-minute POC testing was consistently preferred over same-day 3-hour testing, increasing preference shares by 8.6 to 11.9 percentage points. Fewer than 1.5% chose neither test, and sample type had little effect on preferences. Vietnam showed the strongest overall preferences, while country differences were more visible at lower accuracy levels. In Uganda, community-enrolled participants showed higher preferences for community and home testing than facility-enrolled participants.

Overall, TB-affected individuals generally preferred rapid POC TB testing, especially when accuracy matched standard testing, but willingness declined as sensitivity decreased. Key limitations include reliance on stated preferences rather than observed testing behavior and possible limits to generalizability beyond the included high-burden countries and enrollment settings. 

Source: Nalugwa T, Shah KM, Marcelo D, Nakawunde R, Trinh T, Emmanuel J, Nakaweesa A, Schraufnagel A, Andama A, Christopher DJ, Van Luong D. Predicted Preferences for Tuberculosis Point-of-Care Tests among Tuberculosis-Affected Individuals in Five High Burden Countries. Clinical Infectious Diseases. 2026 Jan 14:ciag022.