Prognostic value of CRP in adults with TB meningitis [TBN 095]

A prospective cohort study investigated whether baseline serum C-reactive protein (CRP), an inexpensive marker of systemic inflammation, predicts poor clinical outcomes in adults with tuberculous meningitis (TBM), particularly among people living with HIV. Participants were enrolled between March 2021 and November 2023 at Mulago and Kiruddu National Referral Hospitals in Kampala, Uganda. The study aimed to evaluate the prognostic value of CRP for disability or death after TBM treatment.

Adults aged 18 years or older with definite, probable, or possible TBM according to the uniform case definition were included. Microbiological confirmation was based on positive cerebrospinal fluid (CSF) Xpert MTB/RIF Ultra or mycobacterial culture. Participants presenting within 3 months of antiretroviral therapy initiation were classified as having unmasking immune reconstitution inflammatory syndrome (IRIS). All participants were enrolled through the HARVEST phase 3 randomized clinical trial, which compared high-dose rifampicin (35 mg/kg/day) with standard-dose rifampicin (10 mg/kg/day) for 8 weeks. All patients received dexamethasone starting at 0.4 mg/kg/day with tapering over 6 weeks. Baseline serum CRP was measured, typically within 24 hours of diagnostic lumbar puncture, using a Cobas c311 clinical chemistry analyzer. The primary outcome was poor neurological outcome, defined as a modified Rankin Scale (mRS) score of 4 or greater at 8 weeks.

Among 178 enrolled adults with TBM, 135 (75.8%) had both baseline CRP measurements and 8-week outcome data available for analysis. The median age was 36 years (IQR, 30 to 42), 46% were female, and 83% were living with HIV, with a median CD4 count of 79 cells/μL (IQR, 38 to 177). Altered mental status at presentation was common, occurring in 76% of participants. As a continuous predictor, baseline CRP demonstrated moderate discrimination for poor outcome, with an area under the receiver operating characteristic curve (AUC) of 0.70 (95% CI, 0.61 to 0.79), improving to 0.76 (95% CI, 0.68 to 0.84) after adjustment for rifampicin dose, TBM diagnostic certainty, Medical Research Council (MRC) severity grade, and HIV status. A CRP threshold of 40 mg/L provided the best balance between sensitivity (66%) and specificity (64%) for predicting mRS ≥4 at 8 weeks. Severe TBM (MRC grade 3) was more common among participants with CRP ≥40 mg/L than among those with lower CRP levels (33% vs 9%). Among participants with poor outcomes (mRS ≥4), 61.2% had baseline CRP ≥40 mg/L compared with 30.9% among those with better outcomes (mRS ≤3). Baseline CRP ≥40 mg/L was associated with a more than threefold increase in the odds of disability or death at 8 weeks (unadjusted OR, 3.53; 95% CI, 1.73 to 7.19; P < .001). This association remained significant after adjustment for potential confounders (adjusted OR, 2.78; 95% CI, 1.28 to 6.04; P = .010). The association did not differ significantly according to TBM diagnostic certainty or suspected unmasking TBM-IRIS status.

Elevated baseline serum CRP was independently associated with a substantially increased risk of disability or death at 8 weeks among adults with TBM, supporting its potential role as a low-cost prognostic biomarker. As an observational cohort analysis nested within a randomized clinical trial, the study provides moderate-level evidence for prognostic utility but does not establish causality. Important limitations include the relatively small sample size, missing CRP or outcome data in a subset of enrolled participants, and restriction to Ugandan referral hospitals, which may limit generalizability to other settings.

Source: Tugume L, Cresswell FV, Engen NW, Tukundane A, Kimuda S, Mugabi T, Namombwe S, Kagimu E, Kabahubya M, Ellis J, Bahr NC. Prognostic value of C-reactive protein in adults with tuberculous meningitis: a prospective cohort study. Clinical Infectious Diseases. 2025 Nov 15;81(5):e410-3.

Stool processing methods for Xpert ultra testing in childhood TB [TBN 094]

A prospective multicountry diagnostic accuracy study evaluated and compared three stool processing methods for Xpert MTB/RIF Ultra (Xpert Ultra) testing in children with presumed pulmonary tuberculosis (TB): the Simple Processing Kit (SPK), the Stool Optimization and Standardization (SOS) method, and the Optimized Sucrose Flotation (OSF) method. Children younger than 15 years were consecutively enrolled between June 2019 and March 2021 from tertiary hospitals and referral networks in India, South Africa, and Uganda. The study also assessed laboratory staff perceptions of the acceptability and usability of these stool processing approaches.

A total of 607 children were included. Eligible participants had microbiologically confirmed TB or at least one symptom suggestive of pulmonary TB, including prolonged cough, fever, failure to thrive, weight loss, or a chest radiograph consistent with TB. Children who had received anti-TB treatment for more than 72 hours were excluded. All participants underwent standardized TB evaluation including clinical assessment, chest radiography, and respiratory specimen collection. Respiratory samples were tested with Xpert Ultra and mycobacterial culture. Stool specimens were collected, processed within 72 hours, and tested using one or more of the three stool processing methods. Confirmed TB was defined by positive sputum Xpert Ultra or culture. Stool Xpert Ultra results were excluded from case classification. Laboratory personnel processing stool samples completed anonymous surveys evaluating usability and acceptability.

Among the 607 children, 61.1% were enrolled in Uganda, 60.5% were younger than 5 years, 50.7% were underweight, and 15.5% were living with HIV. Confirmed TB was diagnosed in 147 children (24.2%), and 92.5% of these cases were sputum Xpert Ultra positive. The proportion of valid stool test results was similar across methods, ranging from 87.4% for OSF to 90.3% for SPK. Positive stool Xpert Ultra results ranged from 9.3% (OSF) to 11.2% (SOS). Against the microbiological reference standard (MRS), all methods showed high specificity (97.1% to 98.2%) but modest sensitivity: 36.9% for SPK, 38.6% for SOS, and 31.3% for OSF. Sensitivities were substantially higher among children with higher sputum bacillary burden, reaching 95.8% to 100% when sputum Xpert Ultra semiquantitative results were low or higher, compared with only 16.7% to 22.6% among children with trace or very low sputum results (P < .001). 

Among the 179 children tested with all three methods, diagnostic performance was similar, with overlapping 95% confidence intervals. Compared with sputum culture, sputum Xpert Ultra sensitivity was 82.4% (95% CI, 56.6% to 96.2%), higher than stool Xpert Ultra, although the difference was not statistically significant. Combining stool and sputum testing increased sensitivity by 17.6% to 23.5% compared with stool testing alone, while adding stool testing to sputum Xpert Ultra increased sensitivity by up to 11.8% at the expense of a small reduction in specificity (2.1% to 2.9%). Survey responses from 17 laboratory staff indicated that all methods were acceptable and perceived as beneficial. SOS was viewed as the least time-consuming method, and 75% of respondents believed it could be performed by nonlaboratory staff in peripheral facilities.

The three stool processing methods demonstrated similar diagnostic accuracy, characterized by high specificity but limited sensitivity for childhood pulmonary TB. The SOS method appeared most favorable operationally because of its ease of use and lower time requirements. Key limitations include incomplete testing of all children with all three methods, variation in method implementation over time, and reliance on a microbiological reference standard that may miss pediatric TB cases. As a prospective multicountry diagnostic accuracy study, the evidence supports stool Xpert Ultra as a useful noninvasive adjunct to respiratory testing, particularly in settings where sputum collection is challenging.

Source: Jaganath D, Nabeta P, Nicol MP, Castro R, Wambi P, Zar HJ, Workman L, Lodha R, Singh UB, Bavdekar A, Sanghavi S. Stool processing methods for Xpert ultra testing in childhood tuberculosis: a prospective, multicountry accuracy study. Clinical Infectious Diseases. 2026 Mar 15;82(3):526-34.

Long-term mortality trends among individuals with TB in Brazil [TBN 093]

A study examined excess mortality among people diagnosed with tuberculosis (TB) in Brazil and assessed how mortality during the TB episode and the post-TB period contributed to long-term mortality. Using a retrospective population-based cohort design, investigators linked TB notifications from Brazil’s National Notifiable Disease Information System (SINAN) with mortality records from the Mortality Information System (SIM) for 2007–2016. The objective was to compare mortality among individuals with TB against the general population and evaluate how causes of death evolved over time after TB diagnosis.

The analysis included 834,594 individuals with TB after excluding records with postmortem diagnoses, revised non-TB diagnoses, missing demographic information, and individuals aged 90 years or older. Participants contributed 4,089,883 person-years of follow-up, with a mean follow-up of 4.9 years. Deaths were identified through linked mortality records and categorized into 11 cause-of-death groups based on ICD-10 codes. The primary outcome was mortality rate ratios (MRRs) comparing the TB cohort with the general population by year since diagnosis. The TB episode was defined as the first 12 months after diagnosis, while follow-up beyond 12 months was considered the post-TB period. Analyses were stratified by age, sex, and region, and adjusted MRRs (aMRRs) were estimated for risk factors associated with mortality.

Among 834,594 individuals, 120,330 deaths occurred during follow-up (14.4%). Mortality was markedly elevated during the first year after TB diagnosis (MRR 11.28, 95% CI 11.18–11.37) and declined over time but remained above that of the general population even 10 years later (MRR 1.46, 95% CI 1.34–1.59). During the TB episode, mortality was highest among individuals aged 30–44 years (MRR 24.97, 95% CI 24.59–25.33) and lowest among those aged 75–89 years (MRR 4.04, 95% CI 3.94–4.15). HIV infection was the strongest predictor of mortality during the TB episode (aMRR 5.16, 95% CI 5.05–5.27). Other factors associated with higher mortality included female sex (aMRR 1.67, 95% CI 1.64–1.70), combined pulmonary and extrapulmonary TB (aMRR 1.57, 95% CI 1.52–1.62), and abnormal chest X-ray findings (aMRR 1.77, 95% CI 1.65–1.89). During the post-TB period, elevated mortality remained associated with HIV infection (aMRR 2.80, 95% CI 2.73–2.87), treatment reinitiation after abandonment (aMRR 1.78, 95% CI 1.74–1.84), alcohol use disorder (aMRR 1.52, 95% CI 1.49–1.55), female sex (aMRR 1.41, 95% CI 1.38–1.43), treatment loss to follow-up, and drug-resistant TB requiring regimen changes (aMRR 1.65, 95% CI 1.53–1.77). Excess mortality accumulated substantially over time. At 1 year, cumulative mortality was 6.82% in the TB cohort versus 0.70% in the general population, yielding 6.12% excess mortality. By year 10, cumulative mortality reached 17.88% versus 7.97%, corresponding to 9.90% excess mortality, of which 5.22% occurred during the post-TB period. Causes of death shifted over time. In the first year, TB (31.3%) and HIV (23.9%) were the leading causes of death. By year 10, respiratory disease (16.3%), cardiovascular disease (16.1%), and cancer (13.3%) became the predominant causes.

The findings indicate that TB is associated with substantial excess mortality that persists for at least a decade after diagnosis, with more than half of total excess mortality occurring after completion of the initial TB episode. This large national cohort provides strong observational evidence, although causal inference is limited by its retrospective design and reliance on routinely collected administrative data. The results suggest that long-term follow-up and management of chronic comorbidities may be important components of care for TB survivors.

Source: Kim S, Pelissari DM, Harada LO, Sanchez M, Oliveira PB, Johansen FD, Maciel EL, Cohen T, Castro MC, Menzies NA. Long-term mortality trends among individuals with tuberculosis: a retrospective cohort study of individuals diagnosed with tuberculosis in Brazil. Clinical Infectious Diseases. 2026 Jan 15;82(1):e1-8.

A point-of-care prediction tool for recurrent tuberculosis [TBN 092]

A study aimed to develop and validate a simple prediction model for recurrent tuberculosis (TB) that could be used at treatment completion by outreach workers to identify TB survivors at highest risk for recurrence in resource-limited, high-burden settings. The analysis used data from the TB Aftermath noninferiority trial conducted in Maharashtra, India. Participants were enrolled between January 2021 and October 2023, and follow-up data through October 2024 were analyzed.

The TB Aftermath trial enrolled 1,076 adults (≥18 years) who had completed or been cured of TB according to India's National TB Elimination Programme (NTEP) definitions. Individuals with pulmonary and/or extrapulmonary TB were eligible regardless of treatment regimen. Participants entered the study within 60 days of treatment completion and were randomized to phone-based or home-based symptom screening at 6 and 12 months after treatment. All participants also received an 18-month home visit. For this analysis, investigators included participants with at least 12 months of follow-up or those who experienced an outcome. Individuals lost to follow-up within 12 months and those who died without documented TB recurrence were excluded. The primary outcome was recurrent TB diagnosed within 18 months of treatment completion, including both microbiologically confirmed and clinically confirmed recurrences. Candidate predictors were evaluated using exploratory analyses and LASSO regression, followed by model development and validation using separate training (60%) and validation (40%) datasets.

Among 1,033 eligible TB survivors, 85 (8.2%) experienced recurrent TB within 18 months. Of these recurrences, 52 (61%) were microbiologically confirmed and 64 (75%) involved pulmonary disease. The median participant age was 35 years (IQR 27-48), 52% were male, and the median BMI was 19.9 kg/m² (IQR 17.6-23.2). Nine predictors were shortlisted: sex, household income, biomass fuel exposure, BMI, unhealthy alcohol use (AUDIT), smoking history, peak expiratory flow (PEF), disease site, and history of more than one TB episode. The highest-performing and most practical models contained five variables. Several five-item models demonstrated moderate discrimination, all including BMI and PEF. The selected model consisted of sex, household income, BMI, PEF, and history of more than one TB episode, achieving a cross-validated c-statistic of 0.69 (95% CI 0.56-0.83). Model calibration in the validation set was acceptable (Hosmer-Lemeshow P=.053; calibration intercept 0.03, 95% CI -0.03 to 0.09; slope 0.66, 95% CI 0.08-1.24). Performance did not differ significantly between early and late recurrence. Sensitivity analyses, including complete-case analyses and analyses restricted to microbiologically confirmed recurrence, identified the same five predictors and supported the robustness of the model.

The study concluded that a parsimonious five-item model using routinely obtainable characteristics can moderately predict TB recurrence after treatment completion among TB survivors in India. As a prediction-model development and validation study, the level of evidence is moderate. Limitations include modest discriminatory performance, relatively low recurrence event numbers, missing and poor-quality PEF measurements, and potential limitations in generalizability beyond similar high-burden public-sector settings. 

Source: Cox SR, Moe AH, Gupte AN, Kadam A, Valawalkar S, Gupte N, Lele G, Kendall EA, Baillie C, Barthwal MS, Kakrani A. A point-of-care prediction tool for recurrent tuberculosis. Clinical Infectious Diseases. 2025 Dec 15;81(6):e612-22.

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.