Access to bedaqualine, pretomanid, linezolid and moxifloxacin (BPaLM) for multidrug-resistant tuberculosis is limited in children <14 years old by insufficient pharmacokinetic/dosing data for pretomanid. Therapeutic drug monitoring of pretomanid at steady state in an 11-year-old, 39 kg child provides useful clinical data and exemplifies the potential for TDM to facilitate access to BPaLM for select younger children.
Purpose:Presumptive tuberculosis refers to individuals who presents with symptoms or signs of suggestive active TB having at least one of these clinical manifestations (more than two weeks of, cough, fever, appetite loss, night sweating, chest pain, or weight loss). Although tuberculosis is both preventable and curable, it continues to cause millions of new infections and fatalities globally. With a national burden that ranks third in Africa and eighth globally, Ethiopia remains a high-burden country for tuberculosis. Tigray had 6700 confirmed tuberculosis cases in 2020, immediately before the war had started. War is an ideal condition for the spread of TB. This has happened in Tigray following the war. Therefore, this study aimed to assess a community-based presumptive tuberculosis among rural and urban residents after the conflict in Tigray region of Ethiopia. Methods:A community-based comparative cross-sectional study design was conducted from January to February 2024 for a total of 2340 participants selected using the multistage cluster sample technique. The data was collected using an open data kit and then exported to SPSS version 23 for analysis. Logistic regression, both bivariate and multivariable analysis, was used to see the association between independent and dependent variables. Findings:The overall prevalence of presumptive tuberculosis was found 10.6% (95% CI: 8.4%,13%), with a slight difference burden between the rural and urban, 12.3% (95% CI, 10.8%, 14%) and 11.8% (10.6%, 13.1%), respectively. Different factors, like inadequate ventilation, sleeping with hunger, close contact with known TB patients, and households unvisited by health extension workers were significantly associated with presumptive tuberculosis. Conclusion:Given the conflict and the region's destroyed medical infrastructure, this finding might help in identifying those who likely have active tuberculosis. Therefore, improving access to TB screening and diagnostic services closer to the communities throughout the region is critically important during post-war to address the burden of tuberculosis.
Background:Pulmonary tuberculosis (PTB) remains a major cause of infectious-disease mortality worldwide. Host metabolic status may shape treatment response, but whether hepatic steatosis affects sputum smear conversion in PTB remains poorly defined. Methods:We performed a retrospective single-center cohort study including newly diagnosed, smear-positive PTB patients treated at Taizhou People's Hospital between January 2022 and December 2025. Patients were classified according to sputum smear conversion status, with delayed conversion defined as persistent smear positivity beyond 8 weeks after initiation of standard anti-tuberculosis therapy. Baseline demographic, clinical, ultrasonographic, laboratory, and cytokine data were collected and compared between groups. Potential factors associated with delayed conversion were evaluated using correlation analysis, multicollinearity assessment, change-in-estimate confounder analysis with the R package chest, and multivariable logistic regression. Results:Clinical screening identified 11 candidate factors. After prioritisation by clinical relevance, correlation structure, collinearity and confounding assessment, six factors were entered into the multivariable model. Hepatic steatosis and IL-18 were positively associated with delayed smear conversion (hepatic steatosis: β = 2.401, OR = 11.036, 95% CI = 2.489-48.934; IL-18: β = 2.396, OR = 10.984, 95% CI = 1.832-65.862). By contrast, T-SPOT positivity was inversely associated with delayed smear conversion (β = -4.199, OR = 0.015, 95% CI = 0.001-0.172). Conclusions:Hepatic steatosis was independently associated with delayed smear conversion in PTB. Baseline cytokine profiles, including IL-6 and IL-18, also differed according to treatment response. These findings suggest that PTB patients with hepatic steatosis may benefit from closer monitoring of treatment response during anti-tuberculosis therapy.
Background:Globally, one-in-two childhood tuberculosis (TB) case remains undiagnosed, and TB remains a leading cause of death among children under 15 years despite favorable treatment outcomes. This study assessed trends in case notification and outcomes among children with TB across ten regions of Tanzania. Methods:We conducted a retrospective cross-sectional study using data from Tanzania's national electronic TB and Leprosy System for children diagnosed between 2018 and 2023. Mann-Kendall Tests were used to assess the existence of monotonic trends in TB notifications, and distribution of outcomes was analyzed using Wilcoxon rank-sum test or Pearson's Chi-squared test, and binary logistic regression at a 5% significance level. Results:25,449 childhood TB cases were notified over six-year period, with 14.4% (n = 3667) HIV/TB co-infected. Case notifications increased from 2688 in 2018 to a peak of 5421 in 2022 then declined to 4493 in 2023 (p = 0.047). Significant differences in unfavorable treatment outcomes were observed between pre- and post-COVID-19 periods (OR 0.52, 95% CI 0.44-0.60). TB/HIV co-infection cases declined from 28.5% (n = 766) in 2018 to 8.9% (n = 400) in 2023 (p = 0.002), while HIV-negative cases rose markedly (p = 0.027). Overall, 97.2% of children achieved favorable outcomes. Unfavorable outcomes were common among children who were HIV/TB co-infected, under five years, and 10-15 years. Conclusion:Childhood TB case notifications increased significantly from 2018 to 2023, indicating improved detection, though with notable regional and HIV-related disparities. Treatment outcomes were generally favorable. HIV-positive children and older age groups faced higher risks of unfavorable outcomes. Targeted interventions are needed to address disparities in case detection and treatment success.
Background:Tuberculosis (TB) remains a major global health challenge, particularly in low-income settings where structural inequities hinder early diagnosis and care. Ethiopia, one of the 30 high TB-burden countries, continues to experience marked geographic disparities. Understanding knowledge, attitudes, and practices (KAP) among affected populations is essential to inform context-specific interventions supporting the End TB Strategy. Methods:A cross-sectional KAP survey was conducted in Woliso District (Oromia Region, Ethiopia) between April 2023 and December 2024, including 152 TB index cases and 326 household contacts. A structured, interviewer-administered questionnaire assessed knowledge of TB symptoms, transmission, diagnosis, and perceived barriers to care. Categorical variables were compared using Chi-square or Fisher's exact test, and continuous variables with Mann-Whitney test. Results:Among 478 participants (median age 28 years [IQR 19-40]; 44.1% female), 69.5% lived in rural areas. The main barriers to timely diagnosis were absence of nearby TB diagnostic facilities (13.4%), poor road conditions (6.3%), health system delays (5.9%), and financial constraints for transportation (3.8%). Poor roads and transport costs were reported more often by rural residents (p < 0.05), while absence of nearby TB diagnostic facilities was reported most often by index cases and older subjects (p < 0.05). Recognition of cough lasting >2 weeks (84.3%) and night sweats (65.7%) was common, while hemoptysis (49.6%) and fever (16.1%) were less recognized. Awareness of sputum and X-ray diagnostics was 87.2%, higher among index cases (95.4% vs. 83.4%, p = 0.0005). Although 77.0% considered TB life-threatening, 52.2% believed it was transmissible only through close or bed-sharing contact (p < 0.0001 for rural vs. urban). Older age correlated with better knowledge across most domains (all p < 0.01). Overall, subjects living in rural area had higher scores about barriers for accessing TB care (p = 0.0004) and attitude on TB (p = 0.01), and lower score about knowledge on TB (p = 0.002). Conclusions:While TB knowledge and attitudes were generally high, misconceptions about transmission and persistent structural barriers hinder access to timely diagnosis and care. Expanding community-based diagnostic capacity, improving rural infrastructure, and integrating social protection strategies are key to advancing Ethiopia's progress toward End TB targets.
Background The intricate interplay of biological factors, living conditions, behaviors, co-morbidities like diabetes and HIV influences tuberculosis (TB) risk. In this study, those critical factors were identified to address gaps in understanding and improve prevention strategies. Methods A cross-sectional study was conducted across three zones to identify key risk factors for active TB. Diagnosis was based on smear microscopy, GeneXpert, clinical evaluation, and X-ray findings. A multistage sampling method was used, with a target of 384 participants from each zone, but due to inconsistencies, 410 were consecutively enrolled: 358 (87.3%) from Bench-Sheko, 23 (5.6%) from Sheka, and 29 (7.1%) from Kaffa.Data were collected through structured interviews and record reviews from December 2018 to June 2020 and analyzed using Stata. Results The study included 410 TB patients (55% male, mean age 27.7 ± 11.4 yrs.). Most (99.3%) were newly diagnosed, with PTB (80%), EPTB (19.3%), and both (0.7%). Concrete housing raised PTB (OR = 37.92) and lowered EPTB (OR = 0.03). Corrugated housing raised PTB (OR = 2.04) and lowered EPTB (OR = 0.491). Houses with 1-3 windows lowered PTB, raised EPTB. Separate bedrooms raised PTB (24.2%) and lowered EPTB (19.5%). Charcoal use lowered PTB (81.4%) and raised EPTB (OR = 5.39). Gas, electricity, and cohabitation reduced PTB odds (OR = 0.40, OR = 0.05, OR = 0.450) but increased EPTB odds (OR = 2.50, OR = 21.1, OR = 2.22, respectively). Raw milk reduced PTB odds (OR = 0.51) and increased EPTB odds (OR = 1.96, both p = 0.02). Alcohol raised PTB odds (OR = 4.44, p = 0.00) and lowered EPTB odds (OR = 0.23, p = 0.00). Awareness of transmission increased PTB odds (OR = 2.72, p = 0.05) and reduced EPTB odds (OR = 0.37, p = 0.05). HIV/AIDS increased PTB odds (OR = 1.78) and reduced EPTB odds (OR = 0.56). Coinfections raised PTB odds (OR = 1.36), lowered EPTB odds (OR = 0.73). Conclusions The findings revealed that housing, environment, and lifestyle influenced PTB and EPTB risks, with mixed and contrasting effects, highlighting the need for targeted interventions.
Lung ultrasound (LUS) is increasingly used as a diagnostic tool in respiratory medicine, particularly in resource-limited, tuberculosis (TB)-endemic settings. Sonographic interstitial syndrome (IS), characterized by B-line artefacts, has proven valuable in diagnosing cardiogenic pulmonary edema, pneumonia, and chronic interstitial lung disease. However, in TB-endemic areas, its interpretation remains challenging due to overlapping pathologies. This illustrated review explores the diagnostic and prognostic relevance of IS across three clinical contexts: acute respiratory distress, chronic interstitial lung disease, and pulmonary TB. We review current evidence and discuss illustrative cases from TB-endemic settings to highlight sonographic pattern variations and guide clinicians in recognizing key diagnostic features and common pitfalls. IS, while inherently non-specific, gains diagnostic value when contextualized within the patient's background and within additional sonographic findings such as pleural line abnormalities, consolidations, and altered lung sliding. Specific TB manifestations—including miliary TB, cavitary TB, HIV-associated TB, and post-TB sequelae—demonstrate diverse IS presentations. Accurate interpretation requires understanding disease-specific patterns, using appropriate scanning techniques, and adhering to standardized protocols. Greater awareness of IS variations among clinicians can improve diagnostic accuracy and clinical decision-making in TB-endemic regions.
Background:Diagnosis of pulmonary tuberculosis (PTB) among people living with HIV (PLHIV) remains challenging, particularly in high TB/HIV burden settings. We evaluated serum biomarkers associated with active PTB and their relationship with TB-related clinical characteristics among hospitalized PLHIV in Uganda. Methods:We analysed archived serum samples from adult PLHIV (n = 60) categorized into three groups (20 each): (i) sputum culture and/or GeneXpert-confirmed PTB (active PTB), (ii) presumptive TB with negative TB culture/GeneXpert (symptomatic PTB-negative), and (iii) asymptomatic PLHIV attending routine HIV care (asymptomatic PLHIV controls). Inflammatory biomarkers including C-reactive protein (CRP) and leptin as well as immune activation markers (interferon gamma-induced protein 10 -IP-10 and β2-microglobulin) were quantified using enzyme-linked immunosorbent assay and Bio-Plex Pro assays. Biomarker levels were compared between active PTB and TB-negative groups. Logistic regression identified biomarkers independent associations with active PTB and Spearman rank correlation assessed biomarkers correlations with TB-related clinical characteristics among active PTB participants. Results:Median serum concentrations of IP-10 (19,566 pg/mL; p = 0.001), β2-microglobulin (33.9 ng/mL; p = 0.023), and CRP (1.77 mg/dL; p = 0.05) were significantly higher among active PTB participants compared to symptomatic PTB-negatives and asymptomatic PLHIV controls. Conversely, leptin levels were significantly lower in the active PTB (35.0 pg/mL) than in asymptomatic PLHIV controls (102.4 pg /mL; p = 0.001). IP-10 (adjusted odds ratio-aOR 2.74; 95% CI: 1.54-4.88; p < 0.001) and β2-microglobulin (aOR 2.09; 95% CI: 1.13-3.86; p = 0.019) were the strongest independent predictors of active PTB. Biomarker concentrations did not correlate significantly with TB-related clinical characteristics. Conclusion:IP-10, β2-microglobulin, and CRP were elevated in PLHIV with active PTB, whereas leptin levels were reduced. These biomarkers did not correlate with clinical characteristics. Our findings show that serum biomarkers may aid in identifying PTB among hospitalized PLHIV but with limited value in assessing clinical presentation. Further research is warranted to rigorously evaluate their diagnostic performance in both simple and combined biomarkers models and to evaluate their point-of-care utility for TB screening and timely treatment initiation in hospitalized PLHIV.
Tuberculosis (TB) remains a major public health challenge in Somalia, where conflict, displacement, delayed diagnosis, and fragile healthcare systems sustain ongoing transmission. While existing TB control efforts largely emphasize household and healthcare-associated exposure, the role of overcrowded public transport systems has received limited attention. In rapidly urbanizing Somali cities, particularly Mogadishu, minibuses and shared taxis represent enclosed, poorly ventilated, high-turnover environments that may facilitate airborne transmission of Mycobacterium tuberculosis. Evidence from high-burden settings demonstrates that public transport can function as a significant transmission setting because of prolonged close contact and inadequate airflow. Somalia's low case detection rates and frequent delays in treatment initiation further increase the likelihood that infectious individuals continue using crowded transport networks during active disease. This letter argues that public transport should be recognized as a neglected but modifiable determinant of TB transmission in Somalia. Integrating transport-focused interventions into national TB strategies, including awareness campaigns, community-based active case finding, improved ventilation practices, and mobility-informed surveillance, could provide a practical and context-appropriate opportunity to reduce transmission. Addressing public transport as a mobile transmission environment may strengthen TB control efforts and contribute to reducing the burden of disease in Somalia's fragile urban settings.
Introduction:In resource-limited settings, access to CD4 lymphocyte counts for prognostication in HIV-associated tuberculosis (HIV-TB) remains limited. Tuberculin skin test (TST) reactivity reflects cell-mediated immunity and may serve as a simple surrogate prognostic marker. This study evaluated the association between tuberculin responsiveness and clinical outcomes in hospitalized HIV-infected patients with pulmonary tuberculosis. Materials and Methods:A hospital-based observational cohort study was conducted among 107 HIV-positive adults admitted with pulmonary tuberculosis. Tuberculin reactivity was assessed using the Mantoux method with 10 TU purified protein derivative. Nutritional status was assessed using body mass index (BMI). The primary outcome was clinical status at hospital discharge. A parallel cohort of 100 HIV-negative pulmonary tuberculosis patients was evaluated using identical methods. Results:Among HIV-positive patients, 33 (30.8%) demonstrated TST induration >10 mm; all had mild-moderate undernutrition and were discharged alive within six weeks. Twenty-six patients (24.3%) had induration 5-10 mm; all were severely undernourished, with 23.1% mortality. Forty-eight patients (44.9%) were anergic or had induration <5 mm; 62.5% died and 25.0% left moribund. Increasing induration showed a graded inverse association with mortality (p < 0.001). HIV-negative patients demonstrated substantially lower overall mortality (3% vs 33.6%). While preserved TST reactivity (>10 mm) predicted 100% survival in both groups, anergy carried dramatically different implications: 5.7% mortality in HIV-negative versus 62.5% in HIV-positive patients. Conclusions:Tuberculin reactivity demonstrated a strong, HIV-specific graded association with outcomes. TST may retain adjunctive prognostic value in resource-limited settings where advanced immunological testing is unavailable.
Background Identifying real-time factors influencing adherence to Tuberculosis (TB) treatment is critical for informing treatment support interventions. Studies often use methods prone to recall bias, failing to capture objective real-time adherence-related factors. Objective To develop and test the functionality of an integrated medication event monitoring system and modified ecological momentary assessment (MEMS-mEMA) technology platform to collect real-time data on factors influencing daily dosing of drug-susceptible TB treatment. Methods We developed backend technology integrating a medication event monitoring (MEM) device with REDCap to deliver electronic surveys. System functionality was tested among individuals initiating TB treatment who received a Wisepill MEM device to store medication and capture dosing data, using device openings as a proxy for medication intake. Modified EMA (mEMA) surveys were administered randomly once every rolling seven days, and when the MEM device was not opened. In-depth interviews, followed by rapid qualitative analysis, were conducted to capture user experiences. Device openings and the total number of EMA surveys delivered and completed, including response rates, were presented. Results We successfully developed and tested the MEMS-mEMA system for collecting data on factors influencing TB treatment adherence. Ten adults newly initiating TB treatment participated in a pilot study for two months (male = 7; female = 3); mean age = 37 years (SD ±13.1), 50% living with TB/HIV coinfection. The median number of days the MEM device was opened during the two-month intensive treatment phase was 61 days. Participants demonstrated good comprehension of study requirements and did not report major challenges responding to surveys. Conclusions Findings suggest that this novel platform can collect real-time data on factors influencing TB treatment adherence for a larger feasibility study to inform intervention development in South Africa.
Background: Tuberculosis (TB) remains a leading cause of global mortality. Current tools for monitoring therapeutic efficacy are suboptimal, creating an urgent need for novel strategies. While emerging evidence suggests that immune biomarkers could fill this gap, our understanding of antibody dynamics during TB treatment remains limited. Beyond neutralization, antibodies play a critical role in the immune response by modulating inflammation and mediating the clearance of infected cells. Methods: In a longitudinal cohort of active TB patients, we analyzed Ag85A-specific antibody-dependent cellular cytotoxicity (ADCC) and perforin-expressing NK cells via flow cytometry. Ag85A-specific IgG subclasses were measured by ELISA to correlate humoral architecture with cytotoxic potency. Results: The analysis revealed a significant increase in Ag85A-specific antibodies capable of mediating cytotoxic activity, which was associated with elevated levels of NK cells producing perforin upon treatment completion. Furthermore, ADCC activity correlates with Mtb-specific IgG subclasses and treatment time duration. Notably, a longitudinal decline in Ag85A-specific IgG3 levels emerged as a distinct signature of bacterial clearance and clinical resolution, suggesting a transition from acute inflammatory responses toward a resolved immune profile characterized by sustained cytotoxic potential. Conclusions: Clinical resolution of TB is characterized by the potentiation of the ADCC-NK cell axis. The reduction in IgG3 levels reflects a shifting inflammatory milieu, while enhanced cellular cytotoxicity serves as a primary immunological hallmark and a potential biomarker for treatment monitoring.
This study presents the first comprehensive bibliometric analysis of scientific publications in the field of the private sector's role in tuberculosis detection and diagnosis from 1964 to 2025. Using PRISMA, data were extracted from Scopus and Web of Science, yielding 616 original research articles published in 224 journals. Bibliometric performance analysis was done using Pivot Tables. Keyword co-occurrence analysis was performed using VOSviewer software to identify thematic structures. The results reveal a steady increase in publication activity since the early 2000s, reflecting growing recognition of the private sector as a critical actor in tuberculosis control. Analysis of the ten most cited articles revealed four recurring issues: suboptimal quality of care, diagnostic delays, high financial burdens on patients, and the critical need for structured public-private collaboration. The co-occurrence analysis identified five main thematic clusters. The largest cluster, "Delays and Catastrophic Costs," highlights persistent diagnostic delays, high costs, and fragmented care within the private sector. The clusters, "Diagnostic Challenges in Private Practice" and "Case Detection and Private Practitioners", further underscore deficiencies in diagnostic quality and coordination. Conversely, the clusters, "Public-Private Mix" and "Diagnostics and Private Providers", demonstrate the sector's potential to expand diagnostic coverage, enhance case notification, and reduce the burden on public facilities when effective collaboration and regulatory oversight exist. Despite encouraging progress being made, we identified gaps, particularly regarding regulatory mechanisms, cost-effectiveness evaluation, and data standardisation. Strengthening governance, integrating innovative diagnostics, and incentivising quality assurance are future research directions to fully harness the private sector's contribution to ending the tuberculosis epidemic.
We present the case of a 34-year-old Polish man with a history of axial spondyloarthritis and Crohn's disease, who presented with respiratory and neurological symptoms whilst on TNF-α inhibitors treatment. He subsequently developed a fulminant pulmonary tuberculosis (TB) with cerebral involvement. Treatment was complicated by a paradoxical reaction and respiratory failure requiring intensive care admission. This case highlights the diagnostic challenges associated with TB screening prior to immunosuppressive therapy and underscores the limitations of single-test screening protocols. It further emphasizes that, in immunocompromised patients, both IGRA and TST have reduced sensitivity, and a dual testing strategy with repeated, risk-based screening may improve detection in selected high-risk populations.This case also demonstrates that tuberculosis in immunosuppressed patients can follow a fulminant course, and that early detection and timely initiation of appropriate therapy are essential determinants of clinical outcome.
Objectives:The BACES model, developed in South Korea, predicts all-cause mortality in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) using BMI, age, cavitary disease, erythrocyte sedimentation rate, and male sex. The total score categorizes patients into low, intermediate, or high mortality risk groups. We evaluated the performance of BACES in a Dutch cohort of patients with NTM-PD. Methods:This retrospective analysis included adults with NTM-PD between January 2008 and August 2019. Time to all-cause mortality was calculated from diagnosis. Performance of the original and modified BACES models were assessed using Kaplan-Meier curves, Harrell's C-statistic, and calibration curves. Cox regression identified independent mortality predictors. Results:We enrolled 183 patients (median age 63 years, 56% female), of whom 86.3% received antimycobacterial therapy. The median (IQR) follow-up time was 6.3 years (3.7-9.0) with 54.1% deaths. BACES risk scores categorized 118 patients: 23.7% low risk, 63.3% intermediate risk, and 12.7% high risk. Among risk groups, Kaplan-Meier curves demonstrated clear stratification (log-rank <0.001). Harrell's C-statistic and calibration curves were evaluated in 86 patients due to missing data. Harrell's C-statistic was 0.67 (95%CI, 0.57-0.76), indicating poor discrimination, but the calibration curve showed good agreement between predicted and observed mortality. After modifying the model by adjusting the ESR cut-off and replacing sex with COPD history, the C-statistic improved to 0.76 (95% CI 0.69-0.84). Conclusions:The BACES model proves useful for group-level risk stratification (e.g., low, intermediate high), but lacks precision in predicting individual prognosis in Dutch patients with NTM-PD. Modifications to the model enhanced its discriminatory performance.
Background:Vitamin D supplementation as adjunctive therapy in tuberculosis has generated multiple systematic reviews with variable conclusions. The proliferation of syntheses in this field requires comprehensive evaluation to determine the temporal evolution of evidence and its translation into clinical recommendations. Objective:To synthesize systematic reviews on vitamin D supplementation in tuberculosis, evaluate the temporal evolution of conclusions, examine heterogeneity in clinical outcomes, and determine the quality of available evidence for clinical practice. Methods:An umbrella review was conducted in accordance with PRIOR guidance for overviews of reviews, searching MEDLINE, Embase, Web of Science, and Scopus. Systematic reviews examining vitamin D as adjunctive therapy in tuberculosis were included. Methodological quality was assessed using AMSTAR-2 and ROBIS, and evidence certainty was evaluated with GRADE adapted for umbrella reviews. Overlap among primary randomized trials was quantified using a citation matrix and the corrected covered area (CCA). Results:Nine systematic reviews (2009-2022) were identified, encompassing 300-2991 participants. A citation matrix identified 16 unique primary RCTs and 64 trial occurrences across nine reviews, corresponding to very high overlap (CCA = 37.5%). Meta-analytic findings consistently demonstrated null effects for primary outcomes: culture conversion RR 1.04-1.05, time to conversion HR 1.04-1.15, and mortality without significant differences. Subgroup analyses revealed potential effects in VDR TaqI tt genotype (HR 8.09, 95% CI 1.36-48.01) and multidrug-resistant tuberculosis (RR 2.40, 95% CI 1.11-5.18), although these findings were based on small sample sizes. Safety profiles were favorable with hypercalcemia <2%. Conclusions:Current evidence from overlapping systematic reviews does not support routine vitamin D supplementation as adjunctive therapy to improve tuberculosis treatment outcomes in unselected populations. Signals in VDR TaqI tt genotype carriers and multidrug-resistant tuberculosis remain hypothesis-generating and require prospective validation before clinical translation.
Background:The four-month rifapentine-moxifloxacin (HPMZ) regimen is an alternative to the standard six-month tuberculosis treatment. While clinical trials confirm its efficacy, real-world data, especially in Asian populations, are limited. This study evaluates the effectiveness and tolerability of HPMZ in Thailand. Methods:A prospective study was conducted at the Central Chest Institute of Thailand (September 2023-June 2025) in drug-susceptible TB patients. The HPMZ regimen included daily rifapentine 1200 mg, moxifloxacin 400 mg, isoniazid 300 mg, and weight-based pyrazinamide for eight weeks, followed by rifapentine, moxifloxacin, and isoniazid for nine weeks. Patients were monitored for adverse events (AEs). Results:Fourteen participants (median age 54 years, weight 55.35 kg) received a mean rifapentine dose of 21.26 mg/kg. Hyperbilirubinemia was the most common AEs, leading to treatment discontinuation in 78.57%. Grade 3 hyperbilirubinemia occurred in 57.14%, with a mean peak bilirubin level of 3.03 mg/dL. Rifapentine overexposure was observed, with five patients showing a mean maximum plasma concentration (Cmax) of 41.89 ± 10.42 μg/mL. Conclusion:The high incidence of hyperbilirubinemia suggests a fixed 1200 mg rifapentine dose may not be suitable for lower-weight populations. Weight-based rifapentine dosing and standardized ADR management are crucial for broader implementation. Larger studies are needed to refine dosing and evaluate effectiveness and tolerability.
