Bachti Alisjahbana

Background: Most tuberculosis (TB) patients first seek care through the private health sector; however, most private practitioners (PPs) are not linked to the National TB Program (NTP). We aimed to map, characterize, and assess the potential contribution of PPs to the Indonesian NTP, particularly for TB diagnosis and care. Methods: This study was conducted between August 2017 and April 2018 in Bandung city, West Java, Indonesia. Trained enumerators surveyed 30 (of 73) randomly selected community health centers (CHCs) areas to identify the location of private health care facilities (HCFs) and recorded service characteristics, including physician’s qualifications and practice schedules. We also asked whether the PPs were managing patients with respiratory tract infection (RTI), ordering a TB diagnosis in the past three months, or treating TB patients at the time of interview. Results: We identified 936 practicing PPs with each CHC areas having a median of 27 (IQR: 12–40). We successfully interviewed 674 (72.0%), 88.1% (594/674) of whom reported managing patients with RTI symptoms. Most PPs worked in clinics with multiple providers (78.6%; 530/674), and the remainder (21.4%; n = 144) in single-provider clinics. A small proportion of PPs practiced in HCFs equipped with an X-ray (10.1%) or laboratory (27.1%) facility, and 23.2% collaborated with the national health insurance system. Almost three-quarters (70.0%) practiced in a HCF with a pharmacy. A third (33.3%; 209/627) provided services after weekday office hours, and 28.3% (191/674) offered weekday and weekend clinics. Of the PPs managing RTI patients, 241 (40.6%) reported encountering TB patients, and 101 (17.0%) had TB patients under their treatment program at the time of the interview. Overall, PPs reported they had diagnosed 937 patients with TB in the past three months and that 354 TB patients were receiving treatment. Conclusions: PPs have great potential to contribute to TB care because they are present in large numbers, are distributed throughout the city, and can provide services after regular office hours. Some PPs even worked in HCFs supported by X-rays, laboratories, and pharmacies. Ways to engage PPs optimally with the NTP should be sought.

Introduction: Most people with tuberculosis (TB) reside in countries with limited resources for prompt TB diagnosis, resulting in diagnosis and treatment delays and ongoing community transmission. Current TB diagnostics rely on sputum, while some people with presumptive TB cannot produce adequate sample. A new generation near-point-of-care (NPOC) tests using sputum or tongue swabs may provide more accessible TB diagnosis. Methods: In this pragmatic cluster randomised controlled trial (cRCT) in Indonesia, a multi-component public health intervention will include: (a) introduction of NPOC MiniDock MTB test (Guangzhou Pluslife Biotech, China) on sputum, tongue swab, or both specimens, (b) optimisation of clinical algorithms incorporating the new test, (c) a promotional package to encourage patient attendance and test utilisation, and (d) TB household contact investigation, including the new test, by community health volunteers. We will randomly stratify 40 community health centre (CHC) areas into intervention and control arms (1:1) in Bandung District. The intervention will be administered in healthcare facilities (HCFs) and in the community of the intervention areas. The control areas will continue standard of care with no intervention, except TB notification refresher training, which will be delivered in both areas before intervention roll-out. The primary outcome is the number of TB cases diagnosed and notified by HCFs per population attending them. It will be measured by abstracting data on TB case notification and the number of HCF attendees over 12 months following completion of the intervention roll-out, compared to 12 months preceding any trial activities. Discussion: This trial will evaluate the effect of an intervention package incorporating the first-in-class NPOC on TB diagnosis and notification. The trial results will inform policy to improve TB diagnostic efforts in Indonesia and other high burden TB countries. Trial Registration: ClinicalTrials.Gov, NCT07293455 .

Background: Access to tuberculosis (TB) diagnostics remains limited in high-burden countries, partly due to centralised and complex testing. We evaluated MiniDock MTB, a low-complexity near point-of-care (nPOC) assay, in sputum for diagnostic accuracy and agreement with Xpert MTB/RIF Ultra (Xpert). Methods: From September 2024 to April 2025, presumptive pulmonary TB cases aged >28 days were consecutively enrolled at 15 community health centres, a lung clinic, and a lung hospital in Bandung, Indonesia. Sputum was tested with MiniDock MTB on sputum swab, Xpert, and liquid culture. We assessed diagnostic accuracy against microbiological and composite reference standards (CRS) and agreement with Xpert. Results: From 3051 individuals screened, 671 were eligible and included; 533 were adults (aged ≥15 years), 138 were children. Overall, 126 were Xpert-positive and 132 culture-positive. In adults, MiniDock MTB sensitivity was 86.2% (110/116; 95% CI 78.8 – 91.3) and 55.8% (110/197; 95% CI 48.9 – 62.6) against liquid culture and CRS, respectively; small numbers of positive results precluded estimation in children. Specificity ranged from 96.8% to 98.8%. Overall agreement between MiniDock MTB and Xpert (excluding trace positive) was 94.8% (95% CI 92.6 – 96.3; K = 0.84). Positive percent agreement was 82.8% (95% CI 75.1 – 88.4) and 25% (95% CI 4.6 – 69.9) in adults and children, respectively, and reduced with lower bacillary burden (p = 0.004). Conclusions: Sensitivity of MiniDock MTB in sputum against liquid culture exceeded the WHO threshold for a sputum-based nPOC TB test in adults. There was high agreement with Xpert but reduced sensitivity in low-bacillary burden TB disease.

We examined if circulating factors protect against tuberculosis infection through induction of trained immunity. Lack of infection among heavily exposed Indonesian contacts was not associated with circulating beta-glucan concentrations at the time of exposure, nor with serum-induced trained immunity in vitro. This argues that cell-intrinsic (e.g. epigenetic) processes may be involved.

Introduction: Advances in HIV management have transformed HIV into a chronic condition, resulting in improved prognosis and increased survival among people living with HIV (PLWH). Traditional risk factors for metabolic dysfunction‐associated steatotic liver disease (MASLD)—including dyslipidemia—are prevalent in PLWH. This systematic review and meta‐analysis aim to synthesize current evidence on lipid profile disturbances as contributors to MASLD in PLWH. Methods: This systematic review and meta‐analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines and registered in PROSPERO with registration number CRD420251054477. We searched seven databases to identify studies reporting the prevalence and characteristics of MASLD in PLWH. Meta‐analysis was conducted using Review Manager 5.4.1. Mean differences (MDs) were calculated using a random‐effects model. Risk of bias was assessed using the ROBINS‐E tool. Results: A total of 17 studies comprising 3933 HIV‐positive participants were included, among whom 1226 (37%) had MASLD. Male sex was significantly associated with MASLD (OR = 1.57; 95% CI: 1.13–2.17; p = 0.007). MASLD was significantly associated with higher body mass index (BMI) (MD = 3.23 kg/m²; p < 0.00001). Lipid profile analysis revealed that MASLD patients had higher total cholesterol (MD = 6.62 mg/dL; p = 0.01), low density lipoprotein (LDL) (MD = 3.83 mg/dL; p = 0.01), triglycerides (MD = 63.02 mg/dL; p < 0.00001), and lower high density lipoprotein (HDL) (MD = −3.73 mg/dL; p < 0.0001). Conclusion: This study demonstrates a significant difference in lipid profiles (higher total cholesterol, LDL, triglycerides, and lower HDL) among PLWH who develop MASLD, suggesting a potential metabolic signature associated with this comorbidity.

A significant proportion of individuals who are heavily exposed to infectious tuberculosis patients do not acquire Mycobacterium tuberculosis (Mtb) infection, as detected by an interferon gamma release assay (IGRA). We examined circulating metabolite profiles and metabolic genotypes in 199 heavily exposed IGRA-negative tuberculosis household contacts in Indonesia. Based on differentially abundant metabolites, activity of several pathways including arachidonic acid, arginine and proline, glutathione, and tryptophan metabolism, correlated with a negative IGRA at three months. SNPs near PRODH (involved in arginine and proline metabolism) were associated with circulating proline concentrations and persistently negative IGRA results, while SNPs near AFMID (involved in tryptophan metabolism) were associated with IGRA conversion. For further validation, plasma metabolomic profiles were correlated with mycobacterial growth inhibition by peripheral blood mononuclear cells from individuals in a low-incidence setting. Lower circulating concentrations of six metabolites, including leukotriene B4, proline, glycine, and tryptophan correlated with better growth control in non-exposed healthy individuals, as well as with stronger protection against IGRA-conversion in the Indonesian tuberculosis household contacts. Collectively, these data support the notion that circulating metabolites impact innate host defense against Mtb infection, and that metabolic interventions may prevent tuberculosis infection and disease.

This study examines the role of host inflammation in the high mortality of tuberculous meningitis (TBM) and identifies potential biomarkers associated with improved survival. We conducted a case-control study involving 131 patients in a discovery cohort, 81 TBM patients in a validation cohort, and 43 non-infected controls from a referral hospital in Indonesia. We measured 94 inflammation-related proteins in cerebrospinal fluid (CSF) and performed genome-wide quantitative trait loci (QTL) mapping. Sixty-seven proteins were found to be differentially expressed between TBM patients and controls, with 64 proteins elevated in patients. Five proteins, including vascular endothelial growth factor (VEGF) and matrix metalloproteinase-10 (MMP-10), were identified as predictors of 180-day mortality in TBM patients. The validation cohort confirmed that MMP-10, but not VEGF, was predictive of mortality. Genome-wide QTL mapping identified two genome-wide significant and four suggestive genetic loci associated with CSF MMP-10, which also predicted survival in an additional cohort of 218 patients. High CSF concentrations of MMP-10, along with specific genetic loci, may be associated with survival in TBM patients, suggesting a potential role for MMP-10 in disease pathogenesis and warranting further investigation into its utility in host-directed therapies.

Community-wide screening for bacteriologically confirmed pulmonary tuberculosis may reduce the tuberculosis burden, although concerns of overtreatment remain because of false positive diagnoses due to subpar specificity of current bacteriological tests for screening. Our review and data analysis show that clinic-based test specificity estimates of Xpert against culture underestimate performance in communities, for both Xpert MTB/RIF(99.8% for community vs 98.4% for clinic) and Xpert Ultra (99.4% vs 95.6%, respectively), reducing the presumed false positivity of sputum Xpert, using culture as the reference, by 86.8% and 85.4%, respectively, compared with clinic-based specificity estimates. These findings support large-scale evaluation of community-wide screening for tuberculosis.

The tuberculosis (TB) program was massively disrupted due to the COVID-19 pandemic, which may have impacted on an increase in costs for people with TB (PWTB) and their households. We aimed to quantify the pre-treatment out-of-pocket costs and the factors associated with these costs from patients’ perspective during the COVID-19 pandemic in Bandung, Indonesia. Adults with pulmonary TB were interviewed using a structured questionnaire for this cross-sectional study recruiting from 7 hospitals, 59 private practitioners, and 10 community health centers (CHCs) between July 2021 to February 2022. Costs in rupiah were converted into US dollars and presented as a median and interquartile range (IQR). Factors associated with costs were identified using quantile regression. A total of 252 participants were recruited. The median total pre-treatment cost was $35.45 (IQR 17.69-67.62). The highest median cost was experienced by participants from private hospitals ($54.51, IQR 29.48-98.47). The rapid antigen and PCR for SARS-CoV-2 emerged as additional medical costs among 26% of participants recruited in private hospitals. Visiting ≥ 6 providers before diagnosis ($38.40 versus $26.20, p < 0.001), presenting first at a private hospital ($50.68, p < 0.05) and private practitioners ($34.97, p < 0.05), and being diagnosed in the private health sector ($39.98 versus $20.30, p < 0.05) were significantly associated with higher pre-treatment costs. PWTB experienced substantial out-of-pocket costs in the process of diagnosis during the COVID-19 pandemic despite free TB diagnosis and treatment. Early detection and identification play an important role in reducing pre-diagnostic TB costs.