Background: Hyponatremia is common in tuberculous meningitis (TBM), but its impact on disease severity and outcomes is unclear.
Methods: In a cohort of 864 adult patients with TBM in Indonesia, we assessed the prevalence and prognostic significance of hyponatremia, classified as moderate (120-130 mEq/L) or severe (<120 mEq/L). Patients received standard antituberculous therapy and corticosteroids and were followed for 1-year mortality.
Introduction: In high tuberculosis (TB) burden countries, the private sector manages a large proportion of initial visits by presumptive patients with TB. In Indonesia, the second largest contributor of TB cases globally, private practitioners (PPs) often do not adhere to national TB guidelines. A district public-private mix programme to mitigate this issue was started in 2019, yet engagement remains low.
View Article and Find Full Text PDFBackground: Efforts to eradicate tuberculosis (TB) are threatened by diabetes mellitus (DM), which confers a 3-fold increase in the risk of TB disease. The changes in the memory phenotypes and functional profiles of ()-specific T cells in latent TB infection (LTBI)-DM participants remain poorly characterised. We, therefore, assessed the effect of DM on T-cell phenotype and function in LTBI and DM clinical groups.
View Article and Find Full Text PDFObjectives: Clofazimine is a promising drug for the treatment of nontuberculous mycobacterial (NTM) diseases. Accumulation of clofazimine to reach steady-state plasma concentrations takes months. A loading dose may reduce the time to steady-state-like concentrations.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2024
Severe and chronic infections, including pneumonia, sepsis, and tuberculosis (TB), induce long-lasting epigenetic changes that are associated with an increase in all-cause postinfectious morbidity and mortality. Oncology studies identified metabolic drivers of the epigenetic landscape, with the tricarboxylic acid (TCA) cycle acting as a central hub. It is unknown if the TCA cycle also regulates epigenetics, specifically DNA methylation, after infection-induced immune tolerance.
View Article and Find Full Text PDFIndonesia has the third highest number of tuberculosis (TB) patients infected with Mycobacterium tuberculosis (MTB) Lineage 1 (L1). Most of these MTB L1 cases can be found in Indonesia's remote easternmost province of Papua, one of Indonesia's most underdeveloped provinces with a particularly high burden for TB. In this study, we sequenced and described 42 MTB L1 isolates from a well-characterized cohort of patients.
View Article and Find Full Text PDFThe Bacille Calmette-Guerin (BCG) vaccine is a well-established inducer of innate immune memory (also termed trained immunity), causing increased cytokine production upon heterologous secondary stimulation. Innate immune responses are known to be influenced by season, but whether seasons impact induction of trained immunity is not known. To explore the influence of season on innate immune memory induced by the BCG vaccine, we vaccinated healthy volunteers with BCG either during winter or spring.
View Article and Find Full Text PDFExisting genotype imputation reference panels are mainly derived from European populations, limiting their accuracy in non-European populations. To improve imputation accuracy for Indonesians, the world's fourth most populous country, we combined Whole Genome Sequencing (WGS) data from 227 West Javanese individuals with East Asian data from the 1000 Genomes Project. This created three reference panels: EAS 1KGP3 (EASp), Indonesian (INDp), and a combined panel (EASp+INDp).
View Article and Find Full Text PDFBackground: Susceptibility to respiratory infections increases with age. Diagnosing and treating tuberculosis in the elderly comes with the challenges of fewer specific symptoms and possibly more side effects of treatment. Much is unknown when it comes to tuberculosis in the elderly, especially in relation to inflammation, which may impact mortality.
View Article and Find Full Text PDFIn Indonesia, government-owned Community Health Centers (CHCs) spearhead tuberculosis (TB) care at the primary level, but a substantial proportion of individuals with pulmonary TB also seek care from Private Practitioners (PPs). However, little is known about PPs' practice in managing patients with TB-associated symptoms. To avoid bias associated with self-administered surveys, we used standardized patients (SPs) to evaluate PPs' adherence to the national TB guidelines.
View Article and Find Full Text PDFWellcome Open Res
May 2024
Background: The clinical management of leprosy is complicated by leprosy reactions (LR) causing irreversible nerve damage and disabilities. LR often require long-term use of corticosteroids causing serious side effects. Adjunct host-directed therapy (HDT) is a potentially attractive strategy in leprosy to prevent LR and associated immunopathology, modulate immunological memory that protects against recurrence, and thereby reduce nerve damage, disability and corticosteroid-associated morbidities.
View Article and Find Full Text PDFDrug development for tuberculosis is hindered by the methodological limitations in the definitions of patient outcomes, particularly the slow organism growth and difficulty in obtaining suitable and representative samples throughout the treatment. We developed target product profiles for biomarker assays suitable for early-phase and late-phase clinical drug trials by consulting subject-matter experts on the desirable performance and operational characteristics of such assays for monitoring of tuberculosis treatment in drug trials. Minimal and optimal criteria were defined for scope, intended use, pricing, performance, and operational characteristics of the biomarkers.
View Article and Find Full Text PDFBackground: Tuberculosis (TB) can induce secondary hemophagocytic lymphohistiocytosis (HLH), a severe inflammatory syndrome with high mortality. We integrated all published reports of adult HIV-negative TB-associated HLH (TB-HLH) to define clinical characteristics, diagnostic strategies, and therapeutic approaches associated with improved survival.
Methods: PubMed, Embase, and Global Index Medicus were searched for eligible records.
PLoS One
March 2024
Background: No gold standard diagnostic test exists for latent tuberculosis infection (LTBI). The intra-dermal tuberculin skin test (TST) has known limitations and Interferon-gamma release assays (IGRA) have been developed as an alternative. We aimed to assess agreement between IGRA and TST, and risk factors for test positivity, in Indonesian healthcare students.
View Article and Find Full Text PDFLancet Reg Health Southeast Asia
March 2024
Background: In Indonesia, drug resistance testing for TB largely relies on Xpert MTB/RIF, and it is unknown what proportion of drug-resistant (DR) TB is adequately diagnosed and treated.
Methods: We conducted a cascade of care analysis on a cohort of presumptive rifampicin-resistant (RR) TB patients registered in 2015-2018 in a tertiary hospital in Indonesia. Estimated incidences of (presumptive) DR-TB cases were assumption-based using global reports.
There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir.
View Article and Find Full Text PDFBackground: Little is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV.
Methods: We included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort between April 2019 and December 2021. Clinical, laboratory, and radiological assessments were standardized.
Immune responses are tightly regulated yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live-attenuated vaccine induces not only an adaptive immune response against tuberculosis but also triggers innate immune activation and memory that are indicative of trained immunity.
View Article and Find Full Text PDFThe effect of acetylator status on the exposure to isoniazid in plasma and CSF in tuberculous meningitis (TBM) patients remains largely unexplored. Here, we describe isoniazid exposures and acetylator status of 48 subjects in the ReDEFINe study (NCT02169882). Fifty percentwere fast (half-life <130 min) or slow (half-life >130 min) acetylators.
View Article and Find Full Text PDFPLOS Glob Public Health
December 2023
Six lineages of Mycobacterium tuberculosis sensu stricto (which excludes M. africanum) are described. Single-country or small observational data suggest differences in clinical phenotype between lineages.
View Article and Find Full Text PDFTreatment of skin and soft tissue infections with nontuberculous mycobacteria sometimes fails despite repeated debridements and long-term systemic antibiotic therapy. These treatment-refractory infections can cause significant morbidity and pose a treatment challenge. Following surgery, we treated three patients with negative pressure wound therapy with the instillation and dwell time of topical antibiotics, in addition to systemic antibiotic treatment.
View Article and Find Full Text PDFObjective: To determine the yield of screening for latent tuberculosis infection (LTBI) among people with HIV (PWH) in low tuberculosis (TB) incidence countries (<10 TB cases per 100 000 persons).
Design: A systematic review and meta-analysis were performed to assess prevalence and predictive factors of LTBI, rate of TB progression, effect of TB preventive treatment (TPT), and numbers needed to screen (NNS).
Methods: PubMed and Cochrane Library were searched for studies reporting primary data, excluding studies on active or paediatric TB.