Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia.

Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained by an IFN-γ-independent adaptive immune response, or an effective innate host response clearing Mycobacterium tuberculosis (Mtb) without adaptive immunity. In heavily exposed Indonesian tuberculosis household contacts (n = 1347), a persistently IGRA negative status was associated with presence of a BCG scar, and - especially among those with a BCG scar - with altered innate immune cells dynamics, higher heterologous (Escherichia coli-induced) proinflammatory cytokine production, and higher inflammatory proteins in the IGRA mitogen tube.

Determinants of adherence towards tuberculosis guidelines among Indonesian private practitioners: a qualitative study.

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.

Impaired -specific T-cell memory phenotypes and functional profiles among adults with type 2 diabetes mellitus in Uganda.

Background: 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.

A loading dose of clofazimine to rapidly achieve steady-state-like concentrations in patients with nontuberculous mycobacterial disease.

Objectives: 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.

TCA metabolism regulates DNA hypermethylation in LPS and -induced immune tolerance.

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.

A description of lineage 1 Mycobacterium tuberculosis from papua, Indonesia.

Indonesia 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.

Correction: The effect of M. tuberculosis lineage on clinical phenotype.

[This corrects the article DOI: 10.1371/journal.pgph.

Seasonal variation in BCG-induced trained immunity.

The 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.

Sequencing whole genomes of the West Javanese population in Indonesia reveals novel variants and improves imputation accuracy.

Existing 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).

Elderly patients with tuberculosis in a low-incidence country - Clinical characteristics, inflammation and outcome.

Background: 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.

Tuberculosis care provided by private practitioners in an urban setting in Indonesia: Findings from a standardized patient study.

In 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.

Allergenicity assessment of new or modified protein-containing food sources and ingredients.

The growing world population, changing dietary habits, and increasing pressure on agricultural resources are drivers for the development of novel foods (including new protein sources as well as existing protein sources that are produced or used in an alternative way or in a different concentration). These changes, coupled with consumer inclination to adopt new dietary trends, may heighten the intake of unfamiliar proteins, or escalate consumption of specific ones, potentially amplifying the prevalence of known and undiscovered food allergies. Assessing the allergenicity of novel or modified protein-based foods encounters several challenges, including uncertainty surrounding acceptable risks and assessment criteria for determining safety.

Metformin as adjunctive therapy in combination with multidrug treatment for multibacillary leprosy: A protocol for a randomized double-blind, controlled Phase 2 trial in Indonesia (MetLep Trial).

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.

Developing biomarker assays to accelerate tuberculosis drug development: defining target product profiles.

Drug 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.

De-simplifying antiretroviral therapy from a single-tablet to a two-tablet regimen: Acceptance, patient-reported outcomes, and cost savings in a multicentre study.

Background: Antiretroviral therapy (ART), which is increasingly used by people with HIV, accounts for significant care costs, particularly because of single-tablet regimens (STRs). This study explored de-simplification to a two-tablet regimen (TTR) for cost reduction. The objectives of this study were: (1) acceptance of de-simplification, (2) patient-reported outcomes, and (3) cost savings.

Higher infection risk for JAK inhibitors tofacitinib and baricitinib compared to subcutaneous biological DMARDs.

Introduction: Rheumatoid arthritis (RA) is usually treated with disease modifying antirheumatic drugs (DMARDs), including biological DMARDs (bDMARDs) and more recently, Janus kinase inhibitors (JAKi). Randomized trials suggest similar infection risks for JAKi and bDMARDs, but real-world data are scarce.

Methods: From a nationally representative prescription database, adult RA patients starting a new JAKi or bDMARD between August 1st, 2018, and January 31st, 2021, were included.

Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis: Diagnostic Challenges and Determinants of Outcome.

Background: 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.

Tuberculin skin test and Interferon-gamma release assay agreement, and associated factors with latent tuberculosis infection, in medical and nursing students in Bandung, Indonesia.

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.

Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen.

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.

Clinical presentation, management, and outcome of suspected central nervous system infections in Indonesia: a prospective cohort study.

Background: 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.