Management of children exposed to Mycobacterium tuberculosis: a public health evaluation in West Java, Indonesia.

Objective: To investigate qualitatively and quantitatively the performance of a programme for managing the child contacts of adult tuberculosis patients in Indonesia.

Methods: A public health evaluation framework was used to assess gaps in a child contact management programme at a lung clinic. Targets for programme performance indicators were derived from established programme indicator targets, the scientific literature and expert opinion.

Inverse relationship of serum hepcidin levels with CD4 cell counts in HIV-infected patients selected from an Indonesian prospective cohort study.

Background: Distortion of iron homeostasis may contribute to the pathogenesis of human immunodeficiency virus (HIV) infection and tuberculosis (TB). We studied the association of the central iron-regulatory hormone hepcidin with the severity of HIV and the association between hepcidin and other markers of iron homeostasis with development of TB.

Methods: Three groups of patients were selected from a prospective cohort of HIV-infected subjects in Bandung, Indonesia.

Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity.

We have recently shown that BCG (Bacillus Calmette-Guérin) vaccination in healthy volunteers induces epigenetic reprogramming of monocytes, leading to increased cytokine production in response to nonrelated pathogens for up to 3 months after vaccination. This phenomenon was named 'trained immunity'. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination.

Severity of psychiatric and physical problems is associated with lower quality of life in methadone patients in Indonesia.

Background And Objectives: The goal of methadone maintenance treatment (MMT) is to reduce the harm and to improve patients' quality of life (Qol). However, the Qol is also influenced by other co-occurring disorders. Data regarding the Qol and the co-occurrence of these disorders is lacking in low-middle income countries.

Low induction of proinflammatory cytokines parallels evolutionary success of modern strains within the Mycobacterium tuberculosis Beijing genotype.

One of the most widespread clades of Mycobacterium tuberculosis worldwide, the Beijing genotype family, consists of ancient (atypical) and modern (typical) strains. Modern Beijing strains outcompete ancient strains in terms of prevalence, while reserving a higher degree of genetic conservation. We hypothesize that their selective advantage lies in eliciting a different host immune response.

Virological failure and drug resistance during first line anti-retroviral treatment in Indonesia.

The virological response and development of drug resistance during first-line anti-retroviral treatment (ART) were studied in Indonesia where the majority of patients infected with HIV have a history of injecting drug use, which is often linked with lower treatment adherence and development of drug-resistance. As many as 575 patients starting ART between September 2007 and March 2010 in Hasan Sadikin Hospital Bandung were followed prospectively. Clinical and laboratory monitoring was performed every 6 months.

[Intravenous drug use and the spread of HIV; an international perspective].

Intravenous drug use is a major international health problem. The transmission of HIV through sharing syringes or needles during drug use is an important part of this problem. Injection drug users (IDUs) also engage in high-risk sexual behaviour which facilitates the transmission between different groups.

Isoniazid, rifampin, and pyrazinamide plasma concentrations in relation to treatment response in Indonesian pulmonary tuberculosis patients.

Numerous studies have reported low concentrations of antituberculosis drugs in tuberculosis (TB) patients, but few studies have examined whether low drug concentrations affect TB treatment response. We examined steady-state plasma concentrations of isoniazid, rifampin, and pyrazinamide at 2 h after the administration of drugs (C(2 h)) among 181 patients with pulmonary tuberculosis in Indonesia and related these to bacteriological response during treatment. C(2 h) values below reference values for either isoniazid, rifampin, or pyrazinamide were found in 91% of patients; 60% had at least two low C(2 h) concentrations.

Implementation of LED fluorescence microscopy for diagnosis of pulmonary and HIV-associated tuberculosis in a hospital setting in Indonesia.

Background: Fluorescence microscopy (FM) has not been implemented widely in TB endemic settings and little evaluation has been done in HIV-infected patients. We evaluated diagnostic performance, time and costs of FM with light-emitting diodes technology (LED-FM), compared with conventional (Zieh-Neelsen) microscopy in a hospital in Indonesia which acts as referral centre for HIV-infected patients.

Method: We included pulmonary tuberculosis suspects from the outpatient and HIV clinic.

Cost-effectiveness of scaling up voluntary counselling and testing in West-Java, Indonesia.

Aim: to evaluate the costs-effectiveness of scaling up community-based VCT in West-Java.

Methods: the Asian epidemic model (AEM) and resource needs model (RNM) were used to calculate incremental costs per HIV infection averted and per disability-adjusted life years saved (DALYs). Locally monitored demographic, epidemiological behavior and cost data were used as model input.

The influence of influenza virus infections on the development of tuberculosis.

Recently, it was shown that interferon-γ mediated immune responses, which play a major role in the control of infection with Mycobacterium tuberculosis (Mtb), can be inhibited by type I interferons. Since type I interferons are abundantly induced during viral infections, we hypothesized that infections with influenza viruses might play a role in the development of active TB disease either directly after exposure to Mtb or through reactivation of latent Mtb infection. To explore this hypothesis we investigated in a retrospective study whether newly diagnosed adult tuberculosis patients from Indonesia had had recent influenza infection.

Cerebral toxoplasmosis mimicking subacute meningitis in HIV-infected patients; a cohort study from Indonesia.

Background: HIV-associated subacute meningitis is mostly caused by tuberculosis or cryptococcosis, but often no etiology can be established. In the absence of CT or MRI of the brain, toxoplasmosis is generally not considered as part of the differential diagnosis.

Methodology/principal Findings: We performed cerebrospinal fluid real time PCR and serological testing for Toxoplasma gondii in archived samples from a well-characterized cohort of 64 HIV-infected patients presenting with subacute meningitis in a referral hospital in Indonesia.

Successful testing and treating of HIV/AIDS in Indonesia depends on the addiction treatment modality.

Background: In many settings, people who inject drugs (PWID) have limited access to human immunodeficiency virus (HIV) care which is provided in several hospitals and primary health centers in big cities. Substance abuse treatment (SAT) can be used as the entry-point to HIV programs. The aim of this study is to describe the characteristics of the PWID who had accessed SAT and determine which SAT modality associates significantly with HIV programs.

Comparison of real time IS6110-PCR, microscopy, and culture for diagnosis of tuberculous meningitis in a cohort of adult patients in Indonesia.

Background: Bacteriological confirmation of tuberculous (TB) meningitis is difficult. Culture is slow and microscopy has insufficient sensitivity. We evaluated real time PCR targeting insertion sequence IS6110 among 230 consecutive adult patients with subacute meningitis in a referral hospital in Indonesia.

Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial.

Background: Intensified antibiotic treatment might improve the outcome of tuberculous meningitis. We assessed pharmacokinetics, safety, and survival benefit of several treatment regimens containing high-dose rifampicin and moxifloxacin in patients with tuberculous meningitis in a hospital setting.

Methods: In an open-label, phase 2 trial with a factorial design in one hospital in Indonesia, patients (aged >14 years) with tuberculous meningitis were randomly assigned to receive, according to a computer-generated schedule, first rifampicin standard dose (450 mg, about 10 mg/kg) orally or high dose (600 mg, about 13 mg/kg) intravenously, and second oral moxifloxacin 400 mg, moxifloxacin 800 mg, or ethambutol 750 mg once daily.

Genome-wide expression profiling identifies type 1 interferon response pathways in active tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains the leading cause of mortality from a single infectious agent. Each year around 9 million individuals newly develop active TB disease, and over 2 billion individuals are latently infected with M.

Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes.

Adaptive features of innate immunity, recently described as "trained immunity," have been documented in plants, invertebrate animals, and mice, but not yet in humans. Here we show that bacille Calmette-Guérin (BCG) vaccination in healthy volunteers led not only to a four- to sevenfold increase in the production of IFN-γ, but also to a twofold enhanced release of monocyte-derived cytokines, such as TNF and IL-1β, in response to unrelated bacterial and fungal pathogens. The enhanced function of circulating monocytes persisted for at least 3 mo after vaccination and was accompanied by increased expression of activation markers such as CD11b and Toll-like receptor 4.

Cost-effectiveness of methadone maintenance therapy as HIV prevention in an Indonesian high-prevalence setting: a mathematical modeling study.

Background: Indonesia faces an HIV epidemic that is in rapid transition. Injecting drug users (IDUs) are among the most heavily affected risk populations, with estimated prevalence of HIV reaching 50% or more in most parts of the country. Although Indonesia started opening methadone clinics in 2003, coverage remains low.

Polymorphisms in autophagy genes and susceptibility to tuberculosis.

Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M.

Preventive therapy in children exposed to Mycobacterium tuberculosis: problems and solutions.

Young children living with a tuberculosis patient are at high risk of Mycobacterium tuberculosis infection and disease. WHO guidelines promote active screening and isoniazid (INH) preventive therapy (PT) for such children under 5 years, yet this well-established intervention is seldom used in endemic countries. We review the literature regarding barriers to implementation of PT and find that they are multifactorial, including difficulties in screening, poor adherence, fear of increasing INH resistance and poor acceptability among primary caregivers and healthcare workers.

Low cost HIV-1 quantitative RT-PCR assay in resource-limited settings: improvement and implementation.

Monitoring of HIV viral load in low and middle income settings is limited by high cost of the commercial assays. Therefore, we developed a novel RT-PCR quantitative assay was developed. This assay targets the HIV-1 pol integrase gene (INT).

The role of autophagy in host defence against Mycobacterium tuberculosis infection.

Autophagy is a vital homeostatic process triggered by starvation and other cellular stresses, in which cytoplasmatic cargo is targeted for degradation in specialized structures termed autophagosomes. Autophagy is involved in nutrient regeneration, protein and organelle degradation, but also in clearance of intracellular pathogens such as Mycobacterium tuberculosis, the causative agent of tuberculosis. Recent studies suggest that induction of autophagy in macrophages is an effective mechanism to enhance intracellular killing of M.

Polymorphisms in SP110 are not associated with pulmonary tuberculosis in Indonesians.

Despite being high transmissible, Mycobacterium tuberculosis (M. tuberculosis) infection causes active disease in only 5-10% of disease-susceptible individuals. This has instigated interest in studying potentially underlying genetic host factors and mechanisms in tuberculosis (TB).