Biology subjects

Alisjahbana, B.

Publications and source records attributed to Alisjahbana, B..

5 recordsLinked to original sources

bioRxiv2024

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-{gamma}-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 BCG-vaccinated individuals - with altered innate immune cells dynamics, higher heterologous (Escherichia coli-induced) proinflammatory cytokine production, and higher inflammatory proteins in the IGRA mitogen tube. Neither circulating concentrations of Mtb-specific antibodies nor functional antibody activity associated with IGRA status at baseline or follow-up. In a cohort of adults in a low tuberculosis incidence setting, BCG vaccination induced heterologous innate cytokine production, but only marginally affected Mtb-specific antibody profiles. Our findings suggest that a more efficient host innate immune response, rather than a humoral response, mediates early clearance of Mtb. The protective effect of BCG vaccination against Mtb infection may be linked to innate immune priming, also termed trained immunity.

immunology↗

bioRxiv2024

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 worlds 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). We also used ten West-Javanese samples with WGS and SNP-typing data for benchmarking. We identified 1.8 million novel single nucleotide variants (SNVs) in the West Javanese population, which, while similar to the East Asians, are distinct from the Central Indonesian Flores population. Adding INDp to the EASp reference panel improved imputation accuracy (R2) from 0.85 to 0.90, and concordance from 87.88% to 91.13%. These findings underscore the importance of including Indonesian genetic data in reference panels, advocating for broader WGS of diverse Indonesian populations to enhance genomic studies.

genetics↗

bioRxiv2020

A Bayesian analysis of the association between Leukotriene A4 Hydrolase genotype and survival probability of tuberculous meningitis patients treated with adjunctive dexamethasone

Tuberculous meningitis (TBM) remains the most devastating form of tuberculosis (TB) with high mortality despite effective antimicrobial treatment. As mortality has been linked to excessive inflammation, anti-inflammatory glucocorticoids are now routinely used as adjunctive treatment with antimicrobial therapy. However, they reduce mortality by only ~ 30%, raising the possibility that only a subset of TBM deaths are caused by inflammatory pathophysiology. Studies in Vietnam found that the survival benefit of adjunctive glucocorticoids was limited to individuals with a common promoter variant in the leukotriene A4 hydrolase (LTA4H) gene encoding an enzyme that regulates inflammatory eicosanoid expression. The variant constitutes a C/T transition with TT homozygotes having increased expression over CT heterozygotes and CC homozygotes. In Vietnam, the LTA4H TT genotype predicted survival, consistent with dexamethasone benefiting only those individuals with a dysregulated hyper-inflammatory response. However, a study of TBM patients in Indonesia did not find the LTA4H TT genotype to confer a significant survival benefit. Given the potential of personalized life-saving anti-inflammatory therapies guided by LTA4H genotype, we have used Bayesian methods to analyze the data from both studies. Bayesian analysis reveals that the LTA4H TT genotype confers survival benefit in both the Vietnam and Indonesia cohorts that begins within days and continues long-term. However, its benefit is nullified in the most severe cases where other factors cause early mortality. LTA4H TT genotype is associated with increased survival in HIV-positive patients also. Thus, our analysis extends the association of LTA4H genotype with TBM survival to populations outside of Vietnam and to HIV-positive patients. Patient LTA4H genotyping used in conjunction with disease severity assessment may help to target glucocorticoids to patients most likely to benefit from this broadly-acting immunosuppressive regimen despite its significant adverse effects.

molecular biology↗

bioRxiv2019

Erythropoiesis differences in various clinical phases of Dengue fever using Immature Reticulocyte Fraction parameter

Dengue fever is the most common cause of hospitalization in otherwise healthy person. The incidence rate increases significantly every year, from 0.05 per 100.000 inhabitants in 1968 to 35-40 per 100.000 inhabitants in 2013. Thrombocytopenia and leucopenia are the most commonly reported changes, whether they are caused by bone marrow suppression or peripheral destruction. Anemia has also been observed to occur in dengue infection with unknown mechanism. Immature Reticulocyte Fraction (IRF) is a parameter reflecting the most immature reticulocyte fraction and it can identify the earliest stage of erythropoiesis disorder. This research aimed to determine the mechanism of erythropoiesis disorders that led to anemia using IRF parameter in the various clinical phases of dengue fever. This study was a comparative analytical research using secondary data derived from the Dengue-associated Endothelial Cell Dysfunction and Thrombocyte Activation (DECENT) research. The baseline characteristic data consists of sex, age, level of hemoglobin, hematocrit, leucocyte, and thrombocyte, also the IRF. The patients were grouped into the fever, critical, recovery, and convalescent phases, plus healthy control group. The data was analyzed using the Kolmogorov-Smirnov normality test, followed by Friedman test and Mann-Whitney post hoc test. There were 244 research subjects and the median age was 24 (14-67), with similar ratio of male and female. The median IRF for all the research subjects was 4.8% with an IQR of 2.4-8.1%. The fever-phase group showed a median of 1.8% with an IQR of 0.5-2.85%. The critical-phase group showed a median of 3.6% with an IQR of 1.8- 5.0%, while the median for the recovery-phase group was 7.05% with an IQR of 4.08-11.85%. The convalescent-phase group showed a median of 7.3 % with an IQR of 3.95-9.3%, and the healthy-control group showed a median of 4.1% with an IQR of 2.2-6.6%. There was a significant difference in IRF between the groups (p<0.05). Immature Reticulocyte Fraction in fever phase was significantly different with IRF in other phases and healthy controls (p<0.05). In the critical phase, IRF was not significantly different from the healthy controls (p=0.218). Summarizing, there are changes in erythropoiesis activity in various clinical phases of dengue infection. Erythropoiesis suppression occurred mainly during the fever phase and it started to restore in the critical phase. In the recovery and convalescent phases, the erythropoiesis activity was increased.

microbiology↗

bioRxiv2018

Associations between impulsivity, risk behavior and HIV, HBV, HCV and syphilis seroprevalence among female prisoners in Indonesia: A cross-sectional study

HIV, hepatitis B and C, and syphilis share common transmission routes of which primarily unsafe sexual contact and injecting drug use are important. Impulsivity is a major factor contributing to this transmission risk behavior, however comprehensive studies within female, prison, and Asian populations are scarce. This cross-sectional study aims to delineate the contributions of different aspects of impulsivity to transmission risk behavior, among female inmates living in a prison in Jakarta (N=214). The relationships between various aspects of impulsivity, risky behavior and seropositivity were tested using analyses of variance and logistic regression analyses. Motor impulsivity was related to alcohol use, reward-related impulsivity to drug use, and cognitive/goal-directed impulsivity to sexual risk behavior. Finally, goal-directed impulsivity was also directly associated with seropositivity. Specific aspects of impulsivity are associated with different types of risky behaviors in Indonesian female prisoners, what can be relevant for future studies on infection prevention strategies for such a population.

epidemiology↗