Determinants of Latent Tuberculosis in Bandung, West Java

Background: TB remains a leading cause of morbidity and mortality in developing countries, including Indonesia. About 7% of all deaths in developing countries are attributed to TB. Latent tuberculosis infection (LTBI) is a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active TB. This study aimed to examine the determinants of latent tuberculosis in Bandung, West Java. Subjects and Method: This was a cross-sectional study conducted in Bandung, West Java. A total of 252 peoples were selected for this study, consisting of latent tuberculosis cases and controls. The dependent variable was latent tuberculosis. The independent variables were age, nutrition status, BCG scar, and smoking. The data were collected by laboratory test and questionnaire. The data was analyzed by a multiple logistic regression. Results: The risk of latent tuberculosis increased with occasional smoking (OR= 9.34; 95% CI= 4.23 to 20.67), frequent smoking (OR= 12.99; 95% CI= 2.49 to 67.94), poor nutrition status (OR= 2.64; 95% CI= 0.49 to 14.31), but decreased with BCG scar (OR= 0.45; 95% CI= 0.21 to 0.95). Conclusion: The risk of latent tuberculosis increases with occasional smoking, frequent smoking, poor nutrition status, but decreases with BCG scar. Keywords : latent tuberculosis, smoking, nutrition status, BCG scar

Higher education in Indonesia: Contemporary challenges in governance, access, and quality

This chapter presents the development of Indonesian higher education since its origins to current challenges in the fields of governance, autonomy, access, equity, quality, and internationalization. Indonesia has a massive and diversified tertiary education, including experiments in community colleges and online programs. The higher educational system remains mainly centralized, with the exception of some reforms towards financial autonomy. Insufficient public funding hinders the capacity to provide adequate teaching, research, and facilities among other aspects. The consequential rise in student fees contributes to an overrepresentation of students from Java, urban centers, and higher social classes

Insufficient quality of sputum submitted for tuberculosis diagnosis and associated factors, in Klaten district, Indonesia

Background Sputum smear microscopy is the standard diagnostic method for detection of smear positive pulmonary tuberculosis (TB). Insufficient quality of sputum might result in missing cases. In this study we aimed at assessing the quality of sputum in a district in Central Java and determining patient and health worker factors associated with submission of three good quality sputum samples. Methods In 16 health centers information was collected on the quality of sputum submitted by TB suspects, i.e. volume, color, and viscosity. TB suspects were interviewed to assess their knowledge of TB, motivation to provide sputum and whether they were informed why and how to produce a sputum sample. Health workers were interviewed to assess what information they provided to TB suspects about the reason for sputum examination, methods to produce sputum and characteristics of a good quality sputum sample. All health worker and patient factors were evaluated for association with sputum quality. Results Of 387 TB suspects, 294 (76.0%) could be traced and interviewed, and of 272 (70.3%) information about sputum quality was available. Of those 203 (74.6%) submitted three samples, 90 (33.1%) provided at least one good sample, and 37 (13.6%) provided three good quality sputum samples. Of the 272 TB suspects, 168 (61.8%) mentioned that information on the reason for sputum examination was provided, 66 (24.3%) remembered that they were informed about how to produce sputum and 40 (14.7%) recalled being informed about the characteristics of good quality sputum. Paramedics reported to provide often/always information on the importance of sputum examination, and when to produce sputum. Information on how to produce sputum and characteristics of a good sputum sample was less often provided. None of the studied patient characteristics or health worker factors was associated with providing good quality sputum. Conclusion A considerable number of TB suspects did not provide three sputum samples and a large number of sputum samples were of insufficient quality. Training of health workers in providing health education to the TB suspect about the reason for sputum examination and how to produce a good quality sputum sample should be a priority of the TB program

Risk of tuberculosis in patients with diabetes: population based cohort study using the UK Clinical Practice Research Datalink.

BACKGROUND: Previous cohort studies demonstrate diabetes as a risk factor for tuberculosis (TB) disease. Public Health England has identified improved TB control as a priority area and has proposed a primary care-based screening program for latent TB. We investigated the association between diabetes and risk of tuberculosis in a UK General Practice cohort in order to identify potential high-risk groups appropriate for latent TB screening. METHODS: Using data from the UK Clinical Practice Research Datalink we constructed a cohort of patients with incident diabetes. We included 222,731 patients with diabetes diagnosed from 1990-2013 and 1,218,616 controls without diabetes at index date who were matched for age, sex and general practice. The effect of diabetes was explored using a Poisson analysis adjusted for age, ethnicity, body mass index, socioeconomic status, alcohol intake and smoking. We explored the effects of age, diabetes duration and severity. The effects of diabetes on risk of incident TB were explored across strata of chronic disease care defined by cholesterol and blood pressure measurement and influenza vaccination rates. RESULTS: During just under 7 million person-years of follow-up, 969 cases of TB were identified. The incidence of TB was higher amongst patients with diabetes compared with the unexposed group: 16.2 and 13.5 cases per 100,000 person-years, respectively. After adjustment for potential confounders the association between diabetes and TB remained (adjusted RR 1.30, 95 % CI 1.01 to 1.67, P = 0.04). There was no evidence that age, time since diagnosis and severity of diabetes affected the association between diabetes and TB. Diabetes patients with the lowest and highest rates of chronic disease management had a higher risk of TB (P <0.001 for all comparisons). CONCLUSIONS: Diabetes as an independent risk factor is associated with only a modest overall increased risk of TB in our UK General Practice cohort and is unlikely to be sufficient cause to screen for latent TB. Across different consulting patterns, diabetes patients accessing the least amount of chronic disease care are at highest risk for TB.This article presents independent research supported by a National Institute for Health Research (NIHR) In Practice Fellowship to LP (grant number NIHR/IPF/11/05). DAJM received Wellcome Trust funding (grant number 092691/Z/10/Z). LS is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science

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

IntroductionIn 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. This study examines what affects the decisions of Indonesian PPs regarding TB management.MethodsWe performed semistructured in-depth interviews and focus group discussions (FGDs) with 24 PPs and 6 relevant stakeholders. Data collection and analysis were based on Flottorp's comprehensive and generic checklist on determinants of healthcare professional practice, including seven domains: guideline factors; individual professional barriers; patient factors; professional interactions; incentives and resources; organisational changes capacity and social, legal and political factors. The interviews and FGDs were recorded and transcribed verbatim. Coding and analysis were conducted by using NVivo software.ResultsBarriers that influenced PPs adherence to following the national TB guideline were found in all seven domains, including incoherence between national and international TB management guidelines, the complex referral and financing system, limited access to appropriate diagnostics tools and drugs, and patient preferences. This was further exacerbated by perceived lack of trust between PPs and local governmental stakeholders. In this study, in addition to seventh Flottorp's domain, we also found the complex nature of TB disease, which also complicates the decision-making process of PPs in TB management.ConclusionPPs face several challenges in complying with TB guidelines to enable optimal clinical decision-making

Sensitivity of the Quantiferon-Gold In-Tube Assay in Sputum Smear Positive TB Cases in Indonesia

BACKGROUND: As part of a formal evaluation of the Quantiferon-Gold in-tube assay (QFT-IT) for latent TB infection we compared its sensitivity to the tuberculin skin test (TST) in confirmed adult TB cases in Indonesia. Smear-positive TB disease was used as a proxy gold standard for latent TB infection. METHODS AND FINDINGS: We compared the sensitivity of QFT-IT and TST in 98 sputum smear and chest x-ray positive TB cases and investigated risk factors for negative and discordant results in both tests. Both tests showed high sensitivity; (QFT-IT; 88.7%: TST; 94.9%), not significantly different from each other (p value 0.11). Very high sensitivity was seen when tests were combined (98.9%). There were no variables significantly associated with discordant results or with a negative TST. For QFT-IT which particular staff member collected blood was significantly associated with test positivity (p value 0.01). Study limitations include small sample size and lack of culture confirmation or HIV test results. CONCLUSIONS: The QFT-IT has similar sensitivity in Indonesian TB cases as in other locations. However, QFT-IT, like the TST cannot distinguish active TB disease from LTBI. In countries such as Indonesia, with high background rates of LTBI, test specificity for TB disease will likely be low. While our study was not designed to evaluate the QFT-IT in the diagnosis of active TB disease in TB suspects, the data suggest that a combination of TST and QFT-IT may prove useful for ruling out TB disease. Further research is required to explore the clinical role of QFT-IT in combination with other TB diagnostic tests

Plasma metabolomics in tuberculosis patients with and without concurrent type 2 diabetes at diagnosis and during antibiotic treatment

Tuberculosis (TB) and type 2 diabetes mellitus (DM), a major TB risk factor, are both accompanied by marked alterations in metabolic processes. Dissecting the specific metabolic changes induced by disease through metabolomics has shown potential to improve our understanding of relevant pathophysiological mechanisms of disease, which could lead to improved treatment. Targeted tandem liquid chromatography-mass spectrometry (LC-MS/MS) was used to compare amine and acylcarnitine levels in plasma samples of patients with TB or TB-DM from Indonesia at time of diagnosis and during antibiotic treatment. Partial least squares discrimination analysis (PLS-DA) showed good separation of patient groups. Amine levels were strongly altered in both disease groups compared to healthy controls, including low concentrations of citrulline and ornithine. Several amino acid ratios discriminated TB from controls (phenylalanine/histidine; citrulline/arginine; kynurenine/tryptophan), possibly reflecting changes in indoleamine-pyrrole 2,3-dioxygenase (IDO) and nitric oxide synthase (NOS) activity. Choline, glycine, serine, threonine and homoserine levels were lower in TB-DM compared to TB, and, in contrast to other analytes, did not normalize to healthy control levels during antibiotic treatment. Our results not only provide important validation of previous studies but also identify novel biomarkers, and significantly enhance our understanding of metabolic changes in human TB and TB-DM.Analytical BioScience

Inflammatory markers in the cerebrospinal fluid linked to mortality in tuberculous meningitis

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