Comparison of Diabetes Mellitus Prevalence between Universal and Targeted Screening among Tuberculosis Patients in Resource Limited Settings

BACKGROUND: Diabetes Mellitus (DM) increases the risk of active Tuberculosis (TB) infection and treatment failure. Therefore, screening of DM is important in TB patients. However, it may not be possible to screen all patients where resources are limited. This study aimed to compare the sensitivity of universal screening and targeted screening methods in the detection of DM among TB patients. SUBJECT AND METHODS: TANDEM study was conducted from February to June 2016. This project consisted of prevalence study and clinical trial on TB-DM. A sample of TB patients aged ≥ 35 years old was selected for this study. The prevalence of the universal screening method was compared with that of the targeted method in the detection of DM among the TB patients. RESULTS: By universal screening, 128 out of 748 (17.11%) TB patients were confirmed to have DM. By targeted screening, 30 out of 85 (35.29%) TB patients were confirmed to have DM. This difference in prevalence between the two screening methods was statistically significant (p<0.001). Mean age (year) of TB patients with DM was 53.38 (SD=9.72), whereas mean HbA1c was 10.77% (SD=3.10). CONCLUSION: The prevalence of targeted screening method in the detection of DM among TB patients was higher than that of universal screening method. The targeted screening method has the potential to be used in resource-poor settings. Keywords: prevalence, diabetes mellitus, universal screening, targeted screening, tuberculosi

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

Efek Suplemen Protein Berbasis-susu Terhadap Keseimbangan Mikroflora Tuberkulosis Paru Dari Pasien Dalam Pengobatan (Effect of Milk-based Protein Supplement on the Microflora Balance of Pulmonary Tuberculosis From Treated Patients)

Background: Pulmonary tuberculosis (TB) patients, in addition to frequently suffering from nutritional deficiency, may have impaired gut microflora balance as effect of low daily dietary intake and antibiotics therapy use, respectively. Lactobacillus acidophilus and Bifidobacterium longum is a normal inhabitant of human gut microflora, which able to improve nutrients absorption and modulate immune response. Objective: To test the effect of milk-based protein (MBP) supplement on the microflora balance of TB (maintaining growth and metabolic activity of probiotic bacteria) from treated patients. Methods: Several methods was applied to determine nutrients concentration and probiotic population. (1) types and carbohydrate amount and vitamin A concentration in MBP supplement was determined by HPLC method, zinc concentration used AAS method and amount of protein used micro Kjeldahl method; (2) total energy, fat and vitamin D concentration was calculated based on their concentration in each ingredient; (3) total cells count for growth and metabolic activity test of probiotics bacteria was used plating technique and HPLC method, respectively; (4) acceptance test to MBP supplement was performed using organoleptic test three point Likert scale. Results: In each 100 gram MBP supplement was containing (a) monosaccharide (1,710 mg), disaccharides (43,870 mg) and oligosaccharides (490 mg), vitamin A, zinc, protein, energy, fat dan vitamin D, (b) it supplement capable maintained growth of probiotics bacteria (&gt; 1x 10 log10 cfu/mL) and stimulated lactic acid production five times higher (4,5 M lactic acid/mL) than placebo (0,9 M lactic acid/ml); (c) MBP supplements has been accepted by all subjects. Conclusion: MBP supplement had capacity to maintain growth and improved metabolic activity of two indigenous probiotic bacteria in the human gut

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

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

Treatment outcomes of fixed-dose combination versus separate tablet regimens in pulmonary tuberculosis patients with or without diabetes in Qatar

Background: Tuberculosis is considered the second most common cause of death due to infectious agent. The currently preferred regimen for treatment of pulmonary tuberculosis (PTB) is isoniazid, rifampin, pyrazinamide, and ethambutol, which has been used either as separate tablets (ST) or as fixed-dose combination (FDC). To date, no studies have compared both regimens in Qatar. We aim to evaluate the safety and effectiveness of FDC and ST regimen for treating PTB, in addition to comparing safety and efficacy of FDC and ST regimens in patients with diabetes treated for TB. Methods: A retrospective observational study was conducted in two general hospitals in Qatar. Patients diagnosed with PTB received anti-tuberculosis medications (either as FDC or ST) administered by the nurse. Sputum smears were tested weekly. We assessed the time to negative sputum smear and incidence of adverse events among FDC and ST groups. Results: The study included 148 patients. FDC was used in 90 patients (61%). Effectiveness was not different between FDC and ST regimens as shown by mean time to sputum conversion (29.9 ± 18.3 vs. 35.6 ± 23 days, p = 0.12). Similarly, there was no difference in the incidence of adverse events, except for visual one that was higher in ST group. Among the 33 diabetic patients, 19 received the FDC and had faster sputum conversion compared to those who received ST (31 ± 12 vs. 49.4 ± 30.9 days, p = 0.05). Overall, diabetic patients needed longer time for sputum conversion and had more hepatotoxic and gastric adverse events compared to non-diabetics. Conclusion: ST group had higher visual side effects compared to FDC. FDC may be more effective in diabetic patients; however, further studies are required to confirm such finding.PublishedN/

Genetic Association and Expression Studies Indicate a Role of Toll-Like Receptor 8 in Pulmonary Tuberculosis

Despite high rates of exposure, only 5–10% of people infected with Mycobacterium tuberculosis will develop active tuberculosis (TB) disease, suggesting a significant role for genetic variation in the human immune response to this infection. Here, we studied TB association and expression of 18 genes involved in the Toll-like receptor (TLR) pathways. Initially, we genotyped 149 sequence polymorphisms in 375 pulmonary TB patients and 387 controls from Indonesia. We found that four polymorphisms in the TLR8 gene on chromosome X showed evidence of association with TB susceptibility in males, including a non-synonymous polymorphism rs3764880 (Met1Val; P = 0.007, odds ratio (OR) = 1.8, 95% c.i. = 1.2–2.7). We genotyped these four TLR8 polymorphisms in an independent collection of 1,837 pulmonary TB patients and 1,779 controls from Russia and again found evidence of association in males (for rs3764880 P = 0.03, OR = 1.2, 95% c.i. = 1.02–1.48). Combined evidence for association is P = 1.2×10−3–6×10−4. In addition, a quantitative PCR analysis indicated that TLR8 transcript levels are significantly up-regulated in patients during the acute phase of disease (P = 9.36×10−5), relative to baseline levels following successful chemotherapy. A marked increase in TLR8 protein expression was also observed directly in differentiated macrophages upon infection with M. bovis bacille Calmette-Guérin (BCG). Taken together, our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB across different populations

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

Comparison of pulmonary and extrapulmonary tuberculosis in Nepal- a hospital-based retrospective study

<p>Abstract</p> <p>Background</p> <p>Studies from developed countries have reported on host-related risk factors for extra-pulmonary tuberculosis (EPTB). However, similar studies from high-burden countries like Nepal are lacking. Therefore, we carried out this study to compare demographic, life-style and clinical characteristics between EPTB and PTB patients.</p> <p>Methods</p> <p>A retrospective analysis was carried out on 474 Tuberculosis (TB) patients diagnosed in a tertiary care hospital in western Nepal. Characteristics of demography, life-style and clinical features were obtained from medical case records. Risk factors for being an EPTB patient relative to a PTB patient were identified using logistic regression analysis.</p> <p>Results</p> <p>The age distribution of the TB patients had a bimodal distribution. The male to female ratio for PTB was 2.29. EPTB was more common at younger ages (< 25 years) and in females. Common sites for EPTB were lymph nodes (42.6%) and peritoneum and/or intestines (14.8%). By logistic regression analysis, age less than 25 years (OR 2.11 95% CI 1.12–3.68) and female gender (OR 1.69, 95% CI 1.12–2.56) were associated with EPTB. Smoking, use of immunosuppressive drugs/steroids, diabetes and past history of TB were more likely to be associated with PTB.</p> <p>Conclusion</p> <p>Results suggest that younger age and female gender may be independent risk factors for EPTB in a high-burden country like Nepal. TB control programmes may target young and female populations for EPTB case-finding. Further studies are necessary in other high-burden countries to confirm our findings.</p