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Dyshelly Nurkartika Pascapurnama,1 Nabilla Ghina Zavitri,1 Raspati Cundarani Koesoemadinata,1 Adi Imam Cahyadi,2 Lidya Chaidir2,3 1Research Center for Care and Control of Infectious Diseases, Universitas Padjadjaran, Bandung, West Java, Indonesia; 2Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java, Indonesia; 3Center for Translational Biomarker Research, Universitas Padjadjaran, Bandung, West Java, IndonesiaCorrespondence: Lidya Chaidir, Faculty of Medicine, Universitas Padjadjaran, Jln. Ir. Soekarno Km. 21 Jatinangor, Sumedang, 45363, West Java, Indonesia, Tel +62-22-8428812, Email lidya.chaidir@unpad.ac.idPurpose: To date, the diagnosis of nontuberculous mycobacteria (NTM) disease primarily relies on clinical symptoms and radiological features. Our objective was to apply a sequence-based analysis method by using partial gene sequencing of heat shock protein 65 (hsp65) to identify NTM species.Patients and Methods: A total of 32 stored isolates obtained from individuals suspected of having pulmonary NTM infection were subjected to solid Ogawa culture. Genomic DNA from each sample was extracted and used in a conventional polymerase chain reaction (PCR) targeting a specific region of hsp65 gene. Identified amplicons from the PCR were then subjected to targeted sequencing. Analysis of the obtained hsp65 sequence was performed using DNA Baser tool. The consensus sequences obtained were compared to references in the GenBank NCBI database to determine NTM species.Results: We identified several important NTM species which posses opportunistic characteristics. M. abscessus and M. chelonae are the most frequent NTM species identified in this study (40.63% and 18.75%, respectively). These two species have the potential to cause significant infections in human, ranging from opportunistic pulmonary infection to localized skin infection. Additionally, pathogenic NTM members of M. fortuitum group (MFG), M. avium, M. intracellulare, M. kansasii, and M. celatum were also found among all identified species.Conclusion: Sequence-based analysis is a promising method for identifying species of NTM. The hsp65 gene has a high discriminatory power to identify opportunistic pathogen NTM species in specimens in Indonesia. Consequently, hsp65 partial gene sequencing is considerable as an alternative and reliable approach for NTM speciation.Keywords: nontuberculous mycobacteria, species identification, hsp65 gene, sequence-based analysis

Immune system dysregulation in people with diabetes mellitus (DM) increases the risk of acquiring severe infection. We compared the clinical characteristics and laboratory parameters of coronavirus disease 2019 (COVID-19) patients with and without DM and estimated the effect of DM on mortality among COVID-19 patients. A retrospective cohort study collecting patients' demographic, clinical characteristics, laboratory parameters and treatment outcomes from medical records was conducted in a hospital in Bandung City from March to December 2020. Univariable and multivariable logistic regression was performed to determine the association between DM and death. A total of 664 COVID-19 patients with positive real-time reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 were included in this study, of whom 147 were with DM. Half of DM patients presented HbA1c ≥10%. DM patients were more likely to present with comorbidities and severe to critical conditions at admission (P <0.001). Laboratory parameters such as neutrophil-lymphocyte count ratio, C-reactive protein, D-dimer, ferritin, and lactate dehydrogenase were higher in the DM group. In the univariate analysis, variables associated with death were COVID-19 severity at baseline, neurologic disease, DM, age ≥60 years, hypertension, cardiovascular disease, and chronic kidney disease. DM remained associated with death (aOR 1.82; 95% CI 1.13-2.93) after adjustment with sex, age, hypertension, cardiovascular disease, and chronic kidney disease. In conclusion, COVID-19 patients with DM are more likely to present with a very high HbA1c, comorbidities, and severe-critical illness. Chronic inflammation in DM patients may be aggravated by the disruption of immune response caused by COVID-19, leading to worse laboratory results and poor outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kusumawati et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

BACKGROUND: Diabetes mellitus (DM) is common among patients with TB. We assessed DM characteristics and long-term needs of DM-TB patients after completing TB treatment. METHODS: Newly diagnosed TB patients with DM were recruited for screening in a randomised clinical trial evaluating a simple algorithm to improve glycaemic control during TB treatment. DM characteristics, lifestyle and medication were compared before and after TB treatment and 6 months later. Risk of cardiovascular disease (CVD), albuminuria and neuropathy were assessed after TB treatment. RESULTS: Of 218 TB-DM patients identified, 170 (78%) were followed up. Half were males, the mean age was 53 years, 26.5% were newly diagnosed DM. High glycated haemoglobin at TB diagnosis (median 11.2%) decreased during TB treatment (to 7.4% with intensified management and 8.4% with standard care), but this effect was lost 6 months later (9.3%). Hypertension and dyslipidemia contributed to a high 10-year CVD risk (32.9% at month 6 and 35.5% at month 12). Neuropathy (33.8%) and albuminuria (61.3%) were common. After TB treatment, few patients used CVD-mitigating drugs. CONCLUSION: DM in TB-DM patients is characterised by poor glycaemic control, high CVD risk, and nephropathy. TB treatment provides opportunities for better DM management, but effort is needed to improve long-term care.

BACKGROUND: The implementation of tuberculosis preventive treatment (TPT) is challenging especially in resource-limited settings. As part of a Phase 3 trial on TPT, we described our experience with the use of rifampicin for 4 months (4R) and isoniazid for 9 months (9H) in Indonesia. METHODS: In 2011-2017, children and adults with latent TB infection were randomised to either 4R or 9H and followed until 16 months after randomisation for children and 28 months for adults. The primary outcome was the treatment completion rate. Secondary outcomes were Grade 3-5 adverse events (AEs), active TB occurrence, and health costs. RESULTS: A total of 157 children and 860 adults were enrolled. The 4R treatment completion rate was significantly higher than that of 9H (78.7% vs. 65.5%), for a rate difference of 13.2% (95% CI 7.1-19.2). No Grade 3-5 AEs were reported in children; in adults, it was lower in 4R (0.4%) compared to 9H (2.8%). The incidence of active TB was lower with 4R than with 9H (0.09/100 person-year vs. 0.36/100 person-year) (rate difference: -0.36/100 person-year). The total cost per patient was lower for the 4R regimen than for the 9H regimen (USD151.9 vs. USD179.4 in adults and USD152.9 vs. USD206.5 in children) CONCLUSIONS: Completion and efficacy rates for 4R were better than for 9H. Compared to 9H, 4R was cheaper in all age groups, safer in adults and equally safe in children. The Indonesian TB program could benefit from these benefits of the 4R regimen.

Setting: Newly diagnosed pulmonary TB with diabetes mellitus (DM) comorbidity attending clinics in Bandung City, Indonesia., Objective: To describe the effect of educational counselling on patients' knowledge about TB (transmission, treatment, risk factors) and DM (symptoms, treatment, complications, healthy lifestyle), adherence to medication, and to assess characteristics associated with knowledge., Design: All patients received counselling and were then randomised to either structured education on TB-DM, combined with clinical monitoring and medication adjustment (intervention arm), or routine care (control arm). Knowledge and adherence were assessed using a questionnaire., Results: Baseline and 6-month questionnaires were available for 108 of 150 patients randomised (60/76 in the intervention arm and 48/74 in the control arm). Patients knew less about DM than about TB. There was no significant difference in the proportion with knowledge improvement at 6 months, both for TB (difference of differences 14%; P = 0.20) or for DM (10%; P = 0.39) between arms. Intervention arm patients were more likely to adhere to taking DM medication, with fewer patients reporting ever missing oral DM drugs than those in the control arm (23% vs. 48%; P = 0.03). Higher education level was associated with good knowledge of both TB and DM., Conclusions: Structured education did not clearly improve patients' knowledge. It was associated with better adherence to DM medication, but this could not be attributed to education alone. More efforts are needed to improve patients' knowledge, especially regarding DM., (© 2021 The Union.)

Background: Indonesia has the second largest tuberculosis (TB) burden globally. Attempts to scale-up TB control efforts have focused on TB households. However, in most high burden settings, considerable Mycobacterium tuberculosis (Mtb) transmission occurs outside TB households. A better understanding of transmission dynamics in an urban setting in Indonesia will be crucial for the TB Control Program in scaling up efforts towards elimination of TB in a more targeted way. Therefore, the study aims to measure TB prevalence and incidence in household contacts and neighbourhoods in the vicinity of known TB cases and to assess their genomic and epidemiological relatedness., Methods and Analysis: Individuals (~1000) living in the same household as a case diagnosed with pulmonary TB (n = 250) or in a neighbouring household (~4500 individuals) will be screened for TB symptoms and by chest x-ray. Two sputum samples will be collected for microbiological analysis from anyone with a productive cough. Any person found to have TB will be treated by the National TB Control Program. All those with no evidence of TB disease will have a repeat screen at 12 months. Whole-genome sequencing (WGS) and social network analysis (SNA) will be conducted on Index cases and contacts diagnosed with TB., Competing Interests: The authors have declared that no competing interests exist.

Background: Diabetes mellitus (DM) patients are three times more likely to develop tuberculosis (TB) than the general population. Active TB screening in people with DM is part of a bidirectional approach. The aim of this study was to conduct pragmatic active TB screening among DM patients in four countries to inform policy., Methods: DM patients were recruited in Indonesia (n=809), Peru (n=600), Romania (n=603) and South Africa (n=51). TB cases were diagnosed using an algorithm including clinical symptoms and chest X-ray. Presumptive TB patients were examined with sputum smear and culture., Results: A total of 171 (8.3%) individuals reported ever having had TB (South Africa, 26%; Indonesia, 12%; Peru, 7%; Romania, 4%), 15 of whom were already on TB treatment. Overall, 14 (0.73% [95% confidence interval 0.40 to 1.23]) TB cases were identified from screening. Poor glucose control, smoking, lower body mass index, education and socio-economic status were associated with newly diagnosed/current TB. Thirteen of the 14 TB cases diagnosed from this screening would have been found using a symptom-based approach., Conclusions: These data support the World Health Organization recommendation for routine symptom-based screening for TB in known DM patients in high TB-burden countries. DM patients with any symptoms consistent with TB should be investigated and diagnostic tools should be easily accessible., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Introduction: We aim to describe the performance of combined IgM and IgG point-of-care antibody test (POC-Ab) (Wondfo®) compared to real-time reverse transcriptase (rRT-PCR) (Allplex™ 2019-nCoV Assay) in detecting coronavirus disease 2019 (COVID-19)., Methodology: We compared POC-Ab with rRT-PCR results among patients in a tertiary hospital from January to March 2020 in Bandung, Indonesia. We selected presumptive COVID-19 patients with positive rRT-PCR consecutively and 20 patients with negative rRT-PCR results were selected randomly from the same group of patients as controls. We described the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) with corresponding 95% confidence interval using serum and capillary blood samples. We also tested POC-Ab using non-COVID-19 (confirmed dengue and typhoid) patients' sera., Results: Twenty-seven patients with positive rRT-PCR result and 20 negative controls were included (68.1% males, mean age 46 (SD: 15.4)). Using the serum, the sensitivity of the POC-Ab was 63.0% (42.4-80.6), specificity was 95.0% (75.1-99.9), PPV was 94.4% (72.7-99.8), NPV was 65.5% (45.7-82.1). A subset of 20 patients was tested using a capillary blood sample. The accuracy of the capillary blood sample is lower compared to serum (50.0% vs. 78.7%). None of the non-COVID-19 sera tested were reactive., Conclusions: POC-Ab for COVID-19 has a high specificity with no false-positive result in non-COVID-19 sera. Therefore, it can be used to guide diagnostic among symptomatic patients in resource limited settings. Given its low sensitivity, patients with high suspicion of COVID-19 but non-reactive result should be prioritized for rRT-PCR testing., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Nisa Fauziah, Raspati C Koesoemadinata, Basti Andriyoko, Lia Faridah, Silvita F Riswari, Leonardus Widyatmoko, Delita Prihatni, Savira Ekawardhani, Azzania Fibriani, Emma Rachmawati, Ryan B Ristandi, Cut NC Alamanda, Susantina Prodjosoewojo, Bony W Lestari, Ida P Santoso.)

Aims: Diabetes mellitus (DM) is associated with worse tuberculosis (TB) treatment outcomes, especially among those with poor glycemic control. We examined whether a structured clinical algorithm could improve glycemic control in TB patients with DM., Methods: In an open label randomized trial, TB-DM patients were randomized to scheduled counselling, glucose monitoring, and adjustment of medication using a structured clinical algorithm (intervention arm) or routine DM management (control arm), with glycated hemoglobin (HbA1c) at month 6 as the primary end point., Results: We randomized 150 pulmonary TB-DM patients (92% culture positive, 51.3% male, mean age 53 years). Baseline mean HbA1c was 11.0% in the intervention arm (n = 76) and 11.6% in the control arm (n = 74). At 6 months, HbA1c had decreased more in the intervention arm compared with the control arm (a difference of 1.82% HbA1c, 95% CI 0.82-2.83, p < 0.001). Five patients were hospitalized in the intervention arm and seven in the control arm. There was more hypoglycemia (35.0% vs 11.8%; p = 0.002) in the intervention arm. Two deaths occurred in the intervention arm, one due to cardiorespiratory failure and one because of suspected septic shock and multiorgan failure., Conclusion: Regular monitoring and algorithmic adjustment of DM treatment led to improved glycemic control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Adult presumptive tuberculosis (TB) patients ( n = 1690) were screened for TB using a questionnaire, chest X-ray (CXR) and sputum microscopy for acid-fast bacilli (AFB); Mycobacterium tuberculosis culture was performed for 74% of the patients and Xpert ® MTB/RIF was done for 17.2%. Among patients recruited, 943 (55.8%) were diagnosed with TB, of whom 870 (92.3%) were bacteriologically confirmed and 73 (7.7%) were clinically diagnosed on the basis of CXR. Using CXR prior to culture or Xpert testing reduces the number needed to screen from 7.6 to 5.0. Using CXR to triage for culture or Xpert testing reduces the number of missed cases and increases the efficiency of culture and Xpert testing., Competing Interests: Conflicts of interest: none declared., (© 2020 The Union.)

Background: Diabetes mellitus (DM) increases active tuberculosis (TB) risk and worsens TB outcomes, jeopardizing TB control especially in TB-endemic countries with rising DM prevalence rates. We assessed DM status and clinical correlates in TB patients across settings in Indonesia, Peru, Romania, and South Africa., Methods: Age-adjusted DM prevalence was estimated using laboratory glycated hemoglobin (HbA1c) or fasting plasma glucose in TB patients. Detailed and standardized sociodemographic, anthropometric, and clinical measurements were made. Characteristics of TB patients with or without DM were compared using multilevel mixed-effect regression models with robust standard errors., Results: Of 2185 TB patients (median age 36.6 years, 61.2% male, 3.8% human immunodeficiency virus-infected), 12.5% (267/2128) had DM, one third of whom were newly diagnosed. Age-standardized DM prevalence ranged from 10.9% (South Africa) to 19.7% (Indonesia). Median HbA1c in TB-DM patients ranged from 7.4% (Romania) to 11.3% (Indonesia). Compared to those without DM, TB-DM patients were older and had a higher body mass index (BMI) (P value < .05). Compared to those with newly diagnosed DM, TB patients with diagnosed DM had higher BMI and HbA1c, less severe TB, and more frequent comorbidities, DM complications, and hypertension (P value < .05)., Conclusions: We show that DM prevalence and clinical characteristics of TB-DM vary across settings. Diabetes is primarily known but untreated, hyperglycemia is often severe, and many patients with TB-DM have significant cardiovascular disease risk and severe TB. This underlines the need to improve strategies for better clinical management of combined TB and DM., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Data regarding the incidence of tuberculosis (TB) among people living with diabetes (PLWD) in TB-endemic settings are scarce. We examined TB incidence among PLWD in Indonesia who had previously been screened for latent TB infection (LTBI) and TB disease., Methods: PLWD (≥18 y of age) in an urban setting were examined a mean 3.4 y after they had been screened for active TB and LTBI. Data on subsequent TB diagnosis were collected by interview and with chest X-ray, sputum smear and Mycobacterium tuberculosis culture. TB incidence rates were stratified for baseline LTBI status, as determined by the QuantiFERON interferon-gamma release assay (IGRA)., Results: Of 590 PLWD, 101 had died and 163 could not be contacted or refused. Among the 326 who were re-examined, 6 (1.8%; 95% confidence interval [CI] 0.7 to 4.0) reported being diagnosed already and a further 5 were diagnosed with active TB (1.5%; 95% CI 0.50 to 3.5). The TB incidence rate was 9.85 (95% CI 4.03 to 15.68) per 1000 person-years. TB incidence was higher among PLWD with baseline LTBI (17.13; 95% CI 5.25 to 29.00/1000 person-years) compared with those without LTBI (4.79; 95% CI -0.63 to 10.21), with an incidence rate ratio of 3.57 (95% CI 0.86 to 20.92; p=0.054)., Conclusions: PLWD with LTBI in Indonesia and similar settings are likely to benefit from TB preventive therapy., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Diabetes mellitus (DM) is common among tuberculosis (TB) patients and often undiagnosed or poorly controlled. We compared point of care (POC) with laboratory glycated haemoglobin (HbA 1c ) testing among newly diagnosed TB patients to assess POC test accuracy, safety and acceptability in settings in which immediate access to DM services may be difficult., Methods: We measured POC and accredited laboratory HbA 1c (using high-performance liquid chromatography) in 1942 TB patients aged 18 years recruited from Peru, Romania, Indonesia and South Africa. We calculated overall agreement and individual variation (mean ± 2 standard deviations) stratified by country, age, sex, body mass index (BMI), HbA 1c level and comorbidities (anaemia, human immunodeficiency virus [HIV]). We used an error grid approach to identify disagreement that could raise significant concerns., Results: Overall mean POC HbA 1c values were modestly higher than laboratory HbA 1c levels by 0.1% units (95%CI 0.1-0.2); however, there was a substantial discrepancy for those with severe anaemia (1.1% HbA 1c , 95%CI 0.7-1.5). For 89.6% of 1942 patients, both values indicated the same DM status (no DM, HbA 1c <6.5%) or had acceptable deviation (relative difference <6%). Individual agreement was variable, with POC values up to 1.8% units higher or 1.6% lower. For a minority, use of POC HbA 1c alone could result in error leading to potential overtreatment ( n = 40, 2.1%) or undertreatment ( n = 1, 0.1%). The remainder had moderate disagreement, which was less likely to influence clinical decisions., Conclusion: POC HbA 1c is pragmatic and sufficiently accurate to screen for hyperglycaemia and DM risk among TB patients.

Objective: To describe the characteristics and management of Diabetes mellitus (DM) patients from low- and middle-income countries (LMIC)., Methods: We systematically characterised consecutive DM patients attending public health services in urban settings in Indonesia, Peru, Romania and South Africa, collecting data on DM treatment history, complications, drug treatment, obesity, HbA1c and cardiovascular risk profile; and assessing treatment gaps against relevant national guidelines., Results: Patients (median 59 years, 62.9% female) mostly had type 2 diabetes (96%), half for >5 years (48.6%). Obesity (45.5%) and central obesity (females 84.8%; males 62.7%) were common. The median HbA1c was 8.7% (72 mmol/mol), ranging from 7.7% (61 mmol/mol; Peru) to 10.4% (90 mmol/mol; South Africa). Antidiabetes treatment included metformin (62.6%), insulin (37.8%), and other oral glucose-lowering drugs (34.8%). Disease complications included eyesight problems (50.4%), EGFR <60 ml/min (18.9%), heart disease (16.5%) and proteinuria (14.7%). Many had an elevated cardiovascular risk with elevated blood pressure (36%), LDL (71.0%) and smoking (13%), but few were taking antihypertensive drugs (47.1%), statins (28.5%) and aspirin (30.0%) when indicated. Few patients on insulin (8.0%), statins (8.4%) and antihypertensives (39.5%) reached treatment targets according to national guidelines. There were large differences between countries in terms of disease profile and medication use., Conclusion: DM patients in government clinics in four LMIC with considerable growth of DM have insufficient glycaemic control, frequent macrovascular and other complications, and insufficient preventive measures for cardiovascular disease. These findings underline the need to identify treatment barriers and secure optimal DM care in such settings., (© 2018 John Wiley & Sons Ltd.)

Background: Diabetes mellitus is a significant risk factor for tuberculosis (TB). We evaluated the performance of computer-aided detection for tuberculosis (CAD4TB) in people living with diabetes mellitus (PLWD) in Indonesia., Methods: PLWD underwent symptom screening and chest X-ray (CXR); sputum was examined in those with positive symptoms and/or CXR. Digital CXRs were scored using CAD4TB and analysed retrospectively using clinical and microbiological diagnosis as a reference. The area under the receiver operator curve (AUC) of CAD4TB scores was determined, and an optimal threshold score established. Agreement between CAD4TB and the radiologist's reading was determined., Results: Among 346 included PLWD, seven (2.0%) had microbiologically confirmed and two (0.6%) had clinically diagnosed TB. The highest agreement of CAD4TB with radiologist reading was achieved using a threshold score of 70 (κ = 0.41, P < 0.001). The AUC for CAD4TB was 0.89 (95%CI 0.73-1.00). A threshold score of 65 for CAD4TB resulted in a sensitivity, specificity, positive predictive value and negative predictive value of respectively 88.9% (95%CI 51.8-99.7), 88.5% (95%CI 84.6-91.7), 17.0% (95%CI 7.6-30.8) and 99.6% (95%CI 98.2-100). With this threshold, 48 (13.9%) individuals needed microbiological examination and no microbiologically confirmed cases were missed., Conclusions: CAD4TB has potential as a triage tool for TB screening in PLWD, thereby significantly reducing the need for microbiological examination.

Background: A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent tuberculosis infection. However, the regimen has been associated with poor adherence rates and with toxic effects., Methods: In an open-label trial conducted in nine countries, we randomly assigned adults with latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid for the prevention of confirmed active tuberculosis within 28 months after randomization. Noninferiority and potential superiority were assessed. Secondary outcomes included clinically diagnosed active tuberculosis, adverse events of grades 3 to 5, and completion of the treatment regimen. Outcomes were adjudicated by independent review panels., Results: Among the 3443 patients in the rifampin group, confirmed active tuberculosis developed in 4 and clinically diagnosed active tuberculosis developed in 4 during 7732 person-years of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin minus isoniazid) were less than 0.01 cases per 100 person-years (95% confidence interval [CI], -0.14 to 0.16) for confirmed active tuberculosis and less than 0.01 cases per 100 person-years (95% CI, -0.23 to 0.22) for confirmed or clinically diagnosed tuberculosis. The upper boundaries of the 95% confidence interval for the rate differences of the confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis were less than the prespecified noninferiority margin of 0.75 percentage points in cumulative incidence; the rifampin regimen was not superior to the isoniazid regimen. The difference in the treatment-completion rates was 15.1 percentage points (95% CI, 12.7 to 17.4). The rate differences for adverse events of grade 3 to 5 occurring within 146 days (120% of the 4-month planned duration of the rifampin regimen) were -1.1 percentage points (95% CI, -1.9 to -0.4) for all events and -1.2 percentage points (95% CI, -1.7 to -0.7) for hepatotoxic events., Conclusions: The 4-month regimen of rifampin was not inferior to the 9-month regimen of isoniazid for the prevention of active tuberculosis and was associated with a higher rate of treatment completion and better safety. (Funded by the Canadian Institutes of Health Research and the Australian National Health and Medical Research Council; ClinicalTrials.gov number, NCT00931736 .).

Setting: A community health clinic catchment area in the eastern part of Bandung City, Indonesia. Objective: To evaluate the feasibility of two different screening interventions using community health workers (CHWs) in detecting tuberculosis (TB) cases. Design: This was a feasibility study of 1) house-to-house TB symptom screening of five randomly selected 'neighbourhoods' in the catchment area, and 2) selected screening of household contacts of TB index patients and their neighbouring households. Acceptability was assessed through focus group discussions with key stakeholders. Results: Of 5100 individuals screened in randomly selected neighbourhoods, 48 (0.9%) reported symptoms, of whom 38 provided sputum samples; no positive TB was found. No TB cases were found among the 88 household contacts or the 423 neighbourhood contacts. With training, regular support and supervision from research staff and local community health centre staff, CHWs were able to undertake screening effectively, and almost all householders were willing to participate. Conclusion: The use of CHWs for TB screening could be integrated into routine practice relatively easily in Indonesia. The effectiveness of this would need further exploration, particularly with the use of improved diagnostics such as chest X-ray and sputum culture., Competing Interests: Conflicts of interest: none declared.

Background: Screening and treatment of latent TB infection (LTBI) and TB disease could reduce diabetes mellitus (DM)-associated TB. We aimed to describe the prevalence of LTBI and pulmonary TB among patients with DM in a TB-endemic setting., Methods: Patients with DM attending a hospital and community centres in Bandung, Indonesia, underwent LTBI screening using interferon gamma release assay (IGRA). TB was investigated by sputum smear, culture and x-ray. TB contacts from a parallel study were age- and sex-matched to patients with DM to compare LTBI and TB disease prevalence., Results: Of 682 patients with DM screened, 651 (95.5%) were eligible. Among 'TB disease-free' patients, LTBI prevalence was 38.9% (206/530; 95% CI 34.7-43.2). Patients with DM were less likely to be IGRA positive than TB contacts (38.6%, 54/140; 95% CI 30.5-46.6 vs 68.6%, 96/140; 95% CI 60.9-72.3: p<0.001); but had a higher disease prevalence (4.9%, 8/164; 95% CI 1.6-8.2 vs 1.2%, 2/164; 95% CI -0.5 to 2.9: p=0.054). Patients with DM in crowded households had increased risk of LTBI (AOR 1.71; 95% CI 1.19-2.45)., Conclusions: LTBI prevalence in patients with DM was lower than in household contacts, but patients with DM were more likely to have TB disease. Further studies should explore possible benefits of LTBI screening and preventive therapy in patients with DM in TB-endemic settings., (© The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We investigated the antibody responses to 10 prospective Mycobacterium tuberculosis (MTB) antigens and evaluated their ability to discriminate between latent (LTBI) and active pulmonary tuberculosis (TB). Our results indicate that plasma levels of anti-α-crystallin (ACR), antilipoarabinomannan, anti-trehalose 6,6'-dimycolate, and anti-tubercular-glycolipid antigen antibodies were higher in patients with active TB, compared to those in the LTBI and control subjects. No differences in the antibodies were observed between the control and LTBI subjects. Antibodies against the glycolipid antigens could not distinguish between Mycobacterium avium complex (MAC)-negative TB patients and MAC-infected LTBI individuals. The most useful serological marker was antibodies to ACR, with MAC-negative TB patients having higher titers than those observed in MAC-positive LTBI and control subjects. Our data indicate that antibody to ACR is a promising target for the serological diagnosis of patients with active TB patients. When dealing with antiglycolipid antibodies, MAC coinfection should always be considered in serological studies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Matricellular proteins such as osteopontin (OPN), galectin-9 (Gal-9), and tenascin-C (TN-C) are expressed not only under normal physiological conditions, but also during infection, inflammation and tumorigenesis. Plasma concentrations of matricellular proteins were studied to determine their diagnostic value as potential markers of tuberculosis (TB) activity. It was found that concentrations of OPN and TN-C were higher in patients with active TB than in healthy controls and individuals with latent infection. Moreover, LTBI patients had higher concentrations of OPN than did healthy controls. Gal-9 concentrations did not differ significantly between groups. Concentrations of matricellular proteins were higher in pleural fluid than in the plasma of patients with TB. Expression of matricellular proteins was also investigated in TB granulomas and other granulomatous diseases. Positive OPN and Gal-9 staining was observed in TB and sarcoidosis granulomas, but not in Crohn disease granulomas. The fibrotic ring around granulomas stained positive for TN-C in TB and sarcoidosis, but not in Crohn disease. Of the three matricellular proteins studied, OPN and TN-C may serve as reliable plasma markers for monitoring TB activity, whereas Gal-9 seems to be expressed more at the site of infection than in the systemic circulation., (© 2015 The Societies and Wiley Publishing Asia Pty Ltd.)