Mueang Nonthaburi, Thailand
Mueang Nonthaburi, Thailand

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Siddiqi U.R.,Tohoku University | Siddiqi U.R.,Khulna Medical College | Punpunich W.,Rangsit University | Chuchottaworn C.,Chest Disease Institute | And 6 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2012

OBJECTIVE: To evaluate immunoglobulin G (IgG) and immunoglobulin A (IgA) responses to tuberculousg lycolipid antigen (TBGL-IgG and -IgA) in pulmonary tuberculosis (TB) patients and healthy controls in Thailand. DESIGN: Anti-TBGL antibody titres and other TB related markers were measured in the serum samples of 24 adults with pulmonary TB (PTB), 28 healthy adults (HA), 23 children with TB and 24 healthy children. RESULT: Both TBGL-IgG and -IgA titres were significantly higher only in adult PTB cases compared to controls (P < 0.001 for all). TBGL-IgG was highly sensitive (92%) in PTB patients, but frequent positive proportions of TBGL-IgG (46%) and -IgA (36%) in HAs were the cause of low specificities of TBGL-IgG (54%) and -IgA (64%); that of TBGL-IgG+IgA (75%) was the highest. Antibody titres were positively correlated in TBGL-IgG+IgA double-positive HAs (HA+, 7/28, P < 0.01), but not in HA- (P > 0.05). Serum IgG and IgA levels were not correlated with TBGL-IgG or -IgA levels (P > 0.05). KL-6 and leptin levels were normal and were not different between HA+ and HA-, indicating absence of active TB in HAs. CONCLUSION: Enhanced TBGL-IgG+IgA responses in HAs could indicate latent TB infection. Careful follow-up studies in HAs could clarify the significance of elevated TBGL antibodies as early disease markers. © 2012 The Union.


Bryant J.M.,Wellcome Trust Sanger Institute | Harris S.R.,Wellcome Trust Sanger Institute | Parkhill J.,Wellcome Trust Sanger Institute | Dawson R.,University of Cape Town | And 17 more authors.
The Lancet Respiratory Medicine | Year: 2013

Background: Recurrence of tuberculosis after treatment makes management difficult and is a key factor for determining treatment efficacy. Two processes can cause recurrence: relapse of the primary infection or re-infection with an exogenous strain. Although re-infection can and does occur, its importance to tuberculosis epidemiology and its biological basis is still debated. We used whole-genome sequencing-which is more accurate than conventional typing used to date-to assess the frequency of recurrence and to gain insight into the biological basis of re-infection. Methods: We assessed patients from the REMoxTB trial-a randomised controlled trial of tuberculosis treatment that enrolled previously untreated participants with Mycobacterium tuberculosis infection from Malaysia, South Africa, and Thailand. We did whole-genome sequencing and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing of pairs of isolates taken by sputum sampling: one from before treatment and another from either the end of failed treatment at 17 weeks or later or from a recurrent infection. We compared the number and location of SNPs between isolates collected at baseline and recurrence. Findings: We assessed 47 pairs of isolates. Whole-genome sequencing identified 33 cases with little genetic distance (0-6 SNPs) between strains, deemed relapses, and three cases for which the genetic distance ranged from 1306 to 1419 SNPs, deemed re-infections. Six cases of relapse and six cases of mixed infection were classified differently by whole-genome sequencing and MIRU-VNTR. We detected five single positive isolates (positive culture followed by at least two negative cultures) without clinical evidence of disease. Interpretation: Whole-genome sequencing enables the differentiation of relapse and re-infection cases with greater resolution than do genotyping methods used at present, such as MIRU-VNTR, and provides insights into the biology of recurrence. The additional clarity provided by whole-genome sequencing might have a role in defining endpoints for clinical trials. Funding: Wellcome Trust, European Union, Medical Research Council, Global Alliance for TB Drug Development, European and Developing Country Clinical Trials Partnership. © 2013 Bryant et al. Open Access article distributed under the terms of CC BY.


Pym A.S.,Kwazulu Research Institute for TB and HIV K RITH | Diacon A.H.,Stellenbosch University | Tang S.-J.,Capital Medical University | Conradie F.,University of Witwatersrand | And 12 more authors.
European Respiratory Journal | Year: 2016

Bedaquiline, a diarylquinoline, improved cure rates when added to a multidrug-resistant tuberculosis (MDR-TB) treatment regimen in a previous placebo-controlled, phase 2 trial (TMC207-C208; NCT00449644). The current phase 2, multicenter, open-label, single-arm trial (TMC207-C209; NCT00910871) reported here was conducted to confirm the safety and efficacy of bedaquiline. Newly diagnosed or previously treated patients with MDR-TB (including pre-extensively drug-resistant (pre-XDR)-TB or extensively drug-resistant (XDR)-TB) received bedaquiline for 24 weeks with a background regimen of anti-TB drugs continued according to National TB Programme treatment guidelines. Patients were assessed during and up to 120 weeks after starting bedaquiline. Of 233 enrolled patients, 63.5% had MDR-TB, 18.9% had pre-XDR-TB and 16.3% had XDR-TB, with 87.1% having taken second-line drugs prior to enrolment. 16 patients (6.9%) died. 20 patients (8.6%) discontinued before week 24, most commonly due to adverse events or MDR-TB-related events. Adverse events were generally those commonly associated with MDR-TB treatment. In the efficacy population (n=205), culture conversion (missing outcome classified as failure) was 72.2% at 120 weeks, and 73.1%, 70.5% and 62.2% in MDR-TB, pre-XDR-TB and XDR-TB patients, respectively. Addition of bedaquiline to a background regimen was well tolerated and led to good outcomes in this clinically relevant patient cohort with MDR-TB. Copyright © 2016 by the European Respiratory Society.


PubMed | University of Witwatersrand, Janssen Research & Development LLC, Chest Disease Institute, Medical Research Council and Kwazulu Research Institute for TB and HIV K RITH and 5 more.
Type: Clinical Trial, Phase II | Journal: The European respiratory journal | Year: 2016

Bedaquiline, a diarylquinoline, improved cure rates when added to a multidrug-resistant tuberculosis (MDR-TB) treatment regimen in a previous placebo-controlled, phase 2 trial (TMC207-C208; NCT00449644). The current phase 2, multicenter, open-label, single-arm trial (TMC207-C209; NCT00910871) reported here was conducted to confirm the safety and efficacy of bedaquiline.Newly diagnosed or previously treated patients with MDR-TB (including pre-extensively drug-resistant (pre-XDR)-TB or extensively drug-resistant (XDR)-TB) received bedaquiline for 24weeks with a background regimen of anti-TB drugs continued according to National TB Programme treatment guidelines. Patients were assessed during and up to 120weeks after starting bedaquiline.Of 233 enrolled patients, 63.5% had MDR-TB, 18.9% had pre-XDR-TB and 16.3% had XDR-TB, with 87.1% having taken second-line drugs prior to enrolment. 16 patients (6.9%) died. 20 patients (8.6%) discontinued before week 24, most commonly due to adverse events or MDR-TB-related events. Adverse events were generally those commonly associated with MDR-TB treatment. In the efficacy population (n=205), culture conversion (missing outcome classified as failure) was 72.2% at 120weeks, and 73.1%, 70.5% and 62.2% in MDR-TB, pre-XDR-TB and XDR-TB patients, respectively.Addition of bedaquiline to a background regimen was well tolerated and led to good outcomes in this clinically relevant patient cohort with MDR-TB.


PubMed | University of Amsterdam, Karolinska Institutet, Hospital for Tropical Diseases, Genome Institute of Singapore and 7 more.
Type: Journal Article | Journal: PloS one | Year: 2014

The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions.Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N=11), moderate (N=40) and mild (N=83) symptoms were compared with the febrile patients of unknown etiology (N=73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis.The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients.


PubMed | Ludwig Maximilians University of Munich, Institute of Respiratory Medicine, Chest Disease Institute, University of St. Andrews and 8 more.
Type: Comparative Study | Journal: The Lancet. Respiratory medicine | Year: 2014

Recurrence of tuberculosis after treatment makes management difficult and is a key factor for determining treatment efficacy. Two processes can cause recurrence: relapse of the primary infection or re-infection with an exogenous strain. Although re-infection can and does occur, its importance to tuberculosis epidemiology and its biological basis is still debated. We used whole-genome sequencing-which is more accurate than conventional typing used to date-to assess the frequency of recurrence and to gain insight into the biological basis of re-infection.We assessed patients from the REMoxTB trial-a randomised controlled trial of tuberculosis treatment that enrolled previously untreated participants with Mycobacterium tuberculosis infection from Malaysia, South Africa, and Thailand. We did whole-genome sequencing and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing of pairs of isolates taken by sputum sampling: one from before treatment and another from either the end of failed treatment at 17 weeks or later or from a recurrent infection. We compared the number and location of SNPs between isolates collected at baseline and recurrence.We assessed 47 pairs of isolates. Whole-genome sequencing identified 33 cases with little genetic distance (0-6 SNPs) between strains, deemed relapses, and three cases for which the genetic distance ranged from 1306 to 1419 SNPs, deemed re-infections. Six cases of relapse and six cases of mixed infection were classified differently by whole-genome sequencing and MIRU-VNTR. We detected five single positive isolates (positive culture followed by at least two negative cultures) without clinical evidence of disease.Whole-genome sequencing enables the differentiation of relapse and re-infection cases with greater resolution than do genotyping methods used at present, such as MIRU-VNTR, and provides insights into the biology of recurrence. The additional clarity provided by whole-genome sequencing might have a role in defining endpoints for clinical trials.Wellcome Trust, European Union, Medical Research Council, Global Alliance for TB Drug Development, European and Developing Country Clinical Trials Partnership.


Su C.-S.,Chang Gung University | Su C.-S.,Cleveland Clinic | Liu K.-T.,Kaohsiung Medical University | Panjapornpon K.,Cleveland Clinic | And 3 more authors.
Journal of Clinical Sleep Medicine | Year: 2012

Study Objectives: To evaluate functional outcomes in adults with REM-related obstructive sleep apnea (OSA) treated with positive airway pressure (PAP) therapy. Design: Retrospective observational study. Setting: Outpatient sleep clinic. Patients: 330 adults (171 males) with OSA receiving PAP therapy, including 130 with REM OSA and 200 with OSA not restricted to REM. Measurements and Results: REM OSA was defined as a REM apnea-hypopnea index (AHI) / NREM AHI > 2 and NREM AHI < 15. Patients had baseline and post-PAP functional outcomes, including Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Patient Health Questionnaire-9 (PHQ-9), and Functional Outcomes Sleep Questionnaire (FOSQ) scores. We compared functional outcomes, demographic, clinical and polysomnographic features, and PAP adherence in patients with REM OSA and OSA not restricted to REM. Female gender was significantly more common in REM OSA. Age, BMI, neck girth, and baseline ESS, FSS, PHQ-9, and FOSQ were similar between groups. Smoking history and comorbid disorders were also similar except for a higher prevalence of depression and cardiovascular disease in OSA not restricted to REM. All functional outcomes improved significantly after PAP therapy in both groups. Change from baseline to post treatment was similar for all functional outcomes between groups. Conclusions: The study is the first addressing clinical outcomes in REM OSA using validated measures. Functional outcomes in patients with REM OSA improve after treatment with PAP therapy comparable to that observed in patients with OSA not restricted to REM.


Zimmet H.,Monash University | Porapakkham P.,Chest Disease Institute | Sata Y.,Japan National Cardiovascular Center Research Institute | Haas S.J.,Monash University | And 3 more authors.
European Journal of Heart Failure | Year: 2012

Aims Bone marrow stem cell (BMSC) treatment of ST-segment elevation myocardial infarction (STEMI) has been primarily via the intracoronary route or via endogenous mobilization using granulocyte colony-stimulating factor (G-CSF). Studies have provided conflicting results. We therefore performed a meta-analysis of these treatments, examining short-and long-term efficacy and safety. Methods and results Randomized controlled trials (RCTs) of BMSC-based therapy for STEMI, delivered within 9 days of reperfusion, were identified by systematic search. Random effects models were used to calculate pooled effects of clinical outcomes, with meta-regression to assess dependence of the magnitude of effect sizes on study characteristics. Twenty-nine RCTs enrolling 1830 patients were included. Intracoronary BMSC therapy resulted in an overall improvement in left ventricular ejection fraction (LVEF) of 2.70% [95 confidence interval (CI) 1.483.92; P < 0.001] in the short term and 3.31% (95% CI 1.874.75; P < 0.001) longer term. Meta-regression suggested a doseresponse relationship between quantity of CD34 + cells delivered and increase in LVEF (P = 0.007). G-CSF treatment resulted in a trend towards similar benefits (P = 0.20). No significant differences were observed in pooled adverse outcome rates between intervention and control groups of either treatment approach, except for lower revascularization rates with intracoronary BMSC vs. control (odds ratio 0.68, 95% CI 0.470.97; P 0.03). Conclusions Intracoronary BMSC therapy post-STEMI improves LVEF beyond standard medical treatment, in both the short and longer term. G-CSF treatment shows positive but non-significant trends. Both treatments demonstrate safety comparable with conventional medical treatment. © 2011 The Author.


Pitaksajjakul P.,Mahidol University | Worakhunpiset S.,Mahidol University | Chaiprasert A.,Mahidol University | Boonyasopun J.,Chest Disease Institute | Ramasoota P.,Mahidol University
Southeast Asian Journal of Tropical Medicine and Public Health | Year: 2011

In order to identify mutations in gyrA and gyrB genes in 92 ofloxacin-resistant Mycobacterium tuberculosis (OFX r-MTB) clinical isolates collected from Siriraj Hospital, Mahidol University and Chest Disease Institute, Thailand. The quinolone resistance-determining regions (QRDR) of gyrA and gyrB in all 92 OFX r-MTB isolates were amplified using polymerase chain reaction and sequenced. There were 70 isolates with point mutations associated with ofloxacin resistance. In gyrA QRDR, 69 isolates had mutations in gyrA Gly88 (Ala/(75), Ala90 (Val), Ser91 (Pro) and Asp94 (Gly/Ala/His/Asn), the latter being the most common (42%). Only one isolate was found with mutation at position Asp495 (Asn). The other 22 isolates had no mutations in both gyrA and gyrB QRDR. Thus, point mutations in gyrA and gyrB QRDR were responsible for OFX r-MTB clinical isolates in Thailand.


Chuchottaworn C.,Chest Disease Institute
Journal of the Medical Association of Thailand | Year: 2010

Objective: To determine prevalence of extensively drug resistant tuberculosis (XDR-TB) in Chest Disease Institute. World Health Organization has given the definition of XDR-TB as multi-drug resistant tuberculosis which also resists fluoroquinolone and aminoglycoside. Material and Method: The present study was a retrospective review and conducted at Microbiology Unit, Chest Disease Institute. Drug susceptibility testing against fluoroquinolone and aminoglycoside have been done routinely since 1997. Laboratory results were studied to find XDR-TB patients and medical record information were reviewed. Laboratory results in 2006-2007 were not completed so were not included in the review. Results: The result of the present study showed that from 1997 to 2005. 10,289 patients were tested for drug susceptibility. XDR-TB was found in 39 patients. Prevalence of XDR-TB was 6, 6, 9, 4, 3, 3, 2, 4 and 2 patients from 1997-2005 respectively. Most of XDR-TB patients were also resistant to Streptomycin and 39% resistant to Ethambutol. No data of resistance to second line drugs of XDR-TB was done in the present study. Conclusion: The present study confirmed the existing of XDR-TB in Thai patient for a long time but not in increasing rate. The authorized TB Control organization should take XDR-TB as an important problem and developed capacity of tuberculosis laboratory in order to be able to diagnose XDR-TB.

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