Biphasic Medium Using Nicotinamide for Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis.

Reliable drug susceptibility testing of pyrazinamide (PZA) is technically difficult, since PZA activity is pH sensitive. The aim of this study was to evaluate a biphasic medium assay (BMA) for the reliable detection of PZA resistance in Mycobacterium tuberculosis (MTB) using nicotinamide (NIC) as a surrogate for PZA and identifying the appropriate cut-off value for the assay. The PZA susceptibility of 122 multidrug-resistant tuberculosis (MDR-TB) isolates and 39 drug-susceptible tuberculosis (DS-TB) isolates was examined using the BMA with NIC at four different concentrations (250, 500, 1000, and 2000 mg/L) and comparing the results with results from the BACTEC MGIT 960 reference method. Out of 122 MDR-TB isolates, 40 were identified as resistant by the BACTEC MGIT 960 system, of which 92.5% contained mutations within their pncA gene plus promoter region. A minimum inhibitory concentration of NIC ≥ 1000 mg/L was used as the cut-off concentration to define resistance in correlation with the MGIT 960 outcomes. NIC-BMA had a sensitivity of 90.91%, a specificity of 100%, and an accuracy of 97.52% compared with the MGIT 960 method. NIC-BMA is a promising assay to screen PZA resistance in microbiological laboratories without automation or advanced molecular instruments.

The use of BPaL containing regimen in the MDR/PreXDR TB treatments in Thailand.

The primary objective of this study was to evaluate the real-world effectiveness, side effects and challenges associated with the implementing of the groundbreaking BPaL-containing regimen in Thailand. Another aim was to investigate the characteristics and severity of the disease, the presence of abnormal extensive lesions in chest X-Rays and the influence of cavitation on sputum conversion. MATERIAL AND METHOD: The case series study included patients at TB clinic of Central chest institute of Thailand between August 2021-April 2023. All 28 Patients fullfilled the diagnostic criterial for MDR-TB by molecular tests and/or sputum culture. Sputum molecular test, utilizing GeneXpert MRB/XDR or Genotype MTBDRsl assay, was conducted. The 8 Pre-XDR patients who exhibited quinolone resistance and the 2 MDR-TB patients who encountered side effected from quinolone drugs were treated with BPaL regimen, while the remainder received BPaLM regimens. RESULTS: Among the 28 patients, 23 (82.1 %) successfully completed the treatment with favorable outcomes. However, one patient from the BpaL regimen died due to severe destroy lung lesion, and four patients from the BpalM regimen discontinued treatment. The investigation into the correlation between extension lesion, cavitation lesions, and culture conversion unveiled that the group with extension lesions and cavitation ≥4 cm had a diminished probability of achieving sputum culture conversion within 8 weeks in comparison to the group without attributes. The associated risk ratio was 0.56 (95 % CI, 0.14-2.27), p = 0.14. Although the study report minimal side effects, 6 patients (22.2 %) experienced peripheral neuropathy and a notable adverse reaction identified was optic neuritis, affecting 2 cases (7.1 %). SUMMARY: The administration of the BPaL-containing regimen resulted in rapid sputum conversion within 8 weeks and had minimal side effects.

Evaluation of the use of GeneXpert MTB/RIF in a zone with high burden of tuberculosis in Thailand.

GeneXpert MTB/RIF is a reliable molecular diagnostic tool capable of detecting Mycobacterium tuberculosis (MTB) and identifying genetic determinants of rifampicin (RIF) resistance. This study aimed to assess physicians' diagnostic decision-making processes for TB based on GeneXpert MTB/RIF results and how this affected the initiation of multidrug resistance (MDR) treatment. This study employed a mixed method: data were collected retrospectively from the medical records of TB patients and in-depth interviews were conducted with healthcare workers in areas with a high TB burden in Thailand. A total of 2,030 complete TB records from 2 patient groups were reviewed, including 1443 suspected cases with negative smear results and 587 with high risk of MDR-TB. GeneXpert MTB/RIF was routinely used to assist the physicians in their decision-making for the diagnosis of pulmonary tuberculosis (PTB) and the initiation of MDR-TB treatment. The physicians used it as a "rule-in test" for all patients with negative chest X-rays (CXR) and smear results, to ensure timely treatment. Approximately one-fourth of the patients with negative CXR/smear and GeneXpert MTB/RIF results were diagnosed with PTB by the physicians, who based their decisions on other evidence, such as clinical symptoms, and did not use GeneXpert MTB/RIF as a "rule-out test." GeneXpert MTB/RIF proved effective in early detection within a day, thereby radically shortening the time required to initiate second-line drug treatment. Despite its high sensitivity for detecting PTB and MDR-TB, GeneXpert MTB/RIF had contradictory results (false positive and/or false negative) for 21.8% of cases among patients with negative smear results and 41.1% of cases among patients with high risk of MDR-TB. Therefore, physicians still used the results of other conventional tests in their decision-making process. It is recommended that GeneXpert MTB/RIF should be established at all points of care and be used as the initial test for PTB and MDR-TB diagnosis.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-Resistant Tuberculosis (MDR-TB): a 5-Year Prospective In Vitro Surveillance Study of Bedaquiline and Other Second-Line Drug Susceptibility Testing in MDR-TB Isolates.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015 to 0.12 µg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cutoff values of 0.12 µg/ml by BMD and 0.25 µg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 µg/ml and 0.5 µg/ml for BMD and AD, respectively. When applied to the 5,036 MDR-TB isolates, bedaquiline-susceptible, -intermediate, and -resistant rates were 97.9%, 1.5%, and 0.6%, respectively, for BMD and 98.8%, 0.8%, and 0.4% for AD. Resistance rates were the following: 35.1% ofloxacin, 34.2% levofloxacin, 33.3% moxifloxacin, 1.5% linezolid, and 2% clofazimine. Phenotypic cross-resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Coresistance to bedaquiline and linezolid and clofazimine and linezolid were 0.1% and 0.3%, respectively, in MDR-TB and 0.2% and 0.4%, respectively, in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naive population. No treatment-limiting patterns for cross-resistance and coresistance have been identified with key TB drugs to date.

Cost-Effectiveness Analysis of Xpert MTB/RIF for Multi-Outcomes of Patients With Presumptive Pulmonary Tuberculosis in Thailand.

OBJECTIVES: The cost-effectiveness of screening adult patients for pulmonary tuberculosis is not clear. As such, this study aims to identify the cost-effectiveness between the Xpert MTB/RIF assay and the sputum acid-fast bacilli (AFB) smear. Multi-outcomes were correct diagnosis, time to achieve correct diagnosis, and gain in quality-adjusted life-years (QALYs). METHODS: A decision tree model was constructed to reveal a possible clinical pathway of tuberculosis diagnosis. The researchers used a clinical study to establish the probability of all clinical pathways for input into this model. The sample size was calculated following the correct diagnosis. Participants were randomly divided into 2 groups. A structural questionnaire and the Thai version of quality of life (EQ-5D-5L) were used for interviewing. RESULTS: The results showed that the time to achieve the correct diagnosis for the group using Xpert MTB/RIF was shorter than that for the group using the sputum AFB smear. Both the correct diagnosis and QALYs of the base case analysis presented the Xpert MTB/RIF method as dominant. A Monte Carlo model, which analyzed the Xpert MTB/RIF method, revealed that the average number of patients who were correctly diagnosed was 673, the QALYs were 945.85 years, and the total cost was $143 110.64. For the sputum AFB smear method, the average number who received a correct diagnosis was 592, the QALYs were 940.40 years, and the total cost was $196 666.84. Probabilistic and one-way sensitivity analysis confirmed that the Xpert MTB/RIF remained dominant. CONCLUSIONS: These results provide useful information for the National Strategic Plan to screen all adult patients for pulmonary tuberculosis.

A structural equation model of health-related quality of life among Thai men with chronic obstructive pulmonary disease.

AIM AND OBJECTIVES: To identify physiological, psychological and socioenvironmental factors that affect the health-related quality of life of Thai men living with chronic obstructive pulmonary disease. The vast majority of Thai persons living with chronic obstructive pulmonary disease are men. BACKGROUND: Little is known about the health-related quality of life of Thai people living with chronic obstructive pulmonary disease or about the physiological and psychosocial factors that most affect it. Applying a prevailing theoretical model of health-related quality of life, we explored how physiological, psychological and socioenvironmental factors simultaneously affect the health-related quality of life of Thai men with chronic obstructive pulmonary disease. DESIGN: A cross-sectional study design was used, together with the STROBE checklist. METHODS: In this study, 290 Thai male outpatients at a chronic obstructive pulmonary disease specialist clinic near Bangkok were recruited using purposive sampling. The participants completed the Satisfaction With Life Scale, the St. George Respiratory Questionnaire, the Center for Epidemiologic Studies Depression Scale, the Short Form Health Survey Version 2, the chronic obstructive pulmonary disease Self-Efficacy Scale and the Social Support Questionnaire. A structural equation model was used to examine the relationships between the assessed variables. RESULTS: Biological function (FEV-1, chronic obstructive pulmonary disease exacerbations), symptoms (chronic obstructive pulmonary disease and depression), functional status, general health perceptions and individual characteristics (age and self-efficacy to control dyspnoea) accounted for 56.9% of the variance in health-related quality of life. CONCLUSIONS: Symptoms of chronic obstructive pulmonary disease and depression were the main factors with statistically significant direct and indirect effects on the health-related quality of life of the Thai men in this study. The effects of both symptoms included an indirect effect on health-related quality of life through functional status and general health perceptions. RELEVANCE TO CLINICAL PRACTICE: The study findings may help nurses to better understand factors affecting health-related quality of life among men with chronic obstructive pulmonary disease. Preventing or minimising symptom exacerbations could be important in nursing practice. Cognitive-behavioural interventions addressing chronic obstructive pulmonary disease symptom management, depression screening and smoking cessation may improve health-related quality of life among Thai men with chronic obstructive pulmonary disease.

Diagnosis and management of latent tuberculosis infection in Asia: Review of current status and challenges.

Asia has the highest burden of tuberculosis (TB) and latent TB infection (LTBI) in the world. Optimizing the diagnosis and treatment of LTBI is one of the key strategies for achieving the WHO 'End TB' targets. We report the discussions from the Asia Latent TubERculosis (ALTER) expert panel meeting held in 2018 in Singapore. In this meeting, a group of 13 TB experts from Bangladesh, Cambodia, Hong Kong, India, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Taiwan, Thailand and Vietnam convened to review the literature, discuss the barriers and propose strategies to improve the management of LTBI in Asia. Strategies for the optimization of risk group prioritization, diagnosis, treatment, and research of LTBI are reported. The perspectives presented herein, may help national programs and professional societies of the respective countries enhance the adoption of the WHO guidelines, scale-up the implementation of national guidelines based on the regional needs, and provide optimal guidance to clinicians for the programmatic management of LTBI.

Effectiveness of Tuberculosis Screening Technology in the Initiation of Correct Diagnosis of Pulmonary Tuberculosis at a Tertiary Care Hospital in Thailand: Comparative Analysis of Xpert MTB/RIF Versus Sputum AFB Smear.

Pulmonary tuberculosis (PTB) is one of the top 10 causes of mortality worldwide in 2016. Early detection is very important, as it can help early treatment. This study compared 2 separate methods of diagnosing PTB among suspected patients, specifically examining correct diagnosis and the duration of receiving a correct diagnosis. It was carried out in a tertiary care public hospital in Bangkok, Thailand. Ninety patients were randomly assigned to 2 groups, one with the Xpert MTB/RIF ( Mycobacterium tuberculosis/rifampicin) and the other with sputum AFB (acid-fast bacilli) smear. The proportion of correct diagnosis was 90.9% and 83.7% for the Xpert MTB/RIF and the comparison group, respectively. The difference was not statistically significant ( P > .05). However, the time to correct diagnosis in the Xpert MTB/RIF group was significantly shorter than the comparison group (2.23 days). This could lead to early diagnosis and lower transmission rate of PTB cases. Results support the provision of Xpert MTB/RIF as the initial diagnostic test for PTB in Thailand.

Genotypic distribution of multidrug-resistant and extensively drug-resistant tuberculosis in northern Thailand.

BACKGROUND: Multidrug/extensively drug-resistant tuberculosis (M/XDR-TB) is a major public health problem, and early detection is important for preventing its spread. This study aimed to demonstrate the distribution of genetic site mutation associated with drug resistance in M/XDR-TB in the northern Thai population. METHODS: Thirty-four clinical MTB isolates from M/XDR-TB patients in the upper northern region of Thailand, who had been identified for drug susceptibility using the indirect agar proportion method from 2005 to 2012, were examined for genetic site mutations of katG, inhA, and ahpC for isoniazid (INH) drug resistance and rpoB for rifampicin (RIF) drug resistance. The variables included the baseline characteristics of the resistant gene, genetic site mutations, and drug susceptibility test results. RESULTS: All 34 isolates resisted both INH and RIF. Thirty-two isolates (94.1%) showed a mutation of at least 1 codon for katG, inhA, and ahpC genes. Twenty-eight isolates (82.4%) had a mutation of at least 1 codon of rpoB gene. The katG, inhA, ahpC, and rpoB mutations were detected in 20 (58.7%), 27 (79.4%), 13 (38.2%), and 28 (82.3%) of 34 isolates. The 3 most common mutation codons were katG 315 (11/34, 35.3%), inhA 14 (11/34, 32.4%), and inhA 114 (11/34, 32.4%). For this population, the best genetic mutation test panels for INH resistance included 8 codons (katG 310, katG 340, katG 343, inhA 14, inhA 84, inhA 86, inhA 114, and ahpC 75), and for RIF resistance included 6 codons (rpoB 445, rpoB 450, rpoB 464, rpoB 490, rpoB 507, and rpoB 508) with a sensitivity of 94.1% and 82.4%, respectively. CONCLUSION: The genetic mutation sites for drug resistance in M/XDR-TB are quite variable. The distribution of these mutations in a certain population must be studied before developing the specific mutation test panels for each area. The results of this study can be applied for further molecular M/XDR-TB diagnosis in the upper northern region of Thailand.

Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis.

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.

Risk Factors for Multidrug-Resistant Tuberculosis among Patients with Pulmonary Tuberculosis at the Central Chest Institute of Thailand.

There are limited data available on the risk factors for multidrug-resistant tuberculosis (MDR-TB). Therefore, we here conducted a retrospective matched case-control study among adults with pulmonary TB who received treatment at the Central Chest Institute of Thailand (CCIT) between January 2007 and December 2013, in order to determine the risk factors associated with MDR-TB among patients with pulmonary TB. We identified 145 patients with pulmonary MDR-TB (cases) and 145 patients with drug-sensitive pulmonary TB (controls). Multivariate analysis identified the independent risk factors for MDR-TB as follows: (1) ≥ 2 episodes of prior pulmonary TB (odds ratio [OR] 39.72, 95% confidence interval (95% CI) 7.86-200.66), (2) duration of illness > 60 days (OR 3.08, 95% CI 1.52-6.22), (3) sputum acid fast bacilli smear 3+ (OR 13.09, 95% CI 4.64-36.91), (4) presence of lung cavities (OR 3.82, 95% CI 1.89-7.73), and (5) presence of pleural effusion (OR 2.75, 95% CI 1.06-7.16). Prior pulmonary TB management with a non-category I regimen (P = 0.012) and having treatment failure or default as treatment outcomes (P = 0.036) were observed in a higher proportion among patients with MDR-TB. Particular characteristics of lung cavities, including the maximum diameter ≥ 30 mm (P < 0.001), the number of cavities ≥ 3 (P = 0.001), bilateral involvement (P < 0.001), and ≥ 2 lung zones involved (P = 0.001) were more commonly observed in patients with MDR-TB. In conclusion, these clinical factors and chest radiographic findings associated with MDR-TB among patients with pulmonary TB may help physicians to provide proper management of cases for prevention of the development and spread of MDR-TB in future.

FACTORS ASSOCIATED WITH DELAY IN TUBERCULOSIS TREATMENT AT 10 TERTIARY LEVEL CARE HOSPITALS IN THAILAND.

Tuberculosis (TB) is common in Thailand. Delay in initiating tuberculosis treatment is a major public health problem. Delay in treatment can result in more severe diseases, risk for death, and greater risk of tuberculosis transmission in the community. We attempted to determine the duration from onset of TB symptoms to the date of first consultation (patient delay) and the factors associated with that delay at 10 tertiary level care hospitals in Thailand. All participants aged 18 years who were willing to participate were included in the study, which was conducted from January to December 2012. A structured questionnaire and medical records were used to collect data. One hundred ninety-nine TB patients were included in the study. The mean age of subjects was 48 years (SD = 15.9); 69.8% were male. The median duration from onset of symptoms to first medical consultation was 30 days. On multivariate analysis, living in an urban area (adjusted odds ratio = 2.81; 95% CI: 1.29-6.14) was an independent risk factor for the delay. Delay in seeking help is a common problem among TB patients in Thailand. At risk populations need to be educated on the importance of presenting for early medical consultation if they have symptoms of TB.

Validation of the new COPD assessment test translated into Thai in patients with chronic obstructive pulmonary disease.

BACKGROUND: The COPD Assessment Test (CAT™) is a new questionnaire that has been developed recently for measuring the COPD patient's health status. It is known to have a good correlation with disease specific health status measured by St. George's Respiratory Questionnaire (SGRQ). For the wider application in clinical practice, it has been validated in many countries. We evaluated the reliability and validity of the translated CAT questionnaire for Thai COPD patients. METHODS: The study was designed as a cross-sectional validation study enrolling stable Thai COPD patients from three academic centers in Thailand at a single visit. The original CAT questionnaire was translated to Thai through linguistic validation process. The official Thai CAT and SGRQ questionnaires were filled by Thai patients after orientation by the out-patient nurse. The reliability of all items was assessed by Cronbach's formula for coefficient using pooled data from all patients. The validity of the questionnaire was tested using Pearson's correlation with SGRQ. RESULTS: A total of 98 Thai COPD patients completed the official Thai CAT questionnaire; 83% were male, mean age 71 years (SD 8.2), and % predicted of FEV1 56.6% (SD 20.9). The official Thai CAT questionnaire was shown to have a high internal consistency (Cronbach's α coefficient = 0.853). The assessment of validity of official Thai CAT questionnaire was moderately correlated with that of SGRQ (r = 0.652). CONCLUSIONS: The official Thai CAT questionnaire has an acceptable reliability and validity. It can be expected to serve as a short and simple tool for assessment of the health status of Thai COPD patients.

Outcomes of MDR/XDR-TB patients treated with linezolid: experience in Thailand.

BACKGROUND: Multi-drug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB) becomes an increasing problem in management. Linezolid has been off-label used in treatment of MDR/XDR-TB with major adverse effects. OBJECTIVE: To study outcomes of MDR/XDR-TB patients treated with linezolid in Central Chest Institute of Thailand. MATERIAL AND METHOD: MDR/XDR-TB patients treated with linezolid from 2009-2012 were retrospective analyzed RESULTS: Seventeen from 24 cases had finished treatment. Linezolid, capreomycin, cycloserine, clofazimine, moxifloxacin, ethambutol, kanamycin, ethionamide, and PAS were used in 24, 21, 8, 7, 5, 5, 2, 2, and 2 cases respectively. Long-term injection of capreomycin was used in 14/17cases for an average of 14.7 months. Three point three drugs were used as an average. Average conversion time of smear and culture were 53.5 and 52.1 days respectively Treatment time averaged 19.1 months. Fifteen of 24 cases were cured, seven were still ongoing treatment, all had sputum culture conversion, and two cases failed. There was no relapse in 13 cases after a follow-up that averaged 10.6 months. Linezolid was stopped in five cases from peripheral or optic neuropathy. Capreomycin was stopped in four cases from vestibulotoxic and nephrotoxic. CONCLUSION: Linezolid has good efficacy in treatment of MDR/XDR-TB with major adverse effect and should be used with caution. If capreomycin is susceptible or likely active, long-term injection should be considered when likely active drugs are not enough to strengthen the regimen.

Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study.

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.

Adverse drug reactions and outcome of short course anti-tuberculosis drugs between single daily dose and split drug dose (BID) in pulmonary tuberculosis.

BACKGROUND: Standard six months short course regimen for treatment of pulmonary tuberculosis is very effective and is recommended as standard treatment. But this regimen composes of many drugs and causes high adverse drug reactions especially gastrointestinal irritation. Spitted administration of drugs to two times a day may reduce adverse drug reactions. OBJECTIVE: To study adverse drug reactions and outcome of single daily versus split drug (two times a day) administration of standard six month short course regimen in newly diagnosed pulmonary tuberculosis. MATERIAL AND METHOD: Newly diagnosed pulmonary tuberculosis patients of the Central Chest Institute of Thailand were randomized to receive standard six months regimen once daily or two times a day (split drug). Patients were followed-up every two weeks and a questionnaire was used to detect adverse drug reactions. Outcome of treatment was evaluated according to national tuberculosis treatment guideline. RESULTS: 122 pulmonary tuberculosis were eligible for the present study and 61 patients were enrolled to each group of once daily or split drug regimen. Pulmonary tuberculosis patients who received split drug regimen had a higher cure rate but not statistical significance because of lower transfer out rate. Adverse drug reactions were similar in both groups of patients who received once daily and split drug regimen. Although split drug group had lower gastrointestinal adverse drug reactions. CONCLUSION: Split drug regimen has the same cure rate of treatment as single daily regimen and same adverse drug reactions.

Influenza A viral loads in respiratory samples collected from patients infected with pandemic H1N1, seasonal H1N1 and H3N2 viruses.

BACKGROUND: Nasopharyngeal aspirate (NPA), nasal swab (NS), and throat swab (TS) are common specimens used for diagnosis of respiratory virus infections based on the detection of viral genomes, viral antigens and viral isolation. However, there is no documented data regarding the type of specimen that yields the best result of viral detection. In this study, quantitative real time RT-PCR specific for M gene was used to determine influenza A viral loads present in NS, NPA and TS samples collected from patients infected with the 2009 pandemic H1N1, seasonal H1N1 and H3N2 viruses. Various copy numbers of RNA transcripts derived from recombinant plasmids containing complete M gene insert of each virus strain were assayed by RT-PCR. A standard curve for viral RNA quantification was constructed by plotting each Ct value against the log quantity of each standard RNA copy number. RESULTS: Copy numbers of M gene were obtained through the extrapolation of Ct values of the test samples against the corresponding standard curve. Among a total of 29 patients with severe influenza enrolled in this study (12 cases of the 2009 pandemic influenza, 5 cases of seasonal H1N1 and 12 cases of seasonal H3N2 virus), NPA was found to contain significantly highest amount of viral loads and followed in order by NS and TS specimen. Viral loads among patients infected with those viruses were comparable regarding type of specimen analyzed. CONCLUSION: Based on M gene copy numbers, we conclude that NPA is the best specimen for detection of influenza A viruses, and followed in order by NS and TS.

Extensively drug resistant tuberculosis (XDR-TB) in Chest Disease Institute, 1997-2005.

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.