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Background: Tuberculosis preventive treatment (TPT) is a key component of tuberculosis elimination. To improve completion and reduce the burden for people and health systems, short, safe, and effective TPT regimens are needed. We aimed to compare safety and treatment completion of various doses and durations of rifampicin in people who were recommended to receive TPT., Methods: This partially blinded, parallel-arm, non-inferiority, randomised, controlled, phase 2b trial was done at seven university-affiliated clinics in Canada, Indonesia, and Viet Nam. Participants aged 10 years or older were included if they had an indication for TPT according to WHO guidelines for Indonesia and Viet Nam, or Canadian guidelines for Canadian sites, and a positive tuberculin skin test or interferon-γ release assay. Participants were randomly assigned (1:1:1) to receive oral rifampicin at 10 mg/kg once daily for 4 months (standard-dose group), 20 mg/kg daily for 2 months (20 mg/kg group), or 30 mg/kg daily for 2 months (30 mg/kg group). The randomisation sequence was computer generated with blocks of variable size (three, six, and nine) and stratified by country for Indonesia and Viet Nam, and by city within Canada. Participants and investigators were masked to dose in high-dose groups, but unmasked to duration in all groups. The two co-primary outcomes were safety (in the safety population, in which participants received at least one dose of the study drug) and treatment completion (in the modified intention-to-treat [mITT] population, excluding those ineligible after randomisation). Protocol-defined adverse events were defined as grade 3 or worse, or rash or allergy of any grade, judged by an independent and masked panel as possibly or probably related to the study. A margin of 4% was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03988933 (active)., Findings: Between Sept 1, 2019, and Sept 30, 2022, 1692 people were assessed for eligibility, 1376 were randomly assigned, and eight were excluded after randomisation. 1368 participants were included in the mITT population (454 in the standard group, 461 in the 20 mg/kg group, and 453 in the 30 mg/kg group). 589 (43%) participants were male and 779 (57%) were female. 372 (82%) in the standard-dose group, 329 (71%) in the 20 mg/kg group, and 293 (65%) in the 30 mg/kg group completed treatment. No participants in the standard-dose group, one (<1%) of 441 participants in the 20 mg/kg group, and four (1%) of 423 in the 30 mg/kg group developed grade 3 hepatotoxicity. Risk of protocol-defined adverse events was higher in the 30 mg/kg group than in the standard-dose group (adjusted risk difference 4·6% [95% CI 1·8 to 7·4]) or the 20 mg/kg group (5·1% [2·3 to 7·8]). There was no difference in the risk of adverse events between the 20 mg/kg and standard-dose groups (-0·5% [95% CI -2·4 to 1·5]; non-inferiority met). Completion was lower in the 20 mg/kg group (-7·8% [95% CI -13·6 to -2·0]) and the 30 mg/kg group (-15·4% [-21·4 to -9·4]) than in the standard-dose group., Interpretation: In this trial, 2 months of 30 mg/kg daily rifampicin had significantly worse safety and completion than 4 months of 10 mg/kg daily and 2 months of 20 mg/kg daily (the latter, a fully blinded comparison); we do not consider 30 mg/kg to be a good option for TPT. Rifampicin at 20 mg/kg daily for 2 months was as safe as standard treatment, but with lower completion. This difference remains unexplained., Funding: Canadian Institutes of Health Research., Competing Interests: Declaration of interests GJF reports receiving peer-reviewed grants as a principal investigator for operating funds for other tuberculosis research projects from the Australian Medical Research Council (paid to institution), and receipt of a AU$50 000 in-kind donation of rifapentine from Sanofi for a study outside the scope of work of the current trial. DM reports receiving peer-reviewed grants as the principal investigator for operating funds for other tuberculosis research projects from the Canadian Institutes of Health Research, and from the TB Trials Consortium of the US Centers for Disease Control and Prevention (paid to institution). All other authors declare no competing interests relevant to this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: TSR reports funding from Unitaid for research on the cost-effectiveness of short-course TPT outside of the submitted manuscript. NS-A declares no competing interests.

Objective: To evaluate the performance of Xpert Mycobacterium Tuberculosis/rifampicin (MTB/RIF) Ultra (Ultra) for diagnosis of childhood tuberculosis (TB) within public health systems., Methods: In this cross-sectional study, children aged <15 years with presumptive pulmonary TB were consecutively recruited and evaluated for TB at tertiary-level hospitals in Benin, Mali, and Ghana. Bivariate random-effects models were used to determine the pooled sensitivity and specificity of Ultra against culture. We also estimated its diagnostic yield against a composite microbiological reference standard (cMRS) of positive culture or Ultra., Results: Overall, 193 children were included in the analyses with a median (interquartile range) age of 4.0 (1.1-9.2) years, 88 (45.6%) were female, and 36 (18.7%) were HIV-positive. Thirty-one (16.1%) children had confirmed TB, 39 (20.2%) had unconfirmed TB, and 123 (63.7%) had unlikely TB. The pooled sensitivity and specificity of Ultra verified by culture were 55.0% (95% confidence interval [CI]: 28.0-79.0%) and 95.0% (95% CI: 88.0-98.0%), respectively. Against the cMRS, the diagnostic yield of Ultra and culture were 67.7% (95% CI: 48.6-83.3%) and 70.9% (95% CI: 51.9-85.8%), respectively., Conclusion: Ultra has suboptimal sensitivity in children with TB that were investigated under routine conditions in tertiary-level hospitals in three West African countries., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

TB is a major concern in the paediatric age group, especially in India. More than 3.33 lakh children between 0 and 14 years of age are affected by TB. Adolescent tuberculosis has been a neglected area and this age group accounts for about 800,000 cases of tuberculosis (TB) cases every year. Information regarding adolescent tuberculosis patient requiring ICU admission/care is very scanty (unlike adult tuberculosis), and the authors believe that the mode of ICU presentation and challenges in adolescents would almost be the same as in adults, although the outcome is generally expected to be better in the adolescent population in view of lesser comorbidities when compared to adults. ARDS, multiorgan dysfunction and meningitis are the most common reasons for admission to ICU. Critically ill patients with TB carry a high mortality and the increased mortality is likely due to multiorgan dysfunction, nosocomial infections and sepsis. Advanced disease with chronic undernourishment influences not just morbidity but mortality as well. Further, the heavy financial burden incurred for ICU care in TB patients with poor expected outcome is a major concern since TB occurs predominantly in low socio-economic populations., 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 © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to assess the role of nanopore sequencing using respiratory specimens in the early diagnosis of pulmonary tuberculosis (PTB) and simultaneously compare it head-to-head with Mycobacterium tuberculosis (MTB) culture, and Xpert MTB/rifampin (RIF)., Methods: The clinical data of 164 patients with suspected PTB were retrospectively reviewed to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of the acid-fast bacilli (AFB) smear, MTB culture, Xpert MTB/RIF, and nanopore sequencing and assess their diagnostic accuracy compared with culture combined with clinical diagnosis., Results: The overall sensitivity, specificity, PPV, NPV, and AUC of the AFB smear were 27.6%, 87.5%, 84.2%, 33.3%, and 0.58, respectively; for MTB culture, these values were 57.8%, 100.0%, 100.0%, 49.5%, and 0.79, respectively; for Xpert MTB/RIF, these values were 62.9%, 97.9%, 98.7%, 52.2%, and 0.80, respectively; and for nanopore sequencing, these values were 94.8%, 97.9%, 99.1%, 88.7%, and 0.96, respectively., Conclusion: The diagnostic accuracy of nanopore sequencing was excellent in terms of PTB diagnosis and was considerably better than that of the Xpert MTB/RIF and MTB culture. Nanopore sequencing could be an effective alternative to Xpert MTB/RIF for the initial detection of PTB to improve the accuracy of PTB diagnosis., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF) Ultra (Xpert-Ultra) has shown better sensitivity in comparison with Xpert MTB/RIF (Xpert) in extrapulmonary tuberculosis (TB), whereas the head-to-head comparison of these methods in TB lymphadenitis had barely been performed., Methods: Patients with undiagnosed lymphadenopathy were recruited prospectively and consecutively, and fine-needle aspiration (FNA) biopsy or lymph node tissue was collected. The specimen was subjected to smear, culture, Xpert, and Xpert-Ultra assays. Culture and/or smear for acid-fast bacilli (AFB) or AFB observed on histopathology were performed as a reference., Results: A total of 106 participants were recruited, including 41 confirmed TB, 33 probable TB, and 32 non-TB lymphadenopathies. The head-to-head comparison for MTB detection showed that Xpert-Ultra produced the highest sensitivity when compared with smear, culture, and Xpert (75.7% vs 5.4 %, 13.5%, and 48.7%). When Xpert-Ultra outcomes were integrated for diagnosis, the percentage of confirmed TB lymphadenitis cases increased from 55.4% (41/74) to 85.1% (63/74). The sensitivities of Xpert-Ultra and Xpert on tissue were 73.6% (95% CI: 59.4-84.3) and 39.6% (95% CI: 26.8-54.0), respectively. The sensitivity of Xpert-Ultra on FNA samples (81.0%, 95% CI: 57.4-93.7) was higher than that of Xpert (71.4%, 95% CI: 47.7-87.8)., Conclusion: Xpert-Ultra detected significantly more TB lymphadenitis cases than Xpert or culture. This superiority was particularly distinct using lymph node tissue than FNA detection., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Treatment outcomes for Multidrug-Resistant Tuberculosis (MDR TB) is generally poor. The study aims to know about the treatment outcomes of MDR-TB under programmatic conditions in Hyderabad District and to analyze the factors influencing the treatment outcomes., Methods: This is a retrospective study in which 377 patients of Hyderabad district, Telangana state who were diagnosed with MDR TB and registered at Drug Resistance TB Treatment site of Government General & Chest Hospital, Hyderabad from 4th quarter 2008 to 4th quarter 2013 were included in the study. Impact of Demographic factors (age, sex; Nutritional status (BMI); Co-morbid condition (Diabetes, HIV, Hypothyroidism); Programmatic factors (time delay in the initiation of treatment); Initial Resistance pattern on the outcomes were studied and analyzed., Results: The treatment outcomes of Multidrug-Resistant Tuberculosis under Programmatic Conditions were: 57% cured, 21.8% died, 19.6% defaulted, 1.1% failed and 0.5% switched to XDR. Age, Sex, BMI had a statistically significant impact on treatment outcomes. Hypothyroidism and Delay in the initiation of treatment >1 a month had an impact on the outcomes though not statistically significant. NO impact on treatment outcomes was found when Rifampicin resistance & INH sensitive patients were compared with those resistant to both INH and Rifampicin., Conclusion: To reduce MDR-TB transmission in the community, improvement of treatment outcomes, via ensuring adherence, paying special attention to elderly patients is required. The Programmatic Management of Drug Resistance Tuberculosis (PMDT) should seriously think of providing Nutritional support to patients with low BMI to improve outcomes. In the programmatic conditions if we could address the problems like delay in initiation of treatment and proper management of comorbidities like HIV, Diabetes, Hypothyroidism would definitely improve the treatment outcomes., Competing Interests: Conflicts of interest All authors have none to declare., (Copyright © 2021 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Objectives: Stigma contributes to diagnostic delay, disease concealment, and reduced wellbeing for people with multidrug-resistant tuberculosis (MDR-TB) and their communities. Despite the negative effects of stigma, there are no scales to measure stigma in people with MDR-TB. This study aimed to develop and validate a scale to measure stigma in people affected by MDR-TB in Vietnam., Study Design and Setting: People with rifampicin-resistant (RR)-MDR-TB who had completed at least 3 months of treatment were invited to complete a survey containing 45 draft stigma items. Data analysis included exploratory factor analysis, internal consistency, content, criterion and construct validity, and test-retest reliability., Results: A total of 315 people with RR/MDR-TB completed the survey. Exploratory factor analysis revealed a 14 item RR/MDR-TB stigma scale with four subscales, including guilt, social exclusion, physical isolation, and blame. Internal consistency and test-retest reliability were good (Cronbach's Alpha = 0.76, ICC = 0.92). Construct validity was adequate with moderate correlations with related constructs., Conclusion: Our RR/MDR-TB Scale demonstrated good psychometric properties in Vietnam. This scale will assist in the measurement of stigma in people with RR/MDR-TB. It will also aid in the evaluation of stigma reduction interventions in people with RR/MDR-TB., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Rapid tests to diagnose tuberculosis relies on molecular detection of the M. tuberculosis. GeneXpert MTB/RIF test identifies M. tuberculosis and rifampicin resistance. We present a case of simultaneous coinfection with M. tuberculosis and M. avium. M. tuberculosis was detected in the sputum by PCR GeneXpert method. Unrecognized coexistence of M. tuberculosis and M. avium modified the results of drug susceptibility tests making the primary identification of M. tuberculosis as multi-drug resistant strain. We performed in vitro experiments to investigate the effect of the coexistence of M. avium with M. tuberculosis on the results of GeneXpert method, and drug susceptibility test., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: WHO endorsed Xpert MTB/RIF assay has proven to be rapid with results obtained within 2h. The evidence base regarding the use of Xpert MTB/RIF in pulmonary TB is strong. Relatively few performance data have been published to date on detection of Mycobacterium tuberculosis in aspirated pus specimens from abscesses., Objectives: The aim of the study was to determine the sensitivity and specificity of Xpert MTB/RIF assay for the detection of M. tuberculosis and rifampicin resistance in aspirated pus specimens using culture on Lowenstein Jensen (LJ) medium and economic variant of proportion method (PM) for drug susceptibility testing (DST) as the reference standard., Results: Xpert MTB/RIF assay in comparison to conventional reference method showed sensitivity and specificity of 76.19% and 68.75% for detection of M. tuberculosis and 71.4% and 100% for detection of rifampicin resistance respectively., Conclusion: The simplicity, sensitivity, speed and automation makes this assay a very promising diagnostic test for detection of M. tuberculosis and rifampicin resistance in aspirated pus specimens., (Copyright © 2018 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Current treatments for tuberculosis (TB) are effective in controlling Mycobacterium tuberculosis (Mtb) growth, yet have significant side effects and do not prevent reinfection. Therefore, it is critical to understand why our host defense system is unable to generate permanent immunity to Mtb despite prolonged anti-tuberculosis therapy (ATT). Here, we demonstrate that treatment of mice with the most widely used anti-TB drugs, rifampicin (RIF) or isoniazid (INH) and pyrazinamide (PYZ), significantly altered the composition of the gut microbiota. Unexpectedly, treatment of mice with the pro-Mtb drugs INH and PYZ, but not RIF, prior to Mtb infection resulted in an increased bacterial burden, an effect that was reversible by fecal transplantation from untreated animals. Mechanistically, susceptibility of INH/PYZ-treated mice was associated with impaired metabolism of alveolar macrophages and defective bactericidal activity. Collectively, these data indicate that dysbiosis induced by ATT administered to millions of individuals worldwide may have adverse effects on the anti-Mtb response of alveolar macrophages.

Background: India has the world's highest estimated burden of multi-drug-resistant tuberculosis (MDR-TB). While prevalence of MDR-TB is known to be 2-3% among new TB patients and 12-17% in previously treated patients, programmatic information on the extent of transmission of TB and MDR-TB among household contacts of known MDR-TB patients is scarce. Systematic screening of household contacts of all MDR-TB patients on treatment was implemented as an intervention in the states of Andhra Pradesh and Telangana states of India. We undertook this prospective interventional study to measure the extent of TB symptoms developed among the household contacts of the known MDR-TB patients treated under Revised National TB Control Programme (RNTCP). The extent of rifampicin sensitive or resistance TB, bacteriologically confirmed using Xpert MTB-RIF, was examined among the symptomatic household contacts., Methods: All MDR-TB patients registered and on treatment under RNTCP between July 2011 and Sep 2013 in Andhra Pradesh and Telangana States were selected for the study. They were contacted through home visit by the trained RNTCP teams during 11th Dec 2013 and 7th Jan 2014. All household contacts of MDR-TB patients were screened once for TB symptoms such as cough, fever, weight loss, night sweats, and haemoptysis and extra pulmonary site specific symptoms if any. If found symptomatic, two sputum specimen were collected (spot-morning) from each of the contact and transported for testing on Xpert MTB-RIF for detection of pulmonary TB with or without RR-TB., Results: A total of 1750 MDR-TB patients were registered between July 2011 and Sep 2013. Of these, 1602 (91.5%) MDR-TB patients were included in the study. A total of 4858 household contacts of these 1602 patients were identified with an average of 3 contacts per MDR-TB patient. Of these, after excluding 87 (1.8%) contacts with past history of diagnosis and/or treatment for TB, 4771 (98.2%) contacts were screened for current signs and symptoms suggestive of TB. Their mean age was 28.5 years and 2151 (45%) were females. Of the 4771 contacts screened, 793 (16.6%) had at least one of the symptoms suggestive of TB of whom 781 (98.5%) had two sputum specimen transported and tested on Xpert MTB-Rif. Specimen could not be collected during the study period in 12 symptomatic patients including 4 with symptoms of extra pulmonary TB. Among 781 symptomatic contacts examined, 34 (4.4%) were bacteriologically confirmed with TB and 15 (44%) also had Rif resistance (RR)., Conclusions: High extent of TB, particularly RR-TB was observed among household contacts of known MDR-TB patients with symptom screening and early diagnosis using Xpert-MTB-Rif. Regular systematic active screening for TB and MDR-TB among this highly vulnerable group using Xpert-MTB-Rif is useful in India for early diagnosis among close contacts of known MDR-TB patients., (Copyright © 2018 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Nigeria is one of the ten countries with the highest tuberculosis (TB) burden globally and is experiencing an increasing incidence of drug resistance. This study aimed to determine the prevalence of mycobacterium tuberculosis and rifampicin resistance (DR-TB) among patients screened at the TB clinic of a tertiary institution in Lagos, South-West, Nigeria., Methods: A review of records of 840 patients with suspected drug-resistant TB was carried out from Gene Xpert test clinic register at a tertiary health facility from November 2013 to April 2015. The Data was analyzed with SPSS version 20, Chi square test was used to determine association between DR-TB and the factors examined and the level of significance was set at P < 0.05., Results: MTB detection among all screened suspects was 43.3%. The prevalence of rifampicin resistance was 17.6% among patients that were investigated for DR-TB and this occurred more in the working age group (15-54 years) with male to female ratio of 1.8:1. However, only history of close contact with known DR-TB patient was associated with DR-TB (P < 0.01)., Conclusion: The burden of DR-TB may be higher than previously thought. Drug resistance testing should be made more available to detect cases and thus control the emerging problem., (Copyright © 2018 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate whether rifabutin can improve treatment outcomes in patients with rifabutin-sensitive MDR-TB., Methods: A retrospective cohort study was performed on 76 patients with rifabutin-sensitive MDR-TB who were treated with or without rifabutin between 2006 and 2011., Results: Overall, 75% (57/76) of patients achieved favorable outcomes, including cure (53/76, 70%) and treatment completion (4/76, 5%). In contrast, 25% (19/76) had unfavorable treatment outcomes, which included treatment failure (6/76, 8%), death (2/76, 3%), loss to follow-up (4/76. 5%), and no evaluation due to transfer to other institutions (7/76, 9%). Rifabutin was given to 52 (68%) of the 76 patients with rifabutin-sensitive MDR-TB. Although favorable treatment outcomes were more frequent in patients who received rifabutin [81% (42/52)] than in those who did not receive rifabutin [63% (15/24)], this difference was not statistically significant (P=0.154). However, in multivariable regression logistic analysis, use of rifabutin was significantly associated with favorable treatment outcomes in patients with rifabutin-sensitive MDR-TB (adjusted odds ratio=9.80, 95% confidence interval=1.65-58.37, P=0.012)., Conclusions: These results suggest that the use of rifabutin can improve treatment outcomes in patients with rifabutin-sensitive MDR-TB., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic and often fatal disease of the CNS which may occur under immunosuppression in transplant patients. Brain stem PML is associated with a particularly bad prognosis. Here, we present a case of a renal transplant patient treated with mycophenolate mofetil (MMF) and tacrolimus who developed brain stem PML with limb ataxia, dysarthria and dysphagia. Diagnosis was established by typical MRI features and detection of JCV-DNA in the CSF. Immune reconstitution after stopping MMF and tacrolimus led to a complete and sustained remission of symptoms with improvement of the brain stem lesion over a follow-up over 20months. In summary, early detection of PML and consequent treatment may improve neurological outcomes even in brain stem disease with a notorious bad prognosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. Country-specific books (Hospice and Palliative Care Formulary USA, and Palliative Care Formulary, British and Canadian editions) are also available and can be ordered from www.palliativedrugs.com. The series editors welcome feedback on the articles (hq@palliativedrugs.com)., (Copyright © 2015. Published by Elsevier Inc.)

Introduction: Drug-resistant tuberculosis (TB) is an important public health problem in Lithuania with MDR rates in new cases reaching 11% in 2012. Currently available diagnostic tools are not fully adequate for an accurate and rapid result for diagnosis of TB and MDR-TB., Objectives: To evaluate the performance of Xpert(®) MTB/RIF assay for an early diagnosis of TB and detection of rifampicin (RIF) resistance in routine settings in Lithuania., Methods: A total of 833 individual respiratory samples obtained from patients previously treated for TB and MDR-TB contacts were tested using the Xpert MTB/RIF assay. Performance characteristics of the assay for TB and RIF resistance detection were calculated using culture and phenotypical DST results as a gold standard., Results: The overall sensitivity and specificity of the Xpert MTB/RIF assay for TB detection were 93.7% and 91.7%, respectively with the sensitivity for smear-negative specimens reaching 82.5%. Resistance to RIF was detected in 81 (20.7%) primary specimens with no false negative results; there were 4/225 (1.8%) false-positives among strains sensitive to rifampicin. Overall sensitivity and specificity of the molecular assay for detection of RIF resistance calculated against phenotypic DST results were 100% and 98.2%, respectively., Conclusions: Our results demonstrate very good performance of the Xpert MTB/RIF assay for the detection of TB and RIF resistance on primary respiratory specimens. It provides strong evidence that implementation of the assay for routine laboratory diagnosis in high drug-resistance settings may improve and facilitate TB diagnosis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Xpert MTB/RIF testing for Mycobacterium tuberculosis and rifampin resistance is being used extensively in countries with a high burden of TB. However, recent evidence suggests that it may not have the same accuracy or impact in high-income, low-burden TB countries., Methods: A prospective, pragmatic study was done between March 2012 and March 2014 to determine the feasibility, accuracy, and impact on TB disease management provided by the Xpert test in a remote, medically underserved, predominantly Inuit population in Iqaluit, Nunavut, Canada., Results: A total of 453 Xpert tests were run on sputum samples from 344 patients with suspected TB. Twenty-seven patients were identified as having active TB disease by culture. There were no cases of drug-resistant TB. Using culture as the gold standard, one Xpert test compared with one, two, or three sputum samples cultured per patient had a sensitivity of 85% (95% CI, 66%-95%) and a specificity of 99% (95% CI, 97%-100%) for detection of M tuberculosis. The indeterminate rate was 4.4% of all samples run. Treatment initiation was significantly shortened using Xpert vs the national standard of three smears (1.8 days vs 7.7 days, P < .007) and particularly shorter in smear-negative, culture-positive cases (1.8 days vs 37.1 days, P < .008)., Conclusions: In a predominantly Inuit population in a remote region of Canada where the burden of TB is high and no TB testing facilities are available, onsite Xpert testing was feasible and accurate and shortened the time to TB treatment initiation.

Early detection and effective treatment are crucial for tuberculosis control, but global case detection rates remain low. The diagnosis of paediatric and extrapulmonary disease is problematic and there are, as yet, no rapid screening tests to assist active case finding in the community. Progress has been made in clinic-based detection tools with the introduction of Xpert MTB/RIF, a nucleic acid amplification test that combines sample processing and analysis in a single instrument to provide a diagnostic result and detection of resistance to rifampicin in under 2h. Enthusiasm for Xpert MTB/RIF has been high and global rollout has been facilitated by donor agencies. However, concerns remain about access and sustainability due to the high cost and infrastructure requirements. Although more sensitive than smear microscopy, early studies suggest the impact of the new test on case detection rates and patient survival has been limited. Alternative technologies are being developed, including non-sputum-based tests to assist the detection of extrapulmonary disease. Evaluation studies are needed to provide evidence of the impact of the new technologies on patient outcomes. This will enable appropriate placement of new diagnostic products in the healthcare system to support the control and eventual eradication of tuberculosis disease., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: We investigated the efficacy of rifabutin (RFB)-containing regimens for the treatment of RFB-susceptible, multidrug-resistant tuberculosis (MDR-TB)., Methods: From 146 patients diagnosed with MDR-TB between January 2006 and December 2009 at Asan Medical Center in South Korea, 31 patients (21.2%) were found to have RFB-susceptible MDR-TB. Of these 31 patients, 14 patients who had been treated with RFB for more than one month were included. Forty-two patients with RFB-resistant MDR-TB were selected as a control group, and the outcomes of both groups were retrospectively compared., Results: Of 14 patients with RFB-susceptible MDR-TB, the mean age was 44.4 years and the proportion of extensively drug-resistant TB (XDR-TB) was 35.7% (5/14). Baseline characteristics and the drug resistance pattern (except RFB) did not differ between the two groups. Treatment success was achieved in 12 (85.7%) patients in the RFB group: cure in 10 (71.4%) and treatment completion in two (14.3%). The treatment success rate was 52.4% (22/42) in the control group (p = 0.032). Treatment failure was more common in patients of the control group (40.5% vs. 14.3%; p = 0.106)., Conclusions: RFB is useful as an additional drug in the treatment of MDR-TB in patients with RFB-susceptible MDR-TB., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Setting: The incidence of multi- and extensively drug-resistant TB cases is increasing in many countries. Resistance to rifampicin is widely considered a surrogate marker for multiple drug resistant TB. No efforts have been made to identify and quantify the drug-resistant genotypes in the Syrian and Lebanese communities., Objective: The genotypic characterization of rpo B mutations in the rifampicin drug-resistance region (RRDR) of resistant Mycobacterium tuberculosis isolates in Syrian and Lebanese patients., Design: The pyrosequencing technique was applied to DNA derived from the M. tuberculosis isolates of 56 patients., Results: RRDR sequencing identified 97 modified codons representing 35 different mutations; 31 (34%) of the 97 modifications were novel and have not been previously reported. The changes were mostly within codons 531 (37/97: 38%), 533 (28/97: 29%) and 526 (9/97: 9%). Additionally, 30 (54%) isolates had multiple codon changes., Conclusion: This study indicates the importance of the RRDR hotspot region for the detection of rifampicin resistance in MTB clinical isolates from Syrian and Lebanese patients. However, new mutations and mutations in other locations within the RRDR were also observed. The vast majority (95%) of the studied isolates from this pool of patients contained mutations in codons 531 and/or 533., (Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

Background: Mycobacterium kansasii infection is one of the most common causes of nontuberculous mycobacterial lung disease in the world. However, it is not possible to differentiate completely between M. kansasii and other nontuberculous mycobacteria (NTM) because of a lack of direct comparative studies. This retrospective study sought to identify their clinical and radiological features systematically., Methods: The sample included 98 consecutive patients with a culture-positive diagnosis of NTM infection, derived from the databases of the Laboratory of Microbiology of a tertiary medical center and two outpatient tuberculosis centers. Sixty-four patients had M. kansasii infection. All patients fulfilled disease criteria for treatment. Data on patient background and clinical features were collected, and chest radiographs were evaluated., Results: In the M. kansasii group, n = 27 (42%) were native-born Israelis compared to 9.4% (n = 3) of all other NTM groups (p = 0.0001). Similar rates of co-morbid diseases, including diabetes mellitus, heart disease, lung diseases, and malignancy were noted in both groups. Old TB was less common in the M. kansasii group compared to the other NTM (3.1% vs. 23.5%, p = 0.003). Clinical symptoms were significantly more common in patients with M. kansasii infection. On radiological study, M. kansasii infection was associated with more cavitations and unilaterality. Patients with M. kansasii infection had a higher likelihood of right upper lobe disease (p = 0.001). Pleural effusions and lymphadenopathy were found only in a few patients in each group., Conclusion: Major differences in the epidemiologic and clinical features of M. kansasii infection and other NTM have important diagnostic and clinical implications., (Copyright © 2012. Published by Elsevier Ltd.)

Background: The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings., Methods: We assessed adults (≥18 years) with suspected tuberculosis or multidrug-resistant tuberculosis consecutively presenting with cough lasting at least 2 weeks to urban health centres in South Africa, Peru, and India, drug-resistance screening facilities in Azerbaijan and the Philippines, and an emergency room in Uganda. Patients were excluded from the main analyses if their second sputum sample was collected more than 1 week after the first sample, or if no valid reference standard or MTB/RIF test was available. We compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with 2-3 sputum smears and 1-3 cultures, dependent on site, and drug-susceptibility testing. We assessed indicators of robustness including indeterminate rate and between-site performance, and compared time to detection, reporting, and treatment, and patient dropouts for the techniques used., Findings: We enrolled 6648 participants between Aug 11, 2009, and June 26, 2010. One-off MTB/RIF testing detected 933 (90·3%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67·1%) of 1041 for microscopy. MTB/RIF test sensitivity was 76·9% in smear-negative, culture-positive patients (296 of 385 samples), and 99·0% specific (2846 of 2876 non-tuberculosis samples). MTB/RIF test sensitivity for rifampicin resistance was 94·4% (236 of 250) and specificity was 98·3% (796 of 810). Unlike microscopy, MTB/RIF test sensitivity was not significantly lower in patients with HIV co-infection. Median time to detection of tuberculosis for the MTB/RIF test was 0 days (IQR 0-1), compared with 1 day (0-1) for microscopy, 30 days (23-43) for solid culture, and 16 days (13-21) for liquid culture. Median time to detection of resistance was 20 days (10-26) for line-probe assay and 106 days (30-124) for conventional drug-susceptibility testing. Use of the MTB/RIF test reduced median time to treatment for smear-negative tuberculosis from 56 days (39-81) to 5 days (2-8). The indeterminate rate of MTB/RIF testing was 2·4% (126 of 5321 samples) compared with 4·6% (441 of 9690) for cultures., Interpretation: The MTB/RIF test can effectively be used in low-resource settings to simplify patients' access to early and accurate diagnosis, thereby potentially decreasing morbidity associated with diagnostic delay, dropout and mistreatment., Funding: Foundation for Innovative New Diagnostics, Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership (TA2007.40200.009), Wellcome Trust (085251/B/08/Z), and UK Department for International Development., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Although rare in occidental countries, leprosy is an endemic disease throughout the world. Physicians may encounter imported cases and thus need to be aware of this diagnosis. We here report a 41-year-old male patient from French West Indies who presented with nonspecific extensive skin lesions and a peripheral neuropathy. Skin biopsy examination led to the diagnosis of borderline lepromatous leprosy.

Background: Sequelae of patients treated for multi-drug resistance tuberculosis (MDR-TB) remain unknown., Objective: To assess the clinical, bacteriological, radiological and functional status of MDR-TB patients after completion of treatment., Methodology: In a cross-sectional study, MDR-TB patients who had initiated standardized, community based therapy from January 2002 to December 2006 at Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases were investigated for their current clinical, bacteriological, radiological and functional status., Results: Between January 2002 to December 2006, 130 patients initiated treatment, of whom 24 died. Among rest 106 patients, 63 (59%) patients could be traced: 51 were currently alive while 12 had died. The 51 alive patients had completed a mean (+/- S.D.) post treatment period of 24 +/- 14.7 months ranging from 6 to 63 months before being enrolled in the study. Among currently alive patients who could be investigated, 78% had persistent respiratory symptoms; 98% had residual radiological sequelae with 40% having far advanced involvement. Abnormal Pulmonary Function Tests were observed in 45 (96%) patients with predominantly mixed type of ventilatory abnormality in 31 (66%) patients, while 9 (19%) had pure restriction and 5 (11%) had pure obstruction. None of the patients was found to be bacteriologically positive., Conclusion: Current study confirms the efficacy of the standardized regimen as none of the patients was bacteriologically positive on follow up. However, after completion of treatment significant number of cured MDR-TB patients are left with residual symptoms, abnormal X-ray chest and impairment of lung functions. These issues need to be addressed as a part of comprehensive management of MDR-TB patients under national programme.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of new multisource and reformulated immediate release (IR) solid oral dosage forms containing rifampicin as the only Active Pharmaceutical Ingredient (API) are reviewed. Rifampicin's solubility and permeability, its therapeutic use and index, pharmacokinetics, excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Solubility and absolute BA data indicate that rifampicin is a BCS Class II drug. Of special concern for biowaiving is that many reports of failure of IR solid oral dosage forms of rifampicin to meet BE have been published and the reasons for these failures are yet insufficiently understood. Moreover, no reports were identified in which in vitro dissolution was shown to be predictive of nonequivalence among products. Therefore, a biowaiver based approval of rifampicin containing IR solid oral dosage forms cannot be recommended for either new multisource drug products or for major scale-up and postapproval changes (variations) to existing drug products.

A rare case of tubercular endometritis occurred in a 63-year-old nullipara, postmenopausal woman, who was referred to our institute with vaginal bleeding and hyperechoic endometrial lesions at transvaginal sonography. At hysteroscopy the endometrial mucosa was lightly hyperemic and almost completely covered by multiple whitish and irregular deposits resulting in a "geographic map-like" aspect of the endometrial surface. The deposits had irregular borders and surface. Their size showed a wide range from less than 1mm to several millimeters. When touched by the tip of hysteroscope they did not bleed and peeled off easily. Diagnosis was performed with histologic examination and by using polymerase chain reaction. At follow-up hysteroscopy 6 months after antitubercular therapy, the endometrial mucosa appeared normal.

Objective: Genitourinary tuberculosis is a form of secondary tuberculosis with vague symptoms and presentation, and is rare in children. Antitubercular therapy is the cornerstone of treatment, although surgical intervention is required in a minority of the cases. We retrospectively evaluated our series of children with this disease, with special emphasis on the role of surgery., Materials and Methods: Case records of 17 children diagnosed and admitted with genitourinary tuberculosis at our center were reviewed. Clinical features, organ involvement, investigations, treatment and outcome of therapy were studied., Results: There were 11 male and six female children with a mean age of 11.6 years, admitted during the period July 1990 to June 2005. The most common presentation was storage lower urinary tract symptoms. The most commonly involved organ was the ureter in seven (41%) cases. Mycobacterium tuberculosis was identified on urinary examination in only five (29%) cases. A total of 28 procedures, including 15 endoscopic, four ablative and five reconstructive, were performed with some children requiring more than one procedure. Renal functional parameters stabilized or improved in four of five children (80%) in whom they were deranged at presentation., Conclusions: Genitourinary tuberculosis presents with a wide variety of clinical features and pathological lesions. Diagnosis is often delayed because of late presentation and many children present with cicatrization sequelae. Antitubercular drug therapy and judicious application of surgery achieve satisfactory results in the majority of cases. With improved drug therapy and experience with the use of bowel segments in the urinary tract, more reconstructive procedures are being performed with satisfactory outcomes. Children undergoing surgical procedures and reconstruction in particular need to be followed up rigorously.

Cytomegalovirus pneumonitis in a patient with pulmonary tuberculosis has been rarely reported. We report on a patient with nephrotic syndrome and documented pulmonary tuberculosis who received antituberculous therapy. Chest radiography showed a newly developed patch, and he underwent high-resolution computed tomography examination of the chest and open lung biopsy. Histopathologic studies of the lung showed interstitial pneumonitis, which had focal syncytial pneumocytes with focal nuclei atypia, inclusion bodies, and prominent eosinophilic nucleoli. Polymerase chain reactions for cytomegalovirus were positive in the sputum and biopsy specimen. The patient recovered well with ganciclovir treatment. When new pulmonary infiltrates develop in patients with pulmonary tuberculosis during antituberculous therapy, cytomegalovirus pneumonitis should not be overlooked.

Introduction: Loss to follow-up in clinical trials compromises achievement of study goals. We evaluated factors associated with loss to follow-up after completion of treatment phase in a large tuberculosis treatment trial (TBTC/USPHS Study 22) in the U.S. and Canada., Methods: Patients who were lost to follow-up were compared to those who reached a study end-point or successfully completed follow-up. A generalized estimating equation model was used to combine patient-specific and site-specific factors., Results: Of 1075 patients enrolled, 965 (89.8%) reached a study end-point, died, or completed the 2 year post-treatment follow-up phase, and 110 (10.2%) did not. Multivariate analysis showed the following factors to be independently associated with loss to follow-up: birth outside USA/Canada (OR 2.07, 95% CI 1.25-3.40, p=0.005), history of homelessness (OR 1.94, 95% CI 1.00-3.80, p=0.05), enrollment at a health department (OR 2.71, 95% CI 1.27-5.79, p=0.010), and use of any kind of incentive (cash/cash equivalent) during treatment phase (OR 3.04, 95% CI 1.73-5.33 p=0.0001)., Conclusions: Cultural or linguistic factors and lack of stable housing contribute to loss to follow-up. Attention to these factors could improve long-term retention in clinical trials. Enrollment at a health department and use of incentives during treatment phase may be markers for other factors leading to loss to follow-up.

Urinary tuberculosis has been rare in recent years and its diagnosis is difficult because there are no disease-specific symptoms. We tried to clarify the occurrence of urinary tuberculosis in recent years in our area. During the past 5 years, there were 12 patients with urinary tuberculosis in the clinics that participated in this study. Their chief complaints were frequent voiding in 7 patients and gross hematuria in 3 patients. They were diagnosed by nucleic acid amplification tests and imaging modalities such as excretory urography, computed tomography, and/or cystoscopy. Most of the patients received multidrug treatment and had relatively favorable treatment outcomes. There has been a small but neglected number of patients with urinary tuberculosis in recent years. We should keep this rare and difficult-to-diagnose disease in mind and suspect it when patients complain of longstanding urinary symptoms with no obvious cause.

Since after the first streptomycin 1944 trials, anti-tuberculous chemotherapy research has been focused upon establishing drug combination regimens capable of overcoming drug resistance and amenable to ambulatory treatment in resource strapped countries. The first milestone being the 1959 Madras trial comparing home and sanatorium treatment in South India. Subsequently, the MRC trials led Fox and Mitchison to indicate rifampicin, isoniazid and pyrazinamide as the first line drugs for short course, 6 month, regimens and the 1982 Hong Kong Chest Service trials established intermittent therapy as the ambulatory treatment standard for directly observed therapy (DOT). The rising of the HIV epidemic at the beginning of the 1980s has refuelled tuberculosis spread in Africa and Asia and contributed to the expansion of drug-resistant tuberculosis worldwide making the development of new drugs and drug regimens for ambulatory treatment a top priority. Led by biotechnological advances, molecular biology has been brought into TB laboratory diagnosis for the highly sensitive and specific rapid identification of Mycobacterium tuberculosis in biological samples. The field of immunological diagnosis of TB infection, dominated since the early 1900s by the intradermal tuberculin reaction has been put back in motion by the discovery of M. tuberculosis-specific proteins and peptides, now employed in blood tests of high sensitivity and specificity for the diagnosis of latent TB which may help with the identification of contacts at higher risk of active disease and the eradication of epidemic cases.

Purpose: To determine the clinical characteristics of 12 patients with Mycobacterium tuberculosis-induced carpal tunnel syndrome. This article also presents our intraoperative findings and surgical treatment results., Methods: Twelve patients with tuberculosis-induced carpal tunnel syndrome who had surgery during a 10-year period that began in March 1991 were reviewed. The entrance criterion was a positive histologic report of tuberculosis for surgical specimens. The preoperative evaluation leading to diagnosis was reviewed for all patients. Transection of the transverse carpal ligament and complete synovectomy were performed for all patients. After surgery the patients were given an antituberculosis regimen for 1 year and were followed up for an average of 6 years., Results: Twelve cases from a total of 1,180 patients with carpal tunnel syndrome were traced to M tuberculosis involvement of synovial tissue of the flexor tendons. Ten patients had large rice bodies in thick synovial membranes, and in the other 2 patients thick synovial tissue with yellow exudates were observed during surgery. In contrast to tendon involvement with rupture, no direct median nerve involvement was noted. Histopathologic study results of surgical specimens were positive for tuberculosis in all patients. Eight of 10 initial smears showed acid-fast bacillus and all 10 cultures of the specimens were positive for tubercle bacilli. Surgery and antituberculosis therapy were associated with a desirable outcome and sensory disturbance in the median nerve distribution resolved in all patients. Anterior wrist swelling disappeared and there has been no clinical or laboratory evidence of recurrence in all treated patients., Conclusions: Early diagnosis and surgical treatment combined with antituberculosis medical treatment are important in treating this condition. All patients treated were relieved of symptoms of synovial proliferation at the wrist, with no recurrence of the condition during the follow-up period., Type of Study/level of Evidence: Therapeutic, Level IV.

To assess whether the occurrence of rifampicin (RFP) resistance in methicillin-resistant Staphylococcus aureus (MRSA) is related to treatment of tuberculosis, we determined the RFP susceptibility of MRSA isolates obtained from tuberculosis patients and screened for mutation(s) in the rpoB gene of these isolates. The MICs of RFP for 84 MRSA isolates obtained from two hospitals in Japan were determined. DNA was sequenced in the region 1318-1602 nucleotides (nt) of the rpoB gene, which includes RFP resistance-determining clusters I (1384-1464 nt, 462-488 amino acids). The majority of MRSA isolates from tuberculosis wards, i.e., 48 of 51 (94%) [33 of 34 in a Tokyo hospital (97%) and 15 of 17 in a Chubu hospital (88%)], were resistant to RFP. Meanwhile, no isolates of 33 from the other wards were resistant to RFP. All RFP-resistant MRSA isolates had a mutation(s), including novel mutation(s) such as Val453-->AEPhe, Asp471-->AEAsn, and Ile527-->AELeu, in rpoB. An emergence of RFP-resistant MRSAs in tuberculosis wards in Japan was strongly suggested.

Patients with cystic fibrosis are particularly at risk of infection with non-tuberculous mycobacteria (NTM). Prevalence of these infections increases with age to around 15 %. The main species involved are M. abscessus and M. avium, the latter not found in children under 15. Diagnosis relies on clinical, radiological and above all bacteriological criteria defined by the ATS. Identification of the causal species of NTM is essential and requires genetic techniques, some of which are currently evaluated. Treatment depends on the mycobacterial species. For M. avium, combined therapy with rifampicin, clarithromycin and ethambutol must be extended 12 months after negativation. M. abscessus infection is particularly resistant to therapy. Usual treatment is a one month course of intravenous imipenem or cefoxitin plus amikacin followed by oral clarithromycin plus ethambutol for at least 12 months after negativation. In case of local lesions, surgery is an option.

The treatment of tuberculosis in children has evolved towards a short course regimen based on 6 months therapy with isoniazid and rifampin supplemented during the first 2 months with pyrazinamide in the case of pulmonary tuberculosis due to susceptible organisms. In the presence of adult type tuberculosis (upper lobe infiltration and cavitation) or in case of increased risk of drug - resistant organisms, a fourth drug is added initially. Extra pulmonary tuberculosis is generally treated similarly to pulmonary disease, except disseminated disease and meningitis, which are treated during 9 to 12 months. The treatment of children co-infected by HIV is more complex due to increased risk of drug resistant organisms and by interaction between rifampin and anti-retroviral agents. Concerning latent tuberculosis infection, the association of isoniazid and rifampin for 3 months is recommended. The drug treatment of tuberculosis should be integrated in a global approach comprising the detection of new cases, organisation of the treatment and follow up of the child to ensure the completion of treatment.

Opportunistic infections by Mycobacterium avium intracellulare complex in HIV infected patients, though common in adults, are rarely seen in infants. We herewith report an interesting case of an eight month old infant presenting with isolated axillary lymphadenitis, later on diagnosed to be tubercular lymphadenitis by Mycobacterium avium intracellulare and finally proved to be seropositive for HIV infection born to previously undetected HIV seropositive parents.

Multidrug-resistant tuberculosis (MDR-TB) presents an increasing threat to global tuberculosis control. Many crucial management issues in MDR-TB treatment remain unanswered. We reviewed the existing scientific research on MDR-TB treatment, which consists entirely of retrospective cohort studies. Although direct comparisons of these studies are impossible, some insights can be gained: MDR-TB can and should be addressed therapeutically in resource-poor settings; starting of treatment early is crucial; aggressive treatment regimens and high-end dosing are recommended given the lower potency of second-line antituberculosis drugs; and strategies to improve treatment adherence, such as directly observed therapy, should be used. Opportunities to treat MDR-TB in developing countries are now possible through the Global Fund to Fight AIDS, TB, and Malaria, and the Green Light Committee for Access to Second-line Anti-tuberculosis Drugs. As treatment of MDR-TB becomes increasingly available in resource-poor areas, where it is needed most, further clinical and operational research is urgently needed to guide clinicians in the management of this disease.

Objectives: Assess treatment effects by following up patients treated for Buruli ulcer in two hospitals with different treatment aspects, including widely differing surgical practices., Patients/methods: Treated patients were retrospectively identified from hospital records. Between 1994 and July 2000, 136 patients had been admitted for Buruli ulcer in both hospitals, and lived in areas covered in the research period. 78 (57%) Patients were included in the study. Treatment and status of the patient were analysed., Results: 27 (35%) Patients were not healed. Of the 33 patients treated in hospital A, six (18%) were not healed at follow-up, whereas of the 45 patients treated in hospital B, 21 (47%) were not healed. The length of stay in hospital A was significantly longer (P=0.002), and more operations on average were done per patient (P=0.002). In a univariate analysis, treatment in hospital A; the use of rifampicin (P=0.013); and BCG vaccination status (P=0.04) were all significantly associated with ulcer healing. Using a logistic regression model for multivariate analysis, only treatment as given in hospital A, with standard practice of wide surgical excision, appeared to predict ulcer healing independently (P=0.02)., Conclusions: This study shows large differences in treatment outcome between the two hospitals; the results support the hypothesis that extent of surgical treatment influences the chance of healing of Buruli ulcer.

We studied the effects of D-cycloserine, a partial NMDA receptor allosteric agonist, on ataxia in patients with spinocerebellar degeneration. Fifteen Japanese ataxic patients enrolled in a 14-day single-blind trial of D-cycloserine (daily oral dose of 50 mg) following a 14-day single-blind placebo phase. At the end of the D-cycloserine administration, there was a significant reduction in the posture, gait and total score of the international cooperative ataxia rating scale and in the time for walking and speech tasks. D-Cycloserine was well-tolerated and no adverse effect was observed. D-Cycloserine may have therapeutic efficacy for spinocerebellar ataxia.