119 results on '"Paramasivan CN"'
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2. Expanding Liquid Culture System for Tuberculosis
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Paramasivan, CN, primary and Balasangameshwara, VH, additional
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- 2009
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3. Antituberculosis Drug Resistance Surveillance
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Paramasivan, CN, primary and Balasangameshwara, VH, additional
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- 2009
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4. Docking studies on novel analogues of 8 methoxy fluoroquinolones against GyrA mutants of Mycobacterium tuberculosis
- Author
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Anand, RS, primary, Somasundaram, Sulochana, additional, Doble, Mukesh, additional, and Paramasivan, CN, additional
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- 2011
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5. Nocardia BACTERAEMIA IN AN HIV POSITIVE PATIENT - A CASE REPORT
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Ramchandran, R, primary, Swaminathan, S, additional, Sulochana, S, additional, and Paramasivan, CN, additional
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- 2003
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6. NocardiaBACTERAEMIA IN AN HIV POSITIVE PATIENT - A CASE REPORT
- Author
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Ramchandran, R, Swaminathan, S, Sulochana, S, and Paramasivan, CN
- Abstract
Nocardiosis has been recognized in recent times as an unusual opportunistic infection associated with HIV. Bacteraemia due to this pathogen is even rarer and only few cases have been reported in the literature. We report here a case of pulmonary nocardiosis with bacteraemia, which was initially diagnosed as pulmonary tuberculosis. A high index of suspicion is required to diagnose this infection as the clinical presentation and radiographic features mimic pulmonary tuberculosis.
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- 2003
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7. Second Correction for Singh et al., "Requirement of the mymA Operon for Appropriate Cell Wall Ultrastructure and Persistence of Mycobacterium tuberculosis in the Spleens of Guinea Pigs".
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Singh A, Gupta R, Vishwakarma RA, Narayanan PR, Paramasivan CN, Ramanathan VD, and Tyagi AK
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- 2022
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8. Correction for Singh et al., "Requirement of the mymA Operon for Appropriate Cell Wall Ultrastructure and Persistence of Mycobacterium tuberculosis in the Spleens of Guinea Pigs".
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Singh A, Gupta R, Vishwakarma RA, Narayanan PR, Paramasivan CN, Ramanathan VD, and Tyagi AK
- Published
- 2021
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9. Tuberculosis preventive treatment: the next chapter of tuberculosis elimination in India.
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Moonan PK, Nair SA, Agarwal R, Chadha VK, Dewan PK, Gupta UD, Ho CS, Holtz TH, Kumar AM, Kumar N, Kumar P, Maloney SA, Mase SR, Oeltmann JE, Paramasivan CN, Parmar MM, Rade KK, Ramachandran R, Rao R, Salhorta VS, Sarin R, Sarin S, Sachdeva KS, Selvaraju S, Singla R, Surie D, Tonsing J, Tripathy SP, and Khaparde SD
- Abstract
The End TB Strategy envisions a world free of tuberculosis-zero deaths, disease and suffering due to tuberculosis by 2035. This requires reducing the global tuberculosis incidence from >1250 cases per million people to <100 cases per million people within the next two decades. Expanding testing and treatment of tuberculosis infection is critical to achieving this goal. In high-burden countries, like India, the implementation of tuberculosis preventive treatment (TPT) remains a low priority. In this analysis article, we explore potential challenges and solutions of implementing TPT in India. The next chapter in tuberculosis elimination in India will require cost-effective and sustainable interventions aimed at tuberculosis infection. This will require constant innovation, locally driven solutions to address the diverse and dynamic tuberculosis epidemiology and persistent programme monitoring and evaluation. As new tools, regimens and approaches emerge, midcourse adjustments to policy and practice must be adopted. The development and implementation of new tools and strategies will call for close collaboration between local, national and international partners-both public and private-national health authorities, non-governmental organisations, research community and the diagnostic and pharmaceutical industry. Leading by example, India can contribute to global knowledge through operational research and programmatic implementation for combating tuberculosis infection., Competing Interests: Competing interests: None declared.
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- 2018
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10. Scaling-up the Xpert MTB/RIF assay for the detection of tuberculosis and rifampicin resistance in India: An economic analysis.
- Author
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Khaparde S, Raizada N, Nair SA, Denkinger C, Sachdeva KS, Paramasivan CN, Salhotra VS, Vassall A, and Hoog AV
- Subjects
- Humans, India, Sputum microbiology, Tuberculosis, Multidrug-Resistant, Antibiotics, Antitubercular therapeutic use, Biological Assay methods, Rifampin therapeutic use, Tuberculosis diagnosis, Tuberculosis drug therapy
- Abstract
Background: India is considering the scale-up of the Xpert MTB/RIF assay for detection of tuberculosis (TB) and rifampicin resistance. We conducted an economic analysis to estimate the costs of different strategies of Xpert implementation in India., Methods: Using a decision analytical model, we compared four diagnostic strategies for TB patients: (i) sputum smear microscopy (SSM) only; (ii) Xpert as a replacement for the rapid diagnostic test currently used for SSM-positive patients at risk of drug resistance (i.e. line probe assay (LPA)); (iii) Upfront Xpert testing for patients at risk of drug resistance; and (iv) Xpert as a replacement for SSM for all patients., Results: The total costs associated with diagnosis for 100,000 presumptive TB cases were: (i) US$ 619,042 for SSM-only; (ii) US$ 575,377 in the LPA replacement scenario; (iii) US$ 720,523 in the SSM replacement scenario; and (iv) US$ 1,639,643 in the Xpert-for-all scenario. Total cohort costs, including treatment costs, increased by 46% from the SSM-only to the Xpert-for-all strategy, largely due to the costs associated with second-line treatment of a higher number of rifampicin-resistant patients due to increased drug-resistant TB (DR-TB) case detection. The diagnostic costs for an estimated 7.64 million presumptive TB patients would comprise (i) 19%, (ii) 17%, (iii) 22% and (iv) 50% of the annual TB control budget. Mean total costs, expressed per DR-TB case initiated on treatment, were lowest in the Xpert-for-all scenario (US$ 11,099)., Conclusions: The Xpert-for-all strategy would result in the greatest increase of TB and DR-TB case detection, but would also have the highest associated costs. The strategy of using Xpert only for patients at risk for DR-TB would be more affordable, but would miss DR-TB cases and the cost per true DR-TB case detected would be higher compared to the Xpert-for-all strategy. As such expanded Xpert strategy would require significant increased TB control budget to ensure that increased case detection is followed by appropriate care.
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- 2017
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11. Index-TB guidelines: Guidelines on extrapulmonary tuberculosis for India.
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Sharma SK, Ryan H, Khaparde S, Sachdeva KS, Singh AD, Mohan A, Sarin R, Paramasivan CN, Kumar P, Nischal N, Khatiwada S, Garner P, and Tharyan P
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- Adrenal Cortex Hormones therapeutic use, Government Agencies legislation & jurisprudence, Guidelines as Topic, Humans, India epidemiology, Tuberculosis microbiology, Tuberculosis diagnosis, Tuberculosis epidemiology, Tuberculosis therapy
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Extrapulmonary tuberculosis (EPTB) is frequently a diagnostic and therapeutic challenge. It is a common opportunistic infection in people living with HIV/AIDS and other immunocompromised states such as diabetes mellitus and malnutrition. There is a paucity of data from clinical trials in EPTB and most of the information regarding diagnosis and management is extrapolated from pulmonary TB. Further, there are no formal national or international guidelines on EPTB. To address these concerns, Indian EPTB guidelines were developed under the auspices of Central TB Division and Directorate of Health Services, Ministry of Health and Family Welfare, Government of India. The objective was to provide guidance on uniform, evidence-informed practices for suspecting, diagnosing and managing EPTB at all levels of healthcare delivery. The guidelines describe agreed principles relevant to 10 key areas of EPTB which are complementary to the existing country standards of TB care and technical operational guidelines for pulmonary TB. These guidelines provide recommendations on three priority areas for EPTB: (i) use of Xpert MTB/RIF in diagnosis, (ii) use of adjunct corticosteroids in treatment, and (iii) duration of treatment. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, which were evidence based, and due consideration was given to various healthcare settings across India. Further, for those forms of EPTB in which evidence regarding best practice was lacking, clinical practice points were developed by consensus on accumulated knowledge and experience of specialists who participated in the working groups. This would also reflect the needs of healthcare providers and develop a platform for future research.
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- 2017
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12. Feasibility and Operational Performance of Tuberculosis Detection by Loop-Mediated Isothermal Amplification Platform in Decentralized Settings: Results from a Multicenter Study.
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Gray CM, Katamba A, Narang P, Giraldo J, Zamudio C, Joloba M, Narang R, Paramasivan CN, Hillemann D, Nabeta P, Amisano D, Alland D, Cobelens F, and Boehme CC
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- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, India, Male, Middle Aged, Peru, Sensitivity and Specificity, Uganda, Young Adult, Molecular Diagnostic Techniques methods, Nucleic Acid Amplification Techniques methods, Tuberculosis diagnosis
- Abstract
Currently available nucleic acid amplification platforms for tuberculosis (TB) detection are not designed to be simple or inexpensive enough to implement in decentralized settings in countries with a high burden of disease. The loop-mediated isothermal amplification platform (LAMP) may change this. We conducted a study in adults with symptoms suggestive of TB in India, Uganda, and Peru to establish the feasibility of using TB-LAMP (Eiken Chemical Co.) in microscopy laboratories compared with using smear microscopy against a reference standard of solid and liquid cultures. Operational characteristics were evaluated as well. A total of 1,777 participants met the eligibility criteria and were included for analysis. Overall, TB-LAMP sensitivities among culture-positive samples were 97.2% (243/250; 95% confidence interval [CI], 94.3% to 98.2%) and 62.0% (88/142; 95% CI, 53.5% to 70.0%) for smear-positive and smear-negative TB, respectively, but varied widely by country and operator. Specificities ranged from 94.5% (446/472; 95% CI, 92.0% to 96.4%) to 98.0% (350/357; 95% CI, 96.0% to 99.2%) by country. A root cause analysis identified high temperatures, high humidity, and/or low reaction volumes as possible causes for false-positive results, as they may result in nonspecific amplification. The study was repeated in India with training focused on vulnerable steps and an updated protocol; 580 participants were included for analysis. Specificity in the repeat trial was 96.6% (515/533; 95% CI, 94.7% to 97.9%). To achieve acceptable performance of LAMP at the microscopy center level, significant training and infrastructure requirements are necessary., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
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- 2016
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13. Line probe assay: a look at non-interpretable results.
- Author
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Paramasivan CN and Raizada N
- Subjects
- Humans, Mycobacterium tuberculosis, Rifampin
- Published
- 2016
- Full Text
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14. Piloting Upfront Xpert MTB/RIF Testing on Various Specimens under Programmatic Conditions for Diagnosis of TB & DR-TB in Paediatric Population.
- Author
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Raizada N, Sachdeva KS, Swaminathan S, Kulsange S, Khaparde SD, Nair SA, Khanna A, Chopra KK, Hanif M, Sethi GR, Umadevi KR, Keshav Chander G, Saha B, Shah A, Parmar M, Ghediya M, Jaju J, Boehme C, and Paramasivan CN
- Subjects
- Adolescent, Antibiotics, Antitubercular pharmacology, Body Fluids microbiology, Child, Child, Preschool, Female, Humans, Infant, Male, Mass Screening methods, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis isolation & purification, National Health Programs, Polymerase Chain Reaction methods, Reagent Kits, Diagnostic, Rifampin pharmacology, Sensitivity and Specificity, Tuberculosis, Multidrug-Resistant microbiology, Tuberculosis, Pulmonary microbiology, Molecular Diagnostic Techniques methods, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Pulmonary diagnosis
- Abstract
Background: India accounts for one-fifth of the global TB incidence. While the exact burden of childhood TB is not known, TB remains one of the leading causes of childhood mortality in India. Bacteriological confirmation of TB in children is challenging due to difficulty in obtaining quality specimens, in the absence of which diagnosis is largely based on clinical judgement. While testing multiple specimens can potentially contribute to higher proportion of laboratory confirmed paediatric TB cases, lack of high sensitivity tests adds to the diagnostic challenge. We describe here our experiences in piloting upfront Xpert MTB/RIF testing, for diagnosis of TB in paediatric population in respiratory and extra pulmonary specimens, as recently recommended by WHO., Method: Xpert MTB/RIF testing was offered to all paediatric (0-14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities in the project areas covering 4 cities of India., Results: Under this pilot project, 8,370 paediatric presumptive TB & presumptive DR-TB cases were tested between April and-November 2014. Overall, 9,149 specimens were tested, of which 4,445 (48.6%) were non-sputum specimens. Xpert MTB/RIF gave 9,083 (99.2%, CI 99.0-99.4) valid results. Of the 8,143 presumptive TB cases enrolled, 517 (6.3%, CI 5.8-6.9) were bacteriologically confirmed. TB detection rates were two fold higher with Xpert MTB/RIF as compared to smear microscopy. Further, a total of 60 rifampicin resistant TB cases were detected, of which 38 were detected among 512 presumptive TB cases while 22 were detected amongst 227 presumptive DR-TB cases tested under the project., Conclusion: Xpert MTB/RIF with advantages of quick turnaround testing-time, high proportion of interpretable results and feasibility of rapid rollout, substantially improved the diagnosis of bacteriologically confirmed TB in children, while simultaneously detecting rifampicin resistance.
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- 2015
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15. The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis.
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Sachdeva KS, Raizada N, Gupta RS, Nair SA, Denkinger C, Paramasivan CN, Kulsange S, Thakur R, Dewan P, Boehme C, and Arinaminpathy N
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- Antitubercular Agents therapeutic use, Humans, Incidence, India epidemiology, Models, Theoretical, Prevalence, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant epidemiology, Tuberculosis, Multidrug-Resistant microbiology, Tuberculosis, Multidrug-Resistant transmission, Epidemics prevention & control, Microbial Sensitivity Tests, Tuberculosis, Multidrug-Resistant prevention & control
- Abstract
Background: In India as elsewhere, multi-drug resistance (MDR) poses a serious challenge in the control of tuberculosis (TB). The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035. A key pillar of this approach is early diagnosis of tuberculosis, including use of higher-sensitivity diagnostic testing and universal rapid drug susceptibility testing (DST). Despite limitations of current laboratory assays, universal access to rapid DST could become more feasible with the advent of new and emerging technologies. Here we use a mathematical model of TB transmission, calibrated to the TB epidemic in India, to explore the potential impact of a major national scale-up of rapid DST. To inform key parameters in a clinical setting, we take GeneXpert as an example of a technology that could enable such scale-up. We draw from a recent multi-centric demonstration study conducted in India that involved upfront Xpert MTB/RIF testing of all TB suspects., Results: We find that widespread, public-sector deployment of high-sensitivity diagnostic testing and universal DST appropriately linked with treatment could substantially impact MDR-TB in India. Achieving 75% access over 3 years amongst all cases being diagnosed for TB in the public sector alone could avert over 180,000 cases of MDR-TB (95% CI 44187 - 317077 cases) between 2015 and 2025. Sufficiently wide deployment of Xpert could, moreover, turn an increasing MDR epidemic into a diminishing one. Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes. Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India.
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- 2015
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16. Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India.
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Sachdeva KS, Raizada N, Sreenivas A, Van't Hoog AH, van den Hof S, Dewan PK, Thakur R, Gupta RS, Kulsange S, Vadera B, Babre A, Gray C, Parmar M, Ghedia M, Ramachandran R, Alavadi U, Arinaminpathy N, Denkinger C, Boehme C, and Paramasivan CN
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- Antitubercular Agents pharmacology, Drug Resistance, Multiple, Bacterial, Female, Geography, Medical, Humans, India epidemiology, Male, Microbial Sensitivity Tests, Rifampin pharmacology, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Pulmonary drug therapy, Molecular Diagnostic Techniques, Public Health Surveillance, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant epidemiology, Tuberculosis, Pulmonary diagnosis, Tuberculosis, Pulmonary epidemiology
- Abstract
Background: Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India., Methods: This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates., Results: In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST., Conclusion: Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefold.
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- 2015
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17. A multi-site validation in India of the line probe assay for the rapid diagnosis of multi-drug resistant tuberculosis directly from sputum specimens.
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Raizada N, Sachdeva KS, Chauhan DS, Malhotra B, Reddy K, Dave PV, Mundade Y, Patel P, Ramachandran R, Das R, Solanki R, Wares DF, Sahu S, O'Brien R, Paramasivan CN, and Dewan PK
- Subjects
- Adult, Female, Humans, India, Isoniazid pharmacology, Male, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis physiology, Rifampin pharmacology, Molecular Diagnostic Techniques methods, Sputum microbiology, Tuberculosis, Multidrug-Resistant diagnosis
- Abstract
Unlabelled: Rifampicin (R) and isoniazid (H) are key first-line anti-tuberculosis drugs. Failure to detect resistance to these two drugs early results in treatment failure and poor clinical outcomes. The study purpose was to validate the use of the GenoType MTBDRplus line probe assay (LPA) to detect resistance to R and H in Mycobacterium tuberculosis strains directly from smear-positive sputum samples in India., Method: Smear positive sputum specimens from 320 patients were subjected to LPA and results compared against those from conventional Lowenstein Jensen (LJ) culture and drug susceptibility testing (C&DST). All specimens with discordant R DST results were subjected to either sequencing of the rpoB gene and/or repeat DST on liquid culture (MGIT 960) at a National Reference Laboratory., Results: Significantly higher proportion of interpretable results were observed with LPA compared to LJ C&DST (94% vs. 80%, p-value <0.01). A total of 248 patients had both LJ and LPA DST results available; 232 (93.5%) had concordant R DST results. Among the 16 discordant R DST results, 13 (81%) were resolved in agreement with LPA results. Final LPA performance characteristics were sensitivity 96% (CI: 90%-98%), specificity 99% (CI: 95%-99%), positive predictive value 99% (CI: 95%-99%), and negative predictive value 95% (CI: 89%-98%). The median turnaround testing time, including specimen transportation time, on LPA was 11 days as compared with 89 days for LJ C&DST., Conclusions: LPA proved highly accurate in the rapid detection of R resistance. The reduction in time to diagnosis may potentially enable earlier commencement of the appropriate drug therapy, leading to some reduction of transmission of drug-resistant strains.
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- 2014
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18. Bactericidal activity of PA-824 against Mycobacterium tuberculosis under anaerobic conditions and computational analysis of its novel analogues against mutant Ddn receptor.
- Author
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Somasundaram S, Anand RS, Venkatesan P, and Paramasivan CN
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- Anaerobiosis, Colony Count, Microbial, Drug Resistance, Bacterial, Humans, Molecular Docking Simulation, Mutant Proteins metabolism, Mycobacterium tuberculosis enzymology, Mycobacterium tuberculosis metabolism, Nitroreductases metabolism, Antitubercular Agents chemistry, Antitubercular Agents pharmacology, Microbial Viability drug effects, Mycobacterium tuberculosis drug effects, Nitroimidazoles chemistry, Nitroimidazoles pharmacology
- Abstract
Background: The resurgence of multi-drug resistant tuberculosis (MDR-TB) and HIV associated tuberculosis (TB) are of serious global concern. To contain this situation, new anti-tuberculosis drugs and reduced treatment regimens are imperative. Recently, a nitroimidazole, PA-824, has been shown to be active against both replicating and non-replicating bacteria. It is activated by the enzyme Deazaflavin-dependent nitroreductase (Ddn) present in Mycobacterium tuberculosis which catalyzes the reduction of PA-824, resulting in the release of lethal reactive nitrogen species (RNS) within the bacteria. In this context, PA-824 was analyzed for its activity against latent tuberculosis under anaerobic conditions and compared with rifampicin (RIF) and pyrazinamide (PZA). Recent mutagenesis studies have identified A76E mutation which affects the above mentioned catalysis and leads to PA-824 resistance. Hence, novel analogues which could cope up with their binding to mutant Ddn receptor were also identified through this study., Results: PA-824 at an optimum concentration of 12.5 μg/ml showed enhanced bactericidal activity, resulting in 0 CFU/ml growth when compared to RIF and PZA at normal pH and anaerobic condition. Further docking studies revealed that a combinatorial structure of PA-824 conjugated with moxifloxacin (ligand 8) has the highest binding affinity with the wild type and mutant Ddn receptor., Conclusions: PA-824 has been demonstrated to have better activity under anaerobic condition at 12.5 μg/ml, indicating an optimized dose that is required for overcoming the detoxifying mechanisms of M. tuberculosis and inducing its death. Further, the development of resistance through A76E mutation could be overcome through the in silico evolved ligand 8.
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- 2013
- Full Text
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19. Comparative evaluation of GenoType MTBDRplus line probe assay with solid culture method in early diagnosis of multidrug resistant tuberculosis (MDR-TB) at a tertiary care centre in India.
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Yadav RN, Singh BK, Sharma SK, Sharma R, Soneja M, Sreenivas V, Myneedu VP, Hanif M, Kumar A, Sachdeva KS, Paramasivan CN, Vollepore B, Thakur R, Raizada N, Arora SK, and Sinha S
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- Adult, Antibiotics, Antitubercular pharmacology, Bacterial Proteins genetics, Catalase genetics, Cross-Sectional Studies, Culture Techniques, Drug Resistance, Multiple, Bacterial, Early Diagnosis, Female, Genotyping Techniques, Humans, India, Isoniazid pharmacology, Male, Microbial Sensitivity Tests, Middle Aged, Multiplex Polymerase Chain Reaction, Mycobacterium tuberculosis drug effects, Nucleic Acid Hybridization, Oxidoreductases genetics, Rifampin pharmacology, Sensitivity and Specificity, Sputum microbiology, Tertiary Care Centers, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant microbiology, Young Adult, Molecular Diagnostic Techniques, Mycobacterium tuberculosis genetics, Tuberculosis, Multidrug-Resistant diagnosis
- Abstract
Background: The objectives of the study were to compare the performance of line probe assay (GenoType MTBDRplus) with solid culture method for an early diagnosis of multidrug resistant tuberculosis (MDR-TB), and to study the mutation patterns associated with rpoB, katG and inhA genes at a tertiary care centre in north India., Methods: In this cross-sectional study, 269 previously treated sputum-smear acid-fast bacilli (AFB) positive MDR-TB suspects were enrolled from January to September 2012 at the All India Institute of Medical Sciences hospital, New Delhi. Line probe assay (LPA) was performed directly on the sputum specimens and the results were compared with that of conventional drug susceptibility testing (DST) on solid media [Lowenstein Jensen (LJ) method]., Results: DST results by LPA and LJ methods were compared in 242 MDR-TB suspects. The LPA detected rifampicin (RIF) resistance in 70 of 71 cases, isoniazid (INH) resistance in 86 of 93 cases, and MDR-TB in 66 of 68 cases as compared to the conventional method. Overall (rifampicin, isoniazid and MDR-TB) concordance of the LPA with the conventional DST was 96%. Sensitivity and specificity were 98% and 99% respectively for detection of RIF resistance; 92% and 99% respectively for detection of INH resistance; 97% and 100% respectively for detection of MDR-TB. Frequencies of katG gene, inhA gene and combined katG and inhA gene mutations conferring all INH resistance were 72/87 (83%), 10/87 (11%) and 5/87 (6%) respectively. The turnaround time of the LPA test was 48 hours., Conclusion: The LPA test provides an early diagnosis of monoresistance to isoniazid and rifampicin and is highly sensitive and specific for an early diagnosis of MDR-TB. Based on these findings, it is concluded that the LPA test can be useful in early diagnosis of drug resistant TB in high TB burden countries.
- Published
- 2013
- Full Text
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20. Randomized clinical trial of thrice-weekly 4-month moxifloxacin or gatifloxacin containing regimens in the treatment of new sputum positive pulmonary tuberculosis patients.
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Jawahar MS, Banurekha VV, Paramasivan CN, Rahman F, Ramachandran R, Venkatesan P, Balasubramanian R, Selvakumar N, Ponnuraja C, Iliayas AS, Gangadevi NP, Raman B, Baskaran D, Kumar SR, Kumar MM, Mohan V, Ganapathy S, Kumar V, Shanmugam G, Charles N, Sakthivel MR, Jagannath K, Chandrasekar C, Parthasarathy RT, and Narayanan PR
- Subjects
- Adult, Antitubercular Agents administration & dosage, Antitubercular Agents adverse effects, Aza Compounds administration & dosage, Drug Administration Schedule, Drug Therapy, Combination, Female, Fluoroquinolones administration & dosage, Fluoroquinolones adverse effects, Gatifloxacin, Humans, Male, Middle Aged, Moxifloxacin, Quinolines administration & dosage, Recurrence, Sputum microbiology, Treatment Outcome, Tuberculosis, Pulmonary diagnosis, Tuberculosis, Pulmonary mortality, Young Adult, Antitubercular Agents therapeutic use, Aza Compounds therapeutic use, Fluoroquinolones therapeutic use, Quinolines therapeutic use, Tuberculosis, Pulmonary drug therapy
- Abstract
Background: Shortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India., Methods: Newly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens., Results: Of 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification., Conclusions: 4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB., Trial Registration: Clinical Trials Registry of India CTRI/2012/10/003060.
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- 2013
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21. Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): lessons learnt & challenges ahead.
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Sharma SK, Mohan A, Chauhan LS, Narain JP, Kumar P, Behera D, Sachdeva KS, Kumar A, Agarwal P, Awadh NT, Bansal A, Baruah S, Baruwa P, Balasangameshwara VH, Balasubramanian R, Bhardwaj AK, Bhargav S, Chadha S, Chaddha VK, Chhatwal M, Da Costa AL, Dash DP, Dep J, Dhingra S, Dhooria Harmeet S, Frieden TR, Garg A, Granich R, Gulati V, Gupta D, Gupta D, Gupta KB, Gupta KN, Jaikishan, Janmeja AK, Jawahar MS, Jethani SL, Jindal SK, John KR, Kalra OP, Kalra VP, Kannan AT, Kayshap S, Keshav Chander G, Khushwa SS, Kushwaha RS, Kumar V, Laskar B, Leela Itty Amma KR, Leuva AT, Maitra Malay K, Mesquita AM, Mathew T, Mundade Y, Munje R, Nagpal S, Nagaraja C, Nair S, Narayanan OR, Paramasivan CN, Parmar M, Prasad R, Phukan AC, Prasanna R, Purty A, Ramachandran R, Ramachandran R, Ravindran C, Reddy Raveendra HR, Sahu S, Santosha, Sarin R, Sarkar S, Sarma KC, Saxena P, Sehgal S, Sharath N, Sharma G, Sharma N, Shridhar PK, Shukla RS, Singh O, Singh NT, Singh V, Singla R, Sinha N, Sinha P, Sinha S, Solanki R, Sreenivas A, Srinath S, Subhakar K, Suri JC, Talukdar P, Tonsing J, Tripathy SP, Vaidyanathan P, Vashist RP, and Venu K
- Subjects
- Coinfection, Education, Medical, Extensively Drug-Resistant Tuberculosis complications, Extensively Drug-Resistant Tuberculosis microbiology, Extensively Drug-Resistant Tuberculosis physiopathology, HIV Infections complications, HIV Infections epidemiology, Humans, India, Antitubercular Agents therapeutic use, Extensively Drug-Resistant Tuberculosis drug therapy, Extensively Drug-Resistant Tuberculosis epidemiology, Mycobacterium tuberculosis pathogenicity
- Abstract
Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of 'new smear-positives' diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement.
- Published
- 2013
22. Global health: Integrating national laboratory health systems and services in resource-limited settings.
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Parsons LM, Somoskovi A, Lee E, Paramasivan CN, Schneidman M, Birx D, Roscigno G, and Nkengasong J
- Abstract
Laboratory systems worldwide are challenged not only by the need to compete for scarce resources with other sections of national health care programmes, but also with the lack of understanding of the critical role that laboratories play in the accurate diagnosis and monitoring of patients suffering from high-burdens of disease. An effective approach to establishing cost-effective laboratory systems that provide rapid and accurate test results for optimal impact on patient care is to move away from disease-specific programmes and establish integrated laboratory services. An integrated laboratory network provides all primary diagnostic services needed for care and treatment without requiring patients to go to different laboratory facilities for specific tests. Such a network focuses on providing quality-assured basic laboratory testing through the use of common specimen collection, reporting and diagnostic platforms that can be used across diseases. An integrated laboratory system also provides specimen transport to specialised laboratories and an environment conducive to the introduction and use of new and more complex technologies that would benefit the patient population and public health systems as a whole. As such, this article described various strategies for, and practical examples of, the successful integration of laboratory services., Competing Interests: The authors declare that they have no financial or personal relationship(s) which may have inappropriately influenced them in writing this article.
- Published
- 2012
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23. Evaluating PCR, culture & histopathology in the diagnosis of female genital tuberculosis.
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Thangappah RB, Paramasivan CN, and Narayanan S
- Subjects
- Adult, Female, Humans, Hysterosalpingography, Infertility, Female pathology, Laparoscopy, Middle Aged, Tuberculosis, Female Genital pathology, Young Adult, Infertility, Female microbiology, Mycobacterium tuberculosis isolation & purification, Polymerase Chain Reaction, Tuberculosis, Female Genital complications, Tuberculosis, Female Genital diagnosis
- Abstract
Background & Objectives: Genital tuberculosis (GTB) is one of the major causes for severe tubal disease leading to infertility. Unlike pulmonary tuberculosis, the clinical diagnosis of GTB is difficult because in majority of cases the disease is either asymptomatic or has varied clinical presentation. Routine laboratory values are of little value in the diagnosis. An absolute diagnosis cannot be made from characteristic features in hysterosalpingogram (HSG) or laparoscopy. Due to the paucibacillary nature of GTB, diagnosis by mycobacterial culture and histopathological examination (HPE) have limitations and low detection rate. The objective of this study was to evaluate the efficacy of PCR technique, culture and histopathological examination in the diagnosis of GTB in female infertility., Methods: This study included 72 infertile women who met the inclusion and exclusion criteria. After a detailed history and clinical examination all patients were subjected to investigations including pelvic sonogram, HSG and laparoscopy. Endometrial samples from were allocated for AFB smear, culture and HPE examination. Only 49 samples were available for PCR using IS 6110 and TRC 4 primers. In seven patients peritoneal fluid was also taken for culture and PCR. Based on the clinical profile and laparoscopic findings, a diagnostic criteria was derived to suspect GTB. Specific diagnostic tests were evaluated against this diagnostic criterion., Results: Laparoscopy was suggestive of tuberculosis in 59.7 per cent of cases, AFB smear was positive in 8.3 per cent, culture was positive in 5.6 per cent, HPE positive in 6.9 per cent and PCR was positive in 36.7 per cent of cases. Based on the diagnostic criteria, GTB was suspected in 28 of the 49 cases. On evaluating against the diagnostic criteria, the sensitivity of PCR, HPE and culture were 57.1, 10.7, 7.14 per cent respectively. The concordance of results between the clinical criteria and specific diagnostic tests were analysed by Kappa measure of agreement. The culture and HPE showed mild agreement with the clinical criteria, whereas PCR showed a moderate agreement. PCR was positive in Two of the 21 cases in whom GTB was not suspected. False positive PCR in these two cases were ruled out by multiple areas of sampling and re-sampling in one case. The PCR results were negative in 12 of the 28 cases. PCR using TRC 4 primers had a higher sensitivity (46.4%) than IS 6110 primers (25%) in detecting clinically suspected GTB., Interpretation & Conclusions: Our results showed that conventional methods of diagnosis namely, HPE, AFB smear and culture have low sensitivity. PCR was found to be useful in diagnosing early disease as well as confirming diagnosis in clinically suspected cases. False negative PCR was an important limitation in this study.
- Published
- 2011
24. Laboratory diagnosis of tuberculosis in resource-poor countries: challenges and opportunities.
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Parsons LM, Somoskövi A, Gutierrez C, Lee E, Paramasivan CN, Abimiku A, Spector S, Roscigno G, and Nkengasong J
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- Developing Countries, Humans, Medical Laboratory Science methods, Clinical Laboratory Techniques methods, Tuberculosis diagnosis, Tuberculosis epidemiology
- Abstract
With an estimated 9.4 million new cases globally, tuberculosis (TB) continues to be a major public health concern. Eighty percent of all cases worldwide occur in 22 high-burden, mainly resource-poor settings. This devastating impact of tuberculosis on vulnerable populations is also driven by its deadly synergy with HIV. Therefore, building capacity and enhancing universal access to rapid and accurate laboratory diagnostics are necessary to control TB and HIV-TB coinfections in resource-limited countries. The present review describes several new and established methods as well as the issues and challenges associated with implementing quality tuberculosis laboratory services in such countries. Recently, the WHO has endorsed some of these novel methods, and they have been made available at discounted prices for procurement by the public health sector of high-burden countries. In addition, international and national laboratory partners and donors are currently evaluating other new diagnostics that will allow further and more rapid testing in point-of-care settings. While some techniques are simple, others have complex requirements, and therefore, it is important to carefully determine how to link these new tests and incorporate them within a country's national diagnostic algorithm. Finally, the successful implementation of these methods is dependent on key partnerships in the international laboratory community and ensuring that adequate quality assurance programs are inherent in each country's laboratory network.
- Published
- 2011
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25. Performance of three LED-based fluorescence microscopy systems for detection of tuberculosis in Uganda.
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Albert H, Manabe Y, Lukyamuzi G, Ademun P, Mukkada S, Nyesiga B, Joloba M, Paramasivan CN, and Perkins MD
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- False Positive Reactions, HIV Infections complications, Humans, Light, Microscopy, Fluorescence methods, Mycobacterium tuberculosis metabolism, Observer Variation, Reagent Kits, Diagnostic, Reproducibility of Results, Sputum metabolism, Uganda, Microscopy, Fluorescence instrumentation, Tuberculosis, Pulmonary diagnosis
- Abstract
Background: Direct smear microscopy using Ziehl-Neelsen (ZN) staining is the mainstay of tuberculosis (TB) diagnosis in most high burden countries, but is limited by low sensitivity in routine practice, particularly in high human immunodeficiency virus (HIV) prevalence settings., Methods: We compared the performance of three commercial light emitting diode (LED)-based microscopy systems (Primostar™ iLED, Lumin™ and AFTER®) for fluorescent detection of Mycobacterium tuberculosis with ZN microscopy on slides prepared from sputum of TB suspects. Examination time for LED-based fluorescent microscopy (LED FM) and ZN slides was also compared, and a qualitative user appraisal of the LED FM systems was carried out., Results: LED FM was between 5.6 and 9.4% more sensitive than ZN microscopy, although the difference was not statistically significant. There was no significant difference in the sensitivity or specificity of the three LED FM systems, although the specificity of Fraen AFTER was somewhat lower than the other LED FM methods. Examination time for LED FM was 2 and 4 times less than for ZN microscopy. LED FM was highly acceptable to Ugandan technologists, although differences in operational performance of the three systems were reported., Conclusions: LED FM compares favourably with ZN microscopy, with equivalent specificity and a modest increase in sensitivity. Screening of slides was substantially quicker using LED FM than ZN, and LED FM was rated highly by laboratory technologists. Available commercial systems have different operational characteristics which should be considered prior to programmatic implementation.
- Published
- 2010
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26. First- and second-line drug resistance patterns among previously treated tuberculosis patients in India.
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Paramasivan CN, Rehman F, Wares F, Sundar Mohan N, Sundar S, Devi S, and Narayanan PR
- Subjects
- Antitubercular Agents administration & dosage, Directly Observed Therapy methods, Extensively Drug-Resistant Tuberculosis microbiology, Extensively Drug-Resistant Tuberculosis prevention & control, Humans, India epidemiology, Microbial Sensitivity Tests, Mycobacterium tuberculosis isolation & purification, Retrospective Studies, Treatment Failure, Tuberculosis, Multidrug-Resistant microbiology, Tuberculosis, Multidrug-Resistant prevention & control, Antitubercular Agents pharmacology, Extensively Drug-Resistant Tuberculosis epidemiology, Mycobacterium tuberculosis drug effects, Tuberculosis, Multidrug-Resistant epidemiology
- Abstract
Culture and drug susceptibility testing results of 2816 tuberculosis (TB) patients from across India who had failed repeated treatments from 2001 to 2004 were retrospectively analysed at the Tuberculosis Research Centre, Chennai. Of 1498 (53%) identified as having multidrug-resistant TB (MDR-TB), 671 (44.8%) were resistant to > or =1 second-line drugs (SLDs): 490 (32.7%) to ethionamide, 245 (16.4%) to ofloxacin and 169 (11.3%) to kanamycin; 69 (4.6%) were extensively drug-resistant TB (XDR-TB). Although from a highly select and non-representative patient group, such high SLD resistance levels, including XDR-TB, among MDR-TB patients is of concern. The prevention of MDR/XDR-TB through quality DOTS services, however, remains the priority. In addition, rapid scale-up of quality programmatic management under the RNTCP is needed, with more control and rational use of SLDs outside the programme.
- Published
- 2010
27. Experience establishing tuberculosis laboratory capacity in a developing country setting.
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Paramasivan CN, Lee E, Kao K, Mareka M, Kubendiran G, Kumar TA, Keshavjee S, Satti H, Alabi G, Raviglione M, and Roscigno G
- Subjects
- Antitubercular Agents pharmacology, Capacity Building, Clinical Laboratory Techniques economics, Clinical Laboratory Techniques standards, Developing Countries economics, HIV Infections complications, HIV Infections epidemiology, Health Policy, Humans, Laboratories economics, Laboratories organization & administration, Lesotho epidemiology, Microbial Sensitivity Tests standards, Quality Assurance, Health Care, Tuberculosis drug therapy, Tuberculosis epidemiology, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant epidemiology, Laboratories standards, Tuberculosis diagnosis, Tuberculosis, Multidrug-Resistant diagnosis
- Abstract
Objective: To describe the experience of strengthening laboratory diagnosis of tuberculosis (TB) in a resource-limited country with high TB-HIV (human immunodeficiency virus) and multidrug-resistant TB (MDR-TB) prevalence., Methods: In the Kingdom of Lesotho, which is confronted with high levels of TB, MDR-TB and HIV prevalence, between 2006 and 2008 a coalition of the Foundation for Innovative New Diagnostics, Partners In Health and the World Health Organization renovated the National TB Reference Laboratory and reinforced microscopy services, streamlined conventional culture and drug susceptibility testing (DST) and introduced modern TB diagnostic methods., Findings: It was feasible to establish a biosafety level three facility for solid culture and DST and an external quality assessment programme for smear microscopy within 4 months, all in 2007. Liquid culture and DST were introduced a month later. Preliminary results were comparable to those found in laboratories in industrialised countries. A year later, line-probe assay for the rapid detection of MDR-TB was introduced., Discussion: Through strong political commitment and collaboration, it is possible to rapidly establish quality assured TB diagnostic capacity, including current methods, in a resource-limited setting. Case detection and management for TB and MDR-TB have been greatly enhanced. From a low baseline, TB culture throughput in the laboratory increased ten-fold and has been sustained. This experience has served as a catalyst to translate policy into practice with new diagnostic technologies. It supports global policy setting to enhance and modernise laboratory work in developing countries.
- Published
- 2010
28. Surveillance of drug-resistant tuberculosis in the state of Gujarat, India.
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Ramachandran R, Nalini S, Chandrasekar V, Dave PV, Sanghvi AS, Wares F, Paramasivan CN, Narayanan PR, Sahu S, Parmar M, Chadha S, Dewan P, and Chauhan LS
- Subjects
- Antitubercular Agents, Bacteriological Techniques, Colony Count, Microbial, Ethionamide, Extensively Drug-Resistant Tuberculosis diagnosis, Extensively Drug-Resistant Tuberculosis microbiology, Female, Humans, India epidemiology, Isoniazid, Kanamycin, Male, Microscopy, Fluorescence, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis isolation & purification, Ofloxacin, Population Surveillance, Prevalence, Rifampin, Sputum microbiology, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant microbiology, Drug Resistance, Multiple, Bacterial, Extensively Drug-Resistant Tuberculosis epidemiology, Tuberculosis, Multidrug-Resistant epidemiology
- Abstract
Background: Limited information about the prevalence of drug-resistant tuberculosis (TB) has been reported from India, the country with the world's highest burden of TB. We conducted a representative state-wide survey in the state of Gujarat (2005 population: 56 million)., Methods: Mycobacterium tuberculosis isolates from a representative sample of new and previously treated smear-positive pulmonary TB (PTB) cases were subjected to drug susceptibility testing (DST) against first-line drugs at a World Health Organization supranational reference laboratory. Isolates found to have at least both isoniazid (INH) and rifampicin (RMP) resistance (i.e., multidrug-resistant TB [MDR-TB]) were subjected to second-line DST., Results: Of 1571 isolates from new patients, 1236 (78.7%) were susceptible to all first-line drugs, 173 (11%) had any INH resistance and MDR-TB was found in 37 (2.4%, 95%CI 1.6-3.1). Of 1047 isolates from previously treated patients, 564 (54%) were susceptible to all first-line drugs, 387 (37%) had any INH resistance and MDR-TB was found in 182 (17.4%, 95%CI 15.0-19.7%). Among 216 MDR-TB isolates, 52 (24%) were ofloxacin (OFX) resistant; seven cases of extensively drug-resistant TB (XDR-TB) were found, all of whom were previously treated cases., Conclusion: MDR-TB prevalence remains low among new TB patients in Gujarat, but is more common among previously treated patients. Among MDR-TB isolates, the alarmingly high prevalence of OFX resistance may threaten the success of the expanding efforts to treat and control MDR-TB.
- Published
- 2009
29. Bactericidal activity of moxifloxacin on exponential and stationary phase cultures of Mycobacterium tuberculosis.
- Author
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Sulochana S, Mitchison DA, Kubendiren G, Venkatesan P, and Paramasivan CN
- Subjects
- Antitubercular Agents pharmacology, Cells, Cultured, Drug Therapy, Combination, Fluoroquinolones, Isoniazid pharmacology, Moxifloxacin, Rifampin pharmacology, Anti-Infective Agents pharmacology, Aza Compounds pharmacology, Mycobacterium tuberculosis drug effects, Quinolines pharmacology
- Abstract
The bactericidal activity of moxifloxacin, alone and in combination with isoniazid and rifampin, was studied on exponential and stationary phase cultures of Mycobacterium tuberculosis H37 Rv strain, the standard strain which is a wild type of M. tuberculosis strain, not exposed to any environment, susceptible to all anti-tuberculosis drugs. Moxifloxacin alone was highly bactericidal, being intermediate in activity between isoniazid and rifampin on both types of culture. The speed of activity was slow with the stationary phase culture, causing a reduction from 6.41 log(10)cfu/ml to 2.70 log(10)cfu/ml on day 6 with the higher moxifloxacin concentration of 4 microg/ml and to 4.08 log(10)cfu/ml with the lower concentration of 0.25 microg/ml. When added to isoniazid, its activity against both exponential and stationary phase cultures was increased. However, when it was added to rifampin, no increase in activity was found with either type of culture. Addition of moxifloxacin to isoniazid and rifampin resulted in a slight increase in activity against the exponential culture but a considerable increase against the stationary culture with counts below the limit of detection at 4 and 6 days with both moxifloxacin concentrations. The synergism found with isoniazid, but not with rifampin, supports the view that isoniazid should be included in combinations with moxifloxacin during the therapy of pulmonary tuberculosis.
- Published
- 2009
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30. Localized Pulmonary Mycobacterium avium Disease in HIV-Infected Patients Without Access to HAART.
- Author
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Swaminathan S, Padmapriyadarsini C, Ramachandran R, Menon PA, Mohan NS, Kubendiran G, and Paramasivan CN
- Subjects
- AIDS-Related Opportunistic Infections drug therapy, CD4 Lymphocyte Count, HIV Infections drug therapy, Humans, Mycobacterium avium-intracellulare Infection, Antiretroviral Therapy, Highly Active, Mycobacterium avium
- Published
- 2007
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31. Simple direct drug susceptibility tests on sputum samples for early detection of resistance in tubercle bacilli.
- Author
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Mathew S, Nalini SM, Rahman F, Dastageer A, Sundaram V, and Paramasivan CN
- Subjects
- Antitubercular Agents pharmacology, Humans, Sensitivity and Specificity, Drug Resistance, Microbial, Microbial Sensitivity Tests methods, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis isolation & purification, Sputum microbiology
- Abstract
Background: Direct sensitivity test either by sputum concentrate (DS) or swab method (DSM) set up along with the primary culture would avoid the delay of four or more weeks required for the indirect test. A comparison of these two methods against the standard indirect sensitivity method under routine laboratory conditions is necessary to prove their merit., Method: Smear positive sputum samples were aliquoted and sensitivity tests were set up by both the direct methods as also an indirect test set up from the primary culture of the same sample., Results: The agreement with the indirect test results for isoniazid (INH) ranged from 97-98% for the DS method and 93-97% for the DSM method. The corresponding figures were 96-98% by the DS and 94-99% by the DSM method for rifampicin (R). The agreement was less satisfactory for ethambutol (Emb)., Conclusion: This study showed that direct sensitivity tests such as DS and DSM methods can detect most of the cultures resistant to INH and R (MDR) from the time growth appears on the primary culture, even as early as the second week of setting up the tests.
- Published
- 2007
32. Cutaneous tuberculosis.
- Author
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Umapathy KC, Begum R, Ravichandran G, Rehman F, Paramasivan CN, and Ramanathan VD
- Subjects
- Antitubercular Agents therapeutic use, Humans, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Cutaneous microbiology
- Published
- 2007
- Full Text
- View/download PDF
33. Surveillance of anti-tuberculosis drug resistance in Ernakulam District, Kerala State, South India.
- Author
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Joseph MR, Shoby CT, Amma GR, Chauhan LS, and Paramasivan CN
- Subjects
- Adolescent, Adult, Child, Female, Humans, India epidemiology, Male, Middle Aged, Population Surveillance, Prevalence, Tuberculosis, Multidrug-Resistant prevention & control, Tuberculosis, Multidrug-Resistant epidemiology
- Abstract
Setting: This is the first report on drug resistance surveillance (DRS) in Ernakulam District, Kerala, South India, based on a standard protocol from World Health Organization (WHO) guidelines., Objectives: To determine the level of drug resistance among smear-positive pulmonary tuberculosis (PTB) patients with no history of previous treatment in Ernakulam District, Kerala State., Design: Two additional sputum samples were collected from all consecutive new smear-positive PTB cases registered under the revised National TB Control Programme (RNTCP) formulated by the Government of India. The generic protocol developed by the Central TB Division for district level DRS in accordance with WHO guidelines was followed. Training of laboratory staff and other health personnel, periodic monitoring and quality assurance of laboratory work were carried out by the Tuberculosis Research Centre, Chennai., Results: A total of 305 (88.7%) sputum samples were positive for culture. Resistance to any drug was seen in 27.9% and multidrug-resistant tuberculosis (MDR-TB) was observed in 2%. Monoresistance to rifampicin and streptomycin was observed in respectively 1% and 17% of cases, and 27.1% resistance was observed to any drug in the younger age group., Conclusion: MDR-TB is within expected ranges in Ernakulam District. Further studies that include the private sector are needed in the state among different age groups.
- Published
- 2007
34. Analysis of fluoroquinolone resistance in clinical isolates of Mycobacterium tuberculosis from India.
- Author
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Sulochana S, Narayanan S, Paramasivan CN, Suganthi C, and Narayanan PR
- Subjects
- Humans, India epidemiology, Microbial Sensitivity Tests, Mycobacterium tuberculosis genetics, Tuberculosis, Multidrug-Resistant epidemiology, Tuberculosis, Multidrug-Resistant microbiology, Antitubercular Agents pharmacology, DNA Gyrase genetics, Drug Resistance, Bacterial genetics, Mutation, Mycobacterium tuberculosis drug effects, Ofloxacin pharmacology, Tuberculosis, Multidrug-Resistant drug therapy
- Abstract
Clinical isolates of Mycobacterium tuberculosis (47 ofloxacin-susceptible and 71 ofloxacin-resistant) strains obtained from individual patients from various parts of India were analyzed for gyr A mutation in quinolone resistant determining region (QRDR). Most of the mutations were seen clustered in the codons 90, 94 and 95, which is a hot spot region of QRDR. The types of mutations were correlated with the in vitro susceptibility pattern of the strains to ofloxacin. The mutations: A90V was found coded for low-level resistance (MIC
64 microg/ml) to ofloxacin. The resistance to fluoroquinolones was observed predominantly due to gyr A mutations. There were 2 highly resistant strains that did not show any mutations for gyr A, were further analyzed for gyr B mutations and were found negative for any mutations. However, there were two novel mutations, namely R68G and L109V, which were found in sensitive strain that did not code for any change in the susceptibility pattern and require further investigation. - Published
- 2007
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35. Moxifloxacin and gatifloxacin in an acid model of persistent Mycobacterium tuberculosis.
- Author
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Kubendiran G, Paramasivan CN, Sulochana S, and Mitchison DA
- Subjects
- Antitubercular Agents pharmacology, Colony Count, Microbial, Drug Synergism, Gatifloxacin, Hydrogen-Ion Concentration, Isoniazid pharmacology, Moxifloxacin, Mycobacterium tuberculosis growth & development, Pyrazinamide pharmacology, Rifampin pharmacology, Time Factors, Aza Compounds pharmacology, Fluoroquinolones pharmacology, Mycobacterium tuberculosis drug effects, Quinolines pharmacology
- Abstract
Studies in the mouse and in humans suggest that use of moxifloxacin and gatifloxacin may shorten the duration of treatment of pulmonary tuberculosis. We describe here the in vitro findings with gatifloxacin and moxifloxacin in regimens similar to those that might be used in the treatment of tuberculosis. The bactericidal activities of moxifloxacin and gatifloxacin were measured alone and in different combinations with isoniazid, rifampicin and pyrazinamide against a 30-day, stationary phase culture, at a pH of 5.9. There was a rapid, irregular fall in colony counts during the first 4 days followed by a slower consistent kill during days 4-21 with a mean kill of -0.36 (SD=2.74) and -0.106 (SD=0.011) log(10)CFU/ml/day, respectively. The 4-21-day kill is considered the best assessment of bactericidal activity against persisting bacilli that prolong treatment. The substitution of either of the quinolones for isoniazid in the control regimen of rifampicin, pyrazinamide and isoniazid did not increase bactericidal activity with log CFU of 5.00 and 4.88, but did result in increased bactericidal action with the log CFU of 4.11 and 4.10 for moxifloxacin and gatifloxacin respectively. Moxifloxacin and gatifloxacin had closely similar activities in all drug combinations. Adding moxifloxacin or gatifloxacin to the control regimen resulted in a significant increase in bactericidal action, considered sufficient to reduce the treatment duration.
- Published
- 2006
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36. National anti-tuberculosis drug resistance survey, 2002, in Myanmar.
- Author
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Ti T, Lwin T, Mar TT, Maung W, Noe P, Htun A, Kluge HH, Wright A, Aziz MA, and Paramasivan CN
- Subjects
- Adolescent, Adult, Antibiotics, Antitubercular therapeutic use, Cross-Sectional Studies, Ethambutol therapeutic use, Female, Health Surveys, Humans, Isoniazid therapeutic use, Male, Middle Aged, Myanmar epidemiology, Rifampin therapeutic use, Risk Factors, Streptomycin therapeutic use, Tuberculosis, Pulmonary epidemiology, Tuberculosis, Multidrug-Resistant epidemiology, Tuberculosis, Pulmonary drug therapy
- Abstract
Setting: Thirty townships of Myanmar., Objectives: To determine the proportions of drug-resistant tuberculosis (TB) in new and previously treated pulmonary tuberculosis (PTB) cases in Myanmar., Design: A cross-sectional study. Drug susceptibility was tested by the proportion method at the National Tuberculosis Reference Laboratory, Yangon., Results: Of 874 TB patients included from 30 sites, 849 isolates obtained from individual patients (733 from new cases and 116 from previously treated cases) were tested for susceptibility to four primary anti-tuberculosis drugs. Of 733 isolates tested from new TB patients, 10% were resistant to any one of the anti-tuberculosis drugs, 6.5% to isoniazid (INH), 4.6% to rifampicin (RMP) and 4.0% were multidrug-resistant (MDR). Of the 116 previously treated patients, 30.2% were resistant to any one of the drugs, 26.7% to INH, 15.5% to RMP and 15.5% were MDR. Previous anti-tuberculosis treatment of more than 1 month was strongly associated with the development of MDR-TB (adjusted OR 4.8, 95% CI 2.5-9.1)., Conclusion: The first national drug resistance survey in Myanmar revealed 4% and 15.5% MDR-TB among new and retreatment cases, respectively. Previous antituberculosis treatment was an important risk factor for MDR-TB. Continuous monitoring of drug resistance trends is needed
- Published
- 2006
37. Comprehensive findings on clinical, bacteriological, histopathological and therapeutic aspects of cutaneous tuberculosis.
- Author
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Umapathy KC, Begum R, Ravichandran G, Rahman F, Paramasivan CN, and Ramanathan VD
- Subjects
- Adult, Age Distribution, Antibiotics, Antitubercular therapeutic use, Child, Extremities, Female, Humans, Lupus Vulgaris drug therapy, Lupus Vulgaris microbiology, Lupus Vulgaris pathology, Male, Middle Aged, Sex Distribution, Skin microbiology, Skin pathology, Treatment Outcome, Tuberculosis, Cutaneous drug therapy, Tuberculosis, Cutaneous pathology, Tuberculosis, Lymph Node drug therapy, Tuberculosis, Lymph Node microbiology, Tuberculosis, Lymph Node pathology, Antitubercular Agents therapeutic use, Isoniazid therapeutic use, Rifampin therapeutic use, Tuberculosis, Cutaneous microbiology
- Abstract
Objective: To define the bacteriological and histological correlates of the three predominant clinical forms of cutaneous tuberculosis and to evaluate the efficacy of a 9-month daily regimen containing rifampicin and isoniazid., Methods: In the dermatological clinics of two major teaching hospitals in Chennai, 213 patients with suspected clinical manifestations of cutaneous tuberculosis underwent examination and a skin biopsy for bacteriological and histological tests. They were treated with a daily regimen of rifampicin and isoniazid for 9 months and follow-up for 3 years., Results: Bacteriological and/or histological confirmation of tuberculosis was obtained in 88% of the cases. Lupus vulgaris lesions were seen mainly in the extremities and verrucosa cutis occurred predominantly on the sole and foot, while the cervical and axillary regions were the commonest sites for scrofuloderma. Ninety-two per cent of the patients showed resolution of the lesions within the first 6 months of chemotherapy; 1% failed to respond to this regimen. There was no relapse in any of the cases during the follow-up period of 3 years., Conclusions: Clinical findings were adequate to identify major forms of cutaneous tuberculosis as evidenced by bacteriological and histopathological examination. A daily regimen of rifampicin and isoniazid for 9 months was effective in treating cutaneous tuberculosis.
- Published
- 2006
- Full Text
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38. Initial drug susceptibility profile of M. tuberculosis among patients under TB programme in South India.
- Author
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Santha T, Thomas A, Chandrasekaran V, Selvakumar N, Gopi PG, Subramani R, Rajeswari R, Rani B, Paramasivan CN, Perumal M, Wares F, and Narayanan PR
- Subjects
- Antitubercular Agents therapeutic use, Drug Resistance, Bacterial, Humans, Isoniazid pharmacology, Isoniazid therapeutic use, Rifampin pharmacology, Rifampin therapeutic use, Streptomycin pharmacology, Streptomycin therapeutic use, Tuberculosis, Pulmonary drug therapy, Antitubercular Agents pharmacology, Microbial Sensitivity Tests, Mycobacterium tuberculosis isolation & purification, Tuberculosis, Pulmonary microbiology
- Abstract
Setting: Pulmonary tuberculosis (PTB) patients enrolled for treatment at government health facilities in a sub-district of Thiruvallur district, Tamil Nadu, India., Objectives: To determine the drug susceptibility profile among PTB patients admitted to treatment according to the Revised National Tuberculosis Control Programme (RNTCP)., Methodology: From May 1999 to December 2003, two additional sputum samples were collected from all patients at the start of anti-tuberculosis treatment under DOTS and were transported to a central laboratory for Mycobacterium tuberculosis culture and drug susceptibility testing (DST)., Results: DST results were available for 1603 new sputum smear-positive patients; 85% of patients had organisms fully susceptible to streptomycin (S), isoniazid (H) and rifampicin (R), 10.4% any resistance to H and 1.7% to HR. Of 443 patients with history of previous anti-tuberculosis treatment, 59% had organisms susceptible to S, H and R, 37% had any resistance to H and 11.7% to HR., Conclusion: The DST profile showed that the vast majority of patients have drug-susceptible organisms, and that currently recommended regimens under the RNTCP would be effective in the treatment of TB.
- Published
- 2006
39. Treatment of lymph node tuberculosis--a randomized clinical trial of two 6-month regimens.
- Author
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Jawahar MS, Rajaram K, Sivasubramanian S, Paramasivan CN, Chandrasekar K, Kamaludeen MN, Thirithuvathas AJ, Ananthalakshmi V, and Prabhakar R
- Subjects
- Adolescent, Adult, Antibiotics, Antitubercular administration & dosage, Antibiotics, Antitubercular adverse effects, Antitubercular Agents adverse effects, Child, Directly Observed Therapy, Drug Administration Schedule, Drug Therapy, Combination, Female, Humans, Isoniazid adverse effects, Lymph Nodes microbiology, Male, Middle Aged, Mycobacterium tuberculosis isolation & purification, Pyrazinamide adverse effects, Recurrence, Rifampin adverse effects, Self Administration, Treatment Outcome, Tuberculin Test methods, Antitubercular Agents administration & dosage, Isoniazid administration & dosage, Pyrazinamide administration & dosage, Rifampin administration & dosage, Tuberculosis, Lymph Node drug therapy
- Abstract
Objective: The currently recommended treatment for lymph node tuberculosis is 6 months of rifampicin and isoniazid plus pyrazinamide for the first 2 months, given either daily or thrice weekly. The objective of this study was to assess the efficacy of a 6-month twice-weekly regimen and a daily two-drug regimen., Methods: Patients with biopsy confirmed superficial lymph node tuberculosis were randomly allocated to receive either a daily self-administered 6-month regimen of rifampicin and isoniazid, or a twice-weekly, directly observed, 6-month regimen of rifampicin and isoniazid plus pyrazinamide for the first 2 months, in Madurai, South India, Patients were followed up for 36 months after completing treatment., Results: Of 277 enrolled patients, data was available for analysis in 268. At the end of treatment, 116 of 134 [87%; 95% confidence interval (CI) 81-93%] patients in each treatment group had a favourable clinical response; 14 (11%; 95% CI 6-16%) and 17 (13%; 95% CI 7-19%) patients had a doubtful response, and 4 (3%; 95% CI 0-6%) and 1 (1%; 95% CI 0-2%) patients had an unfavourable response among those treated with the daily and twice-weekly regimen, respectively. During 36 months after completion of treatment, five patients [2 (2%; 95% CI 1-3%) and 3 (2%; 95% CI 1-3%) patients treated with the daily and twice-weekly regimen, respectively] had relapse of lymph node tuberculosis, of 260 assessed. Adverse reactions probably attributable to the treatment regimens occurred in 1% of the patients treated daily and in 11% of those treated twice-weekly (P < 0.001). At the end of 36 months after treatment, 126 of 134 (94%; 95% CI 90-98%) and 129 of 134 (96%; 95% CI 94-98%) of the patients treated with the daily and twice-weekly regimen, respectively, had a successful outcome., Conclusion: Both the self-administered daily regimen and the fully observed twice-weekly regimen were highly efficacious for treating patients with lymph node tuberculosis and may be considered as alternative options to the recommended regimens.
- Published
- 2005
- Full Text
- View/download PDF
40. Anti-tuberculosis drug resistance in patients with HIV and tuberculosis in South India.
- Author
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Swaminathan S, Paramasivan CN, Ponnuraja C, Iliayas S, Rajasekaran S, and Narayanan PR
- Subjects
- Drug Resistance, Bacterial, Humans, India epidemiology, Prevalence, Prospective Studies, Tuberculosis, Pulmonary etiology, Antitubercular Agents pharmacology, Drug Resistance, Multiple, HIV Infections complications, Tuberculosis, Pulmonary drug therapy
- Abstract
Setting: Tuberculosis Research Centre clinics at Chennai and Madurai, Tamil Nadu, South India., Objectives: To investigate the prevalence and pattern of drug resistance among patients with HIV and pulmonary tuberculosis (PTB)., Design: Prospective cohort study of HIV-positive patients with PTB between January 2001 and May 2003. Sputum mycobacterial culture and drug susceptibility testing were performed., Results: A total of 204 patients with positive sputum cultures for Mycobacterium tuberculosis were included; 167 of them were new cases, and 37 had a history of previous anti-tuberculosis treatment for > 1 month. Among the former, resistance to isoniazid (INH) was observed in 22 (13%) and MDR-TB in 7 (4.2%). Reported resistance rates in this geographic area among new cases ranged from 15% to 28% for INH and 2.8% to 3.4% for MDR (INH + rifampicin [RMP]). In contrast, among HIV-positive patients with a history of previous treatment, resistance was found to INH in 10 (27%) and to RMP in 7 (18.9%), while MDR-TB was seen in 5 (13.5%) patients., Conclusion: Among new TB patients, MDR-TB is marginally higher in HIV-positive patients than in the non-HIV-infected population in this region. Standard treatment guidelines should be followed. Higher rates of drug resistance are observed among previously treated patients.
- Published
- 2005
41. Requirement of the mymA operon for appropriate cell wall ultrastructure and persistence of Mycobacterium tuberculosis in the spleens of guinea pigs.
- Author
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Singh A, Gupta R, Vishwakarma RA, Narayanan PR, Paramasivan CN, Ramanathan VD, and Tyagi AK
- Subjects
- Animals, Antitubercular Agents pharmacology, Bacterial Proteins, Cell Wall physiology, Cell Wall ultrastructure, Drug Resistance, Bacterial, Genes, Bacterial, Guinea Pigs, Hydrogen-Ion Concentration, Macrophages microbiology, Mice, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis pathogenicity, Mycobacterium tuberculosis ultrastructure, Mycolic Acids metabolism, Virulence, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis metabolism, Operon, Spleen microbiology
- Abstract
We had recently reported that the mymA operon (Rv3083 to Rv3089) of Mycobacterium tuberculosis is regulated by AraC/XylS transcriptional regulator VirS (Rv3082c) and is important for the cell envelope of M. tuberculosis. In this study, we further show that a virS mutant (MtbdeltavirS) and a mymA mutant (Mtbmym::hyg) of M. tuberculosis exhibit reduced contents and altered composition of mycolic acids along with the accumulation of saturated C24 and C26 fatty acids compared to the parental strain. These mutants were markedly more susceptible to major antitubercular drugs at acidic pH and also showed increased sensitivity to detergent (sodium dodecyl sulfate) and to acidic stress than the parental strain. We show that disruption of virS and mymA genes impairs the ability of M. tuberculosis to survive in activated macrophages, but not in resting macrophages, suggesting the importance of the mymA operon in protecting the bacterium against harsher conditions. Infection of guinea pigs with MtbdeltavirS, Mtbmym::hyg, and the parental strain resulted in an approximately 800-fold-reduced bacillary load of the mutant strains compared with the parental strain in spleens, but not in the lungs, of animals at 20 weeks postinfection. Phenotypic traits were fully complemented upon reintroduction of the virS gene into MtbdeltavirS. These observations show the important role of the mymA operon in the pathogenesis of M. tuberculosis at later stages of the disease.
- Published
- 2005
- Full Text
- View/download PDF
42. Increased expression of Mycobacterium tuberculosis 19 kDa lipoprotein obliterates the protective efficacy of BCG by polarizing host immune responses to the Th2 subtype.
- Author
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Rao V, Dhar N, Shakila H, Singh R, Khera A, Jain R, Naseema M, Paramasivan CN, Narayanan PR, Ramanathan VD, and Tyagi AK
- Subjects
- Animals, Antigens, Bacterial administration & dosage, Antigens, Bacterial biosynthesis, BCG Vaccine administration & dosage, Genetic Vectors administration & dosage, Guinea Pigs, Interleukin-10 biosynthesis, Lipoproteins administration & dosage, Lipoproteins genetics, Lung pathology, Mice, Mice, Inbred BALB C, Mycobacterium bovis genetics, Mycobacterium tuberculosis pathogenicity, Spleen immunology, Tuberculosis immunology, Tuberculosis pathology, Vaccines, Synthetic administration & dosage, BCG Vaccine immunology, Interferon-gamma biosynthesis, Mycobacterium bovis immunology, Mycobacterium tuberculosis immunology, Tuberculosis prevention & control, Vaccination
- Abstract
Mycobacterium tuberculosis can not only neutralize immune effector functions, but also has the ability to modulate host-signalling cascades involved in the development of these responses. The 19 kDa antigen (Rv3763), a lipoprotein of M. tuberculosis, elicits high levels of interleukin (IL)-12 from macrophages in addition to its powerful immunomodulatory properties, leading to suppression of antigen-presentation signalling cascades. The present study was aimed at analysing the effect of overexpression of this antigen on the immunostimulatory properties of M. bovis Bacille Calmette-Guerin (BCG). We have constructed a recombinant BCG strain (rBCG19N) producing higher levels of the 19 kDa antigen in both the cytoplasmic (approximately eightfold) and extracellular (approximately fivefold) fractions as compared to the wildtype BCG. Immunization of mice with rBCG19N elicited high levels of interferon-gamma (IFN-gamma) and relatively low levels of IL-10 against the purified 19 kDa antigen. However, in response to total BCG sonicate, mice immunized with rBCG19N produced significantly high levels of IL-10 with relatively very low levels of IFN-gamma. This polarization of the host immune responses towards T-helper 2 subtype resulted in complete abrogation of the protective efficacy of BCG, when rBCG19N was used as a live vaccine against M. tuberculosis challenge in guinea pigs.
- Published
- 2005
- Full Text
- View/download PDF
43. In vitro activity of fluoroquinolones against Mycobacterium tuberculosis.
- Author
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Sulochana S, Rahman F, and Paramasivan CN
- Subjects
- Aza Compounds pharmacology, Ciprofloxacin pharmacology, Gatifloxacin, Humans, Microbial Sensitivity Tests, Moxifloxacin, Ofloxacin pharmacology, Quinolines pharmacology, Quinolones pharmacology, Sampling Studies, Sensitivity and Specificity, Drug Resistance, Bacterial, Fluoroquinolones pharmacology, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis isolation & purification
- Abstract
The in vitro activity of fluoroquinolones, including lomefloxacin, ofloxacin, ciprofloxacin, sparfloxacin, moxifloxacin and gatifloxacin, was evaluated against 55 clinical isolates of Mycobacterium tuberculosis by absolute concentration method on Lowenstein-Jensen (L-J) and Middlebrook's 7H11 media. Both ofloxacin susceptible and ofloxacin resistant strains of M. tuberculosis isolates were tested. The in vitro activities of these fluoroquinolones on the M. tuberculosis isolates were in the order: lomefloxacin < ciprofloxacin < or = ofloxacin < sparfloxacin < moxifloxacin = gatifloxacin. Gatifloxacin and moxifloxacin showed low minimal inhibitory concentrations (MIC) for both ofloxacin resistant and ofloxacin susceptible strains even though some cross resistances were observed.
- Published
- 2005
- Full Text
- View/download PDF
44. Computerized tomography detects pulmonary lesions in children with normal radiographs diagnosed to have tuberculosis.
- Author
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Swaminathan S, Raghavan A, Datta M, Paramasivan CN, and Saravanan KC
- Subjects
- Child, Child, Preschool, Female, Humans, Infant, Male, Outpatient Clinics, Hospital, Lung diagnostic imaging, Tomography, X-Ray Computed, Tuberculosis, Pulmonary diagnosis
- Abstract
This report is based on observations during the conduct of a larger study to develop diagnostic criteria for childhood tuberculosis (TB). Of 201 children confirmed to have pulmonary or lymph node TB, 84 had normal chest radiographs. Computerized tomography (CT) of the chest was performed in nine of them, seven of whom had normal chest radiographs while two had visible calcification. Eight of the nine children had definitive lesions detected by computerized tomography of the chest. While five children had primarily hilar lymph node enlargement, three had pulmonary parenchymal lesions. The use of more sensitive diagnostic tests like computed tomography helps to detect tuberculosis lesions not otherwise visualized on chest radiographs. This report highlights the difficulty in excluding active tuberculosis in children. More studies are required on the role of CT scans in the diagnosis of tuberculosis in children.
- Published
- 2005
45. Bactericidal action of gatifloxacin, rifampin, and isoniazid on logarithmic- and stationary-phase cultures of Mycobacterium tuberculosis.
- Author
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Paramasivan CN, Sulochana S, Kubendiran G, Venkatesan P, and Mitchison DA
- Subjects
- Colony Count, Microbial, Gatifloxacin, Mycobacterium tuberculosis growth & development, Anti-Bacterial Agents pharmacology, Antibiotics, Antitubercular pharmacology, Antitubercular Agents pharmacology, Fluoroquinolones pharmacology, Isoniazid pharmacology, Mycobacterium tuberculosis drug effects, Rifampin pharmacology
- Abstract
The bactericidal activity of gatifloxacin, alone and in combination with isoniazid and rifampin, was studied on both exponential- and stationary-phase cultures of Mycobacterium tuberculosis strain H37Rv. On log-phase cultures, the bactericidal activity of gatifloxacin at 4 microg/ml was rapid and was very similar to that of isoniazid. At concentrations of 0.25 and 4 microg/ml, gatifloxacin enhanced the activity of isoniazid. Killing of the stationary-phase culture was biphasic. During the first 2 days, gatifloxacin at 4 microg/ml slightly increased the limited bactericidal activities of isoniazid and rifampin. However, no further additional bactericidal activity was found during further incubation with isoniazid alone or when gatifloxacin was added to either isoniazid or rifampin. This suggested that the stationary-phase culture contained a mixture of occasionally dividing bacilli that were killed during the first 2 days and true static persisters in the residual population that mimicked those in human lesions. In view of the failure of gatifloxacin to add to the sterilizing activity of isoniazid or rifampin during days 2 to 6 of exposure in the stationary-phase culture, it is unlikely to be a sterilizing drug that can be used to shorten the duration of treatment appreciably when it is added to present treatment regimens.
- Published
- 2005
- Full Text
- View/download PDF
46. Two speedier phenotypic methods on drug susceptibility testing of Mycobacterium tuberculosis.
- Author
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Paramasivan CN
- Subjects
- Developing Countries, Humans, Tuberculosis drug therapy, Tuberculosis epidemiology, Tuberculosis metabolism, Antitubercular Agents pharmacology, Microbial Sensitivity Tests methods, Mycobacterium tuberculosis drug effects, Phenotype
- Published
- 2004
47. Drug resistance in tuberculosis in India.
- Author
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Paramasivan CN and Venkataraman P
- Subjects
- Disease Management, Global Health, Humans, India epidemiology, Prevalence, Public Health Practice, Drug Resistance, Tuberculosis, Multidrug-Resistant epidemiology, Tuberculosis, Multidrug-Resistant prevention & control
- Abstract
The current global concern in the treatment of tuberculosis (TB) is the emergence of resistance to the two most potent drugs viz., isoniazid and rifampicin. The level of initial drug resistance is an epidemiological indicator to assess the success of the TB control programme. Though drug resistance in TB has frequently been reported from India, most of the available information is localized, sketchy or incomplete. A review of the few authentic reports indicates that there is no clear evidence of an increase in the prevalence of initial resistance over the years. However, a much higher prevalence of acquired resistance has been reported from several regions, though based on smaller numbers of patients. A strong TB control programme and continuous surveillance studies employing standardized methodology and rigorous quality control measures will serve as useful parameters in the evaluation of current treatment policies as well as the management of multidrug resistant (MDR) TB cases.
- Published
- 2004
48. Unrecognised tuberculosis in HIV-infected patients: sputum culture is a useful tool.
- Author
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Swaminathan S, Paramasivan CN, Kumar SR, Mohan V, and Venkatesan P
- Subjects
- Adult, Diagnosis, Differential, Female, Humans, Male, Mycobacterium tuberculosis isolation & purification, Radiography, Thoracic, Tuberculin Test, Tuberculosis, Pulmonary virology, HIV Infections complications, Sputum cytology, Tuberculosis, Pulmonary diagnosis
- Abstract
Diagnosis of tuberculosis is challenging, especially in human immunodeficiency virus (HIV) positive persons who may have atypical clinical and radiographic features. We report the isolation of Mycobacterium tuberculosis from sputum samples of 10 (4%) HIV-positive persons who were asymptomatic with normal chest radiographs and negative sputum smears for acid-fast bacilli. Six of them had strongly positive tuberculin reactions while four were severely immunosuppressed. Our observation highlights the utility of routine sputum culture in the diagnosis of tuberculosis in high-risk individuals.
- Published
- 2004
49. Evaluation of microplate Alamar blue assay for drug susceptibility testing of Mycobacterium avium complex isolates.
- Author
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Vanitha JD and Paramasivan CN
- Subjects
- Clarithromycin pharmacology, Coloring Agents, Culture Media, Drug Resistance, Bacterial, Female, Humans, Male, Mycobacterium avium Complex growth & development, Mycobacterium avium Complex isolation & purification, Reproducibility of Results, Sensitivity and Specificity, Antibiotics, Antitubercular pharmacology, Antitubercular Agents pharmacology, Microbial Sensitivity Tests methods, Mycobacterium avium Complex drug effects, Oxazines, Xanthenes
- Abstract
Fifty-one clinical isolates and 5 clarithromycin-resistant mutants of Mycobacterium avium complex (MAC) were tested for their susceptibility to clarithromycin by microplate Alamar blue assay (MABA). The susceptibility results were compared with the results obtained by the BACTEC 460 method. All clinical isolates were susceptible, while all mutants were resistant to clarithromycin by BACTEC. Eighty-six percent of the clinical isolates were susceptible by MABA, and one of the resistant mutants was misclassified as susceptible by this method. The overall agreement between MABA and BACTEC was 86%, indicating the usefulness of MABA in drug susceptibility testing of MAC.
- Published
- 2004
- Full Text
- View/download PDF
50. Disruption of mptpB impairs the ability of Mycobacterium tuberculosis to survive in guinea pigs.
- Author
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Singh R, Rao V, Shakila H, Gupta R, Khera A, Dhar N, Singh A, Koul A, Singh Y, Naseema M, Narayanan PR, Paramasivan CN, Ramanathan VD, and Tyagi AK
- Subjects
- Animals, Cells, Cultured, Genetic Complementation Test, Guinea Pigs, Host-Parasite Interactions genetics, Macrophages microbiology, Mice, Mutation, Mycobacterium tuberculosis genetics, Recombination, Genetic, Spleen microbiology, Spleen pathology, Tuberculosis microbiology, Tuberculosis pathology, Virulence genetics, Bacterial Proteins genetics, Bacterial Proteins metabolism, Mycobacterium tuberculosis pathogenicity, Protein Tyrosine Phosphatases genetics, Protein Tyrosine Phosphatases metabolism, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism
- Abstract
Protein tyrosine kinases and tyrosine phosphatases from several bacterial pathogens have been shown to act as virulence factors by modulating the phosphorylation and dephosphorylation of host proteins. The identification and characterization of two tyrosine phosphatases namely MptpA and MptpB from Mycobacterium tuberculosis has been reported earlier. MptpB is secreted by M. tuberculosis into extracellular mileu and exhibits a pH optimum of 5.6, similar to the pH of the lysosomal compartment of the cell. To determine the role of MptpB in the pathogenesis of M. tuberculosis, we constructed a mptpB mutant strain by homologous recombination and compared the ability of parent and the mutant strain to survive intracellularly. We show that disruption of the mptpB gene impairs the ability of the mutant strain to survive in activated macrophages and guinea pigs but not in resting macrophages suggesting the importance of its role in the host-pathogen interaction. Infection of guinea pigs with the mutant strain resulted in a 70-fold reduction in the bacillary load of spleens in infected animals as compared with the bacillary load in animals infected with the parental strain. Upon reintroduction of the mptpB gene into the mutant strain, the complemented strain was able to establish infection and survive in guinea pigs at rates comparable to the parental strain. These observations demonstrate a role of MptpB in the pathogenesis of M. tuberculosis.
- Published
- 2003
- Full Text
- View/download PDF
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