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Randomized clinical trial of thrice-weekly 4-month moxifloxacin or gatifloxacin containing regimens in the treatment of new sputum positive pulmonary tuberculosis patients.

PLoS One. 2013;8(7):e67030

Authors: 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, Narayanan PR

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.

PMID: 23843980 [PubMed - in process]

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Predicting and Analyzing Interactions between Mycobacterium tuberculosis and Its Human Host.

PLoS One. 2013;8(7):e67472

Authors: Rapanoel HA, Mazandu GK, Mulder NJ

Abstract
The outcome of infection by Mycobacterium tuberculosis (Mtb) depends greatly on how the host responds to the bacteria and how the bacteria manipulates the host, which is facilitated by protein-protein interactions. Thus, to understand this process, there is a need for elucidating protein interactions between human and Mtb, which may enable us to characterize specific molecular mechanisms allowing the bacteria to persist and survive under different environmental conditions. In this work, we used the interologs method based on experimentally verified intra-species and inter-species interactions to predict human-Mtb functional interactions. These interactions were further filtered using known human-Mtb interactions and genes that are differentially expressed during infection, producing 190 interactions. Further analysis of the subcellular location of proteins involved in these human-Mtb interactions confirms feasibility of these interactions. We also conducted functional analysis of human and Mtb proteins involved in these interactions, checking whether these proteins play a role in infection and/or disease, and enriching Mtb proteins in a previously predicted list of drug targets. We found that the biological processes of the human interacting proteins suggested their involvement in apoptosis and production of nitric oxide, whereas those of the Mtb interacting proteins were relevant to the intracellular environment of Mtb in the host. Mapping these proteins onto KEGG pathways highlighted proteins belonging to the tuberculosis pathway and also suggested that Mtb proteins might use the host to acquire nutrients, which is in agreement with the intracellular lifestyle of Mtb. This indicates that these interactions can shed light on the interplay between Mtb and its human host and thus, contribute to the process of designing novel drugs with new biological mechanisms of action.

PMID: 23844013 [PubMed - in process]

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Yield of two consecutive sputum specimens for the effective diagnosis of pulmonary tuberculosis.

PLoS One. 2013;8(7):e67678

Authors: Islam MR, Khatun R, Uddin MK, Khan MS, Rahman MT, Ahmed T, Banu S

Abstract
BACKGROUND: From long instances, it is debatable whether three sputum specimens are required for the diagnosis of pulmonary tuberculosis (TB) or TB can be diagnosed effectively using two consecutive sputum specimens. This study was set out to evaluate the significance of examining multiple sputum specimens in diagnosis of TB.
METHODS: We retrospectively reviewed the acid-fast bacillus (AFB) smear and culture results of three consecutive days' sputum specimens from 413 confirmed TB patients which were detected as part of a larger active case finding study in Dhaka Central Jail, the largest correctional facility in Bangladesh.
RESULTS: AFB was detected from 81% (n = 334) patients, of which 89% (n = 297) were diagnosed from the first and additional 9% (n = 30) were from the second sputum specimen. M. tuberculosis growth was observed for 406 patients and 85% (n = 343) were obtained from the first sputum and additional 10% (n = 42) were from the second one. The third specimen didn't show significant additional diagnostic value for the detection of AFB by microscopy or growth of the M. tuberculosis.
CONCLUSIONS: We concluded from our study results that examining two consecutive sputum specimens is sufficient enough for the effective diagnosis of TB. It can also decrease the laboratory workload and hence improve the quality of work in settings with high TB burden like Bangladesh.

PMID: 23844057 [PubMed - in process]