METHODS: The population in this study consisted of all new smear positive PTB patients who were diagnosed at the chest clinic of Penang General Hospital between March 2010 and February 2011. During the study period, a standardized data collection form was used to obtain socio-demographic, clinical and treatment related data of the patients from their medical charts and TB notification forms (Tuberculosis Information System; TBIS). These data sources were reviewed at the time of the diagnosis of the patients and then at the subsequent follow-up visits until their final treatment outcomes were available. The treatment outcomes of the patients were reported in line with six outcome categories recommended by World Health Organization. Multiple logistic regression analysis was used to find the independent risk factors for unsuccessful treatment outcome and longer treatment duration. Data were analyzed using the PASW (Predictive Analysis SoftWare, version 19.0. Armonk, NY: IBM Corp).
RESULTS: Among the 336 PTB patients (236 male and 100 female) notified during the study period, the treatment success rate was 67.26% (n = 226). Out of 110 patients in unsuccessful outcome category, 30 defaulted from the treatment, 59 died and 21 were transferred to other health care facilities. The mean duration of TB treatment was 8.19 (SD 1.65) months. In multiple logistic regression analysis, risk factors for unsuccessful treatment outcome were foreign nationality, male gender and being illiterate. Similarly, risk factors for mortality due to TB included high-grade sputum and presence of lung cavities at the start of treatment, being alcoholic and elderly. Likewise, concurrent diabetes, presence of lung cavities at the start of the treatment and being a smoker were the significant predictors of longer treatment duration.
CONCLUSION: Our findings indicated that the treatment success rate among the new smear positive PTB patients was less than the success target set by World Health Organization. The proportion of patients in the successful outcome category may be increased by closely monitoring the treatment progress of the patients with aforementioned high risk characteristics. Similarly, more aggressive follow-up of the treatment defaulters and transferred out patients could also improve the TB treatment success rate.
OBJECTIVE: A series of new pyrazolines containing novel 2,5-dichloro-3-acetylthiophene chalcone moiety (PZT1-PZT20) have been synthesized, characterized by 1HNMR and 13CNMR and evaluated for them in vitro antitubercular activity against M. tuberculosis H37Rv strain and in vitro anticancer activity against DU-145 prostate cancer cell lines and all compounds were also screened for molecular docking studies against specific targeted protein domains.
METHODS: All compounds were screened for potential activity against Mycobacterium tuberculosis H37Rv (MTB) strain and anticancer activity against DU-149 prostate cancer cell lines using MTT cytotoxicity assay.
RESULTS: Among the series, compound PZT5 with 2", 4"-dichlorophenyl group at 5-position on the pyrazoline ring exhibited the most potent antitubercular activity (MIC=1.60 µg/mL) and compounds PZT2, PZT9, PZT11, PZT15, and PZT20 showed similar antitubercular activity against standard pyrazinamide (MIC=3.12 µg/mL) by broth dilution assay. PZT15 and PZT17 with 4"- pyridinyl and 2"-pyrrolyl groups on pyrazoline ring were found to exhibit better anticancer activity against DU-149 prostate cancer cell lines with IC50 values of 2.0±0.2 µg/mL and 6.0±0.3 µg/mL respectively by MTT assay. The preliminary structure-activity relationship has been summarized. The molecular docking studies with crystalline structures of enoyl acyl carrier protein reductase InhA interaction with target protein (2NSD; PDB and 3FNG; PDB) of Mycobacterium tuberculosis H37Rv (MTB) strain have also exhibited good ligand interaction and binding affinity. Ligand interaction and binding affinity were estimated using crystal structures of both types of enoyl acyl carrier protein reductase InhA (3FNG.pdb) and found to be much higher (-16.70 to - 19.20 kcal/mol) compared with pyrazinamide (-10.70 kcal/mol) as a standard target molecule. Whereas the binding affinities of six active compounds with crystal structure of other type of enoyl acyl carrier protein reductase InhA (2NSD.pdb) were much similar and higher (-9.30 to - 11.20 kcal/mole) than pyrazinamide (-11.10 kcal/mole).
CONCLUSION: These new pyrazolines would be promising potent inhibitors of drug sensitive and drug resistant Mycobacterium tuberculosis strain and potential anticancer agents against prostate cancer and other prototypes of cancers.
Aims: The study aimed to estimate the rate of delayed sputum conversion and explore its predicting factors at the end of the intensive phase among smear-positive PTB (PTB +ve) patients.
Methods: A 3-year retrospective study was conducted in the government hospital in Pulau Pinang from 2016 to 2018. During the study, a standardized, data collection form was used to collect data from the patient record. Patients aged over 18 years were recruited. Multivariable logistic regression analysis was used to identify significant independent variables associated with delayed sputum conversion.
Results: A total 1128 of PTB patients were recorded visiting the TB clinic, 736 (65.2%) were diagnosed as PTB +ve; of these, 606 (82.3%) PTB +ve had a record of sputum conversion at the end of the intensive phase. Age ≥ 50 years, blue-collar jobs, smoking, heavy bacillary load, relapsed and treatment interrupted were significantly (P < 0.05) associated with delayed sputum conversion. Delayed sputum conversion rate at the end of the intensive phase was 30.5%.
Conclusion: The rate of sputum smear conversion in the intensive phase of treatment was independently associated with high sputum smear grading at diagnosis, relapsed and treatment interrupted categories, old age and blue-collar occupations.