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  1. Saifullah B, Hussein MZ, Hussein Al Ali SH
    Int J Nanomedicine, 2012;7:5451-63.
    PMID: 23091386 DOI: 10.2147/IJN.S34996
    Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis, is notorious for its lethality to humans. Despite technological advances, the tubercle bacillus continues to threaten humans. According to the World Health Organization's 2011 global report on TB, 8.8 million cases of TB were reported in 2010, with a loss of 1.7 million human lives. As drug-susceptible TB requires long-term treatment of between 6 and 9 months, patient noncompliance remains the most important reason for treatment failure. For multidrug-resistant TB, patients must take second-line anti-TB drugs for 18-24 months and many adverse effects are associated with these drugs. Drug-delivery systems (DDSs) seem to be the most promising option for advancement in the treatment of TB. DDSs reduce the adverse effects of drugs and their dosing frequency as well as shorten the treatment period, and hence improve patient compliance. Further advantages of these systems are that they target the disease area, release the drugs in a sustained manner, and are biocompatible. In addition, targeted delivery systems may be useful in dealing with extensively drug-resistant TB because many side effects are associated with the drugs used to cure the disease. In this paper, we discuss the DDSs developed for the targeted and slow delivery of anti-TB drugs and their possible advantages and disadvantages.
    Matched MeSH terms: Antitubercular Agents/administration & dosage*
  2. Venugopalan B
    Med J Malaysia, 2004 Mar;59(1):20-5.
    PMID: 15535331 MyJurnal
    In the year 2001, 1459 Tuberculosis (TB) cases (43.1/100,000 population) were notified in Selangor. The highest age specific incidence rate was among those aged above 60 years and foreigners accounted for 15% of the cases notified. Fifteen percent of the TB cases were treated in the private sector where treatment efficacy and compliance could not be evaluated. Co- infection of Human Immunodeficiency Virus (HIV) infection with TB accounted for 51% of the TB deaths notified. Screening programmes in prisons and drug rehabilitation centres had detected 11.7% of HIV/TB coinfection among HIV positive inmates screened in these institutions.
    Matched MeSH terms: Antitubercular Agents/administration & dosage
  3. Aziah AM
    Med J Malaysia, 2004 Mar;59(1):1-3.
    PMID: 15535327 MyJurnal
    Matched MeSH terms: Antitubercular Agents/administration & dosage
  4. Laghari M, Sulaiman SAS, Khan AH, Memon N
    BMC Infect Dis, 2019 Jan 24;19(1):82.
    PMID: 30678656 DOI: 10.1186/s12879-019-3702-3
    BACKGROUND: Understanding the explanations behind unsuccessful treatment outcomes in tuberculosis (TB) patients is important to improve treatment success. Treatment completion for TB is the mainstay of TB prevention and control. The study was aimed to assess the treatment outcomes and predictors for unsuccessful outcomes among children with TB.

    METHODS: This was a prospective multicenter study conducted in Sindh. Children aged ≤14 years enrolled from June to November 2016 were included. A structured data collection tool was used to gather information with respect to patients' socio-demographic, clinical and microbiological data. Additionally, to collect the information related to socio-economic and education level of caregivers, validated questionnaire was administered to the caregivers. Treatment outcomes were assessed according to the World Health Organization (WHO) guidelines. The relationship of unsuccessful treatment outcome with socio-demographic and clinical attributes of TB patients was analyzed using logistic regression model.

    RESULTS: Childhood TB represented 19.3% (508/2634) of all TB cases in selected hospitals. Of these, 268/508 (52.8%) were females and one third of the children were aged ≤2 years (34.3%). In multivariate analysis, pulmonary smear positive TB (PTB+) (AOR = 5.910, 95%CI = 1.64-21.29), those with adverse drug reactions (AOR = 11.601, 95%CI = 4.06-33.12) and those who had known TB contacts (AOR = 3.128, 95%CI = 1.21-8.06) showed statistically significant association with unsuccessful treatment outcomes.

    CONCLUSIONS: The high proportion of childhood TB cases (19.3%) demonstrates the continuation of TB transmission in the study setting. Furthermore, an increased focus on PTB+ patients, those with adverse drug reactions and household contact with TB is warranted.

    Matched MeSH terms: Antitubercular Agents/administration & dosage
  5. Amarnath Praphakar R, Jeyaraj M, Ahmed M, Suresh Kumar S, Rajan M
    Int J Biol Macromol, 2018 Oct 15;118(Pt B):1627-1638.
    PMID: 29981824 DOI: 10.1016/j.ijbiomac.2018.07.008
    Recently, drug functionalized biodegradable polymers have been appreciated to be imperative to fabricate multi-drug delivery nanosystems for sustainable drug release. In this work, amphiphilic chitosan-grafted-(cetyl alcohol-maleic anhydride-pyrazinamide) (CS-g-(CA-MA-PZA)) was synthesized by multi-step reactions. The incorporation of rifampicin (RF) and entrapment of silver nanoparticles (Ag NPs) on CS-g-(CA-MA-PZA) polymer was carried out by dialysis technique. From the FT-IR experiment, the polymer modification, incorporation of drugs and the entrapment of Ag NPs on micelles were confirmed. The surface morphology of Ag NPs, polymeric system and drug loaded micelles was described by SEM, TEM and AFM techniques. In addition, the controlled release behaviour of CS-g-(CA-MA-PZA) micelles was studied by UV-Vis spectroscopy. In vitro cell viability, cell apoptosis and cellular uptake experiments shows that multi-drug delivery system could enhance the biocompatibility and higher the cytotoxicity effect on the cells. Since the prepared amphiphilic polymeric micelles exhibit spotty features and the system is a promising strategy for a novel candidate for immediate therapeutically effects for alveolar macrophages.
    Matched MeSH terms: Antitubercular Agents/administration & dosage*
  6. Dua K, Rapalli VK, Shukla SD, Singhvi G, Shastri MD, Chellappan DK, et al.
    Biomed Pharmacother, 2018 Nov;107:1218-1229.
    PMID: 30257336 DOI: 10.1016/j.biopha.2018.08.101
    Tuberculosis (caused by Mycobacterium tuberculosis, Mtb) treatment involves multiple drug regimens for a prolonged period. However, the therapeutic benefit is often limited by poor patient compliance, subsequently leading to treatment failure and development of antibiotic resistance. Notably, oxidative stress is a crucial underlying factor that adversely influences the various treatment regimens in tuberculosis. Little information is available with advanced drug delivery systems that could be effectively utilized, in particular, for targeting the oxidative stress in tuberculosis. Thus, this presents an opportunity to review the utility of various available, controlled-release drug delivery systems (e.g., microspheres, liposomes, niosomes, solid lipid nanoparticles, dendrimers) that could be beneficial in tuberculosis treatments. This will help the biological and formulation scientists to pave a new path in formulating a treatment regimen for multi-drug resistant Mtb.
    Matched MeSH terms: Antitubercular Agents/administration & dosage*
  7. Zuhaimy H, Leow SN, Vasudevan SK
    BMJ Case Rep, 2017 Aug 09;2017.
    PMID: 28794092 DOI: 10.1136/bcr-2017-221170
    We discuss the diagnostic challenge in an adult patient presented with purely ocular symptoms diagnosed with tuberculous meningitis (TBM). A 38-year-old woman presented with bilateral painless blurring of vision. There were bilateral sixth cranial nerve palsy and bilateral optic disc swelling. Optic nerve function tests were normal. Patient was lucid with no signs of meningism. Brain imaging were normal. She had a positive Mantoux test, high erythrocyte sedimentation rate but no clinical evidence of active pulmonary tuberculosis infection. Her Quantiferon-TB Gold in-tube test was negative. Cerebrospinal fluid analysis revealed a high opening pressure but no biochemical parameters to suggest TBM, hence she was treated as idiopathic intracranial hypertension. A diagnosis of TBM was finally made following a positive PCR for Mycobacterium tuberculosis Her vision improved with reduction in optic disc swelling following antituberculous treatment.
    Matched MeSH terms: Antitubercular Agents/administration & dosage
  8. Atif M, Sulaiman SA, Shafie AA, Ali I, Asif M, Babar ZU
    BMC Infect Dis, 2014;14:399.
    PMID: 25037452 DOI: 10.1186/1471-2334-14-399
    According to the World Health Organization's recent report, in Malaysia, tuberculosis (TB) treatment success rate for new smear positive pulmonary tuberculosis (PTB) patients is still below the global success target of 85%. In this study, we evaluated TB treatment outcome among new smear positive PTB patients, and identified the predictors of unsuccessful treatment outcome and longer duration of treatment (i.e., > 6 months).
    Matched MeSH terms: Antitubercular Agents/administration & dosage
  9. Abuzeid N, Kalsum S, Koshy RJ, Larsson M, Glader M, Andersson H, et al.
    J Ethnopharmacol, 2014 Nov 18;157:134-9.
    PMID: 25261689 DOI: 10.1016/j.jep.2014.09.020
    The emergence of multidrug-resistant strains of Mycobacterium tuberculosis underscores the need for continuous development of new and efficient methods to determine the susceptibility of isolates of Mycobacterium tuberculosis in the search for novel antimycobacterial agents. Natural products constitute an important source of new drugs, and design and implementation of antimycobacterial susceptibility testing methods are necessary to evaluate the different extracts and compounds. In this study we have explored the antimycobacterial properties of 50 ethanolic extracts from different parts of 46 selected medicinal plants traditionally used in Sudan to treat infectious diseases.
    Matched MeSH terms: Antitubercular Agents/administration & dosage
  10. O'Boyle SJ, Power JJ, Ibrahim MY, Watson JP
    Int J Tuberc Lung Dis, 2002 Apr;6(4):307-12.
    PMID: 11936739
    SETTING: Kota Kinabalu and surrounding communities in Sabah, Malaysia.
    OBJECTIVES: To establish factors affecting compliance of patients with anti-tuberculosis chemotherapy, their knowledge of the disease, and views on improving the DOTS strategy.
    DESIGN: Interviews with compliant patients attending clinics for DOTS treatment and with non-compliant patients in their homes, in August and September 2000.
    RESULTS: A total of 63 compliant and 23 non-compliant patients were interviewed. For non-compliant patients, reaching the treatment centre entailed greater cost (P < 0.005) and travel time (P < 0.005) compared to compliant patients. Cost of transport was the reason most frequently given for non-attendance. Non-compliant patients were more likely to have completed secondary education (P < 0.05), and to be working (P < 0.01). More non-compliant patients had family members who had had the disease (P < 0.01). There was no difference between the groups for overall tuberculosis knowledge scores; however, non-compliant patients were more likely to think that treatment could be stopped once they were symptom free (P < 0.01). Most patients (73%) felt that the DOTS system could be improved by provision of more information about tuberculosis.
    CONCLUSION: Compliance with DOTS in the Kota Kinabalu area is affected by travel expenses, time spent travelling to treatment centres, and having family members who have had the disease. Patients would like more information on tuberculosis.
    Study site: Tuberculosis clinics, Kota Kinabalu, Malaysia
    Matched MeSH terms: Antitubercular Agents/administration & dosage*
  11. Simon GK, Lye MS, Ahmad N
    Med J Malaysia, 1991 Mar;46(1):88-94.
    PMID: 1836044
    A retrospective study of 300 tuberculosis patients on short course chemotherapy registered in 1985 at the Chest Clinic, General Hospital Alor Setar, Kedah was carried out with the purpose of identifying patient characteristics, determining incidence of side-effects and modifying treatment regimens in order to minimise these side-effects. One hundred and sixteen (38.7%) patients developed side effects. Twenty seven (9%) had side effects severe enough to warrant a change in treatment regimen. Treatment modifications and ways to minimise or control side effects are discussed.
    Study site: Chest clinic, Hospital Alor Setar, Kedah, Malaysia
    Matched MeSH terms: Antitubercular Agents/administration & dosage
  12. Shah K, Chan LW, Wong TW
    Drug Deliv, 2017 Nov;24(1):1631-1647.
    PMID: 29063794 DOI: 10.1080/10717544.2017.1384298
    The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40-60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.
    Matched MeSH terms: Antitubercular Agents/administration & dosage*
  13. Saifullah B, El Zowalaty ME, Arulselvan P, Fakurazi S, Webster TJ, Geilich BM, et al.
    Drug Des Devel Ther, 2014;8:1029-36.
    PMID: 25114509 DOI: 10.2147/DDDT.S63753
    The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis.
    Matched MeSH terms: Antitubercular Agents/administration & dosage
  14. Saifullah B, Hussein MZ, Hussein-Al-Ali SH, Arulselvan P, Fakurazi S
    Drug Des Devel Ther, 2013;7:1365-75.
    PMID: 24255593 DOI: 10.2147/DDDT.S50665
    We report the intercalation and characterization of para-amino salicylic acid (PASA) into zinc/aluminum-layered double hydroxides (ZLDHs) by two methods, direct and indirect, to form nanocomposites: PASA nanocomposite prepared by a direct method (PASA-D) and PASA nanocomposite prepared by an indirect method (PASA-I). Powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis revealed that the PASA drugs were accommodated within the ZLDH interlayers. The anions of the drug were accommodated as an alternate monolayer (along the long-axis orientation) between ZLDH interlayers. Drug loading was estimated to be 22.8% and 16.6% for PASA-D and PASA-I, respectively. The in vitro release properties of the drug were investigated in physiological simulated phosphate-buffered saline solution of pH 7.4 and 4.8. The release followed the pseudo-second-order model for both nanocomposites. Cell viability (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assays) was assessed against normal human lung fibroblast MRC-5 and 3T3 mouse fibroblast cells at 24, 48, and 72 hours. The results showed that the nanocomposite formulations did not possess any cytotoxicity, at least up to 72 hours.
    Matched MeSH terms: Antitubercular Agents/administration & dosage*
  15. Shariff NM, Safian N
    Int J Mycobacteriol, 2015 Dec;4(4):323-9.
    PMID: 26964816 DOI: 10.1016/j.ijmyco.2015.09.003
    OBJECTIVE/BACKGROUND: Many studies have suggested that sputum smear conversion after 2 months of antituberculosis treatment is an important determinant of treatment success and can be a predictor for relapse. The objective of this study is to determine the factors that influence sputum smear conversion after 2 months of treatment among pulmonary tuberculosis patients receiving treatment in the Institute of Respiratory Medicine in Kuala Lumpur, Malaysia.
    METHODS: A total of 75 cases and 75 controls were interviewed, and their medical records were retrieved in order to extract the information needed. All analyses were conducted using SPSS version 17, and binary logistic regression analysis was used to determine the predictors of sputum smear nonconversion.
    RESULTS: Results showed that the following factors were associated with sputum smear positivity after 2 months of intensive treatment: diabetes mellitus (p=.013, odds ratio [OR]=2.59, 95% confidence interval [CI] 1.27-5.33), underweight body mass index (p=.025, OR=1.67, 95% CI 0.80-3.49), nonadherent to tuberculosis treatment (p=.024, OR=2.85, 95% CI 1.21-6.74), and previous history of tuberculosis (p=.043, OR=2.53, 95% CI 1.09-5.83). Multivariable analysis identified diabetes mellitus (p=.003, OR=4.01, 95% CI 1.61-9.96) as being independently associated with the risk of persistent sputum smear positivity after 2 months of intensive treatment.
    CONCLUSION: Based on the findings, identification of these factors is valuable in strengthening the management and treatment of tuberculosis in Malaysia in the future. This study emphasizes the importance of diabetes screening and integration of diabetic controls among tuberculosis patients in achieving better treatment outcome.
    KEYWORDS: Risk factors; Sputum smear nonconversion; Tuberculosis
    Matched MeSH terms: Antitubercular Agents/administration & dosage*
  16. Javaid A, Ahmad N, Khan AH, Shaheen Z
    Eur Respir J, 2017 01;49(1).
    PMID: 28049176 DOI: 10.1183/13993003.01967-2016
    Matched MeSH terms: Antitubercular Agents/administration & dosage*
  17. Ali MH, Alrasheedy AA, Kibuule D, Godman B, Hassali MA, Ali HMH
    Expert Rev Anti Infect Ther, 2019 11;17(11):927-937.
    PMID: 31689134 DOI: 10.1080/14787210.2019.1689818
    Background: Multidrug-resistant tuberculosis (MDR-TB) has a socioeconomic impact and threatens global public health. We assessed treatment outcomes of MDR-TB and predictors of poor treatment outcomes in Sudan given current high prevalence rates.Methods: Combined retrospective and prospective cohort study at Abu-Anga hospital (TB specialized hospital in Sudan). All patients with MDR-TB between 2013 and 2017 were targeted.Results: A total of 156 patients were recruited as having good records, 117 (75%) were male, and 152 (97.4%) had pulmonary TB. Patients were followed for a median of 18 months and a total of 2108 person-months. The overall success rate was 63.5% and the mortality rate was 14.1%. Rural residency (P < 0.05) and relapsing on previous treatments (P < 0.05) were determinants of time to poor MDR-TB treatment outcomes.Conclusion: Overall, more attention needs to be given to special MDR-TB groups that are highly susceptible to poor outcomes, i.e. rural patients. As a result, it is highly recommended to maintain total coverage of medicines for all MDR-TB patients for the entire period of treatment in Sudan. It is also recommended to instigate more treatment centers in rural areas in Sudan together with programs to enhance adherence to treatments including patient counseling to improve future outcomes.
    Matched MeSH terms: Antitubercular Agents/administration & dosage*
  18. Saifullah B, Chrzastek A, Maitra A, Naeemullah B, Fakurazi S, Bhakta S, et al.
    Molecules, 2017 Oct 12;22(10).
    PMID: 29023399 DOI: 10.3390/molecules22101560
    Tuberculosis (TB) is a bacterial disease responsible for millions of infections and preventable deaths each year. Its treatment is complicated by patients' noncompliance due to dosing frequency, lengthy treatment, and adverse side effects associated with current chemotherapy. However, no modifications to the half-a-century old standard chemotherapy have been made based on a nanoformulation strategy to improve pharmacokinetic efficacy. In this study, we have designed a new nanodelivery formulation, using graphene oxide as the nanocarrier, loaded with the anti-TB antibiotic, ethambutol. The designed formulation was characterized using a number of molecular analytical techniques. It was found that sustained release of the drug resulted in better bioavailability. In addition, the designed formulation demonstrated high biocompatibility with mouse fibroblast cells. The anti-TB activity of the nanodelivery formulation was determined using whole-cell resazurin microtiter plate assay, modified-spot culture growth inhibition assay, and biofilm inhibition assay. The nanodelivery formulation showed good anti-mycobacterial activity. The anti-mycobacterial activity of Ethambutol was unaffected by the drug loading and release process. The results of this study demonstrated the potential of this new nanodelivery formulation strategy to be considered for modifying existing chemotherapy to yield more efficacious antibiotic treatment against TB.
    Matched MeSH terms: Antitubercular Agents/administration & dosage*
  19. Saifullah B, Arulselvan P, El Zowalaty ME, Fakurazi S, Webster TJ, Geilich B, et al.
    ScientificWorldJournal, 2014;2014:401460.
    PMID: 25050392 DOI: 10.1155/2014/401460
    Tuberculosis is a lethal epidemic, difficult to control disease, claiming thousands of lives every year. We have developed a nanodelivery formulation based on para-aminosalicylic acid (PAS) and zinc layered hydroxide using zinc nitrate salt as a precursor. The developed formulation has a fourfold higher efficacy of PAS against mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) found to be at 1.40 μg/mL compared to the free drug PAS with a MIC of 5.0 μg/mL. The newly developed formulation was also found active against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans. The formulation was also found to be biocompatible with human normal lung cells MRC-5 and mouse fibroblast cells-3T3. The in vitro release of PAS from the formulation was found to be sustained in a human body simulated phosphate buffer saline (PBS) solution at pH values of 7.4 and 4.8. Most importantly the nanocomposite prepared using zinc nitrate salt was advantageous in terms of yield and free from toxic zinc oxide contamination and had higher biocompatibility compared to one prepared using a zinc oxide precursor. In summary, these promising in vitro results are highly encouraging for the continued investigation of para-aminosalicylic acid and zinc layered hydroxide nanocomposites in vivo and eventual preclinical studies.
    Matched MeSH terms: Antitubercular Agents/administration & dosage*
  20. Javaid A, Hasan R, Zafar A, Chaudry MA, Qayyum S, Qadeer E, et al.
    Int J Tuberc Lung Dis, 2017 03 01;21(3):303-308.
    PMID: 28225340 DOI: 10.5588/ijtld.16.0444
    BACKGROUND: Drug resistance in general, and multidrug-resistant tuberculosis (MDR-TB) in particular, threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Pakistan.

    OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Pakistan.

    METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in all provinces of Pakistan. We performed culture and drug susceptibility testing on M. tuberculosis isolates from patients with a prior history of anti-tuberculosis treatment (retreatment cases) from all over the country.

    RESULTS: Of 544 isolates from previously treated cases, 289 (53.1%) were susceptible to all first-line drugs, 255 (46.9%) were resistant to at least one anti-tuberculosis drug and 132 (24.3%) were MDR-TB. Among MDR-TB isolates, 47.0% were ofloxacin (OFX) resistant. Extensively drug-resistant TB was found in two (0.4%) isolates.

    CONCLUSION: Prevalence of drug resistance in retreatment isolates was high. The alarmingly high prevalence of OFX resistance among MDR-TB isolates may threaten the success of efforts to control and treat MDR-TB.

    Matched MeSH terms: Antitubercular Agents/administration & dosage
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