Dataset Information

Determination of isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National tuberculosis Control Program (RNTCP) in India.

ABSTRACT: Isoniazid is the most commonly used drug for treatment of tuberculosis, and is administered individually or in combination with other drugs as standard first line therapy. Offsetting its efficacy, severe adverse effects, especially peripheral neuropathy and hepatotoxicity, are associated with isoniazid therapy, limiting its use in tuberculosis. Isoniazid is acetylated in vivo producing hydrazine and acetyl hydrazine, which are responsible for hepatotoxicity. Marked pharmacogenetic differences in acetylation have been reported among different population across the globe. This study evaluates isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National Tuberculosis Control Program (RNTCP) in a specialized tuberculosis hospital in north India. Of 351 patients from whom samples were taken for biochemical analysis of adverse events, 36 were assessed for acetylation patterns. Blood samples were taken 1 h after administration of a 600 mg dose of isoniazid, and plasma concentrations of isoniazid were determined using a validated HPLC method. Of these 36 patients, 20 (55.56%) were slow acetylators and 16 (44.44%) were fast acetylators. Our results are consistent with those of an earlier study conducted in a different region of India. Most biochemical changes produced during long-term isoniazid therapy resolve after therapy is terminated.

SUBMITTER: Imam F

PROVIDER: S-EPMC7292862 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Determination of isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National tuberculosis Control Program (RNTCP) in India.

Imam Faisal F Sharma Manju M Khayyam Khalid Umer KU Khan Mohammad Rashid MR Ali Mohammad Daud MD Qamar Wajhul W

Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society 20200419 6

Isoniazid is the most commonly used drug for treatment of tuberculosis, and is administered individually or in combination with other drugs as standard first line therapy. Offsetting its efficacy, severe adverse effects, especially peripheral neuropathy and hepatotoxicity, are associated with isoniazid therapy, limiting its use in tuberculosis. Isoniazid is acetylated <i>in vivo</i> producing hydrazine and acetyl hydrazine, which are responsible for hepatotoxicity. Marked pharmacogenetic differe ...[more]

PMID: 32550793

Similar Datasets

Project description:INTRODUCTION:There is lack of information on the proportion of new smear-positive pulmonary tuberculosis (PTB) patients treated with a 6-month thrice-weekly regimen under Revised National Tuberculosis Control Programme (RNTCP) who develop recurrent TB after successful treatment outcome. OBJECTIVE:To estimate TB recurrence among newly diagnosed PTB patients who have successfully completed treatment and to document endogenous reactivation or re-infection. Risk factors for unfavourable outcomes to treatment and TB recurrence were determined. METHODOLOGY:Adult (aged ? 18 yrs) new smear positive PTB patients initiated on treatment under RNTCP were enrolled from sites in Tamil Nadu, Karnataka, Delhi, Maharashtra, Madhya Pradesh and Kerala. Those declared "treatment success" at the end of treatment were followed up with 2 sputum examinations each at 3, 6 and 12 months after treatment completion. MIRU-VNTR genotyping was done to identify endogenous re-activation or exogenous re-infection at TB recurrence. TB recurrence was expressed as rate per 100 person-years (with 95% confidence interval [95%CI]). Regression models were used to identify the risk factors for unfavourable response to treatment and TB recurrence. RESULTS:Of the1577 new smear positive PTB patients enrolled, 1565 were analysed. The overall cure rate was 77% (1207/1565) and treatment success was 77% (1210 /1565). The cure rate varied from 65% to 86%. There were 158 of 1210 patients who had TB recurrence after treatment success. The pooled TB recurrence estimate was 10.9% [95%CI: 0.2-21.6] and TB recurrence rate per 100 person-years was 12.7 [95% CI: 0.4-25]. TB recurrence per 100 person-years varied from 5.4 to 30.5. Endogenous reactivation was observed in 56 (93%) of 60 patients for whom genotyping was done. Male gender was associated with TB recurrence. CONCLUSION:A substantial proportion of new smear positive PTB patients successfully treated with 6 -month thrice-weekly regimen have TB recurrence under program settings.

Project description:Teaching methods need continuous innovation to encourage undergraduate medical students to enhance their competency level and skills. Every undergraduate medical student should be able to discuss the Revised National Tuberculosis Control Program (RNTCP) and Direct Observed Treatment Short (DOTS) course recommended by the World Health Organization (WHO). The DOTS strategy was launched in 1992, with the objective of detecting at least 70% of new sputum-positive tuberculosis (TB) patients and curing at least 85% of such patients. The aim of this study was to improve the competency level of Undergraduate (UG) Bachelor of Medicine and Bachelor of Surgery (MBBS) students by teaching them the objectives of the RNTCP at a program implementation site in the medical college. The RNTCP could be considered and conducted as Program-Based Teaching and Learning (PBTL) for the UG medical students. The following skills were to be implemented in the RNTCP PBTL: Sputum Collection, Ziehl-Neelsen staining and Grading, Mantoux test, and TB Culture and Molecular test (Gene Xpert). Phase II undergraduate MBBS students (N = 104) participated in the PBTL. This study was conducted in the RNTCP laboratory of a tertiary-care teaching medical college hospital. This descriptive study included advanced skill-based teaching such as Directly Observed Practical Skill, Demonstration-Observation-Assistance-Performance, Video Demonstrations, Role Play, and Group interaction as teaching tools. Pre-/post-test, Objective Structured Practical Examination, and frequently asked questions were used as assessment tools. The pre- and post-test marks were compared, and other assessments were also analyzed using SPSS. At the end of the teaching program, the feedback forms were collected from students and analyzed. The mean score obtained for 104 MBBS students in the pre-test, post-test, and other assessment tools were 213.3 and 487.5, respectively (p < 0.001). We conclude that skill-based teaching and learning tools to teach public health program like RNTCP provide valuable essential skills for undergraduate medical students. This Program Based Teaching and Learning could be successfully extended to all medical colleges.

Project description:BackgroundThe treatment of latent tuberculosis infection (LTBI) in individuals at risk of reactivation is essential for tuberculosis control. However, blood biomarkers associated with LTBI treatment have not been identified.MethodsBlood samples from tuberculin skin test (TST) reactive individuals were collected before and after one and six months of isoniazid (INH) therapy. Peripheral mononuclear cells (PBMC) were isolated, and an in-house interferon-γ release assay (IGRA) was performed. Expression of chemokine ligand 4 (CCL4), chemokine ligand 10 (CXCL10), chemokine ligand 11 (CXCL11), interferon alpha (IFNA), radical S-adenosyl methionine domain-containing 2 (RSAD2), ubiquitin-specific peptidase 18 (USP18), interferon-induced protein 44 (IFI44), interferon-induced protein 44 like (IFI44L), interferon-induced protein tetratricopeptide repeats 1(IFIT1), and interleukin 2 receptor subunit alpha (IL2RA) mRNA levels were assessed by qPCR before, during, and after INH treatment.ResultsWe observed significantly lower relative abundances of USP18, IFI44L, IFNA, and IL2RA transcripts in PBMC from IGRA-positive individuals compared to levels in IGRA-negative individuals before INH therapy. Also, relative abundance of CXCL11 was significantly lower in IGRA-positive than in IGRA-negative individuals before and after one month of INH therapy. However, the relative abundance of CCL4, CXCL10, and CXCL11 mRNA was significantly decreased and that of IL2RA and USP18 significantly increased after INH therapy, regardless of the IGRA result. Our results show that USP18, IFI44L, IFIT1, and IL2RA relative abundances increased significantly, meanwhile the relative abundance of CCL4, CXCL11, and IFNA decreased significantly after six months of INH therapy in TST-positive individuals.ConclusionsChanges in the profiles of USP18, IL2RA, IFNA, CCL4, and CXCL11 expressions during INH treatment in TST-positive individuals, regardless of IGRA status, are potential tools for monitoring latent tuberculosis treatment.

Project description:This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4(+) T cell count, 104 cells/μl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of rifampin and isoniazid when coadministered with nevirapine or efavirenz were not altered to a clinically significant extent in these severely immunosuppressed HIV-infected patients. Patients experienced favorable clinical outcomes. (This study has been registered at ClinicalTrials.gov under registration no. NCT00495326.).

Dataset Information

Determination of isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National tuberculosis Control Program (RNTCP) in India.

Publications

Determination of isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National tuberculosis Control Program (RNTCP) in India.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets