Evaluation of acetylator phenotype of isoniazid among tuberculosis patients in delta state Nigeria: update on management of toxicity
DOI:
https://doi.org/10.18203/2320-6012.ijrms20161813Keywords:
Clinical practice, Diagnosis and treatment monitoring, Isoniazid efficacy and toxicity, Laboratory methods, TuberculosisAbstract
Background: In 1996, acetylator phenotype of thirteen consenting tuberculosis patients who were being treated with isoniazid was briefly examined as part of an MSc biochemistry program. Initial agenda were to determine the half-life of isoniazid and evaluate potential toxicity associated with long-term treatment regimen. This report presents findings of the study, but with the aim of providing an update on diagnosis and monitoring of the treatment of tuberculosis by laboratory methods.
Methods: Firstly, the report submitted for the award of MSc Biochemistry was reviewed and reformatted. Secondly, a follow up survey was performed to determine the current practice at the general hospital and ‘tuberculosis and leprosy’ referral centres where the original study was carried out. Thirdly, a brief literature review was performed for any potential update on clinical practices.
Results: The study has shown that 53.8% of patients are fast acetylators (t½<2 hr), 30.8% are intermediate acetylators (t½: 2.0–2.5 hr), and 15.4% are slow acetylators (t½>2.5 hr). The follow-up on current practice indicates that molecular technology has been introduced, but limited to susceptibility testing. Whether a patient could be a fast acetylator (requiring long term drug regimen) or slow acetylator (deserving short term drug regiment) is very much appreciated, but test is neither available, nor considered. Conventional diagnostic indices applicable for clinical laboratory monitoring in a drug-responsive patient in terms of efficacy and toxicity of the treatment are discussed.
Conclusions: Development of molecular technology has improved and revolutionized TB diagnosis, especially drug resistance testing. However, it is still limited to being an add-on test to conventional microscopy if a new patient is to be initially investigated for pulmonary TB.
References
Bryant B, Knights K. Antiprotozoal, Antimycobacterial and Antihelmintic Drugs. In: Pharmacology for Health Professionals. 3rd edn. Sydney: Elsevier. 2011:891-909.
Rang HP, Dale MM, Riter JM, Flower RJ, Henderson G. Chapter 50 Antibacterial drugs. In: Rang and Dale's Pharmacology. China. Elsevier Limited; 2012.
Herchline TE. Tuberculosis clinical presentation. Available at: [http://emedicine.medscape.com/ article/ 230802-clinical]
Centers for Disease Control and Prevention (CDC). Laboratory practices for diagnosis of tuberculosis--United States, 1994. MMWR Morb Mortal Wkly Rep. 1995;44(31):587-590.
Lehman LG, Ngapmen Yamadji AL, Ngo Sack F, Bilong Bilong CF. The CyScope(R) fluorescence microscope, a reliable tool for tuberculosis diagnosis in resource-limited settings. Am J Trop Med Hyg. 2010;83(4):906-8.
Yamori S, Ichiyama S, Shimokata K, Tsukamura M. Bacteriostatic and bactericidal activity of antituberculosis drugs against Mycobacterium tuberculosis, Mycobacterium avium-Mycobacterium intracellulare complex and Mycobacterium kansasii in different growth phases. Microbiol and Immunol. 1992;36(4):361-8.
Reidenberg MM, Martin JH. The acetylator phenotype of patients with systemic lupus erythematosus. Drug Metab Dispos. 1974,2(1):71-3.
Jung JA, Kim TE, Lee H, Jeong BH, Park HY, Jeon K, et al. A proposal for an individualized pharmacogenetic-guided isoniazid dosage regimen for patients with tuberculosis. Drug Des Devel Ther. 2015;9:5433-8.
Wang PY, Xie SY, Hao Q, Zhang C, Jiang BF. NAT2 polymorphisms and susceptibility to anti-tuberculosis drug-induced liver injury: a meta-analysis. Int J Tuberc Lung Dis. 2012;16(5):589-95.
Azuma J, Ohno M, Kubota R, Yokota S, Nagai T, Tsuyuguchi K, et al. NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: a randomized controlled trial for pharmacogenetics-based therapy. Eur J Clin Pharmacol. 2013;69(5):1091-101.
Ellard GA. Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis. Clin Pharmacol Ther. 1976;19(5 Pt 2):610-25.
Ellard GA. The potential clinical significance of the isoniazid acetylator phenotype in the treatment of pulmonary tuberculosis. Rev Mal Respir. 1984;1(4):207-19.
Drayer DE, Reidenberg MM. Clinical consequences of polymorphic acetylation of basic drugs. Clin Pharmacol Ther. 1977;22(3):251-8.
Ellard G, Gammon P. Pharmacokinetics of isoniazid metabolism in man. J Pharmacokinet Biopharm. 1976;4(2):83-113.
Krishnamurthy DV, Selkon JB, Ramachandran K, Devadatta S, Mitchison DA, Radhakrishna S, et al. Effect of pyridoxine on vitamin B6 concentrations and glutamic-oxaloacetic transaminase activity in whole blood of tuberculous patients receiving high-dosage isoniazid. Bull World Health Organ. 1967;36(5):853-70.
Snider DE, Jr. Pyridoxine supplementation during isoniazid therapy. Tubercle. 1980;61(4):191-6.
Currie B, Krause V, Mondia P, Hudson B. Acetylator phenotype and short-course chemotherapy for tuberculosis in Papua New Guinea. P N G Med J. 1989;32(4):259-62.
Hutchings A, Routledge PA. A simple method for determining acetylator phenotype using isoniazid. Br J Clin Pharmacol. 1986;22(3):343-5.
Aziz S, Agha F, Hassan R, Fairoz SA, Hassan K. Hepatotoxicity to different antituberculosis drug combinations. J Pak Med Asso. 1990;40(12):290-4.
Chan KM, Leung PC. Conservative treatment of paraplegia following acute trauma in a patient with tuberculous kyphosis: case report and review of the literature. Paraplegia. 1985;23(3):187-91.
Spielman A, Kimsey RB. Zoonosis. In: Encyclopedia of human biology. Edited by Dulbecco R. 1991;7: 789.
World Health Organization. WHO Guidelines Approved by the Guidelines Review Committee. In: Automated Real-Time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF Assay for the Diagnosis of Pulmonary and Extrapulmonary TB in Adults and Children: Policy Update. Geneva. 2013.
Drobniewski F, Cooke M, Jordan J, Casali N, Mugwagwa T, Broda A, et al. Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis. Health Technol Assess. 2015;19(34):1-188,vii-viii.
World Health Organization. Frequently asked questions on xpert mtb/rif assay. Available at: [http://www.who.int/tb/laboratory/xpert_faqs.pdf]
Hayashi PH, Fontana RJ, Chalasani NP, Stolz AA, Talwalkar JA, Navarro VJ, et al. Under-reporting and poor adherence to monitoring guidelines for severe cases of isoniazid hepatotoxicity. Clin Gastroenterol Hepatol. 2015;13(9):1676-82. e1671.
Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, Nolan CM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006;174(8):935-52.
Devarbhavi H. Antituberculous drug-induced liver injury: current perspective. Tropical gastroenterology : official journal of the Digestive Diseases Foundation. 2011;32(3):167-74.
Devarbhavi H, Singh R, Patil M, Sheth K, Adarsh CK, Balaraju G. Outcome and determinants of mortality in 269 patients with combination anti-tuberculosis drug-induced liver injury. J Gastroenterol Hepatol. 2013;28(1):161-7.
World Health Organization. Global tuberculosis report 2014. Available at: [www.who.int/ tb/ publications/ global_report/ gtbr14_main_text.pdf]
Obi P, Sumaina K. Nigeria ranks 11th among countries with high burden of tuberculosis. Available at: [http://www.thisdaylive.com/ articles/ nigeria-ranks-11th-among-countries-with-high-burden-of-tuberculosis/ 175783/]
Dim C, Dim N. Trends of tuberculosis prevalence and treatment outcome in an under-resourced setting: The case of Enugu state, South East Nigeria. Niger Med J. 2013;54(6):397.
Eze LC, Obidoa O. Acetylation of sulfamethazine in a Nigerian population. Biochem Genet. 1978;16(11-12):1073-7.
Eze LC, Okpogba AN, Ogan AU. Acetylation polymorphism and leprosy. Biochem Genet. 1990;28(1-2):1-7.
Fawcett IW, Gammon PT. Determination of the acetylator phenotype in a Northern Nigerian population. Tubercle. 1975;56(3):199-201.
Salako LA, Aderounmu AF. Determination of the isoniazid acetylator phenotype in a West African population. Tubercle.. 1977;58(2):109-12.
Imam F, Anwer MK, Iqbal M, Alam S, Khayyam KU, Sharma M. Tuberculosis: brief overview and its shifting paradigm for management in India. International Journal of Pharmacology. 2010;6:755-83.
Bilgili SG, Karadag AS, Calka O, Altun F. Isoniazid-induced pellagra. Cutan Ocul Toxicol. 2011;30(4):317-9.
Brent J, Vo N, Kulig K, Rumack BH. Reversal of prolonged isoniazid-induced coma by pyridoxine. Arch Intern Med. 1990;150(8):1751-3.
Chaimongkol B, Nanthachit N, Navarawong V, Siriloiratana P. Drug-induced agranulocytosis. J Med Assoc Thai. 1989;72(12):666-72.
Hegyi V. Dermatologic Manifestations of Pellagra Workup. Available at: [http://emedicine.medscape.com /article/ 1095845-workup#c5].
