Determination of Isoniazid Acetylator Phenotype and its Clinical Implication in Rwandan Tuberculosis Patients

Abstract

The purpose was to determine the normal profile of the isoniazid acetylator phenotype, the effect of tuberculosis (TB) on the profile, and the impact of the profile on early clinical responses following a treatment with the first line drug regimen. The study sample comprised 20 healthy volunteers and 22 TB naive patients. The tests for TB and HIV were conducted in the laboratory of the University Teaching Hospital Butare (CHUB). The phenotype was achieved by measuring the percentage of acetylisoniazid in the urine after a unique oral dose of isoniazid 10 mg/kg. TB patients were treated for two months with standard regimen combining rifampicin, isoniazid, pyrazinamide and ethambutol. A trimodal distribution profile was observed in both the healthy and tuberculosis groups, giving 30% versus 13.6% as slow acetylators, 45% versus 54.5% as intermediate acetylators, and 25% versus 23.2% as fast acetylators respectively. After a 2-month treatment of the TB patients, the sputum smear cultures were negative in about 81% independent of the acetylator or HIV status. Early side effects experienced were dominated by peripheral neuropathies mostly in slow and intermediate acetylators.

Effect of TB Therapy on the Health and Nutritional Status of Infants Aged 6 Months to 5 Years Diagnosed with Latent TB

“…This result demonstrates that the success of chemotherapy for antitubercular prophylaxis is maximal in children [12]. This success is explained by a good adherence to treatment, which is due to the rarity of side effects in children [40].…”

“…Considering the overall trends in the 20 high-burden countries for which data are available, the median male-to-female ratio is 1.8:1, with only Afghanistan reporting a ratio of <1: isoniazid, pyrazinamide and ethambutol for the first 2 months and only rifampicin and isoniazid at the continuation phase was applied. This scheme is recommended when resistance to the usual isoniazid is suspected [40]. We have used this scheme as at priory we could not discriminate sensitive and resistant cases.…”

“…We also systematically added Vitamin B6 to prevent isoniazid peripheral neuropathy side effect that occurs especially in malnourished children and in slow acetylors [40] [41] [42].…”

Clinical Prediction of Acetylator Phenotype in Tuberculosis Patients on Medicare using Blood Group

“…The phenotype analysis was determined by spectrophotometric method, a modification of Eidus et al, (1973) and Mukanyangezi et al,( 2015). After a test dose of isoniazid, free isoniazid (INH) and its acetyl derivative (AcINH) were estimated in urine.…”

“…These and several other potential limitations associated with phenotyping test have necessitated the development of alternative methodologies (Selinski et al, 2011). Whereas much work has been reported on individual acetylator status all over the World (Mukanyangezi et al, 2015), there is paucity of information on the use of blood group as a technique for detecting individual acetylator status in human population. The need for an alternative approach that is generic, fast, consistent and specific in predicting individuals'…”