Prevalence of isoniazid resistance-conferring mutations associated with multidrug-resistant tuberculosis in Free State Province, South Africa

Background. Multidrug- and extensively drug-resistant tuberculosis (MDR-TB and XDR- TB) threaten local and global control of the disease. The molecular line-probe assay (LPA) provides rapid diagnosis and early management of MDR-TB. The LPA detects mutations of katG and inhA genes associated with isoniazid (INH) resistance in Mycobacterium tuberculosis isolates. The katG and inhA genes are associated with high- and low-level INH resistance, respectively, as well as cross-resistance to ethionamide in the case of inhA gene mutations. Patients with MDR-TB due to an inhA mutation could benefit from the use of high-dose INH ­ instead of ethionamide ­ in their MDR-TB regimen.Objectives. To determine the frequencies of katG and inhA mutations that conferred INH resistance among MDR-TB isolates during 2014 - 2016 in Free State (FS) Province of South Africa.Methods. We retrospectively reviewed MDR-TB isolates assayed with GenoType MTBDRplus (Hain Lifescience, Germany) (LPA) at the central TB laboratory of Universitas AcademicHospital, Bloemfontein, FS, and calculated the frequencies of katG andinhAmutations.Results. Among 918 MDR-TB isolates, the prevalence of katG, inhA and katG plus inhA mutations was 63.9%, 13.4% and 22.7%,respectively.Approximately 60% (n=536; 58.4%) of the isolates were obtained from male patients. The patients' ages ranged from 1 to 89 (median 37) years. The Xhariep district had the highest incidence of INH resistance-conferring mutations in the province.Conclusions. katG-associated mutations are the predominant INH resistance-conferring mechanism among MDR-TB isolates in the FS. Patients infected with isolates that harbour the katG mutation are unlikely to benefit from high-dose INH therapy in the bedaquiline (BDQ)-containing modified short MDR-TB regimen. They may, however, benefit from the inclusion of ethionamide in the regimen. Dual katG and inhA gene mutations make these patients unlikely to respond to either high-dose INH or ethionamide and should now be considered for either the BDQ-containing long MDR-TB regimen or an individualised treatment regimen, depending on fluoroquinolone susceptibility. Clinicians should familiarise themselves with interpreting various INH resistance-conferring mutation results and their implications for management of MDR-TB treatment

Isoniazid preventive therapy uptake and completion among HIV infected children in two referral hospitals, northwest Ethiopia

Introduction: Isoniazid prevention therapy alone can reduce the risk of tuberculosis in people with HIV regardless of CD4 count or antiretroviral treatment. In Ethiopia, there is scarcity of evidence on implementation of isoniazid prevention therapy and factors associated with its uptake.Objective: The study aimed to assess isoniazid preventive therapy implementation and factors associated with isoniazid completion among human immunodeficiency virus infected children in Felege-Hiwot and Gondar University Referral Hospitals in Northwest Ethiopia.Methods: A facility-based cross-sectional study using a combination of face-to-face interviews of caregivers/parents and retrieval of client records was conducted in May 2014. Trained nurses with experience in human immunodeficiency virus infection and tuberculosis care conducted the document review and interviews. Data were entered onto Epi Info version 3.5.4 for windows, cleaned and exported to Statistical Package for Social Sciences version 20.0 for windows for analysis. Results: A total of 454 HIV infected children (51.8% females and 48.2% males) were studied. Nearly a third, 168 (37%),of children were provided isoniazid prevention therapy and 67.9% completed the full course. Isoniazid completion was associated with distance from hospital (p<0.005), explanation of the reasons to take isoniazid pills (p<0.001), thinking isoniazid may be dangerous to child's health (p<0.001), believing that the chance of getting sick from tuberculosis is high for the child (p<0.001), disclosure of human immunodeficiency virus infection status (p<0.04) and isoniazid preventive therapy disclosure status (p<0.001).Conclusions: Uptake of isoniazid preventive therapy was low among human immunodeficiency virus infected children. In addition, isoniazid therapy completion was very low. The hospitals and Regional Health Bureau should avail isoniazid preventive therapy in the nearby health facilities and strengthen adequate counseling on the role of isoniazid preventive therapy for tuberculosis

Détermination des concentrations plasmatiques de l'isoniazide et la rifampicine chez les patients sous antituberculeux

Introduction : La tuberculose est un problème de santé publique dans le monde entier. Son traitement est basé sur quatre antituberculeux majeurs dont l'isoniazide et la rifampicine qui ont bouleversé le pronostic de cette maladie. L'objectif de cette étude était de montrer l'apport du suivi thérapeutique pharmacologique dans la prévention des échecs thérapeutiques en cas de sous-dosage et de toxicité en cas de surdosage.Matériels et méthodes : Il s'agit d'une étude rétrospective faite à l'Hôpital Moulay Youssef et le laboratoire de toxicologie et de pharmacologie du centre anti-poison et de pharmacovigilance du Maroc sur une période de 9 mois, et menée sur 142 patients ayant tous bénéficié d'un suivi thérapeutique pharmacologique de l'isoniazide et la rifampicine. Les dosages étaient réalisés par chromatographie liquide haute performance après extraction liquide-liquide. Résultats : Notre étude a montré qu'à dose thérapeutique, 78,2% des patients tuberculeux avaient des concentrations plasmatiques de rifampicine au-dessous de la fourchette thérapeutique et 35,4% des patients avaient des concentrations plasmatiques d'isoniazide au-dessus de la fourchette thérapeutique.Conclusion : Dans le cadre du traitement antituberculeux, le recours au suivi thérapeutique pharmacologique permet aux cliniciens

L'interet de l'association de la vitamine B6 a l'Isoniazide dans le traitement antituberculeux chez l'enfant

Les auteurs presentent les resultats d'une etude prospective realisee du 1er octobre 1993 au 31 mars 1995 chez 85 enfants tuberculeux ages de 5 mois a 15 ans dans le service de Pediatrie de l'hopital de l'Institut Medical Evangelique de Kimpese; Bas-Zaire et portant sur l'interet de la Vitamine B6 associee a l'Isoniazide (INH) dans le traitement antituberculeux chez l'enfant. Deux groupes d'etudes ont ete constitues: un groupe recevant la Vitamine B6 et un autre groupe recevant le placebo. Au terme de l'etude; aucune manifestation neurologique ou neuropsychiatrique n'a ete objectee dans l'un ou l'autre groupe. Ces resultats temoignent de l'inutilite de l'association de la vitamine B6 a l'INH dans le traitement antituberculeux chez l'enfant