📖 ABSTRACT/OVERVIEW
Background: North East Nigeria faces compounding challenges of high tuberculosis burden, active insurgency disrupting healthcare delivery, and rising multidrug-resistant tuberculosis (MDR-TB) rates. The phenotypic diversity, drug susceptibility profiles, and optimal pharmacotherapy approaches for MDR-TB in this region are critical knowledge gaps with direct clinical consequences. This translational research programme characterises MDR-TB burden, phenotypes, and pharmacotherapy outcomes in North East Nigeria. Methods: A three-part prospective programme was conducted across DOTS and MDR-TB treatment centres in Borno, Adamawa, and Yobe states. First, culture-confirmed MDR-TB isolates (n = 180) were phenotypically characterised and subjected to second-line drug susceptibility testing. Second, whole genome sequencing of 80 isolates identified resistance mutation profiles and transmission clusters. Third, a pharmacokinetic-pharmacodynamic modelling study of bedaquiline and linezolid dosing in 40 enrolled MDR-TB patients established local PK/PD targets. Results: Pre-extensively drug-resistant TB was identified in 23 percent of MDR-TB isolates. WGS revealed three dominant transmission clusters suggesting institutional acquisition. Bedaquiline PK parameters in North East patients showed lower Cmax values than registration trial data, suggesting dose adjustment consideration. PD modelling confirmed AUC/MIC as the optimal predictor of bactericidal activity. Conclusion: MDR-TB in North East Nigeria exhibits a complex resistance phenotype with ongoing transmission. Local pharmacokinetic data for bedaquiline argue for dose optimisation trials in this population. Keywords: MDR-TB, North East Nigeria, bedaquiline, pharmacokinetics, drug resistance
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