The host determinants of treatment outcomes of multi-drug resistant pulmonary tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) has been an emerging public health problem. MDR-TB is a fatal disease whilst treatment of MDR-TB is prolonged but less effective and toxic. Inter-individual variations in clinical presentation and treatment response have been reported in tuberculosis (TB). Identifying host determinants for MDR-TB is important in the search for adjunctive therapy to improve treatment outcome for MDR-TB. This thesis aims to evaluate the impacts of three host factors of leukotriene A4 hydrolase (LTA4H) genotype, diabetes mellitus (DM) and vitamin D on clinical presentation, treatment response and treatment outcome of pulmonary TB patients, particularly MDR-TB. The first results chapter, chapter 3, illustrates the picture of increasing MDR-TB in Ho Chi Minh City, Vietnam, from 2011 to 2015 and its risk factors for poor treatment outcomes. In chapter 4, LTA4H genotype showed no significant association with clinical presentation, bacterial burden, extent of lung damage, treatment response or outcome in 312 MDR-TB and 600 drug susceptible (DS) TB patients. Although a potential marker for host-targeted therapy for TB meningitis, this genotype does not appear to be such for pulmonary TB. In chapter 5, the detrimental effect of DM on clinical presentation, bacterial load, disease severity, increased inflammation and treatment response was clearly observed in pulmonary TB. Although not a significant risk factor for mortality and poor treatment outcome, DM prolonged sputum culture conversion of MDR-TB and should be considered as an important host factor to adjust for. Chapter 6 reveals the association between vitamin D and extent of lung damage, severity and inflammatory response through blood biomarkers among 309 MDR-TB and 301 DS-TB patients. Vitamin D deficiency caused an adverse effect on MDR-TB, but not on DS-TB during treatment. The work of this thesis has provided more evidence on host factors in efforts to improve treatment outcomes for pulmonary MDR-TB.