Molecular characterization of Mycobacterium tuberculosis complex and prevalence of nontuberculous mycobacteria and other potential pathogenic bacteria from Tubercolisis suspents in Northeastern, Tanzania

Molecular typing is increasingly essential to tuberculosis (TB) control programmes, providing public health practitioners with a tool to characterize transmission patterns, track the emergence and spread of strains of M. tuberculosis complex (MTC) in populations. While molecular typing is already used extensively as a tool for TB control in many developed settings across the globe, its use in resource-poor settings is still limited. Moreover, information on the role, contribution and burden of nontuberculous mycobacteria (NTM) and other pathogens in aetiology of TB-like syndromes is also lacking in such settings. The broad objective of this dissertation was to determine the genetic diversity of MTC and their drug resistance profiles as well as the prevalence of NTM and other potentially pathogenic bacteria among TB suspects in Northeastern, Tanzania in order to generate insights that may inform the design of a rational TB control programmes. A total of 18 distinct spoligotypes were identified in this study area, with CAS1-KILI and EAI8 being the most predominant families. Major lineages prediction by conformal Bayesian network (CBN) revealed that 70% of TB infections in this area is due to modern lineages, whereas 30% of TB infections is due to the ancestral lineages mainly of Indo-oceanic lineage. The study also revealed that the overall proportions of any drug resistance and MDR-TB were 12.7% and 6.3% respectively. With the prevalence of any drug resistance and MDR-TB among new cases being 11.4% and 4.3% respectively, among previously, treated cases were 22.2%. The prevalence of NTM was found to be 9.7 %, with HIV being a significant predictor of NTM detection (P < 0.001). Four out of 30 patients with NTM diagnosed by culture received 1st line anti-TB treatment suggesting that a proportion of patients diagnosed by smear microscopy (4/65, 6.2%) were mistreated as TB patients. Our findings further showed that 17 (4.6%) out of 372 TB suspects were due to pulmonary nocardiosis. Overall this dissertation has revealed that TB is still a major problem in Tanga and is characterized by a diverse array of MTB strains. Additionally, modern MTB strains contribute significantly to TB infections in this area. High proportions of anti-TB drug resistance among new treated cases observed suggest that more efforts need to be done to identify individual cases at facility level for improved TB control programmes. Inefficient screening of TB patients and a prevalent increase of NTM may contribute to both unrealistic and mismanagement of TB cases. A diverse array of pathogenic Nocardia species among TB suspects further indicates that they are likely cause of human disease in this population. Therefore, need to integrate NTM and pathogens causing TB-like syndromes in diagnosis and management of TB is urgent. Results of these investigations contribute to the understanding of the dynamics of TB transmission in resource poor settings of Tanzania and highlight key factors that should be considered in the development of rational approaches to design effective TB prevention and control programmes in the country