Non-tuberculous Mycobacteria in The Gambia: Prevalent Species, Carriage and Disease

Pulmonary tuberculosis-like disease caused by non-tuberculous mycobacteria (NTM) has gained attention, in part, because of its increased recognition especially in the elderly and immunocompetent population. This is an emerging problem of public health significance. With the increasing incidence of case reports and series from diverse countries and regions of the world, the distribution of NTM species isolated from clinical samples appear to vary significantly by region. However, very little is known about the contribution(s) of NTM to tuberculosis-like disease, and significant knowledge gaps exist regarding their geographical distribution, clinical and molecular epidemiology in low and middle income countries (LMIC) where there is a high burden of disease caused by Mycobacterium tuberculosis complex (MTBC). This dissertation provides a state of the art review of the current epidemiology of NTM carriage and disease in sub-Saharan Africa and presents results from a study of the epidemiology of NTM in The Gambia on pulmonary carriage and disease. I systematically searched electronic databases (PubMed, Embase, Popline, Ovid and Africa Wide Information) for English language articles on pulmonary NTM in sub-Saharan Africa published from Jan 1,1940 to Oct 1, 2016. The American Thoracic Society and Infectious Disease Society of America (ATS/IDSA) diagnostic criteria was applied to differentiate between colonisation of NTM and clinically relevant pulmonary NTM disease. Mycobacterium avium complex (MAC) species were the most frequently isolated NTM (15.0% - 57.8%) in colonisation while M. kansasii, was the most common (184 [69.2%] of 266) cause of confirmed pulmonary NTM disease. A significant proportion (2,623 [29.2%] of 8,980) of NTM isolates in the studies reviewed were not identified to species level. This and the absence of detailed clinical and radiological data hampered the assessment of the clinical relevance of all NTM isolates. A nationwide Tuberculosis prevalence survey provided a platform for me to investigate the population prevalence and molecular epidemiology of NTM in pulmonary samples in the general population of the Gambia. Here, I confirmed suspected NTM cultures from decontaminated sputa stored from the parent survey by 16S rRNA gene sequencing analysis and applied the ATS/IDSA diagnostic criteria to determine clinical relevance of identified NTM. The prevalence of NTM in pulmonary samples was 39.8% [95% Confidence Interval, CI: 35.8% – 44.0%). M. avium complex was by far the most commonly isolated NTM (71.0%), followed by M. fortuitum (9.5%) and M. nonchromogenicum (2.9%). All age groups were three times as likely to have NTM in their sputa as the 15-24 age group (p= 0.017), while urban compared to rural residents were 40 times less likely to be NTM positive (p =0.012). Collectively, these findings highlight the contribution of NTM to colonisation and the risk for over diagnosis of smear positive TB, given the prevalence in presumptive TB cases in The Gambia. I have highlighted the knowledge gap resulting from incomplete identification of NTM species in the sub-continent and the risk of misdiagnosis of pulmonary NTM as PTB when smear microscopy is the sole diagnostic modality. Additional research and surveillance is therefore required to investigate the full contribution of NTM to pulmonary disease, particularly in high risk groups and it is important to review the existing tuberculosis identification methods for presumptive tuberculosis suspects in The Gambia, and sub-continent