Insights into the genetic diversity ofMycobacterium tuberculosisin Tanzania

Abstract

24 Background: Human tuberculosis (TB) is caused by seven phylogenetic lineages of the 25 Mycobacterium tuberculosis complex (MTBC), Lineage 1-7. Recent advances in rapid 26 genotyping of MTBC based on single nucleotide polymorphisms (SNP), allow for rapid and 27 phylogenetically robust strain classification, paving the way for defining genotype-phenotype 28 relationships in clinical settings. Such studies have revealed that, in addition to host and 29 environmental factors, different strains of the MTBC influence the outcome of TB infection 30 and disease. In Tanzania, such molecular epidemiological studies of TB however are scarce in 31 spite of a high TB burden. 32 Methods and Findings: Here we used a SNP-typing method to genotype a nationwide 33 collection of 2,039 MTBC clinical isolates obtained from new and retreatment TB cases 34 diagnosed in 2012 and 2013. Four lineages, namely Lineage 1-4 were identified. The 35 distribution and frequency of these lineages varied across the regions but overall, Lineage 4 36was the most frequent (n = 866, 42.5%), followed by Lineage 3 (n = 681, 33.4%) and 1 (n = 37 336, 16.5%), with Lineage 2 being the least frequent (n = 92, 4.5%). A total of 64 (3.1%) 38 isolates could not be assigned to any lineage. We found Lineage 2 to be associated with 39 female sex (adjusted odds ratio [aOR] 2.25; 95% confidence interval [95% CI] 1.38 -3.70, p < 40 0.001) and retreatment (aOR 1.78; 95% CI 1.00 -3.02, p = 0.040). We found no associations 41 between MTBC lineage and patient age or HIV status. Our sublineage typing based on spacer 42 oligotyping revealed the presence of mainly EAI, CAS and LAM families. Finally, we detected 43 low levels of multidrug resistant isolates among a subset of retreatment cases 44 Conclusions: This study provides novel insights into the influence of pathogen-related 45 factors on the TB epidemic in Tanzania. 46 an estimated 10.0 million people developed TB globally, with 1.3 million dying of the 50 disease. More than 80% of the TB burden lies in the thirty high burden countries [1]. 51 Tanzania is among these countries, with a national average TB notification rate of 129 cases 52 per 100,000; however, some regions show higher notification rates [2]. Like in most sub-53 Saharan African countries, the HIV epidemic contributes to the high TB incidence in 54 Tanzania, where a-third of the TB patients are co-infected with HIV [2]. Contrarily, drug 55 resistant-TB is still low in this setting [3]. Other risk factors such poverty also influence the 56 epidemiology of TB in Tanzania [4].57 Transmission of TB occurs via infectious aerosols, and upon exposure individuals can either 58 develop active disease or remain latent infected [5]. It is estimated that a-quarter of the 59 world's population is latently TB infected [6], with a 5 -10% life time risk to develop active 60 TB disease; this risk is 50% in case of HIV co-infected individuals [7]. 61 The complex dynamics of TB infection and disease are determined by the environment, the 62 host and the pathogen [8]....

Spoligotyping of Mycobacterium tuberculosis isolates using Luminex®-based method in Lebanon

“…L3, the Central-Asian lineage, appears to have a moderate prevalence rate among MTB isolates in our study. This lineage is mainly found in Central Asia, preferentially North India and Pakistan, some countries of the West Asia (Afghanistan), and several countries in East and North-East Africa such as Sudan, Tanzania, Ethiopia [28][29][30]. In our study, the CAS1-Delhi sublineage of the L3 totaled 10.2% of the tested isolates.…”