Mycobacterium tuberculosisComplex Lineage 3 as Causative Agent of Pulmonary Tuberculosis, Eastern Sudan1

Abstract

T uberculosis (TB) remains a major global health problem; 10 million new cases were reported in 2018 (1). In Sudan, the estimated national TB incidence in 2018 was 71/100,000 persons; a total of 20,638 cases were reported (1). However, the TB burden is by no means homogeneous across the country. For instance, in eastern Sudan, TB notifications reached 275/100,000 persons in 2012 (2,3). Prevalence of multidrug-resistant TB (MDR TB) (i.e., resistant to isoniazid and rifampin) was estimated at 2.9% in new and 13% in retreatment cases; however, studies have reported MDR TB rates of 6%-22% (1,4-10). Ongoing transmission is one of the key challenges for TB control programs, especially in countries with a high TB burden (1,11). In recent years, molecular techniques have been increasingly used to clarify and trace transmission of Mycobacterium tuberculosis complex (MTBC) strains and to direct and guide targeted TB control actions (12,13). However, availability of molecular techniques is limited in many countries in Africa with a high TB burden (11). In Sudan, drug-resistant TB often goes undetected, resulting in inadequate treatment, illness, death, and ongoing transmission (1,14). Local laboratories have limited access to mycobacterial culture and drug susceptibility testing (DST) or DNA-based techniques (14). Therefore, MDR TB rates might be underestimated in eastern Sudan. In addition, mutations that mediate drug resistance have not been investigated. Taken together, these factors indicate that, although TB is a huge health problem in eastern Sudan, precise data on the phylogeny and transmission dynamics of MTBC strains, as well as on resistance patterns, is sparsely available (2,3,7,8,15). Studies using molecular epidemiologic tools are rare and have used classical genotyping techniques, such as

Clusters of Drug-Resistant Mycobacterium tuberculosis Detected by Whole-Genome Sequence Analysis of Nationwide Sample, Thailand, 2014–2017

“…Our 11-SNP cutoff was proportionally 0.0004 of the 26,541 SNPs in our total set. This proportion was concordant with that in a previous study ( 21 ), and more stringent than those in other studies ( 18 , 20 ). A <12-SNP cutoff has been previously proposed as the upper boundary for possible cluster transmission events ( 2 ).…”

“…First, the < 11 SNP difference cutoff for a cluster was derived directly from the maximum number of differences between the 11 paired isolates used as an internal control. Second, we used an SNP cutoff concordant with, or more stringent than, those in previous studies ( 17 – 20 ). Our 11-SNP cutoff was proportionally 0.0004 of the 26,541 SNPs in our total set.…”

Genetic diversity of the Mycobacterium tuberculosis complex strains from newly diagnosed tuberculosis patients in Northwest Ethiopia reveals a predominance of East-African-Indian and Euro-American lineages

“…The predominance of the East-African-Indian L3 and Euro-American L4 was consistent with other studies in Ethiopia (Tessema et al, 2013;Biadglegne et al, 2015;Tadesse et al, 2017;Damena et al, 2019), albeit with less L7 than the expected prevalence of 9-15% (Biadglegne et al, 2015;Yimer et al, 2015). L3 and L4 have also been reported in other African countries, particularly in neighboring Sudan (Mbugi et al, 2016;Chihota et al, 2018;Couvin et al, 2019b;Shuaib et al, 2020). The current findings confirm that L3 and L4 are endemic TB strains in this study area, possibly due to co-adaptation with its human host (Gagneux, 2012;Couvin et al, 2019b), and capable of evading the host immune response and progress to rapid TB disease and transmis- It has been also shown that strains of evolutionarily modern L3 and L4 lineages are successful human pathogens with increased virulence, enabling their worldwide distribution (Hershberg et al, 2008;Gagneux, 2012).…”

Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia

“…Therefore, based on this understanding, it can be speculated that possibly the strains first acquired drug resistance to isoniazid (KatG, Ser315Thr) and ethambutol ( EmbB 306) then independently became resistant to other drugs, rifampicin, streptomycin, and pyrazinamide, while propagating to the next patients ( Figure 1 ). As a result, rapid and low-cost diagnostic techniques for detecting embB 306 mutations in drug-resistant strains, particularly in high-burden drug-resistant TB areas, are encouraged to guide patient management and control of drug-resistant TB [ 28 , 31 , 32 ].…”