Abstract
In molecular epidemiological studies of drug resistant Mycobacterium tuberculosis (TB) in Sweden a large outbreak of an isoniazid resistant strain was identified, involving 115 patients, mainly from the Horn of Africa. During the outbreak period, the genomic pattern of the outbreak strain has stayed virtually unchanged with regard to drug resistance, IS6110 restriction fragment length polymorphism and spoligotyping patterns. Here we present the complete genome sequence analyses of the index isolate and two isolates sampled nine years after the index case as well as experimental data on the virulence of this outbreak strain. Even though the strain has been present in the community for nine years and passaged between patients at least five times in-between the isolates, we only found four single nucleotide polymorphisms in one of the later isolates and a small (4 amino acids) deletion in the other compared to the index isolate. In contrast to many other evolutionarily successful outbreak lineages (e.g. the Beijing lineage) this outbreak strain appears to be genetically very stable yet evolutionarily successful in a low endemic country such as Sweden. These findings further illustrate that the rate of genomic variation in TB can be highly strain dependent, something that can have important implications for epidemiological studies as well as development of resistance.
Highlights
Tuberculosis (TB) is a major global health concern and the increasing drug resistance makes TB-control even more demanding
The cluster is defined by a low-level resistance to INH, a 14-band IS6110 restriction fragment length polymorphism (RFLP) pattern and a spoligotyping pattern belonging to SIT52, of the T2 lineage, according to the SITVIT2 database (Fig. 2)
The first isolate (S96-129) from August 1996 was from the source case, a 19-year old male originating from Zaire ( Democratic Republic of the Congo)
Summary
Tuberculosis (TB) is a major global health concern and the increasing drug resistance makes TB-control even more demanding. Drug- and multidrug resistance (MDR, i.e. resistance to at least rifampicin (RIF) and isoniazid (INH)) was assessed, and the median global prevalence of drug resistance was estimated to be 20% [2]. An estimated 2.9% of all new TB cases worldwide have MDR-TB. Strains resistant to the agents used in the therapy of MDR-TB such as the fluoroquinolone ofloxacin (OFL) and the injectable second-line drugs amikacin (AMI) were more recently described and named extensively drug resistant (XDR) [3]. A growing proportion of such XDR-TB cases will seriously obstruct TB control globally [4,5]
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