Molecular characterization of Mycobacterium tuberculosis complex isolates from Sweden

Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex (MTC), is a serious infection in man and animals. According to the World Health Organisation (WHO), about one third of the world´s population is infected with this organism, around nine million new cases are registered every year and two million people die from the infection. Because of the failure of TB treatment regimens, drug resistant (DR) and multi-drug resistant (MDR) TB are increasing. At present, Sweden is one of the countries with the lowest incidence of TB in the world, the majority of TB patients coming from countries with a high incidence of TB.

The current study aimed at invistigating the prevalence and transmission of DRTB in Sweden. In the first part of the study 400 DR strains isolated from 315 foreign-born patients and 85 Swedish-born patients from 1994-2005 were analysed using the molecular techniques restriction fragment length polymorphism (RFLP) and spoligotyping. The isolates were resistant to at least one of the first line drugs; streptomycin (SM), isoniazid (INH), ethambutol (EMB) or rifampicin (RIF). Fifty one percent (203/400) of the isolates were clustered by RFLP in 35 different clusters. The size of the clusters varied from 2 to 96 isolates. Most of the clusters comprised only two to three individuals except one large cluster that consisted of 96 patients harbouring isolates with an identical RFLP pattern. The majority of the patients in this cluster were from East Africa, but during the later part of the study several Swedishborn patients infected with this strain appeared.

In the second part of the study the presence and transmission of DR MTC isolates of the Beijing genotype was investigated. The Beijing genotype is a distinct genetic lineage, which has caused substantial transmission of disease in many regions of the world. Seventy DR isolates of the Beijing genotype, 17 of which were MDR and one extensively drug resistant (XDR) were identified during 1994-2008. The majority of the patients came from countries where the Beijing lineage is prevalent. Using different genotyping methods (IS6110 and IS1547 RFLP, spoligotyping, Rv1335 gene polymorphism, regions of difference RD105, RD142, RD150, RD181 and mutations in mutT2, mutT4 genes) the 70 isolates were allocated to 11 different genetic sublineages. The majority of the isolates (54/70) belonged to the typical modern Beijing lineages. Ten clusters of Beijing strains were found, the largest cluster comprising five patients. Contact tracing only established epidemiological linkage between two patients. Thus, there is no extensive spread of the Beijing genotype in Sweden.

These studies illustrate that molecular characterization of DRTB strains offers a powerful tool to trace and monitor transmission as well as to identify deficiencies in national TB control programs.

List of scientific papers

I. Ghebremichael S, Petersson R, Koivula T, Pennhag A, Romanus V, Berggren I, Petrini B, Hoffner S, Källenius G (2008). "Molecular epidemiology of drug-resistant tuberculosis in Sweden." Microbes Infect 10(6): 699-705. Epub 2008 Mar 29
https://pubmed.ncbi.nlm.nih.gov/18485780

II. Ghebremichael S, Groenheit R, Pennhag A, Koivula T, Andersson E, Bruchfeld J, Romanus V, Källenius G (2010). "Drug resistant Mycobacterium tuberculosis of the Beijing genotype does not spread in Sweden." (Submitted)