Molecular genetics of drug-resistant Mycobacterium tuberculosis isolates in Finland, 1995-2004.
METHODS
Modern molecular methods help us to understand the transmission and epidemiology of Mycobacterium tuberculosis.


OBJECTIVE
To analyse the molecular epidemiology of drug-resistant tuberculosis (TB), and to characterise isoniazid (INH) and rifampicin (RMP) resistance conferring mutations in Finland during 1995-2004.


METHODS
A total of 3959 new M. tuberculosis isolates underwent drug susceptibility testing; all phenotypically resistant isolates were genotyped by IS6110 restriction fragment length polymorphism and spoligotyping if necessary. INH- and/or RMP-resistant isolates were sequenced for their resistance associated genes, katG locus 315 and rpoB, respectively.


RESULTS
Of the 3959 isolates tested (92.4% of culture-positive cases), 183 (4.6%) were resistant to at least one first-line anti-tuberculosis drug; 14 (0.4%) isolates were multidrug-resistant. Thirty-seven (20.4%) resistant isolates belonged to 17 clusters, and the largest cluster included four isolates. The Beijing family genotype accounted for 8.8% (16 isolates) of all drug-resistant isolates. A Ser315Thr mutation in katG was found in 46.7% (56 isolates) of the INH-resistant isolates and rpoB was mutated in 85.7% (18 isolates) of the isolates resistant to RMP.


CONCLUSIONS
Transmission of drug-resistant TB is rare in Finland, especially between indigenous and immigrant populations. Screening of mutations that confer INH and RMP resistance seems to be feasible if risk factors for multidrug resistance exist.
Marttila
H J
HJ
Mycobacterial Reference Laboratory, National Public Health Institute, Turku, Finland. harmar@utu.fi
Mäkinen
J
J
Marjamäki
M
M
Ruutu
P
P
Soini
H
H
D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D002374:Catalase / Q000235:genetics; D004252:DNA Mutational Analysis; D012321:DNA-Directed RNA Polymerases; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D017354:Point Mutation; D012293:Rifampin / Q000494:pharmacology; D016036:Seroepidemiologic Studies; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology*
D000995:Antitubercular Agents; D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D007538:Isoniazid; D012293:Rifampin