Molecular Epidemiology of <em>Mycobacterium tuberculosis</em> in Western Sweden

Karine Brudey

Max Gordon

Peter Moström

Liselott Svensson

Unité de la Tuberculose et des Mycobactéries, Institut Pasteur de Guadeloupe, Pointe-à-Pitre, Guadeloupe,^{Institute of Medical Microbiology and Immunology, Göteborg University,}^{Sahlgrenska University Hospital, Göteborg, Sweden}³

^{Corresponding author. Mailing address: Unité de la Tuberculose et des Mycobactéries, Institut Pasteur de Guadeloupe, Morne Jolivière, BP 484, 97165 Pointe-à-Pitre, Cedex, Guadeloupe. Phone: 590 (590) 893 881. Fax: 590 (590) 893 880. E-mail:}rf.epuoledaug-ruetsap@igotsarn.

Received 2004 Feb 9; Revised 2004 Mar 15; Accepted 2004 Mar 25.

Abstract

The genetic diversity of Mycobacterium tuberculosis isolates among patients from Sweden was determined by a combination of two PCR-based techniques (spoligotyping and variable number of tandem repeats analysis). It resulted in a clustering of 23.6% of the isolates and a rate of recent transmission of 14.1%. The clustered isolates mainly belonged to the Haarlem family (23.2%), followed by the Beijing (9.8%), Latin American and Mediterranean (LAM; 8%), and East African-Indian (EAI; 6.2%) families. A comparison of the spoligotypes with those in the international spoligotyping database showed that 62.5% of the clustered isolates and 36.6% of all isolates typed were grouped into six major shared types. A comparison of the spoligotypes with those in databases for Scandinavian countries showed that 33% of the isolates belonged to an ill-defined T family, followed by the EAI (22%), Haarlem (20%), LAM (11%), Central Asian (5%), X (5%), and Beijing (4%) families. Both the highest number of cases and the proportion of clustered cases were observed in patients ages 15 to 39 years. Nearly 10% of the isolates were resistant to one or more drugs (essentially limited to isoniazid monoresistance). However, none of the strains were multidrug resistant. Data on the geographic origins of the patients showed that more than two-thirds of the clustered patients with tuberculosis were foreign-born individuals or refugees. These results are explained on the basis of both the historical links within specific countries and recently imported cases of tuberculosis into Sweden.

Abstract

About 2 million humans die from tuberculosis (TB) each year, and it is estimated that about one-third of the world's population is infected with Mycobacterium tuberculosis (20). The disease is most common in developing countries and is spreading fast because of the human immunodeficiency virus pandemic. In Western European countries, the rates of TB, determined from rates of notification to public health authorities, have increased recently, particularly because of cases among immigrants from countries with a high incidence of TB (2). In Eastern European countries, the rates of mortality and morbidity from TB have also increased dramatically because of socioeconomic difficulties or problems with TB control programs (2). Despite a low reported TB incidence of 5.2/100,000 inhabitants in Sweden, there remains a risk of spread of multidrug-resistant (MDR) TB due to migration from the countries of Eastern Europe, where the incidence of MDR TB is alarming (6).

During the last decade, molecular epidemiological methods have been developed with the aim of revealing epidemiological features of the disease, surveying its spread, and identifying risk factors associated with the dissemination of MDR strains (18). Although the “gold standard” method for studying the epidemiology of TB is IS6110-based restriction fragment length polymorphism analysis, it remains a cumbersome method. It may be successfully replaced by easier PCR-based methods, such as spoligotyping and variable number of tandem DNA repeats (VNTR) analysis, which have high discriminatory indices and reproducibilities when they are used in combination (9, 18). The aim of this study was to determine the genetic diversity of M. tuberculosis isolates from Swedish patients by using this combination of PCR-based methods and to compare the data obtained with those from neighboring countries to highlight the dissemination of major phylogenetic clades of TB within Scandinavia.

Acknowledgments

This work was supported by grants from the Réseau International des Instituts Pasteur et Instituts Associés, Institut Pasteur, Paris, France, and EU Project QLK2-CT-2000-630, entitled New Generation Genetic Markers and Techniques for the Epidemiology and Control of Tuberculosis. K.B. was cofunded by the Institut Pasteur and European Social Funds, provided through the Regional Council of Guadeloupe.

Acknowledgments

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