<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0873-2159</journal-id>
<journal-title><![CDATA[Revista Portuguesa de Pneumologia]]></journal-title>
<abbrev-journal-title><![CDATA[Rev Port Pneumol]]></abbrev-journal-title>
<issn>0873-2159</issn>
<publisher>
<publisher-name><![CDATA[Sociedade Portuguesa de Pneumologia]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0873-21592008000200006</article-id>
<title-group>
<article-title xml:lang="pt"><![CDATA[Epidemiologia molecular de Mycobacterium tuberculosis em Lisboa]]></article-title>
<article-title xml:lang="en"><![CDATA[Molecular epidemiology of Mycobacterium tuberculosis in Lisbon]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Portugal]]></surname>
<given-names><![CDATA[Isabel]]></given-names>
</name>
<xref ref-type="aff" rid="A01"/>
<xref ref-type="aff" rid="A02"/>
<xref ref-type="aff" rid="A03"/>
<xref ref-type="aff" rid="A04"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Barreiro]]></surname>
<given-names><![CDATA[Luís]]></given-names>
</name>
<xref ref-type="aff" rid="A04"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Vultos]]></surname>
<given-names><![CDATA[Tiago]]></given-names>
</name>
<xref ref-type="aff" rid="A04"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Macedo]]></surname>
<given-names><![CDATA[Rita]]></given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Furtado]]></surname>
<given-names><![CDATA[Cristina]]></given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Antunes]]></surname>
<given-names><![CDATA[António Fonseca]]></given-names>
</name>
<xref ref-type="aff" rid="A05"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Brum]]></surname>
<given-names><![CDATA[Laura]]></given-names>
</name>
<xref ref-type="aff" rid="A02"/>
<xref ref-type="aff" rid="A04"/>
<xref ref-type="aff" rid="A06"/>
</contrib>
</contrib-group>
<aff id="A01">
<institution><![CDATA[,Universidade de Lisboa Faculdade de Farmácia ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<aff id="A02">
<institution><![CDATA[,Instituto Nacional de Saúde Dr. Ricardo Jorge  ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<aff id="A03">
<institution><![CDATA[,Universidade de Lisboa Faculdade de Farmácia Centro de Patogénese Molecular]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="A04">
<institution><![CDATA[,Instituto Nacional de Saúde Dr. Ricardo Jorge Centro de Bacteriologia Unidade de Micobactérias]]></institution>
<addr-line><![CDATA[Lisboa ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="A05">
<institution><![CDATA[,Ministério da Saúde Direcção-Geral de Saúde ]]></institution>
<addr-line><![CDATA[Lisboa ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="A06">
<institution><![CDATA[,Universidade Nova de Lisboa Faculdade de Ciências Médicas ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>03</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>03</month>
<year>2008</year>
</pub-date>
<volume>14</volume>
<numero>2</numero>
<fpage>239</fpage>
<lpage>259</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_arttext&amp;pid=S0873-21592008000200006&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_abstract&amp;pid=S0873-21592008000200006&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_pdf&amp;pid=S0873-21592008000200006&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="pt"><p><![CDATA[Foi realizado um estudo de epidemiologia molecular a estirpes de Mycobacterium tuberculosis isoladas em hospitais de Lisboa. Analisaram-se geneticamente os isolados de Mycobacterium tuberculosis com o método restriction fragment length polymorphism (RFLP) utilizando a sequência de inserção IS6110 como sonda, com o objectivo de detectar as estirpes da família Lisboa e determinar a diversidade genética das estirpes de Mycobacterium tuberculosis isoladas em Lisboa, identificando os mais importantes factores de risco de transmissão da tuberculose. Foram analisados 290 isolados de Mycobacterium tuberculosis, dos quais 64,8% se encontraram agrupados em clusters; mesmo excluindo as estirpes que apresentaram mais de 5 cópias de IS6110, a percentagem de agrupamento foi de 60,7%. A multirresistência foi observada em 4,1% das estirpes e encontraram-se todas em clusters. Quarenta e cinco isolados (18,2%) pertenciam à família Lisboa. Considerando a percentagem relativamente alta de estirpes em cluster detectada neste estudo, cremos que a transmissão activa continua a ser uma realidade em Lisboa. Para além disso, as estirpes dos clusters Lisboa representam as estirpes predominantes que circulam em Lisboa. Continuando muito relacionadas com a resistência aos antibacilares, embora correspondam a uma percentagem inferior à verificada em estudos anteriores.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[We conducted a molecular epidemiology study of Mycobacterium tuberculosis strains isolated from patients in Lisbon hospitals. We used restriction fragment length polymorphism (RFLP) to detect Lisbon family strains and to determine the genetic diversity of Mycobacterium tuberculosis strains isolated in Lisbon, through identification of the most important risk factors of tuberculosis transmission analysis, with the insertion sequence IS6110 as a probe to fingerprint isolates of Mycobacterium tuberculosis. 64.8% of the 290 Mycobacterium tuberculosis isolates were grouped in clusters. This figure was 60.7% if we excluded strains with five or fewer IS6110 copies. Multidrug-resistance was observed in 4.1% of the strains and they were all in clusters. Forty-five (18.2%) strains were included in the Lisbon family. Considering the relatively high percentage of strains in cluster detected in this study, we believe that active transmission is still taking place in Lisbon. Moreover, clusters of Lisbon strains represent the predominant strains circulating in Lisbon and are still related to drug resistance although presenting a lower percentage than that observed in previous studies.]]></p></abstract>
<kwd-group>
<kwd lng="pt"><![CDATA[Mycobacterium tuberculosis]]></kwd>
<kwd lng="pt"><![CDATA[multirresistência]]></kwd>
<kwd lng="pt"><![CDATA[epidemiologia molecular]]></kwd>
<kwd lng="en"><![CDATA[Mycobacterium tuberculosis]]></kwd>
<kwd lng="en"><![CDATA[multidrugresistance]]></kwd>
<kwd lng="en"><![CDATA[molecular epidemiology]]></kwd>
</kwd-group>
</article-meta>
</front><body><![CDATA[ <p><b>Epidemiologia molecular de </b><b><i>Mycobacterium tuberculosis </i></b><b>em Lisboa</b></p>      <p>&nbsp;</p>      <p><b>Molecular epidemiology of </b><b>Mycobacterium tuberculosis </b><b>in Lisbon</b></p>      <p>&nbsp;</p>      <p><b>Isabel Portugal<sup><a href="#1">1</a><a name="top1"></a></sup></b></p>      <p><b>Luís Barreiro<sup><a href="#2">2</a><a name="top2"></a></sup></b></p>      <p><b>Tiago Vultos<sup><a href="#2">2</a><a name="top2"></a></sup></b></p>      <p><b>Rita Macedo<sup><a href="#3">3</a><a name="top3"></a></sup></b></p>      <p><b>Cristina Furtado<sup><a href="#4">4</a><a name="top4"></a></sup></b></p>      <p><b>António Fonseca Antunes<sup><a href="#5">5</a><a name="top5"></a></sup></b></p>      ]]></body>
<body><![CDATA[<p><b>Laura Brum<sup><a href="#6">6</a><a name="top6"></a></sup></b></p>      <p>&nbsp;</p>      <p><b>Resumo</b></p>      <p>Foi realizado um estudo de epidemiologia molecular a estirpes de <i>Mycobacterium tuberculosis </i>isoladas em hospitais de Lisboa. Analisaram-se geneticamente os isolados de <i>Mycobacterium tuberculosis </i>com o método <i>restriction fragment length polymorphism </i>(RFLP) utilizando a sequência de inserção IS6110 como sonda, com o objectivo de detectar as estirpes da família Lisboa e determinar a diversidade genética das estirpes de <i>Mycobacterium tuberculosis </i>isoladas em Lisboa, identificando os mais importantes factores de risco de transmissão da tuberculose.</p>      <p>Foram analisados 290 isolados de <i>Mycobacterium tuberculosis, </i>dos quais 64,8% se encontraram agrupados em <i>clusters; </i>mesmo excluindo as estirpes que apresentaram mais de 5 cópias de IS6110, a percentagem de agrupamento foi de 60,7%. A multirresistência foi observada em 4,1% das estirpes e encontraram-se todas em <i>clusters. </i>Quarenta e cinco isolados (18,2%) pertenciam à família Lisboa. Considerando a percentagem relativamente alta de estirpes em <i>cluster </i>detectada neste estudo, cremos que a transmissão activa continua a ser uma realidade em Lisboa. Para além disso, as estirpes dos <i>clusters </i>Lisboa representam as estirpes predominantes que circulam em Lisboa. Continuando muito relacionadas com a resistência aos antibacilares, embora correspondam a uma percentagem inferior à verificada em  estudos anteriores.</p>      <p><b>Palavras-chave: </b><i>Mycobacterium tuberculosis, </i>multirresistência,  epidemiologia molecular.</p>      <p>&nbsp;</p>      <p><b>Abstract</b></p>      <p>We conducted a molecular epidemiology study of <i>Mycobacterium tuberculosis </i>strains isolated from patients in Lisbon hospitals. We used restriction fragment length polymorphism (RFLP) to detect Lisbon family strains and to determine the genetic diversity of <i>Mycobacterium tuberculosis </i>strains isolated in Lisbon, through identification of the most important risk factors of tuberculosis transmission analysis, with the insertion sequence IS6110 as a probe to fingerprint isolates of <i>Mycobacterium tuberculosis. </i>64.8% of the 290 <i>Mycobacterium tuberculosis </i>isolates were grouped in clusters.  This figure was 60.7% if we excluded strains with five or fewer IS6110 copies. Multidrug-resistance was observed in 4.1% of the strains and they were all in clusters. Forty-five (18.2%) strains were included in the Lisbon family. Considering the relatively high percentage of strains in cluster detected in this study, we believe that active transmission is still taking place in Lisbon. Moreover, clusters of Lisbon strains represent the predominant strains circulating in Lisbon and are still related to drug resistance although presenting a lower percentage than that observed in previous studies.</p>      <p><b>Key-words: </b><i>Mycobacterium tuberculosis, </i>multidrugresistance, molecular epidemiology.</p>      ]]></body>
<body><![CDATA[<p>&nbsp;</p>      <p>&nbsp;</p>      <p>Texto completo disponível apenas em PDF.</p>     <p>Full text only available in PDF format.</p>      <p>&nbsp;</p>     <p>&nbsp;</p>      <p><b>Bibliografia / Bibliography</b></p>      <!-- ref --><p>1. Direcção Geral de Saúde. Programa Nacional de Luta Contra a Tuberculose. Ponto da situação epidemiológica e de desempenho. 2003.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;[&#160;<a href="javascript:void(0);" onclick="javascript: window.open('/scielo.php?script=sci_nlinks&ref=000030&pid=S0873-2159200800020000600001&lng=','','width=640,height=500,resizable=yes,scrollbars=1,menubar=yes,');">Links</a>&#160;]<!-- end-ref --><p>2. van Embden JD, Cave MD, Crawford JT, <i>et al. </i>Strain identification of <i>Mycobacterium tuberculosis </i>by DNA fingerprinting: recommendations for a standardized methodology. J Clin Microbiol 1993;31:406 -9.</p>      <p>3. van Soolingen D. Molecular epidemiology of tuberculosis and other mycobacterial infections: main methodologies and achievements. J Intern Med 2001;249:1 -26. </p>      ]]></body>
<body><![CDATA[<p>4. Yang ZH, Bates JH, Eisenach KD, Cave MD. Secondary typing of <i>Mycobacterium tuberculosis </i>isolates with matching IS<i>6110 </i>fingerprints from different geographic regions of the United States. J Clin Microbiol 2001;39:1691 -5.</p>      <p>5. Kremer K, van Soolingen D, Frothingham R, <i>et al. </i>Comparison of methods based on different molecular epidemiological markers for typing <i>Mycobacterium tuberculosis </i>complex strains: inter-laboratory study of discriminatory power and  reproducibility. J Clin Microbiol 1999;37:2607 -18.</p>      <p>6. Kamerbeek J, Schouls L, Kolk A, <i>et al. </i>Rapid detection and simultaneous strain differentiation of <i>Mycobacterium tuberculosis </i>for diagnosis and tuberculosis control. J Clin Microbiol 1997;35:907 -14.</p>      <p>7. Portugal I, Covas MJ, Brum L, <i>et al. </i>Outbreak of multiple drug-resistant tuberculosis in Lisbon: detection by restriction fragment length polymorphism analysis. Int J Tub Lung Dis 1999;3:207 -13.</p>      <p>8. David H, Levy-Frébault V, Thorel MF. Méthodes de laboratoire pour mycobactériologie clinique. 1989 Institut Pasteur, Paris.</p>      <p>9. Hermans P W, Messadi F, Guebrexabher H, <i>et al. </i>Usefulness of DNA typing for global tuberculosis epidemiology. J Inf Dis 1995;171:1504 -13.</p>      <p>10. Murray M, Alland D. Methodological problems in the molecular epidemiology of tuberculosis. Am J Epidemiol 2000;155: 565 -71.</p>      <p>11. van Soolingen D, Borgdorff MW, de Haas PEW, <i>et al. </i>Molecular epidemiology in the Netherlands: a nation-wide study from 1993 trough 1997. J Inf Dis 1999; 180: 726 -736.</p>      <p>12. Murray M, Nardell E. Molecular epidemiology of tuberculosis: achievements and challenges to current knowledge. Bull World Health Organ 2002;80:477 -82.</p>      <p>13. Bauer J, Yang Z, Poulsen S, Andersen AB. Results from 5 y of nation -wide  DNA fingerprint of <i>Mycobacterium tuberculosis </i>complex isolates in a country with  a low incidence of <i>Mycobacterium tuberculosis </i>infection. J Clin Microbiol 1998;36:305 -8.</p>      ]]></body>
<body><![CDATA[<p>14. van Soolingen D, Hermans P W, de Haas PEW, Soll D R, van Embden J D A. Occurrence and stability of insertion sequences in <i>Mycobacterium tuberculosis </i>complex strains: evaluation of insertion sequence–dependent DNA polymorphism as a tool in the epidemiology of tuberculosis. J Clin Microbiol 1991;29:2578 -86.</p>      <p>15. Small PM, Hopewell PC, Singh SP, <i>et al. </i>The epidemiology of tuberculosis in San Francisco. N Engl J Med 1994;330:1703 -9.</p>      <p>16. Direcção Geral de Saúde. Programa Nacional de Luta Contra a Tuberculose. Ponto da situação epidemiológica e de desempenho. 2002.</p>      <p>17. Yeh RW, Ponce de León A, Agasino CB, <i>et al. </i>Stability of <i>Mycobacterium tuberculosis </i>DNA genotypes. J Infect Dis 1998;177:1170 -1111.</p>      <p>18. Glynn J R, Whiteley J, Bifani P J, Kremer K, van Soolingen D. Worldwide occurrence of Beijing/W strains of <i>Mycobacterium tuberculosis</i>: a systematic review. Emerg Infect Dis 2002;8:843 -9.</p>      <p>19. Lillebaek T, Dirksen A, Kok -Jensen A, Andersen A.B. A dominant <i>Mycobacterium tuberculosis </i>strain emerging in Denmark. Int J Tuberc Lung Dis 2004;8:1001 -6.</p>      <p>20. Victor T C, de Haas P, Jordaan A, <i>et al. </i>Warren R. Molecular characteristics and global spread of <i>Mycobacterium tuberculosis </i>with a Western Cape F11 genotype. J Clin Microbiol 2004;42:769 -72.</p>      <p>21. Blackwood K, Al -Azem A, Elliott L, Hershfield E, Kabani A. Conventional and molecular epidemiology of tuberculosis in Manitoba. BMC Infect Dis 2003;3:1 -11.</p>      <p>22. Hermans P W, Messadi F, Guebrexabher H, <i>et al. </i>Analysis of the population structure of <i>Mycobacterium tuberculosis </i>in Ethiopia, Tunisia, and The Netherlands: usefulness of DNA typing for global tuberculosis epidemiology. J Infect Dis 1995;171:1504 -13.</p>      <p>23. Chevrel -Dellagi D, Abderrahman A, Haltiti R, Koubaji H, Gicquel B, Dellagi K. Large-scale DNA fingerprinting of <i>Mycobacterium tuberculosis </i>strains as a tool for epidemiological studies of tuberculosis. J Clin Microbiol 1993;31:2446 -50.</p>      ]]></body>
<body><![CDATA[<p>24. World Health Organization. Anti-tuberculosis drug resistance in the World. Report No.2: Prevalence and trends. 2000. WHO/CDS/TB/2000.278. Geneva: WHO, 2000.</p>      <p>25. World Health Organization. Anti-tuberculosis drug resistance in the World. Report No.3. 2004. WHO/, Geneva: WHO, 2004.</p>      <p>&nbsp;</p>     <p><sup><a href="#top1">1</a><a name="1"></a></sup> Professora Auxiliar da Faculdade    de Farmácia da Universidade de Lisboa. Investigadora Visitante de Instituto    Nacional de Saúde Dr. Ricardo Jorge, Centro de Patogénese Molecular, Faculdade    de Farmácia da Universidade de Lisboa, Portugal. Unidade de Micobactérias, Centro    de Bacteriologia, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal    / <i>Assistant Professor, Molecular Pathogenesis Centre, University of Lisbon    School of Pharmacy. </i><i>Guest Researcher, Micobacteria Unit, Bacteriology    Centre, Dr Ricardo Jorge National Institute of Health, Lisbon, Portugal</i></p>      <p><sup><a href="#top2">2</a><a name="2"></a></sup> Licenciado em Engenharia Biotecnológica,    Unidade de Micobactérias, Centro de Bacteriologia, Instituto Nacional de Saúde    Dr. Ricardo Jorge, Lisboa, Portugal / <i>BSc, Biotechnological Engineering,    Micobacteria Unit, Bacteriology Centre, Dr Ricardo Jorge National Institute    of Health, Lisbon, Portugal</i></p>      <p><sup><a href="#top3">3</a><a name="3"></a></sup> Licenciada em Química, Ramo    de Bioquímica. Aluna de Mestrado em Microbiologia Clínica. Direcção-Geral de    Saúde, Lisboa, Portugal / <i>BSc, Chemistry (Biochemistry). </i><i>Clinical    Microbiology MSc student</i></p>      <p><sup><a href="#top4">4</a><a name="4"></a></sup> Licenciada em Ciências Farmacêuticas.    Aluna de Doutoramento em Epidemiologia da Tuberculose; Unidade de Micobactérias,    Centro de Bactereologia, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa,    Portugal / <i>BSc, Pharmaceutical Sciences. </i> <i>Tuberculosis Epidemiology    PhD student. </i><i>Micobacteria Unit, Bacteriology Centre, Dr Ricardo Jorge    National Institute of Health, Lisbon, Portugal</i></p>      <p><sup><a href="#top5">5</a><a name="5"></a></sup> Direcção-Geral de Saúde, Lisboa,    Portugal / <i>Directorate-General for Health</i></p>      <p><sup><a href="#top6">6</a><a name="6"></a></sup> Professora Auxiliar Convidada    da Faculdade de Ciências Médicas da Universidade Nova de Lisboa. Assessora de    Bacteriologia do Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal.    Unidade de Micobactérias, Centro de Bacteriologia, Instituto Nacional de Saúde    Dr. Ricardo Jorge, Lisboa, Portugal / <i>Guest Assistant Professor, University    of Lisbon School of Medical Sciences. Bacteriology Assistant, Micobacteria Unit,    Bacteriology Centre, Dr. Ricardo Jorge National Institute of Health, Lisbon,    Portugal</i></p>      <p>&nbsp;</p>      ]]></body>
<body><![CDATA[<p>Recebido para publicação/<i>Received for publication:</i> 07.10.08</p>     <p>Aceite para publicação/<i>accepted for publication:</i> 07.12.17</p>       ]]></body><back>
<ref-list>
<ref id="B1">
<nlm-citation citation-type="">
<collab>Direcção Geral de Saúde</collab>
<source><![CDATA[Programa Nacional de Luta Contra a Tuberculose: Ponto da situação epidemiológica e de desempenho]]></source>
<year>2003</year>
</nlm-citation>
</ref>
</ref-list>
</back>
</article>
