SciELO - Scientific Electronic Library Online

 
vol.14 número4Qualidade do ar interior e sintomas respiratórios em escolas do PortoTosse em pediatria índice de autoresíndice de materiabúsqueda de artículos
Home Pagelista alfabética de revistas  

Servicios Personalizados

Revista

Articulo

Indicadores

Links relacionados

  • No hay articulos similaresSimilares en SciELO

Compartir


Revista Portuguesa de Pneumologia

versión impresa ISSN 0873-2159

Rev Port Pneumol v.14 n.4 Lisboa jul. 2008

 

Utilização estratégica da genotipagem do Mycobacterium tuberculosis no controlo da tuberculose

 

Strategical use of genotyping of Mycobacterium tuberculosis in tuberculosis control

 

Susana David 1

 

Resumo

A situação da tuberculose em Portugal justifica a aplicação de uma estratégia de genotipagem do Mycobacterium tuberculosis, tanto mais que Portugal encontra-se inserido no contexto global de mobilidade das populações humanas e das suas consequências sobre a pandemia.

Vários estudos internacionais posicionam as técnicas do spoligotyping e MIRU -VNTR typing como de primeira linha na epidemiologia molecular do M. Tuberculosis por estarem baseadas em tecnologias simples (PCR) e produzirem padrões, podendo ser traduzidos em código numérico de interpretação directa. Assim, tem sido proposta a aplicação do spoligotyping a todos os isolados clínicos, enquanto o MIRU -VNTR typing seria aplicado aos isolados com spoligotype comum. Outras técnicas, incluindo o IS6110 -RFLP, seriam reservadas a aplicações segundo critérios seleccionados.

Os trabalhos anteriores em Portugal utilizando o spoligotyping apontaram para a vantagem de uma estraté-secutiva e sem critério de pré-selecção. Esta permite a caracterização da estrutura populacional do M. Tuberculosis através do conhecimento da distribuição dos genotipos geograficamente, no tempo e dentro dos vários grupos de risco.

Por outro lado, a associação do spoligotyping com o MIRU -VNTR typing e, eventualmente, outras técnicas, deverá ser avaliada em vários contextos, como na identificação de situações de transmissão recente, na distinção entre episódios de reinfecção e recaída, na caracterização da amplitude e dinâmica de transmissão da doença.

A solução do problema da tuberculose em Portugal passa por uma estruturação na utilização da genotipagem em apoio à luta contra a tuberculose, a ser avaliada através de exemplos e resultados concretos.

Palavras-chave: Mycobacterium tuberculosis, Epidemiologia molecular, genotipagem.

 

Abstract

The tuberculosis situation in Portugal justifies the use of a strategy for the genotyping of Mycobacterium tuberculosis,particularly as Portugal is part of the global backdrop of human mobility, something which has a knock-on effect on the pandemic.

Several international studies have placed spoligotyping and MIRU- VNTR typing as first line techniques for the molecular epidemiology of Mycobacterium tuberculosis as these techniques rely on simple technologies (PCR) and produee patterns which are easily translated into a direct interpretation numerical code. Spoligotyping has been accordingly proposed for all the isolates, while MIRU-VNTR typing should be applied to isolates with a common spoliotype.

Other techniques, including IS6110-RFLP, should be reserved for use ill accordance with selected criteria.

Previous studies in Portugal using spoligotyping have underlined the advantages of a strategy based on sampling consecutive patient isolates with no prior selection criteria. This allows characterisation of the M. tuberculosis population structure through monitoring the distribution of the genotypes geographically over time and within the various risk groups.

On the other hand, the association of spoligotyping, MIRU-VNTF (typing and, possibly, other techniques, needs evaluating as part of bigger pictures, including identifying recent transmission situations, distinguishing between reinfection and relapse episodes and ma pping the size and dynamics of disease transmission.

The solution to the tuberculosis problem in Portugal implies structuring genotyping’s role in tuberculosis prevention and control and its evaluation through concrete examples and results.

Key-words: Mycobacterium tuberculosis, molecular epidemiology, genotyping.

 

Texto completo disponível apenas em PDF.

Full text only available in PDF format.

 

Bibliografia

1. Brudey K, Driscoll JR, Rigouts L, Prodinger WM, Gori A, Al -Hajoj SA, Allix C, Aristimuno L, Arora J, Baumanis V, Binder L, Cafrune P, Cataldi A, Cheong S, Diel R, Ellermeier C, Evans JT, Fauville-Dufaux M, Ferdinand S, Garcia de Viedma D, Garzelli C, Gazzola L, Gomes HM, Guttierez MC, Hawkey PM, van Helden PD, Kadival GV, Kreiswirth BN, Kremer K, Kubin M, Kulkarni SP, Liens B, Lillebaek T, Ho ML, Martin C, Martin C, Mokrousov I, Narvskaia O, Ngeow YF, Neumann L, Niemann S, Parwati I, Rahim Z, Rasolofo-Razanamparany V, Rasolonavalona T, Rossetti ML, Rusch -Gerdes S, Sajduda A, Samper S, Shemyakin IG, Singh UB, Somoskovi A, Skuce RA, van Soolingen D, Streicher EM, Suffys PN, Tortoli E, Tracevska T, Vincent V, Victor TC, Warren RM, Yap SF, Zaman K, Portaels F, Rastogi N, Sola C. Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology. BMC Microbiol 2006; 6: 23 -39.        [ Links ]

2. Cowan LS, Diem L, Monson T, Wand P, Temporado D, Oemig TV, Crawford JT Evaluation of a Two–Step Approach for Large-Scale, Prospective Genotyping of Mycobacterium tuberculosis Isolates in the United States. J Clin Microbiol 2005; 43: 688-95.

3. Filliol I, Driscoll JR, van Soolingen D, Kreiswirth BN, Kremer K, Valetudie G, Dang DA, Barlow R, Banerjee D, Bifani PJ, Brudey K, Cataldi A, Cooksey RC, Cousins DV, Dale JW, Dellagostin OA, Drobniewski F, Engelmann G, Ferdinand S, Gascoyne -Binzi D, Gordon M, Gutierrez MC, Haas WH, Heersma H, Kassa-Kelembho E, Ho ML, Makristathis A, Mammina C, Martin G, Mostrom P, Mokrousov I, Narbonne V, Narvskaya O, Nastasi A, Niobe-Eyangoh SN, Pape JW, Rasolofo-Razanamparany V, Ridell M, Rossetti ML, Stauffer F, Suffys PN, Takiff H, Texier-Maugein J, Vincent V, de Waard JH, Sola C, Rastogi N. Snapshot of moving and expanding clones of Mycobacterium tuberculosis and their global distribution assessed by spoligotyping in an international study. J Clin Microbiol 2003; 41: 1963-70.

4. Filliol I, Driscoll JR, Van Soolingen D, Kreiswirth BN, Kremer K, Valetudie G, Anh DD, Barlow R, Banerjee D, Bifani PJ, Brudey K, Cataldi A, Cooksey RC, Cousins DV, Dale JW, Dellagostin OA, Drobniewski F, Engelmann G, Ferdinand S, Gascoyne -Binzi D, Gordon M, Gutierrez MC, Haas WH, Heersma H, Kallenius G, Kassa -Kelembho E, Koivula T, Ly HM, Makristathis A, Mammina C, Martin G, Mostrom P, Mokrousov I, Narbonne V, Narvskaya O, Nastasi A, Niobe-Eyangoh SN, Pape JW, Rasolofo–Razanamparany V, Ridell M, Rossetti ML, Stauffer F, Suffys PN, Takiff H, Texier-Maugein J, Vincent V, De Waard JH, Sola C, Rastogi N. Global distribution of Mycobacterium tuberculosis spoligotypes. Emerg Infect Dis 2002; 8:1347 -9.

5. Filliol I, Ferdinand S, Negroni L, Sola C, Rastogi N. Molecular typing of Mycobacterium tuberculosis based on variable number of tandem DNA repeats used alone and in association with spoligotyping. J Clin Microbiol 2000; 38: 2520 -4.

6. Kamerbeek J, Schouls L, Kolk A, van Agterveld M, van Soolingen D, Kuijper S, Bunschoten A, Molhuizen H, Shaw R, Goyal M, van Embden J. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J Clin Microbiol 1997; 35: 907 -14.

7. Mazars E, Lesjean S, Banuls AL, Gilbert M, Vincent V, Gicquel B, Tibayrenc M, Locht C, Supply P. High-resolution minisatellite-based typing as a portable approach to global analysis of Mycobacterium tuberculosis molecular epidemiology. Proc Natl Acad Sci USA 2001; 98: 1901 -6.

8. Sola C, Filliol I, Gutierrez MC, Mokrousov I, Vincent V, Rastogi N. Spoligotype database of Mycobacterium tuberculosis: biogeographic distribution of shared types and epidemiologic and phylogenetic perspectives. Emerg Infect Dis 2001; 7: 390 -6.

9. Sola C, Filliol I, Legrand E, Lesjean S, Locht C, Supply P, Rastogi N. Genotyping of the Mycobacterium tuberculosis complex using MIRUs: association with VNTR and spoligotyping for molecular epidemiology and evolutionary genetics. Infect Genet Evol 2003; 3: 125 -33.

10. Sun YJ, Lee AS, Ng ST, Ravindran S, Kremer K, Bellamy R, Wong SY, van Soolingen D, Supply P, Paton NI. Characterization of ancestral Mycobacterium tuberculosis by multiple genetic markers and proposal of genotyping strategy. J Clin Microbiol 2004; 42: 5058 -64.

11. Supply P, Allix C, Lesjean S, Cardoso -Oelemann M, Rüsch -Gerdes S, Willery E, Savine E, de Haas P, van Deutekom H, Roring S, Bifani P, Kurepina N, Kreiswirth B, Sola C, Rastogi N, Vatin V, Gutierrez MC, Fauville M, Niemann S, Skuce R, Kremer K, Locht C, van Soolingen D. Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable–number tandem repeat typing of Mycobacterium tuberculosis. J  Clin Microbiol 2006; 44: 4498 -510.

12. Supply P, Lesjean S, Savine E, Kremer K, van Soolingen D, Locht C. Automated high -throughput genotyping for study of global epidemiology of Mycobacterium tuberculosis based on mycobacterial interspersed repetitive units. J Clin Microbiol 2001; 39: 3563 -71.

13. van Embden JD, Cave MD, Crawford JT, Dale JW, Eisenach KD, Gicquel B, Hermans P, Martin C, McAdam R, Shinnick TM, et al. Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology. J Clin Microbiol 1993; 31: 406 -9.

14. van Soolingen D, Hermans PW, de Haas PE, Soll DR, van Embden JD. Occurrence and stability of insertion sequences in Mycobacterium tuberculosis complex strains: evaluation of an insertion sequence–dependent DNA polymorphism as a tool in the epidemiology of tuberculosis. J Clin Microbiol 1991; 29: 2578 -86.

15. Wilson SM, Goss S, Drobniewski F. Evaluation of strategies for molecular fingerprinting for use in the routine work of a Mycobacterium reference unit. J Clin Microbiol 1998; 36: 3385 -8.

16. Sebban M, Mokrousov I, Rastogi N, Sola C. A data-mining approach to spacer oligonucleotide typing of Mycobacterium tuberculosis. Bioinformatics 2002; 18:235 -43.

17. David S, Raposo Ribeiro D, Antunes A, Portugal C, Sancho L, Germano de Sousa J. Contribution of spoligotyping to the characterization of the population structure of Mycobacterium tuberculosis isolates in Portugal. Infect Genet Evol 2007; 7: 609 -17.

18. David S , Barros V, Portugal C, Antunes A, Cardoso A, Calado A, Sancho L, Germano de Sousa J. Novos dados sobre o Spoligtyping de estirpes do complexo Mycobacterium tuberculosis isoladas no Hospital Fernando Fonseca (Amadora-Sintra, Portugal). Rev Port Pneumol XI 2006; 6: 513 -31.

19. David S, Portugal C, Antunes A, Calado A, Cardoso A, Barros V, Sancho L, Germano de Sousa J. Spoligtyping e polimorfismo do gene pncA um cenário em duas etapas para o diagnóstico de Mycobacterium bovis em Portugal. Rev Port Pneumol XI 2006; 6: 533 -56.

20. David S, Portugal C, Antunes A, Cardoso A, Calado A, Barros V, Sancho L. Identificação molecular pelo método de Spoligotyping de estirpes do complexo Mycobacterium tuberculosis isoladas no Hospital Fernando Fonseca. Rev Port Pneumol X 2004; 3:195 -204.

21. Bifani PJ, Mathema B, Kurepina NE, Kreiswirth BN. Global dissemination of the Mycobacterium tuberculosis W-Beijing family strains. Trends Microbiol 2002; 10: 45 -52.

22. Drobniewski F, Balabanova Y, Nikolayevsky V, Ruddy M, Kuznetzov S, Zakharova, S Melentyev A, Fedorin I. Drug-resistant tuberculosis, clinical virulence, and the dominance of the Beijing strain family in Russia. JAMA 2005; 293: 2726 -31.

23. Vitol I, Driscoll J, Kreiswirth B, Kurepina N, Bennett  KP. Identifying Mycobacterium tuberculosis complex strain families using spoligotypes. Infect Genet Evol 2006, 6: 491 -504.

24. Aranaz A, Liébana E, Mateos A, Dominguez L, Vidal D, Domingo M, Gonzolez O, Rodriguez -Ferri EF, Bunschoten AE, Van Embden JDA, Cousins D. Spacer oligonucleotide typing of Mycobacterium bovis strains from cattle and other animals: a tool for studying epidemiology of tuberculosis. J Clin Microbiol 1996, 34: 2734 -40.

25. Groenen PMA, Bunschoten AE; Van Soolingen D; Van Embden JDA. Nature of DNA polymorphism in the direct repeat cluster of Mycobacterium tuberculosis; Application for strain differentiation by a novel method. Mol Microbiol 1993; 10:1057 -65.

 

1 Investigadora Principal

Centro de Tuberculose e Micobactérias

Instituto Nacional de Saúde Dr. Ricardo Jorge

Rua do Campo Alegre 823, 4150-180 Porto

Email: sdavid@ibmc.up.pt

 

Recebido para publicação/received for publication: 08.01.30

Aceite para publicação/accepted for publication: 08.03.26