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Upgrade Diagno MDR-TB
Framework programme: 5
Project number:
EC contribution: € 1 600 000
Duration: 36 months
Type: CA
Starting date: 1 January 2002
Graphic element Improved Diagnosis, Drug Resistance Detection and Control of Tuberculosis in Latin America


A strategic obstacle to the improvement of tuberculosis (TB) control is the lack of inexpensive and simple techniques that can replace the slow and laborious conventional methods for diagnosing TB and detecting drug resistance. However, there are newer, more appropriate methodologies that warrant further evaluation. This concerted action (CA) will develop, adapt and evaluate some of these promising new tools. It will build upon collaborations that have developed between a network of European researchers and their Latin America colleagues. Preliminary studies by this group have begun to address some of the objectives in this CA, and the work outlined will expand these collaborations to develop useful and appropriate methodologies. This project will test them in multicentre pilot studies, modify them where necessary and run prospective clinical trials in high endemic TB areas for accuracy, cost, ease of implementation and impact on TB control.


The objectives are:

1) to develop, standardise and evaluate new methods for tuberculosis diagnosis, including improvements in microscopy, rapid culture techniques, serological markers, rapid speciation, and diagnosis of animal mycobacteroses of human importance
2) to develop, standardise and evaluate new methods for the detection of rifampicin resistance as a surrogate marker for MDR-TB
3) to design simple, rapid and inexpensive methods for drug susceptibility testing of M. tuberculosis. Sensitivity, specificity and predictive values will be determined by comparison with the conventional proportion method
4) to extend initial molecular and traditional epidemiological studies on Latin American MDR-TB strains in order to delineate transmission patterns.


The project contains two main areas: diagnosis and detection of drug resistance. The diagnostic component is multidisciplinary, involving new and improved methods for detection, cultivation, and identification of M. tuberculosis. In preliminary studies done by the partners, encouraging results were obtained with several techniques, which will be further evaluated and validated against conventional methodologies. These are a simple and inexpensive method of cultivation employing a thin layer of agar, a simple and direct method of cultivation appropriate for field conditions, and a rapid molecular method of species identification. It will also investigate additional diagnostic strategies: an improved microscopical detection, various M. tuberculosis antigens for their diagnostic value in a serological test, and, since M. bovis TB can be transmitted to humans and has a distinct drug susceptibility, the diagnosing of bovine TB. The second component will develop and evaluate methods for the rapid detection of drug resistant TB, using resistance to rifampicin (RIF) as a marker for MDR-TB. These will include Rifoligotyping evaluation and adaptation for direct use with clinical samples, RIF added into the thin-layer agar format as a direct test for resistance, the luciferase phage test adapted as a rapid direct test for RIF resistance, and exploring colorimetric methods for use on solid media containing RIF. This component will also evaluate faster, easier and more accurate methods for drug susceptibility testing, including second-line and newer anti-tuberculosis drugs. Rapid colorimetric methods will be used for detecting bacterial growth in an ELISA format conventional culture techniques adapted to a multi-well plate. A database of MDR genotypes for Latin America will be created, and will include traditional epidemiologic information so that transmission patterns can be delineated.


1. Development of various techniques into inexpensive, simple, accurate and reproducible formats.
2. Testing in multi-centre pilot studies and modifying where necessary.
3. Most promising tools evaluated in prospective clinical trials in TB endemic areas.
4. The concerted action will recommend methods for improved TB diagnosis, drug resistance detection and drug susceptibility testing.
5. Delineation of transmission patterns of MDR-TB in Latin America.


Françoise Portaels
Instituut voor Tropische Geneeskunde
Mycobacteriology Unit
3000 Antwerp
Tel: +32 3 247 6317
Fax: +32 3 247 6333


  1. Instituto Venezolano De Investigaciones Cientificas - Centro De Microbiología Y Biología Celular, Caracas, Venezuela
  2. Laboratorio De Tuberculosis, Instituto De Biomedicina, Caracas, Venezuela
  3. Universidade Federal De Sao Paulo / Escola Paulista De Medicina - Departamento De Microbiologia, Immunologia E Parasitologia, Sao Paulo, Brazil
  4. Instituto Nacional De Enfermadedes Infecciosas. Anlis ‘Carlos G. Malbran’ - Servicio De Microbacterias, Buenos Aires, Argentina
  5. Cetranglo Hospital Tuberculosis Control Programme - Mycobacteria Regional Reference Laboratory Vicente Lopez, Argentina
  6. Instituto De Biotecnología, Instituto Nacional De Tecnología Agropecuaria ,Castelar, Argentina
  7. Servicio Nacional De Sanidad Y Colidad Agroalimentaria - Microbacterias Dilacot Martinez-Peia, Buenos Aires, Argentina
  8. Oswaldo Foundation - Department of Biochemistry and Molecular Biology, Rio de Janeiro, Brazil
  9. Instituto De Salud Pública De Chile - Department of Health / Section Microbacteria and Molecular Biology, Santiago, Chile
  10. Secretaria Da Agricultura E Abastecimento Do Estado De Sao Paulo - Instituto Biologico Sao Paulo, Sao Paolo, Brazil
  11. National Institute of Public Health and the Environment - Mycobacteria Department (PB22), Diagnostic Laboratory for Infectious Diseases and Perinatal Screening (LIS), NE-Bilthoven, The Netherlands
  12. Instituto Adolfo Lutz - Setor De Micobacterias Instituto Adolfo Lutz, Sao Paulo, Brazil
  13. Universidad Nacional Autonoma De Mexico, Instituto De Investigaciones Biomédicas, Immunology Department, Mexico City, Mexico
  14. Escuela Nacional De Ciencias Biológicas, Instituto Politécnico Nacional - Departamento De Microbiología, Mexico City, Mexico
  15. Instituto De Medicina Tropical ‘Pedro Kouri’ (IPK) - Bacteriology-Mycology, Ciudad De La Babana, Cuba
  16. Centro Nacional De Diagnóstico Y Referencia, Ministerio De Salud De Nicaragua - Departamento De Microbacterias, Managua, Nicaragua
  17. Universidade Do Rio Grande - Departamento De Patologia, Rio Grande, Brazil
  18. Tuberculosis Research Unit - Pulmonology Discipline, University Hospital - Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
  19. Especialidades En Laboratorio Clínico - Laboratorio Clínico, Quito, Ecuador
  20. Instituto Nacional De Laboratorios De Salud - Laboratorio Nacional De Referencia De Tuberculosis, La Paz, Bolivia
  21. Universidad De Zaragoza - Departamento De Microbiologia, Medecina Preventiva Y Salud Publica, Zaragoza, Spain
  22. Erasmus University Rotterdam, Laboratory of Pediatrics, NE-Rotterdam,The Netherlands
  23. Institut Pasteur - Département de Physiopathologie, FR-Paris, France
  24. Universidad Autónoma De Madrid - Departamento De Medicina Preventiva Facultad De Medecina, ES-Madrid, Spain
  25. Corporacion Para Investigaciones Biológicas - Bacteriology Unit, Medellín, Colombia
  26. Instituto Nacional De Salud - Laboratorio De Microbacterias. Subdirección De Investigación Y Desarrollo, Santa Fe De Bogotá, Colombia
  27. Corporation Corpogen - Molecular Diagnostic, Bogotá, Columbia.

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