Improved Diagnosis, Drug Resistance Detection and Control of Tuberculosis in Latin America
Summary:
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.
Objectives:
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.
Description:
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.
Milestones:
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.
Coordinator:
Françoise Portaels
Instituut voor Tropische Geneeskunde
Mycobacteriology Unit
3000 Antwerp
Belgium
Tel: +32 3 247 6317
Fax: +32 3 247 6333
E-mail: portaels@itg.be
Partners:
- Instituto Venezolano De Investigaciones Cientificas - Centro De Microbiología Y Biología Celular, Caracas, Venezuela
- Laboratorio De Tuberculosis, Instituto De Biomedicina, Caracas, Venezuela
- Universidade Federal De Sao Paulo / Escola Paulista De Medicina - Departamento De Microbiologia, Immunologia E Parasitologia, Sao Paulo, Brazil
- Instituto Nacional De Enfermadedes Infecciosas. Anlis ‘Carlos G. Malbran’ - Servicio De Microbacterias, Buenos Aires, Argentina
- Cetranglo Hospital Tuberculosis Control Programme - Mycobacteria Regional Reference Laboratory Vicente Lopez, Argentina
- Instituto De Biotecnología, Instituto Nacional De Tecnología Agropecuaria ,Castelar, Argentina
- Servicio Nacional De Sanidad Y Colidad Agroalimentaria - Microbacterias Dilacot Martinez-Peia, Buenos Aires, Argentina
- Oswaldo Foundation - Department of Biochemistry and Molecular Biology, Rio de Janeiro, Brazil
- Instituto De Salud Pública De Chile - Department of Health / Section Microbacteria and Molecular Biology, Santiago, Chile
- Secretaria Da Agricultura E Abastecimento Do Estado De Sao Paulo - Instituto Biologico Sao Paulo, Sao Paolo, Brazil
- National Institute of Public Health and the Environment - Mycobacteria Department (PB22), Diagnostic Laboratory for Infectious Diseases and Perinatal Screening (LIS), NE-Bilthoven, The Netherlands
- Instituto Adolfo Lutz - Setor De Micobacterias Instituto Adolfo Lutz, Sao Paulo, Brazil
- Universidad Nacional Autonoma De Mexico, Instituto De Investigaciones Biomédicas, Immunology Department, Mexico City, Mexico
- Escuela Nacional De Ciencias Biológicas, Instituto Politécnico Nacional - Departamento De Microbiología, Mexico City, Mexico
- Instituto De Medicina Tropical ‘Pedro Kouri’ (IPK) - Bacteriology-Mycology, Ciudad De La Babana, Cuba
- Centro Nacional De Diagnóstico Y Referencia, Ministerio De Salud De Nicaragua - Departamento De Microbacterias, Managua, Nicaragua
- Universidade Do Rio Grande - Departamento De Patologia, Rio Grande, Brazil
- Tuberculosis Research Unit - Pulmonology Discipline, University Hospital - Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- Especialidades En Laboratorio Clínico - Laboratorio Clínico, Quito, Ecuador
- Instituto Nacional De Laboratorios De Salud - Laboratorio Nacional De Referencia De Tuberculosis, La Paz, Bolivia
- Universidad De Zaragoza - Departamento De Microbiologia, Medecina Preventiva Y Salud Publica, Zaragoza, Spain
- Erasmus University Rotterdam, Laboratory of Pediatrics, NE-Rotterdam,The Netherlands
- Institut Pasteur - Département de Physiopathologie, FR-Paris, France
- Universidad Autónoma De Madrid - Departamento De Medicina Preventiva Facultad De Medecina, ES-Madrid, Spain
- Corporacion Para Investigaciones Biológicas - Bacteriology Unit, Medellín, Colombia
- Instituto Nacional De Salud - Laboratorio De Microbacterias. Subdirección De Investigación Y Desarrollo, Santa Fe De Bogotá, Colombia
- Corporation Corpogen - Molecular Diagnostic, Bogotá, Columbia.
