TUBERCULOSIS COURSE. Academic Year
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1 TUBERCULOSIS COURSE Academic Year
2 PROGRAMME OF THE TUBERCULOSIS COURSE May 23 to June 3, 2016! The Course on Tuberculosis will be at The Institut Pasteur Pavillon Louis Martin (Building 09) 28, rue du Docteur Roux PARIS Cedex 15 Theoretical training and Practical training : Ground floor - Pavillon Louis Martin (Building 09)
3 GENERAL PRESENTATION One third of the world s population is infected with Tuberculosis (TB) and at risk to develop the disease. The WHO estimates that there are nine million new TB cases and 1.5 million deaths from TB. Multi-drug resistant (MDR) strains are a growing problem, with new cases every year, 10% of these being extremely drug resistant (XDR). Many laboratories and international consortia are searching for effective new anti-tb drugs and new vaccines, and clinical trials are testing new therapeutic regimens that might shorten the standardized treatments. However, despite considerable efforts for the discovery of new drugs, only ten new antibiotic candidates or repurposed drugs have advanced to preclinical trials. Perhaps the greatest progress has been in the introduction of rapid diagnostic tools based on molecular biology. The incorporation of new technologies has revolutionized the detection of microbial pathogens and resistance to antibiotics. The growing availability of high capacity sequencing has opened new doors for understanding host-pathogen interactions and immunological responses by identifying important determinants in both the bacterial and human genomes. The availability of new tuberculosis diagnostic tests, with frequent technical improvements, requires thorough evaluation in the different settings in which they will be employed. The training course will review all techniques currently used for the rapid diagnosis of tuberculosis and detection of antibiotic resistance, together with a description of their genetic and metabolic bases. This should facilitate the work of laboratories responsible for the diagnosis and treatment of tuberculosis, and also aid laboratories undertaking trials to test new antibiotics and new vaccines. Genomic markers are used to study tuberculosis transmission and also the phylogeny and evolution of M. tuberculosis complex bacteria. The first techniques were based on the detection of polymorphisms in repetitive DNA sequences, but newer tools are based on single nucleotide polymorphisms that are not subject to homoplasia. These tools are useful for molecular epidemiology, but need to be practiced and evaluated to determine how they can be applied in local and regional mycobacterial laboratories. The course will include lectures by international experts to provide up-to-date information on all of these new developments in the study and control of Tuberculosis. Lectures will cover general aspects on Tuberculosis, host pathogen interactions and the immune response, diagnosis and drug susceptibility testing, treatment of MDR TB, new drugs, molecular epidemiology and the phylogeny and evolution of M. tuberculosis complex bacteria. In the practical sessions, the participants will work with the latest diagnostic tests commercially available, together with PCR-based genotyping techniques. They will also identify drug resistance using new methods not yet commercialized. These include direct sequencing of antibiotic resistance determinants and an introduction to genomic analysis for complete drug sensitivity determination. The information presented will be posted on the WEB site The tuberculosis course at the Institut Pasteur in Paris promotes laboratory up-grading, intercontinental exchanges and the discussion of future projects amongst the participants. It is an exceptional opportunity for the participants to acquire new knowledge and to exchange experience and criticism. The course will stress the importance of implementing the right tools in the right settings for optimal efficacy.
4 Programme - WEEK 1 - Monday May :00-10:00 Welcome and introduction to the course Pre-test for practical session Brigitte GICQUEL Catherine PIERRE-AUDIGIER Howard TAKIFF 10:30-11:00 Lecture: The fight against Tuberculosis - general aspects Brigitte GICQUEL 11:15-12:15 Lecture: Clinical aspects in Tuberculosis Steffen STENGER (Ulm University - Ulm - Germany) 14:00-15:00 Laboratory presentation and use of available material 15:00-15:30 Lecture: Mechanisms of resistance to RIF and Fluoroquinolones Howard TAKIFF (Institut Pasteur -Paris) 15:30-16:00 Practical workshop: Kudoh innoculation Howard TAKIFF (Institut Pasteur -Paris) 16:00-18:00 Practical workshop: Antibiotic Resistance sequencing Principal of test Preparaton of mix and amplification Howard TAKIFF Tuesday May :00 10:00 Lecture: Immunology of TB Steffen STENGER (Ulm University - Ulm - Germany) 10:15 11:15 Lecture: Pediatric TB Christophe DELACOURT (Necker Enfants Malades Hospital - Paris France) 11:30 12:30 Lecture: Genetic Susceptibility to TB Laurent ABEL (Necker Enfants Malades Hospital - Paris France) 13:30 14:15 Lecture: Phenotypic and molelcular tests for diagnosis Catherine PIERRE-AUDIGIER (Institut Pasteur Paris) 14:30 16:00 Practical workshop: Z-N staining and microscopy 16:00 18:00 Practical workshop: continue rpob and gyra Analysis results PCR, Purify PCR product for sequencing Howard TAKIFF (Institut Pasteur Paris) 3
5 Wednesday May :00 10:00 Lecture: TB HIV/Diabetes Veronique JOLY (Hopital Bichat Claude Bernard - Paris) 10:15 11:15 Lecture: Evaluation of new diagnostic techques Muriel VRAY 11:30-13:00 Lecture: TB mol Epi and Spoligotyping Dick VAN SOOLINGEN (National Institute for Public Health and the Environment - Netherlands) 14:00-16:00 Practical workshop: Spoligotyping Principle of test Preparation of Mix and amplification Dick VAN SOOLINGEN (National Institute for Public Health and the Environment - Netherlands) 16:00-18:00 Practical workshop: MIRU Principle of test Preparation of Mix and amplification Philip SUPPLY (Institut Pasteur - Lille -France) Thursday May :00 10:00 MIRU Philip SUPPLY (Institut Pasteur - Lille - France) 10:15 11:15 Lecture: Population structures and evolution of M. Tuberculosis Sébastien GAGNEUX (Swiss Tropical and Public Health Institute, Basel - Switzerland) 12:00 13:00 TBA Roland BROSCH 14:00 16:00 Practical workshop: Spoligotyping Electrophoresis, Hybridization Dick VAN SOOLINGEN (National Institute for Public Health and the Environment - Netherlands) 16:00-18:00 Practical workshop: MIRU, electrophoresis Philip SUPPLY (Institut Pasteur - Lille - France) 4
6 Friday May :00 10:30 Lecture: NTM Detection and speciation; when to treat Jean-Louis HERRMANN (Hôpital Raymond Poincaré- Garches-France) 11:00-12:30 Lecture: WGS and SNPs and Transmission Sébastien GAGNEUX (Swiss Tropical and Public Health Institute, Basel - Switzerland) 13:30 15:00 Practical workshop: Spoligotyping: Results and Discussion Dick VAN SOOLINGEN (National Institute for Public Health and the Environment - Netherlands) 15:00-16:30 Practical workshop: MIRU Results and Discussion Philip SUPPLY (Institut Pasteur - Lille -France) 16:30-18:00 Comparison of results: Mol Epi. 5
7 s Programme - WEEK 2 - Monday May :30 Lecture: Treatment of Tuberculosis Including MDR and XDR cases Nicolas VEZIRIS (Hôpital Pitié Salpétrière, Paris- France) 10:45-11:15 Lecture: The short term treatment for MDR tuberculosis Arnaud TREBUCQ (The Union - Paris - France) 11:30-13:30 Practical workshop: Line Probe assay test (Hain) Genotype MTBDRplus/sl Preparation of Mix and amplification Catherine PIERRE-AUDIGIER (Institut Pasteur Paris) 14:30-16:30 Practical workshop: GeneXpert Principal of test Test, Installation and maintenance Indira SOUNDIRAM (Cepheid Europe - Maurens Scopont - France) 16:30-18:30 Practical workshop: Genotype MDBDRplus/sl Electrophoresis-hybridization Catherine PIERRE-AUDIGIER Tuesday May :00-10:00 Lecture: New methods for detecting drug resistance David ALLAND (New Jersey Medical School - U.S.A.) 10:00-12:00 Lecture: Drug action and Resistance Mechanisms Ying ZHANG (Johns Hopkins Center for Tuberculosis Research - Baltimore - U.S.A.) 12:00-13:00 Public Lecture: The chemistry, biology and genomics required to design the next generation of drug resistance tests for Mycobacterium tuberculosis David ALLAND (New Jersey Medical School - U.S.A.) 14:30-15:30 Practical workshop: Interpretation of Genotype MTBDRplus/sl Catherine PIERRE-AUDIGIER 16:00-18:00 Practical workshop: Interpretation and Discussion of GeneXpert Indira SOUNDIRAM (Cepheid Europe - Maurens Scopont - France) David ALLAND (New Jersey Medical School - U.S.A.) 6
8 Wednesday June :00-9:45 Lecture: New Drugs, New Regimens, Drug trials Susan DORMAN (Johns Hopkins Center for Tuberculosis Research - Baltimore - U.S.A.) 10:00-12:00 Lecture: Survey and monitoring of Antibiotic Resistance and impact on diagnosis and treatment Sara EYANGOH (Centre Pasteur - Yaoundé - Cameroun) 12:15-13:30 Lecture: Clinical usefulness of WGS Tanne CLARK (London School of Hygiene & Tropial Medicine - London - United Kingdom) 13:00-17:00 Practical workshop: Basic Bioinformatics -- Analysis of sequencing results Magnus FONTES and team (Institut Pasteur -Paris) 17:00-18:00 Practical workshop: WGS scanning, databases Tanne CLARK (London School of Hygiene & Tropial Medicine - London - United Kingdom) Thursday June :00-11:00 EXAM 11: Pasteur Museum visit 14:00-18:00 Practical workshop: Bioinformatics exercises Databases, WGS Magnus FONTES and team Friday June :00 Lecture: General Epidemiology of Tuberculosis Philip GLAZIOU (World Health Organisation - Geneva - Switzerland) 10:15-11:00 Lecture: BCG and new vaccines Brigitte GICQUEL 11:15-12:30 Correction of Tests 13:30-15:30 Correction of Tests Group Discussion, Course Evaluation 15:30-18:00 Presentation of Diplomas and course closure 7
9 ORGANIZATION OF EXAMINATIONS Attendees will be evaluated based on the following aspects: Participation in the theoretical course: active participation, relevance of questions asked; On a scale of 5 possible points. Participation in the practical workshop: preparation of the work, ability to work in a group, time management, respect for security rules, completion of protocols. On a scale of 10 possible points. Final written exam. On a scale of 20 possible points. 3
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