CCITB - EUCO-Net

Colombian Center for
Tuberculosis Research
-CCITB“Tuberculosis: Research integrated
to public health to improve disease
control”
A Colombian Excellence Research
Center
“A national network of high level research groups
joined around a common area considered to be
strategic for the country”
COLCIENCIAS (Colombian Institute for development of science and
Technology) 2004
Strategic Area
Infectious diseases prevalent in the tropics
Main Objectives: Colombian Center
for Tuberculosis Research –CCITB„
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To contribute to disease knowledge and its control
in the country, with basic and applied research
and make transference of these results to the
national program of tuberculosis control.
To develop a model of research groups network
working around a common area of interest for the
country
To develop and improve the national capacity in
research dedicated to infectious diseases
prevalent in the country
CCITB: Consortium of 6 private and public
institutions with 7 research groups, located in 4
main cities in Colombia
CIB, U de A)
INS, CORPOGEN
CIDEIM
UNICAUCA
- Grupo de Investigacion en
inmunología y enfermedades infecciosas
(UNICAUCA, public university )
– Unidad de Bacteriología y
Micobacterias (CIB, private non for profit
research institute)
– Grupo de Biotecnología Molecular
(CORPOGEN, private non for profit
research institute)
– Grupo Epidemiología-GEPI- (UdeA,
public university )
– Grupo de inmunología celular e
inmuno-genética –GICIG- (UdeA, public
university)
– Grupo de Micobacterias (INS, National
Institute of Health, public)
– Tuberculosis research group (CIDEIM,
private non for profit institute)
Relationships Between CCITB Activities and
National Policies in Tuberculosis Control
WP2
TB transmission
dynamics in index cases
and contacts in 3
different cohorts of
patients and their
contacts
WP5
Developing and
evaluating new
diagnostics tests for
TB
WP1
WP4
Developing a national
capacity for evaluating
new drugs, treatments
and vaccines for TB
Development of relational
databases and collection
of biological materials
and TB isolates
WP3
Basic studies in
virulence of TB bacillus
and host inmune
response (genomics and
proteomics)
National Policies for Tuberculosis Control
National Program for Tuberculosis
Control
Work package 1: Developing data bases
and collections of biological material
from patients with tuberculosis
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Data bases of patients and contacts
and data bases for the collections (500
patients and 2600 contacts from
cohorts in Colombia)
Collections of biological material
– DNA and sera from patients and
contacts
– M. tuberculosis isolates and DNA
Work package 2
Factors Associated to Tuberculosis Transmission in
Three Colombian Cohorts
500 index cases/2600 households contacts/3 year followup
1. Risk of infection in
contacts (PPD, CFP10,
ESAT6)
2. Molecular epidemiology
(RFLP-IS6110, Spoligotyping,
MIRU)
3. Risk of disease in contacts
4. Factors associated to
infection and disease (HIV,
drug resistance, bacillary
load and genotyping)
Results for RFLP-IS6110 in Patiens
from Medellin´s cohort
Dic e ( Op t:1 .00 %) ( T ol 1 .0%- 1.0 %) ( H> 0.0 % S> 0.0 %) [0 .0 %-10 0. 0%]
IS6110 RFLP
1 00
95
90
85
80
75
70
65
60
55
50
45
40
35
30
IS6110 RFLP
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357 isolates
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217 isolates belonging to
45 (60%) clusters
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clusters with 2 to 32
isolates
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11 (3%) isolates with
less than 5 copies of
IS6110
Non Beijing pattern
More Common
Spoligotypes in Medellin´s cohort
Dice (Opt:1.00%) (Tol 1.0%-1.0%) (H>0.0% S>0.0%) [0.0%-100.0%]
spoligoFP43
0
9
spoligoFP43
5
9
0
0
1
IS6110 RFLP
.UT125
.UT133
.UT135
.UT144
SIT
Family
50
H-3
42
LAM-09
727
H-1
62
H-1 var.1
.UT156
.UT220
.UT226
.UT230
.UT251
.UT259
.UT312
.UT108
.UT174
.UT213
.UT245
.UT164
.UT171
.UT194
.UT201
.UT214
.UT228
Latino american and Mediterranean (LAM): 34%
Haarlem (H): 40%
LAM+H= 74%
More Common Families Defined by Spoligotyping in
3 Colombian Cohorts of Patients with Tuberculosis
Familia SIT
Medellín
N (%)
Cali
N (%)
Popayán
N (%)
Base
Datos
Nacional
Haarlem
147 (40.6)
30 (37.0)
1 (3.2)
68 (33)
LAM
122 (34)
32 (39.4)
10 (32.2)
113 (55)
T
14
(3.9)
7
(8.6)
10 (32.2)
17 (8.3)
X
5
(1.4)
1
(1.2)
1 (3.2)
2 (1.0)
U (unknown)
3
(0.8)
4 (4.9)
4 (12.9)
4 (2.0)
Beijing
0
(0)
0
(0)
1 (3.2)
4 (2.0)
NO
70
(19)
7
(8.6)
4 (12.9)
TOTAL
361 (100)
81 (100)
31 (100)
204(100)
Work package 3
Basic studies on microorganism genetics and
host inmune response
Virulence factors
Genetic
characteristics
associated to
transmission
Pathogenesis
Host immune response
and susceptibility
UT3
Basic studies in the
microorganisms and
Immune response
Role of Toll receptors in tuberculosis infection
¾ Analysis of drug efects in macrophage
fagolysosomal function
¾ Cell response of: T CD4, TCD8 y NK to ESAT-6,
CFP-10 y PPD in patients with tuberculosis and
households contacts
¾ Genetics and metabolism of alanine racemase
¾ Identification of regulators for gen fbpABC
¾ Analysis of M. tuberculosis IS6110 adjacent regions
¾ Comparative genomics and proteomics in
M. tuberculosis isolates
¾
Workpackage 4
Evaluation of New Drugs, Treatment
and Prevention Strategies
Design and implementation of a
strategy to strengthen the country
capacity to perform clinical studies in
tuberculosis treatment and
prevention
Participation in the C study: evaluation of efficacy,
acceptability and toxicity of combined administration
of antituberculous drugs
Workpackage 5
Developing and evaluation of
new diagnostic methods
• Developing a country capacity to evaluate
new diagnostic methods
• Foresigth and technology surveillance studies in
new diagnostics methods and generation of health
policies in tuberculosis
• Develop and evaluate new diagnostic
methods
• DIAPOPS
• Thin layer agar for MDR screening
• MGIT for first and second line drugs
Technique for Tuberculosis Diagnosis
Phase II Evaluation
1
2
3
4
5
6
7
8
9
10
11 12
ADN
1
50 ng Mtb
2
25 ng Mtb
3
1 ng Mtb
4
50ng Mtb + human ADN
5
25ng Mtb + human ADN
6
1 ng Mtb + human ADN
7
25ng M. bovis
8
25 ng M. bovis + human ADN
9
25ng M. gordonae + human ADN
10
25 ng M. chelonae + human ADN
11
Human ADN
12
V. Cholerae 25 ng
Grupo Corpogen
Established International
Collaborations
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Colorado State University
McGill University
Institute of Tropical Medicine (Antwerp, Belgium)
REDETB (Brasil)
PHRI, New Jersey
The Galton Laboratory, Department of Biology,
University College London (United Kingdom)
University of San Luis
Broad Institute
Publications 2005-2008
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Robledo JA et al. Int J of Tuberc Lung Dis 2006;10:613-619.
Arias MA et al. Immunology 2006;118:171-184.
Zea AH et al. J Infect Dis 2006;194(10):1385-93.
Henao MI et al. Tuberculosis 2006;86(1):11-9.
Puerto G et al. Infectio 11:87-94, 2007
Henao J et al. Tuberculosis 2007; 87:509–517
Olano J et al. Tuberculosis 2007. 87:502-508.
Rodriguez JG. 2008. Tuberculosis “in press” doi: 10.1016/J.
Tube.2007.11.011
Martin A. J Antimicrob Chemother 2008;61:123-127
Cubillos-Ruiz A et al. Submitted to: BMC Genomics
Ritacco V. Mem Inst Oswaldo Cruz. 2008;103(5):
Robledo J et al . Int J Tuberc Lung Dis 2008;12(12):
Main Achievements 2005-2008
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Cohorts are implemented and follow up is in
progress. This has allowed transference of
knowledge and data to local, regional and national
health authorities
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Diagnostic and drug susceptibility tests are in
several stages of evaluation
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MSc and PhD students are working in project
activities
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Publications and divulgation of findings have been
done in national and international meetings
Collaborations with international partners are
established
Additional Publications in
Tuberculosis Colombia 2007-2008
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Mateus Solarte et al. Int J Tuberc Lung Dis
2008:520-526
Restrepo B et al. Trop Med Int Health 2008:653658
Hernandez J et al. Rev Salud Publica 2008126-136
Caceres-Manrique et al. Rev Salud Publica
2008:94-104
Arbelaez P et al. Biomedica 2007:515-525
Caceres F et al. Biomedica 2007:498-504
Kantor et al.Tuberculosis 2008:358-365
Rodriguez J et al. Tuberculosis 2008:273-282
Murcia MI et al. Rev Salud Publica 2007:97-105