TB Prognosis IRSES: 319007
Update 2015
TB Prognosis IRSES is based on exchange of researchers between 4 partner
organizations from Spain, Sweden and Ukraine. Researchers are exchanged to
participate in investigations, workshops, clinical and diagnostics training in the field
of tuberculosis (TB) diagnostics and metabolomics.
TB is a severe chronic disease caused by Mycobacterium tuberculosis. Globally, TB
kills 1.5-2 million people yearly and is a leading cause of mortality from a single
infection. There is still no efficient vaccine against TB, while HIV co-infection is a
major risk factor for development of TB, increasing it by 27%. The European region of
World Health Organization reported an extremely high incidence of multidrugresistant (MDR) TB with total number of cases approaching 100 000. It is estimated
that in 2013 there were about 9 000 MDR-TB patients in Ukraine only.
Our goal is to improve diagnostics and treatment of TB through the development of
new biomarkers and better understanding host-pathogen interaction. Global and
targeted analysis of metabolites in patient/culture samples is our main method,
which is combined with microbiological and molecular methods of diagnostics.
The proposed work plan is as follows:
Samples are collected from Ukrainian TB and HIV/TB patients under treatment and
analyzed with several chromatographic methods in order to detect relevant
biomarkers.
M. tuberculosis isolates from patients are genotyped and possible antibiotic
resistance development should be monitored and the host response evaluated.
An array of these methods is helping to assign the levels of certain small molecules to
respective events during treatment of TB, MDR-TB and HIV/TB co-infection. The
identified small molecules – biomarkers can be further used to improve the existing
tools for diagnostics of TB as well as to device new sensitive tools for TB diagnostics
and treatment monitoring.
Research achievements
1. Samples from TB patients under antibiotic treatment are collected according
to the plan
2. A pilot study with patient’s samples (urine) has been done, which allowed
establishing the method for metabolite analysis by nuclear magnetic resonance
(NMR) on our instrumentation at Umeå University (Figure 1).
3. Clinical samples of M. tuberculosis DNA was collected in Ukraine and
analyzed at University Hospital Germans Trias, Spain, using molecular
genetic methods
4. M. tuberculosis grown in presence of antibiotics was analyzed with liquid
chromatography to detect possible metabolites of antibiotics effect on bacterial
metabolism (relevant for evaluation of treatment progress).
TB Prognosis IRSES: 319007
Update 2015
Additionally, the project has organized/participated in organization of 7 seminars, 2
workshops and 1 course in cross-disciplinary topics including, metabolomics for
diagnostics, multivariate analysis and molecular methods in TB diagnostics.
A very important achievement is the establishment/further development of scientific
collaboration with a large European network for tuberculosis diagnostics and
treatment - TB NET and Ohio State University (OSU), USA.
Sharp economic decline in Ukraine can influence vulnerable groups who live with
HIV and MDR-tuberculosis. High number of affected people was located in the area
of military action and it is not clear whether these people acquire proper medical help
and treatment at the moment. Together with TB-NET members we highlighted this
issue in a publication in a scientific journal (IJTLD V19 (4), 492-493, 2015) and also
our early stage researchers carried out a small study to investigate how well internally
displaced people from affected areas in Ukraine are supported by TB healthcare. Both
above mentioned activities definitely have a high socioeconomic impact.
Collaboration with OSU is in our main research area – diagnostics of tuberculosis
using metabolites as biomarkers. Colleagues from OSU have improved a test for
detection of one of the key metabolites of M. tuberculosis in urine. This is very
promising tool for detection and treatment evaluation of TB in HIV infected
individuals and is very relevant for Ukraine as this is the most HIV affected country
in Europe. The new test may be further improved by including biomarkers from our
study.
More information on our web site: http://irses-tuberculosis.info/index.php/en/
Fig.1 The potential of NMR diagnostics of TB