A progress of tuberculosis and HIV/tuberculosis treatment assessed by fingerprinting of small molecule-biomarkers in patients from Eastern Europe
From 2013-04-01 to 2017-03-31
TB prognosis-IRSES is a programme launched in April 2013 and funded by Marie Curie Actions/FP7. It aims to exchange researchers between Spain, Sweden and Ukraine. Researchers from 4 partner organizations are exchanged to participate in investigations, workshops, clinical and diagnostics training in the field of tuberculosis (TB) diagnostics and metabolomics. 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.
A network has been created between Umea University, Sweden, Metchnikovs University/TB Clinics, Ukraine and University Hospital Germans Trias i Pujol, Spain that has access to a modern metabolomics facility and an extensive work experience with TB and chemical analysis of biomedical samples. We propose to collect samples from Ukrainian TB and HIV/TB patients under treatment and analyse them with several chromatographic methods in order to detect relevant biomarkers. We plan also to genotype M.tuberculosis isolates from these patients, monitor possible antibiotic resistance development and evaluate the host response. An array of these methods will help to get a detailed and dynamic clinical description of the cases and assign certain small molecules levels to respective events during treatment of TB, MDR-TB and HIV/TB co-infection.
This site describes our work and provides information about TB research, diagnostics and useful methods for investigation of metabolism.
One of the largest Swedish universities, the University of Umeå, is associated with Norrland’s University Hospital, the most important center for healthcare and medical research in the North of Sweden. Umeå University was listed among the 100 best in Europe in 2011 according to the Times Higher Education magazine. This university identifies biomedical science as one of its prioritized areas of research and has a broad network of internal, national, and international collaboration. Two groups with different backgrounds and belonging to different departments will represent Umeå University in this project.
Odessa National University is one of the leading Ukrainian universities with a longstanding history of biological and microbiological studies. The Department of Microbiology and Virology is well equipped and its research is focused on plant and human pathogens, marine ecology and biotechnology. Due to the teaching activity at the Dept. of Microbiology and Virology, about 20 Master of Science graduate yearly, with knowledge and skills that make them attractive employees for clinical and research labs. ONU has also a Biotech Center with the necessary facilities to support up-to-date biomedical research. ONU is officially nominated as FP7 NCP in FAFB (Agriculture and Fisheries, and Biotechnology) and has participated in such research and educational projects like inter alia FP6 and FP7 projects, TEMPUS, TASIS, INTAS and Erasmus Mundus. ONU has wide experience in international cooperation and signed bilateral agreements with more than 100 universities from Europe and other parts of the world.
This is a university hospital that covers a population of 200,000 inhabitants, and that acts as reference center for 800,000 inhabitants. The Microbiology Department is a reference center of the area. The research of the hospital is coordinated by the Institut Germans Trias I Pujol. The Centre is considered between the six first centres of Catalonia attending to their quality and quantity of research production. The Institute is the second of Spain in number of citations by article.
The Department of Microbiology has large experience in conventional techniques for the diagnosis of mycobacterial infections, receiving samples for mycobacterial studies from the hospital, from a specialized TB center from the Public Health Department, and from two penitentiary centers. It is also the reference center for tuberculosis of Catalonia (7 million inhabitants), receiving strains from other centers when necessary and specially for molecular typing. Blood samples are also received from the Unit for Prevention and Control of Tuberculosis of Barcelona and other centers for interferon gamma release assays (IGRA).
Over the last 10 years, the Research Team has succeeded in building a multidisciplinary group that has been working in research related to respiratory tract infections, and especially in tuberculosis. The group is involved in several research projects and is member of a Thematic Network of Cooperative Research call at the Carlos III Health Institute. Cristina Prat belongs to the educational commission of this network. The team of the Department of Microbiology is also affiliated to the Tuberculosis Network European Trials Group (TBNET) and Dr. Jose Domínguez is a member of the steering committee in charge of microbiology and drug resistance.
The group has contributed to the enhancement of the conventional tuberculosis diagnostic techniques and of genetic amplification techniques. In the last years the research lines have derived from the real need of new and alternative methods for the diagnosis of active and latent tuberculosis infection; the rapid detection of multi-drug resistant strains of M.tuberculosis and their molecular epidemiology control; and also the host-pathogen interaction. In general, research objectives can be grouped into the following areas:
- Rapid diagnosis of active tuberculosis and new molecular methods for drug susceptibility testing of M. tuberculosis
The group has participated in the development and evaluation of new methods for detection of resistance to first and second line drugs (PCR-hibridization as well as pyrosequencing). This research line is further explored in collaboration with other groups of the above mentioned CIBERES network. We have also collaborated in in vitro studies of newly developed drugs.
As a reference laboratory, the group has large experience in molecular typing of the strains by the conventional methods Restriction Fragment Length Polymorphism (RFLP) and spoligotyping for epidemiological studies. From a research point of view, we participate in projects of CIBERES together with other reference groups of Spain.
Partner 4 - TB Clinic, Odessa, Ukraine
The Regional Clinic for TB (RCTB) is one of the biggest centers dedicated to TB healthcare and diagnostics in the South of Ukraine. It has 5 departments including surgery and children department and the staff of 400 people with 26 of those employees working in a diagnostics lab. The clinical diagnostics lab (CDL) is a certified P3 facility armed with modern lab equipment thanks to funding from USAID and has a function of a reference lab for the region. CDL performs a significant amount of investigations of the samples from the patients of RCTB itself and TB clinics of the city and region with an average of 40 000 patients per year. Bacteriology Division of CDL is focused on medical microbiology and epidemiology. In 2011, 169 246 tests on pathological samples were carried out including general clinical, hematological and biochemical analysis. Among those, there were 16879 culture tests to detect M.tuberculosis and 2487 antibiotics resistance tests of M.tuberculosis.The number of studies has also increased due to the introduction to the automated Mycobacterial detection system Bactec MGIT 960 (BD).
CDL performs inter-laboratory quality control of AFB (acid fast bacilli) smear tests and quality control of diagnostics of TB based on clinical and biochemical tests. Training in TB diagnostics for new personnel is carried out with final “blind” examination. CDL conducts supervisory visit to the laboratory of the city and region.
CDL is also involved in scientific research. For example, in 2010, they carried out a survey of a group of HIV positive TB patients that allowed obtaining a detail picture of their clinical and behavioral profiles.