Tuberculosis is a major problem for Moldova Public Health
Tuberculosis (TB) is a major public health threat in Moldova. The recent escalation of the occurrence of the disease has been complicated due to the appearance and development of multi drug resistant tuberculosis (MDR TB) or extensively drug resistant tuberculosis (XDR TB). The ability for the Moldovan and worldwide community of TB researchers to understand the nature of the TB disease will be greatly improved by using a common database containing patients’ medical images, treatment information, lab work, and clinical data. This common database can facilitate adherence to the treatment protocol as well as serve as a consistent repository of records of the treatment regime for particular histories of disease.
The Phthisiopneumology Institute “Chiril Draganiuc” (PPI) apply on CRDM for the research project and in March 2015 the project starts to be implement in the Moldova site. Successful implementation of the proposal is secured by the fact that it will be executed by a leading Moldova research institutions working in the tuberculosis and ICT domains in close collaboration with NIAID OCICB. The PPI is a strategically medical unit for the Republic of Moldova and coordinate the achievement of the National TB Control Programme. The Institute grants yearly specialized medical assistance to about 30000 patients with tuberculosis and nonspecifically affections of the breathing apparatus.
The goal of the project is to develop the Moldova TB Portal to facilitate research aimed at diagnosis and treatment of drug-resistant tuberculosis. The clinical images of lungs (CT and X-ray) will be used for development of computational methods of TB diagnosis. Clinical data will be collected and stored in Portal’s database for computer-aided analysis of factors contributing to the development of the disease. Connection of Portal’s metadata with the original clinical samples collection (clinical lab samples taken from TB patients) would allow researchers to establish various cohorts for subsequent partial or full-genome sequencing of Moldovan TB strains. Analysis of genomes of Moldovan TB strains would allow for improved analysis of epidemiological situation in Moldova, and forming informed opinion about required drug regiments and efficiency of diagnosis with common microbiological tools.
To leverage the design and deployment of Moldova TB Portal, we plan on using the common core developed for the Belarus TB Portal. The Moldova TB Portal will store anonymized medical images, lab work, treatment information and clinical data from the Moldovan TB patients and use user interface developed for Moldova Portal. The Moldova TB Portal will utilize the software and populate it with the anonymized data from the participating Moldovan TB patients including medical images, lab work, treatment information and clinical data. Information submitted into the Portal will be appropriately de-identified and authorized for upload by the Moldova researchers ensuring compliance with the appropriate Moldova laws and regulations.
One of the projects emphases is on the full genome sequencing of bacterial DNA collected from patients in Moldova.
Criteria for inclusion clinical cases in the database of the portal:
Male and female New or Relapse TB patients of any ethnicity and race, both HIV negative and positive, are eligible for the study if they:
- have signed informed consent to specimen collection,
- are 18 years of age or older; and
- are known to be sputum smear-positive, based on prior examination of sputum; and
- have positive culture on liquid or solid media and
- have DST result by phenotypic or genotypic tests and
- are sensitive strain to all first line TB drugs, or
- are confirmed resistance to INH&RIF, or
- are confirmed resistance to INH&RIF and quinolone and one injectable drugs
The participant that meat inclusion criteria will be recruited to participate into the study and will be followed for the informed consent process. After submission of the informed consent, participants will be asked to provide at least 2 sputum specimens of min 3 ml in volume. The sputum will be tested on microscopy, GeneXpert MTB/RIF, MGIT, LJ culture.
Participants with positive MGIT, LJ culture will be retained into the study.
a) Patients are not eligible for the study if the quantity of respiratory secretions is not sufficient;
b) Subjects with only extra-pulmonary disease;
c) Subjects under 18 years of age;
d) Inability to provide informed consent (e.g. prisoners, mentally impaired subjects).
Title: Moldova TB Portal
CRDF program: Grant Assistance Program/Focus
CRDF Project No.: OISE-15-61136-1
Starting Date: March 1, 2015
Duration: 12 month
The goal of the project is to establish the new public health resource for TB in Moldova and to create open access information resources on tuberculosis (TB) in Moldova.
Establish a sustainable ongoing clinical database for the Moldova TB public health program based on both new data acquired from incoming patients (medical images and other clinical data) as well as extracting data from existing medical records and histories of interest.
Establish a comprehensive large scale clinical portal for TB researchers worldwide by making the de-identified data available via Internet.
Extract the initial set of M. tb strains isolated from TB patients residing in various regions of Moldova. The strain selection strategies shall be determined after full review of optimal methods. Selected strains shall be sequenced and analyzed using the corresponding genomes for unique markers and SNPs associated with known drug resistance.
Comparative sequence analysis of genes and genomic markers from these genomes will contribute to understanding of local strains of Mycobacterium tuberculosis and hopefully suggest possible novel diagnostics, therapies and drug combinations.
The specific purpose of this the first year project was to sequencing about 150 genomes of M&XDR-TB strains from samples collected in Moldova in order to:
- Reveal phylogenetic/phylogeographic peculiarities of Mtb strains in Moldova;
- To establish the profiles of M.tuberculosis isolates genotypes and the importance of these in transmission of infection; to reveal the local characteristics of causative agent circulation throughout the country.
- Further investigate differences between genomes of TB strains with varied resistance to drugs and varied clinical manifestation of disease;
- Perform comparative analysis of MDR- and XDR-TB M.tuberculosis strains from Moldova with reference strains H37Rv, tuberculosis CDC1551 and strains from other countries;
- Add to the existing body of information and knowledge to promote research resulting in creating new generation of TB drugs, vaccines, and diagnostics.
Expected resultsThe first year of the project will mostly be dedicated to the accumulation of the first data set, and DNA strains, and DNA sequences, selection, verification and preprocessing of study groups and research materials as well as demonstration of a prototype of the open-access database.
The full text of the proposal.
Successful implementation of the proposal is secured by the fact that it will be executed by a leading Moldova research institutions working in the tuberculosis and ICT domains in close collaboration with NIAID OCICB
National Institute of Allergy and Infectious Diseases (NIAID)
Office of Cyber Infrastructure & Computational Biology
5601 Fishers Lane
Rockville, MD 20850 USA
Telephone: (301) 496-8219
Phthisiopneumology Institute “Chiril Draganiuc”
Strada Constantin Vârnav 13
Chișinău MD2025, Moldova