Construction of an epidemiological framework for MDR-TB in urban and rural areas of Western India.


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2004-2007

FUNDING AMOUNT

161078 GBP

ABSTRACT

A structured study has been to assess the frequency of clustering of multiple drug resistant tuberculosis (MDR-TB) strains in urban (Mumbai) and rural areas of Western India. A molecular epidemiological approach to address this question will be adopted in TB endemic situations as conventional epidemiological linkage for the spread of M. tuberculosis (MTB) strains is difficult in high incidence environments. The strain of MTB in 200 five month treatment failures (Cat I failures) will be determined, as will the extent of spread of these strains in 1000 subsequently arising smear positive TB patients attending the same health post. In rural areas, MTB strain types will be determined from 200 new sputum smear positive (Cat I) cases as a prelude to a more detailed study in the future. The primary method of strain determination will be by PCR based spoligotyping with secondary typing by IS6110-RFLP. As low IS6110 copy number can compromise discrimination, variable number of tandem repeat (VNTR) typing will be used as an alternative to RFLP in these circumstances. The phenotypic drug resistance of isolates determined by a radiorespirometric assay will be compared with detection of mutations for rifampicin to ascertain phenotype to genotypic relationships. In addition, the ability of strains to grow within and induce cytokines from macrophages will also be ascertained. These factors will be correlated with the strain's capacity to spread as indicated by greater clustering, to shed light on virulence mechanisms. As an exploratory exercise analysis relating clustering of strains to the patient's demographic background, past medical and social history will be undertaken to ascertain risk factors for the spread of TB strains. This study will provide crucial information on the current status of MDR-TB in a part of Western India, provide a basis for addressing this problem in the future and will be of wider relevance to efforts to control the spread of MDR-TB globally. More... »

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