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HOMITB


Host and mycobacterial molecular dissection of immunity and pathogenesis of tuberculosis
 
 
Framework programme:
 7
Contract/Grant agreement number:
200732
EC contribution:
3.000.000 €
Duration:
36 months
Funding scheme:
Collaborative Project
Starting date:
01/11/2008
 
 

Keywords: Tuberculosis, genetics, susceptibility, T cells, macrophages, latency, chemokine

Background

The global incidence of tuberculosis (TB) is rising, with 8.8 million new cases and 2 million deaths each year. The rate of progression from infection to disease is highly variable, and approximately 90% of infected individuals never develop clinical disease. About half of the 10% of Mycobacterium tuberculosis-infected individuals who do develop overt clinical disease are diagnosed with TB within 2 years of infection and can be considered fast progressors. This 'primary' TB is particularly common in children and is often disseminated due to early haematogenous spread of the mycobacterium with miliary and/or extra-pulmonary disease.

About 50% of TB patients who develop clinical disease more than two years after infection are commonly described as cases of 'reactivation' or post-primary TB. Post-primary TB is predominantly a pulmonary disease of adults, involving extensive damage to the lungs and efficient airborne transmission of bacteria. Although neonatal immunisation with the Mycobacterium bovis-derived Bacillus Calmette-Guérin (BCG) vaccine can provide protection against childhood TB, BCG is relatively ineffective in preventing disease in older children and adults.

Latently infected individuals run a lifelong risk of reactivation. The risk is particularly high when these individuals are immunocompromised, as the result of either HIV infection or of immunosuppressive treatment.

Tightly controlled genetically determined interactions between the mycobacteria and different host target cells that are regulated by the host innate and adaptive immune responses dictate the outcome of mycobacterial infection in humans, ranging from an asymptomatic infection to a life-threatening disease.

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