For Non-Scientists

 

The group aim is to understand the genetic basis of susceptibility to different infectious diseases, especially mycobacterial tuberculosis and leprosy, severe respiratory infections including invasive pneumococcal disease and thoracic empyema, as well as bacteraemia and sepsis. Host genetic factors play an important role in explaining inter-individual variation in susceptibility, although the current understanding of the specific host genetic factors which influence the development of these diseases is limited. Candidate gene studies have established a small number of replicated susceptibility loci for tuberculosis, leprosy, invasive pneumococcal disease, bacteraemia, and sepsis.

Tuberculosis and leprosy are both common infectious diseases caused by Mycobacterium spp. Tuberculosis accounts for more than 1.5 million deaths annually while leprosy remains prevalent in certain parts of the world, affecting populations in Asia, Africa and South America. It is estimated that one third of the world population is infected with M. tuberculosis, the causative agent of tuberculosis. While pulmonary tuberculosis is the commonest presentation, the tuberculosis disease can extend to other organs including peritoneum, bones, joints or even meninges. Leprosy can affect the skin and the nerves, causing significant morbidity to the affected individuals. The treatment of tuberculosis and leprosy involves an extended course of medication, and certain bacterial strains are resistant to treatment. Novel preventive and therapeutic measures are urgently needed to stop the endemic mycobacterial diseases.

Invasive pneumococcal disease is defined by the isolation of pneumococcus bacteria (Streptococcus pneumonia) in the normally sterile site. Colonisation of the nasopharynx by the pneumococcus is widespread, yet only a minority of patients develop invasive disease. Thoracic empyema is a form of invasive disease, which leads to a bacterial infection of the pleura (the space surrounding the lungs) and collection of pus within a pleural space. Infection of the bloodstream by bacteria (bacteraemia) is a common pathway in the progression to death from severe pneumonia and meningitis, and accounts for an estimated 3 million deaths annually in children under the age of 5 years - the leading cause of death in children worldwide. Even in developed countries the mortality rate from bacteraemia remains unacceptably high. A key question is why only a proportion of individuals develop invasive disease when asymptomatic carriage of bacteria is widespread. Bacteraemia can trigger a serious body wide response; this inflammatory state is called sepsis.

Identification of functional genetic variants that predispose to these diseases is likely to have major implications also for the study of other infectious and inflammatory disease processes and may translate into clinical benefit, for example through the discovery of novel therapeutic targets.