TB epidemiology and human genetics

Abstract

The impact of tuberculosis (TB) is considerably lower than one may expect, since in the absence of immunosuppression, fewer than 10% of infected individuals will develop active disease. The relatively low proportion of individuals who progress to active disease after infection can probably be ascribed to innate resistance in most infected individuals, since vaccination using BCG or a previous episode of TB does not work reliably or effectively to confer protection in high burden parts of the world. Innate factors affecting resistance or susceptibility can be modulated by the environment and such external influences cannot be ignored. Specifically, we will address bacterial variability as well as environmental factors such as diet, smoking, helminths and hormones. We will also discuss host genes that may be involved in susceptibility or resistance at various stages of infection or disease. The discovery of as yet unknown genes impacting on TB susceptibility or disease course may lead to new insights into mechanisms of disease and novel therapies. With adaptive immunity being of little value and good TB control programmes being rare, innate resistance is still our best defence against this