The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era.

The pre-chemotherapy literature documented the natural history of tuberculosis in childhood. These disease descriptions remain invaluable for guiding public health policy and research, as the introduction of effective chemotherapy radically changed the history of disease. Specific high-risk groups were identified. Primary infection before 2 years of age frequently progressed to serious disease within the first 12 months without significant prior symptoms. Primary infection between 2 and 10 years of age rarely progressed to serious disease, and such progression was associated with significant clinical symptoms. In children aged >3 years the presence of symptoms represented a window of opportunity in which to establish a clinical diagnosis before serious disease progression. Primary infection after 10 years of age frequently progressed to adult-type disease. Early effective intervention in this group will reduce the burden of cavitating disease and associated disease transmission in the community. Although the pre-chemotherapy literature excluded the influence of human immune deficiency virus (HIV) infection, recent disease descriptions in HIV-infected children indicate that immune-compromised children behave in a similar fashion to immune immature children (less than 2 years of age). An important concept deduced from the natural history of tuberculosis in childhood is that of relevant disease. Deciding which children to treat may be extremely difficult in high-prevalence, low-resource settings. The concept of relevant disease provides guidance for more effective public health intervention.