Tuberculosis during childhood and adulthood

Children with tuberculosis usually present with lymphadenopathy or the complications thereof, or with systemic spread of the organism. In contrast, adults usually have pronounced systemic effects (such as weight loss and high fever) and immunopathology (such as cavitation and fibrosis). Adulthood disease ('secondary' tuberculosis) is usually ascribed to a secondary immune response following re-infection or re-activation (the Koch phenomenon). Other factors may however contribute to the differences in the immune response of children versus adults. We have seen a number of children presenting with culture proven childhood ('primary') tuberculosis, who were fully treated but developed culture proven tuberculosis again several years later, before the onset of puberty. These children were HIV negative and did not have any evidence for immune deficiency. On second presentation, they again had the childhood form of disease. Differences in the immune response between adults and children are also seen in viral diseases. Young children are more susceptible to viral infections than adults, but adults develop immunopathology, such as viral pneumonitis, more frequently than children during infection with measles or chicken pox. Factors contributing to the decreased immune responses in children include decreased chemotaxis and microbicidal activity of macrophages, decreased antigen presentation by dendritic cells, a larger proportion of naïve cells (requiring more efficient co-stimulation), reduced expression of CD40 ligand by activated neonatal T cells and a reduced secretion of cytokines other than IL-2 (Smith et al 1997).

Several studies showed that peripheral blood mononuclear cells (PBMC) from cord blood produce markedly reduced levels of IFN-y following stimulation with mitogen invitro (Holt 1995, Smith et al 1997). Adult levels of IFN-y production are only reached by the age of three to four years. Given that adrenal and sex steroids can modulate cytokine responses, we decided to compare the cytokine responses of children to those of adults following phytohaemagglutinin stimulation in serumfree medium. PBMC of healthy children (two to five years of age) produced barely detectable levels of IFN-y, whereas PBMC from most adults produced large amounts. No significant differences were detected in IL-2, IL-4, IL-10 and TNF secretion. The decreased production of IFN-y by PBMC from children is not only due to a higher ratio of naïve versus experienced T cells in infants, but also to other mechanisms including intrinsic defects of the T cells themselves and reduced APC function (Holt 1995, Smith et al 1997).

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