Immune responses in a high incidence community

The epidemiology and molecular epidemiology of tuberculosis have been studied in great detail in two adjacent suburbs of Cape Town: Ravensmead and Uitsig (Beyers et al 1996). These suburbs have a population of 34 000 with a high incidence of tuberculosis (1192 per 100 000). More than 90% of the population have been vaccinated with Bacillus Calmette—Guerin (BCG) and less than 2% are HIV positive. There was a remarkable variation in the incidence of tuberculosis (78 to 3150 per 100 000; Beyers et al 1996), socioeconomic status, literacy and crowding in enumerator subdistricts (A. van Rie, unpublished observations 1997). The incidence of tuberculosis correlated with socioeconomic status (r = — 0.57, p< 0.001). Infestation with intestinal parasites, especially Ascaris lumbricoides and Trichuris trichuria, is rampant in deprived communities in the Western Cape, where up to 90% of children are infested with A. lumbricoides. Parasite infestation induces high polyclonal IgE responses and the mean serum IgE levels of 33 healthy children (< 5 years) and 227 healthy adults from this community was 421 and 481 IU/ml, respectively. (Normal IgE levels in Caucasians are <100IU/ml, and <200IU/ ml in the Coloured population of the Western Cape, the subjects of this study.) Median log IgE levels correlated with the incidence of tuberculosis in subdistricts (r = 0.57, p <0.001; Fig.2) and with socioeconomic status (r = — 0.45, p< 0.001). Although the association between IgE levels and tuberculosis incidence does not necessarily imply a causal relationship, we hypothesize that intestinal parasites and stress in this community, particularly in the most disadvantaged subdistricts, contribute to chronic Th2 stimulation, manifested by high IgE levels and an enhanced susceptibility to tuberculosis. In this community, we have previously shown that 34% of children exposed to an index case of

FIG. 2. Correlation of the incidence of tuberculosis (TB) in adults (>15 years of age) per enumerator subdistrict with median log IgE level per enumerator subdistrict of the Ravensmead and Uitsig suburbs of Cape Town (r = 0.57, p <0.001, Spearman rank correlation).

tuberculosis in the household develop tuberculosis, compared to 5—10% in other studies (Beyers et al 1997).

In mouse models, the initial response to M. tuberculosis is type 1 and the response changes to a mixture of type 1 and type 2 during the course of disease. We were interested to measure how IgE levels, a surrogate marker for Th2 activation, changed during the course of tuberculosis. In each of 29 patients with tuberculosis, IgE levels at presentation were higher (mean = 463+86 IU/ml) than at two months following completion of treatment (mean = 166+30 IU/ml, p< 0.0001). Parasite loads have not been determined in these individuals, but standard tuberculosis therapy is not known to affect intestinal parasites. We hypothesize that chronic Th1 immune stimulation during the course of infection reduced the Th2 response driving IgE production in these individuals. If this is the case, a Th2 to Th1 immune modulation may explain why tuberculosis and asthma (both common diseases in the Western Cape) are rarely seen in the same patient (A. D. Beyers, R. Gie, N. Beyers, J. R. Joubert

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