Tuberculin skin-test reactions are unaffected by the severity of hyperendemic intestinal helminth infections and co-infections

Abstract

The tuberculin skin test (TST) quantifies cell-mediated immunity to tuberculosis antigens. Helminths suppress cell-mediated immunity, so we studied the effect of helminth infection and deworming on the TST in a randomized, double-blind, placebo-controlled study in an indigenous Amazon community (N = 195). Stool microscopy diagnosed helminths in 98% and co-infection with multiple species in 24% of study subjects. The TST was positive (> or = 10 mm) for 49%, and responses increased with age (P < 0.001), Bacille Calmette Guerin (BCG) vaccination (P = 0.01), and tuberculosis contact (P = 0.05). TST results had no association with helminth-egg concentrations, species, or co-infections (all P > 0.1). One month after deworming with albendazole (three daily 400-mg doses), helminths were reduced, but 63% remained infected with helminths. Albendazole did not cause a change in TST size (P = 0.8) or positivity (P = 0.9) relative to placebo. Thus, TST reactions were unaffected by albendazole therapy that partially cured intestinal helminth infections, and TST interpretation was unaffected by high-burden helminth infections and co-infection with multiple helminth species.

Figure 1.

Study flowchart. TST indicates tuberculin skin test, and stool indicates stool parasitology diagnostic tests. * Follow-up TST was only done if the baseline TST was negative (< 10 mm).

Figure 2.

Intestinal helminth infections in study participants at recruitment. Stool parasitology was graded as strongly positive (++) if an average of more than one helminth egg was seen per microscopy field, weakly positive (+) if the infection was present at lower egg density, and negative (-) if no eggs were seen. For the co-infection with > 1 helminth bar, the highest helminth egg concentration data for either helminth species are shown. Five stool samples were excluded from this analysis, because they were sufficient only for helminth egg detection but not for quantification.

Figure 3.

TST associations in univariate analyses at the time of recruitment. Box plots (A and C) show the median, inter-quartile range (shaded), and range, excluding outliers (whiskers), for the TST size; the bar graphs (B and D) show the percentage of positive TST reactions. (A) TST size and age quartiles. (B) TST positivity and age quartiles. (C) TST size and BCG vaccination. (D) TST positivity and BCG vaccination.