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The TB skin-test results were read in a blinded manner, and reactions to tests with zinc cream applications were an average of 32% larger than the contralateral control skin test reactions with placebo cream applied (Figure 1; p<0.001). TB skin-test results were considered positive if the average diameter of induration was >10 mm 48 h after injection, according to national policy. Skin tests with zinc applications were significantly more likely to have positive results than the simultaneous contralateral control skin tests with placebo cream applications (94% zinc vs. 76% placebo, p = 0.01). Topical zinc caused greater TB skin-test augmentation in persons with lower plasma zinc concentrations (correlation coefficient [R] = 0.3, p = 0.05), and persons with absolute plasma zinc deficiency (<0.6 mg/L) had significantly greater zinc-mediated augmentation (Figure 2, p = 0.02). Zinc cream had no effect in persons with normal plasma zinc concentrations. Thus, zinc cream significantly augmented TB skin-test reactions only in persons deficient in zinc (Figure 2).
TB skin tests are usually read 48 h after PPD injection; however, in this study, additional readings were done at 24 and 72 h, at which time results, similar to those at 48 h, demonstrated that zinc cream caused larger TB skin-test reactions (both p<0.02) and more positive test results (both p<0.006). Furthermore, at 72 and 48 h, this zinc-mediated augmentation was greater in zinc-deficient persons (p = 0.006), although the similar trend at 24 h was not statistically significant. The magnitude of skin-test augmentation with zinc cream, the plasma zinc concentration, and the anthropometric measures had no significant associations with other studied factors except as noted in the Table.
The effect of zinc on the Candida skin-test results was similar to the effect on the TB skin-test results. Specifically, the Candida skin-test reactions with zinc cream were an average of 23% larger than the contralateral skin-test reactions associated with placebo cream applied in a double-blind manner (p<0.001). Candida skin-test results were considered positive if the average diameter of induration was >5 mm (1), and 78% of Candida skin-test results associated with zinc application were positive, compared with 64% with placebo cream (p = 0.01). Zinc-mediated TB and Candida skin-test augmentation were associated (R = 0.3, p = 0.05), but zinc-mediated Candida skin-test augmentation was not significantly associated with any of the variables in the Table.
The control skin tests with placebo cream yielded larger reactions (p = 0.005) and were more likely to be positive (p = 0.005) than concurrent skin tests on 97 other randomly selected healthy volunteers in the same community (data not shown). These 97 skin tests were each performed on 1 arm only, and no creams were applied; the mean diameter of induration was 16.4 mm (SEM 1.9 mm), and 52% were TB skin-test positive (>10 mm). Although the design of this part of the study prevented blinded assessment, this comparison implies that in the 50 persons with simultaneous bilateral skin tests, zinc absorption through the skin may have partially augmented the contralateral control skin-test reactions to which placebo cream was applied. Although the local direct effect at the site of zinc cream application was significantly greater, systemic zinc absorption may have caused the effect of zinc cream to be underestimated; this hypothesis is being further investigated.
Zinc status is difficult to reliably assess (2–4). However, low plasma zinc significantly predicted small skin-test reactions and the magnitude of the immunologic response to topical supplementation. Thus, zinc cream had a specific effect, namely, reversing the skin-test suppression of zinc deficiency. Topical zinc supplementation applied to the arms of persons who received TB skin tests therefore identified persons in whom zinc deficiency was sufficient to suppress antimycobacterial immune responses and quantified the immune-potentiating effect of supplementation. This approach may simil