Figure 5. The association of prenatal malaria exposure with the frequency of malaria antigen and tetanus toxoid-driven cytokine production measured biannually to 36 months of age.

(A) Exposed not sensitized children have a lower frequency of IFNγ and IL-2 production, and/or lymphocyte proliferation by PBMCs (a positive response is defined in the text and method section) compared to exposed sensitized children and not-exposed children using a generalized estimating equations that adjusts for time, location, and repeated measures as more fully described in the Methods section (relative risk, [95% confidence interval], exposed not sensitized children compared to exposed sensitized children: 0.28 [0.15–0.37], p = 0.0003 for MSP1; 0.33 [0.20–0.51], p = 0.0008 for PfP0; 0.36 [0.19–0.74], p = 0.005 for EBA175; and 1.07 [0.89–1.65] for tetanus toxoid). Similar effect sizes were observed for exposed not sensitized children compared to not exposed children (unpublished data). (B) The frequency of antigen-driven IL-10 is higher in the exposed not sensitized children than in exposed sensitized (relative risk for MSP1, 1.67 [1.35–2.73], p = 0.0007; for PfP0 1.45 [1.03–2.51], p = 0.02; for EBA175 1.38 [0.99–2.42], p = 0.05; and for tetanus toxoid 1.04 [0.85–1.12], p = 0.73. (C) The frequency of malaria antigen-induced IL-5 and/or IL-13 cytokine responses are equivalent for the three groups (relative risk for exposed not sensitized compared to exposed sensitized children: for MSP1, 0.97 [0.79–1.21], p = 0.35; for PfP0 0.92 [0.73–1.36], p = 0.47; for EBA175, 0.83 [0.64–1.09], p = 0.16; and for tetanus toxoid, 1.01 [0.93–1.06], p = 0.61. Similar effect sizes were observed for exposed not sensitized children compared to not exposed children (unpublished data).