Evidence for a peak shift in a humoral response to helminths: age profiles of IgE in the Shuar of Ecuador, the Tsimane of Bolivia, and the U.S. NHANES

Abstract

Background: The peak shift model predicts that the age-profile of a pathogen's prevalence depends upon its transmission rate, peaking earlier in populations with higher transmission and declining as partial immunity is acquired. Helminth infections are associated with increased immunoglobulin E (IgE), which may convey partial immunity and influence the peak shift. Although studies have noted peak shifts in helminths, corresponding peak shifts in total IgE have not been investigated, nor has the age-patterning been carefully examined across populations. We test for differences in the age-patterning of IgE between two South American forager-horticulturalist populations and the United States: the Tsimane of Bolivia (n=832), the Shuar of Ecuador (n=289), and the U.S. NHANES (n=8,336). We then examine the relationship between total IgE and helminth prevalences in the Tsimane.

Methodology/principal findings: Total IgE levels were assessed in serum and dried blood spots and age-patterns examined with non-linear regression models. Tsimane had the highest IgE (geometric mean =8,182 IU/ml), followed by Shuar (1,252 IU/ml), and NHANES (52 IU/ml). Consistent with predictions, higher population IgE was associated with steeper increases at early ages and earlier peaks: Tsimane IgE peaked at 7 years, Shuar at 10 years, and NHANES at 17 years. For Tsimane, the age-pattern was compared with fecal helminth prevalences. Overall, 57% had detectable eggs or larva, with hookworm (45.4%) and Ascaris lumbricoides (19.9%) the most prevalent. The peak in total IgE occurred around the peak in A. lumbricoides, which was associated with higher IgE in children <10, but with lower IgE in adolescents.

Conclusions: The age-patterning suggests a peak shift in total IgE similar to that seen in helminth infections, particularly A. lumbricoides. This age-patterning may have implications for understanding the effects of helminths on other health outcomes, such as allergy, growth, and response to childhood vaccination.

Figure 1. Distribution and geometric mean value of IgE antibody levels in three populations.

Density plots were generated with a Gaussian smooth with bandwidth 0.5.

Figure 2. Models for IgE by age in Tsimane, Shuar, and NHANES.

A) Generalized additive models for Tsimane (top, blue), Shuar (middle, green), and NHANES (bottom, yellow). Points show the mean lnIgE value for males (triangles) and females (circles) between knots specified in the initial model basis (vertical lines), while lines indicate the thin plate regression spline for each sex. For all three populations males have the higher fit line. Numbers indicate the estimated ages at which the initial peak in IgE occurs. Shading indicates local 95% confidence intervals for the spline, with dark areas indicating overlap between male and female confidence intervals and light areas indicating no overlap. B) Ordinal step models and non-linear regression models. Ordinal model parameters were entered in stepwise fashion according to AIC minimization, resulting in the final models. Numbers indicate a significant transition at greater than the age given, symbols the significance of the parameter in the model: ^t p≤0.10, * p≤0.05, ** p≤0.01, *** p≤0.001. Dashed lines indicate the model fits for non-linear models, including the population specific models in Table 3 (red), and the interaction models in Table 4 (Model 1 in green, Model 2 in brown, and Model 3 in blue). For simplicity only the models for females are shown.

Figure 3. Association between model parameters and population geometric mean IgE levels.

The upper panel shows fits between age parameters and mean log IgE by population. The lower shows fits between slope parameters and geometric mean IgE by population. Note that the fit for B1 is linear with regard to log IgE, but is shown on the lower graph due to the parameter scale. Correlation coefficients for all parameters are given in the text.

Figure 4. Odds-ratios for Tsimane helminth infection by age relative to the Tsimane population as a whole.

Odds-ratios were estimated with generalized additive models with a binomial logit link function. Shading shows the 95% confidence interval for the odds-ratio. All age functions were significant at p<0.001, except the age function for T. trichiura, which was non-significant.

Figure 5. Association between helminth infection and IgE levels by Tsimane age group.

Y-values are the regression coefficients from linear models with lnIgE as the dependent variable and infection status for all four parasites entered simultaneously, to control for coinfection status. Models were run separately for each age group indicated. Parameter significance: * p≤0.05, ** p≤0.01, *** p≤0.001.