Influence of maternal filariasis on childhood infection and immunity to Wuchereria bancrofti in Kenya

Abstract

To determine whether maternal filariasis influences the risk of infection by and immunity to Wuchereria bancrofti in children, we performed a cross-sectional study in an area of Kenya where filariasis is endemic. Residents of 211 households were enrolled; 376 parents and 938 of their offspring between the ages of 2 and 17 years were examined for filarial infection status as determined by blood-borne microfilariae and filarial antigenemia. Children of infected mothers had a three- to fourfold increased risk of filarial infection, as ascertained by circulating filarial antigen, relative to children of uninfected mothers (P < 0.001). Paternal infection did not correlate with childhood infection status, indicating a specific maternal effect. Peripheral blood mononuclear cells from children of filaria-infected mothers (n = 33) had higher levels of constitutive interleukin-5 (IL-5) and IL-10, increased microfilarial antigen-specific IL-5 production, and diminished microfilarial antigen-driven lymphocyte proliferation than cells from children of uninfected mothers (n = 46; P < 0.05). In contrast, there were no differences between the two groups in adult worm antigen-driven gamma interferon, IL-2, IL-4, IL-5, and IL-10 production and lymphocyte proliferation. These data indicate that maternal filarial infection increases childhood susceptibility to W. bancrofti and skews filaria-specific immunity toward a Th2-type cytokine response. The results support the notion that in utero exposure to filarial antigens affects the natural history of filariasis during childhood.

FIG. 1.

(A) Relationship between age and prevalence of infection among all individuals residing in two adjacent villages where filariasis is endemic in the Coast Province, Kwale District, Kenya (n = 1,522). Microfilaremia was determined by collection of 200 μl of blood at night and CAg was determined based on the Og4C3 assay. (B) Prevalence of infection in children 1 to 10 years of age in the same population (n = 251).

FIG. 2.

Cytokine production by PBMC from children of infected (CAg⁺) versus uninfected (CAg⁻) mothers. (Upper panel) Constitutive cytokine production. (Middle panel) Net (antigen-driven minus spontaneous) BmA-driven cytokine production. (Lower panel) Net MFE-induced cytokine production. Each point represents the mean for duplicate cultures from a single individual. Bars represent geometric means. Triangles, offspring of infected mothers; open triangles, samples that were further examined for CD4⁺ cell depletion; diamonds, offspring of uninfected mothers. The percentage of individuals showing a positive response is shown below each panel. Significant differences between groups, based on chi-square analysis (media) or Student's t test of log-transformed data (BmA- and MFE-driven responses) are indicated.

FIG. 3.

Lymphocyte proliferation responses of PBMC from children of infected and uninfected mothers. Bars indicate means ± SEM of counts per minute determined in triplicate for each individual. For studies of spontaneous and BmA-driven lymphocyte proliferation, PBMC from 33 children of infected mothers and 46 children of uninfected mothers were examined. Since childhood infection affected proliferation responses to MFE, responses to this antigen preparation were limited to 22 children of infected mothers and 38 children of uninfected mothers. **, P < 0.01.