Heightened anti-filarial immune responsiveness in a Haitian pediatric population.

The immunological consequences of exposure to filarial infection were examined by cross-sectional serological studies. Serum samples from 121 pediatric patients (18 months-15 years of age) were analyzed in parallel with a panel of sera from adults residing in the same area of Haiti. Parasite antigen specific IgG and IgE levels were determined by ELISA. IgG levels in children were significantly elevated in humoral immunoreactivity to Brugia pahangi extracts compared to adults. In addition, anti-filarial IgG levels in amicrofilaremic children were significantly greater than in microfilaremic children. In contrast, IgG levels in adults were equivalent independent of microfilaremic status. Anti-filarial IgE levels in sera from both children and adults were low in comparison to that of a subject with tropical pulmonary eosinophilia and were unrelated to clinical status. No correlations were found between humoral responses and age, sex, or degree of parasitemia. Sera from amicrofilaremic children and, to a lesser extent, adults recognize more antigens, particularly those of high molecular weight (greater than 55 kDa), than sera from microfilaremic patients.

Analysis of isotype-specific antifilarial antibody levels in a Haitian pediatric population.

Previous studies of antifilarial antibodies in a pediatric population residing in an area with endemic Wuchereria bancrofti filariasis have demonstrated age related shifts in antifilarial immunity. To further characterize humoral responses in Haitian children, serum samples from 129 patients (3 months-15 years of age) were analyzed by ELISA for isotype-specific antifilarial antibody responses. Age-stratified analysis of geometric mean antibody titers showed significant increases in antibody titers of all isotypes with age in the amicrofilaremic population. Antifilarial IgG1, 2, and 3 levels were higher in amicrofilaremic children than in microfilaremic children, significantly so for IgG2 and IgG3. In contrast, IgG4 antibody levels were higher in microfilaremic subjects than in amicrofilaremic subjects. A multivariate, unconditional, logistic regression model was developed from these data to predict infection status. The model correctly classified 91.6% of the amicrofilaremic subjects, but only 55.6% of the microfilaremic subjects.

Transplacental transmission of Wuchereria bancrofti in Haitian women.

To document the occurrence of transplacental transmission of microfilariae and to determine how frequently it occurred, umbilical cord blood samples and placental tissues were collected from 22 microfilaria-positive women in an area with endemic Wuchereria bancrofti. Microfilaria (mf) counts in the women ranged from 1 to 3,820 mf/ml. Microfilariae were detected in 2 placenta samples and a single cord blood sample. The positive cord blood sample and 1 of the positive placenta samples came from the same woman; no microfilariae were found in a finger prick sample taken from the infant 3 wk after delivery. Our results suggest that microfilariae cross the placenta in less than 10% of pregnancies of microfilaria-positive mothers. Furthermore, the microfilaria count of the mother does not seem to influence directly whether microfilariae are present in the placental blood pool. Although actual transfer of microfilariae to the fetus may occur infrequently, exposure to parasite antigens occurs with much greater frequency. The effect of in utero exposure to either microfilariae or parasite antigens may render newborns tolerant and explain why children born to infected mothers are almost 3 times more likely to become infected than are children born to uninfected women.

Investigation of the influence of maternal infection with Wuchereria bancrofti on the humoral and cellular responses of neonates to filarial antigens.

Epidemiological data indicate that maternal filarial infection might be associated with increased susceptibility to filarial infection in offspring. To examine the influence of maternal infection on development of antifilarial immunity in neonates, paired cord and maternal sera and mononuclear cells were collected in an area where Wuchereria bancrofti infection is endemic. Anti-filarial humoral responses (IgG, IgM and IgE) non-parasite-specific humoral responses (total IgE), proliferation induced by filarial antigen and production of cytokines (interleukin-2, interleukin-4 and interferon-gamma) were all monitored. Few cord serum samples had detectable antifilarial IgM of IgE and neither these responses nor total IgE levels differed as a function of maternal infection status. Of cord-blood mononuclear cells assayed, a relatively small proportion exhibited reactivity to filarial antigens. Based on these limited responses to filarial antigens, few neonates display evidence of in-utero sensitization to filarial antigens.

Maternal filarial infection as risk factor for infection in children.

Familial clustering of filarial infection was investigated through random house-to-house surveys of 643 individuals in Leogane, Haiti, an area with endemic Bancroftian filariasis. Children of infected mothers were 2.4 to 2.9 times more likely to be infected than were those of amicrofilaraemic mothers. Filarial-specific cellular responsiveness in amicrofilaraemic children born to infected mothers was lower than that in amicrofilaraemic children born to amicrofilaraemic mothers. No effect of paternal infection status was seen. The findings show that maternal infection is a risk factor for filarial infection in children and is associated with altered parasite-specific immune reactivity.

Antifilarial cellular responses detected in a Haitian pediatric population by use of a microblastogenesis assay.

Previous reports have demonstrated age-related shifts in antifilarial humoral immune responses in 6- to 10-year-old Haitian children; the responses consisted of elevated parasite-specific IgG2 and IgG3 in amicrofilaremic children and elevated IgG4 in microfilaremic children. In this study, the cell-mediated immune responses to soluble adult and microfilarial extracts of Brugia pahangi, determined by use of a microblastogenesis assay, were examined. Capillary blood samples were collected by finger prick from 176 Haitian children in an area with endemic Wuchereria bancrofti. Antigen-specific cellular responsiveness varied as a function of infection status but not age or sex; amicrofilaremic children had significantly greater responses to adult antigens than did microfilaremic children. Significant responses were detected in children less than 2 years of age; thus, correlations observed between filarial antigen-specific responses and infection status are established early in life.