Abstract
BackgroundCurrent Global Program to Eliminate Lymphatic Filariasis (GPELF) that prohibits pregnant mothers and children below two years of age from coverage targeted interruption of transmission after 5–6 rounds of annual mass drug administration (MDA). However, after more than 10 rounds of MDA in India the target has not been achieved, which poses challenge to the researchers and policy makers. Several studies have shown that in utero exposure to maternal filarial infections plays certain role in determining the susceptibility and disease outcome in children. But the mechanism of which has not been studied extensively. Therefore the present study was undertaken to understand the mechanism of immune modulation in children born to filarial infected mother in a MDA ongoing area.Methodology and principal findingTo our knowledge this is the first study to conduct both cellular and humoral immunological assays and follow up the children until older age in a W bancrofti endemic area,where the microfilariae (Mf) rate has come down to <1% after 10 rounds of MDA. A total 57 (32: born to infected, 25: born to uninfected mother) children were followed up. The infection status of children was measured by presence of Mf and circulating filarial antigen (CFA) assay. Filaria specific IgG1, IgG2, IgG3 and IgG4 responses were measured by ELISA. Plasma level of IL-10 and IFN-γ were evaluated by using commercially available ELISA kit. The study reveals a high rate of acquisition of filarial infection among the children born to infected mother compared to uninfected mothers. A significantly high level of IgG1 and IgG4 was observed in children born to infected mother, whereas high level of IgG3 was marked in children born to uninfected mother. Significantly high level of IL-10 positively correlated with IgG4 have been observed in infected children born to infected mother, while high level of IFN-γ positively correlated with IgG3 was found in infection free children born to mother free from infection at the time of pregnancy. Moreover a negative correlation between IL-10 and IFN-γ has been observed only among the infected children born to infected mother.Significance conclusionThe study shows a causal association between maternal filarial infection and impaired or altered immune response in children more susceptible to filarial infection during early childhood. As lymphatic damage that commences in childhood during asymptomatic stage has major implications from public health point of view, understanding maternal programming of the newborn immune system could provide a basis for interventions promoting child health by implementing MDA campaigns towards all women of childbearing age and young children in achieving the target of global elimination of LF.
Highlights
As placental mammals, the pregnant women and the foetus have intense and prolonged interactions during gestation that alters immunity of the new born during their childhood through transferring multiple molecular as well as cellular components [1].With the accumulation of evidences on long-term impact upon responses to helminth and non-helminth antigens, the research on prenatal sensitization or in utero exposure has gathered momentum in the field of infectious diseases as it is suspected to expose the neonates to infectious agents during gestation
It is known that regulatory T cells are responsible for development of hyporesponsiveness, a condition that supports parasite growth and maternal filarial infection influences the development of T-regulatory cells from infancy to early childhood
Since T-reg cell can induce the production of regulatory cytokine IL-10 that often implicated in induction of IgG4 and we have observed an increased level of IL-10 / IgG4 and decreased levels of IFN- γ/ IgG3 in cord blood of infected mothers, we have thought that the modulation that takes place in utero affects the immune response and eventually disease outcome in early childhood
Summary
The pregnant women and the foetus have intense and prolonged interactions during gestation that alters immunity of the new born during their childhood through transferring multiple molecular as well as cellular components [1].With the accumulation of evidences on long-term impact upon responses to helminth and non-helminth antigens, the research on prenatal sensitization or in utero exposure has gathered momentum in the field of infectious diseases as it is suspected to expose the neonates to infectious agents during gestation. Over the past few years we have been analysing the influences of maternal filarial infection on neonatal immune response It appears that trans-placental trafficking of filarial antigens from mother to foetus occurs on a frequent basis [6].Studies have shown that high level of T-regulatory (T-reg) cells at the time of birth and early childhood in children born to infected mother emphasizes that maternal filarial infection influences the development of T-reg cells from infancy to early childhood [7]. We have made an attempt to investigate the effect of prenatal sensitization to filarial antigens on filarial specific IgG isotype response, IL-10 level, IFNγ levels and disease outcome in children This deserves to be explored because patent filarial infection is being recognised to occur in much earlier age than previously thought [10, 11] and GPELF excludes the pregnant mothers and children below two years. The present study was undertaken to understand the mechanism of immune modulation in children born to filarial infected mother in a MDA ongoing area
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