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Filarial infection during pregnancy has profound consequences on immune response and disease outcome in children: A birth cohort study

BACKGROUND: Current 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...

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Autores principales: Bal, Madhusmita, Ranjit, Manoranjan, Satapathy, Ashok K., Khuntia, Hemant K., Pati, Sanghamitra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173457/
https://www.ncbi.nlm.nih.gov/pubmed/30252839
http://dx.doi.org/10.1371/journal.pntd.0006824
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author Bal, Madhusmita
Ranjit, Manoranjan
Satapathy, Ashok K.
Khuntia, Hemant K.
Pati, Sanghamitra
author_facet Bal, Madhusmita
Ranjit, Manoranjan
Satapathy, Ashok K.
Khuntia, Hemant K.
Pati, Sanghamitra
author_sort Bal, Madhusmita
collection PubMed
description BACKGROUND: Current 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 FINDING: To 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 CONCLUSION: The 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.
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spelling pubmed-61734572018-10-19 Filarial infection during pregnancy has profound consequences on immune response and disease outcome in children: A birth cohort study Bal, Madhusmita Ranjit, Manoranjan Satapathy, Ashok K. Khuntia, Hemant K. Pati, Sanghamitra PLoS Negl Trop Dis Research Article BACKGROUND: Current 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 FINDING: To 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 CONCLUSION: The 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. Public Library of Science 2018-09-25 /pmc/articles/PMC6173457/ /pubmed/30252839 http://dx.doi.org/10.1371/journal.pntd.0006824 Text en © 2018 Bal et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bal, Madhusmita
Ranjit, Manoranjan
Satapathy, Ashok K.
Khuntia, Hemant K.
Pati, Sanghamitra
Filarial infection during pregnancy has profound consequences on immune response and disease outcome in children: A birth cohort study
title Filarial infection during pregnancy has profound consequences on immune response and disease outcome in children: A birth cohort study
title_full Filarial infection during pregnancy has profound consequences on immune response and disease outcome in children: A birth cohort study
title_fullStr Filarial infection during pregnancy has profound consequences on immune response and disease outcome in children: A birth cohort study
title_full_unstemmed Filarial infection during pregnancy has profound consequences on immune response and disease outcome in children: A birth cohort study
title_short Filarial infection during pregnancy has profound consequences on immune response and disease outcome in children: A birth cohort study
title_sort filarial infection during pregnancy has profound consequences on immune response and disease outcome in children: a birth cohort study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173457/
https://www.ncbi.nlm.nih.gov/pubmed/30252839
http://dx.doi.org/10.1371/journal.pntd.0006824
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