Skip to main content Accessibility help

Immunological footprint: the development of a child's immune system in environments rich in microorganisms and parasites



The shaping of a child's immune system starts in utero, with possible long-term consequences in later life. This review highlights the studies conducted on the development of the immune system in early childhood up to school-age, discussing the impact that environmental factors may have. Emphasis has been put on studies conducted in geographical regions where exposure to micro-organisms and parasites are particularly high, and the effect that maternal exposures to these may have on an infant's immune responses to third-party antigens. In this respect we discuss the effect on responses to vaccines, co-infections and on the development of allergic disorders. In addition, studies of the impact that such environmental factors may have on slightly older (school) children are highlighted emphasizing the need for large studies in low to middle income countries, that are sufficiently powered and have longitudinal follow-up components to understand the immunological footprint of a child and the consequences throughout life.


Corresponding author

*Corresponding author: Yenny Djuardi, MD. Department of Parasitology, Faculty of Medicine University of Indonesia, Salemba 6, Jakarta 10430, Indonésia. Tel: +6221 3914607. Fax: +6221 39832018. E-mail:
Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Tel: +3171 5265072. Fax: +3171 5266907. E-mail:


Hide All
Adegnika, A. A., Agnandji, S. T., Chai, S. K., Ramharter, M., Breitling, L., Kendjo, E., Issifou, S., Yazdanbakhsh, M., Kombila, M. and Kremsner, P. G. (2007). Increased prevalence of intestinal helminth infection during pregnancy in a Sub-Saharan African community. Wiener Klinische Wochenschrift 119, 712716.
Adlerberth, I., Carlsson, B., De Man, P., Jalil, F., Khan, S. R., Larsson, P., Mellander, L., Svanborg, C., Wold, A. E. and Hanson, L. A. (1991). Intestinal colonization with Enterobacteriaceae in Pakistani and Swedish hospital-delivered infants. Acta Paediatrica Scandinavica 80, 602610.
Alm, J. S., Swartz, J., Bjorksten, B., Engstrand, L., Engstrom, J., Kuhn, I., Lilja, G., Mollby, R., Norin, E., Pershagen, G., Reinders, C., Wreiber, K. and Scheynius, A. (2002). An antroposophic lifestyle and intestinal microflora in infancy. Pediatric Allergy and Immunology 13, 402411.
Attallah, A. M., Abbas, A. T., Dessouky, M. I., El-emshaty, H. M. and Elsheikha, H. M. (2006). Susceptibility of neonate mice born to Schistosoma mansoni-infected and noninfected mothers to subsequent S. mansoni infection. Parasitology Research 99, 137145.
Babu, S., Blauvelt, C. P., Kumaraswami, V. and Nutman, T. B. (2006). Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: implications for parasite persistence. Journal of Immunology 176, 32483256.
Bal, M. S., Mandal, N. N., DAS, M. K., Kar, S. K., Sarangi, S. S. and Beuria, M. K. (2010). Transplacental transfer of filarial antigens from Wuchereria bancrofti-infected mothers to their offspring. Parasitology 137, 669673.
Barker, D. J. (1995). Foetal origins of coronary heart disease. British Medical Journal 311, 171174.
Barker, D. J., Gelow, J., Thornburg, K., Osmond, C., Kajantie, E. and Eriksson, J. G. (2010). The early origins of chronic heart failure: impaired placental growth and initiation of insulin resistance in childhood. European Journal of Heart Failure 12, 819825.
Belderbos, M. E., van Bleek, G. M., Levy, O., Blanken, M. O., Houben, M. L., Schuijff, L., Kimpen, J. L. and Bont, L. (2009). Skewed pattern of Toll-like receptor 4-mediated cytokine production in human neonatal blood: low LPS-induced IL-12p70 and high IL-10 persist throughout the first month of life. Clinical Immunology 133, 228237.
Belkaid, Y. (2007). Regulatory T cells and infection: a dangerous necessity. Nature Reviews. Immunolology 7, 875888.
Beltran, S., Gourbal, B., Boissier, J., Duval, D., Kieffer-Jaquinod, S., Pierce, R. J., Grunau, C., Theron, A. and Mitta, G. (2010). Vertebrate host protective immunity drives genetic diversity and antigenic polymorphism in Schistosoma mansoni. Journal of Evolutionary Biology 24, 554572. doi: 10.1111/j.1420-9101.2010.02190.x.
Bjorksten, B. (2004). Effects of intestinal microflora and the environment on the development of asthma and allergy. Springer Seminars in Immunopathology 25, 257270.
Bourke, C. D., Maizels, R. M. and Mutapi, F. (2010). Acquired immune heterogeneity and its sources in human helminth infection. Parasitology 138, 139159.
Braun-Fahrlander, C., Gassner, M., Grize, L., Neu, U., Sennhauser, F. H., Varonier, H. S., Vuille, J. C. and Wuthrich, B. (1999). Prevalence of hay fever and allergic sensitization in farmer's children and their peers living in the same rural community. SCARPOL team. Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution. Clinical and Experimental Allergy 29, 2834.
Brooker, S., Akhwale, W., Pullan, R., Estambale, B., Clarke, S. E., Snow, R. W. and Hotez, P. J. (2007). Epidemiology of plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia, and prospects for combining control. American Journal of Tropical Medicine and Hygiene 77, 8898.
Brustoski, K., Moller, U., Kramer, M., Petelski, A., Brenner, S., Palmer, D. R., Bongartz, M., Kremsner, P. G., Luty, A. J. and Krzych, U. (2005). IFN-gamma and IL-10 mediate parasite-specific immune responses of cord blood cells induced by pregnancy-associated Plasmodium falciparum malaria. Journal of Immunology 174, 17381745.
Conrad, M. L., Ferstl, R., Teich, R., Brand, S., Blumer, N., Yildirim, A. O., Patrascan, C. C., Hanuszkiewicz, A., Akira, S., Wagner, H., Holst, O., von Mutius, E., Pfefferle, P. I., Kirschning, C. J., Garn, H. and Renz, H. (2009). Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78. Journal of Experimental Medicine 206, 28692877.
Conroy, M. E. and Walker, W. A. (2008). Intestinal immune health. Nestle Nutrition Workshop Series. Pediatric Program 62, 111121.
Cooper, P. J. (2004). The potential impact of early exposures to geohelminth infections on the development of atopy. Clinical Reviews in Allergy and Immunology 26, 514.
Cooper, P. J., Chico, M., Sandoval, C., Espinel, I., Guevara, A., Levine, M. M., Griffin, G. E. and Nutman, T. B. (2001). Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR. Infection and Immunity 69, 15741580.
Cooper, P. J., Espinel, I., Paredes, W., Guderian, R. H. and Nutman, T. B. (1998). Impaired tetanus-specific cellular and humoral responses following tetanus vaccination in human onchocerciasis: a possible role for interleukin-10. Journal of Infectious Diseases 178, 11331138.
Darrah, P. A., Patel, D. T., De Luca, P. M., Lindsay, R. W., Davey, D. F., Flynn, B. J., Hoff, S. T., Andersen, P., Reed, S. G., Morris, S. L., Roederer, M. and Seder, R. A. (2007). Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nature Medicine 13, 843850.
de Rooij, S. R., Painter, R. C., Roseboom, T. J., Phillips, D. I., Osmond, C., Barker, D. J., Tanck, M. W., Michels, R. P., Bossuyt, P. M. and Bleker, O. P. (2006). Glucose tolerance at age 58 and the decline of glucose tolerance in comparison with age 50 in people prenatally exposed to the Dutch famine. Diabetologia 49, 637643.
De Filippo, C., Cavalieri, D., Di Paola, M., Ramazzotti, M., Poullet, J. B., Massart, S., Collini, S., Pieraccini, G. and Lionetti, P. (2010). Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proceedings of the National Academy of Sciences, USA 107, 1469114696.
Djuardi, Y., Sartono, E., Wibowo, H., Supali, T. and Yazdanbakhsh, M. (2010). A longitudinal study of BCG vaccination in early childhood: the development of innate and adaptive immune responses. PLoS One 5, e14066.
Djuardi, Y., Wibowo, H., Supali, T., Ariawan, I., Bredius, R. G., Yazdanbakhsh, M., Rodrigues, L. C. and Sartono, E. (2009). Determinants of the relationship between cytokine production in pregnant women and their infants. PLoS One 4, e7711.
Dominguez-Bello, M. G., Costello, E. K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N. and Knight, R. (2010). Delivery mode shapes the acquitition and structure of the initial microbiota across multiple body habitats in newborns. Proceedings of the National Academy of Sciences USA 107, 1197111975.
Eberhard, M. L., Hitch, W. L., McNeeley, D. F. and Lammie, P. J. (1993). Transplacental transmission of Wuchereria bancrofti in Haitian women. Journal of Parasitology 79, 6266.
Ebrahim, S. (2004). Cohorts, infants and children. International Journal of Epidemiology 33, 11651166. doi: 10.1093/ije/dyh368.
Ege, M. J., Bieli, C., Frei, R., van Strien, R. T., Riedler, J., Ublagger, E., Schram-Bijkerk, D., Brunekreef, B., van Hage, M., Scheynius, A., Pershagen, G., Benz, M. R., Lauener, R., von Mutius, E. and Braun-Fahrlander, C. (2006). Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children. Journal of Allergy and Clinical Immunology 117, 817823.
Elias, D., Britton, S., Aseffa, A., Engers, H. and Akuffo, H. (2008). Poor immunogenicity of BCG in helminth infected population is associated with increased in vitro TGF-beta production. Vaccine 26, 38973902.
Elliott, A. M., Mawa, P. A., Webb, E. L., Nampijja, M., Lyadda, N., Bukusuba, J., Kizza, M., Namujju, P. B., Nabulime, J., Ndibazza, J., Muwanga, M. and Whitworth, J. A. (2010). Effects of maternal and infant co-infections, and of maternal immunisation, on the infant response to BCG and tetanus immunisation. Vaccine 29, 247–55.
Elliott, A. M., Mpairwe, H., Quigley, M. A., Nampijja, M., Muhangi, L., Oweka-Onyee, J., Muwanga, M., Ndibazza, J. and Whitworth, J. A. (2005 a). Helminth infection during pregnancy and development of infantile eczema. Journal of the American Medical Association 294, 20322034.
Elliott, A. M., Namujju, P. B., Mawa, P. A., Quigley, M. A., Nampijja, M., Nkurunziza, P. M., Belisle, J. T., Muwanga, M. and Whitworth, J. A. (2005 b). A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to Bacille Calmette-Guerin (BCG) immunisation [ISRCTN32849447]. BMC Infectious Diseases 5, 115.
Endara, P., Vaca, M., Chico, M. E., Erazo, S., Oviedo, G., Quinzo, I., Rodriguez, A., Lovato, R., Moncayo, A. L., Barreto, M. L., Rodrigues, L. C. and Cooper, P. J. (2010). Long-term periodic anthelmintic treatments are associated with increased allergen skin reactivity. Clinical and Experimental Allergy 40, 16691677.
Engelmann, I., Santamaria, A., Kremsner, P. G. and Luty, A. J. (2005). Activation status of cord blood gamma delta T cells reflects in utero exposure to Plasmodium falciparum antigen. Journal of Infectious Diseases 191, 16121622.
Erb, K. J. (2009). Can helminths or helminth-derived products be used in humans to prevent or treat allergic diseases?. Trends in Immunology 30, 7582.
Eriksson, J. G., Forsen, T., Tuomilehto, J., Jaddoe, V. W., Osmond, C. and Barker, D. J. (2002). Effects of size at birth and childhood growth on the insulin resistance syndrome in elderly individuals. Diabetologia 45, 342348.
Ferguson, A. C. (1978). Prolonged impairment of cellular immunity in children with intrauterine growth retardation. Journal of Pediatrics 93, 5256.
Fievet, N., Ringwald, P., Bickii, J., Dubois, B., Maubert, B., Le Hesran, J. Y., Cot, M. and Deloron, P. (1996). Malaria cellular immune responses in neonates from Cameroon. Parasite Immunology 18, 483490.
Flohr, C., Quinnell, R. J. and Britton, J. (2009). Do helminth parasites protect against atopy and allergic disease? Clinical and Experimental Allergy 39, 2032.
Garcia-Hernandez, M. H., Alvarado-Sanchez, B., Calvo-Turrubiartes, M. Z., Salgado-Bustamante, M., Rodriguez-Pinal, C. Y., Gamez-Lopez, L. R., Gonzalez-Amaro, R. and Portales-Perez, D. P. (2009). Regulatory T Cells in children with intestinal parasite infection. Parasite Immunology 31, 597603.
Haider, B. A., Humayun, Q. and Bhutta, Z. A. (2009). Effect of administration of antihelminthics for soil transmitted helminths during pregnancy. Cochrane Database of Systematic Reviews 2, 120. CD005547. doi: 10.1002/14651858.CD005547.pub2.
Hara, T., Ohashi, S., Yamashita, Y., Abe, T., Hisaeda, H., Himeno, K., Good, R. A. and Takeshita, K. (1996). Human V delta 2+ gamma delta T-cell tolerance to foreign antigens of Toxoplasma gondii. Proceedings of the National Academy of Sciences, USA 93, 51365140.
Hartgers, F. C., Obeng, B. B., Kruize, Y. C., Dijkhuis, A., McCall, M., Sauerwein, R. W., Luty, A. J., Boakye, D. A. and Yazdanbakhsh, M. (2009). Responses to malarial antigens are altered in helminth-infected children. Journal of Infectious Diseases 199, 15281535.
Hayes, K. S., Bancroft, A. J., Goldrick, M., Portsmouth, C., Roberts, I. S. and Grencis, R. K. (2010). Exploitation of the intestinal microflora by the parasitic nematode Trichuris muris. Science 328, 13911394.
Herter, U., Petney, T., Pipitgool, V., Sithithaworn, P., Vivatpatanakul, K., Hinz, E. and Andrews, R. (2007). The influence of pregnancy on intestinal parasite infection in Thai women. Acta Tropica 101, 200206.
Hochberg, Z., Feil, R., Constancia, M., Fraga, M., Junien, C., Carel, J. C., Boileau, P., Le Boug, Y., Deal, C. L., Lillycrop, K., Scharfmann, R., Sheppard, A., Skinner, M., Szyf, M., Waterland, R. A., Waxman, D. J., Whitelaw, E., Ong, K. and Albertsson-Wikland, K. (2010). Child Health, Developmental Plasticity, and Epigenetic Programming. Endocrine Reviews 32, 159224. doi:10.1210/er.2009-0039.
Holmlund, U., Amoudruz, P., Johansson, M. A., Haileselassie, Y., Ongoiba, A., Kayentao, K., Traore, B., Doumbo, S., Schollin, J., Doumbo, O., Montgomery, S. M. and Sverremark-Ekstrom, E. (2010). Maternal country of origin, breast milk characteristics and potential influences on immunity in offspring. Clinical and Experimental Immunology 162, 500509.
Hosea Blewett, H. J., Cicalo, M. C., Holland, C. D. and Field, C. J. (2008). The immunological components of human milk. Advances in Food and Nutrition Research 54, 4580.
Huurre, A., Kalliomäki, M., Rautava, S., Rinne, M., Salminen, S. and Isolauri, E. (2008). Mode of delivery-effects on gut microbiota and humoral immunity. Neonatology 93, 236240.
Karadag, B., Ege, M., Bradley, J. E., Braun-Fahrlander, C., Riedler, J., Nowak, D. and von Mutius, E. (2006). The role of parasitic infections in atopic diseases in rural schoolchildren. Allergy 61, 9961001.
King, C. L., Malhotra, I., Mungai, P., Wamachi, A., Kioko, J., Ouma, J. H. and Kazura, J. W. (1998). B cell sensitization to helminthic infection develops in utero in humans. Journal of Immunology 160, 35783584.
Kalliomäki, M., Salminen, S., Poussa, T., Arvilommi, H. and Isolauri, E. (2007). Probiotics during the first 7 years of life: A cumulative risk reduction of eczema in a randomized, placebo-controlled trial. Journal of Allergy and Clinical Immunology 119, 10191021.
Koenig, J. E., Spor, A., Scalfone, N., Fricker, A. D., Stombaugh, J., Knight, R., Angenent, L. T. and Ley, R. E. (2010). Microbes and Health Sackler Colloquium: Succession of microbial consortia in the developing infant gut microbiome. Proceedings of the National Academy of Sciences, USA 108, 45784585. doi: 10.1073/pnas.1000081107.
Kohler, C., Adegnika, A. A., Van der Linden, R., Agnandji, S. T., Chai, S. K., Luty, A. J., Szepfalusi, Z., Kremsner, P. G. and Yazdanbakhsh, M. (2008). Comparison of immunological status of African and European cord blood mononuclear cells. Pediatric Research 64, 631636.
Kuitunen, M., Kukkonen, K., Juntunen-Backman, K., Korpela, R., Poussa, T., Tuure, T., Haahtela, T. and Savilahti, E. (2009). Probiotics prevent IgE-associated allergy until age 5 years in caesarian-delivered children but not in total cohort. Journal of Allergy and Clinical Immunology 123, 335341.
Kusel, M. M., de Klerk, N. H., Kebadze, T., Vohma, V., Holt, P. G., Johnston, S. L. and Sly, P. D. (2007). Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. Journal of Allergy and Clinical Immunology 119, 11051110.
Labeaud, A. D., Malhotra, I., King, M. J., King, C. L. and King, C. H. (2009). Do antenatal parasite infections devalue childhood vaccination? PLoS Neglected Tropical Diseases 3, e442.
Lammie, P. J., Hitch, W. L., Walker Allen, E. M., Hightower, W. and Eberhard, M. L. (1991). Maternal filarial infection as risk factor for infection in children. Lancet 337, 10051006.
Lauener, R. P., Birchler, T., Adamski, J., Braun-Fahrlander, C., Bufe, A., Herz, U., von Mutius, E., Nowak, D., Riedler, J., Waser, M. and Sennhauser, F. H. (2002). Expression of CD14 and Toll-like receptor 2 in farmers’ and non-farmers’ children. Lancet 360, 465466.
Lenzi, J. A., Sobral, A. C., Araripe, J. R., Grimaldi, F. G. and Lenzi, H. L. (1987). Congenital and nursing effects on the evolution of Schistosoma mansoni infection in mice. Memoriás do Instituto Oswaldo Cruz 82 (Suppl 4), 257267.
Levy, O. (2005). Innate immunity of the human newborn: distinct cytokine responses to LPS and other Toll-like receptor agonists. Journal of Endotoxin Research 11, 113116.
Maas, T., Dompeling, E., van Schayck, C. P., Muris, J. W. M., Schönberger, H. J. A. M., Wesseling, G., Platts-Mills, T. A. E. and Knottnerus, J. A. (2005). Birth cohort studies on asthma development. Pediatric Asthma, Allergy and Immunology 18, 201215. doi: 10.1089/pai.2005.18.201.
Maizels, R. M. (2009). Exploring the immunology of parasitism–from surface antigens to the hygiene hypothesis. Parasitology 136, 15491564.
Maizels, R. M., Balic, A., Gomez-Escobar, N., Nair, M., Taylor, M. D. and Allen, J. E. (2004). Helminth parasites – masters of regulation. Immunological Reviews 201, 89116.
Malhotra, I., Mungai, P., Wamachi, A., Kioko, J., Ouma, J. H., Kazura, J. W. and King, C. L. (1999). Helminth- and Bacillus Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. Journal of Immunology 162, 68436848.
Malhotra, I., Mungai, P. L., Wamachi, A. N., Tisch, D., Kioko, J. M., Ouma, J. H., Muchiri, E., Kazura, J. W. and King, C. L. (2006). Prenatal T cell immunity to Wuchereria bancrofti and its effect on filarial immunity and infection susceptibility during childhood. Journal of Infectious Diseases 193, 10051013.
Malhotra, I., Ouma, J. H., Wamachi, A., Kioko, J., Mungai, P., Njzovu, M., Kazura, J. W. and King, C. L. (2003). Influence of maternal filariasis on childhood infection and immunity to Wuchereria bancrofti in Kenya. Infection and Immunity 71, 52315237.
Malhotra, I., Ouma, J., Wamachi, A., Kioko, J., Mungai, P., Omollo, A., Elson, L., Koech, D., Kazura, J. W. and King, C. L. (1997). In utero exposure to helminth and mycobacterial antigens generates cytokine responses similar to that observed in adults. The Journal of Clinical Investigation 99, 17591766.
May, K., Grube, M., Malhotra, I., Long, C. A., Singh, S., Mandaliya, K., Siegmund, W., Fusch, C., Schneider, H. and King, C. L. (2009). Antibody-dependent transplacental transfer of malaria blood-stage antigen using a human ex vivo placental perfusion model. PLoS One 4, e7986.
Melo, G. C., Reyes-Lecca, R. C., Vitor-Silva, S., Monteiro, W. M., Martins, M., Benzecry, S. G., Alecrim, M. G. and Lacerda, M. V. (2010). Concurrent helminthic infection protects schoolchildren with Plasmodium vivax from anemia. PLoS One 5, e11206.
Moore, S. E., Collinson, A. C., Tamba, N. P., Aspinall, R. and Prentice, A. M. (2006). Early immunological development and mortality from infectious disease in later life. Proceedings of the Nutrition Society 65, 311318.
Moore, S. E., Prentice, A. M., Wagatsuma, Y., Fulford, A. J., Collinson, A. C., Raqib, R., Vahter, M., Persson, L. A. and Arifeen, S. E. (2009). Early-life nutritional and environmental determinants of thymic size in infants born in rural Bangladesh. Acta Paediatrica 98, 11681175.
Neves, S. F., Eloi-Santos, S., Ramos, R., Rigueirinho, S., Gazzinelli, G. and Correa-Oliveira, R. (1999). In utero sensitization in Chagas’ disease leads to altered lymphocyte phenotypic patterns in the newborn cord blood mononuclear cells. Parasite Immunology 21, 631639.
Nookala, S., Srinivasan, S., Kaliraj, P., Narayanan, R. B. and Nutman, T. B. (2004). Impairment of tetanus-specific cellular and humoral responses following tetanus vaccination in human lymphatic filariasis. Infection and Immunity 72, 25982604.
Othman, A. A., Shoheib, Z. S., Saied, E. M. and Soliman, R. H. (2010). Congenital exposure to Schistosoma mansoni infection: impact on the future immune response and the disease outcome. Immunobiology 215, 101112.
Penders, J., Thijs, C., Vink, C., Stelma, F. F., Snijders, B., Kummeling, I., van den Brandt, P. A. and Stobberingh, E. E. (2006). Factors influencing the composition of the intestinal microflora in early infancy. Pediatrics 118, 511521.
Peroni, D. G., Pescollderungg, L., Piacentini, G. L., Rigotti, E., Maselli, M., Watschinger, K., Piazza, M., Pigozzi, R. and Boner, A. L. (2010). Immune regulatory cytokines in the milk of lactating women from farming and urban environments. Pediatric Allergy and Immunology 21, 977982.
Pfefferle, P. I., Buchele, G., Blumer, N., Roponen, M., Ege, M. J., Krauss-Etschmann, S., Genuneit, J., Hyvarinen, A., Hirvonen, M. R., Lauener, R., Pekkanen, J., Riedler, J., Dalphin, J. C., Brunekeef, B., Braun-Fahrlander, C., von Mutius, E. and Renz, H. (2010). Cord blood cytokines are modulated by maternal farming activities and consumption of farm dairy products during pregnancy: the PASTURE Study. Journal of Allergy and Clinical Immunology 125, 108115.
Pinelli, E., Willers, S. M., Hoek, D., Smit, H. A., Kortbeek, L. M., Hoekstra, M., de Jongste, J., van Knapen, F., Postma, D., Kerkhof, M., Aalberse, R., van der Giessen, J. W. and Brunekreef, B. (2009). Prevalence of antibodies against Ascaris suum and its association with allergic manifestations in 4-year-old children in The Netherlands: the PIAMA birth cohort study. European Journal of Clinical Microbiology and Infectious Diseases 28, 13271334.
Pinot de Moira, A., Fulford, A. J., Kabatereine, N. B., Ouma, J. H., Booth, M. and Dunne, D. W. (2010). Analysis of complex patterns of human exposure and immunity to Schistosomiasis mansoni: the influence of age, sex, ethnicity and IgE. PLoS Neglected Tropical Diseases 4, pii: e820.
Raqib, R., Alam, D. S., Sarker, P., Ahmad, S. M., Ara, G., Yunus, M., Moore, S. E. and Fuchs, G. (2007). Low birth weight is associated with altered immune function in rural Bangladeshi children: a birth cohort study. American Journal of Clinical Nutrition 85, 845852.
Riedler, J., Eder, W., Oberfeld, G. and Schreuer, M. (2000). Austrian children living on a farm have less hay fever, asthma and allergic sensitization. Clinical and Experimental Allergy 30, 194200.
Schaub, B., Liu, J., Hoppler, S., Schleich, I., Huehn, J., Olek, S., Wieczorek, G., Illi, S. and von Mutius, E. (2009). Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. Journal of Allergy and Clinical Immunology 123, 774782.
Schram-Bijkerk, D., Doekes, G., Douwes, J., Boeve, M., Riedler, J., Ublagger, E., von Mutius, E., Benz, M. R., Pershagen, G., van Hage, M., Scheynius, A., Braun-Fahrlander, C., Waser, M. and Brunekreef, B. (2005). Bacterial and fungal agents in house dust and wheeze in children: the PARSIFAL study. Clinical and Experimental Allergy 35, 12721278.
Sepp, E., Julge, K., Vasar, M., Naaber, P., Bjorksten, B. and Mikelsaar, M. (1997). Intestinal microflora of Estonian and Swedish infants. Acta Paediatrica 86, 956961.
Serazin, A. C., Shackelton, L. A., Wilson, C. and Bhan, M. K. (2010). Improving the performance of enteric vaccines in the developing world. Nature Immunology 11, 769773.
Sjogren, Y. M., Tomicic, S., Lundberg, A., Bottcher, M. F., Bjorksten, B., Sverremark-Ekstrom, E. and Jenmalm, M. C. (2009). Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses. Clinical and Experimental Allergy 39, 18421851.
Smits, H. H., Everts, B., Hartgers, F. C. and Yazdanbakhsh, M. (2010). Chronic helminth infections protect against allergic diseases by active regulatory processes. Current Allergy and Asthma Reports 10, 312.
Soboslay, P. T., Geiger, S. M., Drabner, B., Banla, M., Batchassi, E., Kowu, L. A., Stadler, A. and Schulz-Key, H. (1999). Prenatal immune priming in onchocerciasis-onchocerca volvulus-specific cellular responsiveness and cytokine production in newborns from infected mothers. Clinical and Experimental Immunology 117, 130137.
Specht, S. and Hoerauf, A. (2007). Does helminth elimination promote or prevent malaria? Lancet 369, 446447.
Standley, C. J., Kabatereine, N. B., Lange, C. N., Lwambo, N. J. S. and Stothard, J. R. (2010). Molecular epidemiology and phylogeography of Schistosoma mansoni around Lake Victoria. Parasitology 137, 19371949.
Steel, C., Guinea, A., McCarthy, J. S. and Ottesen, E. A. (1994). Long-term effect of prenatal exposure to maternal microfilaraemia on immune responsiveness to filarial parasite antigens. Lancet 343, 890893.
Stewardt, J. A., Chadwick, V. S. and Murray, A. (2005). Investigations into the influence of host genetics on the predominant in the faecal microflora of children. Journal of Medical Microbiology 54, 12391242.
Techau, M. E., Johansen, M. V., Aasted, B., Lind, P., Ornbjerg, N. and Oswald, I. P. (2007). Cytokine mRNA profiles in pigs exposed prenatally and postnatally to Schistosoma japonicum. Veterinary Research 38, 2536.
Thornton, C. A., Holloway, J. A., Popplewell, E. J., Shute, J. K., Boughton, J. and Warner, J. O. (2003). Foetal exposure to intact immunoglobulin E occurs via the gastrointestinal tract. Clinical and Experimental Allergy 33, 306311.
Tweyongyere, R., Mawa, P. A., Emojong, N. O., Mpairwe, H., Jones, F. M., Duong, T., Dunne, D. W., Vennervald, B. J., Katunguka-Rwakishaya, E. and Elliott, A. M. (2009). Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial. BMC Infectious Diseases 9, 32.
Tweyongyere, R., Mawa, P. A., Ngom-Wegi, S., Ndibazza, J., Duong, T., Vennervald, B. J., Dunne, D. W., Katunguka-Rwakishaya, E. and Elliott, A. M. (2008). Effect of praziquantel treatment during pregnancy on cytokine responses to schistosome antigens: results of a randomized, placebo-controlled trial. Journal of Infectious Diseases 198, 18701879.
Urban, J. F. Jr., Steenhard, N. R., Solano-Aguilar, G. I., Dawson, H. D., Iweala, O. I., Nagler, C. R., Noland, G. S., Kumar, N., Anthony, R. M., Shea-Donohue, T., Weinstock, J. and Gause, W. C. (2007). Infection with parasitic nematodes confounds vaccination efficacy. Veterinary Parasitology 148, 1420.
van den Biggelaar, A. H., Prescott, S. L., Roponen, M., Nadal-Sims, M. A., Devitt, C. J., Phuanukoonnon, S., Pomat, W., Tulic, M. K., Lehmann, D., Siba, P. M., Richmond, P. C. and Holt, P. G. (2009). Neonatal innate cytokine responses to BCG controlling T-cell development vary between populations. Journal of Allergy and Clinical Immunology 124, 544–50, 550.
van Riet, E., Adegnika, A. A., Retra, K., Vieira, R., Tielens, A. G., Lell, B., Issifou, S., Hartgers, F. C., Rimmelzwaan, G. F., Kremsner, P. G. and Yazdanbakhsh, M. (2007 a). Cellular and humoral responses to influenza in gabonese children living in rural and semi-urban areas. Journal of Infectious Diseases 196, 16711678.
van Riet, E., Hartgers, F. C. and Yazdanbakhsh, M. (2007 b). Chronic helminth infections induce immunomodulation: consequences and mechanisms. Immunobiology 212, 475490.
van Riet, E., Retra, K., Adegnika, A. A., Jol-van der Zijde, C. M., Uh, H. W., Lell, B., Issifou, S., Kremsner, P. G., Yazdanbakhsh, M., van Tol, M. J. and Hartgers, F. C. (2008). Cellular and humoral responses to tetanus vaccination in Gabonese children. Vaccine 26, 36903695.
Vekemans, J., Amedei, A., Ota, M. O., D'Elios, M. M., Goetghebuer, T., Ismaili, J., Newport, M. J., Del, P. G., Goldman, M., McAdam, K. P. and Marchant, A. (2001). Neonatal bacillus Calmette-Guerin vaccination induces adult-like IFN-gamma production by CD4+ T lymphocytes. European Journal of Immunology 31, 15311535.
Vekemans, J., Truyens, C., Torrico, F., Solano, M., Torrico, M. C., Rodriguez, P., onso-Vega, C. and Carlier, Y. (2000). Maternal Trypanosoma cruzi infection upregulates capacity of uninfected neonate cells To produce pro- and anti-inflammatory cytokines. Infection and Immunity 68, 54305434.
Von Ehrenstein, O. S., von Mutius, E., Illi, S., Baumann, L., Bohm, O. and von Kries, R. (2000). Reduced risk of hay fever and asthma among children of farmers. Clinical and Experimental Allergy 30, 187193.
Walk, S. T., Blum, A. M., Ewing, S. A., Weinstock, J. V. and Young, V. B. (2010). Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus. Inflammatory Bowel Disease 16, 18411849.
Wammes, L. J., Hamid, F., Wiria, A. E., de Gier, B., Sartono, E., Maizels, R. M., Luty, A. J., Fillie, Y., Brice, G. T., Supali, T., Smits, H. H. and Yazdanbakhsh, M. (2010). Regulatory T cells in human geohelminth infection suppress immune responses to BCG and Plasmodium falciparum. European Journal of Immunology 40, 437442.
Watanabe, K., Mwinzi, P. N., Black, C. L., Muok, E. M., Karanja, D. M., Secor, W. E. and Colley, D. G. (2007). T regulatory cell levels decrease in people infected with Schistosoma mansoni on effective treatment. American Journal of Tropical Medicine and Hygiene 77, 676682.
Webb, E. L., Mawa, P. A., Ndibazza, J., Kizito, D., Namatovu, A., Kyosiimire-Lugemwa, J., Nanteza, B., Nampijja, M., Muhangi, L., Woodburn, P. W., Akurut, H., Mpairwe, H., Akello, M., Lyadda, N., Bukusuba, J., Kihembo, M., Kizza, M., Kizindo, R., Nabulime, J., Ameke, C., Namujju, P. B., Tweyongyere, R., Muwanga, M., Whitworth, J. A. and Elliott, A. M. (2011). Effect of single-dose anthelmintic treatment during pregnancy on an infant's response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial. Lancet 377, 5262.
Wickens, K., Black, N. P., Stanley, T. V., Mitchell, E., Fitzharris, P., Tannock, G. W., Purdie, G., Crane, J. and The Probiotic Study Group. (2008). A differential effect of 2 probioticsin the prevention of eczema and atopy: A double blind, randomized, placebo-controlled trial. Journal of Allergy and Clinical Immunology 122, 788794.
Wickman, M., Kull, I., Pershagen, G. and Nordvall, S. L. (2002). The BAMSE project: presentation of a prospective longitudinal birth cohort study. Pediatric Allergy and Immunology 13 (Suppl 15), 1113.
Wilson, M. S. and Maizels, R. M. (2004). Regulation of allergy and autoimmunity in helminth infection. Clinical Reviews in Allergy and Immunology 26, 3550.
Wiria, A. E., Prasetyani, M. A., Hamid, F., Wammes, L. J., Lell, B., Ariawan, I., Uh, H. W., Wibowo, H., Djuardi, Y., Wahyuni, S., Sutanto, I., May, L., Luty, A. J., Verweij, J. J., Sartono, E., Yazdanbakhsh, M. and Supali, T. (2010). Does treatment of intestinal helminth infections influence malaria? Background and methodology of a longitudinal study of clinical, parasitological and immunological parameters in Nangapanda, Flores, Indonesia (ImmunoSPIN Study). BMC Infectious Diseases 10, 77.
Yazdanbakhsh, M. (1999). Common features of T cell reactivity in persistent helminth infections: lymphatic filariasis and schistosomiasis. Immunology Letters 65, 109115.
Yazdanbakhsh, M., Kremsner, P. G. and van Ree, R. R. (2002). Allergy, parasites, and the hygiene hypothesis. Science 296, 490494.
Yazdanbakhsh, M. and Luty, A. J. (2010). Wormy mothers, healthy babies: case closed or conundrum? Lancet 37, 68. doi: 10.1016/S0140-6736(10)62271-4.
Zhang, G., Rowe, J., Kusel, M., Bosco, A., McKenna, K., de Klerk, N., Sly, P. D. and Holt, P. G. (2009). Interleukin-10/interleukin-5 responses at birth predict risk for respiratory infections in children with atopic family history. American Journal of Respiratory and Critical Care Medicine 179, 205211.


Immunological footprint: the development of a child's immune system in environments rich in microorganisms and parasites



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed