The geohelminth (also known as intestinal or soil-transmitted helminth infections) parasites, Ascaris lumbricoides, Trichuris trichiura, hookworm, and Stronglyoides stercoralis, are common infectious diseases of childhood in tropical regions and are estimated to infect over 2 billion humans worldwide . Geohelminth infections are considered to cause significant morbidity in endemic areas through affects on nutrition, growth, and cognition affecting school performance .
Geohelminth infections induce an immune responses in humans characterized by elevated IgE levels, eosinophilia, and increased production of Th2 cytokines from peripheral blood leukocytes in response to stimulation by parasite antigen . While initial exposures to these parasites may be associated with enhanced allergic inflammatory responses to the parasite, in long-term infections and with repeated exposures, the host inflammatory response becomes more tightly controlled [4, 5]. Chronic infections have potent regulatory effects on anti-parasite inflammatory responses [5, 6], being associated with a modulated or 'modified' Th2 responses that may facilitate parasite survival but protect the host from damaging immune-mediated disease . The regulation of host immunity by chronic geohelminth infections may not just affect responses to parasite antigens but also other exogenous antigens such as the antigenic constituents of vaccines and aeroallergens. Such effects may contribute to the impaired vaccine immunogenicity [7–10] and decreased prevalence of allergic diseases [5, 11] reported from the rural Tropics.
The prevalence of allergic diseases has increased over the past 40 years and has reached epidemic levels in many developed countries such as the UK,  where they are now the most prevalent chronic diseases of childhood. International surveys showed that the prevalence of asthma varied 20-fold between countries, ranging 1.6-36.8% , and a surprising finding was the high prevalence of asthma in urban centres in Latin America with prevalence rates as high as those reported from traditional high prevalence countries [13, 14].
The causes of the high prevalence of allergic diseases in developed countries and the increasing prevalence in many developing countries are not known. The most widely accepted explanation is the 'hygiene hypothesis' that has attributed the increases in prevalence to a decline in infectious and microbial exposures during childhood [12, 15, 16]. This was initially explained in the context of the effects of early infectious exposures on the Th1/Th2 cytokine balance: a greater infectious burden induces stronger Th1 responses that counterbalanced the effects of pro-allergic Th2 responses. The observation that chronic helminth infections, that induce strong Th2 immunity, appeared to protect against allergy stimulated a re-working of the hypothesis to emphasize the role of immune regulatory mechanisms to control Th1 and Th2-mediated inflammation [17, 18]. Current thinking has emphasized the importance of multiple early infectious exposures including helminths in the induction of an immune regulatory network [6, 11, 19] that controls inflammatory responses to both Th1 and Th2-inducing stimuli. Important mediators of immune regulation may include subsets of regulatory immune cells [4, 20–23].
There is evidence from experimental animal models that intestinal and tissue helminth infections have deleterious effects on vaccine immune responses [24, 25]. Further, intestinal helminth infections have been shown to either enhance [26, 27] or suppress [27–29] allergic inflammatory responses in different experimental models of allergic inflammation. Studies conducted in children and adults indicate that concurrent geohelminth infections can suppress protective immune responses to both parenteral [30, 31] and oral  vaccines and are inversely associated with the prevalence of allergen skin test reactivity [5, 33] used as a marker for atopy or allergic sensitization. Geohelminth infections have also been associated with either a reduced  or increased prevalence [5, 34] of asthma depending on the prevalence and type of geohelminth parasite present.
Because the antecedents of allergic diseases are considered to occur in early life and most vaccines are administered during the first year of life before geohelminth infections are acquired, there is interest in the potential effects of maternal geohelminth infections on infant morbidity , and the effects of such exposures on vaccine immune responses during infancy [31, 35–37] and the development of allergic sensitization and allergic diseases [5, 35, 38, 39]. There is evidence that maternal helminth infections bias the fetal immune response  an effect that persists into infancy and that may interfere with protective immunity associated with vaccines such as BCG . Similarly, maternal ascariasis is associated with sensitization to A. lumbricoides antigens in newborns , although the long-term consequences of such sensitization are unclear.
The present study is investigating the potential effects of intrauterine and postnatal exposures to geohelminths on vaccine immune responses in infancy, and the development of allergic sensitization and allergic inflammatory diseases in childhood. The study will also investigate the immunological mechanisms by which such effects occur. The findings of this study have clear policy implications given that anthelmintic treatment of school-age children for the control of geohelminth infections is now a widely implemented public health strategy [42, 43], and the use of anthelmintic treatment during pregnancy has been advocated to improve the health of mothers and infants [43, 44]. Few opportunities, therefore, still exist to study the development of allergic disease in early childhood in the context of endemic geohelminth infections.
This study has been designed to investigate four specific hypotheses relating to the effect of maternal and infant infections with geohelminths on host immune responses and development of allergic inflammatory diseases: 1) chronic exposures to geohelminth infections (i.e. maternal geohelminth infections and infant geohelminth infections within the first 2 years of life) suppress immune responses to childhood vaccines; 2) chronic exposures to geohelminth infections suppress aeroallergen skin test reactivity; 3) chronic exposures to geohelminth infections protects against the development of eczema; and 4) chronic exposures to geohelminth infections protect against the development of asthma but non-chronic exposures (i.e. later childhood exposures occurring after 2 years in the absence of maternal geohelminth infections) increase the risk of asthma.