Impact of early life exposures to geohelminth infections on the development of vaccine immunity, allergic sensitization, and allergic inflammatory diseases in children living in tropical Ecuador: the ECUAVIDA birth cohort study

Philip J Cooper,Martha E Chico,Irene Guadalupe,George E Griffin,David P Strachan,Edward Mitre,Mauricio L Barreto,Laura C Rodrigues,Carlos A Sandoval,Thomas Ae Platts-Mills

doi:10.1186/1471-2334-11-184

Abstract

BackgroundGeohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease.Methods/DesignA cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also.DiscussionThe study will provide information on the potential effects of early exposures to geohelminths (during pregnancy and the first 2 years of life) on the development of vaccine immunity and allergy. The data will inform an ongoing debate of potential effects of geohelminths on child health and will contribute to policy decisions on new interventions designed to improve vaccine immunogenicity and protect against the development of allergic diseases.Trial registrationCurrent Controlled Trials ISRCTN41239086.

Highlights

Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children
The regulation of host immunity by chronic geohelminth infections may not just affect responses to parasite antigens and other exogenous antigens such as the antigenic constituents of vaccines and aeroallergens. Such effects may contribute to the impaired vaccine immunogenicity [7,8,9,10] and decreased prevalence of allergic diseases [5,11] reported from the rural Tropics
The mechanisms are: 1) Th2 polarizationmeasured by the ratio of IL-5 to IFN-g protein produced by peripheral blood leukocytes (PBLs); 2) immune homeostasis-production of IL-10 spontaneously in 5-day PBL cultures [50]; 3) immune suppression-antigen-specific suppression measured by frequencies of IL-10+CD4 + T cells or IL-10 production by antigen-stimulated PBLs [51,52,53] or ‘bystander suppression’ measured by IL10 production by A. lumbricoides antigen-stimulated PBLs [54,55]; 4) immune maturation-capacity of PBLs to produce IFN-g to sub-optimal stimulus with Staphylococcal enterotoxin B (SEB); and 5) pro-inflammatory responses-IL-8 production by PBLs stimulated with LPS [56], and quantities of IL-17, IFN-g, and IL-5 produced by SEB-stimulated PBLs

Summary

Introduction

Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. The regulation of host immunity by chronic geohelminth infections may not just affect responses to parasite antigens and other exogenous antigens such as the antigenic constituents of vaccines and aeroallergens. Such effects may contribute to the impaired vaccine immunogenicity [7,8,9,10] and decreased prevalence of allergic diseases [5,11] reported from the rural Tropics

Methods

Findings

Discussion

Conclusion