Infection-exposure in infancy is associated with reduced allergy-related disease in later childhood in a Ugandan cohort.

Angela Nalwoga,Swaib A Lule,Jonathan Levin,Emily L Webb,Lawrence Lubyayi,Alison M Elliott,Harriet Mpairwe,Gyaviira Nkurunungi

doi:10.7554/elife.66022

Abstract

Lack of early infection-exposure has been associated with increased allergy-related disease (ARD) susceptibility. In tropical Africa, little is known about which infections contribute to development of ARDs, and at which time. We used latent class analysis to characterise the early infection-exposure of participants in a Ugandan birth cohort and assessed ARDs in later childhood. Of 2345 live births, 2115 children (90%) had data on infections within the first year of life while 1179 (50%) had outcome data at 9 years. We identified two latent classes of children based on first-year infection-exposure. Class 1 (32% membership), characterised by higher probabilities for malaria (80%), diarrhoea (76%), and lower respiratory tract infections (LRTI) (22%), was associated with lower prevalence of wheeze, eczema, rhinitis, and Dermatophagoides skin prick test (SPT) positivity at 9 years. Based on 5-year cumulative infection experience, class 1 (31% membership), characterised by higher probabilities for helminths (92%), malaria (79%), and LRTI (45%), was associated with lower probabilities of SPT positivity at 9 years. In this Ugandan birth cohort, early childhood infection-exposure, notably to malaria, helminths, LRTI, and diarrhoea, is associated with lower prevalence of atopy and ARDs in later childhood. This work was supported by several funding sources. The Entebbe Mother and Baby Study (EMaBS) was supported by the Wellcome Trust, UK, senior fellowships for AME (grant numbers 064693, 079110, 95778) with additional support from the UK Medical Research Council. LL is supported by a PhD fellowship through the DELTAS Africa Initiative SSACAB (grant number 107754). ELW received funding from MRC Grant Reference MR/K012126/1. SAL was supported by the PANDORA-ID-NET Consortium (EDCTP Reg/Grant RIA2016E-1609). HM was supported by the Wellcome's Institutional Strategic Support Fund (grant number 204928/Z/16/Z).

Highlights

Lack of early infection-exposure has been associated with increased allergy-related disease (ARD) susceptibility later in life, the so-c alled ‘hygiene hypothesis’ (Strachan, 1989; Bloomfield et al, 2006; Schaub et al, 2006) or ‘old friends hypothesis’ (Rook, 2010; Rook, 2011)
52 % of the children were male, 90 % were of normal birth weight, 57 % were second to fourth born; maternal characteristics included 55 % with none/primary education, 3 % with history of asthma, 3 % with history of eczema, 44 % with hookworm infections, 21 % with Mansonella perstans, 18 % with S. mansoni, and 12 % with Strongyloides stercoralis (Mpairwe et al, 2014); 1214 children were seen at 9 years, 52 % of whom were male and 1179 had data collected on atopy and ARDs (Lule et al, 2017)
Prevalence of childhood infections during the first five years of life Diarrhoea and lower respiratory tract infections (LRTI) were common in the first year of life but declined by the fifth year, malaria was most common in the second year of life and declined, URTI were consistently common throughout the first 5 years, helminth infections increased slightly, herpes simplex virus (HSV) increased steadily over the 5 years while CMV and norovirus seropositivity increased to over 85 % by the second year (Figure 3)

Summary

Introduction

Lack of early infection-exposure has been associated with increased allergy-related disease (ARD) susceptibility later in life, the so-c alled ‘hygiene hypothesis’ (Strachan, 1989; Bloomfield et al, 2006; Schaub et al, 2006) or ‘old friends hypothesis’ (Rook, 2010; Rook, 2011). Despite increasing evidence indicating inverse relationships between pathogen-exposure and atopy, other studies suggest no association (Jarvis et al, 2004; Cooper et al, 2003) or even increased risk of atopy following a combination of early infections (Seaton and Devereux, 2000; Bager et al, 2002) It remains unclear which infections, and at which times, possibly contribute to reducing the risk of atopy or ARDs. There is a paucity of data from countries in tropical Africa where the infectious diseases burden remains high, yet prevalence of ARDs remains low, despite reasonably high prevalence of atopy.

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Results

Conclusion