Maternal hookworm modifies risk factors for childhood eczema: results from a birth cohort in Uganda

Abstract

BackgroundWorms may protect against allergy. Early-life worm exposure may be critical, but this has not been fully investigated.ObjectivesTo investigate whether worms in pregnancy and in early childhood are associated with childhood eczema incidence.MethodsThe Entebbe Mother and Baby Study, an anthelminthic treatment trial, enrolled pregnant women between 2003 and 2005 in Uganda. Mothers were investigated for worms during pregnancy and children annually. Eczema was doctor-diagnosed from birth to age five years. A planned observational analysis was conducted within the trial cohort to investigate associations between worms and eczema.ResultsData for 2345 live-born children were analysed. Hookworm was the most prevalent maternal worm (45%). Childhood worms were less prevalent. Eczema incidence was 4.68/100 person-years. Maternal hookworm was associated with reduced eczema incidence [adjusted hazard ratio (95% confidence interval), p-value: 0.71(0.51–0.99), 0.04] and modified effects of known risk factors for eczema: Dermatophagoides-specific IgE in children was positively associated with eczema incidence if the mother had no hookworm [2.72(1.11–6.63), 0.03], but not if the mother had hookworm [0.41(0.10–1.69), 0.22], interaction p-value = 0.03. Similar interactions were seen for maternal history of eczema {[2.87(1.31–6.27, 0.008) vs. [0.73(0.23–2.30), 0.60], interaction p-value = 0.05}, female gender {[1.82(1.22–2.73), 0.004 vs. [0.96(0.60–1.53), 0.87], interaction p-value = 0.04} and allergen-specific IgE. ChildhoodTrichuris trichiura and hookworm were inversely associated with eczema.ConclusionsMaternal hookworm modifies effects of known risk factors for eczema. Mechanisms by which early-life worm exposures influence allergy need investigation. Worms or worm products, and intervention during pregnancy have potential for primary prevention of allergy.

Effects of treating helminths during pregnancy and early childhood on risk of allergy‐related outcomes: Follow‐up of a randomized controlled trial

“…This implies that possible effects of helminths are not mediated by a reduction in the specific IgE response to allergens. Indeed, within this cohort and elsewhere, it has been shown that in the presence of helminths, the link between asIgE and ARD is suppressed and, similarly, the link between asIgE and histamine release …”

Parasites and allergy: Observations from Africa

“…However, the effects of anthelmintic treatment in pregnancy on clinical asthma could not be measured due to the small number of children who developed asthma in this cohort . This birth cohort also showed that the children's own helminth infections in early life (hookworm and Trichuris ) were associated with a reduced risk of eczema in later childhood . Furthermore, dust mite‐specific IgE in childhood was strongly associated with eczema if the mother had no hookworm [adjusted HR (95% CI), P ‐value: 2.72 (1.11‐6.63), P = 0.03] but not if the mother had hookworm during pregnancy [0.41 (0.10‐1.69), P = 0.22; interaction P ‐value = 0.03] .…”

“…This study, conducted in Uganda, was a randomized placebo‐controlled trial of albendazole vs placebo and praziquantel vs placebo (2 × 2 factorial design) in pregnancy, followed by albendazole vs placebo for the offspring between 15 months to 5 years of age . This investigation showed that anthelmintic treatment during pregnancy resulted in increased risk of eczema in infancy in the first 5 years and that maternal hookworm during pregnancy was associated with reduced risk of eczema in infancy and in the first 5 years of life . Albendazole treatment in early childhood was not associated with allergy‐related outcomes .…”

Breastfeeding and perinatal exposure, and the risk of asthma and allergies

“…Hookworm infection in pregnant Ugandan mothers (N ¼ 2345) reduced the risk of childhood eczema up to 5 years (hazard ratio: 0.71; 0.51-0.99) and, interestingly modified the presence of specific IgE to dust mite (Dermatophagoides). Although some children with hookworm infected mothers did develop eczema, these children had less risk (lower prevalence) of specific IgE sensitization to dust mite than children with eczema whose mothers had not been infected with hookworm during pregnancy [9]. In contrast, febrile and gynaecological infections during pregnancy were found to increase the risk of eczema [10] and an increased risk of infant wheeze was found in the children of asthmatic mothers with proven viral respiratory infections during pregnancy [11].…”