Do helminth infections underpin urban‐rural differences in risk factors for allergy‐related outcomes?

Abstract

Summary Background It is proposed that helminth exposure protects against allergy‐related disease, by mechanisms that include disconnecting risk factors (such as atopy) from effector responses. Objective We aimed to assess how helminth exposure influences rural‐urban differences in risk factors for allergy‐related outcomes in tropical low‐ and middle‐income countries. Methods In cross‐sectional surveys in Ugandan rural Schistosoma mansoni (Sm)‐endemic islands, and in nearby mainland urban communities with lower helminth exposure, we assessed risk factors for atopy (allergen‐specific skin prick test [SPT] reactivity and IgE [asIgE] sensitization) and clinical allergy‐related outcomes (wheeze, urticaria, rhinitis and visible flexural dermatitis), and effect modification by Sm exposure. Results Dermatitis and SPT reactivity were more prevalent among urban participants, urticaria and asIgE sensitization among rural participants. Pairwise associations between clinical outcomes, and between atopy and clinical outcomes, were stronger in the urban survey. In the rural survey, SPT positivity was inversely associated with bathing in lakewater, Schistosoma‐specific IgG4 and Sm infection. In the urban survey, SPT positivity was positively associated with age, non‐Ugandan maternal tribe, being born in a city/town, BCG scar and light Sm infection. Setting (rural vs urban) was an effect modifier for risk factors including Sm‐ and Schistosoma‐specific IgG4. In both surveys, the dominant risk factors for asIgE sensitization were Schistosoma‐specific antibody levels and helminth infections. Handwashing and recent malaria treatment reduced odds of asIgE sensitization among rural but not urban participants. Risk factors for clinical outcomes also differed by setting. Despite suggestive trends, we did not find sufficient evidence to conclude that helminth (Sm) exposure explained rural‐urban differences in risk factors. Conclusions and clinical relevance Risk factors for allergy‐related outcomes differ between rural and urban communities in Uganda but helminth exposure is unlikely to be the sole mechanism of the observed effect modification between the two settings. Other environmental exposures may contribute significantly.

Urban-rural differences in immune responses to mycobacterial and tetanus vaccine antigens in a tropical setting: A role for helminths?

“…The “rural survey” was the outcomes survey (September 2015 – August 2016) following three years of the Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA; ISRCTN47196031), a cluster-randomised trial of community-based standard versus intensive anthelminthic treatment, described previously [ 24 , 26 ]. The “urban survey” (September 2016 – September 2017) was designed purposely to collect data for comparison with the rural survey [ 28 ]. Urban survey participants were not randomised to standard versus intensive anthelminthic intervention; however, all other procedures were designed to be equivalent between the two surveys.…”

“…We surveyed helminth-endemic Lake Victoria islands of Koome, Uganda [ [24] , [25] , [26] , [27] ] and proximate mainland urban communities with lower helminth exposure [ 28 ] as part of a set of studies on helminths and allergy-related outcomes. Vaccine responses were measured as a secondary outcome in these surveys.…”

Association of bacterial load in drinking water and allergic diseases in childhood

“…Our findings that early‐life exposure to high bacterial content in drinking water is associated with a reduced risk of asthma and other atopic phenotypes lend further support to the hygiene hypothesis 21,22 and add to the growing number of potentially important exposures which may explain the lower prevalence of allergic diseases in rural environments 16,17,23,24 . It is becoming increasingly evident that biodiversity of microbial exposure provides resilience against asthma and allergies 25 .…”

Contrasting impact of rural, versus urban, living on glucose metabolism and blood pressure in Uganda

“…The metabolic outcomes survey was conducted between April and November 2017 after four years of the anthelminthic intervention 22 . The survey in the urban setting was deliberately formulated to collect data in parallel with the LaVIISWA outcome surveys to enable rural-urban comparison of allergy-related 23,24 and metabolic outcomes. It was conducted in Entebbe municipality, Wakiso district, Uganda from September 2016 to September 2017.…”