Effects of helminth co-infections on atopy, asthma and cytokine production in children living in a poor urban area in Latin America

Alcântara-Neves et al. BMC Research Notes 2014, 7:817 http://www.biomedcentral.com/1756-0500/7/817 RESEARCH ARTICLE Open Access Effects of helminth co-infections on atopy, asthma and cytokine production in children living in a poor urban area in Latin America Neuza Maria Alcântara-Neves1,9*, Gabriela de S G Britto1, Rafael Valente Veiga1, Camila A Figueiredo1, Rosimeire Leovigildo Fiaccone2,3, Jackson S da Conceição3, Álvaro Augusto Cruz4, Laura Cunha Rodrigues5, Philip John Cooper6,7, Lain C Pontes-de-Carvalho8 and Maurício Lima Barreto3 Abstract Background: Helminths are modulators of the host immune system, and infections with these parasites have been associated with protection against allergies and autoimmune diseases. The human host is often infected with multiple helminth parasites and most studies to date have investigated the effects of helminths in the context of infections with single parasite or types of parasites (e.g. geohelminths). In this study, we investigated how co-infections with three nematodes affect markers of allergic inflammation and asthma in children. We selected Ascaris lumbricoides and Trichuris trichiura, two parasites that inhabit the human intestine and Toxocara spp (Toxocara canis and/or T. cati), intestinal roundworms of dogs and cats that cause systemic larval infection in humans. These parasites were selected as the most prevalent helminth parasites in our study population. Results: 36.4% of children were infected with one parasite; 12.7% with 2 and 5.2% with 3. Eosinophilia >4% and >10% was present in 74.3% and 25.5% of the children, respectively. Total IgE > 200 IU/mL, sIgE ≥ 0.70 kU/L and SPT positivity were present in 59.7%, 37.1% and 30% of the children, respectively. 22.7% had recent asthma (12.0% non-atopic and 10.7% atopic). Helminth infections were associated in a dose-dependent way to decrease in the prevalence of SPT and increase in eosinophilia, total IgE, and the production of the regulatory cytokine IL-10 by unstimulated peripheral blood leukocytes. No association with asthma was observed. Conclusions: Helminth co-infections in this population were associated with increased markers of the Th2 immune response, and with a host immune regulatory phenotype that may suppress allergic effector responses such as immediate hypersensitivity reactions in the skin. Keywords: Helminth infections, Eosinophilia, Total IgE, Atopy, Asthma, Cytokines, Treg cells Background Infections with helminths that inhabit the vasculature or tissues of the host such as Schistosoma spp. and filarial parasites have potent modulatory effects on the immune system of humans and experimental animals [1]. In children, such infections have been associated with the suppression of the immune response to vaccines [2], decreased skin * Correspondence: 1 Departamento de Ciências da Biointeração, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil 9 Address: Instituto de Ciências da Saúde, Universidade Federal da Bahia, Avenida Reitor Miguel Calmon, sem n°, Canela, CEP – 40110-100 Salvador, Bahia, Brazil Full list of author information is available at the end of the article hypersensitivity to aeroallergens [3,4], a milder form of asthma [5], and a reduction of inflammation in an animal model of autoimmune disease [6]. Although some studies in humans have shown that infections with intestinal helminths such as Ascaris lumbricoides and Trichuris trichiura are associated with immune modulation [7] and the downregulation of atopy [8], studies of the effect of these parasites on asthma prevalence have been inconsistent, with some studies demonstrating a reduced prevalence [9], others no association [10], and others an increased risk [11,12]. These discrepancies have been attributed to differences between populations with respect to the parasites present, timing of first infections, © 2014 Alcântara-Neves et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Alcântara-Neves et al. BMC Research Notes 2014, 7:817 http://www.biomedcentral.com/1756-0500/7/817 size of worm burdens and infection chronicity [1]. For example, Rodrigues and collaborators [8] showed that children who had infections with T. trichiura in early childhood had a reduced prevalence of skin test reactivity to aeroallergens later in childhood, while in the same population, Alcântara-Neves and collaborators [11] reported a positive association between T. trichiura infection and wheeze symptoms when the children were of preschool age. The prevalence of infection with intestinal helminths is decreasing in large cities of developing countries, where sanitation has been introduced [13]. However, infections with Toxocara spp. (T. canis and T. cati) are highly prevalent in such environments, since they are not affected by sanitation. A decrease in the prevalence of toxocariasis depends on the control of stray animals and antihelminthic treatment of pets to prevent the exposure of children to this parasite, neither of which are easy to achieve [14]. In the Brazilian city of Salvador, where the present study was done, Datolli and collaborators [15] found a Toxocara infection seroprevalence of 46% in blood donors who were not infected with intestinal helminths. Seropositive individuals were more likely to have elevated allergic markers of blood eosinophilia and total IgE. Previous studies have indicated that individuals with toxocariasis may have an increased risk of atopy and asthma [16]. We have shown previously that pathogens causing chronic infections, including intestinal helminths [17] and Toxocara spp [18], can modulate atopy in children, but not wheezing. We have also shown that Ascaris lumbricoides and Trichuris trichiura in this population are positively associated to IL-10 production by non-stimulated whole blood cells [7]. In the present study, we investigated the effects of single and co-infections with intestinal parasites (A. lumbricoides and T. trichiura) and Toxocara spp. on the following outcomes: blood eosinophils total and allergen-specific IgE, skin reactivity to aeroallergen, atopic and non-atopic asthma and cytokine responses, in children living in poor neighborhoods of a Brazilian city. Results Frequencies of study variables Of the 1,445 children enrolled in this study, 1,271 with complete outcome data were analyzed. Analyses for associations with eosinophilia were done for 1,155 of the latter with data for this variable. No statistically significant differences were seen between the 174 excluded children and thos (...truncated)