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      Anthelminthic treatment during pregnancy is associated with increased risk of infantile eczema: randomised-controlled trial results

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          Abstract

          Background

          Allergy is commoner in developed than in developing countries. Chronic worm infections show inverse associations with allergy, and prenatal exposures may be critical to allergy risk.

          Objective

          To determine whether anthelminthic treatment during pregnancy increases the risk of allergy in infancy.

          Methods

          A randomised, double-blind, placebo-controlled trial on treatment in pregnancy with albendazole versus placebo and praziquantel versus placebo was conducted in Uganda, with a 2 × 2 factorial design; 2507 women were enrolled; infants’ allergy events were recorded prospectively. The main outcome was doctor-diagnosed infantile eczema.

          Results

          Worms were detected in 68% of women before treatment. Doctor-diagnosed infantile eczema incidence was 10.4/100 infant years. Maternal albendazole treatment was associated with a significantly increased risk of eczema [Cox HR (95% CI), p: 1.82 (1.26–2.64), 0.002]; this effect was slightly stronger among infants whose mothers had no albendazole-susceptible worms than among infants whose mothers had such worms, although this difference was not statistically significant. Praziquantel showed no effect overall but was associated with increased risk among infants of mothers with Schistosoma mansoni [2.65 (1.16–6.08), interaction p = 0.02]. In a sample of infants, skin prick test reactivity and allergen-specific IgE were both associated with doctor-diagnosed eczema, indicating atopic aetiology. Albendazole was also strongly associated with reported recurrent wheeze [1.58 (1.13–2.22), 0.008]; praziquantel showed no effect.

          Conclusions

          The detrimental effects of treatment suggest that exposure to maternal worm infections in utero may protect against eczema and wheeze in infancy. The results for albendazole are also consistent with a direct drug effect. Further studies are required to investigate mechanisms of these effects, possible benefits of worms or worm products in primary prevention of allergy, and the possibility that routine deworming during pregnancy may promote allergic disease in the offspring.

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          Most cited references25

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          Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee.

          Systematic international comparisons of the prevalences of asthma and other allergic disorders in children are needed for better understanding of their global epidemiology, to generate new hypotheses, and to assess existing hypotheses of possible causes. We investigated worldwide prevalence of asthma, allergic rhinoconjunctivitis, and atopic eczema. We studied 463,801 children aged 13-14 years in 155 collaborating centres in 56 countries. Children self-reported, through one-page questionnaires, symptoms of these three atopic disorders. In 99 centres in 42 countries, a video asthma questionnaire was also used for 304,796 children. We found differences of between 20-fold and 60-fold between centres in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema, with four-fold to 12-fold variations between the 10th and 90th percentiles for the different disorders. For asthma symptoms, the highest 12-month prevalences were from centres in the UK, Australia, New Zealand, and Republic of Ireland, followed by most centres in North, Central, and South America; the lowest prevalences were from centres in several Eastern European countries, Indonesia, Greece, China, Taiwan, Uzbekistan, India, and Ethiopia. For allergic rhinoconjunctivitis, the centres with the highest prevalences were scattered across the world. The centres with the lowest prevalences were similar to those for asthma symptoms. For atopic eczema, the highest prevalences came from scattered centres, including some from Scandinavia and Africa that were not among centres with the highest asthma prevalences; the lowest prevalence rates of atopic eczema were similar in centres, as for asthma symptoms. The variation in the prevalences of asthma, allergic rhinoconjunctivitis, and atopic-eczema symptoms is striking between different centres throughout the world. These findings will form the basis of further studies to investigate factors that potentially lead to these international patterns.
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            Allergy, parasites, and the hygiene hypothesis.

            The increase of allergic diseases in the industrialized world has often been explained by a decline in infections during childhood. The immunological explanation has been put into the context of the functional T cell subsets known as T helper 1 (TH1) and T helper 2 (TH2) that display polarized cytokine profiles. It has been argued that bacterial and viral infections during early life direct the maturing immune system toward TH1, which counterbalance proallergic responses of TH2 cells. Thus, a reduction in the overall microbial burden will result in weak TH1 imprinting and unrestrained TH2 responses that allow an increase in allergy. This notion is contradicted by observations that the prevalence of TH1-autoimmune diseases is also increasing and that TH2-skewed parasitic worm (helminth) infections are not associated with allergy. More recently, elevations of anti-inflammatory cytokines, such as interleukin-10, that occur during long-term helminth infections have been shown to be inversely correlated with allergy. The induction of a robust anti-inflammatory regulatory network by persistent immune challenge offers a unifying explanation for the observed inverse association of many infections with allergic disorders.
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              Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10.

              Most of the effort directed at understanding the role infections have in preventing allergy has focused on bacteria and viruses and their ability to divert the immune system towards T-helper-1 responses and away from proallergic T-helper-2 responses. However, helminth infections, highly prevalent in large parts of the developing world, where allergy is uncommon, stimulate strong T-helper-2 responses. We investigated the influence of chronic helminth infections on the prevalence of atopy and aimed to understand the relation at a detailed immunological level. 520 Gabonese schoolchildren were tested for skin reaction to house-dust mite and other allergens, for Schistosoma haematobium eggs in urine, and for microfilariae in blood samples. Total and mite-specific IgE antibodies were measured. A subsample selected on the basis of their skin test to house-dust mite received detailed immunological investigations. Children with urinary schistosomiasis had a lower prevalence of a positive skin reaction to house-dust mite than those free of this infection (odds ratio 0.32 [95% CI 0.16-0.63]). The degree of sensitisation to house-dust mite could not explain this difference in skin-prick positivity. Schistosome-antigen-specific concentrations of interleukin-10 were significantly higher in infected children, and higher specific concentrations of this anti-inflammatory cytokine were negatively associated with the outcome of skin-test reactivity to mite (0.53 [0.30-0.96]). No association between polyclonal IgE antibodies and skin-test results was found. The anti-inflammatory cytokine, interleukin-10, induced in chronic schistosomiasis, appears central to suppressing atopy in African children.
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                Author and article information

                Journal
                Pediatr Allergy Immunol
                pai
                Pediatric Allergy and Immunology
                Blackwell Publishing Ltd
                0905-6157
                1399-3038
                May 2011
                : 22
                : 3
                : 305-312
                Affiliations
                [1 ]simpleMRC/UVRI Uganda Research Unit on AIDS Entebbe, Uganda
                [2 ]simpleLondon School of Hygiene and Tropical Medicine London, UK
                [3 ]simpleEntebbe Hospital Entebbe, Uganda
                [4 ]simpleDepartment of Pathology, University of Cambridge Cambridge, UK
                Author notes
                Harriet Mpairwe, MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda. Tel.: +256 414 320042 Fax: +256 414 321137 E-mail: mpairweus@ 123456yahoo.com

                Trial registration: controlled-trials.com; Identifier ISRCTN32849447.

                Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms.

                Article
                10.1111/j.1399-3038.2010.01122.x
                3130136
                21255083
                bb375178-f1bc-439e-b07a-d3d71d54e111
                © 2011 John Wiley & Sons A/S

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 21 November 2010
                Categories
                Original Articles
                Skin and Eye Diseases

                Pediatrics
                praziquantel,pregnancy,clinical trial,albendazole,infantile eczema,worms
                Pediatrics
                praziquantel, pregnancy, clinical trial, albendazole, infantile eczema, worms

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