Helminth Therapy: A New Tool for Treatment of Allergic Diseases
Dalia S. Ashour* Medical Parasitology Department, Faculty of Medicine, Tanta University, Gharbyia, Egypt
Abstract
The reduced prevalence of allergic disorders in patients infected with helminths and in experimental animal models has prompted the concept of helminth therapy (HT). It was the successful outcome of cooperation between parasitologists, immunologists and epidemiologists, based on the host-parasite immune regulatory interactions. This new approach aims at helping allergic patients especially those with unmet medical needs such as treating severe steroid-resistant asthmatic patients. Although HT is successful in regulating the proinflammatory responses in the host, it may predispose to possible risk of side effects of live worm infections. Thus, it would be more practical to isolate and characterize specific helminth-derived products. Epidemiological and experimental studies of HT in allergic diseases were very promising. However, there are some considerations that should be taken in account for further clinical trials. This chapter highlights the interaction between helminth infection and allergic diseases, the current status of HT, its challenges and future perspectives.
Keywords: Airway hypersensitivity, Allergic disorders, Clinical trials, Helminth therapy, Helminth-derived products, IL-10, Immune regulation, Necator americanus larvae, Self-treatment, Treg cells, Trichuris suis ova.
* Corresponding author: Dalia S. Ashour: Medical Parasitology Department, Faculty of Medicine, Tanta University, Gharbyia, Egypt; Tel: 00201093727625; E-mail: [email protected] INTRODUCTION
Allergic diseases are increasing in the recent decades especially in Western industrialized countries on the contrary to their low prevalence in the developing countries which may be attributed to low exposure to infectious agents including helminths [1].
An inverse global distribution of allergic and autoimmune diseases and helminths infections is noticed [2-4]. Helminths are mainly prevalent in sub-Saharan Africa, Asia, and South America [5]. While allergic diseases are described more in the developed countries [6]. Control of helminth infections in industrialized countries in the past three decades had a great influence on the increased
incidence of allergic disorders [7]. Additionally, epidemiological studies have reported that helminths-infected populations showed decreased prevalence of some immunopathological disorders; either Th1-related autoimmune diseases or aberrant Th2-related allergic diseases. Thus, it was suggested that the immune system has coevolved to function in the presence of the immunoregulatory arm of helminth infections, while this immunomodulatory component that would normally prevent allergic and autoimmune diseases become weakened in the absence of helminths [8, 9]. The most accepted explanation is the hygiene hypothesis.
Hygiene Hypothesis
Strachan, in 1989, hypothesized that increased hygiene that results in reduced exposure to infections is responsible for the increased allergic disorders. Currently, this hypothesis is known as the âhygiene hypothesisâ [10]. In addition to improved personal hygiene and health care, urbanization decreased the exposure to infectious agents and their products. Consequently, the insufficient stimulation of the immune system by different organisms allows uncontrolled expression of inflammatory molecules [4], thus explaining the increased prevalence inflammatory bowel diseases (e.g., Crohnâs disease and ulcerative colitis), autoimmune disorders (e.g., type 1 diabetes and multiple sclerosis) [11] and allergic diseases in Western countries [12].
Helminths induce T helper (Th)2 immune response, thus, lack of childhood infections allow the expansion of the Th2 responses towards different allergens. Hence came the idea that helminth infection can protect from allergic disorders [13]. It is clear now that the interaction between helminth infection and allergy involves T regulatory (Treg) cells that dampen both Th1 and Th2 effector responses [14]. Therefore, the hygiene hypothesis has been extended to include the role of these cells and other immunomodulatory mechanisms involved in the interaction between helminth infection and allergy [1].
This coincidence between helminth infections and the decreased allergic disorders in patients and animal models has evolved the concept of helminth therapy (HT) and the search for helminths molecules with anti-allergic and anti-inflammatory potential and also exploring the mechanisms underlying the interface between allergy and helminth infections.
Allergy
Allergy is a hypersensitivity immune response initiated by exposure to allergens. Allergic disorders include asthma, allergic rhinoconjunctivitis, skin allergies, food and drug allergies and anaphylaxis [15]. Rising prevalence of atopic disorders has been described in the developed countries since the end of World War II [16] and currently constitutes a public health problem affecting at least one-fifth of the world's population [1, 17].
Approximately, 300 million people suffer from asthma worldwide [18]. According to the British Allergy Foundation, 1 in 3 people suffer from allergy at some time in their lives in the United Kingdom [19]. The incidence of asthma varies between 5 and 17% (average 8%) and allergic rhinitis ranges between 23 and 44% (average 30%) in 12 European countries [20]. An average increase in the prevalence of childhood asthma of 4.3% per year from 1980 to 1996 in the United States [21]. On the other hand, decreased prevalence...