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The hygiene hypothesis, as originally proposed, postulated an inverse relation between the incidence of infectious diseases in early life and the subsequent development of allergies and asthma. New evidence from epidemiological, biological and genetic studies has significantly enlarged the scope of the hypothesis. It now appears probable that environmental 'danger' signals regulate the pattern of immune responses in early life. Microbial burden in general, and not any single acute infectious illness, is the main source of these signals. The latter interact with a sensitive and complex receptor system, and genetic variations in this receptor system may be an important determinant of inherited susceptibility to asthma and allergies.

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Urogenital schistosomiasis, due to Schistosoma haematobium, is one of the helminth infections of public health importance in sub-Saharan Africa where children carry the heaviest burden of infection. Treatment with the drug praziquantel is the only widely available tool for control. Current schistosome control programs are essentially school-based and exclude younger pre-school children. However, increasing reports of significant infection levels in this age group call for the inclusion of these young children in control programs. The hygiene hypothesis suggests that helminth infections, including schistosome infection, may protect against atopy, implying that helminth eradication may carry a detrimental burden of immune disorders. However, this conjecture is controversial. This study was designed to investigate the relationship between schistosome infection and atopy. In a comparative epidemiological approach between two schistosome endemic areas with differing infection levels, it is shown that atopy is inversely associated with current schistosome infection intensity but not with cumulative history of infection. This inverse relationship was subsequently shown to be associated with the levels of soluble CD23, the low affinity IgE receptor, but not with the polyclonal IgE stimulation. However, while praziquantel treatment was associated with an increase in schistosome-specific responses, a decline in atopic responses was observed in these communities, suggesting that treatment differentially affect anti-schistosome and atopic responses. In addition, the study has shown that praziquantel treatment of preschool age children increases, quantitatively and qualitatively, their schistosome-specific antibody responses purportedly associated with resistance to schistosome infection/reinfection.

Background Immune responses, including those to allergens, may be T helper (Th)2 skewed in newborns. In order to redress the fetal Th1/Th2 imbalance, Th1-stimulating factors, such as bacterial endotoxin, may be required. The increasing prevalence and severity of atopic diseases in industrialized countries, which are in marked contrast with the low prevalence of allergy among children in the formerly socialist countries of Europe, have been suggested to be caused by a reduced microbial stimulation. Aim To relate the endotoxin levels in house dust from two countries with a low (Estonia) and a high (Sweden) prevalence of allergy to the development of atopic disease and sensitization in the children during the first 2 years of life. Methods The study included 108 children from Tartu, Estonia and 111 children from Linköping, Sweden. Skin prick tests were performed at 3, 6, 12 and 24 months of age, and questionnaires were distributed to the families. At 24 months, a paediatrician examined the children. Dust samples were collected from mattresses and carpets and the endotoxin concentration was determined by a chromogenic Limulus assay. Results The endotoxin levels were higher in Estonian than in Swedish house dust (median levels 29 (range 0.25–280) and 14 (range 0.25–99) EU/mg dust, respectively, P < 0.001). Furthermore, the levels were inversely related to the development of atopic disease and sensitization in the Swedish, but not in the Estonian, children. Conclusions The low prevalence of atopic disease in Estonia may, at least in part, be related to the high endotoxin levels in this country. The findings support that high levels of endotoxin, or other bacterial products with Th1-stimulating properties, might protect children from developing atopic disease.

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Thesis (Master, Microbiology & Immunology) -- Queen's University, 2013-09-30 22:46:35.072