Fatores associados à esquistossomose e à modulação da reatividade alérgica em indivíduos infectados com baixa carga parasitária no norte de Minas Gerais, antes e após um ano de tratamento com Praziquantel

Abstract

Helminths and allergies are strong inducers of the Th2 immune response. In schistosomiasis, this response is stimulated by egg antigens and is usually accompanied by induction of regulatory mechanisms, resulting in a modulated chronic infection, whereas in allergic diseases the Th2 response is not modulated. Many epidemiological studies report inverse associations between allergy and helminths; however, this association depends on the species of the parasite, its intensity and chronicity. In order to verify the effect of the parasite load and anthelmintic treatment on the induction of allergic modulation, the present work carried out a population-based study to evaluate epidemiological characteristics of S. mansoni infection in residents of Brejo do Amparo, Januária- MG and its association with allergic reactivity. Initially (time 0 – T0), residents answered a socioeconomic questionnaire and provided stool samples to perform a combination of parasitological (Kato-Katz, Helmintex, Saline Gradient and HPJ) and molecular tests for the diagnosis of schistosomiasis, and blood samples for blood count, evaluation of immune response and allergic reactivity to dust antigens. Those infected with S. mansoni were treated and reassessed after 30 days, 3 and 6 months to confirm cure, and after 12 months (T12) the entire T0 population was reassessed. At T0, 140 individuals were infected for S. mansoni (54%), and the load intensity was low (median = 4), with 108 of them eliminating ≤12 eggs per gram of feces (OPG). Regarding immunological alterations, it was observed that the frequency of responders to the cytokine IL-17 and the serum concentration of CCL3 were significantly higher among those infected with S. mansoni, while those infected with a load ≤12 OPG had significantly higher serum levels of IL-27. Logistic regression models demonstrated that residents with higher serum levels of IL-17 are about five times more likely to be infected with S. mansoni, while individuals aged >40 years are about five times less likely to have the infection more intense. The evaluated population consists of a very homogeneous group, subjected to precarious sanitary and socioeconomic conditions, which has a similar impact on the transmission of schistosomiasis. In this population, 47 (24%) individuals had IgE reactive to common allergens in house dust, and the median intensity of reactivity was 7UI/mL. Multivariate analysis showed that both the prevalence and intensity of S. mansoni infection were negatively associated with allergic reactivity. However, very low parasite loads (≤12 OPG) were insufficient to trigger modulatory mechanisms, and the inverse relationship between allergy and schistosomiasis was demonstrated only in patients with a higher parasite load (≥ 12 opg), who were 6 times less likely to develop allergy. Infection by S. mansoni, in a load-dependent manner, was also associated with induction of an anti-inflammatory response, including increased production of IL-10 and reduced frequency of responders to IL-33 or TNF-α, a profile associated with decreased allergic reactivity. After 12 months of treatment (T12), 185 subjects were reassessed, with a reduction in schistosomiasis positivity to 23% and an increase in allergic reactivity both in prevalence (29%) and intensity (median = 9 IU/mL). Follow-up evidenced the importance of active infection in the development of a regulatory response, demonstrating a significant increase in the intensity of allergic reactivity among those who were treated and cured for schistosomiasis. Helminth reinfection and higher serum levels of CCL3 were also associated with lower chances of having allergic reactivity, even at low parasite load. Together these data indicate that the modulatory effect of schistosomiasis on allergic reactivity is dependent on active infection, high parasite load and/or frequent reinfection.