No abstract

ObjectiveGiven that helminth infections have been shown to improve insulin sensitivity in animal studies, which may be explained by beneficial effects on energy balance or by a shift in the immune system to an anti-inflammatory profile, we investigated whether soil-transmitted helminth (STH)-infected subjects are more insulin sensitive than STH-uninfected subjects.DesignWe performed a cross-sectional study on Flores island, Indonesia, an area with high prevalence of STH infections.MethodsFrom 646 adults, stool samples were screened for Trichuris trichiura by microscopy and for Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, and Strongyloides stercoralis by qPCR. No other helminth was found. We collected data on body mass index (BMI, kg/m2), waist-to-hip ratio (WHR), fasting blood glucose (FBG, mmol/L), insulin (pmol/L), high sensitive C-reactive protein (ng/ml) and Immunoglobulin E (IU/ml). The homeostatic model assessment for insulin resistance (HOMAIR) was calculated and regression models were used to assess the association between STH infection status and insulin resistance.Results424 (66%) participants had at least one STH infection. STH infected participants had lower BMI (23.2 vs 22.5 kg/m2, p value = 0.03) and lower HOMAIR (0.97 vs 0.81, p value = 0.05). In an age-, sex- and BMI-adjusted model a significant association was seen between the number of infections and HOMAIR: for every additional infection with STH species, the HOMAIR decreased by 0.10 (p for linear trend 0.01). This effect was mainly accounted for by a decrease in insulin of 4.9 pmol/L for every infection (p for trend = 0.07).ConclusionSTH infections are associated with a modest improvement of insulin sensitivity, which is not accounted for by STH effects on BMI alone.

To establish the relationships among T and B cell responses, active infection, and clinical manifestations in lymphatic filariasis, filarial-specific lymphocyte proliferation, IgG antibody isotypes, and IgE levels were determined in an exposed population: 31 asymptomatic amicrofilaremics, 43 microfilaremics, 12 symptomatic amicrofilaremics, and 52 elephantiasis patients. Lymphocyte proliferation was higher in elephantiasis patients and asymptomatic amicrofilaremics than in microfilaremics (P < .004). A proportion of asymptomatic amicrofilaremics (32%), elephantiasis patients (37%), and symptomatic amicrofilaremics (58%) showed antigen-specific lymphocyte unresponsiveness, and lymphocyte proliferation to filarial antigens correlated negatively with specific IgG4 levels (rho = -0.315, P < .001). As elevated specific IgG4 is an indicator of active infection, it is argued that active infection may result in lymphocyte hyporesponsiveness irrespective of clinical category. Of those with elevated specific IgE levels and high T cell proliferative responses, 70% had elephantiasis, suggesting these factors have a role in pathology. However, the existence of a proportion of elephantiasis patients with low anti-filarial IgE and T cell unresponsiveness to filarial antigens suggests that elephantiasis can be caused by distinct processes.

Cellular immune responses to filarial antigens were examined in persons before and 1 year after beginning treatment with diethylcarbamazine (DEC). The subjects (17 microfilaremics, 13 asymptomatic amicrofilaremics, and 13 with elephantiasis) had not responded to Brgia malayi adult worm antigen (BmA) before chemotherapy. T cell proliferative responses to BmA improved significantly after therapy in the 3 clinical groups (P < .05) but was highest in the elephantiasis patients and asymptomatic amicrofilareimics. Cytokine release profiles after stimulation with parasite antigen were analyzed. Production of interferon (IFN)-gamma by BmA-stimulated mononuclear cells increased significantly after DEC treatment (geometric mean, 39.6-55.7 U/mL; P < .05), largely due to improved responses in elephantiasis patients and asymptomatic amicrofilaremics. In contrast, BmA-induced interleukin (IL)-4 release did not change significantly in these same patients after treatment. Thus, both microfilaremic and amicrofilaremic infections with B. malayi are associated with similar down-regulation of proliferative T cell function and IFN-gamma release.