In this thesis we reported our investigations of the relationship between soil-transmitted helminths (STH) and a number of outcomes, in particular malaria, insulin resistance (a marker for type-2... Show moreIn this thesis we reported our investigations of the relationship between soil-transmitted helminths (STH) and a number of outcomes, in particular malaria, insulin resistance (a marker for type-2 diabetes (T2D)) and atherosclerosis (a marker for cardiovascular diseases (CVD)) on Flores island, Indonesia. In the study on Flores Island, the use of albendazole as a single dose at three monthly intervals decreased helminth infections significantly. However, this intensive deworming could not eliminate helminth infections. Despite no effect on malaria parasitemia and clinical symptoms was found, we noted that in vitro immune responses were improved after albendazole treatment and significant increases in malaria-specific and mitogen-induced tumor necrosis factor and interferon _ cytokine production were observed. We also reported that helminth infections are associated with improved insulin sensitivity and lower risk factors for CVD. A possible approach to confirm our results will be a long-term, well-powered, placebo controlled (adequate) anthelminthic trials to investigate asymptomatic malaria (in area where clinical malaria is highly prevalent); as well as to study whether alleviation of helminthic pressure is inversely correlated with anti-inflammation, lipid levels and insulin sensitivity, and therefore leads to an accelerated development of T2D and CVD. Show less
Helminth parasites are able to induce immune regulation in their host. Suppression of the host immune system is beneficial for both the parasite, by inhibiting anti-parasite immunity, and for the... Show moreHelminth parasites are able to induce immune regulation in their host. Suppression of the host immune system is beneficial for both the parasite, by inhibiting anti-parasite immunity, and for the host, by preventing tissue damage due to excessive inflammation. There are indications that in countries where parasites have been eliminated the immune regulatory network is impaired, leading to inflammatory diseases such as allergies and asthma. An important player in immune regulation is the regulatory T cell (Treg). We have shown that the number and/or function of Tregs were indeed enhanced in several helminth and also malaria infections in humans. Tregs were not only involved in suppression of anti-parasite responses, but also of responses to other infections or vaccines. We further investigated the effect of helminth elimination in a randomized placebo-controlled trial. Treatment of helminths led to a strong increase in __mainly pro-inflammatory__ immune responses, which confirms the importance of immune regulation during infection. Furthermore, the prevalence of malaria was transiently increased and allergy was slightly on the rise in treated school children. These results further endorse the possible beneficial effects of helminthic therapy, which is currently being tested in a number of clinical trials. Show less
