Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most... Show moreSchistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. In this tehsis we adressed the spatial and temporal expression of glycans expressed during the critical larval stages of schistosome development and we studied the (protective) antibody responses against these glycans in animals and infected human populations. Together these studies thereby contribute to an important basis for the understanding of the anti-glycan antibody responses towards Schistosoma in general and towards the vulnerable schistosomulum in particular. Show less
There has been a global increase in prevalence of allergic diseases. This is particularly so in developed and in urban centres of developing countries. At the same time, in rural areas of... Show moreThere has been a global increase in prevalence of allergic diseases. This is particularly so in developed and in urban centres of developing countries. At the same time, in rural areas of developing countries helminth infections are still highly prevalent. The immune response against helminths and allergens is generally characterized by high levels of IgE and increased numbers of Th2 cells, eosinophils, and mast cells, yet the clinical outcome with respect to immediate hypersensitivity and inflammation is clearly not the same. High levels of IgE are seen to allergens during helminth infections; however, these IgE responses do not translate into allergy symptoms. The role of socio-economic status (SES) which can be intertwined with presence or absence of helminth infections, has been examined in relation to development of allergic disorders in several studies. This thesis summarizes the evidence of the association between helminth infections and allergic disorders. It discusses how helminth infection can lead to IgE cross-reactivity with allergens and how this IgE has poor biological activity. The studies presented in this thesis shed light on the relationship between helminth infection, SES and atopic disorders in a developing country (Indonesia) where large differences in life-style, environmental exposure and SES are seen. Show less
Tahapary, D.L.; Ruiter, K. de; Martin, I.; Lieshout, L. van; Guigas, B.; Soewondo, P.; ... ; Supali, T. 2015
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
Djuardi, Y.; Supali, T.; Wibowo, H.; Kruize, Y.C.M.; Versteeg, S.A.; Ree, R. van; ... ; Yazdanbakhsh, M. 2013
The studies present in this thesis fall into two broad areas: the first focusing on filarial infection, Ig (immunoglobulin)E levels and risk factors for infection, while the second deals with the... Show moreThe studies present in this thesis fall into two broad areas: the first focusing on filarial infection, Ig (immunoglobulin)E levels and risk factors for infection, while the second deals with the possible associations between nematode infection and allergy. Compared to ELISA, RAST is superior in detecting filarial specific IgE in endemic area of Brugia malayi. Levels of filaria-specific IgE and IgG4 in children up to 10 years correlated with maternal antibody levels. Genetic factors had a more pronounced effect in children than in adults. The use of objective measurements, such as skin prick test (SPT) and IgE levels are required when conducting epidemiological studies of allergic diseases in Indonesia. Study on risk factors of allergy in Indonesia showed that nutritional status of children in the high socioeconomic school negatively associate with SPT and IgE positivity but we did not show a statistically significant role for helminths in inhibiting SPT responses. In endemic area of lymphatic filariasis, genetic factors contribute significantly to both total and allergen-specific IgE, whereas environmental factors influence the clustering of SPT positivity. By using several TLR ligands it was demonstrated that the dynamics of cytokine production following the innate immune stimulation can differ according to helminth infection status. Show less
