This thesis focuses on cellular immunity against mycobacteria during latency with the aim to contribute to improved immunodiagnosis of latent TB and to gain insight into immune responses which play... Show moreThis thesis focuses on cellular immunity against mycobacteria during latency with the aim to contribute to improved immunodiagnosis of latent TB and to gain insight into immune responses which play a role in controlling latent infection. Several new highly M. tuberculosis-specific peptides mixtures were identified to optimize the sensitivity of immunodiagnostic assays. The performance of interferon-gamma-release-assays (IGRA) for detection of latent TB were evaluated. Two short-incubation IGRA, QuantiFERON-TB Gold and T-SPOTTM.TB, were found to correlate better to the level of exposure to M. tuberculosis than the tuberculin skin test (TST), indicating that these assays are very sensitive for detection of recent infections. However, short-incubation IGRA are less sensitive than prolonged-incubation IGRA and TST for detection of latent TB acquired in the past. The search for proteins that are specifically targeted by the immune system during latency led to the identification of several antigens encoded within the DosR-regulon. This set of genes of M. tuberculosis is strongly upregulated by during in vitro models of latency. These antigens, including 16kDa _-crystallin, were preferentially recognized by latently infected individuals, which suggest that T-cell responses to latency antigens are associated with natural protection against reactivation of TB, warranting their further study as vaccine candidates. Show less
In the first part of this thesis we described two new diagnostic algorithms for patients with clinically suspected deep venous thrombosis and pulmonary embolism. These management strategies include... Show moreIn the first part of this thesis we described two new diagnostic algorithms for patients with clinically suspected deep venous thrombosis and pulmonary embolism. These management strategies include both pretest clinical probability and D-dimer assay, and reduce the need for non-invasive imaging tests. These novel strategies are safe in excluding deep venous thrombosis and pulmonary embolism. The results of the first part of this thesis led to a different, more simple diagnostic strategy in patients with venous thromboembolism. In the second part of this thesis we described two follow-up studies which led to the identification of new risk factors and early predictors for PTS. At present, the results of these studies enable us to provide individualized information to patients with a first deep venous thrombosis about their risk for the development of PTS. Future research should focus on validating and standardizing diagnostic criteria for PTS. A standardized diagnosis is necessary to improve the uniformity of the diagnosis and to enhance the ability to compare results of different studies. Moreover, objective diagnosis of PTS will allow physicians to monitor the development and course of PTS in their own patients. Show less
Schistosomiasis, also known as bilharzia, is a disease that still occurs in many parts of Africa, the Middle East and Southern America, mainly Brasil and the Caribbean. Schistosomiasis is, after... Show moreSchistosomiasis, also known as bilharzia, is a disease that still occurs in many parts of Africa, the Middle East and Southern America, mainly Brasil and the Caribbean. Schistosomiasis is, after malaria, the second most common parasitic infection. Currently 200 million people are infected with the worms that cause the disease. Schistosoma mansoni is the most common schistosome species that infects humans. The schistosome produces many different sugar structures (glycans) that are not made by humans. Central to this thesis are sugar structures with a __double fucose__. Such fucosylated glycans are mainly produced by the eggs, which play a major role in the disease schistosomiasis. The human immune defence system responds to these parasite glycans in several ways. High antibody responses have been measured against sugar structures with a __double fucose__ moiety and different types of immune cells interact with these glycan structures. Despite these immunological responses the human host is not able to clear the parasitic infection. Glycans are thought to play a role in the mechanisms that S. mansoni has developed to survive in the hostile environment of the human blood. In this thesis the structures of several glycans containing the __double fucose__ moiety have been characterised using different mass spectrometric techniques. Show less
Human schistosomiasis (bilharzia) is one of the major parasitic diseases in the world, affecting 200 million people predominantly in third world countries. In areas where the disease is highly... Show moreHuman schistosomiasis (bilharzia) is one of the major parasitic diseases in the world, affecting 200 million people predominantly in third world countries. In areas where the disease is highly prevalent it causes important health problems, and it also has socially-economic effects on the population. Schistosomiasis is caused by the presence of the blood-fluke Schistosoma in the blood-vessels of mammalian hosts. The current method for diagnosis of schistosomiasis in developing countries is the parasitological examination of urine and faeces for the presence of Schistosoma eggs. An alternative method which is now increasingly used is based on the detection of Schistosoma antigens in the circulatory system or the urine of the host. The gut of the parasite is an important source of these antigens since many gut-associated antigens are excreted into the circulation of the host following digestion of food (e.g. blood cells, proteins) by the parasite. Two major gut–associated antigens which have been thoroughly studied with regard to diagnostic detectability, are the circulating anodic antigen (CAA) and the circulating cathodic antigen (CCA). In this thesis, these two unique antigens are further analysed with respect to their biochemical carbohydrate structure, localization, in vitro and in vivo excretion and detection patterns, and their role in a number of host-parasite immune interactions (granulocytes, complement system). Show less
