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De Geest B.G.,Ghent University | Willart M.A.,Ghent University | Lambrecht B.N.,Ghent University | Pollard C.,Ghent University | And 5 more authors.
Angewandte Chemie - International Edition | Year: 2012

Immunizing: To evoke highly potent immune responses against recombinant antigens, hollow capsules consisting of layers of dextran sulphate and poly-L-arginine that encapsulate the antigen ovalbumin (orange circles) were coated with immune-activating CpG-containing oligonucleotides (green). These capsules were readily internalized by dendritic cells (see picture) and showed activity in further immunization experiments. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Lejon V.,Antwerp Institute of Tropical Medicine | Bentivoglio M.,University of Verona | Franco J.R.,World Health Organization
Handbook of Clinical Neurology | Year: 2013

Human African trypanosomiasis or sleeping sickness is a neglected tropical disease that affects populations in sub-Saharan Africa. The disease is caused by infection with the gambiense and rhodesiense subspecies of the extracellular parasite Trypanosoma brucei, and is transmitted to humans by bites of infected tsetse flies. The disease evolves in two stages, the hemolymphatic and meningoencephalitic stages, the latter being defined by central nervous system infection after trypanosomal traversal of the blood-brain barrier. African trypanosomiasis, which leads to severe neuroinflammation, is fatal without treatment, but the available drugs are toxic and complicated to administer. The choice of medication is determined by the infecting parasite subspecies and disease stage. Clinical features include a constellation of nonspecific symptoms and signs with evolving neurological and psychiatric alterations and characteristic sleep-wake disturbances. Because of the clinical profile variability and insidiously progressive central nervous system involvement, disease staging is currently based on cerebrospinal fluid examination, which is usually performed after the finding of trypanosomes in blood or other body fluids. No vaccine being available, control of human African trypanosomiasis relies on diagnosis and treatment of infected patients, assisted by vector control. Better diagnostic tools and safer, easy to use drugs are needed to facilitate elimination of the disease. © 2013 Elsevier B.V. Source


Agyepong I.A.,University Utrecht | Orem J.N.,Health Systems and Services Cluster | Hercot D.,Antwerp Institute of Tropical Medicine
Tropical Medicine and International Health | Year: 2011

This brief paper addresses some of the difficulties inherent in international ideological approaches to solving the complex problems of health care financing and delivery in poor countries using Ghana as an example. It concludes with an appeal for problem solving approaches involving informed debate as to optimal ways forward to solve low income country health financing woes that are open minded about possible options rather than vested in particular positions. © 2010 Blackwell Publishing Ltd. Source


Vanham G.,Antwerp Institute of Tropical Medicine | Vanham G.,University of Antwerp | Van Gulck E.,Antwerp Institute of Tropical Medicine | Van Gulck E.,Present Address Community Of Research Excellence And Advanced Technology Create
Retrovirology | Year: 2012

Immunotherapy aims to assist the natural immune system in achieving control over viral infection. Various immunotherapy formats have been evaluated in either therapy-naive or therapy-experienced HIV-infected patients over the last 20 years. These formats included non-antigen specific strategies such as cytokines that stimulate immunity or suppress the viral replication, as well as antibodies that block negative regulatory pathways. A number of HIV-specific therapeutic vaccinations have also been proposed, using in vivo injection of inactivated virus, plasmid DNA encoding HIV antigens, or recombinant viral vectors containing HIV genes. A specific format of therapeutic vaccines consists of ex vivo loading of autologous dendritic cells with one of the above mentioned antigenic formats or mRNA encoding HIV antigens.This review provides an extensive overview of the background and rationale of these different therapeutic attempts and discusses the results of trials in the SIV macaque model and in patients. To date success has been limited, which could be explained by insufficient quality or strength of the induced immune responses, incomplete coverage of HIV variability and/or inappropriate immune activation, with ensuing increased susceptibility of target cells.Future attempts at therapeutic vaccination should ideally be performed under the protection of highly active antiretroviral drugs in patients with a recovered immune system. Risks for immune escape should be limited by a better coverage of the HIV variability, using either conserved or mosaic sequences. Appropriate molecular adjuvants should be included to enhance the quality and strength of the responses, without inducing inappropriate immune activation. Finally, to achieve a long-lasting effect on viral control (i.e. a " functional cure" ) it is likely that these immune interventions should be combined with anti-latency drugs and/or gene therapy. © 2012 Vanham and Van Gulck; licensee BioMed Central Ltd. Source


Vanaerschot M.,Antwerp Institute of Tropical Medicine
Critical reviews in microbiology | Year: 2013

Drug-resistant microorganisms (DRMs) are generally thought to suffer from a fitness cost associated with their drug-resistant trait, inflicting them a disadvantage when the drug pressure reduces. However, Leishmania resistant to pentavalent antimonies shows traits of a higher fitness compared to its sensitive counterparts. This is likely due the combination of an intracellular pathogen and a drug that targets the parasite's general defense mechanisms while at the same time stimulating the host's immune system, resulting in a DRM that is better adapted to withstand the host's immune response. This review aims to highlight how this fitter DRM has emerged and how it might affect the control of leishmaniasis. However, this unprecedented example of fitter antimony-resistant Leishmania donovani is also of significance for the control of other microorganisms, warranting more caution when applying or designing drugs that attack their general defense mechanisms or interact with the host's immune system. Source

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