Introduction

Intestinal infections with parasitic protozoa display a global distribution and can cause serious morbidity depending on the infectious agents and immune status of the patient. Even in resource-rich countries infections with parasitic protozoa constitute a serious problem, e.g. due to increasing development of resistance to standard therapies. The infections are primarily transmitted by oral ingestion of infectious dormant stages of the parasite (cysts) with contaminated food or contaminated water. Gut-associated parasitic protozoa are comprised of many different pathogen groups but Giardia duodenalis and Cryptosporidium ssp. are responsible for most of the notifiable parasitoses in Germany.

The most frequent notifiable intestinal parasitosis, giardiasis, is caused by an infection with Giardia duodenalis (syn. G. intestinalis, G. lamblia). These flagellated organisms belong taxonomically to the diplomonads. The disease-associated proliferative stages (trophozoites) populate the epithelium of the anterior small intestine and can cause diarrhoeas with different symptoms. The disease has often a mild course and is self-limiting but can also have a serious chronic progression. Host factors, such as the immune status, age or nutritional status, and parasite virulence factors, both are responsible for the pathogenesis. The latter are, however, only insufficiently understood. G. duodenalis is comprised of at least 8 distinct genetic groups (assemblages A-H) and is also referred to as a ‘species complex’ since it is not clear yet whether these distinct genetic groups represent one single species. The human-pathogenic assemblages A and B have the broadest host spectrum and are not only found in humans but also in many domestic and wild animals. Whether and to what extent they should, therefore, be classified as potentially zoonotic is unclear.

We aim at a better understanding of virulence and pathogenicity mechanisms of intestinal parasitoses and at identifying the underlying factors in order to improve the current diagnostic and therapeutic strategies and to improve molecular approaches to study the epidemiology and find the answer to the question "Is autochthonous Giardiasis a zoonosis, yes or no?".

Functional epidemiology of Giardia duodenalis infections

Principle Investigator: Anton Aebischer and Christian Klotz

In this project a Giardia duodenalis database and biobank with clinical and environmental isolates is built up. Epidemiological data and relevant case information for clinical infections are collected and the parasites are isolated, as possible cultivated and centrally preserved. This is done in co-operation with partners from human and animal medicine institutions. Giardia isolates of this biobank are classified based on known molecular marker loci and new, possibly virulence-associated genes. Furthermore, functional tests are developed for potential virulence factors in order to identify possible correlations between sequence and function-types with the epidemiological data. Finally, the diagnostic potential of such correlations will be evaluated to clarify whether giardiasis in Germany is a zoonosis. The biobank will contribute to the infrastructure of zoonosis research in Germany and will be openly available also for interested third parties for further Giardia research projects.

Application of in vitro-models to investigate pathogen-host relationships of gastro-intestinal protozoa infections

Principle Investigator: Christian Klotz and Anton Aebischer

This project focuses on investigations of the molecular, immunological and cell biological mechanisms of pathogen-host interactions. The goal is to characterise mechanisms which are essential for the virulence and pathogenicity of gut-associated parasitic protozoa occurring in Germany, in order to identify new control and/or prevention approaches.

For most of the intestinal parasites there are no appropriate cell culture systems outside the host to adequately examine the parasites themselves or pathogen-host interactions. This applies particularly to disease-associated field isolates or novel pathogens for which sufficient models have not yet been developed. In order to counter this, the group deals with the establishment of novel stem cell based intestinal culture models to investigate these intestinal infections and the following topics with the primary focus on G. duodenalis infections:

• Interactions of G. duodenalis with host cells, in particular intestinal epithelium cells and cells of the innate immune system.
• Mode of action of potential virulence factors of G. duodenalis.
• Immune modulation mechanisms by G. duodenalis.
• Application of stem cell-based cell culture models for the investigation of gastrointestinal infections.