Das Institut beschäftigt sich mit Parasitosen bei Haus- und Nutztieren, sowie auch mit Parasitosen des Menschen, dies in den Bereichen Lehre, Forschung und Dienstleistung.
Britta Lundström-Stadelmann untersucht den für Tiere und Menschen gefährlichen Hunde- und Fuchsbandwurm. Im Video spricht sie darüber, was ihre Arbeit als Forscherin und Ko-Leiterin eines Instituts besonders macht.
We congratulate our PhD candidate Kai Hänggeli to the successful defence of his thesis "Characterisation and validation of putative targets for intervention in Toxoplasma gondii and Neospora caninum infection".
We congratulate Marc Kaethner for successfully having defended his thesis "Food for thought: Investigation and inhibition of the threonine metabolism of Echinococcus multilocularis and further approaches towards novel treatment options for echinococcosis".
Metacestodes of the fox tapeworm Echinococcus multilocularis cause the severe disease alveolar echinococcosis in humans and animals. Current drug treatment options are not curative and there is a strong need for the development of novel therapeutic agents against this parasite. In the search for compounds, we apply an established in vitro drug screening cascade against E. multilocularis metacestode vesicles and isolated primary cells of this parasite. In this manuscript, we tested disulfiram and 51 dithiocarbamate derivatives in this screening cascade, because these compounds have been shown to have promising activity against the trematode Schistosoma mansoni. Our studies revealed that the structure class of dithiocarbamate derivatives can provide new potential anti-echinococcal drugs.
The first Bern Parasitology Meeting (BPM) took place on February 2, 2024 and it was very well received. This meeting unites professionals from all areas of parasitology—including clinicians, researchers, molecular biologists, epidemiologists, pharmacologists, diagnosticians, and others working on human and veterinary parasites in the Bern region. BPM II takes place on Feb 11 2025.
Wir gratulieren Lea Hiller zum Alumni Preis 2023 der Vetsuisse-Fakultät Bern für ihre Masterarbeit "Drug testing on Echinococcus multilocularis - Searching for new therapeutic options against Alveolar Echinococcosis".
Prof. Dr. Andrew Hemphill received the titel Honorary Professor at the Complutense University of Madrid. Congratulations Andrew!
We congratulate PhD student Maria Cristina Ferreira de Sousa for her perfect talk on "Activity and efficacy of the bumped kinase inhibitor BKI-1708 in vitro and in non-pregnant and pregnant toxoplasmosis and neosporosis mouse models" that was awarded as the BEST ORAL PRESENTATION at the annual meeting of the Swiss Society of Tropical Medicine and Parasitology (SSTMP)!
We congratulate Dr. Dennis Imhof for having been awarded the Young Investigator Award of the Swiss Society for Tropical Medicine and Parasitology (SSTMP) for his excelling PhD thesis.
We congratulate Dr. Natalie Wiedemar to her successful Ambizione grant application to the SNSF! We are looking forward to exciting research on your project "Dissecting resistance mechanisms and identifying new drug targets for the liver fluke Fasciola hepatica"!
We here report and share protocols on an improved in vitro culture protocol for Echinococcus granulosus metacestodes, protoscoleces and germinal layer cells, including various parasite damage and viability assays combined to an in vitro drug screening cascade. The novel E. granulosus screening cascade will allow for assessment of drug efficacies and mode of action, as well as comparative analyses to analogue tests on E. multilocularis.
In the publication "Targeted and non-targeted proteomics to characterize the parasite proteins of Echinococcus multilocularis metacestodes" we analyzed the proteome of metacestode tissues and their secretions in vitro and in vivo. We then followed the protein dynamics of the most abundant proteins, the Antigen B polypeptides, and showed in a targeted proteomic approach that these peptides are not only released, but also taken up by the parasite. This is a very important step in deciphering the role of Antigen B and the ongoing discussions about a potential role in lipid uptake by the parasite through these proteins.
In this work we studied the mechanism of action of mefloquine and derivatives against Echinococcus multilocularis by a differential affinity chromatography and proteomics approach.
We congratulate our PhD student Dennis Imhof to successfully defending his thesis "Vaccine and chemotherapy strategies to control toxoplasmosis and neosporosis"!
Die neue englischsprachige ESCCAP-Empfehlung Nr. 4 zur Diagnose von Parasitosen bei Katzen, Hunden und Pferden steht tierärztlichen Praxen und Kliniken zur Verfügung. Sie richtet sich sowohl an TierärztInnen, die in ihren Praxen Diagnoseverfahren zum Nachweis von Parasiteninfektionen durchführen, als auch an solche, die regelmässig Proben an externe Labors versenden.
Vor allem bei Hunden und Katzen kommt Flohbefall häufig vor. Er ist lästig und kann Auslöser der Flohspeichel-Allergie-Dermatitis sein. Es handelt sich um eine der häufigsten Allergien bei Hund und Katze. Sie führt zu Juckreiz, Haarausfall und entzündlichen Hautreaktionen. Bei Verdacht auf FAD ist mindestens eine 6-monatige Flohprophylaxe ohne Unterbruch vorzunehmen. Bei FAD und Auslauf bzw. Kontakt zu potentiellen Überträgern ist eine ganzjährige Flohprophylaxe angezeigt.
Wir gratulieren Dr. Diana Gliga ganz herzlich zu ihrer Dissertation zum Thema "Switzerland-wide Neospora caninum seroprevalence in female cattle and identification of risk factors for infection"
Wir gratulieren Dr. Seraina Meister ganz herzlich zu ihrer Dissertation zum Thema "Parasites in white storks (Ciconia ciconia) and captive bird species in Switzerland"
Manche TierhalterInnen sind besorgt, dass bei häufigen Wurmkuren die Wirkstoffe ihren Effekt verlieren und irgendwann nicht mehr helfen. Die Sorge vor Resistenzen ist verständlich, aber für Hunde und Katzen, die in einem normalen Haushalt leben, bisher unbegründet. Anders ist dies bei Schafen und Pferden. Hier gibt es zahlreiche nachgewiesene Fälle solcher Wirkverluste.
Der Sinn von Kotuntersuchungen und Entwurmungen ist, Hunde und Katzen über ihre gesamte Lebenszeit vor gesundheitlichen Schäden durch einen Wurmbefall zu schützen. Gleichzeitig sollen Diagnostik, Medikation und Prävention dafür sorgen, dass die Vierbeiner möglichst wenige Wurmeier mit ihrem Kot ausscheiden, an denen sich andere Tiere und auch Menschen anstecken können. Um entscheiden zu können, ob Kotuntersuchungen oder regelmässige Entwurmungen besser zur individuellen Situation passen, sind die folgenden Fakten in einer Risikoanalyse gegeneinander abzuwägen.
An der Generalversammlung der Schweizerischen Gesellschaft für Tropenmedizin und Parasitologie (SGTP) wurde Prof. Dr. Britta Lundström-Stadelmann als Präsidentinn wiedergewählt. Herzlichen Glückwunsch!
Phantastische Neuigkeiten: Prof. Dr. Andrew Hemphill wurde für das Jahr 2022 als einer der top 2% Wissenschaftler weltweit ausgezeichnet! Ganz herzliche Gratulation für die ausserordentliche Leistung!
Die Jagdsaison hat begonnen. Die Jagd gehört zu den ältesten Traditionen der Menschheit; sie ist auch in der Bundesverfassung als behördliche Aufgabe verankert. Die Verwaltung kann auf die freiwillige und fachmännische Unterstützung der Jägerschaft (rund 30'000 Personen) und ihrer Jagdhunde zählen. Jäger müssen eine strenge Prüfung bestehen und sich weiterbilden. Der Einsatz der Jagdhunde beruht auf klaren gesetzlichen Regelungen. Haltung, Fütterung und Ausbildung der Jagdhunde ab Welpenalter müssen auch parasitologische Fragen beinhalten. Jagdhunde gehören zu den Risikogruppen für Parasiteninfektionen.
In this study we studied the mitochondrial energy metabolism of the fox tapeworm Echinococcus multilocularis, which is based on two pathways. We tested a series of inhibitors of one of these pathways, the electron transfer chain, and showed that the activity of these inhibitors is lost under anaerobic conditions. The second pathway, the malate dismutation, works under anaerobic conditions. The combination of inhibitors of both pathways successfully blocked the energy generation in the parasite and damaged it strongly.
This paper is the product of a wonderful collaboration between the Oevermann and Hemphill laboratories. The study shows that the Listeria monocytogenes vaccine vector Lm3Dx_SAG1-BKI-1748 combination treatment induced significantly enhanced protection against vertical transmission in N. caninum infected mice, and also lead to decreased pup mortality, as well a decreased cerebral parasite load in adult mice. Overall, vaccine-linked chemotherapy was more efficacious than vaccination or drug treatment alone and should be considered for further evaluation in a more relevant experimental large animal model.
Die Reisesaison steht vor der Türe. Wenn Hund oder Katze in die Auslandferien mitgenommen werden, gibt es einiges zu beachten. Nicht nur die Einreise in andere Länder unterliegt Regelungen, auch die Rückkehr in die Schweiz. Die Einfuhrbestimmungen sind komplex und die Zollkontrollen streng – zum Schutz von Tier und Mensch. Informieren Sie sich frühzeitig und überlegen Sie sich vor der Reise, ob Sie den Hund oder die Katze wegen des Infektionsrisikos mit unterschiedlichen Erregern überhaupt mitnehmen wollen!
Wir gratulieren Prof. Dr. Andrew E. Hemphill zur Verleihung des Titels eines Ehrenprofessors der Universidad Complutense de Madrid, Spanien, für das akademische Jahr 2021/2022!
We congratulate our PhD student Nicoleta Anghel to successfully defending her thesis "Advances, efficacy, and safety of compounds for the treatment against the protozoan parasites Toxoplasma, Neospora and Trypansosma"!
Avian malaria was diagnosed in cases of sudden death in captive Atlantic puffins (Fratercula arctica) at Berne Animal Park by histopathological examination, one-step multiplex PCR and by nested PCR. Plasmodium relictum lineage SGS1 and P. matutinum lineage LINN1 were identified as the involved etiologic agents.
We congratulate our PhD student Pablo Winzer to successfully defending his thesis "Molecular changes of Neospora caninum treated with the calcium dependent protein kinase 1 inhibitor BKI-1294 and implications on the immune response"!
Leucinostatins are fascinating natural antimicrobial peptides, with high potency against many pathogens, but their acute toxicity has prevented therapeutic use. This work demonstrated how these could be converted into synthetically more accessible and more selective anti-protozoal agents with broad efficacy and undetectable resistance. This study has not only led to therapeutically applicable agents against a wide range of parasites but also shows how peptides can be made clinically useful by targeted synthetic transformations.
This review reports on the the development of bumped-kinase inhibitors (BKIs) for the therapy of toxplasmosis, neosporosis and cryptosporidiosis. Proof-of-concept for BKI therapy has been demonstrated in livestock models of cryptosporidiosis (newborn calves infected with Cryptosporidium parvum), toxoplasmosis (pregnant sheep infected with Toxoplasma gondii), and neosporosis (pregnant sheep infected with Neospora caninum). The potential uses of BKIs for the treatment of diseases caused by apicomplexan parasites in animals and humans are discussed, as well as the pitfalls in the development, and the improvements that need to be made.
This paper originates from a Sinergia project that aims to develop novel ruthenium based organometallic compounds as anti-parasitic drugs. Synthesis, characterization, and in vitro anti-Toxoplasma and anti-cancer activity evaluation of a series of new conjugates containing two and three dinuclear trithiolato-bridged ruthenium(II)-arene units are presented. Overall, compound flexibility and size impacted on the anti-Toxoplasma and anti-cancer cell activities. Irrespective of the nature of the connectors (alkyl/aryl) or the numbers of the di-ruthenium units (two/three), ester conjugates were more cytotoxic against cancer cells than amide analogues. Thus, polynuclear conjugates with multiple trithiolato-bridged di-ruthenium(II)-arene moieties deserve further investigation.
A new genus and species of archiacanthocephalan, Intraproboscis sanghae, is described infecting the African black-bellied pangolin Phataginus tetradactyla in the Central African Republic and causing intestinal perforation and peritonitis. In addition, the parasite fauna of this endangered animal species was reviewed.
A cooperation with the Institute of Parasitology in Zurich identified the Sarcocystis species infecting red deer showing greenish carcass discoloration due to eosinophilic myositis/fasciitis from the canton of Grisons. Red foxes and hunting dogs from the region were shown to be definitive hosts of some of these species, and also of other species infecting domestic ruminants and swine. Although Sarcocystis species infecting red deer are not regarded as zoonotic, the affected carcasses can be declared as unfit for human consumption due to the extensive pathological changes.
A nationwide cross-sectional study demonstrated for the first time the presence of antibodies against the protozoan parasites Toxoplasma gondii and Neospora caninum in Swiss llamas and alpacas, highlighting a high seroprevalence for T. gondii and a low prevalence for N. caninum, and allowed the identification of risk factors, which may favour T. gondii infection. The study also presented the evaluation and optimization of different serological tests to be used for diagnosis in these animal species.
Dr. Reto Rufener received the Young Investigator Award of the Swiss Society of Tropical Medicine and Parasitology (SSTMP) for his PhD thesis. Congratulations!
Minimal prevalence of E. multilocularis infection in Swiss domestic pigs as well as risk factors for infection were established in this recently published study that reached about 85% of the pigs produced annually in Switzerland. The parasite is widespread, but risk of infection in pigs can be mitigated by relatively simple measures such as increased hygiene.
Mosquitoes of the genus Aedes transmit the viruses responsible for yellow fever, Dengue, Zika and Chikungunya. A surprising recent finding is that Aedes mosquitoes in Sri Lanka have adapted to breed in brackish water as well, thereby extending the area where transmission of viruses can occur. The aim of this collaborative grant (University of Bern and University of Jaffna, Sri Lanka) is to elucidate the physiological and molecular basis of adaptation using next generation sequencing (RNA-seq) and immuno-electron microscopy, to hold a bioinformatics workshop for students in Sri Lanka, and enable 2-3-month stays in the Swiss laboratories for Sri Lankan PhD students to learn recombinant protein technology and electron microscopy.
A major challenge for the development of anti-cancer vaccines is the induction of a safe and effective immune response, particularly mediated by CD8+ T lymphocytes, in an adjuvant‐free manner. A simple strategy is presented to improve the specific CD8+ T cell responses using KFE8 nanofibers bearing a Class I (Kb)‐restricted peptide epitope (called E.nanofibers) without the use of adjuvant. Incorporation of Tat, a cell‐penetrating peptide (CPP) of the
HIV transactivator protein, into E. nanofibers remarkably enhanced tumor‐specific CD8+ T cell responses. This approach could potentially also be applicable for parasitic infections.
In this invited review article we summarize our most recent findings in the search for novel chemotherapies against alveolar echinococcosis. In particular, we focus on the anti-malarial mefloquine, which showed promising activities in vitro and in different mouse models of the disease.
Wir gratulieren Caroline Frey zur Wahl als Vizepräsidentin von ESCCAP Schweiz!
We congratulate our PhD student Dominic Ritler to successfully defending his thesis "New ways to target the deadly parasite Echinococcus multilocularis"!
Small extracellular vesicles (EVs) play major roles in intercellular communication by delivering various cargo molecules to target cells. They could potentially represent an alternative delivery strategy to treat ocular toxoplasmosis, a parasitosis affecting the retinal pigment epithelium (RPE). This study, reports on the intracellular uptake of fluorescently labelled human urine and fibroblast-derived small EVs by human RPE cells. BODIPY-labelled small EVs were found in close vicinity to Toxoplasma gondii. Additionally, an ultrastructural method was enabled to distinguish between labelled exogenous and endogenous small EVs within target cells. Cooperation between IPA and Veterinary Anatomy Division, Vetsuisse Bern.
We congratulate Nicoleta Anghel to her successful PhD half-time presentation with the title “Studies on activity and safety of novel compounds against apicomplexan parasites”
Using shotgun mass spectrometry, we compared the proteomes of tachyzoites to BKI-1294 induced MNCs. More than half of the identified proteins are downregulated in MNCs as compared to tachyzoites. Only 12 proteins are upregulated, the majority of them containing SAG1 related sequence (SRS) domains, and some also known to be expressed in bradyzoites. Thus, MNCs share some bradyzoite-like features, but may constitute a third stage, which remains viable and ensures survival under adverse conditions such as drug pressure. We propose the term “baryzoites” for this stage (from Greek βαρυσ = massive, bulky, heavy, inert).
We present a comprehensive analysis of the hepatic microRNAs (miRNAs) transcriptome at early stage of experimental primary alveolar echinococcosis. Expression of miRNAs was significantly altered in infected livers; miRNAs were mainly down regulated. Target genes of the most extensively down-regulated miRNAs were involved in angiogenesis and fatty acid synthesis. Furthermore, expression of key angiogenic and lipogenic genes was higher in infected livers. Some precursor miRNAs exhibited different arm selection preferences in normal versus infected liver tissues. Further research on how E. multilocularis contribute to the regulation of the hepatic miRNA transcriptome is needed.
BKI-1294 exposure of N. caninum results in the formation of multinucleated complexes (MNCs), which remain viable in vitro under constant drug pressure. We investigated the formation of BKI-1294 induced MNCs by TEM and SEM, the re-emergence of viable tachyzoites following drug removal by immunofluorescence microscopy using various antibodies against surface antigens and secretory proteins, and studied the localization of CDPK1, the molecular target of BKIs by immunogold-TEM.
Tritrichomonas foetus is a protozoan parasite that colonizes the reproductive tract of cattle, the gastrointestinal tract of cats, or the nasal cavity of pigs. We generated whole genome sequencing data from bovine, feline and porcine T. foetus strains. These data clearly indicated a close phylogenetic relationship between bovine and porcine T. foetus but a remarkable genetic distinctness of these two strains from the feline strain. Our comparative genome sequencing approach granted deep insights into the genetic diversity of T. foetus in relation to the different host origins of the parasite. Furthermore, our study identified a large number of SNP- and indel-containing sequences that may be useful molecular markers for future epidemiological studies aimed at the elucidation of the transmission patterns of T. foetus within different host species.
BKIs that target CDPK1 in apicomplexan parasites with a glycine gatekeeper are promising new therapeutics. Numerous challenges have shaped the selection of pre-clinical BKI candidates. These include chirality, hERG, teratogenicity, cardiovascular, GI, and toxicity issues, and poor efficacy due to PK/PD. The BKI-consortium is comprised of many laboratories worldwide (US, Spain, including the IPA).
The synthesis, characterization, photophysical and biological properties of 13 new conjugate coumarin‐diruthenium(II)⋅arene complexes against Toxoplasma gondii were studied. An almost complete loss of fluorescence efficacy was observed. The in vitro activity against T. gondii depends on the various chemical properties of the conjugates and ranges from 105 to 735 nM. Nine compounds displayed lower IC50 than the standard drug pyrimethamine. TEM showed that treatment predominantly affected the parasite mitochondrion. Cooperation between IPA and Department of Chemistry, University of Bern (Sinergia).
A series of new ferrocenyl and ruthenocenyl derivatives of the organic drug ABZ were synthesized and were assessed for their activity against different helminths and protozoans, namely Trichuris muris, Heligmosomoides polygygrus, Schistosoma mansoni, Giardia lamblia, Haemonchus contortus and Toxoplasma gondii. The derivatives show a species-specific in vitro activity and the choice of the organometallic moieties attached to the organic drug plays a very important role. This study confirms the potential of organometallic complexes against parasites of medical and veterinary importance. Carried out within a consortium comprised of several laboratories (France, Switzerland, Australia, including the IPA (protozoans)).
We congratulate our PhD student Reto Rufener to successfully defending his thesis "New drugs against Echinococcus multilocularis - targeting the energy metabolism"!
390 compounds of the MMV Malaria Box were screened against Neospora caninum tachyzoites Five compounds exhibited promising IC50 values ranging from 25-200 nM. By TEM, aberrant structural changes were first detected in the parasite mitochondrion, and subsequently alterations progressed to other cytoplasmic compartments of the tachyzoites. The pharmacokinetic (PK) data obtained in mice suggest that treatment with MMV665941 could be potentially useful for further in vivo studies.
ELQs target the cytochrome b and interfere with oxidative phosphorylation and pyrimidine biosynthesis in many apicomplexans. 14 different ELQs were assessed against B. besnoiti by quantitative real time PCR and TEM. The IC50s on B. besnoiti were higher than previously observed for P. falciparum and T. gondii. However, the cytochrome b sequence and the predicted Qo and Qi ELQ-binding sites are virtually identical. TEM demonstrated alterations in the mitochondrion and the nuclear membrane, as well as increased vacuolization within the tachyzoite cytoplasm. Long-term treatments did not act parasiticidal. Cooperation with groups in the US and Portugal.
In Giardia lamblia, enzymes involved in anaerobic nitro reduction have been investigated in detail as potential targets. Their role within the normal metabolic context is, however, not understood. Using 1H HR-MAS NMR spectroscopy, we analyzed the metabolomes of G. lamblia trophozoites overexpressing three nitroreductases (NR1 – NR3) and thioredoxin reductase (TrxR), most likely a scavenger of reactive oxygen species. We compared the patterns to convenient controls and to the situation in the strain nitro drug resistant strain C4 where NR1 is downregulated. Trophozoites overexpressing NR1 presented a distinct pattern of nine metabolites, in particular arginine catabolites, differing from the respective controls. This pattern matched a differential pattern between wildtype and strain C4. This suggests that NR1 interferes with arginine and thus energy metabolism. The exact metabolic function of NR1 (and the other nitroreductases) remains to be elucidated.
We analyzed the unknown metabolic footprint of the parasite E. multilocularis and identified that the metacestode of E. multilocularis consumed glucose, and, surprisingly, threonine, whereas it released succinate, acetate, and alanine as major fermentation end products. This study provides the basis for analyses of potentially targetable pathways for future drug development.
Wir gratulieren Prof. Dr. Caroline Frey zur Haller Medaille.
Prof. Dr. Andrew Hemphill received the titel Visiting Professor at the National University La Plata (Argentina). Congratulations Andrew!
Prof. Dr. Britta Lundström-Stadelmann was elected president of the Swiss Society of Tropical Medicine and Parasitology at the society's general assembly in Lausanne on Sept 19.
