Gastrointestinal parasites in pigs : prevalence, risk factors and control

Gastrointestinal parasites are common in pigs worldwide, and in all production types. Clinical disease is rare and mainly associated with heavy nematode infections, or piglets infected with the coccidia Cystoisospora suis. Subclinical infections are more common and may result in reduced growth and poor feed utilisation. This can in turn affect pig health as well as the sustainability and productivity of the farm. The aim of this thesis was to update the knowledge of gastrointestinal parasites in Swedish pig herds, as this was last done in the 1980s. Since then, major changes in the national pig production have occurred with e.g., higher demands on animal welfare and improved biosecurity. Management routines related to parasite control were investigated using a questionnaire. Strategic hygiene and biosecurity practices were commonly practiced for growing pigs but less so for adult animals. Moreover, antiparasitic drugs were frequently used by routine. The occurrence of gastrointestinal parasites was assessed in three different studies. Oesophagostomum spp. were the most common parasites and found mainly in sows. The prevalence of Ascaris suum in growing pigs was reduced compared to previous studies. C. suis was common in piglets on a herd basis and Cryptosporidium spp. were found on all sampled farms. Finally, the efficacy of the available anthelmintic drugs was investigated, and for the first time in Sweden a reduced efficacy of ivermectin on Oesophagostomum spp. was identified. In conclusion, several changes in both the prevalence and control of gastrointestinal parasites were identified in this thesis. This new knowledge can in turn contribute to healthier pigs and a more sustainable and profitable pig production

This Gut Ain't Big Enough for Both of Us. Or Is It? Helminth-Microbiota Interactions in Veterinary Species

Gastrointestinal helminth parasites share their habitat with a myriad of other organisms, that is, the commensal microbiota. Increasing evidence, particularly in humans and rodent models of helminth infection, points towards a multitude of interactions occurring between parasites and the gut microbiota, with a profound impact on both host immunity and metabolic potential. Despite this information, the exploration of the effects that parasite infections exert on populations of commensal gut microbes of veterinary species is a field of research in its infancy. In this article, we summarise studies that have contributed to current knowledge of helminth-microbiota interactions in species of veterinary interest, and identify possible avenues for future research in this area, which could include the exploitation of such relationships to improve parasite control and delay or prevent the development of anthelmintic resistance

Development of an effective feeding regimen using dry chocory (cichorium intybus) roots to eradicate zoonotic helminths in pigs

Published Thesi

Gastrointestinal worms and bacteria: From association to intervention

A plethora of studies, both experimental and epidemiological, have indicated the occurrence of associations between infections by gastrointestinal (GI) helminths and the composition and function of the host gut microbiota. Given the worldwide risk and spread of anthelmintic resistance, particularly for GI parasites of livestock, a better understanding of the mechanisms underpinning the relationships between GI helminths and the gut microbiome, and between the latter and host health, may assist the development of novel microbiome-targeting and other bacteria-based strategies for parasite control. In this article, we review current and prospective methods to manipulate the host gut microbiome, and/or to exploit the immune stimulatory and modulatory properties of gut bacteria (and their products) to counteract the negative impact of GI worm infections; we also discuss the potential applications of these intervention strategies in programmes aimed to aid the fight against helminth diseases of humans and livestock.Javier Sotillo is a Miguel Servet Fellow funded by Instituto de Salud Carlos III (CP17III/00002).S

The relationships between faecal egg counts and gut microbial composition in UK Thoroughbreds infected by cyathostomins

A growing body of evidence, particularly in humans and rodents, supports the existence of a complex network of interactions occurring between gastrointestinal (GI) helminth parasites and the gut commensal bacteria, with substantial effects on both host immunity and metabolic potential. However, little is known of the fundamental biology of such interactions in other animal species. Nonetheless, given the considerable economic losses associated with GI parasites, particularly in livestock and equines, as well as the global threat of emerging anthelmintic resistance, further explorations of the complexities of host-helminth-microbiota interactions in these species are needed. This study characterises, for the first time, the composition of the equine bacterial commensal flora associated with the presence, in faecal samples, of low (Clow) - and high (Chigh) numbers of eggs of an important group of equine GI parasites (i.e. the cyathostomins), prior to and following anthelmintic treatment. High-throughput sequencing of microbial 16S rRNA amplicons and associated bioinformatics and statistical analyses of sequence data revealed strong clustering according to faecal egg counts (FEC) (P = 0.003). A trend towards increased populations of Methanomicrobia (class) and Dehalobacterium (genus) was observed in Clow in comparison to Chigh. Anthelmintic treatment in Chigh was associated with a significant reduction of the bacterial phylum TM7 14 days post-ivermectin administration, as well as a transient expansion of Adlercreuzia spp. at 2 days post-treatment. This study provides a first insight into the discovery of the intimate mechanisms governing host-parasite-microbiota interactions in equids, and sets a basis for the development of novel, biology-based intervention strategies against equine GI helminths based on the manipulation of the commensal gut flora.L.E.P. is a Post-Doctoral Research Fellow co-funded by the Horserace Betting Levy Board (UK), the Thoroughbred Breeders’ Association (UK) and the British European Breeders Fund (Grant no. VET/EPDF/2016-2). T.P.J. is the grateful recipient of a Ph.D. scholarship from the Biotechnology and Biological Sciences Research Council (UK). Research in C.C. laboratory is funded by grants by the Royal Society, UK and the Isaac Newton Trust/Wellcome Trust/University of Cambridge, UK

The costs and benefits of sociality in semi-free ranging Barbary macaques (Macaca sylvanus)

Infektionen mit Parasiten sind im Tierreich allgegenwärtig, und ein erhöhtes Risiko für Parasitenübertragung gilt als einer der größten Nachteile des Gruppenlebens. Mit zunehmender Gruppengröße und Anzahl an Interaktionen sollte es zu häufigeren Kontakten mit Krankheitserregern und damit zu vermehrter Krankheitsübertragung kommen. Im Gegensatz dazu tragen soziale Integration und enge affiliative Beziehungen bei sozial lebenden Tierarten zu besserem Gesundheitszustand, höherer Lebenserwartung und höherem Reproduktionserfolg bei. Es wird daher angenommen, dass durch soziale Interaktionen positive Einflüsse auf die Gesundheit, unter anderem niedrigere Anfälligkeit für Krankheiten, entstehen, die zu Fitnessvorteilen führen. Besonders bei wildlebenden Tieren sind die Mechanismen, über die Sozialverhalten zu Gesundheitsvorteilen führt, noch weitestgehend unbekannt. Jüngste methodologische und theoretische Fortschritte auf den Gebieten der Krankheitsökologie und Öko-Immunologie erleichtern die Erforschung der Verbindungen zwischen Parasiten und dem Sozialverhalten des Wirts. Somit rückt die Erforschung der Dynamik zwischen Wirtstieren und Parasiten und die verbindung zwischen Sozialverhalten und Gesundheit zunehmend auch in den Fokus der Verhaltensökologie und Evolutionsbiologie. Gastrointestinale Parasiten sind ein vielversprechendes System, um die Zusammenhänge zwischen Sozialverhalten und Gesundheit zu untersuchen, da sie nicht-invasiv analysiert werden können. Allerdings sind Wirt-Parasitenbeziehungen komplex und beinhalten oft Rückkopplungsschleifen: Während Infektionen mit Parasiten das Verhalten des Wirtes beeinflussen, bestimmen Verhalten und Physiologie des Wirtes Kontaktraten mit Krankheitserregern und Anfälligkeit für Infektionen. Da zumeist Korrelationsstudien vorliegen, sind die kausalen Zusammenhänge zwischen den Interaktionen von Wirtsverhalten, Physiologie und Parasiteninfektionen weitestgehend unbekannt. Zusätzlich kann das Verhalten des Wirtes gleichzeitig zum Kontakt mit Krankheitserregern und der Infektionsanfälligkeit beitragen und beide Komponenten können miteinander verwoben sein, so dass es schwierig ist, die Rolle von sozialen Interaktionen für Parasitenübetragung zu entschlüsseln. Um die Ursachen und Konsequenzen von Infektionen mit gastrointestinalen Helminthen zu verstehen, werden in dieser Dissertation die Zusammenhänge zwischen gastrointestinalen Parasiten, Physiologie, Verhalten und sozialen Interaktionen bei sozialen Primaten, den Berberaffen (Macaca sylvanus) untersucht. Dabei mache ich mir die routinemäßige Entwurmung einer halbwilden Population zu Nutze, die zur Freiheit von Infektionen mit Strongiliden führt. Durch die experimentelle Veränderung des Parasitenstatuses können eher Schlüsse über Kausalzusammenhänge der Interaktionen zwischen Wirt und Parasiten, insbesondere im Bezug auf das Sozialverhalten, gezogen werden, als es in Korrelationsstudien möglich ist. Hierzu werden Verhaltensdaten (ca. 3500 Stunden) mit Analysen von molekularen Marker der Immunregulation (Neopterin im Urin), der körperlichen Verfassung (C-Peptide im Urin) und der Aktivität der Hypothalamus-Hypophysen-Nebennieren-(HPA)-Achse und die Bestimmung des Infektionsstatuses verbunden. Um die methodische Ungenauigkeit der nicht-invasiver Parasitenanalysen zu berücksichtigen, werden Patch-Occupancy-Modelle zur Abschätzung der Infektionswahrscheinlichkeiten und des Risikos der Wiederansteckung genutzt. Zusätzlich wird analysiert, ob infektionsbezogene Verhaltensänderungen eine Folge von Krankheitsverhalten oder der Vermeidung infizierter Artgenossen sind. Dies lässt Rückschlüsse auf den Einfluss von Parasiteninfektionen auf das Sozialverhalten zu, die möglicherweise auf die soziale Evolution der Tiere übertragen werden können. Ich überprüfe auch, ob soziale Fellpflege als möglicher direkter Übertragungsweg das Risiko einer Ansteckung mit Darmparasiten vorhersagt. Infektionen mit Strongiliden, zumeist Oesophagostomum spp., waren in der Studiengruppe allgegenwärtig und zeigten meist geringe Ei-Ausscheidungsraten, aber große interindividuelle Unterschiede in der Wiederansteckungswahrscheinlichkeit. Diese Infektionen verursachten keine offensichtlichen Symptome oder eine Veränderung der körperlichen Verfassung. Sie riefen dennoch Anzeichen für Krankheitsverhalten hervor, messbar als stärkere Aktivität der HPA-Achse und geringere Aktivität infizierter Tiere. Die Entwurmung rief keine Veränderungen der Neopterinlevel hervor. Diese stiegen jedoch im Alter an, was auf Immunoseneszenz hindeutet. Da Infektionen mit weiteren Helminthen vorwiegend in älteren Individuen vorkommen, könnte dies darauf hindeuten, dass Immunoseneszenz die Fähigkeit der Tiere, Parasiteninfektionen einzudämmen, beeinflusst. Die Rate, mit der die Tiere sich Artgenossen annäherten, hing nicht mit dem eigenen Parasitenstatus, sondern dem des Partners zusammen, was auf eine Vermeidung infizierter Artgenossen hindeutet. Wiederansteckung wurde durch Marker für Parasitenanfälligkeit und -kontakt bestimmt. Der stärkste Prädiktor für eine schnellere Wiederansteckung war eine Ko-Infektion mit weiteren gastrointestinalen Helminthen. Es gab keine Hinweise darauf, dass HPA-Achsenaktivität oder Immunfunktion starke Prädiktoren für eine Wiederansteckung sind. Eine gute körperliche Verfassung führte zu einer tendenziellen Erhöhung des Ansteckungsrisikos, was wahrscheinlich ein Zeichen für Toleranz gegenüber Darmparasiteninfektionen in Berberaffen ist. Der Übertragunsweg von Strongyliden über die Umwelt wurde bestätigt: Tiere, die viel Zeit in Gebieten mit hoher Kotkontamination verbrachten, d.h. wahrscheinlich häufig Kontakt mit infektiösen Parasitenstadien hatten, hatten auch ein erhöhtes Ansteckungsrisiko. Starke soziale Bindungen zu Partnern des anderen Geschlechts verringerten das Infektionsrisiko, wahrscheinlich auf Grund positiver Effekte sozialer Interaktionen auf die Funktion des Immunsystems. Im Gegensatz dazu führten soziale Fellpflege mit einer Vielzahl an Partnern und enge Bindungen mit gleichgeschlechtlichen Partnern zu einer höheren Ansteckungswahrscheinlichkeit, was eine soziale Komponente bei der Parasitenübertragung nahelegt. Dabei deutet die Diskrepanz zwischen den Effekten von Bindungen zu getrennt- und gleichgeschlechtlichen Partnern wahrscheinlich darauf hin, dass spezifische Verhaltensweisen unterschiedlich stark zum Kontakt mit Parasiten und der Infektionsanfälligkeit beitragen. Zusammenfassend legen die Ergebnisse nahe, dass Infektionen mit gastrointestinalen Parasiten das Sozialverhalten nichtmenschlicher Primaten beeinflussen können. In Anbetracht der zweischneidigen Rolle sozialer Beziehungen erscheint das Ausprägen weniger, starker Bindungen als mögliche Strategie, die Vorteile von Beziehungen voll auszukosten und gleichzeitig die Nachteile zu minimieren - mit dem Vorbehalt, dass einige Interaktionsmuster mehr Vorteile mit sich bringen können als andere. Durch meine Ergebnisse ergeben sich eine Reihe neuer Fragen, die in zukünftigen Studien beantwortet werden sollten, insbesondere ob Primaten Parasitentoleranzstrategien nutzen können, um die Kosten von Parasiteninfektionen einzudämmen. Zu entschlüsseln, welche Komponenten des Sozialverhaltens mit Kontakt zu Krankheitserregern und der Anfälligkeit für Infektionen zusammenhängen ist wichtig, um die Variation des Infektionsrisikos zwischen einzelnen Tieren und deren Beitrag zur Übertragung von Krankheiten innerhalb einer Population zu verstehen. Zu untersuchen, ob Unterschiede in der Reaktion auf Parasiteninfektionen Langzeitfolgen für Gesundheit und Fitness vorhersagen, ist ein wichtiger nächster Schritt, um den Einfluss der Wirt-Parasitenbeziehung auf das Verhalten möglicherweise die soziale Evolution von Wirtstieren zu verstehen.Parasite infections are ubiquitous throughout the animal kingdom, and increased risk of parasite transmission has been suggested as one of the major costs of group living. With bigger group size and higher interaction frequencies, transmission is expected to increase due to higher pathogen exposure. In contrast, social integration and close affiliative relationships are known predictors of increased health, longevity and reproductive success in social animals. Sociality is thus hypothesized to offer fitness benefits by improving health, including reduced susceptibility to infectious diseases. The underlying mechanisms mediating the health benefits of social interactions are still largely unclear, particularly in wildlife. Recent methodological and theoretical advances in the fields of disease ecology and eco-immunology make studying the links between host sociality and parasites more feasible. Consequently, understanding host-parasite dynamics and the role of sociality for health has received increasing attention in behavioural ecology and evolutionary biology. Gastrointestinal (GI) helminths are a powerful tool to study the links between sociality and health, as they can be assessed noninvasively. However, host-parasite interactions are complex and can function as feedback loops: parasites alter their host’s physiology and behaviour, which in turn predict exposure and susceptibility to parasite infection. Often the directionality of the links between host behaviour, sociality and physiology and infection isn’t clear due to the correlational nature of conducted studies. Additionally, host behaviour can contribute to both exposure and susceptibility simultaneously and both factors can be intertwined, so understanding the role of sociality for parasite transmission is challenging. In this thesis I investigate the host-parasite dynamic between GI helminth infections and a social primate, the Barbary macaque (Macaca sylvanus), aiming at understanding the causes and consequences of GI helminth infection. Capitalizing on strongyle nematode clearance by routine anthelmintic treatment in a semi-free ranging population, I can take a step beyond correlational studies and draw more causal inferences about the direction of host-parasite interactions, placing a special focus on social behaviour. I combine behavioural observation data (~ 3500 hours) with analyses of molecular markers of immune regulation (urinary neopterin, uNEO), physical condition (urinary C-peptide, uCP) and hypothalamic-pituitary-adrenal (HPA) axis activation and parasite status assessment. This enables me to assess the consequences of parasite clearance and investigate the predictors of reinfection with GI helminths. To account for uncertainty of noninvasively assessed parasite status, I use patch occupancy modelling to estimate infection probabilities and individual reinfection risk. I test whether infection related behavioural changes are attributable to sickness behaviour or avoidance of infected conspecifics to extrapolate the impact of GI helminth infections on social behaviour and potentially evolution. With regard to parasite transmission, I test whether grooming predicts reinfection risk, indicating transmission due to social contact. Strongyle nematode infections, mostly caused by Oesophagostomum spp., were ubiquitous within the study population, with generally low egg shedding and large inter-individual variation in reinfection risk. Infections did not cause overt symptoms or affect physical condition. They nonetheless elicited sickness behaviour responses, namely increased HPA axis activation in combination with reduced activity. Anthelmintic treatment did not alter uNEO levels, but uNEO increased with age, implying immunosenescence. As coinfections with further GI helminths occurred mostly in old individuals, immunosenescence might influence an individual’s ability to cope with GI helminth infections in general. Individual frequency to initiate proximity to others was not predicted by an individual’s, but by the potential partner’s infection status, indicating avoidance of infected individuals. Reinfection was predicted by measures of both susceptibility and exposure. The strongest predictor of earlier reinfection was coinfection with further GI helminth taxa. I found no evidence for HPA axis activation and immune function as strong predictors of reinfection. Being in good physical condition tended to increase reinfection risk, indicating the presence of parasite tolerance strategies in Barbary macaques. Time spent in areas likely contaminated with faeces, a measure of exposure to infective parasite stages, emerged as a predictor of increased infection risk, confirming the direct environmental transmission route of strongyle nematodes. High social bond strength with opposite sex partners decreased reinfection probability, probably due to reduced susceptibility resulting from immunomodulatory effects of affiliative interactions. In contrast, grooming a high number of partners and strong bonds with same sex partners emerged as predictors of increased infection probability, implying a social component of transmission. Social interactions can thus have an ambivalent effect, contributing to both protection from and increased risk of GI helminth infections. The discrepancy between same and opposite sex bond effects is likely attributable to differences in interaction patterns, resulting in different relative contributions of same and opposite sex bonds to exposure and susceptibility. In conclusion, the results suggest that GI parasite infections can influence social behaviour in nonhuman primates. Given the dual role of social interactions for GI helminth transmission, a possible strategy to maximize benefits while limiting costs of sociality could be selective formation of strong bonds with a small number of partners, with the caveat that particular interaction patterns might be more beneficial than others. My results lead to a range of questions which need to be addressed by future research, particularly whether primates mitigate costs of infection by employing tolerance strategies. Causally linking components of social behaviour to exposure and susceptibility will be important for understanding individual variation in infection risk and contribution to transmission through a population. Investigating whether variation in responses to GI helminth infections predict long-term health and fitness outcomes will be vital to assess the impact of host-parasite dynamics on behaviour and potentially host social evolution

Untersuchung zur Wurmausscheidung, Resistenz und Toleranz gegenüber Nematoden-Infektionen in Hühnergenotypen mit unterschiedlichen Leistungsrichtungen

The main objective was to investigate whether selection for divergent performance directions resulted in a different ability to cope with nematode infections. Therefore male and female birds of divergent genotypes developed either for meat or egg production or for both purposes were separately investigated. The worm expulsion and associated immune responses have been studied in the chicken host, too. It was found that tolerance to nematode infections is dependent on both growth rate and laying performance level in male and female chickens, respectively. In males the infection reduced the body weight in the fast-growing chickens only, whereas infection had no effect on slower growing genotypes. Differences found between male birds may be associated with a mismatch between the genotype-specific nutrient requirements and the nutrient supply during infectious challenges. In females, the laying rate (LR) of the high performing genotype was reduced by infection in the early infection period, whereas the LR of the lower performing genotype was reduced in the advanced infection period only. The time dependent impairment in laying performance was likely due to differences in genetic programming for production peak and persistency of the two genotypes. Both the host individual performance level as well as the nutrient supply appears to play a key role in tolerance against nematode infections in chickens. Resistance to infections, however, is dependent on the type of infection (i.e., experimentally vs. naturally infections). While overall resistance against infections likely depend on the host immunity and the intestinal conditions of the host, susceptibility to re-infections, which finally determines the risk for an infection, may be associated with host behaviour. Worm expulsion was found to take place non-linearly in three distinct phases, in which juvenile worms were especially targeted. Expulsion of the worms was associated with humoral and cell-mediated immune responses

Infection with soil-transmitted helminths and their impact on coinfections

The most important soil-transmitted helminths (STHs) affecting humans are roundworms, whipworms, and hookworms, with a large proportion of the world’s population infected with one or more of these intestinal parasites. On top of that, concurrent infections with several viruses, bacteria, protozoa, and other helminths such as trematodes are common in STH-endemic areas. STHs are potent immunomodulators, but knowledge about the effects of STH infection on the direction and extent of coinfections with other pathogens and vice versa is incomplete. By focusing on Kenya, a country where STH infections in humans are widespread, we provide an exemplary overview of the current prevalence of STH and co-occurring infections (e.g. with Human Immunodeficiency Virus, Plasmodium falciparum, Giardia duodenalis and Schistosoma mansoni). Using human data and complemented by experimental studies, we outline the immunomechanistic interactions of coinfections in both acutely STH transmigrated and chronically infected tissues, also highlighting their systemic nature. Depending on the coinfecting pathogen and immunological readout, STH infection may restrain, support, or even override the immune response to another pathogen. Furthermore, the timing of the particular infection and host susceptibility are decisive for the immunopathological consequences. Some examples demonstrated positive outcomes of STH coinfections, where the systemic effects of these helminths mitigate the damage caused by other pathogens. Nevertheless, the data available to date are rather unbalanced, as only a few studies have considered the effects of coinfection on the worm’s life cycle and associated host immunity. These interactions are complex and depend largely on the context and biology of the coinfection, which can act in either direction, both to the benefit and detriment of the infected host