The ascarids are a large group of parasitic nematodes that infect a wide range of animal species. In humans, they cause neglected diseases of poverty; many animal parasites also cause zoonotic infections in people. Control measures include hygiene and anthelmintic treatments, but they are not always appropriate or effective and this creates a continuing need to search for better ways to reduce the human, welfare and economic costs of these infections. To this end, Le Studium Institute of Advanced Studies organized a two-day conference to identify major gaps in our understanding of ascarid parasites with a view to setting research priorities that would allow for improved control. The participants identified several key areas for future focus, comprising of advances in genomic analysis and the use of model organisms, especially Caenorhabditis elegans, a more thorough appreciation of the complexity of host-parasite (and parasite-parasite) communications, a search for novel anthelmintic drugs and the development of effective vaccines. The participants agreed to try and maintain informal links in the future that could form the basis for collaborative projects, and to co-operate to organize future meetings and workshops to promote ascarid research.

The civilizations of ancient Egypt and Nubia played a key role in the cultural development of Africa, the Near East, and the Mediterranean world. This study explores how their location along the River Nile, agricultural practices, the climate, endemic insects and aquatic snails impacted the type of parasites that were most successful in their populations. A meta-analysis approach finds that up to 65% of mummies were positive for schistosomiasis, 40% for headlice, 22% for falciparum malaria, and 10% for visceral leishmaniasis. Such a disease burden must have had major consequences upon the physical stamina and productivity of a large proportion of the workforce. In contrast, the virtual absence of evidence for whipworm and roundworm (so common in adjacent civilizations in the Near East and Europe) may have been a result of the yearly Nile floods fertilising the agricultural land, so that farmers did not have to fertilise their crops with human faeces.

For over a century, vector ecology has been a mainstay of vector-borne disease control. Much of this research has focused on the sensory ecology of blood-feeding arthropods (black flies, mosquitoes, ticks, etc.) with terrestrial vertebrate hosts. Of particular interest are the cues and sensory systems that drive host seeking and host feeding behaviours as they are critical for a vector to locate and feed from a host. An important yet overlooked component of arthropod vector ecology are the phenotypic changes observed in infected vectors that increase disease transmission. While our fundamental understanding of sensory mechanisms in disease vectors has drastically increased due to recent advances in genome engineering, for example, the advent of CRISPR-Cas9, and high-throughput "big data" approaches (genomics, proteomics, transcriptomics, etc.), we still do not know if and how parasites manipulate vector behaviour. Here, we review the latest research on arthropod vector sensory systems and propose key mechanisms that disease agents may alter to increase transmission.

Intestinal trematodes constitute a major group of helminths that parasitize humans and animals with relevant morbidity and mortality. Despite the importance of the intestinal trematodes in medical and veterinary sciences, immunology and pathology of these helminth infections have been neglected for years. Apart from the work focused on the members of the family Echnistomatidae, there are only very isolated and sporadic studies on the representatives of other families of digeneans, which makes a compilation of all these studies necessary. In the present review, the most salient literature on the immunology and pathology of intestinal trematodes in their definitive hosts in examined. Emphasis will be placed on members of the echinostomatidae family, since it is the group in which the most work has been carried out. However, we also review the information on selected species of the families Brachylaimidae, Diplostomidae, Gymnophallidae, and Heterophyidae. For most of these families, coverage is considered under the following headings: (i) Background; (ii) Pathology of the infection; (iii) Immunology of the infection; and (iv) Human infections.

The mouse whipworm, Trichuris muris, has been used for over 60 years as a tractable model for human trichuriasis, caused by the related whipworm species, T. trichiura. The history of T. muris research, from the discovery of the parasite in 1761 to understanding the lifecycle and outcome of infection with different doses (high versus low dose infection), as well as the immune mechanisms associated with parasite expulsion and chronic infection have been detailed in an earlier review published in 2013. Here, we review recent advances in our understanding of whipworm biology, host-parasite interactions and basic immunology brought about using the T. muris mouse model, focussing on developments from the last decade. In addition to the traditional high/low dose infection models that have formed the mainstay of T. muris research to date, novel models involving trickle (repeated low dose) infection in laboratory mice or infection in wild or semi-wild mice have led to important insights into how immunity develops in situ in a multivariate environment, while the use of novel techniques such as the development of caecal organoids (enabling the study of larval development ex vivo) promise to deliver important insights into host-parasite interactions. In addition, the genome and transcriptome analyses of T. muris and T. trichiura have proven to be invaluable tools, particularly in the context of vaccine development and identification of secreted products including proteins, extracellular vesicles and micro-RNAs, shedding further light on how these parasites communicate with their host and modulate the immune response to promote their own survival.

The proteasome is a proteolytically active molecular machine comprising many different protein subunits. It is essential for growth and survival in eukaryotic cells and has long been considered a drug target. Here, we summarize the biology of the proteasome, the early research relating to the development of specific proteasome inhibitors (PIs) for treatment of various cancers, and their translation and eventual evolution as exciting therapies for parasitic diseases. We also highlight the development and adaptation of technologies that have allowed for a deep understanding of the idiosyncrasies of individual parasite proteasomes, as well as the preclinical and clinical advancement of PIs with remarkable therapeutic indices.

The most severe form of malaria, caused by infection with Plasmodium falciparum parasites, continues to be an important cause of human suffering and poverty. The P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of clonally variant antigens, which mediates the adhesion of infected erythrocytes to the vascular endothelium in various tissues and organs, is a central component of the pathogenesis of the disease and a key target of the acquired immune response to malaria. Much new knowledge has accumulated since we published a systematic overview of the PfEMP1 family almost ten years ago. In this chapter, we therefore aim to summarize research progress since 2015 on the structure, function, regulation etc. of this key protein family of arguably the most important human parasite. Recent insights regarding PfEMP1-specific immune responses and PfEMP1-specific vaccination against malaria, as well as an outlook for the coming years are also covered.

The broad fish tapeworm, Dibothriocephalus latus (Diphyllobothriidea), is the most important causative agent of diphyllobothriosis, a fish-borne zoonosis, in Europe. Part I of this review focused on the occurrence of D. latus in northwestern and central Europe, particularly in Fennoscandia, the Baltic, the Alpine lakes and Danube River regions during 1900-2020. Part II summarises data on D. latus from the European and Asian parts of Russia and from Asian countries. The tapeworm has occurred throughout Russia, with the most important foci in (i) the Republic of Karelia in the northwest of European Russia, (ii) the Volga River basin in the central and southern parts of European Russia, (iii) the Ob-Irtysh rivers region in the Ural region, (iv) the Yenisei-Lena rivers region in Siberia, and (v) the Lake Baikal basin in Siberia. The incidence of diphyllobothriosis has declined in recent decades, especially in European Russia, but zoonosis is still prevalent in some regions of Siberia. Cases reported from Arctic regions, the region around Lake Baikal, and the Pacific coast, including the Amur basin, however, were probably misidentifications with D. dendriticus and/or D. nihonkaiensis. No other Asian country where D. latus findings represented either imported cases or misidentifications had natural focus of diphyllobothriosis. Patterns of distribution of D. latus occurrence were similar in all Eurasian foci between 1900 and 2020. The numbers of records were associated with historical and epidemiological milestones of particular time periods.

Parasitic nematodes infect over 2 billion individuals worldwide, primarily in low-resource areas, and are responsible for several chronic and potentially deadly diseases. Throughout their life cycle, these parasites are thought to use astacin metalloproteases, a subfamily of zinc-containing metalloendopeptidases, for processes such as skin penetration, molting, and tissue migration. Here, we review the known functions of astacins in human-infective, soil-transmitted parasitic nematodes - including the hookworms Necator americanus and Ancylostoma duodenale, the threadworm Strongyloides stercoralis, the giant roundworm Ascaris lumbricoides, and the whipworm Trichuris trichiura - as well as the human-infective, vector-borne filarial nematodes Wuchereria bancrofti, Onchocerca volvulus, and Brugia malayi. We also review astacin function in parasitic nematodes that infect other mammalian hosts and discuss the potential of astacins as anthelmintic drug targets. Finally, we highlight the molecular and genetic tools that are now available for further exploration of astacin function and discuss how a better understanding of astacin function in human-parasitic nematodes could lead to new avenues for nematode control and drug therapies.

The emergence of high-throughput methodologies such as next-generation sequencing and proteomics has necessitated significant advancements in biological databases and bioinformatic tools, therefore reshaping the landscape of research into parasitic peptidases. In this review we outline the development of these resources along the -omics technologies and their transformative impact on the field. Apart from extensive summary of general and specific databases and tools, we provide a general pipeline on how to use these resources effectively to identify candidate peptidases from these large datasets and how to gain as much information about them as possible without leaving the office chair. This pipeline is then applied in an illustrative case study on the endothelin-converting enzyme 1 homologue from Schistosoma mansoni and attempts to highlight the contemporary capabilities of bioinformatics. The case study demonstrate how such approach can aid to hypothesize enzyme functions and interactions through computational analysis alone effectively and emphasizes how such virtual investigations can guide and optimize subsequent wet lab experiments therefore potentially saving precious time and resources. Finally, by showing what can be achieved without traditional wet laboratory methods, this review provides a compelling narrative on the use of bioinformatics to bridge the gap between big data and practical research applications, highlighting the key role of these technologies in furthering our understanding of parasitic diseases.

Over the last decade, research on the most studied parasite, Plasmodium falciparum, has disclosed significant findings in protease research. Detailed descriptions of the individual roles of protease isoenzymes from various protease classes encoded by the parasite genome have been elucidated, along with their functional and biochemical characterizations. These insights have enabled the development of innovative chemotherapy using low molecular weight inhibitors targeting specific molecular sites. Progress has been made in understanding the proteolytic cascade associated with the apical complex, particularly the roles of aspartyl proteases plasmepsins IX and X as master regulators. Additionally, advancements in direct and alternative methods of proteasome inhibition and expression regulation have been achieved. Research on digestive/food vacuole-associated proteases, with a focus on essential metalloproteases, has also seen significant developments. The rise of extensive genomic datasets and functional genomic tools for other parasitic organisms now allows these approaches to be applied to the study and treatment of other, less known parasitic diseases, aiming to uncover specific biological mechanisms and develop innovative, less toxic chemotherapies.

Hard ticks (family Ixodidae) are significant vectors of pathogens affecting humans and animals. This review explores the composition of tick saliva, focusing on proteases and protease inhibitors, their biological roles, and their potential in vaccines and therapies. Tick saliva contains various proteases, mostly metalloproteases, serpins, cystatins, and Kunitz-type inhibitors, which modulate host hemostatic, immune, and wound healing responses to facilitate blood feeding and pathogen transmission. Proteases inhibit blood clotting, degrade extracellular matrix components, and modulate immune responses. Serpins, cystatins, and Kunitz-type inhibitors further inhibit key proteases involved in coagulation and inflammation, making them promising candidates for anticoagulant, anti-inflammatory, and immunomodulatory therapies. Several tick proteases and protease inhibitors have shown potential as vaccine targets, reducing tick feeding success and pathogen transmission. Future research should focus on comprehensive proteomic and genomic analyses, detailed structural and functional studies, and vaccine trials. Advanced omics approaches and bioinformatics tools will be crucial in uncovering the complex interactions between ticks, hosts, and pathogens, improving tick control strategies and public health outcomes.

Malaria remains a major health hazard for humans, despite the availability of efficacious antimalarial drugs and other interventions. Given that the disease is often deadly for children under 5 years and pregnant women living in malaria-endemic areas, an efficacious vaccine to prevent transmission and clinical disease would be ideal. Plasmodium, the causative agent of malaria, uses proteases and protease inhibitors to control and process to invade host, modulate host immunity, and for pathogenesis. Plasmodium parasites rely on these proteases for their development and survival, including feeding their metabolic needs and invasion of both mosquito and human tissues, and have thus been explored as potential targets for prophylaxis. In this chapter, we have discussed the potential of proteases like ROM4, SUB2, SERA4, SERA5, and others as vaccine candidates. We have also discussed the role of some protease inhibitors of plasmodium and mosquito origin. Inhibition of plasmodium proteases can interrupt the parasite development at many different stages therefore understanding their function is key to developing new drugs and malaria vaccines.

Soil-transmitted helminths continue to be a serious problem causing disease and morbidity globally. Children, mostly school-aged, are more at risk of these infections. The main strategy for control remains to be the mass drug administration (MDA) of antihelminthic drugs. With the limitation of MDA to prevent re-infection, the need for additional approaches such as hygiene education and improvements in water, sanitation and hygiene (WASH) infrastructure are required. Although the importance of health education as a crucial component of an integrated approaches to STH control is highlighted, this component has often been disregarded because the other more complex solutions have been the focus of most studies and programmes. We performed literature searches from four bibliographic databases - Scopus, PubMed, Web of Science and Cochrane Library - to determine availability of studies on the impact of health education interventions targeting STH infections on schoolchildren in Southeast Asia. Our review found only three studies that evaluated health education interventions targeting children. The current lack of evidence in this area suggests the need for more studies assessing the impact of health education intervention for STH control. A successful health education programme for STH called "The Magic Glasses" has been developed targeting schoolchildren in China and the Philippines. This public health intervention displayed significant impact in terms of improving knowledge, attitude and practices, reducing prevalence of STH infections in schoolchildren and encouraging compliance to MDA. This article details the successes and benefits of the Magic Glasses programme as a promising control tool for STH in the Southeast Asian region.

Fish parasitology is a dynamic and internationally important discipline with numerous biological, ecological and practical applications. We reviewed optimal fish and parasite sampling methods for key ectoparasite phyla (i.e. Ciliophora, Platyhelminthes, Annelida and Arthropoda) as well as recent advances in molecular detection of ectoparasites in aquatic environments. Ideally, fish capture and anaesthesia as well as parasite recovery methods should be validated to eliminate potential sampling bias and inaccuracy in determining ectoparasite population parameters. There are considerable advantages to working with fresh samples and live parasites, when combined with appropriate fixation methods, as sampling using dead or decaying materials can lead to rapid decomposition of soft-bodied parasites and subsequent challenges for identification. Sampling methods differ between target phyla, and sometimes genera, with optimum techniques largely associated with identification of parasite microhabitat and the method of attachment. International advances in fish parasitology can be achieved through the accession of whole specimens and/or molecular voucher specimens (i.e. hologenophores) in curated collections for further study. This approach is now critical for data quality because of the increased application of environmental DNA (eDNA) for the detection and surveillance of parasites in aquatic environments where the whole organism may be unavailable. Optimal fish parasite sampling methods are emphasised to aid repeatability and reliability of parasitological studies that require accurate biodiversity and impact assessments, as well as precise surveillance and diagnostics.

Zanzibar is among the few places in sub-Saharan Africa where interruption of Schistosoma transmission seems an achievable goal. Our systematic review identifies and discusses milestones in schistosomiasis research, control and elimination efforts in Zanzibar over the past 100 years. The search in online databases, libraries, and the World Health Organization Archives revealed 153 records published between May 1928 and August 2022. The content of records was summarised to highlight the pivotal work leading towards urogenital schistosomiasis elimination and remaining research gaps. The greatest achievement following 100 years of schistosomiasis interventions and research is undoubtedly the improved health of Zanzibaris, exemplified by the reduction in Schistosoma haematobium prevalence from>50% historically down to<5% in 2020, and the absence of severe morbidities. Experiences from Zanzibar have contributed to global schistosomiasis guidelines, whilst also revealing challenges that impede progression towards elimination. Challenges include: transmission heterogeneity requiring micro-targeting of interventions, post-treatment recrudescence of infections in transmission hotspots, biological complexity of intermediate host snails, emergence of livestock Schistosoma species complicating surveillance whilst creating the risk for interspecies hybridisation, insufficient diagnostics performance for light intensity infections and female genital schistosomiasis, and a lack of acceptable sanitary alternatives to freshwater bodies. Our analysis of the past revealed that much can be achieved in the future with practical implementation of integrated interventions, alongside operational research. With continuing national and international commitments, interruption of S. haematobium transmission across both islands is within reach by 2030, signposting the future demise of urogenital schistosomiasis across other parts of sub-Saharan Africa.

As we strive towards the ambitious goal of malaria elimination, we must embrace integrated strategies and interventions. Like many diseases, malaria is heterogeneously distributed. This inherent spatial component means that geography and geospatial data is likely to have an important role in malaria control strategies. For instance, focussing interventions in areas where malaria risk is highest is likely to provide more cost-effective malaria control programmes. Equally, many malaria vector control strategies, particularly interventions like larval source management, would benefit from accurate maps of malaria vector habitats - sources of water that are used for malarial mosquito oviposition and larval development. In many landscapes, particularly in rural areas, the formation and persistence of these habitats is controlled by geographical factors, notably those related to hydrology. This is especially true for malaria vector species like Anopheles funestsus that show a preference for more permanent, often naturally occurring water sources like small rivers and spring-fed ponds. Previous work has embraced geographical concepts, techniques, and geospatial data for studying malaria risk and vector habitats. But there is much to be learnt if we are to fully exploit what the broader geographical discipline can offer in terms of operational malaria control, particularly in the face of a changing climate. This chapter outlines potential new directions related to several geographical concepts, data sources and analytical approaches, including terrain analysis, satellite imagery, drone technology and field-based observations. These directions are discussed within the context of designing new protocols and procedures that could be readily deployed within malaria control programmes, particularly those within sub-Saharan Africa, with a particular focus on experiences in the Kilombero Valley and the Zanzibar Archipelago, United Republic of Tanzania.

The rise to prominence of some Angiostrongylus species through associated emerging disease in humans and dogs has stimulated calls for a renewed focus on the biology of this genus and three related genera. Although significant research efforts have been made in recent years these have tended to focus on individual species and specific aspects such as diagnosis and treatment of disease or new records of occurrence and hosts. This comprehensive review takes a comparative approach, seeking commonalities and differences among species and asking such questions as: Which species belong to this and to closely related genera and how are they related? Why do only some species appear to be spreading geographically and what factors might underlie range expansion? Which animal species are involved in the life cycles as definitive, intermediate, paratenic and accidental hosts? How do parasite larvae find, infect and develop within these hosts? What are the consequences of infection for host health? How will climate change affect future spread and global health? Appreciating how species resemble and differ from each other shines a spotlight on knowledge gaps and provides provisional guidance on key species characteristics warranting detailed study. Similarities exist among species, including the basic life cycle and transmission processes, but important details such as host range, climatic requirements, migration patterns within hosts and disease mechanisms differ, with much more information available for A. cantonensis and A. vasorum than for other species. Nonetheless, comparison across Angiostrongylus reveals some common patterns. Historically narrow definitive host ranges are expanding with new knowledge, combining with very broad ranges of intermediate gastropod hosts and vertebrate and invertebrate paratenic and accidental hosts to provide the backdrop to complex interactions among climate, ecology and transmission that remain only partly understood, even for the species of dominant concern. Key outstanding questions concern larval dynamics and the potential for transmission outside trophic relations, relations between infection and disease severity in different hosts, and how global change is altering transmission beyond immediate impacts on development rate in gastropods. The concept of encounter and compatibility filters could help to explain differences in the relative importance of different gastropod species as intermediate hosts and determine the importance of host community composition and related environmental factors to transmission and range. Across the group, it remains unclear what, physiologically, immunologically or taxonomically, delimits definitive, accidental and paratenic hosts. Impacts of infection on definitive host fitness and consequences for population dynamics and transmission remain mostly unexplored across the genus. Continual updating and cross-referencing across species of Angiostrongylus and related genera is important to synthesise rapid advances in understanding of key traits and behaviours, especially in important Angiostrongylus species that are emerging causative agents of disease in humans and other animals.

Neospora caninum is an apicomplexan and obligatory intracellular parasite, which is the leading cause of reproductive failure in cattle and affects other farm and domestic animals, but also induces neuromuscular disease in dogs of all ages. In cattle, neosporosis is an important health problem, and has a considerable economic impact. To date there is no protective vaccine or chemotherapeutic treatment on the market. Immuno-prophylaxis has long been considered as the best control measure. Proteins involved in host cell interaction and invasion, as well as antigens mediating inflammatory responses have been the most frequently assessed vaccine targets. However, despite considerable efforts no effective vaccine has been introduced to the market to date. The development of effective compounds to limit the effects of vertical transmission of N. caninum tachyzoites has emerged as an alternative or addition to vaccination, provided suitable targets and safe and efficacious drugs can be identified. Additionally, the combination of both treatment strategies might be interesting to further increase protectivity against N. caninum infections and to decrease the duration of treatment and the risk of potential drug resistance. Well-established and standardized animal infection models are key factors for the evaluation of promising vaccine and compound candidates. The vast majority of experimental animal experiments concerning neosporosis have been performed in mice, although in recent years the numbers of experimental studies in cattle and sheep have increased. In this review, we discuss the recent findings concerning the progress in drug and vaccine development against N. caninum infections in mice and ruminants.

Around 25% of the global population suffer from one or more parasitic infections, of which food- and vector-borne parasitic zoonotic diseases are a major concern. Additionally, zoonoses and communicable diseases, common to man and animals, are drawing increased attention worldwide. Significant changes in climatic conditions, cropping pattern, demography, food habits, increasing international travel, marketing and trade, deforestation, and urbanization play vital roles in the emergence and re-emergence of parasitic zoonoses. Although it is likely to be underestimated, the collective burden of food- and vector-borne parasitic diseases accounts for ∼60 million disability-adjusted life years (DALYs). Out of 20 neglected tropical diseases (NTDs) listed by the World Health Organization (WHO) and the Centres for Disease Control and Prevention (CDC), 13 diseases are of parasitic origin. There are about 200 zoonotic diseases of which the WHO listed eight as neglected zoonotic diseases (NZDs) in the year 2013. Out of these eight NZDs, four diseases, namely cysticercosis, hydatidosis, leishmaniasis, and trypanosomiasis, are caused by parasites. In this review, we discuss the global burden and impacts of food- and vector-borne zoonotic parasitic diseases.

Trematodes, a class of parasitic flatworms, are responsible for a variety of devastating diseases in humans and animals, with schistosomiasis and fascioliasis being prominent examples. Trematode proteolytic systems involved in the host-parasite interaction have emerged as key contributors to the success of trematodes in establishing and maintaining infections. This review concentrates on diverse proteases and protease inhibitors employed by trematodes and provides an update on recent advances in their molecular-level characterization, with a focus on function, structure, and therapeutic target potential.