Advances in Parasitology最新文献

The Neotropical region stands out as a megadiverse area in terms of herpetofauna, hosting more than 4457 species, 2233 of which are distributed across South America. Reptiles are recognized as amplifiers and reservoirs of several pathogens, yet their role in disease cycles and the vectorial potential of their mites and ticks remain poorly understood. These hosts are infested by over 500 species of mites and ticks, classified into 61 genera across 13 families within the orders Trombidiformes (Acariformes), Mesostigmata, and Ixodida (Parasitiformes). Some of these arthropods may serve as vectors of reptile vector-borne diseases (RVBDs), that include bacterial, viral and protozoal pathogens of zoonotic concern. In this article, we explore the main groups of mites and ticks that infest reptiles in the Neotropical region, with a particular focus on vector-borne zoonotic pathogens of reptiles. In addition, we discuss the intricate relationships between these animals, arthropod vectors, and the zoonotic pathogens they may transmit.

A myriad of diseases can be treated by efficacious and potent drugs, yet the delivery efficiency is often hindered due to absorption issues, loss during first-pass metabolism, non-specific delivery, degradation before action and failure to comply to treatment. This has motivated researchers to develop novel methods for drug delivery, including live biotherapeutic products, notably transgenic bacteria delivering foreign therapeutic molecules. Recent advancements demonstrate that controlled experimental human helminth infections are tolerated and safe and may have natural protective attributes for other maladies. Helminths continuously release a cocktail of excretory/secretory proteins (ESP) during infection to aid migration and feeding, and to modulate the host's immune system. Genetic modification, and most specifically Clustered Regularly Interspaced Palindromic Repeats (CRISPR) and CRISPR-associated nucleases, has transformed the study and manipulation of the eukaryotic genome. Using these approaches to target regions of the helminth genome, it is now possible to genetically modify parasitic helminths to constitutively release therapeutic biologics. This approach could be applied to targeting diseases such as Inflammatory Bowel Disease, metabolic diseases such as type 2 diabetes, Coeliac Disease and arthritis, all of which represent a severe burden on both patients and the community. Here, we review the current evidence that wild type and genetically engineered helminths could serve as novel drug-delivery platforms. We specifically focus on species of human hookworms and schistosomes, following published controlled human infections and clinical trials in healthy and diseased human subjects.

Cystoisospora suis, the cause of suckling piglet coccidiosis, is an intestinal protozoan pathogen of worldwide distribution and major economic and animal health significance in swine industry. It is closely related to cyst-forming, facultatively heteroxenic Coccidia like Toxoplasma gondii and Neospora caninum, but its biology resembles more that of the non-cyst-forming, homoxenic genus Eimeria. Lately, a unique in vitro cultivation system for C. suis was developed by which sporozoites infect monolayer cell cultures to produce merozoites which can in turn be propagated in a host-cell free system and develop into sexually differentiated gamonts, gametes and finally oocysts. This system has been used to produce and analyse developmental stages throughout the life cycle of C. suis. Transcriptomic, proteomic and secretomic data are now available, providing information for fundamental and applied research not only on this coccidian species but extrapolation to related parasites. In addition, antiparasitic compounds can be tested in this in vitro model, and further upscaling will provide a higher-throughput system for (pre-clinical) compound screening and in vitro efficacy testing for anticoccidial drugs, supporting the early detection of anticoccidial resistance in C. suis field strains. With these developments, C. suis can be considered a "non-model model" for the Coccidia, bridging the gap between the cyst-forming Sarcocystidae and the non-cyst-forming Eimeriidae, and between parasites of One Health relevance, such as T. gondii, and those members of the Coccidia that are of relevance in veterinary medicine and animal health.

The nematode parasites of Australasian macropodoid and vombatoid marsupials (kangaroos, wallabies and wombats) comprise a variety of endemic species, dominated by members of the superfamily Strongyloidea. Thus far, more than 300 species of strongyloid nematodes have been described from the gastrointestinal tracts of macropodoid (kangaroos, wallabies, rat-kangaroos and potoroos) and vombatoid (wombats) marsupials. These nematodes belong to the family Cloacinidae which is subdivided into two subfamilies, the Cloacininae and Phascolostrongylinae. This chapter reviews the historical and current understanding of their morphology, biology, ecology and recent advances in molecular phylogeny. Knowledge gaps in the systematics, phylogenetic relationships and evolutionary origins of the cloacinid nematodes and possible avenues for future research are also discussed.

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.

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.

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.

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.

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.

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.