Advances in Parasitology最新文献

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 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.

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.

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.

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.

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.

Vector-borne pathogens (VBPs) of canines are a diverse range of infectious agents, including viruses, bacteria, protozoa and multicellular parasites, that are pernicious and potentially lethal to their hosts. Dogs across the globe are afflicted by canine VBPs, but the range of different ectoparasites and the VBPs that they transmit predominate in tropical regions. Countries within the Asia-Pacific have had limited prior research dedicated to exploring the epidemiology of canine VBPs, whilst the few studies that have been conducted show VBP prevalence to be high, with significant impacts on dog health. Moreover, such impacts are not restricted to dogs, as some canine VBPs are zoonotic. We reviewed the status of canine VBPs in the Asia-Pacific, with particular focus on nations in the tropics, whilst also investigating the history of VBP diagnosis and examining recent progress in the field, including advanced molecular methods, such as next-generation sequencing (NGS). These tools are rapidly changing the way parasites are detected and discovered, demonstrating a sensitivity equal to, or exceeding that of, conventional molecular diagnostics. We also provide a background to the armoury of chemopreventive products available for protecting dogs from VBP. Here, field-based research within high VBP pressure environments has underscored the importance of ectoparasiticide mode of action on their overall efficacy. The future of canine VBP diagnosis and prevention at a global level is also explored, highlighting how evolving portable sequencing technologies may permit diagnosis at point-of-care, whilst further research into chemopreventives will be essential if VBP transmission is to be effectively controlled.

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.

One of the most widely distributed African freshwater fish is the African sharptooth catfish Clarias gariepinus (Burchell) that is naturally distributed in 8 of the 10 ichthyofaunal regions of this continent. Clarias gariepinus is a highly valued and cheap staple to local communities and an ideal aquaculture species. Consequently, interest in the parasitic communities of C. gariepinus has increased as parasites may accidentally be ingested by humans when eating uncooked fish or can be introduced into culture systems through fish stocks supplied from local rivers which affect yield, growth, and marketability. This review provides an overview of the ∼107 metazoan parasite species known to parasitise C. gariepinus in Africa and their general life cycles, morphology, paratenic and post-cyclic infections, and the biogeography and validity of records are discussed. A brief overview is included on the application of some of these parasites in environmental studies and their link to human health.

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.