Advances in Parasitology最新文献

Parasitic worms (helminths) release extracellular vesicles (EVs) -membrane-surrounded, nanosized structures loaded with a repertoire of active biomolecules- as part of their excretory/secretory products. These particles play key roles in intercellular communication, not only within multicellular organisms but also between organisms that establish stable biological associations, as it occurs during parasitism. Since their "rediscovery" in 2012, the field of helminth EVs has expanded significantly, with a wealth of research conducted both in model organisms and parasites of human and veterinary importance. These investigations have revealed that helminth EVs play active roles in host-parasite interactions. In this article, we review milestone literature on helminth EVs and point out remaining knowledge gaps regarding several aspects of their biogenesis, composition, and interaction with the host. Furthermore, we outline current perspectives on the potential application of these bio-nanoparticles to the theragnostic of helminth infections, highlighting the main challenges hindering the translation of experimental evidence into actual EV-based tools for the control of human and livestock helminthiases.

Leishmaniasis, caused by vector-borne Leishmania spp., continues to cause a significant burden of disease around the world. These sand fly-transmitted protozoan parasites, of which numerous species exist, are responsible for cutaneous (CL), mucocutaneous (MCL), and visceral leishmaniasis (VL) - diseases which can be debilitating or even fatal, especially in immunocompromised individuals. In many areas, dogs serve as a reservoir for Leishmania. Treatment of leishmaniasis relies on a minute arsenal of chemotherapeutic drugs that are toxic, costly, or difficult to source. Meanwhile, an effective vaccine formula remains elusive, although vaccines for the prevention of canine leishmaniasis (CanL) have been in use for decades. Treatment failure (TF) is an important concern for leishmaniasis. Incomplete cure or relapse is relatively common in cases of VL and CL. When it comes to CanL, TF or relapse is typical; host immunity and drug characteristics play a major role. Meanwhile, drug resistance (DR) has also become a major issue in some regions and may play an important role in TF. Leishmania parasites possess an impressively plastic genome and utilize copy number variations (CNVs) and single-nucleotide polymorphisms (SNPs) to escape drug pressure. Futhermore, studies have shown that they deploy extracellular vesicles (EVs) with a variety of key molecules as cargo, contributing not only to host-pathogen interaction & pathogenesis, but also to spread of DR. TF and DR are discussed here in detail, as well as the current state of vaccine development and available and prospective therapies for CL, MCL, VL, and CanL. Variables affecting the course of disease are addressed. Finally, the role of dogs as a reservoir for Leishmania parasites, as well as their potential to contribute to the spread of DR parasites, is considered.

Intestinal protozoan infections remain highly prevalent among children and women of reproductive age, particularly across low- and middle-income countries. However, their impact on maternal-child outcomes-including birth weight, prematurity, intrauterine growth restriction (IUGR), and/or childhood stunting remains largely undetermined. Here, we conducted a systematic literature search across six databases for studies published between 1976 and 2024 that examined potential associations between gastrointestinal (GI) protozoan infections, and childbirth and growth outcomes. A total of 99 cross-sectional and longitudinal studies were included. Cross-sectional studies reporting odds ratios (ORs) or adjusted odds ratios (AORs) for stunting, unadjusted and adjusted mean differences (MD) in height-for-age z-score (HAZ), and those reporting regression coefficients for HAZ differences were included in meta-analysis. Meta-analyses of cross-sectional data revealed significant associations between child protozoan infections and stunting, with the strongest evidence for Cryptosporidium spp. (AOR = 2.38, 95 % CI: 1.55 to 3.64). Giardia spp. infections were also associated with higher odds of stunting (AOR = 1.70, 95 % CI: 1.12 to 2.58) and reduced HAZ (MD: -0.42, 95 % CI: -0.53 to -0.30). Narrative synthesis of longitudinal studies supported these associations, providing robust evidence that asymptomatic infections are significantly associated with reduced growth. Five studies examined maternal protozoan infections and birth/stunting outcomes, revealing mixed evidence. Findings underscore the need for improved detection, treatment strategies, and targeted public health interventions, including better access to water, sanitation and hygiene (WASH), to address both symptomatic and asymptomatic protozoan infections. Further research is needed in particular to disentangle the relationship between maternal GI protozoan infections and child health outcomes, and to encompass a broader range of protozoan species to elucidate their impact on childhood stunting.

The giant roundworm Ascaris is an important nematode parasite of humans and pigs worldwide. Ascariasis, the disease associated with Ascaris infection, is classified as a neglected tropical disease and has been targeted for elimination as a public health problem by 2030. Despite increased efforts to control Ascaris in humans, it remains highly prevalent. A major challenge is the long-term viability of Ascaris eggs in the environment, resulting in a significant reservoir. Here, we review present understanding of Ascaris environmental contamination, and existing and emerging approaches for surveillance and control. Another potential challenge is represented by the emergence of resistance to the drugs (benzimidazoles) used for Ascaris control and treatment. We describe the current evidence for resistance in Ascaris and related ascarid parasites and recent work to understand mechanisms of resistance, which may be different to those described for other nematodes. There has been much recent progress in the availability and use of 'omic resources for Ascaris. We review how 'omic data is being employed to provide insights into Ascaris population structure, drug pressure and transmission dynamics at different scales. We also describe how 'omic data is being exploited through reverse vaccinology to identify new vaccine targets for Ascaris, offering a possible alternative avenue for control. We conclude by highlighting some emerging research areas which could be applied to Ascaris and reflecting on how recent advances can impact on progress towards achievement of the WHO 2030 target.

Neglected tropical diseases (NTDs) encompass 20 conditions or groups of diseases that affect almost exclusively the rural poor in low- and middle-income countries (LMIC). NTDs cause severe and chronic disabilities, from disfigurement and cognitive defects to death, and present substantial public health and socioeconomic burdens. Amongst NTDs, infections by parasitic protozoans, helminths and arthropod and non-arthropod ectoparasites, are of critical importance, with soil-transmitted helminths (STHs) representing the most widespread and prevalent NTDs globally. Whilst mass drug administration is the current strategy for control of helminth (STH and schistosomiasis) infections, treatment alone is inadequate due to the absence of lasting immunity against reinfections and the persisting concern of emerging drug resistance. The prevention and ultimate elimination of parasitic NTDs would avoid unnecessary suffering and significantly reduce poverty; hence, the potential of effective antiparasitic vaccines offers hope to billions, particularly those in sub-Saharan Africa. Given the strong links between NTDs and poverty - both regarding the demographics of the most affected communities and the socio-economic impact that these diseases exert - vaccines for these conditions are often referred to as "antipoverty vaccines". Here, a comprehensive analysis of the current state of antipoverty vaccine development is provided, with a focus on the potential for antiparasitic vaccines. This encompasses both a review of the current scientific literature and an assemblage of key stake-holder perspectives obtained through semi-structured interviews, all aimed to assess the future directives, utility and acceptability of these vaccines. The causes behind the current paucity of antipoverty vaccines are explored and global policy recommendations to assist their development and acceptance addressed. There was unanimous agreement among stakeholder interviewees on the importance and value of antipoverty vaccines, although it was felt that this sentiment does not extend to funders or policymakers from the Global North. Such findings highlight the scientific challenges in/of creating these vaccines, and how such challenges are amplified by financial constraints. The lack of funding reflects low profitability and biases against diseases largely of morbidity rather than mortality, as well as potentially the issues of poor people in poor countries and race/ethnicity. Solutions to how barriers affecting vaccine uptake on the ground can be addressed are proposed, primarily involving increased access to healthcare infrastructure, enhanced compliance through education, and involvement of local communities in all stages of development and rollout.

Resistance to chemotherapy continues to limit the ability to cure infectious diseases and cancer. Resistance to antiparasitic drugs is affecting control of many pathogens in human and veterinary medicine. In veterinary medicine, particular attention has been focused on resistance to parasites of livestock, including helminths, ectoparasites and protozoa, as an effect of intensive treatment regimens that promote economic sustainability of production systems. Less attention has been given to drug resistance in parasites of companion animals. We provide a comprehensive review of current knowledge of drug resistance in ectoparasites, helminths and protozoa of importance in dogs and cats to establish a baseline assessment of the field and provide recommendations for research priorities and therapeutic alternatives.

Epithelial barriers are critical in our interaction with the outside world. They mediate gas exchange in the lung, nutrient absorption in the gut and provide a barrier against pathogen entry throughout the body. Until relatively recently, these mechanical barrier functions were thought to represent the primary mechanism by which the epithelium protects against infection; however, current research is unveiling a broad range of interactions between epithelial barrier cells and the immune response. This Chapter reviews current evidence that the epithelium is central to the immune response to soil-transmitted helminths, with a focus on the cytokines and other mediators that epithelial cells produce. We compare and contrast the cellular sources and initiating factors that lead to epithelial cytokine production, the role of the epithelium in ejecting and killing parasitic worms, and the techniques by which these parasites counteract the activities of the epithelium.

Anisakidosis is a fish-borne zoonosis characterised by mild to severe gastrointestinal (GI) symptoms and potentially linked to the onset of allergic reactions and cancer. The disease follows the ingestion of marine products infected with third-stage (L3) larvae of the genera Anisakis and Phocanema. Epidemiologically, anisakiasis is most prevalent in countries where fish consumption is high, such as Japan and the Mediterranean regions; however, the globalization of dietary habits has contributed to the expansion of its incidence worldwide. In this Chapter, we provide an overview of aspects related to the disease, from the description of the biological features of L3 and fourth-stage (L4) larvae, to the mechanisms likely responsible for allergic reactions and GI lesions. Multiple factors contribute to the allergenicity of Anisakis spp., including exposure time, GI and endo-lysosomal stability and antigenic structure. A growing body of research focuses on the parasite excretory/secretory (E/S) products, including extracellular vesicles, encompassing proteolytic enzymes, immunomodulatory molecules, and potential virulence factors. E/S products play key roles in host-parasite interactions, such as tissue invasion, immune evasion, and allergic sensitization. Both in vivo and in vitro studies (conducted in murine models of infection and human epithelial and dendritic cell cultures, respectively) have enhanced current understanding of anisakidosis pathophysiology, elucidating mechanisms of mucosal damage, cytokine production, and adaptive immune responses. These models also offer insights into chronic disease outcomes, that include formation of eosinophilic granulomas, chronic abdominal pain, and a potential correlation between anisakidosis and the occurrence of a tumorigenic microenvironment in the GI tract.

The development of parasite cultures has long been pivotal in advancing parasitology, with broad applications in medicine, veterinary science, and biology. Laboratory cultures are invaluable tools for studying parasite biology, host-parasite interactions, and the development of treatments and vaccines. However, cultures of digenean trematodes under laboratory conditions remain a challenging yet critical endeavour in parasitology. These parasites hold significant importance to both human health and ecological systems. Nevertheless, trematodes exhibit a complex life cycle involving multiple hosts, which demands innovative culture methods. This review aims to provide a comprehensive overview of laboratory culture techniques for digenean trematodes, covering in vitro, in vivo, and in ovo approaches. These techniques are discussed in order across the different parasitic life stages of trematodes, from sporocyst/redia to adults, as well as the handling of trematode eggs, with a focus on optimising media composition, host-cell integration, and environmental parameters. In vitro approaches, particularly those using host-cell-based media or host-derived sera, have shown promise for certain zoonotic species. However, cultures of marine trematodes often face limitations due to suboptimal media protocols. On the other hand, in vivo and in ovo methods, while generally achieving higher success rates, raise ethical and logistical concerns. Despite notable progress, the standardisation of protocols and the adaptation of techniques for a broader range of species remain significant challenges in digenean trematode cultures. Future research should prioritise the development of host-cell-based media, innovative culture technologies, and integrative molecular and proteomic tools to address these limitations and further our understanding of trematode biology.

Alveolar echinococcosis (AE) caused by Echinococcus multilocularis is a rare but serious animal and human disease in the northern hemisphere. We review published data and reports of E. multilocularis in animals and humans in Europe and North America since 2015. New findings in Europe include the first detection of AE in a wild canid (golden jackal, Canis aureus) and brown hare (Lepus europaeus); evidence for and against the role of domestic and wild felids as definitive hosts of E. multilocularis; new reports in wildlife in 2 countries and human AE in 8 countries; slow range expansion in France, Italy, and Sweden; and increased prevalence in red fox (Vulpes vulpes) in endemic regions of Austria, Italy, and Germany. New findings in North America include rapid range expansion to the west, south, and east (from 5 to 9 of the 13 provinces/territories in Canada, and from 13 to 24 of 50 states in the USA); an unprecedented number of canine and human cases of AE associated with European haplotypes, especially in Alberta, Canada; the first detection of the parasite in a new rodent intermediate host (eastern chipmunk, Tamias striatus); and the first detections in dogs as definitive hosts. Surveillance in wild canids (red fox in Europe, as well as coyotes, Canis latrans, in North America) is key to determining local risk in endemic areas, and to maintain country freedom status in Europe; in addition, recent findings suggest that large-scale screening of livers of horses and pigs may also be useful. From a One Health perspective, control of AE would benefit from voluntary case registries, regulation to prevent introduction of novel strains or hosts into new areas, increased clinical suspicion and access to early diagnoses, broad application of standardized disease staging approaches, standardized molecular classification schemes to enable source attribution and tracing between animals and humans, and increased access to established and novel chemotherapeutic options.