Pub Date : 2024-09-01Epub Date: 2024-08-08DOI: 10.1016/j.pt.2024.07.005
Frederic Risch, Alexander Kazakov, Sabine Specht, Kenneth Pfarr, Peter U Fischer, Achim Hoerauf, Marc P Hübner
Although lymphatic filariasis and onchocerciasis have been targeted for global elimination, these helminth infections are still a major public health problem across the tropics and subtropics. Despite decades of research, treatment options remain limited and drugs that completely clear the infections, and can be used on a large scale, are still unavailable. In the present review we discuss the strengths and weaknesses of currently available treatments and new ones in development. Novel candidates (corallopyronin A, DNDi-6166, emodepside, and oxfendazole) are currently moving through (pre)clinical development, while the development of two candidates (AWZ1066S and ABBV-4083/flubentylosin) was recently halted. The preclinical R&D pipeline for filarial infections continues to be limited, and recent setbacks highlight the importance of continuous drug discovery and testing.
{"title":"The long and winding road towards new treatments against lymphatic filariasis and onchocerciasis.","authors":"Frederic Risch, Alexander Kazakov, Sabine Specht, Kenneth Pfarr, Peter U Fischer, Achim Hoerauf, Marc P Hübner","doi":"10.1016/j.pt.2024.07.005","DOIUrl":"10.1016/j.pt.2024.07.005","url":null,"abstract":"<p><p>Although lymphatic filariasis and onchocerciasis have been targeted for global elimination, these helminth infections are still a major public health problem across the tropics and subtropics. Despite decades of research, treatment options remain limited and drugs that completely clear the infections, and can be used on a large scale, are still unavailable. In the present review we discuss the strengths and weaknesses of currently available treatments and new ones in development. Novel candidates (corallopyronin A, DNDi-6166, emodepside, and oxfendazole) are currently moving through (pre)clinical development, while the development of two candidates (AWZ1066S and ABBV-4083/flubentylosin) was recently halted. The preclinical R&D pipeline for filarial infections continues to be limited, and recent setbacks highlight the importance of continuous drug discovery and testing.</p>","PeriodicalId":23327,"journal":{"name":"Trends in parasitology","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-15DOI: 10.1016/j.pt.2024.07.014
Sylvia Cremer, Christopher D Pull
Socially living animals can counteract disease through cooperative defences, leading to social immunity that collectively exceeds the sum of individual defences. In superorganismal colonies of social insects with permanent caste separation between reproductive queen(s) and nonreproducing workers, workers are obligate altruists and thus engage in unconditional social immunity, including highly specialised and self-sacrificial hygiene behaviours. Contrastingly, cooperation is facultative in cooperatively breeding families, where all members are reproductively totipotent but offspring transiently forgo reproduction to help their parents rear more siblings. Here, helpers should either express condition-dependent social immunity or disperse to pursue independent reproduction. We advocate inclusive fitness theory as a framework to predict when and how indirect fitness gains may outweigh direct fitness costs, thus favouring conditional social immunity.
{"title":"Unconditional versus condition-dependent social immunity.","authors":"Sylvia Cremer, Christopher D Pull","doi":"10.1016/j.pt.2024.07.014","DOIUrl":"10.1016/j.pt.2024.07.014","url":null,"abstract":"<p><p>Socially living animals can counteract disease through cooperative defences, leading to social immunity that collectively exceeds the sum of individual defences. In superorganismal colonies of social insects with permanent caste separation between reproductive queen(s) and nonreproducing workers, workers are obligate altruists and thus engage in unconditional social immunity, including highly specialised and self-sacrificial hygiene behaviours. Contrastingly, cooperation is facultative in cooperatively breeding families, where all members are reproductively totipotent but offspring transiently forgo reproduction to help their parents rear more siblings. Here, helpers should either express condition-dependent social immunity or disperse to pursue independent reproduction. We advocate inclusive fitness theory as a framework to predict when and how indirect fitness gains may outweigh direct fitness costs, thus favouring conditional social immunity.</p>","PeriodicalId":23327,"journal":{"name":"Trends in parasitology","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-21DOI: 10.1016/j.pt.2024.07.013
Christian Bogdan, Noor-A-Kasida Islam, David Barinberg, Didier Soulat, Ulrike Schleicher, Baplu Rai
Leishmania is an intracellular protozoan transmitted by sand fly vectors; it causes cutaneous, mucocutaneous, or visceral disease. Its growth and survival are impeded by type 1 T helper cell responses, which entail interferon (IFN)-γ-mediated macrophage activation. Leishmania partially escapes this host defense by triggering immune cell and cytokine responses that favor parasite replication rather than killing. Novel methods for in situ analyses have revealed that the pathways of immune control and microbial evasion are strongly influenced by the tissue context, the micro milieu factors, and the metabolism at the site of infection, which we collectively term the 'immunomicrotope'. Understanding the components and the impact of the immunomicrotope will enable the development of novel strategies for the treatment of chronic leishmaniasis.
利什曼原虫是一种通过沙蝇媒介传播的细胞内原生动物,可引起皮肤、粘膜或内脏疾病。它的生长和存活受到 1 型 T 辅助细胞反应的阻碍,其中包括干扰素(IFN)-γ 介导的巨噬细胞活化。利什曼病通过引发有利于寄生虫复制而非杀死寄生虫的免疫细胞和细胞因子反应,部分躲过了宿主的这种防御。原位分析的新方法揭示了免疫控制和微生物逃避的途径受到感染部位的组织环境、微环境因素和新陈代谢的强烈影响,我们将其统称为 "免疫微环境"。了解免疫微环境的组成和影响将有助于开发治疗慢性利什曼病的新策略。
{"title":"The immunomicrotope of Leishmania control and persistence.","authors":"Christian Bogdan, Noor-A-Kasida Islam, David Barinberg, Didier Soulat, Ulrike Schleicher, Baplu Rai","doi":"10.1016/j.pt.2024.07.013","DOIUrl":"10.1016/j.pt.2024.07.013","url":null,"abstract":"<p><p>Leishmania is an intracellular protozoan transmitted by sand fly vectors; it causes cutaneous, mucocutaneous, or visceral disease. Its growth and survival are impeded by type 1 T helper cell responses, which entail interferon (IFN)-γ-mediated macrophage activation. Leishmania partially escapes this host defense by triggering immune cell and cytokine responses that favor parasite replication rather than killing. Novel methods for in situ analyses have revealed that the pathways of immune control and microbial evasion are strongly influenced by the tissue context, the micro milieu factors, and the metabolism at the site of infection, which we collectively term the 'immunomicrotope'. Understanding the components and the impact of the immunomicrotope will enable the development of novel strategies for the treatment of chronic leishmaniasis.</p>","PeriodicalId":23327,"journal":{"name":"Trends in parasitology","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-31DOI: 10.1016/j.pt.2024.08.001
Matthew E Rogers, Luis Miguel de Pablos, Jack D Sunter
Leishmania make an abundant glycoprotein and proteophosphoglycan-rich gel, called the promastigote secretory gel, in the anterior midgut of their sand fly vector. This gel is a multi-faceted virulence factor which promotes the survival and transmission of the parasites between hosts. Here, we present the case that Leishmania parasites embedded in the promastigote secretory gel should be redefined as a biofilm as it shares striking similarities in biogenesis, form, and function with biofilms of other unicellular organisms. We believe that this reinterpretation will stimulate new hypotheses and avenues of research to improve our understanding of the developmental programme of Leishmania and the interaction these parasites and other kinetoplastids have with their insect hosts.
{"title":"Gels and cells: the Leishmania biofilm as a space and place for parasite transmission.","authors":"Matthew E Rogers, Luis Miguel de Pablos, Jack D Sunter","doi":"10.1016/j.pt.2024.08.001","DOIUrl":"https://doi.org/10.1016/j.pt.2024.08.001","url":null,"abstract":"<p><p>Leishmania make an abundant glycoprotein and proteophosphoglycan-rich gel, called the promastigote secretory gel, in the anterior midgut of their sand fly vector. This gel is a multi-faceted virulence factor which promotes the survival and transmission of the parasites between hosts. Here, we present the case that Leishmania parasites embedded in the promastigote secretory gel should be redefined as a biofilm as it shares striking similarities in biogenesis, form, and function with biofilms of other unicellular organisms. We believe that this reinterpretation will stimulate new hypotheses and avenues of research to improve our understanding of the developmental programme of Leishmania and the interaction these parasites and other kinetoplastids have with their insect hosts.</p>","PeriodicalId":23327,"journal":{"name":"Trends in parasitology","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.1016/j.pt.2024.08.002
Jan Šlapeta, Fiona Vande Velde, María Martínez-Valladares, Candela Canton, Edwin Claerebout, John Stuart Gilleard
The management of parasitic nematodes calls for a shift from conventional, indiscriminate, anthelmintic use to a more precise approach, directed by diagnostics. We should accept those parasite infection intensities that have minimal impact on production and welfare rather than attempt to eliminate them. The diagnostic toolbox for gastrointestinal nematodes (GINs) faces challenges due to anthelmintic resistance (AR), which is species-specific, drug-class-specific, and varies by region. We discuss which traditional tools may become obsolete and which tools need development to gain widespread use. Social science research highlights the need for dialogue between farmers and veterinarians that emphasises effective parasite management and upskilling the veterinary workforce for more sustainable practices centred on diagnostics to be adopted in practice by 2030.
{"title":"Towards precision parasite management for livestock gastrointestinal nematodes in 2030.","authors":"Jan Šlapeta, Fiona Vande Velde, María Martínez-Valladares, Candela Canton, Edwin Claerebout, John Stuart Gilleard","doi":"10.1016/j.pt.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.pt.2024.08.002","url":null,"abstract":"<p><p>The management of parasitic nematodes calls for a shift from conventional, indiscriminate, anthelmintic use to a more precise approach, directed by diagnostics. We should accept those parasite infection intensities that have minimal impact on production and welfare rather than attempt to eliminate them. The diagnostic toolbox for gastrointestinal nematodes (GINs) faces challenges due to anthelmintic resistance (AR), which is species-specific, drug-class-specific, and varies by region. We discuss which traditional tools may become obsolete and which tools need development to gain widespread use. Social science research highlights the need for dialogue between farmers and veterinarians that emphasises effective parasite management and upskilling the veterinary workforce for more sustainable practices centred on diagnostics to be adopted in practice by 2030.</p>","PeriodicalId":23327,"journal":{"name":"Trends in parasitology","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1016/j.pt.2024.08.005
Peter Mergaert, Eric Giraud
Cyst nematode parasites disrupt beneficial associations of crops with rhizobia and mycorrhiza. Chen et al. discovered the mechanism and demonstrated that the soybean cyst nematode Heterodera glycines secretes a chitinase that destroys key symbiotic signals from the microbial symbionts. The authors further developed a chitinase inhibitor that alleviates symbiosis inhibition.
{"title":"Pathogenic nematodes exploit Achilles' heel of plant symbioses.","authors":"Peter Mergaert, Eric Giraud","doi":"10.1016/j.pt.2024.08.005","DOIUrl":"https://doi.org/10.1016/j.pt.2024.08.005","url":null,"abstract":"<p><p>Cyst nematode parasites disrupt beneficial associations of crops with rhizobia and mycorrhiza. Chen et al. discovered the mechanism and demonstrated that the soybean cyst nematode Heterodera glycines secretes a chitinase that destroys key symbiotic signals from the microbial symbionts. The authors further developed a chitinase inhibitor that alleviates symbiosis inhibition.</p>","PeriodicalId":23327,"journal":{"name":"Trends in parasitology","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-20DOI: 10.1016/j.pt.2024.07.008
Anne Lespine, Clara Blancfuney, Roger Prichard, Mélanie Alberich
P-glycoprotein (PGP) is a pivotal transmembrane transporter governing the cellular flux of diverse substances shielding mammals from toxics. It can thwart the effectiveness of medicines such as ivermectin (IVM) and other macrocyclic lactone (ML) anthelmintics, undermining therapeutic efforts. We analyze the role of PGPs in limiting the toxicity of these drugs in hosts, and their potential contribution to anthelmintic resistance in nematodes. Targeting nematode PGPs to increase drug sensitivity to MLs seems interesting, but is hampered by the lack of selective inhibitors. The nuclear hormone receptor (NHR)-8 should be seriously considered as a target because it upregulates multiple PGPs involved in anthelmintic resistance and it is specific to nematodes. This would advance our understanding of host-pathogen dynamics and foster innovative therapeutic strategies.
{"title":"P-glycoproteins in anthelmintic safety, efficacy, and resistance.","authors":"Anne Lespine, Clara Blancfuney, Roger Prichard, Mélanie Alberich","doi":"10.1016/j.pt.2024.07.008","DOIUrl":"https://doi.org/10.1016/j.pt.2024.07.008","url":null,"abstract":"<p><p>P-glycoprotein (PGP) is a pivotal transmembrane transporter governing the cellular flux of diverse substances shielding mammals from toxics. It can thwart the effectiveness of medicines such as ivermectin (IVM) and other macrocyclic lactone (ML) anthelmintics, undermining therapeutic efforts. We analyze the role of PGPs in limiting the toxicity of these drugs in hosts, and their potential contribution to anthelmintic resistance in nematodes. Targeting nematode PGPs to increase drug sensitivity to MLs seems interesting, but is hampered by the lack of selective inhibitors. The nuclear hormone receptor (NHR)-8 should be seriously considered as a target because it upregulates multiple PGPs involved in anthelmintic resistance and it is specific to nematodes. This would advance our understanding of host-pathogen dynamics and foster innovative therapeutic strategies.</p>","PeriodicalId":23327,"journal":{"name":"Trends in parasitology","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-10DOI: 10.1016/j.pt.2024.07.012
Sofia Capasso, Bruno Fusaro, Eliana Lorenti, Juliana Sánchez, Julia Inés Diaz
{"title":"Ixodes uriae (The seabird tick).","authors":"Sofia Capasso, Bruno Fusaro, Eliana Lorenti, Juliana Sánchez, Julia Inés Diaz","doi":"10.1016/j.pt.2024.07.012","DOIUrl":"https://doi.org/10.1016/j.pt.2024.07.012","url":null,"abstract":"","PeriodicalId":23327,"journal":{"name":"Trends in parasitology","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-10DOI: 10.1016/j.pt.2024.07.011
Isabella V F Martins, Guilherme G Verocai
{"title":"Fasciola hepatica.","authors":"Isabella V F Martins, Guilherme G Verocai","doi":"10.1016/j.pt.2024.07.011","DOIUrl":"https://doi.org/10.1016/j.pt.2024.07.011","url":null,"abstract":"","PeriodicalId":23327,"journal":{"name":"Trends in parasitology","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}