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Viruses of protozoan parasites and viral therapy: Is the time now right?

ABSTRACT: Infections caused by protozoan parasites burden the world with huge costs in terms of human and animal health. Most parasitic diseases caused by protozoans are neglected, particularly those associated with poverty and tropical countries, but the paucity of drug treatments and vaccines combined with increasing problems of drug resistance are becoming major concerns for their control and eradication. In this climate, the discovery/repurposing of new drugs and increasing effort in vaccine development should be supplemented with an exploration of new alternative/synergic treatment strategies. Viruses, either native or engineered, have been employed successfully as highly effective and selective therapeutic approaches to treat cancer (oncolytic viruses) and antibiotic-resistant bacterial diseases (phage therapy). Increasing evidence is accumulating that many protozoan, but also helminth, parasites harbour a range of different classes of viruses that are mostly absent from humans. Although some of these viruses appear to have no effect on their parasite hosts, others either have a clear direct negative impact on the parasite or may, in fact, contribute to the virulence of parasites for humans. This review will focus mainly on the viruses identified in protozoan parasites that are of medical importance. Inspired and informed by the experience gained from the application of oncolytic virus- and phage-therapy, rationally-driven strategies to employ these viruses successfully against parasitic diseases will be presented and discussed in the light of the current knowledge of the virus biology and the complex interplay between the viruses, the parasite hosts and the human host. We also highlight knowledge gaps that should be addressed to advance the potential of virotherapy against parasitic diseases.

SUBMITTER: Barrow P

PROVIDER: S-EPMC7522927 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundAt the start of the COVID-19 pandemic, guidance was needed more than ever to direct frontline healthcare and national containment strategies. Rigorous guidance based on robust research was compromised by the emergence of the pandemic and the urgency of need for guidance. Rather than aiming to "get guidance right", guidance developers needed to "get guidance right now".AimTo examine how guidance developers have responded to the need for credible guidance at the start of the COVID-19 pandemic.MethodsAn exploratory mixed-methods study was conducted among guidance developers. A web-based survey and follow-up interviews were used to examine the most pertinent challenges in developing COVID-19 guidance, strategies used to address these, and perspectives on the implications of the COVID-19 pandemic on future guidance development.ResultsThe survey was completed by 46 guidance developers. Survey findings showed that conventional methods of guidance development were largely unsuited for COVID-19 guidance, with 80% (n = 37) of respondents resorting to other methods. From the survey and five follow-up interviews, two themes were identified to bolster the credibility of guidance in a setting of extreme uncertainty: (1) strengthening end-user involvement and (2) conjoining evidence review and recommendation formulation. 70% (n = 32) of survey respondents foresaw possible changes in future guidance production, most notably shortening development time, by reconsidering how to balance between rigour and speed for different types of questions.Conclusion"Getting guidance right" and "getting guidance right now" are not opposites, rather uncertainties are always part of guidance development and require guidance developers to balance scientific robustness with usability, acceptability, adequacy and contingency. This crisis points to the need to acknowledge uncertainties of scientific evidence more explicitly and points to mechanisms to live with such uncertainty, thus extending guidance development methods and processes more widely.

Project description:Parasitic food-borne diseases, particularly those caused by the protozoan parasites Cryptosporidium, Giardia, Cyclospora cayetanensis and Entamoeba are increasingly becoming common and have received considerable attention in the last two decades. The ability of the transmission stages of the parasites to survive in the environment for prolonged periods, globalization of the food industry and changes in eating habits have contributed to the numbers of human infections. This systematic scoping review highlights these important water- and foodborne parasites in the African context, detailing the burden in African water sources, wastewater/effluents and fresh produce. A scoping review search targeting African countries was conducted in Medline, Web of science and African journals online as well as back referencing from included studies covering the period 1990 to January 2020. Out of 1134 studies, 68 were included in the review. The articles covered 17 out of 54 African countries. There were 39/68 studies reporting on water sources while the rest reported on fresh produce. Cryptosporidium prevalence ranged from 6 to 100% in surface water, 4 to 100% in tap water and up to 100% in wastewater and sludge. In fresh produce, Cryptosporidium was reported from five countries with prevalence of 0.8–75%. Giardia was reported in 47 out of 68 articles; prevalence ranged from 2.4% in surface water; 1% to over 70% in tap water; 28–100% in wastewater and 2% - 99% in fresh produce. Prevalence of Cyclospora cayetanensis was lower. Prevalence of Entamoeba was 78% in surface water; 100% in wastewater and up to 99% in fresh produce. This study finds that Africa is no exception to the risk presented by the subject parasites from water and/or food sources. Routine screening for these parasites particularly at household level and provision of adequate and safe drinking water would help to control the parasites. Graphical abstract Unlabelled Image Highlights • African rural communities faced with clean water challenges.• African water bodies and sources contaminated with Cryptosporidium, Giardia, Cyclospora, and Entamoeba and other pathogens• Fresh produce are carriers of protozoan parasites Cryptosporidium, Giardia, Cyclospora, Entamoeba.

Project description:Because parasites have an inextricable relationship with their host, they have the potential to serve as viral reservoirs or facilitate virus host shifts. And yet, little is known about viruses infecting parasitic hosts except for blood-feeding arthropods that are well-known vectors of zoonotic viruses. Herein, we uncovered viruses of flatworms (phylum Platyhelminthes, group Neodermata) that specialize in parasitizing vertebrates and their ancestral free-living relatives. We discovered 115 novel viral sequences, including 1 in Macrostomorpha, 5 in Polycladida, 44 in Tricladida, 1 in Monogenea, 15 in Cestoda, and 49 in Trematoda, through data mining. The majority of newly identified viruses constitute novel families or genera. Phylogenetic analyses show that the virome of flatworms changed dramatically during the transition of neodermatans to a parasitic lifestyle. Most Neodermata viruses seem to codiversify with their host, with the exception of rhabdoviruses, which may switch hosts more often, based on phylogenetic relationships. Neodermata rhabdoviruses also have a position ancestral to vertebrate-associated rhabdo viruses, including lyssaviruses, suggesting that vertebrate-associated rhabdoviruses emerged from a flatworm rhabdovirus in a parasitized host. This study reveals an extensive diversity of viruses in Platyhelminthes and highlights the need to evaluate the role of viral infection in flatworm-associated diseases. IMPORTANCE Little is known about the diversity of parasite-associated viruses and how these viruses may impact parasite fitness, parasite-host interactions, and virus evolution. The discovery of over a hundred viruses associated with a range of free-living and parasitic flatworms, including parasites of economic and clinical relevance, allowed us to compare the viromes of flatworms with contrasting lifestyles. The results suggest that flatworms acquired novel viruses after their transition to a parasitic lifestyle and highlight the possibility that they acquired viruses from their hosts and vice versa. An interesting example is the discovery of flatworm rhabdoviruses that have a position ancestral to rabies viruses and other vertebrate-associated rhabdoviruses, demonstrating that flatworm-associated viruses have emerged in a vertebrate host at least once in history. Therefore, parasitic flatworms may play a role in virus diversity and emergence. The roles that parasite-infecting viruses play in parasite-associated diseases remain to be investigated.

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Viruses of protozoan parasites and viral therapy: Is the time now right?

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