Recent reports of CRISPR/Cas9 genome editing in parasitic helminths open up new avenues for research on these dangerous pathogens. However, the complex morphology and life cycles inherent to these parasites present obstacles for the efficient application of CRISPR/Cas9‐targeted mutagenesis. This is especially true with the trematode flukes where only modest levels of gene mutation efficiency have been achieved. Current major challenges in the application of CRISPR/Cas9 for study of parasitic worms thus lie in enhancing gene mutation efficiency and overcoming (...) issues involved in host passage so that mutated parasites survive. Strategies developed for CRISPR/Cas9 studies on Caenorhabditis elegans, protozoa and mammalian cells, including novel delivery methods, the choice of selectable markers, and refining mutation precision represent novel tactics whereby these impediments can be overcome. Furthermore, employing CRISPR/Cas9‐mediated gene drive to interfere with vector transmission represents a novel approach for the control of parasitic worms that is worthy of further exploration. (shrink)

In this manuscript, we explore the potential therapeutic use of helminths. After analyzing helminths’ role in connection with human health from the perspective of their symbiotic and evolutionary relationship, we critically examine some studies on their therapeutic applications. In doing so, we focus on some prominent mechanisms of action and potential benefits, but also on the exaggerations and theoretical and methodological difficulties of such proposals. We conclude that further studies are needed to fully explore the potential benefits of (...) this perspective, and we encourage the scientific community in doing so. (shrink)

Schistosoma mansoni is one of several species of trematode helminths responsible for schistosomiasis, a major parasitic infection of man. Genetic analysis in mice has revealed that the protective immunity induced against this parasite by an attenuated larval vaccine is strongly influenced by genes regulating the activation of macrophage effector cells. The latter finding suggests that the induction of cell‐mediated immunity may be a successful strategy for a non‐living vaccine against the human infection.

SummaryA health facility-based approach to delivering anthelminthic drugs to children aged 12–59 months in Zambia was compared with an approach where community-directed treatment was added to the HF approach. This paper reports on the socio-demographic factors associated with treatment coverage in the HF+ComDT and HF areas after 18 months of implementation. Data were collected by interviewing 288 and 378 caretakers of children aged 12–59 months in the HF+ComDT and HF areas, respectively. Bivariate and multivariate logistic regression analyses were used for (...) data analysis. Statistically significant predictors of a child being treated were: a child coming from the HF+ComDT area, being 12–36 months old, the family having lived in the area for >20 years, coming from a household with only one under-five child and living ≤3 km from the health facility. It is concluded that socio-demographic factors are of public health relevance and affect treatment coverage in both the HF+ComDT and the HF approaches. The implementation and strengthening of interventions like ComDT that bring treatment closer to households will enable more children to have access to treatment. (shrink)

Schistosomes are intravascular parasitic helminths (blood flukes) that infect more than 200 million people globally. Proteomic analysis of the tegument (skin) of these worms has revealed the surprising presence of glycolytic enzymes on the parasite's external surface. Immunolocalization data as well as enzyme activity displayed by live worms confirm that functional glycolytic enzymes are indeed expressed at the host–parasite interface. Since these enzymes are traditionally considered to function intracellularly to drive glycolysis, in an extracellular location they are hypothesized to (...) engage in novel “moonlighting” functions such as immune modulation and blood clot dissolution that promote parasite survival. For instance, several glycolytic enzymes can interact with plasminogen and promote its activation to the thrombolytic plasmin; some can inhibit complement function; some induce B cell proliferation or macrophage apoptosis. Several pathogenic bacteria and protists also express glycolytic enzymes externally, suggesting that moonlighting functions of extracellular glycolytic enzymes can contribute broadly to pathogen virulence. Also see the video abstract here https://youtu.be/njtWZ2y3k_I. (shrink)

The Hygiene Hypothesis has been recognized as an important cornerstone to explain the sudden increase in the prevalence of asthma and allergic diseases in modernized culture. The recent epidemic of allergic diseases is in contrast with the gradual implementation of Homo sapiens sapiens to the present-day forms of civilization. This civilization forms a gradual process with cumulative effects on the human immune system, which co-developed with parasitic and commensal Helminths. The clinical manifestation of this epidemic, however, became only visible (...) in the second half of the twentieth century. In order to explain these clinical effects in terms of the underlying IgE-mediated reactions to innocuous environmental antigens, the low biodiversity of antigens in the domestic environment plays a pivotal role. The skewing of antigen exposure as a cumulative effect of reducing biodiversity in the immediate human environment as well as in changing food habits, provides a sufficient and parsimonious explanation for the rise in allergic diseases in a highly developed and helminth-free modernized culture. Socio-economic tendencies that incline towards a further reduction of environmental biodiversity may provide serious concern for future health. This article explains that the “Hygiene Hypothesis”, the “Old Friends Hypothesis”, and the “Skewed Antigen Exposure Hypothesis” are required to more fully explain the rise of allergy in modern societies. (shrink)

CRISPR‐Cas technology accelerates development of fast, accurate, and portable diagnostic tools, typified by recent applications in COVID‐19 diagnosis. Parasitic helminths cause devastating diseases afflicting 1.5 billion people globally, representing a significant public health and economic burden, especially in developing countries. Currently available diagnostic tests for worm infection are neither sufficiently sensitive nor field‐friendly for use in low‐endemic or resource‐poor settings, leading to underestimation of true prevalence rates. Mass drug administration programs are unsustainable long‐term, and diagnostic tools – required to (...) be rapid, specific, sensitive, cost‐effective, and user‐friendly without specialized equipment and expertise – are urgently needed for rapid mapping of helminthic diseases and monitoring control programs. We describe the key features of the CRISPR‐Cas12/13 system and emphasise its potential for the development of effective tools for the diagnosis of parasitic and other neglected tropical diseases (NTDs), a key recommendation of the NTDs 2021–2030 roadmap released by the World Health Organization. (shrink)

Cytokines, also referred to as interleukins, are the major orchestrators of host defence processes, and, as such, are involved in insults, repair and restoration of tissue homeostasis. This review summarises recent findings on and emerging models of the biological roles of the double-edged sword interleukin-13 (IL-13), which have been principally obtained from studies in mice that are deficient for IL-13, or its components. IL-13-mediated functions not only contribute to the susceptible phenotype in Leishmania major infection but also seem to play (...) a protective role in chronic leishmaniasis. Moreover, IL-13 plays a key protective role in the expulsion of helminths from the gut while also actively contributing to the pathology in schistosomiasis. In allergic asthma, IL-13 has also been found to be a key factor. Therapeutic administration of an IL-13 inhibitor in mice successfully prevents both the allergic disease phenotype and schistosoma egg-induced lung pathology. If this scenario holds true in humans, we soon may have an efficient drug for treatment of IL-13-mediated diseases. BioEssays 22:646–656, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Background In the context of limited health care budgets in countries where Neglected Tropical Diseases are endemic, scaling up disease control interventions entails the setting of priorities. However, solutions based solely on cost-effectiveness analyses may lead to biased and insufficiently justified priorities. Objectives The objectives of this paper are to 1) demonstrate how a range of equity concerns can be used to identify feasible priority setting criteria, 2) show how these criteria can be fed into a multi-criteria decision-making matrix, and (...) 3) discuss the conditions under which this decision-making procedure should be carried out in a real-world decision-making context. Methods This paper draws on elements from theories of decision analysis and ethical theories of fair resource allocation. We explore six typical NTD interventions by employing a modified multi-criteria decision analysis model with predefined criteria, drawn from a priority setting guide under development by the WHO. To identify relevant evidence for the six chosen interventions, we searched the PubMed and Cochrane databases. Discussion Our in vitro multi-criteria decision analysis suggested that case management for visceral leishmaniasis should be given a higher priority than mass campaigns to prevent soil-transmitted helminthic infections. This seems to contradict current health care priorities and recommendations in the literature. We also consider procedural conditions that should be met in a contextualised decision-making process and we stress the limitations of this study exercise. Conclusion By exploring how several criteria relevant to the multi-facetted characteristics of NTDs can be taken into account simultaneously, we are able to suggest how improved priority settings among NTDs can be realised. (shrink)

BackgroundIn the context of limited health care budgets in countries where Neglected Tropical Diseases (NTDs) are endemic, scaling up disease control interventions entails the setting of priorities. However, solutions based solely on cost‐effectiveness analyses may lead to biased and insufficiently justified priorities.ObjectivesThe objectives of this paper are to 1) demonstrate how a range of equity concerns can be used to identify feasible priority setting criteria, 2) show how these criteria can be fed into a multi‐criteria decision‐making matrix, and 3) discuss (...) the conditions under which this decision‐making procedure should be carried out in a real‐world decision‐making context.MethodsThis paper draws on elements from theories of decision analysis and ethical theories of fair resource allocation. We explore six typical NTD interventions by employing a modified multi‐criteria decision analysis model with predefined criteria, drawn from a priority setting guide under development by the WHO. To identify relevant evidence for the six chosen interventions, we searched the PubMed and Cochrane databases.DiscussionOur in vitro multi‐criteria decision analysis suggested that case management for visceral leishmaniasis should be given a higher priority than mass campaigns to prevent soil‐transmitted helminthic infections. This seems to contradict current health care priorities and recommendations in the literature. We also consider procedural conditions that should be met in a contextualised decision‐making process and we stress the limitations of this study exercise.ConclusionBy exploring how several criteria relevant to the multi‐facetted characteristics of NTDs can be taken into account simultaneously, we are able to suggest how improved priority settings among NTDs can be realised. (shrink)

La filosofía de la ciencia de Kuhn se ha utilizado en distintas áreas de la biología, y aquí examinamos la posibilidad utilizar dicha filosofía en la helmintología. Ofrecemos dos posibles interpretaciones de la historia de esa disciplina. En la primera de ellas, utilizamos únicamente los conceptos de la primera etapa de la obra de Kuhn. En la segunda interpretación, hacemos uso de los conceptos de matriz disciplinaria y ejemplar. Según la primera interpretación, la etapa preparadigmática de la helmintología se inició (...) entre los siglos XVI y XVII inclusive, y continuó hasta la segunda mitad del siglo XIX, época en donde la helmintología adquiere su primer paradigma. Desde el punto de vista de la segunda interpretación, la primera matriz disciplinaria de la zoología fue inaugurada por Aristóteles, quien también proporcionó el primer "ejemplar" para el estudio de los helmintos. Thomas Kuhn's philosophy of science has been used in several areas of biology, and here we examine the possibility of applying kuhnian philosophy to helminthology. We offer two possible interpretations of the history of that discipline. In our first interpretation, we only use the concepts Kuhn introduces in the first stage of his works. In the second interpretation, we use the concepts of disciplinary matrix and exemplar. According to the first interpretation, the pre-paradigmatic period of helminthology started between the 16th and 17th centuries, and continued up until the second half of the 19th century, when helminthology acquired its first paradigm. From the point of view of the second interpretation, the first disciplinary matrix for zoology was inaugurated by Aristotle, who also delivered the first exemplar for the study of helminths. (shrink)

The history of helminthology in the Early Modern Period has been characterized as a debate between two camps, the internalists and the externalists. The internalists believed that helminths are spontaneously generated within the body of the host, whereas the externalists claimed that helminths enter the host from the external environment. According to the this account, the debate between these two camps ended in the nineteenth century with the victory of the externalist viewpoint. Here, we redefine these two terms, (...) as well as the beliefs that the two groups upheld. We suggest that internalists were not necessarily committed to the theory of spontaneous generation, nor were externalists committed to its rejection. These terms only refer to the place where helminths supposedly originate, but not to the process by which they are generated. Thus, some internalists rejected the theory of spontaneous generation, while others held externalist viewpoints and at the same time accepted this theory. We claim that the debate did not end with the victory of the externalist camp; rather, a new position which we call “life-cyclism”, emerged and incorporated some elements of the two earlier positions. (shrink)

In the last few years, annexins have been discovered in several nematodes and other parasites, and distinct differences between the parasite annexins and those of the hosts make them potentially attractive targets for anti‐parasite therapeutics. Annexins are ubiquitous proteins found in almost all organisms across all kingdoms. Here, we present an overview of novel annexins from parasitic organisms, and summarize their phylogenetic and biochemical properties, with a view to using them as drug or vaccine targets. Building on structural and biological (...) information that has been accumulated for mammalian and plant annexins, we describe a predicted additional secondary structure element found in many parasite annexins that may confer unique functional properties, and present a specific antigenic epitope for use as a vaccine. (shrink)

Graphical AbstractThe recent development of transgenic mouse strains depleted in basophils has helped in elucidating the diverse functions of basophils in the primary in secondary immune responses: from acting as antigen-presenting cells and contributing to B cell activation to their role in allergic inflammation, worm expulsion and tick resistance.