Trained immunity: a cutting edge approach for designing novel vaccines against parasitic diseases?

The preventive situation of parasitosis, a global public health burden especially for developing countries, is not looking that good. Similar to other infections, vaccines would be the best choice for preventing and controlling parasitic infection. However, ideal antigenic molecules for vaccine development have not been identified so far, resulting from the complicated life history and enormous genomes of the parasites. Furthermore, the suppression or down-regulation of anti-infectious immunity mediated by the parasites or their derived molecules can compromise the effect of parasitic vaccines. Comparing the early immune profiles of several parasites in the permissive and non-permissive hosts, a robust innate immune response is proposed to be a critical event to eliminate the parasites. Therefore, enhancing innate immunity may be essential for designing novel and effective parasitic vaccines. The newly emerging trained immunity (also termed innate immune memory) has been increasingly recognized to provide a novel perspective for vaccine development targeting innate immunity. This article reviews the current status of parasitic vaccines and anti-infectious immunity, as well as the conception, characteristics, and mechanisms of trained immunity and its research progress in Parasitology, highlighting the possible consideration of trained immunity in designing novel vaccines against parasitic diseases.

Laboratory associated zoonotic parasitic infections: a review of main agents and biosecurity measures.

Laboratory workers are exposed to the risk of acquiring infections due to the manipulation of infectious materials. The biological hazard for researchers is seven times higher when compared with hospital and public health laboratory workers. Despite the implementation of standardized practices to control infections, multiple cases of Laboratory Associated Infections (LAIs) usually go unreported. There has been a lack of comprehensive epidemiological data regarding the situation of LAIs for parasitic zoonosis and besides, the available sources are not completely updated. Since most accounts of laboratory infections are organism-specific, this study has focused on common pathogenic/zoonotic species handled at parasitological laboratories and summarising the standard biosecurity protocols for the infectious agents. The main characteristics of Cryptosporidium spp., Entamoeba spp, Giardia duodenalis, Toxoplasma gondii, Leishmania spp., Echinococcus spp., Schistosoma spp., Toxocara canis, Ancylostoma caninum, Strongyloides stercoralis are considered in this review in order to assess the potential risk of developing occupational infections in the workplace along with stating prevention and prophylactic measures for each species. It was concluded that the LAIs from these agents can be prevented by using personal protective measures and good laboratory practices. However, further studies are necessary to better understand the environmental resistance of cysts, oocysts and eggs, with a view to select the most suitable disinfection methods. Furthermore, it is fundamental to constantly update epidemiological data of infection acquired by laboratory workers, to develop accurate risk indicators.

The most prominent modulated Annexins during parasitic infections.

Annexins (ANXs) exert different functions in cell biological and pathological processes and are thus known as double or multi-faceted proteins. These sophisticated proteins might express on both parasite structure and secretion and in parasite-infected host cells. In addition to the characterization of these pivotal proteins, describing their mechanism of action can be also fruitful in recognizing their roles in the pathogenesis of parasitic infections. Accordingly, this study presents the most prominent ANXs thus far identified and their relevant functions in parasites and infected host cells during pathogenesis, especially in the most important intracellular protozoan parasitic infections including leishmaniasis, toxoplasmosis, malaria and trypanosomiasis. The data provided in this study demonstrate that the helminth parasites most probably express and secret ANXs to develop pathogenesis while the modulation of the host-ANXs could be employed as a crucial strategy by intracellular protozoan parasites. Moreover, such data highlight that the use of analogs of both parasite and host ANX peptides (which mimic or regulate ANXs physiological functions through various strategies) might suggest novel therapeutic insights into the treatment of parasitic infections. Furthermore, due to the prominent immunoregulatory activities of ANXs during most parasitic infections and the expression levels of these proteins in some parasitic infected tissues, such multifunctional proteins might be also potentially relevant as vaccine and diagnostic biomarkers. We also suggest some prospects and insights that could be useful and applicable to form the basis of future experimental studies.

Statin and aspirin use in parasitic infections as a potential therapeutic strategy: A narrative review.

Infections, including zoonoses, constitute a threat to human health due to the spread of resistant pathogens. These diseases generate an inflammatory response controlled by a resolving mechanism involving specialized membrane lipid-derived molecules called lipoxins, resolvins, maresins, and protectins. The production of some of these molecules can be triggered by aspirin or statins. Thus, it is proposed that modulation of the host response could be a useful therapeutic strategy, contributing to the management of resistance to antiparasitic agents or preventing drift to chronic, host-damaging courses. Therefore, the present work presents the state of the art on the use of statins or aspirin for the experimental management of parasitic infections such as Chagas disease, leishmaniasis, toxoplasmosis or malaria. The methodology used was a narrative review covering original articles from the last seven years, 38 of which met the inclusion criteria. Based on the publications consulted, modulation of the resolution of inflammation using statins may be feasible as an adjuvant in the therapy of parasitic diseases. However, there was no strong experimental evidence on the use of aspirin; therefore, further studies are needed to evaluate its role inflammation resolution process in infectious diseases.

The mRNA Vaccine Technology Era and the Future Control of Parasitic Infections.

Despite intensive long-term efforts, with very few exceptions, the development of effective vaccines against parasitic infections has presented considerable challenges, given the complexity of parasite life cycles, the interplay between parasites and their hosts, and their capacity to escape the host immune system and to regulate host immune responses. For many parasitic diseases, conventional vaccine platforms have generally proven ill suited, considering the complex manufacturing processes involved and the costs they incur, the inability to posttranslationally modify cloned target antigens, and the absence of long-lasting protective immunity induced by these antigens. An effective antiparasite vaccine platform is required to assess the effectiveness of novel vaccine candidates at high throughput. By exploiting the approach that has recently been used successfully to produce highly protective COVID mRNA vaccines, we anticipate a new wave of research to advance the use of mRNA vaccines to prevent parasitic infections in the near future. This article considers the characteristics that are required to develop a potent antiparasite vaccine and provides a conceptual foundation to promote the development of parasite mRNA-based vaccines. We review the recent advances and challenges encountered in developing antiparasite vaccines and evaluate the potential of developing mRNA vaccines against parasites, including those causing diseases such as malaria and schistosomiasis, against which vaccines are currently suboptimal or not yet available.

[Construction of a human health literacy indicator system for prevention of parasitic diseases based on Delphi method].

OBJECTIVE: To construct a human health literacy indicator system for prevention of parasitic diseases based on Delphi method. METHODS: Based on literature reviews and expert interviews, a questionnaire was designed and a two-round Delphi consultation was performed. A human health literacy indicator system for prevention of parasitic diseases was constructed according to the deletion criteria and experts' advice. RESULTS: A total of 14 experts completed the two-round consultation. The second-round authority coefficients were 0.91 to 0.96 for the first-level indicators, 0.87 to 0.97 for the second-level indicators and 0.86 to 0.97 for the third-level indicators. A human health literacy indicator system for prevention of parasitic diseases was constructed with the main framework of basic knowledge and awareness, healthy behaviors, and healthy skills, which contained 3 first-level indicators, 12 second-level indicators and 48 third-level indicators. Among the three first-level indicators, basic knowledge and awareness had the highest weighting coefficient (0.336 5), followed by healthy behaviors (0.334 9), and healthy skills had the lowest weighting coefficient (0.328 6). The three secondary-level indicators with the highest combined weights included awareness of the epidemic status (0.088 2), awareness of the resource of infection (0.085 8) and basic awareness of parasitic diseases (0.085 5). CONCLUSION: A human health literacy indicator system for prevention of parasitic diseases is preliminarily constructed, which provides insights into the development of health literacy evaluation tools for prevention of parasitic diseases in the new era.

[Potential transmission risk of key parasitic diseases and responses to the risk during the construction of an ecological city in Shanghai Municipality].

A blueprint on Shanghai's ecological space design between 2021 and 2035 was released in 2021, aiming to build an ecological city and improve the development of ecological civilization. The transmission of parasitic diseases is strongly associated with climate and ecological environments. Currently, the prevalence of parasitic diseases has been maintained at extremely low-transmission levels, and there are almost no local cases; however, the alteration of ecological environments may results in a potential transmission risk of parasitic diseases. Hereby, the current status of key parasitic diseases in Shanghai Municipality was described, and the potential transmission risk of parasitic diseases and responses to this risk were analyzed during the construction of an ecological city in Shanghai Municipality. In addition, the suggestions pertaining to surveillance and management of parasitic diseases were proposed during the mid- and long-term construction of an ecological city in Shanghai Municipality.

Control of parasitic diseases in aquaculture.

Finfish aquaculture in freshwater and marine environments is continuously expanding globally, and the potential for a substantial further increase is well documented. The industry is supplying fish products for human consumption to the same extent as capture fisheries, and new fish species for domestication are still being selected by the industry. The challenge faced by all aquacultured species, classical and novel, is the range of pathogens associated with each new fish type. A fish host in its natural environment carries a series of more or less specific parasites (specialists and generalists). Some of these show a marked ability to propagate in aquaculture settings. They may then elicit disease when infection intensities in the confined aquaculture environment reach high levels. In addition, the risk of transmission of parasites from aquaculture enterprises to wild fish stocks adds to the parasitic challenge. Control programmes of various kinds are needed and these may include chemotherapeutants and medicines as the farmer's first and convenient choice, but mechanical, biological, immunological and genetic control methods are available solutions. New methods are still to be developed by scrutinizing the life cycle of each particular parasite species and pin-pointing the vulnerable stage to be targeted. As parasites exhibit a huge potential for adaptation to environmental changes, one must realize that only one approach rarely is sufficient. The present work therefore elaborates on and advocates for implementation of integrated control strategies for diseases caused by protozoan and metazoan parasites.

Crop protection practices and risks associated with infectious tropical parasitic diseases.

Two recent literature reviews have shown that: i) agroecological crop protection (ACP) practices generally reduce risks of viral zoonoses, unlike conventional (agrochemical-based) practices which tend to increase them; ii) substitution-based crop protection (CP) practices (mainly biocontrol-based) could result in fewer health risks from bacterial infectious diseases. Here, we present an analysis of the scientific literature to determine to what extent the conclusions regarding viruses or bacteria can be extended to infectious diseases caused by protozoan or helminthic parasites. This analysis of cases of both vector-transmitted and water- or food-borne parasitic diseases, shows, in terms of reduction of health risks: i) an overall negative effect arising from the use of synthetic plant protection products; ii) the relevance of substitution CP practices not strictly under the ACP banner. On the other hand, the public and veterinary health issue of antiparasitic resistance is not affected by CP practices. The positive effects at the large spatio-temporal scales of ACP approaches remain valid, although to a slightly lesser extent than for bacterial diseases and viral zoonoses, in particular through biodiversity conservation which fosters natural regulations and control, preventing the undesirable effects of synthetic pesticides.

Effects of deworming medication on anaemia among children aged 6-59 months in sub-Saharan Africa.

BACKGROUND: Despite the limited knowledge regarding the effects of deworming medication (DM) on nutritional indicators in sub-Saharan Africa (SSA), deworming programmes continue to be implemented in resource-limited countries. Therefore, the current study aimed to examine the effects of DM on anaemia among children aged 6-59 months in SSA. METHODS: The analysis was performed using data obtained from 17 demographic and health surveys (DHSs) conducted in SSA. Children were considered to be anaemic if their haemoglobin (Hb) concentration was less than 11.0 g/dl, adjusting for altitude. To account for both multiple measures at the cluster level and the clustering of children within the same country, generalized linear mixed models were used to analyse the anaemia outcomes in 50,075 children aged 6-59 months. RESULTS: Overall, anaemia was reported in 61.8% of the children, and their median Hb concentration was 10.5 g/dl (interquartile range 9.4-11.5). The prevalence of anaemia ranged from 34.5% in Rwanda to 81.1% in Mali. Multivariate analyses showed that children who did not receive DM had increased odds of being anaemic (adjusted odds ratio [aOR]: 1.11; 95% confidence interval [CI] 1.07-1.16). CONCLUSIONS: The current study revealed that DM can decrease the risk of anaemia among preschool-age children (pre-SAC) in SSA. Thus, tailored public health programmes aimed at reducing childhood anaemia need to consider deworming. However, longitudinal studies are needed to validate the association that has been reported in this cross-sectional study.

[Application of integrated species distribution models in parasitic diseases prevention and control: a review].

Species distribution model, a mathematical model theoretically based on the temporal and spatial locations of species in the ecosystem and their associations with other species, is useful to display the current species distribution and predict the future species distribution, which has been widely applied in ecology, biogeography and spatial transmission of infectious diseases. Integrated species distribution model is a comprehensive, summative and reliable combination model that simultaneously uses multiple species distribution models or integrates multiple data sources for modeling. This review describes the theory and classification of species distribution models, and summarizes the creation and verification of integrated species distribution models and their applications in parasitic disease prevention and control. During the practical applications of integrated species distribution models, the study scale, niche matching, big data utilization, combination of multidisciplinary methods and knowledge background and ecological implications should be emphasized.

Impact of the COVID-19 Duration on Neglected Parasitic Diseases

The Coronavirus disease-2019 (COVID-19) pandemic, which started in Wuhan, China in December 2019, has affected the whole world and caused approximately four million deaths. Consequently, scientists have done a great deal of research in such a short time about the disease. Meanwhile, parasites, whose evolutionary process is as old as human history, are often underestimated despite their high prevalence and lethality. Recent studies; however, have shown that immunity changes caused by parasitic infections affect the course of viral diseases. For example, because severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and Plasmodium use a common CD147 receptor to enter the cell and have similarities in their MHC-presented antigenic determinants, scientists suggest that immunity against parasitic infections protects the body against SARS-CoV-2 infections. This could explain the low COVID-19 incidence in malaria-endemic countries. Additionally, the cytokine storm, which is responsible for mortality in COVID-19 infections, is caused by the activation of the immune system to Th1 way. On the other hand, helminth infections, which activate the immune system to Th2 way, can reduce mortality by preventing the cytokine storm. The relationship between COVID-19 and parasites is not limited to changes in the immune system changes. Studies have shown that the pause in the fight against parasitic infections due to the diversion of all attention toward COVID-19 since the beginning of the pandemic will lead to an increase in incidences of malaria, leishmaniasis, schistosomiasis, and soil-transmitted helminths. For this reason, efforts to mitigate this increase should be resumed as soon as possible by taking additional measures globally.

Towards global control of parasitic diseases in the Covid-19 era: One Health and the future of multisectoral global health governance.

Human parasitic infections-including malaria, and many neglected tropical diseases (NTDs)-have long represented a Gordian knot in global public health: ancient, persistent, and exceedingly difficult to control. With the coronavirus disease (Covid-19) pandemic substantially interrupting control programmes worldwide, there are now mounting fears that decades of progress in controlling global parasitic infections will be undone. With Covid-19 moreover exposing deep vulnerabilities in the global health system, the current moment presents a watershed opportunity to plan future efforts to reduce the global morbidity and mortality associated with human parasitic infections. In this chapter, we first provide a brief epidemiologic overview of the progress that has been made towards the control of parasitic diseases between 1990 and 2019, contrasting these fragile gains with the anticipated losses as a result of Covid-19. We then argue that the complementary aspirations of the United Nations Sustainable Development Goals (SDGs) and the World Health Organization (WHO)'s 2030 targets for parasitic disease control may be achieved by aligning programme objectives within the One Health paradigm, recognizing the interdependence between humans, animals, and the environment. In so doing, we note that while the WHO remains the preeminent international institution to address some of these transdisciplinary concerns, its underlying challenges with funding, authority, and capacity are likely to reverberate if left unaddressed. To this end, we conclude by reimagining how models of multisectoral global health governance-combining the WHO's normative and technical leadership with greater support in allied policy-making areas-can help sustain future malaria and NTD elimination efforts.

[Status and control of common food-borne parasitic diseases in China: a review].

Food-borne parasitic diseases include meat-borne, fish-borne, plant-borne, water-borne, mollusk-borne and freshwater crustacean-borne parasitic diseases. The review summarizes the current status and control of 6 major food-borne parasitic diseases in China, including clonorchiasus, paragonimiasis, Taenia solium taeniasis, toxoplasmosis, trichinellosis and angiostrongyliasis, aiming to increase the understanding of food-borne parasitic diseases and provide insights into the development of the control strategy for food-borne parasitic diseases. The transmission of food-borne parasitic diseases are predominantly associated with diet, and neither eating raw nor semi-cooked food is the most effective measure to prevent the development of food-borne parasitic diseases.

The impact of COVID-19 on neglected parasitic diseases: what to expect?

Here we highlight coinfections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with ectoparasites, helminths, and protozoa, described in the literature, and the urgent need to understand the conditions of these associated pathologies. We emphasize the notion that such information is crucial for the continuity of measures that have been used for decades to control neglected parasitic diseases.

The host mTOR pathway and parasitic diseases pathogenesis.

The mechanistic (or mammalian) target of rapamycin (mTOR) is considered as a critical regulatory enzyme involved in essential signaling pathways affecting cell growth, cell proliferation, protein translation, regulation of cellular metabolism, and cytoskeletal structure. Also, mTOR signaling has crucial roles in cell homeostasis via processes such as autophagy. Autophagy prevents many pathogen infections and is involved on immunosurveillance and pathogenesis. Immune responses and autophagy are therefore key host responses and both are linked by complex mTOR regulatory mechanisms. In recent years, the mTOR pathway has been highlighted in different diseases such as diabetes, cancer, and infectious and parasitic diseases including leishmaniasis, toxoplasmosis, and malaria. The current review underlines the implications of mTOR signals and intricate networks on pathogen infections and the modulation of this master regulator by parasites. Parasitic infections are able to induce dynamic metabolic reprogramming leading to mTOR alterations in spite of many other ways impacting this regulatory network. Accordingly, the identification of parasite effects and interactions over such a complex modulation might reveal novel information regarding the biology of the abovementioned parasites and might allow the development of therapeutic strategies against parasitic diseases. In this sense, the effects of inhibiting the mTOR pathways are also considered in this context in the light of their potential for the prevention and treatment of parasitic diseases.

Epidemiological aspects of visceral leishmaniasis in the municipality of Montes Claros-MG

Visceralleishmaniasis (VL), also known as 'calazar', is a serious chronic disease caused by Leishmania species from Leishmania(Leishmania) donovanicomplex, which the disease is characterized by abdominal swelling (hepatosplenomegaly) and may evolve to death in extreme cases.In this sense, the aim of our study was to assess the epidemiological profile of the cases found in Montes Claros (Minas Gerais state).A retrospective or cross-sectional study was carried out using secondary data provided by Health Information System (SINAN/HM) of Brazil from January 2010 to February 2020. Our data has shown that VL is an endemic disease in Montes Claros region, with 413 VL cases reported, 62.00% (252) male, average age ± standard deviation (years), and 93.46% (386) lived inMontes Claros city. The presence of comorbidities was observed in 13.70% (54) of the patients and in 7.26% (30). As for the evolution of the disease, 246 (59.56%) were cured, 30 (7.26%) died due to VL. Between 2010 and 2015, Glucantime®stands out, in which 46 (11.13%) patients used the drug, followed by common Amphotericin B 24 (13.48%) and liposomal Amphotericin B 38 (21.34%). In the period between 2016 and 2020, the most prevalent drug was liposomal Amphotericin B, with 71 (29.83%) patients using it, followed by Glucantime®45 (18.9%). The condition evolved to death. We conclude thatMontes Claros is still an endemic area for VL with an increased number of cases over time and a noticeable shift in patient profile towards children and young people. Joint efforts from different areas of scientific knowledge and public health services are needed to improve the effectiveness of visceral leishmaniasis surveillance and control actions. The population can contribute to this process of disease prevention and control, through educational actions in health and the environment.

Effect of Homeopathic Preparations on Lettuce, Parasitized or Not by Meloidogyne enterolobii.

BACKGROUND: There are relatively few scientific works on the use of homeopathy to manage plant pathogens, particularly nematodes. A handful of studies focused on Meloidogyne spp. parasitizing vegetables have brought contradictory results on nematode control and enhancement of plant tolerance to parasitism. OBJECTIVE: Our goal was to assess the effect of Cina-a well-known anti-nematode ingredient-on Meloidogyne enterolobii parasitizing lettuce. METHODS: Cina was applied daily on nematode-inoculated plants, from the seedling stage until harvest. We tested an evenly spaced range of Hahnemannian concentrations (c), which were applied though irrigation with a constant dose of the ingredient. Several absolute and relative controls were employed to allow the assessment of the effect of Cina on nematode reproduction and lettuce growth. RESULTS: Cina affected growth of non-parasitized plants, both positively and negatively; this effect was modulated by the c applied and the thermal stress suffered by the plants in one of the assays. The effect of Cina on the growth of nematode-parasitized plants was neutral or negative. Cina reduced nematode reproduction by 25-36%. CONCLUSION: Based on the moderate negative effect of Cina on M. enterolobii reproduction, it seems this ingredient may be useful as a complementary strategy for Meloidogyne control. But Cina did not enhance the tolerance of lettuce to Meloidogyne spp.

A cross-sectional survey on parasitic infections in schoolchildren in a rural Tanzanian community.

Infectious diseases remain the leading cause of death in children in low- and middle-income countries. Infection with helminths and intestinal protozoa cause considerable morbidity. The aim of this study was to assess the health status of schoolchildren in nine villages of the Kilombero district in Tanzania. We conducted a cross-sectional survey and subjected 427 children aged 6-12 years to standardized diagnostic tests. We found that 15% of children were infected with Entamoeba histolytica/Entamoeba dispar/Entamoeba moshkovskii, 12% with Schistosoma mansoni, and 5% with Plasmodium falciparum. The most common soil-transmitted helminth species was Trichuris trichiura (7%). Strongyloides stercoralis, Schistosoma haematobium, Giardia intestinalis and lymphatic filariasis were rare. Having a latrine inside the house was associated with a lower odds of parasite infections (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.27-0.96, p = 0.04). Children from households with goats were at higher odds of E. histolytica/E. dispar/E. moshkovskii infection (OR 3.03, 95%%CI 1.29-7.10, p = 0.01).When compared to a cross-sectional survey conducted in the same district in the 1980s, there seems to have been a substantial reduction in the prevalence and intensity of parasitic infections, except for T. trichiura, which showed a similar prevalence. Our data suggest that the general development, coupled with infectious disease control programmes improved children's health markedly. However, continued efforts to control parasitic diseases, including new approaches of drug combinations, stronger intersectoral collaboration, rigorous surveillance and public health responses tailored to the local settings are needed to move from control to elimination.