Pathogenic Helminths Research Articles

Epidemiology and diagnostics of intestinal parasitic infections in Italy: a multicentric survey

Background and Aims: parasitic infections are becoming more common in non-endemic countries because of intensified immigration and international travels; however, the parasitic disease burden is often underestimated because of underdiagnosis and lack of surveillance in industrialized countries. Also, in Italy, epidemiological data on intestinal parasites affecting humans are scarce and scattered in different areas of the country. The aim of this retrospective, observational study was to evaluate the prevalence of intestinal parasitic infections employing Parasitological Stool Examination (PSE) and to verify the quality of the diagnostic methodologies adopted to identify intestinal parasites in Italian laboratories. Materials and Methods: the study involved 28 Italian diagnostic laboratories and 36389 patients, from June 2015 to May 2016. Results: our data showed that 3173 out of 36389 subjects (8.7%) were carriers of one or more pathogenic or non-pathogenic protozoa or helminths. When only organisms known to cause intestinal disease were considered, an overall positive rate of 3.8% was found (1400/36389). Among the 1400 patients carrying one or more pathogenic species, protozoan infections predominated and were identified in 1138 subjects (3.1%); Dientamoeba fragilis and Giardia duodenalis represent the main intestinal pathogens. Concerning parasitic worms, only 262 individuals (0.7%) exhibited helminth infection; the most frequent finding was represented by Enterobius vermicularis, followed by Taenia spp. Conclusions: this survey also indicated that not all diagnostic laboratories can guarantee proper performance for parasitological diagnosis. In this context, close collaboration between physicians and clinical microbiologists is warranted to improve the diagnostics of intestinal parasitic infections, thus ensuring good quality service.

Control of Helminth Infections in Captive Herbivores: An Overview of Experience

There are numerous challenges associated with helminth control in captive animals. The aim of the present paper is to provide an overview of the research on deworming of captive herbivorous mammals, the associated problems and the solutions sought, in order to derive recommendations for practice in the relevant institutions. The research was conducted by searching electronic internet databases and following the bibliographies in the published articles. The articles found are presented in summarized form. Most of the results relate to herbivores of the family Bovidae, followed by the families Cervidae, Equidae, Elephantidae, Camelidae and Giraffidae. Systematic data are presented on the types of anthelmintics used, dosages and application regimens for different animal species. Anthelmintics were administered at doses similar to or even higher than those used in farm animals, with no evidence of side effects. Treatment results often depended on the animal and parasite species. Incomplete cure, reinfection, and resistance to anthelmintics were the most common problems in the field. Based on the literature reviewed, the optimal prevention measures include the following: quarantine of newly arrived animals; daily or as intensive as possible cleaning of droppings; regular change of substrate in the enclosures; and monitoring of possible infections and their qualitative and quantitative composition (monthly or at least every two months). For treatments and monitoring effectiveness, recommendations include the following: individual assessment of the need for treatment; selective choice of anthelmintics; post-treatment examination between the 10th and 14th day after deworming; carrying out a group treatment after a preliminary drug effect test; conducting mass deworming only in case of a significant increase in fecal egg counts, highly pathogenic helminth species and a deterioration in the condition of the animals. In the future, more attention should be paid to new approaches such as biological control by saprophytic fungi or natural compounds as an alternative to anthelmintics. This would help minimize the use of anthelmintics, protect refugia and allow animals to remain healthy by maintaining a balance with the low levels of parasites present.

Microbial community dynamics in blood, faeces and oral secretions of neotropical bats in Casanare, Colombia

Bats are known reservoirs for a wide range of pathogenic microorganisms, including viruses, bacteria, fungi, helminths, and protozoa, which can be transmitted and infect other zoonotic organisms. Various studies have utilised next-generation sequencing (NGS) to describe the pathogens associated with bats. Although most have characterised microbial communities in specific body fluids, few have analysed the composition and diversity of these microbial communities across different body fluids at the individual level. In this study, we employed two next-generation sequencing techniques: amplicon-based sequencing of the V4 hypervariable region of the 16S- and 18S-rRNA genes and viral metagenomics, to describe the prokaryotic, eukaryotic, and viral communities present in blood, faeces, and oral swab samples collected from two genera of bats (Carollia and Phyllostomus) in the department of Casanare, eastern Colombia. A total of 60 samples corresponding to the three bodily fluids were processed and analysed. The results indicated that the microbial communities across the body fluids were mainly composed of bacteria, fungi, protozoa, and various DNA and RNA viruses, showing a variability of microbial genera and species. The abundances, diversity metrics, and correlations of these microorganisms displayed patterns associated with bat genus and body fluids, suggesting that the ecological characteristics of these microbial communities may be influenced by the ecological and physiological traits of the bats. Additionally, we found similar community compositions of bacteria, some fungal genera, and viruses in the three body fluids, indicating a possible circulation of these microbes within the same bat. This could be due to microbial movement from the gut microbiota to other physiological systems or transmission via blood-feeding vectors. Furthermore, our results revealed the presence of various microbes of public health concern, including Bartonella spp., Mannheimia haemolytica, Rhodotorula spp., Piroplasmida spp., Toxoplasma gondii, Alphacoronavirus spp., and Bat circovirus. The abundance of these pathogenic microbial species across the three bodily fluids suggests potential transmission routes from bats to other organisms, which may contribute to the emergence of zoonotic disease outbreaks. These findings highlight the variability of microorganisms present within the same bat and the different pathogen-host interactions that may regulate the presence and transmission of these zoonotic microbes. Further research is required to elucidate the genomic features, ecological interactions, and biological activities of these microbial communities in bats.

Innate lymphoid cells and infectious diseases.

Innate lymphoid cells (ILCs) are the main resident lymphocytes that mostly reside in tissues owing to the lack of adaptive antigen receptors. These cells are involved in early anti-infective immunity, antitumour immunity, regulation of tissue inflammation, and maintenance of homeostasis in the internal environment of tissues and have been referred to as the "first armies stationed in the human body". ILCs are widely distributed in the lungs, colon, lymph nodes, oral mucosa and even embryonic tissues. Due to the advantage of their distribution location, they are often among the first cells to come into contact with pathogens.Relevant studies have demonstrated that ILCs play an early role in the defence against a variety of pathogenic microorganisms, including bacteria, viruses, fungi and helminths, before they intervene in the adaptive immune system. ILCs can initiate a rapid, nonspecific response against pathogens prior to the initiation of an adaptive immune response and can generate a protective immune response against specific pathogens, secreting different effectors to play a role.There is growing evidence that ILCs play an important role in host control of infectious diseases. In this paper, we summarize and discuss the current known infectious diseases in which ILCs are involved and ILC contribution to the defence against infectious diseases. Further insights into the mechanisms of ILCs action in different infectious diseases will be useful in facilitating the development of therapeutic strategies for early control of infections.

Synthesis, Molecular Docking and Pharmacological Evaluation of Some New Schiff and Mannich Bases of 5-Methylisatin Derivatives

Two novel series of Schiff and Mannich based 5-methylisatin were synthesized by Mannich reactions and evaluated for anthelmintic and antibacterial activities. The Mannich bases were synthesized from the Schiff base using various secondary amines and formaldehyde along with the derivatives of piperazinyl groups. N-Methyl piperazinyl (ICP-2B and ICM-2B) and piperidinyl derivatives (ICP-2C and ICM-2C) were found to have a highly significant anthelmintic potential. For compound ICP-2B, the paralysis time was observed at 4.936 ± 0.12 min at low concentration (0.1 % w/v) and 1.95 ± 0.10 min at high concentration (1% w/v). At low concentration (0.1%), compound ICM-2B, the paralysis time is 4.43 ± 0.17 min; at high concentration (1% w/v), it is 1.675 ± 0.08 min. These data indicated that compounds ICP-2B and ICM-2B has immense potential as anthelminthic and antimicrobial drug in future. Moreover, the in vitro study was confirmed by molecular docking studies, indicating both compounds ICP-2B and ICM-2B can find its use as novel drug against various pathogenic helminthes and bacteria.

Structural insights into the molecular effects of the anthelmintics monepantel and betaine on the Caenorhabditis elegans acetylcholine receptor ACR-23

Anthelmintics are drugs used for controlling pathogenic helminths in animals and plants. The natural compound betaine and the recently developed synthetic compound monepantel are both anthelmintics that target the acetylcholine receptor ACR-23 and its homologs in nematodes. Here, we present cryo-electron microscopy structures of ACR-23 in apo, betaine-bound, and betaine- and monepantel-bound states. We show that ACR-23 forms a homo-pentameric channel, similar to some other pentameric ligand-gated ion channels (pLGICs). While betaine molecules are bound to the classical neurotransmitter sites in the inter-subunit interfaces in the extracellular domain, monepantel molecules are bound to allosteric sites formed in the inter-subunit interfaces in the transmembrane domain of the receptor. Although the pore remains closed in betaine-bound state, monepantel binding results in an open channel by wedging into the cleft between the transmembrane domains of two neighboring subunits, which causes dilation of the ion conduction pore. By combining structural analyses with site-directed mutagenesis, electrophysiology and in vivo locomotion assays, we provide insights into the mechanism of action of the anthelmintics monepantel and betaine.

ЭКОЛОГО-ЭПИЗООТОЛОГИЧЕСКАЯ ХАРАКТЕРИСТИКА АНОПЛОЦЕФАЛИДОЗОВ МЕЛКОГО РОГАТОГО СКОТА В ФЕРМЕРСКИХ ХОЗЯЙСТВАХ АЛТАЙСКОГО КРАЯ

The purpose of the study is to identify in the Altay Region the most pathogenic helminths among small livestock that threaten the health of farm animals, and their harmfulness and extent of spread. Using the coprooscopic method, fecal samples from sheep of 3 groups were examined: up to one year, from 1 to 2 years and over 2 years. Using the method of complete helminthological autopsies, 18 heads of sheep were opened on farms, of which 11 were aged from 1 to 2 years and 7 heads were older than 2 years. We studied the timing of infection in lambs by monthly examination of the same animals, starting from two months of age until they reach two years of age. All lambs were from the same farm; no anticestodal measures were carried out, so the natural course of the invasion was not disturbed. The survey began at the end of May 2020 with a group of lambs that reached two months of age in the amount of 26 heads. The number of oribatid mites was studied by collecting oribatid mites using a special technique. From the class of cestodes among sheep, 5 species are most often recorded with an average level of extensive infestation from 0.5 to 44.4 %. Anoplocephalid eggs were first discovered in lambs of the current year of birth in July. Moniesia were found throughout the year in young animals from one to two years of age. In March, April, and May they were recorded in single animals in this group of sheep. The seasonal dynamics of the number of oribatid ticks is directly dependent on natural and climatic conditions: significantly fewer ticks were recorded in the steppe zone than in the forest-steppe and floodplain zones. The results of the study show that monieziosis in young lambs kept on pasture is detected coprologically in the conditions of the Altai Region no earlier than July. Two peaks of activity of the intermediate hosts of moniesia, oribatid mites, have been recorded: spring and autumn.

Efficiency of using levamisole-based anthelmintics

Animal parasitic diseases cause major losses to the livestock industry and require constant monitoring and control. The purpose of this study was to monitor the livestock (calves, goats, sheep, pigs, dogs, chickens) for the presence of helminthic pathogens, to determine the therapeutic efficacy of levamisole-based preparations and the general toxicity of meat of experimental animals using the Colpoda steinii test culture. In 2020-2022, a considerable spread of invasive animal diseases was detected in the Kharkiv region of Ukraine. In a study of 3,500 calves, 1,000 (28.6%) were found to be persistently infected with nematodes with an intensity of 25.0-150.0 worm eggs per 1 g of faeces. In goats, the intensity of endoparasite infection ranged within 10.0-15.0 worm eggs per 1 g of faeces, while in sheep this figure reached 25.0 worm eggs per 1 g of faeces. In the study of faeces from pigs, 800 (34.8%) samples revealed the presence of helminth eggs, while mono-infestation was detected in 300 samples (37.5%). In the study of canine faeces, 10 (66.7%) positive samples were found. When examining the manure from chickens, 200 (44.4%) positive samples revealed the presence of helminth eggs. The use of levamisole dosage forms can reduce the extent of infection in animals by 50% as early as on Day 5. No worm eggs were detected in the faeces of animals from Day 14 to Day 30 of observation, and therefore the extensional efficacy of the studied products under modern conditions is 100%. Meat obtained from farm animals (pigs, calves, sheep) treated with levamisole-based preparations shows signs of general toxicity within 5...9 days after the use of the products: 5 days for pigs and 9 days for calves and sheep. At the same time, meat obtained from poultry (chickens) treated with levamisole-based preparations shows signs of general toxicity within 2 days after the end of the treatment course

Subolesin knockdown in tick cells provides insights into vaccine protective mechanisms

Ticks as obligate blood-feeding arthropod vectors of pathogenic viruses, bacteria, protozoa and helminths associated with prevalent tick-borne diseases (TBDs) worldwide. These arthropods constitute the second vector after mosquitoes that transmit pathogens to humans and the first vector in domestic animals. Vaccines constitute the safest and more effective approach to control tick infestations and TBDs, but research is needed to identify new antigens and improve vaccine formulations. The tick protein Subolesin (Sub) is a well-known vaccine protective antigen with a highly conserved sequence at both gene and protein levels in the Ixodidae and among arthropods and vertebrates. In this study, transcriptomics and proteomics analyses were conducted together with graph theory data analysis in wild type and Sub knockdown (KD) tick ISE6 cells in order to identify and characterize the functional implications of Sub in tick cells. The results support a key role for Sub in the regulation of gene expression in ticks and the relevance of this antigen in vaccine development against ticks and TBDs. Proteins with differential representation in response to Sub KD provide insights into vaccine protective mechanisms and candidate tick protective antigens.

Physicochemical Parameters and Abundance of Pathogenic Protozoans and Helminths in Abattoirs within Minna Metropolis, Niger State, Nigeria

Physicochemical Parameters and Abundance of Pathogenic Protozoans and Helminths in Abattoirs within Minna Metropolis, Niger State, Nigeria

Helminthofauna and the level of infection of the main commercial species of semi-migratory and riverine fish in the lower zone of the Volga delta

On the territory of the Volga Delta and the northern part of the Caspian Sea, there are natural epizootic foci of anisakiosis, corynosomiasis, eustrongilidosis, pseudamphistomosis and opisthorchiasis. Many species of commercial semi-migratory and riverine fish have a high epidemiological significance. Therefore, monitoring the level of their infection with larvae of pathogens of anthropozoonosis is very relevant. The aim of the work was to determine the qualitative composition of epidemiologically significant helminth fauna and the level of infection with pathogenic helminth larvae of the main commercial species of semi-aquatic and riverine fish in the lower zone of the Volga delta in modern conditions. The material for the study was 660 copies . mature commercial fish of eight species, the study of parasitic purity of which was carried out by the method of incomplete helminthological research in accordance with the requirements of regulatory documents of the Russian Federation. The qualitative composition of the epidemiologically significant component of the helminth fauna was represented by seven species. All examined fish species are infested with larvae of pathogenic helminths. The maximum species diversity of dangerous parasites was found in the roach (5 species), the minimum — in the bream (1 species). The localization of helminth larvae was diverse, but most of the identified pathogenic species also invaded the muscle tissues of fish. The exceptions were Anisakis schupakovi and Corynosoma strumosum, which were located only in the abdominal fat and internal organs of the examined representatives of the ichthyofauna. Parasitological parameters of infection with dangerous parasites in different species of hydrobionts differed significantly. The larvae of the nematodes A. schupakovi and Eustrongylides excisus were characterized by the maximum distribution, while the frequency of their occurrence prevailed in predatory fish. Metacercariae Apophallus muehlingi dominated in number. The rarest representative of the community of pathogens of biohelminthiasis was C. strumosum, which was parasitized only in walleye. Most of the identified pathogenic organisms were viable, which indicated the need for mandatory disinfection of fish before sale.

Prevalence of soil-transmitted helminth infections in HIV patients: a systematic review and meta-analysis

Soil-transmitted Helminth (STH) infections have been found associated with people living with human immunodeficiency virus (HIV) but little is known about the overall burden of STH coinfection in HIV patients. We aimed to assess the burden of STH infections among HIV patients. Relevant databases were systematically searched for studies reporting the prevalence of soil-transmitted helminthic pathogens in HIV patients. Pooled estimates of each helminthic infection were calculated. The odds ratio was also determined as a measure of the association between STH infection and the HIV status of the patients. Sixty-one studies were finally included in the meta-analysis, consisting of 16,203 human subjects from all over the world. The prevalence of Ascaris lumbricoides infection in HIV patients was found to be 8% (95% CI 0.06, 0.09), the prevalence of Trichuris trichiura infection in HIV patients was found to be 5% (95% CI 0.04, 0.06), the prevalence of hookworm infection in HIV patients was found to be 5% (95% CI 0.04, 0.06), and prevalence of Strongyloides stercoralis infection in HIV patients was found to be 5% (95% CI 0.04, 0.05). Countries from Sub-Saharan Africa, Latin America & Caribbean and Asia were identified with the highest burden of STH-HIV coinfection. Our analysis indicated that people living with HIV have a higher chance of developing Strongyloides stercoralis infections and decreased odds of developing hookworm infections. Our findings suggest a moderate level of prevalence of STH infections among people living with HIV. The endemicity of STH infections and HIV status both are partially responsible for the burden of STH-HIV coinfections.

Testing of sand from recreational areas and sandpits in Warsaw, for presence of Ascaris Lumbricoides and Toxocara spp.

Improper maintenance of the cleanliness of sand in sandboxes can be a source of human pathogenic helminths, including Toxocara spp., Enterobius vermicularis, Ascaris lumbricoides, leading to parasitic infections. The purpose of this study was to evaluate the sanitary condition of sandboxes in playgrounds and recreational areas in Warsaw for the presence of Human roundworm (Ascaris lumbricoides) and Toxocara spp. in sand. 450 sand samples from 90 sandboxes in the city of Warsaw were analyzed. The flotation method was used for the study, and the material was evaluated using a light microscope. RESULTS. The conducted examinations did not reveal the presence of parasite eggs, indicating that hygiene rules were observed and appropriate recommendations were followed. The analyzed sand samples are free of the tested parasites.

Long-term impacts of an urban sanitation intervention on enteric pathogens in children in Maputo city, Mozambique: study protocol for a cross-sectional follow-up to the Maputo Sanitation (MapSan) trial 5 years postintervention

IntroductionWe previously assessed the effect of an onsite sanitation intervention in informal neighbourhoods of urban Maputo, Mozambique on enteric pathogen detection in children after 2 years of follow-up (Maputo Sanitation...

Drivers behind co-occurrence patterns between pathogenic bacteria, protozoa, and helminths in populations of the multimammate mouse, Mastomys natalensis

Advances in experimental and theoretical work increasingly suggest that parasite interactions within a single host can affect the spread and severity of wildlife diseases. Yet empirical data to support predicted co-infection patterns are limited due to the practical challenges of gathering convincing data from animal populations and the stochastic nature of parasite transmission. Here, we investigated co-infection patterns between micro- (bacteria and protozoa) and macroparasites (gastro-intestinal helminths) in natural populations of the multimammate mouse (Mastomys natalensis). Fieldwork was performed in Morogoro (Tanzania), where we trapped 211 M. natalensis and tested their behaviour using a modified open-field arena. All animals were checked for the presence of helminths in their gastro-intestinal tract, three bacteria (Anaplasma, Bartonella, and Borrelia) and two protozoan genera (Babesia and Hepatozoon). Besides the presence of eight different helminth genera (reported earlier), we found that 19% of M. natalensis were positive for Anaplasma, 10% for Bartonella, and 2% for Hepatozoon species. Hierarchical modelling of species communities was used to investigate the effect of the different host-related factors on these parasites’ infection probability and community structure. Our results show that the infection probability of Bartonella increased with the host's age, while the infection probability of Anaplasma peaked when individuals reached adulthood. We also observed that less explorative and stress-sensitive individuals had a higher infection probability with Bartonella. Finally, we found limited support for within-host interactions between micro-and macroparasites, as most co-infection patterns could be attributed to host exposure time.

Enteric helminth infection confers protection against lethal respiratory influenza virus infection

Abstract Chronic helminth infection has been considered a serious public health issue. Due to the widespread of helminthiasis, people co-infected with helminth and other pathogens, such as virus, may be common. Studies suggest that helminth infection exert immunomodulatory effects that may alter host susceptibility to subsequent unrelated pulmonary pathogens, such as Mycobacterium tuberculosis. However, the outcome of helminth-respiratory viral co-infection remains controversial. Here, we established an enteric helminth Heligomosomoides polygyrus bakeri(Hpb)-influenza virus co-infection mouse model, then characterized the immune responses modulated by Hpb infection in the lungs of the helminth chronically infected mice. Our results showed that enteric helminth-infected mice exhibited increased survival and reduced weight loss after lethal influenza virus infection compared with helminth-inexperienced mice. Further analysis revealed that enteric helminth infection altered immune landscape in the lungs by increasing effector CD4 +and CD8 +T cells infiltrated into the airway, as well as upregulating type I interferons and pro-inflammatory cytokines in the lung tissues before influenza virus infection. After influenza virus infection, viral titers were significantly decreased, whereas the viral-specific antibody responses and cellular responses were increased in the lungs of helminth-infected mice. Moreover, histological examination of the lungs revealed that cell infiltration in lung parenchyma and airway lumen was reduced in helminth-infected mice. Taken together, these results suggested that enteric helminth infection confers “bystander” protection against pulmonary influenza virus infection. Supported by grants from MOST (109-2320-B-002-074-MY3), NHRI (EX110/111-11033SI) and NTU (111L7829), Taiwan

Plastic pollution and fungal, protozoan, and helminth pathogens – A neglected environmental and public health issue?

Plastic waste is ubiquitous in the environment and can become colonised by distinct microbial biofilm communities, known collectively as the ‘plastisphere.’ The plastisphere can facilitate the increased survival and dissemination of human pathogenic prokaryotes (e.g., bacteria); however, our understanding of the potential for plastics to harbour and disseminate eukaryotic pathogens is lacking. Eukaryotic microorganisms are abundant in natural environments and represent some of the most important disease-causing agents, collectively responsible for tens of millions of infections, and millions of deaths worldwide. While prokaryotic plastisphere communities in terrestrial, freshwater, and marine environments are relatively well characterised, such biofilms will also contain eukaryotic species. Here, we critically review the potential for fungal, protozoan, and helminth pathogens to associate with the plastisphere, and consider the regulation and mechanisms of this interaction. As the volume of plastics in the environment continues to rise there is an urgent need to understand the role of the plastisphere for the survival, virulence, dissemination, and transfer of eukaryotic pathogens, and the effect this can have on environmental and human health.

Ecological study on helminths of three species of Gobiidae from the Danube River, Bulgaria.

A total of 72 specimens of Babka gymnotrachelus (Kessler, 1857), Neogobius fluviatilis (Pallas, 1814), and Neogobius melanostomus (Pallas, 1814) from four sampling sites along the Bulgarian section of the Danube River (Kudelin, Novo selo, Koshava, and Kutovo), Northwestern Bulgaria were submitted to ecologohelminthological investigation. During the examination 6 species of helminths have been identified from 3 classes: Trematoda (Nicolla skrjabini (Iwanitzky, 1928) Dollfus, 1960), Acanthocephala (Acanthocephalus anguillae (Müller, 1780) Lühe, 1911; Acanthocephalus lucii (Müller, 1776) Lühe, 1911; Pomphorhynchus laevis (Zoega in Müller, 1776) Porta, 1908) and Nematoda (Contracaecum sp., Eustrongylides excisus Jägerskiöld, 1909). Ecological indices of the established endohelminth species were tracked. The four sampling sites from the Danube River are new habitats for the discovered endohelminth species of racer goby, monkey goby, and round goby. The three goby species are new host records: B. gymnotrachelus and N. fluviatilis for Ac. lucii; N. melanostomus for Ac. lucii, Ac. anguillae and Contracaecum sp. New species of helminths are found in the helminth fauna of the three studied species of gobies from the Danube River and the river basin (Ac. lucii of N. fluviatilis) and in Bulgaria (Ac. lucii of B. gymnotrachelus; Ac. lucii, Ac. anguillae and Contracaecum sp. of N. melanostomus). The pathogenic species helminths for the fish and humans are found.

Omega-Class Glutathione Transferases Protect DNA from Oxidative Stress in Pathogenic Helminth Reproductive Cells

Pathogenic helminths have evolved mechanisms to preserve reproductive function while surviving long-term in the host via robust protective responses. A protective role of antioxidant enzymes in preventing DNA degradation has long been proposed, but little evidence has been provided. Here, we show that omega-class glutathione transferases (GSTOs) are critical for maintaining viability by protecting the reproductive cell DNA of the carcinogenic liver fluke, Clonorchis sinensis. Clonorchis sinensis GSTO (CsGSTO) activities modified by changes in the GSH/GSSG and NADPH/NADP+ molar ratios suppressed the overproduction of reactive oxygen species. CsGSTO1 and CsGSTO2 catalyzed deglutathionylation under physiologic and low-stress conditions (GSH/GSSG ratio of 6:1 or higher) but promoted glutathionylation under high-stress conditions (GSH/GSSG ratio of 3:1 or lower). Gliotoxin-induced functional disruption of CsGSTOs in living C. sinensis reduced the GSH/GSSG molar ratio and increased the production of protein glutathionylation (PSSG) under physiologic and low-stress conditions, indicating that suppression of GSTO function did not affect deglutathionylation. However, the perturbation of CsGSTOs decreased the GSH/GSSG ratio but also reduced PSSG production under high oxidative stress, demonstrating that glutathionylation was impeded. In response to oxidative stimuli, C. sinensis decreased GSTO-specific dehydroascorbate reductase and thiol transferase activities and the GSH/GSSG ratio, while it increased the NADPH/NADP+ ratio and PSSG. CsGSTOs utilized GSH to regulate GSH/GSSG and NADPH/NADP+ recycling and triggered a redox signal leading to nuclear translocation. Nuclear-imported CsGSTOs were modified by glutathionylation to prevent DNA damage. Antibodies specific to CsGSTOs dose-dependently inhibited this process. Disruption of CsGSTOs or the depletion of GSH caused glutathionylation defects, leading to DNA degradation. Our results demonstrate that CsGSTOs and the GSH system play a previously unappreciated role in protecting DNA from oxidative stress.

Clinical features of hepatozoonosis in dogs and cats

Canine and feline vector-borne diseases are emerging diseases caused by a multitude of worldwide distributed pathogens (bacteria, viruses, protozoa and helminths) and transmitted by ectoparasites (ticks, fleas, sandflies and mosquitoes). They are important because of their increasing prevalence and distribution, great pathogenic potential in companion animals and the zoonotic potential of some of them. Among vector-borne diseases, hepatozoonosis is a neglected but emerging tick-borne disease of dogs and cats. It is caused by different protozoa species belonging to the genus Hepatozoon and is characterized by variable clinical pictures, from subclinical and subtle to potentially life-threatening signs. Data on the biology, epidemiology, clinical features and treatment of canine and feline hepatozoonosis are still limited and the disease is often overlooked in clinical settings. This article discusses the current literature on clinical aspects of canine and feline hepatozoonosis, to increase awareness of this disease.