Paradoxical Worsening of Chronic Spontaneous Urticaria Following Omalizumab Administration: The Missing Link.

Omalizumab, a humanized anti-IgE monoclonal antibody, is commonly employed in the treatment of antihistamine-refractory chronic spontaneous urticaria (CSU), where it significantly reduces free IgE levels, minimizing histamine release from basophils and mast cells. Despite its efficacy, there are concerns regarding its effect on parasitic defense due to IgE's role in combating parasitic infestations. We present a case of a 28-year-old female agriculturist with a six-month history of CSU who experienced a paradoxical exacerbation of her symptoms following an increase in the omalizumab treatment dose. This deterioration coincided with a serologically confirmed parasitic infection with Echinococcus granulosus and Toxocara canis. Despite normal eosinophil counts and IgE levels, which are typically used to identify parasitic infections, the patient's clinical worsening prompted further investigation that led to the identification of the parasitic infection. Treatment with albendazole and omalizumab discontinuation led to the resolution of her CSU, suggesting that the parasitic infection was contributing to the symptom exacerbation. This case highlights the need for careful screening for parasitic infections before initiating omalizumab in antihistamine-refractory CSU patients from endemic regions, or patients who deteriorate clinically on omalizumab, especially when other indicators such as eosinophil count and IgE levels might not suggest infection. It also underscores the importance of considering a tailored approach to managing CSU that balances effective treatment with the potential for adverse effects related to immunomodulation.

Evaluation of Somatic Antigens of Adult Toxocara helminthes for Detection of Human Toxocariasis.

We aimed to develop an indirect enzyme-linked immunosorbent assay (ELISA) to evaluate the presence of specific IgG against Toxocara canis and Toxocara cati somatic antigens on the serum of patients with toxocariasis. The sensitivity, specificity, positive and negative predictive values for indirect-ELISA were calculated by receiver operating characteristic curve (ROC) analysis and Youden's J using Likelihood ratio. All statistics were analysed and graphs are plotted using GraphPad Prism version 8.4.3 (Graph Pad Software, La Jolla, CA, USA), with 95% confidence interval (CI). The sensitivity, specificity, positive and negative predictive values for T. canis were 100%, 82%, 79% and 100%, respectively. The mentioned variables for T. cati were 97%, 82%, 78% and 98%, respectively. Five immune reactive bands of 38, 40, 72, 100 and 250 kDa were common in both species. Toxocara crude antigens were highly immunogenic in human sera. Immunoreactive bands against T. canis compared to T. cati somatic antigen were about two times more. Unlike Toxocara excretory-secretory antigen, that was homologue in two species, somatic antigens of T. canis and T. cati showed different immunoreactive bands in our western blot.

Organ-specific Toxocara canis larvae migration and host immune response in experimentally infected mice.

We investigated organ specific Toxocara canis larval migration in mice infected with T. canis larvae. We observed the worm burden and systemic immune responses. Three groups of BALB/c mice (n=5 each) were orally administered 1,000 T. canis 2nd stage larvae to induce larva migrans. Mice were sacrificed at 1, 3, and 5 weeks post-infection. Liver, lung, brain, and eye tissues were collected. Tissue from 2 mice per group was digested for larval count, while the remaining 3 mice underwent histological analysis. Blood hematology and serology were evaluated and compared to that in a control uninfected group (n=5) to assess the immune response. Cytokine levels in bronchoalveolar lavage (BAL) fluid were also analyzed. We found that, 1 week post-infection, the mean parasite load in the liver (72±7.1), brain (31±4.2), lungs (20±5.7), and eyes (2±0) peaked and stayed constant until the 3 weeks. By 5-week post-infection, the worm burden in the liver and lungs significantly decreased to 10±4.2 and 9±5.7, respectively, while they remained relatively stable in the brain and eyes (18±4.2 and 1±0, respectively). Interestingly, ocular larvae resided in all retinal layers, without notable inflammation in outer retina. Mice infected with T. canis exhibited elevated levels of neutrophils, monocytes, eosinophils, and immunoglobulin E. At 5 weeks post-infection, interleukin (IL)-5 and IL-13 levels were elevated in BAL fluid. Whereas IL-4, IL-10, IL-17, and interferon-γ levels in BAL fluid were similar to that in controls. Our findings demonstrate that a small portion of T. canis larvae migrate to the eyes and brain within the first week of infection. Minimal tissue inflammation was observed, probably due to increase of anti-inflammatory cytokines. This study contributes to our understanding of the histological and immunological responses to T. canis infection in mice, which may have implications to further understand human toxocariasis.

Alterations of plasma circulating microRNAs in BALB/c mice with Toxocara canis visceral and cerebral larva migrans.

BACKGROUND: Human toxocariasis is a neglected parasitic disease characterised by the syndromes visceral, cerebral, and ocular larva migrans. This disease is caused by the migrating larvae of Toxocara roundworms from dogs and cats, affecting 1.4 billion people globally. Via extracellular vesicles (EVs), microRNAs have been demonstrated to play roles in host-parasite interactions and proposed as circulating biomarkers for the diagnosis and follow-up of parasitic diseases. METHODS: Small RNA-seq was conducted to identify miRNAs in the infective larvae of T. canis and plasma EV-containing preparations of infected BALB/c mice. Differential expression analysis and target prediction were performed to indicate miRNAs involved in host-parasite interactions and miRNAs associated with visceral and/or cerebral larva migrans in the infected mice. Quantitative real-time polymerase chain reaction (PCR) was used to amplify circulating miRNAs from the infected mice. RESULTS: This study reports host and parasite miRNAs in the plasma of BALB/c mice with visceral and cerebral larva migrans and demonstrates the alterations of these miRNAs during the migration of larvae from the livers through the lungs and to the brains of infected mice. After filtering unspecific changes in an irrelevant control, T. canis-derived miRNAs and T. canis infection-induced differential miRNAs are predicted to modulate genes consistently involved in mitogen-activated protein kinase (MAPK) signalling and pathways regulating axon guidance and pluripotency of stem in the infected mice with visceral and cerebral larva migrans. For these plasma circulating miRNAs predicted to be involved in host-parasite crosstalk, two murine miRNAs (miR-26b-5p and miR-122-5p) are experimentally verified to be responsive to larva migrans and represent circulating biomarker candidates for visceral and cerebral toxocariasis in BALB/c mice. CONCLUSIONS: Our findings provide novel insights into the crosstalk of T. canis and the mammalian host via plasma circulating miRNAs, and prime agents and indicators for visceral and cerebral larva migrans. A deep understanding of these aspects will underpin the diagnosis and control of toxocariasis in humans and animals.

Echinococcus multilocularis and Other Intestinal Parasites of the Red Fox (Vulpes vulpes) from the Pomerania Region, Northern Poland.

The aim of the study was to determine the species composition of the intestinal parasite fauna of foxes from the Pomerania region, with a particular emphasis on helminth species considered dangerous to humans, and to determine their prevalence and intensity of infection. In total, 165 digestive systems from foxes inhabiting the Pomeranian region were examined. The prevalence of intestinal parasites among the studied foxes was 61.8%. Our findings confirm that foxes in Pomerania carry various parasites, some of which pose a direct threat to human health. As such, constant monitoring of their infestation is essential. Particular attention should be paid to parasite species with potential for transmission to humans, such as Echinococcus multilocularis, Alaria alata and Toxocara canis, whose respective prevalence was found to be 10.9%, 17.6% and 28.5%.

Proteomic change in the upper lobe of the left lung of Beagle dogs at the lung migration stage of Toxocara canis infection.

BACKGROUND: Toxocara canis is considered one of the most neglected parasitic zoonoses and threatens the health of millions of people worldwide with a predilection for pediatric and adolescent populations in impoverished communities. Exploring the invasion and developmental mechanisms associated with T. canis infection in its definitive canine hosts will help to better control zoonotic toxocariasis. METHODS: Proteomic changes in samples from the upper lobe of the left lung of Beagle puppies were systematically analyzed by quantitative proteomic technology of data-independent acquisition (DIA) at 96 h post-infection (hpi) with T. canis. Proteins with P-values < 0.05 and fold change > 1.5 or < 0.67 were considered proteins with differential abundance (PDAs). RESULTS: A total of 28 downregulated PDAs and 407 upregulated PDAs were identified at 96 hpi, including RhoC, TM4SFs and LPCAT1, which could be associated with the maintenance and repair of lung homeostasis. GO annotation and KEGG pathway enrichment analyses of all identified proteins and PDAs revealed that many lung proteins have correlation to signal transduction, lipid metabolism and immune system. CONCLUSIONS: The present study revealed lung proteomic alterations in Beagle dogs at the lung migration stage of T. canis infection and identified many PDAs of Beagle dog lung, which may play important roles in the pathogenesis of toxocariasis, warranting further experimental validation.

C-type lectin 4 of Toxocara canis activates NF-ĸB and MAPK pathways by modulating NOD1/2 and RIP2 in murine macrophages in vitro.

Toxocara canis is a parasitic zoonose that is distributed worldwide and is one of the two pathogens causing toxocariasis. After infection, it causes serious public health and safety problems, which pose significant veterinary and medical challenges. To better understand the regulatory effects of T. canis infection on the host immune cells, murine macrophages (RAW264.7) were incubated with recombinant T. canis C-type lectin 4 (rTc-CTL-4) protein in vitro. The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2), receptor-interacting protein 2 (RIP2), nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) on mRNA level and protein expression level in macrophages. Our results indicated that 10 µg/mL rTc-CTL-4 protein could modulate the expression of NOD1, NOD2, and RIP2 at both the transcriptional and translational levels. The protein translation levels of NF-κB, P-p65, p38, and P-p38 in macrophages were also modulated by rTc-CTL-4 protein. Macrophages were co-incubated with rTc-CTL-4 protein after siRNA silencing of NOD1, NOD2, and RIP2. The expression levels of NF-κB, P-p65, p38, and P-p38 were significantly changed compared with the negative control groups (Neg. Ctrl.). Taken together, rTc-CTL-4 protein seemed to act on NOD1/2-RIP2-NF-κB and MAPK signaling pathways in macrophages and might activate MAPK and NF-κB signaling pathways by regulating NOD1, NOD2, and RIP2. The insights from the above studies could contribute to our understanding of immune recognition and regulatory mechanisms of T. canis infection in the host animals.

Extracellular traps development in canine neutrophils induced by infective stage Toxocara canis larvae.

Neutrophils, a crucial element of the host defense system, develop extracellular traps against helminth parasites. Neutrophils accumulate around the larvae of Toxocara canis (T. canis) in the tissues of the organism. This study aimed to determine the reaction in canine neutrophils after incubation with infective stage T. canis larvae (L3) in vitro. Most L3 were still active and moved between the extracellular traps (NETs) after 60-min incubation. NETs were not disintegrated by L3 movement. The L3 was only immobilized by NETs, entrapped larvae were still motile between the traps at the 24 h incubation. NETs were observed not only to accumulate around the mouth, excretory pole or anus but also the entire body of live L3. The extracellular DNA amount released from the canine neutrophils after being induced with phorbol 12-myristate 13-acetate was not affected by T. canis excretory/secretory products obtained from 250 L3. To the Authors'knowledge, the extracellular trap structures was firstly observed in canine neutrophils against T. canis L3 in vitro. NETs decorated with myeloperoxidase, neutrophil elastase and histone (H3) were observed under fluorescence microscope. There were not significant differences in the amount of extracellular DNA (P > 0.05), but the morphological structure of NETs was different in the live and head-inactivated T. canis larvae.

Comparison of extracellular vesicle isolation methods for the study of exosome cargo within Toxocara canis and Toxocara cati excretory secretory (TES) products.

Toxocara is a genus of nematodes, which infects a variety of hosts, principally dogs and cats, with potential zoonotic risks to humans. Toxocara spp. larvae are capable of migrating throughout the host tissues, eliciting eosinophilic and granulomatous reactions, while surviving for extended periods of time, unchanged, in the host. It is postulated that larvae are capable of altering the host's immune response through the release of excretory-secretory products, containing both proteins and extracellular vesicles (EVs). The study of EVs has increased exponentially in recent years, largely due to their potential use as a diagnostic tool, and in molecular therapy. To this end, there have been multiple isolation methods described for the study of EVs. Here, we use nanoparticle tracking to compare the yield, size distribution, and % labelling of EV samples acquired through various reported methods, from larval cultures of Toxocara canis and T. cati containing Toxocara excretory-secretory products (TES). The methods tested include ultracentrifugation, polymer precipitation, magnetic immunoprecipitation, size exclusion chromatography, and ultrafiltration. Based on these findings, ultrafiltration produces the best results in terms of yield, expected particle size, and % labelling of sample. Transmission electron microscopy confirmed the presence of EVs with characteristic cup-shaped morphology. These findings can serve as a guide for those investigating EVs, particularly those released from multicellular organisms, such as helminths, for which few comparative analyses have been performed.

Anthelmintic efficacy of nitazoxanide in dogs naturally infected with Toxocara canis.

Toxocara canis (T. canis) is a gastrointestinal nematode in dogs, and its larvae also infect humans, causing severe larval migratory disease. Anthelmintic drugs have become the primary means to combat T. canis. In this study, the efficacy of nitazoxanide (NTZ) was tested against all the internal stages of T. canis, including L3 larval stage in vitro experiments and gastrointestinal worm in vivo experiments. In the in vitro experiment, after treatment with NTZ at 7.81 and 62.5 µg/mL for 12 h, the larval mortality efficacy reached 90.0 and 100.0%, respectively. In the in vivo experiments, 100 mg/kg NTZ possessed good anthelmintic efficacy against T. canis, with an egg per gram (EPG) reduction of 99.19%, and 90.00% of dogs cleared with residual worms. These results were comparable to those of the positive control drug. The highest anthelmintic efficacy was observed in the group treated with 150 mg/kg NTZ. Based on faecal egg counts, the number of T. canis eggs decreased by 100.00%, and the percentage of dogs cleared with residual worms achieved 90.00% after 7 days of treatment in the 150-mg/kg NTZ treatment group. In general, NTZ showed great potential to be applied as an anthelmintic against T. canis.

Sexual Dimorphism in the Physiopathology and Immune Response during Acute Toxocara canis Infection.

BACKGROUND: Toxocara canis (T. canis) is a helminth parasite of zoonotic and veterinary health significance that causes the disease known as Toxocariasis. This disease has been associated with conditions of poverty, especially in tropical climate zones throughout the world. Although it rarely causes important clinical manifestations, T. canis can lead to blindness, meningoencephalitis, or other nervous manifestations in humans. Moreover, some studies show its importance in the development of tumor growth, which have been associated with the parasite's ability to modulate the host's immune response. While different studies have evaluated the immune response during this disease, currently, there are no studies where the infection is analyzed from the perspective of sexual dimorphism. METHODS: To evaluate sex differences in susceptibility, we analyzed lesions and parasite loads in lung and liver at 7 days post-infection. In addition, immune cell subpopulations were analyzed in spleen, mesenteric and peripheral lymph nodes. Finally, the production of cytokines and specific antibodies were determined in the serum. Statical analyses were performed using a Two-way ANOVA and a post-hoc Bonferroni multiple comparison test. RESULTS: Female rats had a higher number of larvae in the liver, while male rats had them in the lungs. The percentages of immune cells were evaluated, and in most cases, no significant differences were observed. Regarding the cytokines production, infection can generate a decrease in Th1 such as IL-1ß in both sexes and IL-6 only in females. In the case of Th2, IL-4 increases only in infected males and IL-5 increases in males while decreasing in females due to the effect of infection. IL-10 also decreases in both sexes as a consequence of the infection, and TGF-ß only in females. Finally, the infection generates the production of antibodies against the parasite, however, their quantity is lower in females. CONCLUSIONS: This study demonstrates that T. canis infection is dimorphic and affects females more than males. This is due to a polarization of the inadequate immune response, which is reflected as a higher parasite load in this sex.

Toxocara canis infection in multiple types of animals: ophthalmological and pathological observations.

Human ocular toxocariasis (OT), caused by pet roundworm Toxocara canis (Nematoda Ascaridoidea), is a worldwide ocular parasitic infection that poses a severe threat to eyesight, especially in school-aged children. However, the infection process and pathological mechanism of Toxocara are difficult to study in the human body. This study was designed to explore long-term ocular manifestations in different rodents infected with Toxocara canis, uncovering the specific pathological mechanism and migration pathway of larvae after infection. The three types of experimental animals we selected were C57BL/6 mice, Mongolian gerbils and Brown Norway rats. Mice were randomly divided into five groups and infected orally with 1000, 2000, 4000, 8000 and 10,000 T. canis eggs; gerbils were randomly divided into four groups and infected orally with 1000, 2000, 4000 and 10,000 T. canis eggs; rats were randomly divided into three groups and infected orally with 2000, 6000 and 10,000 T. canis eggs. Their ocular changes were closely observed and recorded for at least 2 months. We also enucleated the eyeballs of some animals to perform pathological sectioning and hematoxylin-eosin staining. After 3 dpi (days post-infection), hemorrhagic lesions, mechanical injury of the retina and larval migration could be observed in some infected animals. The ocular infection and mortality rates tended to be stable at 7 dpi. Larval tissue, structure disorder and inflammation could be observed in the pathological sections. In conclusion, the mice infected with 2000 T. canis eggs and gerbils infected with 1000, 2000 and 4000 T. canis eggs showing obvious ocular lesions and lower mortality rates could provide a basis for long-term observation.

A cross-sectional study to quantify the prevalence of Toxocara canis in dogs in the Central Highlands of Vietnam.

Toxocara canis is a globally distributed zoonotic parasite. The parasite has recently become a concern for public health in Vietnam. This cross-sectional study aimed to identify and quantify the risk factors associated with T. canis infection in dogs in Dak Lak province in the Central Highlands of Vietnam. The risk factors were identified using a mixed-effects logistic regression model and quantified using population attributable fractions. Examination of fecal samples collected from 1455 dogs using the sodium nitrate flotation technique showed 37.32% (95% CI: 34.83-39.86) of dogs infected with T. canis. The factors, including study location, multiple dogs living in a household, dog age, dog breed, and places keeping dogs were associated with a dog's likelihood of being T. canis infection. The household and individual dog levels contributed 17% and 82%, respectively, to the prevalence of T. canis in dogs. The adjusted population attributable fraction for confining dogs and raising an individual dog per household was 52% and 27%, respectively. The result of this study indicated that to minimize the burden of T. canis, intervention measures should target individual dogs and household levels.

CANINE HOOKWORM PRESENCE IN TONGATAPU, TONGA.

Dogs are common in Tonga, where they exist in a close relationship with humans as pets and guard dogs and often are free-roaming due to limited property fencing and the need to scavenge for food. Little is known about the health status of these dogs and the type and level of pathogens carried by them. In this study, blood and fecal samples were analyzed to identify the presence of endoparasites and determine packed cell volume (PCV) values for dogs in Tonga. The current data deficit in this area made it necessary to develop a methodology and collect preliminary data to assist with future research in Tonga. Fecal analysis revealed hookworm in 73% of dogs, primarily those 4-12 mo old. Hematologic evaluation revealed low to borderline low PCV in 87% of dogs. The zoonotic nature of some of the pathogens identified poses a public health risk, with a particular risk for children.

The larvicidal effect of the supernatant of Lactobacillus acidophilus ATCC 4356 on Toxocara canis.

Human toxocariasis is a parasitic anthropozoonosis that is difficult to treat and control. A previous study carried out with Lactobacillus acidophilus ATCC 4356 revealed that the cell free supernatant (CFS) of this probiotic killed 100% of Toxocara canis larvae in vitro. The present study aimed to investigate the characteristics of the CFS of L. acidophilus ATCC 4356, which may be involved in its larvicidal effects on T. canis. L. acidophilus ATCC 4356 was cultured, and lactic and acetic acids present in the CFS were quantified by high performance liquid chromatography (HPLC). The levels of pH and H2O2 were also analyzed. To assess the larvicidal effect of the CFS, this was tested pure and diluted (1:2 to 1:128) on T. canis larvae. High concentrations of lactic and acetic acids were detected in the CFS. The acidity of the pure CFS was observed at pH 3.8, remaining acidic at dilutions of 1:2 to 1:16. Regarding the in vitro larvicidal effect, 100% death of T. canis larvae was observed using the pure CFS and 1:2 dilution. Based on these results, it can be inferred that the presence of higher concentrations of organic acids and low pH of the medium contributed to the larvicidal activity of the CFS of L. acidophilus ATCC 4356. In addition, the maintenance of the larvicidal effect, even after dilution, suggests a greater chance of the larvicidal effect of this CFS against T. canis in vivo.

Risk Factors Associated with Soil-Transmitted Helminths in Dog Feces That Contaminate Public Areas of Warsaw, Poland.

A constant increase in dog numbers, especially in large towns, has been observed recently. The presence of dogs in urban spaces increases the risk of pollution by dogs' feces, which may contain growth forms of parasites including canine, soil-transmitted helminths (cSTHs), most of which have a proven zoonotic potential. This study assessed the frequency of occurrence and estimated the potential risk associated with the presence of cSTHs in dogs' feces left uncollected in urban areas. The study material consisted of 200 fecal samples obtained from city and dog parks situated in selected Warsaw districts. Each fecal sample was processed using the flotation technique. Eggs of cSTHs, including Toxocara canis, Toxascaris leonina, Trichuris vulpis, and hookworms from the Ancylostomatidae family were found in 23 (11.5%) of the examined fecal samples. The most prevalent species were hookworms from the family Ancylostomatidae (8%). The presence of parasites was confirmed in 14 out of 20 studied locations (70%), including eight city parks (72.7%) and six dog parks (66.7%). City and dog parks did not differ significantly in the frequency of parasite occurrence. This study indicated that dogs' feces, left uncollected, may cause environmental contamination with cSTHs. It also indicated that the presence of dogs' feces in public areas and the associated presence of parasites is still a problem.

Migratory pattern of zoonotic Toxocara cati and T. canis in experimentally infected pigs.

BACKGROUND: Over a billion people are infected with Toxocara canis or T. cati, the roundworms of dogs and cats. Historically, T. canis has been considered the main species responsible for human toxocarosis, but as serodiagnosis cannot discriminate between the two species, this remains unresolved. We used pigs as a relevant large animal model for human infection to assess the migratory pattern of T. cati and T. canis. METHODS: Pigs were inoculated with T. cati or T. canis eggs or PBS (negative controls) and necropsied 14 or 31 days later. Different organs and tissues were examined for parasites and pathological changes. RESULTS: Overall, the two parasite species had a similar migration pattern reaching multiple organs and tissues, including the mesenteric lymph nodes, liver, lungs, and diaphragm. We recovered larvae of both species in the brain, suggesting that T. cati also can cause neurological toxocarosis in humans. Both species induced systemic eosinophilia and histopathological changes in the lungs, livers, and mesenteric lymph nodes. CONCLUSION: This study emphasises the importance of T. cati as a zoonotic agent and the need to develop diagnostic methods that can differentiate between sources of infection in humans.

Occurrence of zoonotic enteric parasites in fecal samples from dogs in shelters, parks, squares and public roads, and the dog guardians' perception of zoonoses as for the risk to public health in the city of Guarapuava, Paraná, Brazil.

The aim of this study was to determine the occurrence of zoonotic enteroparasites in the feces of dogs from public shelters, squares, parks, and public roads in the city of Guarapuava, Paraná, Brazil, and to evaluate the perception of dog guardians regarding zoonoses and their risk to public health. Fecal samples were collected, coproparasitological examinations were performed to detect zoonotic enteroparasites, and polymerase chain reaction (PCR) was used to identify Giardia spp. and Cryptosporidium spp. Questionnaires were given to guardians who walked their dogs in parks, squares, and public roads, as to assess their perception of zoonoses. A total of 333 samples were collected, of these 75, 123, and 135 of them were from public shelters, squares and parks, and public roads, respectively. One or more parasites were identified in 166 (50 %) samples, of which 58/75 (77 %) were from public shelters, 50/123 (41 %) from squares and parks, and 58/135 (43 %) from public roads. The parasites detected included Ancylostoma spp., Giardia spp., Trichuris spp., Toxocara spp., and Cystoisospora spp., with Ancylostoma spp. having the highest occurrence. PCR was performed on 161 samples for convenience due to financial limitations, because only a portion of the study was funded by the municipal government, of which 15.6 % were positive for Giardia spp., and all were negative for Cryptosporidium spp. In total, 246 guardians were interviewed, of which 36 % said they did not collect their animals' feces during walks, 20 % did not use anti-helminthics on their dogs, and 23 % did not know which diseases could be transmitted by feces. Therefore, we conclude that there is a high infection rate of parasites with zoonotic potential in public places, showing the need to raise awareness among guardians about the diseases transmitted by dog feces, correct vermifugation and the importance of collecting feces in public places.

Toxocara Canis Increases the Potential of Breast Cancer by Reducing the Expression of the P53 Protein.

INTRODUCTION: Breast cancer is considered the most frequent type of cancer in women with high mortality worldwide, and most importantly, it is the second most common cancer. However, some breast cancer-related risk factors remain unknown. So, the current study was designed to evaluate the effect of Toxocara canis on the biomarkers correlated with proliferation, apoptosis, inflammation, and angiogenesis in 4T1 tumor-bearing mice infected with Toxocara canis for the first time. METHODS: Mice were categorized into four groups: A) control, B) treated with 4T1+ Toxocara canis, C) treated with Toxocara canis, and D) treated with 4T1. The expression of Ki-67 and P53 was then evaluated by using the immunohistochemical technique. In addition, the levels of transforming growth factor-ß, Interferon gamma-γ, Interleukin 10, tumor necrosis factor-α and vascular endothelial growth factor as well as anti- Toxocara canis IgG were determined using the enzyme-linked immunosorbent assay method. RESULTS: The expression of Ki-67 was significantly increased in the 4T1+ Toxocara canis group than control and Toxocara canis groups (P < 0.001 and P < 0.001, respectively). Moreover, a significant decrease in P53 was found in the 4T1+ Toxocara canis group than in the control and Toxocara canis groups (P < 0.001 and P < 0.001, respectively). Also, the 4T1+ Toxocara canis group significantly reduced the expression of P53 more than 4T1 tumor-bearing mice (P = 0.005). In addition, the 4T1+ Toxocara canis group had an increasing tumor necrosis factor-α and vascular endothelial growth factor than controls (P = 0.004 and P = 0.002, respectively). Furthermore, a significant reduction in Interleukin 10 was found in the 4T1+ Toxocara canis group than in the control group (P = 0.004). CONCLUSION: Our findings showed that Toxocara canis could probably increase the potential of breast cancer by reducing P53 in 4T1 tumor-bearing mice infected with Toxocara canis more than other groups.

Efficacy of artemether against toxocariasis in mice: parasitological and immunopathological changes in brain, liver, and lung.

Toxocariasis is a zoonosis that represents a serious threat to public health particularly in tropical and subtropical areas. Currently, albendazole, the most effective drug for treating visceral toxocariasis, shows moderate efficacy against the larvae in tissues and has some adverse effects. Artemether is an antiparasitic drug mainly used in the treatment of malaria and showed effectiveness against numerous helminthic infections. Besides, it possesses potent anti-inflammatory, antiapoptotic, antifibrotic, and neuroprotective properties. Thus, the study's aim was to investigate artemether's effects in comparison with albendazole on the therapeutic outcome of experimental toxocariasis. For this aim, 140 laboratory-bred mice were divided into four main groups: uninfected control, treatment control, albendazole-treated, and artemether-treated groups. The treatment regimens were started at the 15th dpi (early treatment), and at the 35th dpi (late treatment). The effectiveness of treatment was determined by brain larval count, histopathological, immunohistochemical, and biochemical examination. Artemether showed more effectiveness than albendazole in reducing brain larval counts, markers of brain injury including NF-κB, GFAP, and caspase-3, the diameter and number of hepatic granulomas, hepatic oxidative stress, hepatic IL-6, and TG2 mRNA, and pulmonary inflammation and fibrosis. The efficacy of artemether was the same when administered early or late in the infection. Finally, our findings illustrated that artemether might be a promising therapy for T. canis infection and it could be a good substitution for albendazole in toxocariasis treatment.