Moxidectin versus Ivermectin in the prevention and treatment of acute and chronic experimental trichinellosis.

The limited activity of the traditional medications against T. spiralis encysted larvae handicaps complete cure of trichinellosis till now due to decreased permeability and absorption through tissues. MOX is listed worldwide for prevention and treatment of several internal and external nematodes. Consequently, the aim of this work was to investigate the effect of moxidectin versus ivermectin on experimental acute and chronic trichinellosis and to illuminate the potential mechanisms of their effects. 105 Mice were divided into four groups; Group I: Uninfected healthy control; Group II: Infected untreated control; Group III: Infected and treated with IVM and Group IV: Infected and treated with MOX. The groups (II, III and IV) were later subdivided equally into three subgroups (a, b, and c) according to the stage of treatment. Parasitological counting of adults and larvae besides immune-histopathological examination of intestines and muscles were done. Results exhibited that both IVM and MOX succeeded in reducing adults and larvae counts with higher potential of MOX in both intestinal and muscle phase. The preeminence of MOX was indicated by decreased inflammation, a significant reduction in the microvascular density (CD31 immunostaining) as well as a reduction in the percentage of fibroblast activation protein (FAP) immunostaining in muscle tissues. Accordingly, the current work recommends moxidectin as an innovative treatment for trichinellosis.

Trichinella spiralis Larval Extract as a Biological Anti-Tumor Therapy in a Murine Model of Ehrlich Solid Carcinoma.

Trichinella spiralis (T. spiralis) is an immunomodulating parasite that can adversely affect tumor growth and extend host lifespan. The aim of this study was to elucidate the mechanisms by which T. spiralis larval antigens achieve this effect using Ehrlich solid carcinoma (ESC) murine model. Assessment was done by histopathological and immunohistochemical analysis of caspase-3, TNF-α, Ki-67 and CD31. Additionally, Bcl2 and Bcl2-associated protein X (Bax) relative gene expression was assessed by molecular analysis for studying the effect of T. spiralis crude larval extract (CLE) antigen on tumor necrosis, apoptosis, cell proliferation and angiogenesis. We found that both T. spiralis infection and CLE caused a decrease in the areas of necrosis in ESC. Moreover, they led to increased apoptosis through activation of caspase-3, up-regulation of pro-apoptotic gene, Bax and down-regulation of anti-apoptotic gene, Bcl2. Also, T. spiralis infection and CLE diminished ESC proliferation, as evidenced by decreasing Ki-67. T. spiralis infection and CLE were able to suppress the development of ESC by inhibiting tumor proliferation, inducing apoptosis and decreasing tumor necrosis, with subsequent decrease in tumor metastasis. T. spiralis CLE antigen may be considered as a promising complementary immunotherapeutic agent in the treatment of cancer.

Trichinella spiralis: A new parasitic target for curcumin nanoformulas in mice models.

Trichinosis spiralis is a global disease with significant economic impact. Albendazole is the current-treatment. Yet, the world-widely emerging antimicrobial resistance necessitates search for therapeutic substitutes. Curcumin is a natural compound with abundant therapeutic benefits. This study aimed to evaluate the potential of crude-curcumin, chitosan and for the first time curcumin-nano-emulsion and curcumin-loaded-chitosan-nanoparticles against Trichinella spiralis adults and larvae in acute and chronic trichinosis models. Trichinosis spiralis was induced in 96 Swiss-albino mice. Infected mice were divided into 2 groups. Group I constituted the acute model, where treatment started 2 h after infection for 5 successive days. Group II constituted the chronic model, where treatment started at the 30th day-post-infection and continued for 10 successive days (Refer to graphical abstract). Each group contained 8 subgroups that were designated Ia-Ih and IIa-IIh and included; a; Untreated-control, b; Albendazole-treated (Alb-treated), c; Crude-curcumin-treated (Cur-treated), d; Curcumin-nanoemulsion-treated (Cur-NE-treated), e; Albendazole and crude-curcumin-treated (Alb-Cur-treated), f; Albendazole and curcumin-nanoemulsion-treated (Alb-Cur-NE-treated), g; Chitosan-nanoparticles-treated (CS-NPs-treated) and h; Curcumin-loaded-chitosan-nanoparticles-treated (Cur-CS-NPs-treated). Additionally, six mice constituted control-uninfected group III. The effects of the used compounds on the parasite tegument, in-vivo parasitic load-worm burden, local pathology and MDA concentration in small intestines of acutely-infected and skeletal muscle of chronically-infected mice were studied. Results showed that albendazole was effective, yet, its combination with Cur-NE showed significant potentiation against adult worms and muscle larvae and alleviated the pathology in both models. Cur-CS-NPs exhibited promising results in both models. Crude-curcumin showed encouraging results especially against muscle larvae on long-term use. Treatments effectively reduced parasite load, local MDA level and CD31 expression with anti-inflammatory effect in intestine and muscle sections.

Parasitic infections as potential risk factors for attention deficit hyperactivity disorder (ADHD) in children.

Attention deficit hyperactivity disorder (ADHD) represents a mysterious neuropsychiatric alarming concern due to indefinite etiopathogenesis among children. Notably, the studies which investigated the correlation between ADHD and parasitic infections are insufficient. Therefore, this research aimed to assess the correlation between ADHD and some tissue dwelling and intestinal parasitic infections in children. The study was conducted on 200 children, including 100 children suffering from ADHD (Group I) and 100 healthy children as a control group (Group II). All caregivers fulfilled predesigned sociodemographic form and Conners parent rating scale (CPRS-48) questionnaire. Blood samples were collected to determine hemoglobin level as well as relative eosinophilic count. The presence of anti-Toxoplasma IgG and anti-Toxocara IgG in serum by Enzyme-Linked Immunosorbent Assay (ELISA) was further investigated. Also, micronutrients as zinc, iron, and copper levels were measured. Schistosoma antigen was investigated in urine samples. Stool samples were subjected to direct wet smear, concentration technique and modified Ziehl-Neelsen (MZN) staining for coccidian parasites detection. Cryptosporidium parvum, Giardia lamblia and Entamoeba histolytica antigens were investigated in stool samples. Group I expressed more liability to sociodemographic risk factors, decreased levels of Hb, iron, zinc, and copper with statistically significant difference (P < 0.001). Comparison between Group I and Group II regarding the detected parasitic infections exhibited statistically significant difference except Schistosoma antigen positivity which expressed no statistical significance. The present study concluded that the parasitic infections with their consequences are potential risk factors in children with ADHD indicating that their early diagnosis and treatment may help in ADHD prevention.

Direct and indirect antiparasitic effects of chloroquine against the virulent RH strain of Toxoplasma gondii: An experimental study.

BACKGROUND: Toxoplasmosis is a deleterious parasitic disease with harmful impact on both humans and animals. The present study was carried out to evaluate the antiparasitic effect of chloroquine (CQ), spiramycin (SP), and combination of both against the highly virulent RH HXGPRT (-) strain of Toxoplasma gondii (T. gondii) and to explore the mechanisms underlying such effect. METHODS: We counted the tachyzoites in the peritoneal fluid and liver smears of mice and performed scanning and transmission electron microscopy and immunofluorescence staining of tachyzoites. Moreover, relative caspase 3 gene expression was measured by real time polymerase chain reaction of liver tissues and immunoassay of anti-apoptotic markers [B cell lymphoma-2 (Bcl-2) and X-chromosome linked inhibitor of apoptosis (XIAP)] and interferon gamma (IFN-γ) was done in liver tissues by ELISA. In addition, we estimated serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) and performed histopathological examination of liver sections for scoring of inflammation. RESULTS: We found that both CQ and CQ/SP combination significantly reduced parasitic load in the peritoneal fluid and liver smears, induced apical disruption of tachyzoites, triggered host cell apoptosis through elevation of relative caspase 3 gene expression and suppression of both Bcl-2 and XIAP. Also, they upregulated IFN-γ level, reduced serum AST and ALT, and ameliorated liver inflammation. CONCLUSIONS: Either of CQ and CQ/SP combination was more effective than SP alone against T. gondii with the CQ/SP combination being more efficient. Therefore, adding CQ to other anti-Toxoplasma therapeutic regimens may be considered in future research.

Immunoprotective inference of experimental chronic Trichinella spiralis infection on house dust mites induced allergic airway remodeling.

Allergic bronchial asthma is characterized by chronic inflammation of the respiratory airways mediated by T-helper 2 (Th2), Th17 and their cytokines. Although most asthmatic patients suffer from allergic airway remodeling (AAR), aggressive anti-allergic treatment failed to reverse it. The hygiene hypothesis illuminated the counter relationship between allergy and helminthic infections. The immune system is modulated by Trichinella spiralis (T. spiralis) infection to maintain homeostasis. Therefore, this work aimed to investigate the impact of chronic T. spiralis infection on induced AAR in C57BL/6 mice sensitized by house dust mites (HDM) allergens. Forty mice were divided into 3 groups: I (10 healthy mice), IΙ (15 HDM sensitized mice), and ΙΙI (15 T. spiralis chronically infected mice and sensitized with HDM allergens). The assessment aimed to evaluate the effects of regulatory CD4+CD25+FOXP3+ cells (Tregs) and their cytokines comparative to hypersensitivity mediated cytokines. Chronic T. spiralis infection effectively prevented the host's AAR. This result was evidenced by upregulated Tregs in blood by flow cytometric analysis and increased interleukin-10 (IL-10) levels in bronchoalveolar lavage (BAL) by Enzyme linked immunosorbent assay (ELISA) as well as improved lung histopathological changes. Also, serum HDM specific immunoglobulin E (IgE), BAL eosinophils, BAL IL-5 levels, and IL-17 gene expression in lung tissues were significantly reduced in T. spiralis chronically infected mice. In conclusion, the immune response in chronic T. spiralis infection could provide a promising mechanistic tool for protection against AAR, which paves the way for innovative preventive measures of other immunological disorders.

Oxidative stress mediated apoptotic potential of mefloquine on experimental trichinellosis.

Conventional anthelmintics such as albendazole could not achieve complete cure of trichinellosis till now. The antimalarial mefloquine mediates oxidative stress and disrupts lysosomal functions leading to cell death. Therefore, the aim of this work was to investigate the effect of mefloquine on experimental acute and chronic trichinellosis and to clarify the possible mechanisms of such effects. Mice were divided into four groups; Group I: Uninfected untreated control (20 mice); Group II: Infected untreated control (40 mice); Group III: infected and treated with albendazole (400 mg/kg) (40 mice); Group IV: infected and treated with mefloquine (300 mg/kg) (40 mice). All infected treated groups were equally subdivided into 2 subgroups; (a) treated on the 2nd day post infection (dpi) for 3 days, (b) treated on the 35th dpi for 5 days. Parasitological adults and larvae counting besides immunohistopathological examination of intestines and muscles were done. Biochemical assay of oxidant/antioxidant status, apoptotic, cytoprotective and inflammatory biomarkers in intestinal and muscle homogenates were achieved. Results showed that both albendazole and mefloquine significantly reduced adults and larvae counts with higher efficacy of albendazole in the intestinal phase and superiority of mefloquine in the muscle phase. The superiority of mefloquine was indicated by increased inflammatory immune infiltration and decreased anti-apoptotic immunohistochemical markers expression in both jejunal and muscle tissues. Biochemically, mefloquine treatment showed highly significant oxidative, apoptotic and inflammatory effects. So, our results suggest that mefloquine might be a superior treatment for chronic trichinellosis.