Metagenomic analysis of the ocular toxoplasmosis in children uveitis from Fayoum governorate, Egypt.

Granulomatous anterior uveitis with single or numerous gelatinous nodules was found in children living in rural Egypt. All ocular diseases were originally thought to be water-born and related to digenic flukes. The current study sought to learn more about the causes of anterior granulomatous uveitis in Egyptian youngsters who used to swim in rural water canals. 50 children with eye lesions that had not responded to medical treatment were recruited. Four samples were surgically extracted and examined using real-time PCR, transmission electron microscopy (TEM), and shotgun metagenomic sequencing (SMS). Toxoplasma gondii was detected free within the syncytium's distal section, while the proximal part exhibited active synthesis of a presumably extra-polymeric material, possibly released by the microbial population. Toxoplasma gondii was found in 30 samples. Serologically, distinct anti-Toxoplasma antibodies were not found in 91.6% of patients. SMS showed that the T. gondii ME 49 strain had the greatest percentage (29-25%) in all samples within an Acinetobacter-containing microbial community. These findings suggested that these bacteria entered the body via the exterior route rather than the circulatory route. The lack of genetic evidence for subsequent parasite stages invalidates the prior findings about the assumed trematode stage.

Efficacy of clofazimine and nitazoxanide combination in treating intestinal cryptosporidiosis and enhancing intestinal cellular regeneration in immunocompromised mice.

Cryptosporidium is a widely distributed food and water-borne enteric protozoan that affects a wide range of vertebrates, resulting in life-threatening consequences, particularly in immunocompromised hosts. The lack of effective anti-cryptosporidial drugs may be related to the parasite's unique intestinal location, plus the lack of studies on the process by which the protozoan is able to impair intestinal cellular function. The present work aimed to assess the effect of clofazimine (CFZ), an FDA-approved drug for the treatment of leprosy, as an anti-cryptosporidial drug, using transmission electron microscopy (TEM) and an immunocompromised mouse model. The affected intestinal mucosa with parasitic stages in the infected non-treated group showed signs of severe cellular degeneration, including the loss of tight junctions, deformed and damaged microvilli and irregularly distributed nuclei with a severely vacuolated cytoplasm. Comparatively, nitazoxanide (NTZ) monotherapy showed the lowest efficacy as the drug was associated with the lowest rate of oocyst shedding. In addition, NTZ treatment failed to achieve the return of complete cellular function; abnormalities were evident in the microvilli, cytoplasmic organelles and nuclear features. Clofazimine demonstrated an improvement of the mucosal cellular components, including mitochondria and significantly reduced oocyst shedding. Combined treatment with low-dose CFZ and half-dose NTZ resulted in a significant improvement in the enterocyte cellular structures with an absence of intracellular parasitic stages. These results indicate that CFZ, a safe and readily prescribed drug, effectively reduces cryptosporidiosis when used in combination with only half the dose of NTZ. Used in combination, these drugs were shown to be efficient in regaining intestinal cellular activity following Cryptosporidium-induced functional damage in an immunocompromised mouse model.

Effect of mast cell stabilization on angiogenesis in primary and secondary experimental Trichinella spiralis infection.

BACKGROUND: Mast cells are known to affect the primary and secondary immune responses against parasites, and this effect is partially mediated through the release of pro-angiogenic mediators. The aim of this study was to explore the effect of the mast cell stabilizer (MCS), ketotifen, with and without albendazole, an anti-parasitic prescription medicine, on the inflammatory response against Trichinella spiralis, with the overall aim to investigate its effect on angiogenesis accompanying nurse cell formation. METHODS: The effect of ketotifen and albendazole was explored in eight groups of female BALB/c mice. Four groups were sensitized with a small dose of T. spiralis larvae. The drug regimen was then applied to both sensitized (challenged) and non-sensitized mice. The parasite load was assessed by histopathological examination of the small intestine and muscle tissue, and angiogenesis was assessed by immunohistochemistry to determine the expression of vascular endothelial growth factor (VEGF). RESULTS: Sensitized mice showed a significantly lower parasite load and a more pronounced inflammatory response than mice receiving a single infective dose of T. spiralis larvae. All treated groups showed a significant reduction in parasite count compared to the control groups (groups IAa and IBa), reaching approximately an 98.8% reduction in adult parasite count in the sensitized group treated with albendazole (groups IIAb and IIBb). MCS significantly decreased the parasite count during both the intestinal or muscular phases, reduced tissue inflammation, and decreased local VEGF expression, both in the non-sensitized and sensitized groups. CONCLUSION: Sensitization with a low dose of T. spiralis larvae was found to confer a partial protective immunity against re-infection and to positively affect the study outcomes, thus underlining the importance of vaccination, but after extensive studies. The anti-angiogenic effect of MCS protects against larval encystation during the muscle phase. The anti-angiogenic potential of albendazole suggests that the action of this anti-helminthic during trichinellosis is not confined to structural damage to the parasite cuticle but includes an effect on host immunopathological response.