Encephalitozoon intestinalis: A new target for auranofin in a mice model.

Despite the fact that many approaches have been developed over years to find efficient and well-tolerated therapeutic regimens for microsporidiosis, the effectiveness of current drugs remains doubtful, and effective drugs against specific targets are still scarce. The present study is the first that was designed to evaluate the potency of auranofin, an anti-rheumatoid FDA approved drug, against intestinal Encephalitozoon intestinalis. Evaluation of the drug was achieved through counting of fecal and intestinal spores, studying the intestinal histopathological changes, measuring of intestinal hydrogen peroxide level, and post therapy follow-up of mice for 2 weeks for detection of relapse. Results showed that auranofin has promising anti-microsporidia potential. It showed a promising efficacy in mice experimentally infected with E. intestinalis. It has revealed an obvious reduction in fecal spore shedding and intestinal tissue spore load, amelioration of intestinal tissue pathological changes, and improvement of the local inflammatory infiltration without significant changes in hydrogen peroxide level. Interestingly, auranofin prevented the relapse of infection. Thus, considering the results of the present work, auranofin could be considered a therapeutic alternative for the gold standard drug 'albendazole' against the intestinal E. intestinalis infection especially in relapsing cases.

Silver nanoparticles as a therapeutic agent in experimental cyclosporiasis.

Cyclosporiasis is an emerging worldwide infection caused by an obligate intracellular protozoan parasite, Cyclospora cayetanensis. In immunocompetent patients, it is mainly manifested by self-limited diarrhea, which is persistent and may be fatal in immunocompromised patients. The standard treatment for cyclosporiasis is a combination of two antibiotics, trimethoprim and sulfamethoxazole. Gastrointestinal, haematologic and renal side effects were reported with this combination. Moreover, sulfa allergy, foetal anomalies and recurrence were recorded with no alternative drug treatment option. In this study, silver nanoparticles were chemically synthesized to be evaluated for the first time for their anti-cyclospora effects in both immunocompetent and immunosuppressed experimental mice in comparison to the standard treatment. The effect of silver nanoparticles was assessed through studying stool oocyst load, oocyst viability, ultrastructural changes in oocysts, and estimation of serum gamma interferon. Toxic effect of the therapeutic agents was evaluated by measuring liver enzymes, urea and creatinine in mouse sera. Results showed that silver nanoparticles had promising anti-cyclospora potentials. The animals that received these nanoparticles showed a statistically significant decrease in the oocyst burden and number of viable oocysts in stool and a statistically significant increase in serum gamma interferon in comparison to the corresponding group receiving the standard treatment and to the infected non-treated control group. Scanning electron microscopic examination revealed mutilated oocysts with irregularities, poring and perforations. Biochemical results showed no evidence of toxicity of silver nanoparticles, as the sera of the mice showed a statistically non-significant decrease in liver enzymes in immunocompetent subgroups, and a statistically significant decrease in immunosuppressed subgroups. Furthermore, a statistically non-significant decrease in urea and creatinine was recorded in all subgroups. Thus, silver nanoparticles proved their effectiveness against Cyclospora infection, and this will draw the attention to its use as an alternative to the standard therapy.

A new scope for orlistat: Effect of approved anti-obesity drug against experimental microsporidiosis.

As the current therapies for intestinal microsporidiosis are either inconsistent in their efficacies or hampered by several adverse effects, alternative antimicrosporidial agents are being sought. The present study is the first that was designed to evaluate the potency of orlistat, an approved anti-obesity drug, against intestinal microsporidiosis caused by both Enterocytozoon bieneusi and Encephalitozoon intestinalis. Results were assessed through studying fecal and intestinal spore load, intestinal histopathological changes, viability, and infectivity of spores from treated animals. Results showed that orlistat has promising antimicrosporidia potential, with better results in E. intestinalis than E. bieneusi. The animals that received orlistat showed statistically significant decrease in the fecal and intestinal spore load, when compared to the corresponding control infected nontreated mice. The results were insignificant compared to fumagillin and albendazole. Light microscopic examination of stained intestinal sections revealed amelioration of the pathological changes and decreased inflammatory cells detected in the control infected nontreated mice. Spores encountered from stool of orlistat-treated E. bieneusi and E. intestinalis mice showed low viability and significant reduction of infectivity versus their control. Thus, considering the results of the present work, orlistat proved its effectiveness against the intestinal microsporidial infection.

Protective capacity of cercarial transformation fluid alone or in combination with crude cercarial antigen against challenge infections of Schistosoma mansoni in mice.

Schistosomiasis is the second major parasitic disease in the world after malaria. It affects 201.5 million cases in Africa alone. The aim of this research was to explore alternative vaccination strategies against experimental schistosomiasis mansoni. We assessed the effect of cercarial transformation fluid (CTF) singly and in combination with crude cercarial antigen (CCA) using alum as an adjuvant. The combined antigens gave the best results, as evidenced by a significant reduction in the worm load (62.07%), tissue egg count (78.16%, 86.46%) in liver and intestine respectively, and hepatic granuloma size (29.96%). Scanning electron microscopy revealed changes in the tegument, in the form of roughness and appearance of vesicles and furrows between the tegumental tubercles. Also, resorption of the ventral sucker and dimples replacing its spines were observed. The female tegument was irregular and its posterior end showed loss of spines and sensory bulbs. Moreover, there was a significant decrease in liver enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)) compared to infected control mice. A significant elevation in CD4+T-lymphocytes, denoting amelioration of the immune status, in mice that received combined antigens was also observed. It can be concluded that combined antigens demonstrate potential as a vaccine against Schistosoma mansoni.

Evaluation of ImmunoCard STAT test and ELISA versus light microscopy in diagnosis of giardiasis and cryptosporidiosis.

This study was designed to evaluate ImmunoCard STAT Cryptosporidium/Giardia rapid assay and ELISA copro-antigen assays in detecting Giardia lamblia and Cryptosporidium species in fecal samples in comparison to microscopy. Both ImmunoCard STAT and ELISA assays were evaluated with 90 stool specimens that were tested by the standard ova and parasite examination including staining with both iron hematoxylin stain and modified Ziehl Neelson stains. Counting the number of Giardia cysts and Cryptosporidia oocysts in the positive stool samples was done in order to quantify the lower limit of parasite number that was able to be detected by all included assays. Both ImmunoCard STAT and ELISA assays were compared on the basis of the attributes which are number of detected cases, sensitivity, specificity, time required for the procedure and screening, ease of performance and interpretation, and cost. Microscopic examination revealed that 13.3% of the samples were positive for Giardia and 2.2% for Cryptosporidium. By ELISA, 16.7% of the samples were infected with Giardia and 3.3% with Cryptosporidium, while by ImmunoCard STAT, 17.8 and 4.45% of the samples were positive for Giardia and Cryptosporidium, respectively. There is no statistically significant difference between the results of ELISA and ImmunoCard STAT assays. The lowest concentration detected in the stool samples was 10.50 ± 1.05 Giardia cysts and 2.83 ± 1.72 Cryptosporidium oocysts. The ImmunoCard STAT was extremely easy to read, thus requiring much less time, but its cost was much higher than ELISA. We concluded that although the overall ranking of both assays was high, the ImmunoCard STAT rapid assay was a more desirable test despite its higher cost.

Chitosan and silver nanoparticles: promising anti-toxoplasma agents.

Toxoplasmosis is a worldwide infection caused by obligate intracellular protozoan parasite which is Toxoplasma gondii. Chitosan and silver nanoparticles were synthesized to be evaluated singly or combined for their anti-toxoplasma effects as prophylaxis and as treatment in the experimental animals. Results were assessed through studying the parasite density and the ultrastructural parasite changes, and estimation of serum gamma interferon. Weight of tissue silver was assessed in different organs. Results showed that silver nanoparticles used singly or combined with chitosan have promising anti-toxoplasma potentials. The animals that received these compounds showed statistically significant decrease in the mean number of the parasite count in the liver and the spleen, when compared to the corresponding control group. Light microscopic examination of the peritoneal exudates of animals receiving these compounds showed stoppage of movement and deformity in shape of the tachyzoites, whereas, by scanning electron microscope, the organisms were mutilated. Moreover, gamma interferon was increased in the serum of animals receiving these compounds. All values of silver detected in different tissues were within the safe range. Thus, these nanoparticles proved their effectiveness against the experimental Toxoplasma infection.