Biological evaluation of newly synthesized quinoline-based compound PPQ-8 in acute and chronic toxoplasmosis: An experimental study.

Toxoplasma gondii is a widely distributed protozoan parasite, which affects worm-blooded animals including human. The commonest chemotherapeutics used for treatment of symptomatic toxoplasmosis have numerous adverse effects. Thus there is an eminent need to develop new therapeutic agents. Here we described the therapeutic efficacy of 4-(2-chloroquinolin-3-yl)-6-(2,5-dimethoxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (PPQ-8); a quinoline-related compound in a mouse model of acute and chronic toxoplasmosis. In acute infection, PPQ-8 decreased the parasite load in liver and spleen with amelioration of the hepatic and splenic pathology. In addition, recovered tachyzoites showed distorted shapes, reduced sizes, irregularities, surface protrusions, erosions and peeling besides apical region distortion when seen by scanning electron microscopy. In chronic toxoplasmosis, PPQ-8 produced degeneration and reduction of the brain cysts without stimulating a damaging inflammatory response within the brain. In both models acute and chronic, PPQ-8 prolonged the survival time of mice. These findings hold promise for the development of a novel anti-toxoplasmosis drug using PPQ-8, but further in vivo studies should be carried out to elucidate PPQ-8 mechanism of action and to report its efficacy in combination with other anti-toxoplasmosis agents.

Comparative study between immunohistochemical grading and giardia genotyping among symptomatic and asymptomatic humans.

In the last years, multiple studies indicated the potential effectiveness of the polymerase chain reaction (PCR) for detection of Giardia in pathological specimens. By using the difference at the triose phosphate isomerase (tpi) gene locus, we investigated the genotype groups of Giardia lamblia isolated directly from fecal specimens collected from humans living in Dakahlia Governorate, Egypt. Immunohistochemical staining for detection of Giardia local antigenic and cellular immune-determinants focusing on CD4 and CD8 T-lymphocytes was also applied. The sensitivity of the ABC (avidine-biotin-peroxidase complex) immunoperoxidase technique for detection of the antigen was 97.3% and the specificity was 100%. Our study clearly demonstrated a highly significant difference between patients and controls as regards the grade of CD4 and CD8 lymphocyte infiltration (p < 0.001 for each correlation) but no significant difference was found between Giardia symptomatic and asymptomatic patients. Using the PCR technique, 89.3% sensitivity, 100% specificity and diagnostic accuracy of 92% were reached. Nevertheless, there was statistically insignificant difference between symptomatic and asymptomatic groups regarding the prevalence of different Giardia genotypes and the prevalence of CD4 and CD8 lymphocyte infiltration grading in different Giardia genotypes.

The histo-pathology of human giardiasis.

In giardiasis symptomatic group (I) the prevalence of diarrhoea was 5/7 (71.43%), 13/13 (100%) in Grade 0, I, II, III and IV pathology respectively which is statistically insignificant in comparison to each other (P > 0.05). The prevalence of abdominal pain is 71.43%, 73.33%, 95%, 91.67% and 100% in Grade 0, I, II, I & IV pathology respectively which is statistically insignificant to each other (P > 0.05). The prevalence of flatulence is 42.86%, 40%, 80%, 83.33% and 100% in Grade 0, I, II, III & IV pathology respectively, was statistically significant in comparison to each other (P < or = 0.05) So, the prevalence of flatulence is more frequent in patients with marked pathological changes in the duodenum. The prevalence of anorexia was 14.29%, 53.33%, 65%, 50% & 100% in Grade 0, I, II, III & IV pathology respectively, statistically significant in comparison to each other (P < or = 0.05). The prevalence of vomiting was 0%, 13.33%, 15%, 16.67 & 85.71% in Grade 0, I, II, III and IV pathology respectively, significant increased in Grade IV and absent in Grade 0 (P < or = 0.001).

Evaluation of two serological tests in diagnosis of human cases of biliary and ectopic fascioliasis.

In the present study, sera were examined using Fasciola-IHA, F-ELISA and Schistosoma-IHA. The sero-positive schistosomal patients were subjected to rectal snip, while the sero-positive fascioliasis ones were examined radiologically by plain chest X-ray and abdominal ultrasonography. Both F-IHA and F-ELISA gave 100% sensitivity. The specificity of both testes were 90.4% and 100% respectively. With the S-IHA, the parasitologically proven schistosomal mansoni patients gave 95% positivity, while the proven fascioliasis patients gave false positive (8%) with this S-IHA. The radiological findings of the fascioliasis patients confirmed ectopic pleuro-pulmonary infection in five patients. Ascitis was detected in one patient, the pleural effusion and ascitic fluids showed high eosinophils. However, Fasciola eggs were detected in three patients only. Two patients showed hepatic nodules, and another two had hepatic cystic lesions. Three patients had immature Fasciola worms in gall bladder. For diagnosis of human fascioliasis, serological and radiological means should be done side by side with the stool examination. This is particularly true in chronic cases and in schistosomiasis mansoni endemic areas.