Nitazoxanide, Ivermectin, and Artemether effects against cryptosporidiosis in diabetic mice: parasitological, histopathological, and chemical studies.

Human cryptosporidiosis is one of the most significant causes of water borne epidemics of diarrhea worldwide. It is extremely important in immunocompromised hosts and malnourished children as it could cause severe life-threatening diarrhea. Despite the global burden of the disease, there are only few available therapies against cryptosporidiosis. Diabetes mellitus is a common metabolic disorder that impair both the innate and adaptive immune responses of the patient. This study aimed to test the effect of Nitazoxanide, Ivermectin, and Artemether against cryptosporidiosis in diabetic mice. Sixty white albino mice were categorized into 6 groups; 10 mice each: GI: normal non-infected non-treated (healthy- control), GII-GVI (diabetic groups), GII: non-infected non treated (diabetic control), GIII: infected non treated (infected control), GIV: infected and treated with Nitazoxanide (NTZ), GV: infected and treated with Ivermectin (IVC), GVI: infected and treated with Artemether (ART). Parasitological, histopathological, and chemical examinations were done to evaluate the effect of NTZ, IVC, and ART against cryptosporidiosis in diabetic mice. Parasitological examination revealed maximum reduction of oocyst shedding in GVI, while histopathological examination showed the least pathologic changes in GV with mild vascular wall fibrosis and moderate lymphocytic infiltration of islets of Langerhans. Measurement of blood glucose level showed the best results with GIV. Nitazoxanide is effective against cryptosporidiosis in diabetic patients with minimal hyperglycemia, Artemether is especially effective in reducing the oocyst shedding in stool, whereas Ivermectin is associated with the least pathological changes in pancreatic islets of Langerhans.

Toxoplasmosis an Overlooked Disease: Seroprevalence in Cancer Patients

Background: Toxoplasmosis is one of the most important cosmopolitan life-threatening diseases in immune-compromised patients. It is caused by an intracellular protozoon: Toxoplasma gondii (T. gondii). The parasite can cause pneumonia, encephalitis or disseminated disease in immune-deficient patients and dangerous congenital anomalies in infants born to mothers infected during early pregnancies. The present study aims to evaluate the prevalence of toxoplasmosis in Egyptian cancer patients and to correlate the prevalence with type of malignancy and the different cancer treatment modalities. Materials and Methods: Blood samples from 150 cancer patients and 50 control subjects have been examined for presence of anti-toxoplasma antibodies using a lateral flow chromatographic immunoassay. Results: Among cancer patients included in this study, the prevalence of anti- T.gondii antibodies was 20% for IgG and 4% for IgM, while in the control group it was 8% and 2% in the same order. This difference was statistically significant for IgG (P =0.003) but not for IgM (P = 0.44). Patients with solid organ tumors treated with chemotherapy had the highest prevalence rate of toxoplasmosis (28%). It was also found higher in males (26%) than females (10%) and higher among urban (18%) than rural dwellers (16%). Conclusion: Cancer patients showed a significantly higher rate of infection with T. gondii than their cross-matched control. For that reason, we recommend the inclusion of a screening test for toxoplasmosis in their routine workup.

Efficacy and safety of artemether in the treatment of chronic fascioliasis in Egypt: exploratory phase-2 trials.

BACKGROUND: Fascioliasis is an emerging zoonotic disease of considerable veterinary and public health importance. Triclabendazole is the only available drug for treatment. Laboratory studies have documented promising fasciocidal properties of the artemisinins (e.g., artemether). METHODOLOGY: We carried out two exploratory phase-2 trials to assess the efficacy and safety of oral artemether administered at (i) 6×80 mg over 3 consecutive days, and (ii) 3×200 mg within 24 h in 36 Fasciola-infected individuals in Egypt. Efficacy was determined by cure rate (CR) and egg reduction rate (ERR) based on multiple Kato-Katz thick smears before and after drug administration. Patients who remained Fasciola-positive following artemether dosing were treated with single 10 mg/kg oral triclabendazole. In case of treatment failure, triclabendazole was re-administered at 20 mg/kg in two divided doses. PRINCIPAL FINDINGS: CRs achieved with 6×80 mg and 3×200 mg artemether were 35% and 6%, respectively. The corresponding ERRs were 63% and nil, respectively. Artemether was well tolerated. A high efficacy was observed with triclabendazole administered at 10 mg/kg (16 patients; CR: 67%, ERR: 94%) and 20 mg/kg (4 patients; CR: 75%, ERR: 96%). CONCLUSIONS/SIGNIFICANCE: Artemether, administered at malaria treatment regimens, shows no or only little effect against fascioliasis, and hence does not represent an alternative to triclabendazole. The role of artemether and other artemisinin derivatives as partner drug in combination chemotherapy remains to be elucidated.

Fasciola gigantica: evaluation of the effect of phenyl vinyl sulfone in vitro.

Phenyl vinyl sulfone is a synthetic inhibitor of cysteine protease and has antihelminthic and antiprotozoal properties. Phenyl vinyl sulfone was assayed in vitro for antifasciola activity against adult Fasciola gigantica worms using a well-established culture medium. Worms were treated with phenyl vinyl sulfone for incubation periods ranging from 0 to 12h and its activity was assessed in terms of viability, motility and death of worms. Phenyl vinyl sulfone exhibited a minimum effective concentration of 50 ppm after 12h. Three hundred parts per million concentrations were most potent causing immediate death of adult flukes in vitro. Histopathological studies showed that there was tegumental flattening, rupture of vesicles, and spine loss. Marked reduction in size and number of ova and sperms in the convoluted tubules of the reproductive organs was observed in comparison to the untreated control group. In conclusion, phenyl vinyl sulfone shows potent activity against F. gigantica in vitro, and the authors recommend carrying out more studies to detect its efficacy in vivo.

Epidemiologic approach for early detection and control of renal and urinary tract diseases in rural populations.

The dipstick testing, microscopic examination of urine and urine cytology were performed for inhabitants from two rural villages (El Shobak El Sharki, V.1 & El Katta, V.2) in Giza G. The proliferating cell nuclear antigen (PCNA) and Schistosoma haematobium antigen were done by immuno-histochemical stain to confirm diagnosis. Also, they were subjected to medical questionnaire, clinical examination, ultra-sonography of kidneys and urinary tract. The results showed that V.2 had higher percentage of haematuria, proteinuria, glucosuria and lower urinary tract infection than V.1. Crystaluria was higher in V.1. Sensitivity of dipstick testing compared to microscopic examination was 26.6%, & specificity was 78.7%. Lower urinary tract infection cytologically detected was 44.2% sensitivity & 62.5% specificity compared to pyuria detected by microscopic examination of urine. Among those suffering variable urinary abnormalities, schistosome antigen was not detected in any fixed urine samples in comparison to corresponding confirmed positive controls. Urine cytology detected urinary tract infection, crystaluria, dysplasia and atypia, squamous metaplasia and transitional cell carcinoma (TCC). PCNA positivity was found in TCC (100%), dysplasia (50%) and squamous metaplasia (28.6%). So, microscopic examination of urine proved valuable for tract abnormalities as pyuria, haematuria and crystaluria. Also, urine cytology is a must for malignancy of urinary tract especially in adult males.

Efficacy of mirazid in comparison with praziquantel in Egyptian Schistosoma mansoni-infected school children and households.

This trial investigated the anti-schistosomal activity of mirazid in comparison with that of praziquantel in Schistosoma mansoni-infected Egyptian patients. The sample population was composed of 1,131 individuals (459 school children and 672 household members). Screening for S. mansoni was conducted using the standard Kato Katz technique. Four slides from a single stool sample were examined before treatment, and four slides per sample from stool samples obtained on three consecutive days were examined post-treatment. All positive eligible subjects were randomly assigned into two groups, the first received mirazid at a dose of 300 mg/day for three consecutive days, and the second received praziquantel at a single dose of 40 mg/kg. All treated subjects were examined 4-6 weeks post-treatment. Mirazid showed low cure rates of 9.1% and 8.9% in S. mansoni-infected school children and household members, respectively, compared with cure rates of 62.5% and 79.7%, respectively, in those treated with praziquantel. Therefore, we do not recommend mirazid as an agent to control schistosomiasis.

Epidemiology of Schistosoma mansoni infection and its relationship to snail distribution in a village at the Nile bank south to Cairo.

The relationship between epidemiology of S. mansoni infection and snail distribution at a village, related to Guiza Governorate and lies south to Cairo, was investigated. A systematic random sample of houses was selected. All inhabitants of the houses were invited to share in the study. The Number examined was 704. Urine and stools were examined using Nucleopore filtration and standard Kato-Katz techniques, respectively. Snail collection was done from 35 sites along the water bodies related to the village. Snails collected were examined by cercariae shedding under light. Snail differentiation was done. The results showed that the prevalence of Schistosoma mansoni human infection was 25.1 % and GMEC was 2.4 +/- 5.5. Schistosoma haematobium infection was zero percent. Biomphlaria alexandrina snail infection rate was 3.7% with density equal 0.5 +/- 1.3. Bulinus truncatus snail infection rate was zero percent. The pattern of S. mansoni human infection was closely related to snail distribution and infection. Presence of a hybrid species of B. alexandrina and B. glabrata may explain the epidemiological pattern found in the studied village.

Incidence of cryptosporidiosis in immunodeficient cancer patients in Egypt.

A coproprotozoal study was carried out on 63 patients suffering from malignancy. The majority had cancer of haemopoietic system. All patients were under chemotherapy and included: Group A (33 children) and Group B (30 adults) of whom 20 immunocompetent diarrhoeic patients of matched age and sex were considered as controls. Stool samples were examined by merthiolate iodine-formaldehyde concentration technique (MIF). Modified Zeihl-Neelsen (ZN) stain was performed for Cryptosporidium oocysts. Detection of Cryptosporidium coproantigen by enzyme-linked immunoassay test (Ridascreen test), was used. Immunoglobulins (IgG, IgM, IgE & IgA), C3, C4 and CD4:CD8 ratio, were measured. According to their levels 25 out of 63 patients had both humoral and cellular immunodeficiency. The incidence of Cryptosporidium in cancer patients was 23.8%, while it was 37.7% and 91% in children and adults immunodeficient patients, respectively. ZN stain was able in diagnosed Cryptosporidium in 13 out of 35 immunodeficient cases while ELISA detected only 11 cases. Cryptosporidium infection in immunodeficient cancer patients had significantly more frequent and prolonged duration of diarrhoea than in negative ones.

Upgrading of Kato-Katz technique for diagnosis of S. mansoni infection in rural Egypt.

Processing of the same stool samples was done using standard Kato-Katz (KK) technique with 41.7 mg of stools and one of the three modifications. These included KK technique using a higher concentration of glycerin (one and quarter, usual one) for preparation, or another stain (negrosin-eosin), with a specified formula, instead of the standard malachite green, or processing a smaller volume of stools (20mg). The results showed that, using cumulative infection rate from the two comparable tests as the reference, KK with higher concentration of glycerin was more sensitive than standard KK (sensitivities 77.6% and 61.2%. respectively). Using negrosin-eosin stain showed higher sensitivity (75.0%) in relation to standard KK technique (70.8%). Kato-Katz with higher concentration of glycerin showed the same sensitivity as KK with negrosin-eosin stain (85.7%) in relation to others. All comparisons showed statistically insignificant differences ((P>0.5). Using 20 mg of stools showed very low sensitivity in relation to standard KK technique (57.9% & 100.0% respectively). The statistical difference was highly significant. All specificities were 100%. Other screening indices showed the same trend of sensitivities. Degree of microscope clarity was optimal with higher concentration of glycerin. Negrosin-eosin showed better visualization of ova than the standard KK. All modifications took only an hour after processing to be examined. KK technique used with any of these modifications, is simple, inexpensive. use of either a higher concentration of glycerin or negrosin-eosin stain and recommended for both field studies and primary health care settings.