Potent efficiency of the novel nitazoxanide-loaded nanostructured lipid carriers against experimental cyclosporiasis.

Cyclosporiasis is a ubiquitous infection caused by an obligate intracellular protozoan parasite known as Cyclospora cayetanensis (C. cayetanensis). The disease is characterized by severe diarrhea which may be regrettably fatal in immunosuppressed patients. The commercially available treatment options have either severe side effects or low efficiency. In the present study, the novel formula of nitazoxanide (NTZ)-loaded nanostructured lipid carriers (NLCs) was assessed for the first time for C. cayetanensis treatment in both immunocompetent and immunosuppressed mice in comparison to commercially available drugs (trimethoprim-sulfamethoxazole (TMP-SMX) and NTZ). Swiss Albino mice were orally infected by 104 sporulated oocysts. The experimental groups were treated with the gold standard TMP-SMX, NTZ, blank NLCs and NTZ-loaded NLCs. The results demonstrated that NTZ-loaded NLCs represented the highest significant parasite percent reduction of (>98% reduction) in both immunocompetent and immunosuppressed mice designating successful tissue penetration and avoiding recurrence of infection at the end of the study. Oocysts treated with NTZ-loaded NLCs demonstrated the most mutilated rapturing morphology via scanning electron microscope examination as well as representing the most profound improvement of the histopathological picture. In conclusion, NTZ-loaded NLCs exhibited the uppermost efficacy in the treatment of cyclosporiasis. The safe nature and the anti-parasitic effect of the novel formulation encourage its use as a powerful treatment for human cyclosporiasis.

Key cytokines and hematological parameters in patients with uncomplicated falciparum malaria in Hodeidah, Yemen.

Immunity to malaria has a major role in controlling disease and pathogenesis with cytokine production being involved in almost every phase of the immune response. The present study aimed to assess hematological variables and to measure plasma levels of TNFα, IFNγ and IL10, their ratios, and their relation to parasitemia among patients with uncomplicated falciparum malaria in Hodeidah, Yemen. Forty patients with uncomplicated P. falciparum monoinfection and 40 healthy age and sex-matched controls were enrolled in the study. Parasitological diagnosis was confirmed, and parasite density was estimated. Plasma cytokine levels, hematologic parameters, and the presence of gametocytes were determined. Results revealed higher TNFα, IFNγ and IL10 in patients than in controls. A relatively higher IL10 production was demonstrated by the significantly lower TNFα/IL10 and IFNγ/IL10 ratios in patients than in controls. TNFα and IL10 correlated positively with parasite density. Lower Hb levels, RBC, lymphocyte and platelet counts, and higher neutrophil and reticulocyte counts were observed in patients compared to controls. Reticulocyte count was higher and IFNγ level was lower in the presence of gametocytes. Conclusively, uncomplicated falciparum malaria is associated with the ability to regulate the production of pro-inflammatory and anti-inflammatory cytokines. This mediates parasite clearance while simultaneously avoiding severe pathology.

Synthesis, Characterization and Nanoformulation of Novel Sulfonamide-1,2,3-triazole Molecular Conjugates as Potent Antiparasitic Agents.

Toxoplasma gondii (T. gondii) is a highly prevalent parasite that has no gold standard treatment due to the poor action or the numerous side effects. Focused sulfonamide-1,2,3-triazole hybrids 3a-c were wisely designed and synthesized via copper catalyzed 1,3-dipolar cycloaddition approach between prop-2-yn-1-alcohol 1 and sulfa drug azides 2a-c. The newly synthesized click products were fully characterized using different spectroscopic experiments and were loaded onto chitosan nanoparticles to form novel nanoformulations for further anti-Toxoplasma investigation. The current study proved the anti-Toxoplasma effectiveness of all examined compounds in experimentally infected mice. Relative to sulfadiazine, the synthesized sulfonamide-1,2,3-triazole (3c) nanoformulae demonstrated the most promising result for toxoplasmosis treatment as it resulted in 100% survival, 100% parasite reduction along with the remarkable histopathological improvement in all the studied organs.

Remarkable histopathological improvement of experimental toxoplasmosis after receiving spiramycin-chitosan nanoparticles formulation.

The present study investigated the anti-Toxoplasma effect of chitosan nanoparticles [CS NPs], spiramycin, spiramycin co-administered with metronidazole and spiramycin-CS NPs formulation on the parasite burden and histopathological changes in the liver, spleen and brain in experimentally infected mice. Seventy male Swiss albino mice were classified into seven equal groups: healthy control (I), infected untreated control (II), infected group receiving CS NPs (III), spiramycin administered infected group (IV), infected group receiving spiramycin-metronidazole (V), infected receiving 400 mg/kg spiramycin-CS NPs (VI) and infected treated with spiramycin-loaded CS NPs 100 mg/kg (VII). All groups were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain except the healthy control group. All groups were sacrificed on the 8th day after infection. Density of the parasite and histopathological examination of the liver, spleen and brain of all treated mice revealed reduction in the mean tachyzoites count as well as decreased inflammation, congestion and necrosis within tissue sections. Spiramycin-loaded NPs displayed the highest significant reduction in the pathological insult tailed by spiramycin-metronidazole and CS NPs. In conclusion, spiramycin-loaded CS NPs showed a promising synergistic combination in the treatment of the histopathology caused by toxoplasmosis.

The powerful synergistic effect of spiramycin/propolis loaded chitosan/alginate nanoparticles on acute murine toxoplasmosis.

The novel formula of spiramycin/propolis loaded chitosan (CS)/alginate (Alg) nanoparticles (NPs) was assessed for Toxoplasma gondii (T. gondii) treatment in comparison with the commercially available spiramycin regarding tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally by 2500 tachyzoites of the virulent T. gondii RH strain. The experimental groups were treated with oral spiramycin, propolis, CS/Alg NPs, spiramycin loaded CS/Alg NPs, propolis loaded CS/Alg NPs, and spiramycin/propolis loaded CS/Alg NPs. The results demonstrated that spiramycin/propolis loaded CS/Alg NPs exerted the longest survival time with no mortality on the sacrifice day (8th) in addition to representing the highest significant parasite percent reduction of (≥96% reduction) in liver, spleen and brain designating successful tissue penetration and BBB passage. Tachyzoites treated with spiramycin/propolis loaded CS/Alg NPs demonstrated the most disfigured rapturing organism via scanning electron microscope examination along with representing an overall remarkable improvement of the histopathological pictures of liver, spleen and brain. In conclusion, spiramycin/propolis loaded CS/Alg NPs showed the uppermost efficacy in the treatment of acute murine toxoplasmosis. The safe nature and the anti-parasitic effect of each of CS, Alg, spiramycin and propolis encourage the synergistic use of spiramycin/propolis loaded CS/Alg NPs as a potent treatment for human toxoplasmosis.

Intestinal schistosomiasis among preschool and school-aged children in a rural setting near Alexandria: initiative for elimination.

OBJECTIVE: To assess the status of intestinal schistosomiasis among preschool-aged (PSAC) and school-aged children (SAC) and to compare the efficacy of praziquantel (PZQ) in both groups. METHODS: The study was conducted on 400 children; 103 PSAC and 297 SAC. Diagnosis of Schistosoma mansoni was based on triplicate Kato-Katz thick smears from a single stool sample. To identify the missed cases by Kato-Katz, 120 randomly selected negative cases (38 PSAC and 82 SAC) were screened by real-time PCR. All S. mansoni-positive cases by Kato-Katz were treated by crushed PZQ tablets. Four weeks after treatment, the cure rate was assessed by Kato-Katz smears and real-time PCR. RESULTS: The prevalence of S. mansoni with Kato-Katz was 7.8% among PSAC and 7.4% among SAC. Most of children (63.3%) had light-intensity infection. The cure rate was 100% among PSAC by both techniques, and 91%, and 77.2% among SAC by Kato-Katz and real-time PCR, respectively. In the 120 stool samples screened by real-time PCR, S. mansoni prevalence was 25%; 15.8% and 29.3% were among PSAC and SAC respectively. Treated cases showed a lower range of Ct values than untreated cases. Two melting temperature ranges (Tm = 83-87°C and 89-93°C) were recognised among uncured cases which may point to S. mansoni genetic variability. CONCLUSION: Continuous monitoring and inclusion of PSAC in schistosomiasis control programmes are crucial. Real-time PCR and other molecular tools are recommended for evaluation of the true prevalence, assessment of cure and further studies on genetic diversity.

Successful treatment of acute experimental toxoplasmosis by spiramycin-loaded chitosan nanoparticles.

Spiramycin-metronidazole and spiramycin-loaded chitosan (CS) nanoparticles (NPs) were tested in comparison with the current spiramycin treatment of T.gondii concerning tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain and were divided into experimental and control groups. The experimental groups orally received CS NPs, spiramycin, spiramycin-metronidazole, spiramycin-loaded CS NPs 400 mg/kg and spiramycin-loaded CS NPs 100 mg/kg. Drug efficacy was assessed by mice survival time, mortality rate, parasite load in different organs and morphological study of the tachyzoites movement by light microscope and the ultra-structure by SEM. The results revealed that the maximum survival time of more than 200 days with no mortality on the sacrifice day (8th) was observed in mice receiving spiramycin-loaded NPs. Spiramycin-loaded NPs showed the highest significant percent reduction of tachyzoites (about 90% reduction) in liver, spleen and brain as compared to the other used drugs denoting successful bypass of BBB. Light microscopy of the treated peritoneal tachyzoites showed sluggish tachyzoites movement while the NPs caused loss of their movement. SEM of the treated tachyzoites were more mutilated and some of them appeared rupturing in those receiving CS NPs and spiramycin-loaded NPs. In conclusion, spiramycin-loaded NPs showed the highest efficiency in the treatment of acute toxoplasmosis. The non-toxic nature and the anti-parasitic effect of both CS and spiramycin make the use of spiramycin-loaded CS NPs a potential material for treatment of human toxoplasmosis.