Sulfadiazine analogs: anti-Toxoplasma in vitro study of sulfonamide triazoles.

Toxoplasmosis is an infection that prevails all over the world and is caused by the obligate intracellular protozoan parasite Toxoplasma gondii (T. gondii). Promising novel compounds for the treatment of T. gondii are introduced in the current investigation. In order to test their in vitro potency against T. gondii tachyzoites, six 1,2,3-triazoles-based sulfonamide scaffolds with terminal NH2 or OH group were prepared and investigated as sulfadiazine equivalents. When compared to sulfadiazine, which served as a positive control, hybrid molecules showed much more anti-Toxoplasma activity. The results showed that the IC50 of the examined compounds 3(a-f) were recoded as 0.07492 µM, 0.07455 µM, 0.0392 µM, 0.03124 µM, 0.0533 µM, and 0.01835 µM, respectively, while the sulfadiazine exhibited 0.1852 µM. The studied 1,2,3-triazole-sulfadrug molecular conjugates 3(a-f) revealed selectivity index of 10.4, 8.9, 25.4, 21, 8.3, and 29; respectively. The current study focused on the newly synthesized amino derivatives 3(d-f), as they contain the more potent amino groups which are recognized to be essential elements and promote better biological activity. Extracellular tachyzoites underwent striking morphological alterations after 2 h of treatment as seen by scanning electron microscopy (SEM). Additionally, the intracellular tachyzoite exposed to the newly synthesized amino derivatives 3(d-f) for a 24-h period of treatment revealed damaged and altered morphology by transmission electron microscopic (TEM) indicating cytopathic effects. Moreover, compound 3f underwent the most pronounced changes, indicating that it had the strongest activity against T. gondii.

Nanoformulation-Based 1,2,3-Triazole Sulfonamides for Anti-Toxoplasma In Vitro Study.

Toxoplasma gondii is deemed a successful parasite worldwide with a wide range of hosts. Currently, a combination of pyrimethamine and sulfadiazine serves as the first-line treatment; however, these drugs have serious adverse effects. Therefore, it is imperative to focus on new therapies that produce the desired effect with the lowest possible dose. The designation and synthesis of sulfonamide-1,2,3-triazole hybrids (3a-c) were performed to create hybrid frameworks. The newly synthesized compounds were loaded on chitosan nanoparticles (CNPs) to form nanoformulations (3a.CNP, 3b.CNP, 3c.CNP) for further in vitro investigation as an anti-Toxoplasma treatment. The current study demonstrated that all examined compounds were active against T. gondii in vitro relative to the control drug, sulfadiazine. 3c.CNP showed the best impact against T. gondii with the lowest IC50 value of 3.64 µg/mL. Using light microscopy, it was found that Vero cells treated with the three nanoformulae showed remarkable morphological improvement, and tachyzoites were rarely seen in the treated cells. Moreover, scanning and transmission electron microscopic studies confirmed the efficacy of the prepared nanoformulae on the parasites. All of them caused parasite ultrastructural damage and altered morphology, suggesting a cytopathic effect and hence confirming their promising anti-Toxoplasma activity.

Proposed morbidity markers among Schistosoma mansoni patients.

Background: Fecal calprotectin (FC) and fecal occult blood (FOB) were suggested as potential inflammatory markers for assessing intestinal schistosomiasis morbidity that are conventionally detected through invasive methods. Aim and Objectives: The present work aimed to evaluate FC and FOB as morbidity markers of Schistosoma mansoni infection before and after praziquantel treatment. Materials and Methods: A total of 205 stool samples (117 schoolchildren and 88 adults) were collected and examined by Kato Katz. A questionnaire enquiring about diarrhea, history of blood in stool, and abdominal pain was designed and applied. Results: S. mansoni prevalence rates were 20.5% and 11.36% among children and adults, respectively; the majority of cases had light infection intensity. FC and FOB were studied among 25 cured S. mansoni cases (17 children and 8 adults) pre and one-month post treatment. Before treatment, six and four children of moderate and high S. mansoni infection intensity tested positive for FC and FOB, respectively, all turning negative after treatment. FC showed borderline statistical significance before and after treatment among children. However, all adults tested negative for FC and FOB. Conclusion: FC and FOB could be possibly used as morbidity monitoring tools for S. mansoni infection in children with moderate and high infection intensity.

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.

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.

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.

Zinc PVA versus potassium dichromate for preservation of microsporidian spores of human origin.

Microsporidia are emerging opportunistic parasites. Preservation of the biological properties of microsporidian spores is often required in research work. The present study compared two preservatives; zinc polyvinyl alcohol (zinc PVA) and potassium dichromate solutions for preservation of microsporidian spores separated from human faecal samples. After 0, 1, 2 and 4 months of storage, morphological features and staining characters of the spores were assessed by light microscopy in modified trichrome-stained smears and their viability percentages were calculated using acridine orange/ethidium bromide mixture. Also, spore infectivity was evaluated by faecal spore shedding and intestinal spore load in mice orally inoculated with the preserved spores. Results revealed that morphological features, staining characters and viability of the spores were maintained in both solutions throughout the study period. Spore infectivity was completely preserved in zinc PVA solution but showed significant reduction in potassium dichromate solution at the fourth month of the preservation duration.

The serum gastrin level in patients with schistosomiasis and fascioliasis.

The study assessed changes in fasting serum gastrin level in early schistosomiasis and chronic fascioliasis in 52 patients. Forty patients had either schistosomiasis or fascioliasis alone. Twelve patients had combined infection with both parasitosis. Also, ten healthy parasite free individuals were selected as a control. All were clinically examined and subjected to stool analysis, liver function tests and sero-diagnosis for H. pylori. Serum gastrin was measured by radioimmunoassay and showed significant elevation in all patients (with schistosomiasis, fascioliasis or both parasites) compared to controls. A significantly higher serum gastrin level was detected among patients with combined infection relative to either with schistosomiasis or fascioliasis. Alkaline phosphatase activity increased significantly in all patients as compared to control. The activity of the enzyme had significant positive correlation with egg counts in patients with either parasite and with serum gastrin level in those with combined infection. The results were discussed.