Evaluation of mono and combined nitrofurantoin therapy for toxoplasmosis in vivo using murine model.

Toxoplasmosis is a frequent disease with an estimated prevalence of more than one billion human cases worldwide and over one million new infections each year. It is classified as a neglected tropical disease by the CDC since 2019. The disease may pass unnoticed in healthy individuals but could be fatal in the immunocompromised. Moreover, no effective treatment is available against the chronic form of the disease. Available anti-Toxoplasma drugs are associated with many side effects. Therefore, search for new more reliable, more efficient, and less toxic therapeutic agents is a continuous endeavor. This study assesses the potential use of nitrofurantoin, a compound with well-established antimicrobial properties, as a potential anti-Toxoplasma drug in vivo. It compares its efficacy to the commonly used anti-Toxoplasma agent spiramycin by molecular and histopathological methods in acute and chronic infection. The results demonstrate a significant ability to eliminate the parasite (P < 0.001) whether used as mono- or combined therapy with spiramycin in the acute and chronic stages. When compared to the anti-Toxoplasma drug spiramycin, nitrofurantoin achieved similar efficacy in the acute and chronic infection (P = 0.65 and P = 0.096, respectively). However, better results were obtained when using a combination of both drugs (P < 0.001). Additionally, nitrofurantoin showed good inhibitory effects on the inflammatory process in the liver, kidney, and uterus of the experimentally infected animals. In conclusion, nitrofurantoin can be considered as a potential anti-Toxoplasma agent. Nevertheless, further studies are recommended before consideration for clinical trials.

Role of a schistosoma haematobium specific microRNA as a predictive and prognostic tool for bilharzial bladder cancer in Egypt.

Urinary bladder cancer is a common malignancy in Egypt, thus reliable methodologies are required for screening and early detection. In this study, we analyzed the gene expression of a Schistosoma hematobium specific microRNA "Sha-miR-71a" and mitogen-associated protein kinase-3 (MAPK-3) in the urine samples of 50 bladder cancer patients and 50 patients with benign bilharzial cystitis. Fifty control subjects were also tested. Indirect hemagglutination test (IHA) diagnosed 70% of studied cancer cases as bilharzial associated bladder cancer (BBC), while histopathological examination detected only 18%. Urinary Sha-miR-71a & MAPK-3 revealed enhanced expression in BBC (p-value = 0.001) compared to non-bilharzial bladder cancer (NBBC) cases. Patients with chronic bilharzial cystitis exhibited a significant increase in gene expression compared to those with acute infection (p-value = 0.001). Sha-miR-71a and MAPK-3 showed good sensitivity and specificity in the diagnosis of BBC when analyzed by the receiver operating characteristic (ROC) curve. They were also prognostic regarding malignancy grade. Both biomarkers showed a positive correlation. Our results revealed that IHA is a reliable test in the diagnosis of bilharziasis associated with bladder cancer, and that Sha-miR-71a and MAPK-3 provide non-invasive specific biomarkers to diagnose BBC, as well as a potential role in testing bilharzial patients for risk to develop cancer.

In vitro Effect of Silver Nanoparticles on Blastocystis hominis.

INTRODUCTION: This study aims to assess the efficacy of silver nanoparticles (Ag Nps) alone and combined with metronidazole (Ag Nps + MTZ) as potential alternative therapeutic agents for Blastocystis hominis. METHODS: The parasites were challenged with Ag Nps, Ag Nps + MTZ and MTZ. To assess the efficacy of drugs, counting of viable parasites was done after 1, 2, and 3 hours of adding the drugs. RESULTS: Blastocystis hominis count was reduced by 20.72%, 28.23%, and 18.92% after one hour of adding Ag Nps, Ag Nps + MTZ, and MTZ, respectively. Cysts count was further reduced by 51.49%, 61.61%, and 40.78% after 2 hours and by 71.69%, 79.67%, and 62.65% after 3 hours of adding the drugs in the same order, respectively. CONCLUSION: There was a statistically significant difference (P<0.05) in the in vitro growth inhibition of the parasite over the different time intervals when using the tested drugs against the control drug.

Can Toxoplasma gondii Pave the Road for Dementia?

Dementia is an ominous neurological disease. Scientists proposed a link between its occurrence and the presence of Toxoplasma gondii (T. gondii). The long-term sequels of anti-Toxoplasma premunition, chiefly dominated by TNF-α, on the neurons and their receptors as the insulin-like growth factor-1 receptor (IGF-1R), which is tangled in cognition and synaptic plasticity, are still not clear. IGF-1R mediates its action via IGF-1, and its depletion is incorporated in the pathogenesis of dementia. The activated TNF-α signaling pathway induces NF-κß that may induce or inhibit neurogenesis. This study speculates the potential impact of anti-Toxoplasma immune response on the expression of IGF-1R in chronic cerebral toxoplasmosis. The distributive pattern of T. gondii cysts was studied in association with TNF-α serum levels, the in situ expression of NF-κß, and IGF-1R in mice using the low virulent ME-49 T. gondii strain. There was an elevation of the TNF-α serum level (p value ≤ 0.004) and significant upsurge in NF-κß whereas IGF-1R was of low abundance (p value < 0.05) compared to the controls. TNF-α had a strong positive correlation with the intracerebral expression of NF-κß (r value ≈ 0.943, p value ≈ 0.005) and a strong negative correlation to IGF-1R (r value -0.584 and -0.725 for area% and O.D., respectively). This activated TNF-α/NF-κß keeps T. gondii under control at the expense of IGF-1R expression, depriving neurons of the effect of IGF-1, the receptor's ligand. We therefore deduce that T. gondii immunopathological reaction may be a road paver for developing dementia.

Validity of a new immunochromatographic test in detection of Toxoplasma gondii in cancer patients.

Screening of toxoplasmosis in cancer patients is mandatory especially before starting treatment to guard against life-threatening disseminated disease. Diagnosis of toxoplasmosis rely mainly on serology. The most widely used method for detection of anti-Toxoplasma gondii (T. gondii) antibodies is the enzyme linked immunosorbent assay (ELISA), being available and reliable. Immunochromatographic tests (ICT) attracted a lot of attention recently being one of the high quality, rapid and easy to perform tests. Available data comparing the performance of ICT versus ELISA techniques have yielded inconsistent results and none compared their performance among the immunocompromised cancer patients. Therefore, we designed this study to compare the performance of a new ICT (the OnSite Toxo IgG/IgM Combo Rapid test) and ELISA techniques for the detection of anti-T. gondii antibody as a tool for screening for toxoplasmosis among cancer patients in Cairo-Egypt. Among 180 cancer patients, a total of 110 patients (61.1%) were positive for anti-T. gondii antibodies by one or both methods. Agreement between both methods was found in 78.8% of the samples. By using ELISA technique as a gold standard test for the detection of anti-T. gondii antibodies, our results showed 87.5% specificity and 74% sensitivity of ICT technique. Moreover, our results proved that ICT is more sensitive in detecting lower level of antibodies than ELISA, that makes it preferable as a screening test for the immunocompromised patients.

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.

MODIFIED CULTURE METHODOLOGY FOR SPECIFIC DETECTION OF BLASTOCYSTIS HOMINIS IN STOOL SAMPLES.

Blastocystis hominis provides major challenges for laboratory diagnosis due to its polymorphic nature in wet mounts which can result in confusion with other protozoa, yeast or even fat globules. Studies revealed that simple smears were less sensitive than in vitro cultivation using different media for the detection of B. hominis in stool specimens. Cultures of B. hominis are usually enriched by different types of sera to enhance growth and multiplication of the parasite. The aim of this study is to assess the use of two sera types other than horse serum that is commonly used in culture media for the growth, multiplication and detection of B. hominis in examined stool samples and comparing the results with those obtained using horse serum. Fifty stool samples were collected from patients suffering from different colonic manifestations attending Cairo University Hospitals. The samples were freshly cultured in three different culture media using horse serum (in Jones' medium), donkey serum (as a modification ii Jones' medium) and human plasma (in modified Pavlova's medium) in adequate preparations. Cultures were then left for incubation and examined by direct microscopy to detect Blastocystis hominis. The result showed of 50 stool samples studied,. 18 samples (36%) were positive results for B. hominis. The number of positive results obtained by horse serum, donkey serum and human plasma were 13,18and 11 respectively. Paired comparisons were made between each 2 cultures with each culture set as a reference once to detect the most appropriate one for diagnosis When horse was set as the reference method, donkey serum showed a sensitivity of 100% and specificity of 86.5% with a 90% agreement between the 2 methods. While human plasma showed a sensitivity of 46.2% and specificity of 86.5% with an agreement of 76%. In addition, the vacuolar form was the commonest pattern observed in this study throughout all the three cultures.