Nahed M. Baddour

Miltefosine, a promising novel agent for schistosomiasis mansoni.

This research aims towards developing an alternative antischistosomal drug using miltefosine, which is primarily used in the treatment of leishmaniasis. The treatment and control of schistosomiasis, a notable neglected tropical disease (NTD), rely on a single drug, praziquantel (PZQ). The dependency on PZQ exclusively is quite alarming, given the spread of the disease (over 200 million people infected and close to 800 million people at risk in three continents) and the threat of drug resistance. This study shows that the oral administration of miltefosine in a daily dose of 20mg/kg for five successive days to mice infected with either invasive, juvenile or adult stages of Schistosoma mansoni resulted in significant reduction of worm burden, hepatic granulomata size and amelioration of hepatic pathology. Scanning Electron Microscopy revealed that miltefosine induced severe tegumental damage in adult schistosomes. In conclusion, we believe this is the first study highlighting miltefosine as a promising novel agent for schistosomiasis mansoni.

Initial characterization of an autoclaved Toxoplasma vaccine in mice

Toxoplasmosis is a zoonotic protozoal disease that has a major significance from the perspectives of public health and veterinary medicine. Therefore, an obvious long-term goal of many scientists would be the development of an effective vaccine. In this study, autoclaved vaccine was evaluated for its ability to protect mice against Toxoplasma gondii RH challenge as an acute infection model. Results showed that autoclaved Toxoplasma vaccine (ATV) when combined with BCG as an adjuvant was effective in triggering cell mediated immunity as shown by a significant increase in the percentage of splenic CD8+ T-lymphocytes. Following challenge, death of mice vaccinated with ATV was delayed for nine days. There was a significant decrease in parasite density in different organs, and a marked reduction of pathological changes in the liver suggesting that significant immune responses were mounted following vaccination. Future studies are warranted to test the vaccine against challenge with brain cysts as a chronic infection model and to evaluate it with other recent immunization strategies that can further enhance its immunogenicity.

Miltefosine for Old World cutaneous leishmaniasis: An experimental study on Leishmania major infected mice

Abstract Background Leishmaniasis is one of the neglected diseases included in the World Health Organizations list of the top guns of antimicrobial resistance. Miltefosine (MIL) was the first successful oral agent used against visceral leishmaniasis in India. As regards cutaneous leishmaniasis (CL), multiple experimental and clinical studies have investigated its efficacy in treatment of New World CL, while only few trials have focused on Old World CL. Therefore, this work was designed to study the efficacy of MIL in experimental Old World CL caused by Leishmania major (MHOM/IL/81/FEBNI), one of the causative species of CL in the Middle East. Results Groups of infected mice were given MIL orally, at a dose of 20 mg/kg/day for 20 days. Results showed that untreated infected mice suffered from autoamputation of the inoculated footpads. While, those treated with MIL showed complete clinical cure, significant reduction of parasite burden and improvement of the histopathological changes of the cutaneous lesions. The drug causes evident ultrastructural morphological alterations of L. major amastigote form. One month post-treatment, no clinical sings of relapse were observed, and parasite density continued to decrease significantly. Conclusion The present study revealed activity of MIL against experimental Old World CL in the mouse model caused by L. major (MHOM/IL/81/FEBNI), one of the causative species of CL in the Middle East.

Chronic hepatitis C in children: Clinical spectrum and histopathological study

Abstract Introduction Hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease. An estimated 180 million people are infected worldwide. The prevalence of hepatitis C virus (HCV) infection is relatively low in children, with an anti-HCV prevalence rate of 0.2–0.4% in the Western world. Egypt has the highest prevalence of adult HCV infection in the world, averaging 15–25% in rural communities. The main (90%) HCV genotype is type 4. The magnitude of HCV infection in children is not well studied. Asymptomatic HCV infection is detectable in 2.02% of Egyptian children. Aim To study the clinical presentation and histopathological features of the liver in children with chronic hepatitis C infection. Methods The study population included 40 children from 2 to 16 years who had been diagnosed with chronic hepatitis C (HCV-RNA positive for 6 months or more by Real-time PCR) in the liver clinic at El-Shatby Children Hospital. Results Among the 40 patients’ biopsies, 26 (65%) were stage 0, 10 (25%) were stage 1, 4 (10%) were stage 2–3 (HAI). The grades of all 40 children ranged between 0 and 1 (HAI). Developing fibrosis was significantly associated with age (P = 0.015). Conclusion Children with chronic HCV infection are generally asymptomatic. Significant hepatic fibrosis was present in 10% of children with HCV infection. Fibrosis stage was significantly higher in older age children. There was no significant association between fibrosis stage and any biochemical parameter.

In vivo assessment of the hepatotoxicity of a new Nostoc isolate from the Nile River: Nostoc sp. strain NRI

ABSTRACT Nostoc sp. is one of the most widely distributed cyanobacterial genera that produce potentially protein phosphatase (PP) inhibitor; microcystins (MCs). MCs have posed a worldwide concern due to predominant hepatotoxicity to human health. We have previously isolated a Nostoc strain (NR1) from the Nile River (the main water supply in Egypt) and this strain exerted production of rare and highly toxic MC; demethylated microcystin‐LR. There is no data concerning risk factors of liver diseases for human and animal exposure to NR1‐contaminated drinking water yet. It is thus important to evaluate acute (LD50 dose), subacute (0.01% and 10% of LD50 dose) and subchronic (0.01% and 10% of LD50 dose) hepatotoxicitys NR1 extract using experimental mice. Mice groups, who orally received 0.01% LD50, represented a permissible concentration of the World Health Organization (WHO) for MC in drinking water. Several parameters were detected, including hepatotoxicity (i.e. PP activity, liver function, oxidative stress markers and DNA fragmentation), pro‐inflammatory cytokine (TNF‐&agr;) and liver histopathology. Our results demonstrated LD50 of NR1 extract was at 15,350 mg/kg body weight and caused hepatotoxicity that attributed to PP inhibition and a significant increase of hepatic damage biomarkers with lipid accumulation. Moreover, NR1 extract induced hepatic oxidative damage that may have led to DNA fragmentation and production of TNF‐&agr;. As demonstrated from the histopathological study, NR1 extract caused a severe collapse of cytoskeleton with subsequent focal degeneration of hepatocytes, necroinflammation and steatosis. The grade of hepatotoxicity in subacute (10% of LD50) group was higher than that in the subchronic (10% of LD50 and 0.01% of LD50, WHOch, respectively) groups. No significant hepatotoxicity was detectable for subacute (0.01% of LD50, WHOac) group. NR1 is therefore considered as one of the harmful and life‐threatening cyanobacteria for Egyptian people being exposed to dose above WHO guideline. Thus, biological indicators and thresholds for water treatment are extremely needed. Graphical abstract Figure. No caption available. HighlightsIn vivo investigation of hepatotoxicity of our identified Nile River Nostoc sp. strain (Nostoc sp. NR1) extract.Hepatotoxicity signs of Nostoc sp. NR1 extract included cytoskeleton alteration, oxidative damage and necroinflammation.Hepatotoxicity of Nostoc sp. NR1 extract is highly related to its microcystins.Severe hepatotoxicity grade was recorded in the subacute animal group (10% LD50 Nostoc sp. NR1 extract) than subchronic group.Human and animals who exposed to excessive Nostoc sp. NR1‐contaminated water, may be at risk of major health problems.