Computer-Assisted Discovery of Alkaloids with Schistosomicidal Activity

Schistosomiasis is a chronic parasitic disease caused by trematodes of the genus Schistosoma; it is commonly caused by Schistosoma mansoni, which is transmitted by Bioamphalaria snails. Studies show that more than 200 million people are infected and that more than 90% of them live in Africa. Treatment with praziquantel has the best cost–benefit result on the market. However, hypersensitivity, allergy, and drug resistance are frequently presented after administration. From this perspective, ligand-based and structure-based virtual screening (VS) techniques were combined to select potentially active alkaloids against S. mansoni from an internal dataset (SistematX). A set of molecules with known activity against S. mansoni was selected from the ChEMBL database to create two different models with accuracy greater than 84%, enabling ligand-based VS of the alkaloid bank. Subsequently, structure-based VS was performed through molecular docking using four targets of the parasite. Finally, five consensus hits (i.e., five alkaloids with schistosomicidal potential), were selected. In addition, in silico evaluations of the metabolism, toxicity, and drug-like profile of these five selected alkaloids were carried out. Two of them, namely, 11,12-methylethylenedioxypropoxy and methyl-3-oxo-12-methoxy-n(1)-decarbomethoxy-14,15-didehydrochanofruticosinate, had plausible toxicity, metabolomics, and toxicity profiles. These two alkaloids could serve as starting points for the development of new schistosomicidal compounds based on natural products.

A machine learning-based system for detecting leishmaniasis in microscopic images

Background Leishmaniasis, a disease caused by a protozoan, causes numerous deaths in humans each year. After malaria, leishmaniasis is known to be the deadliest parasitic disease globally. Direct visual detection of leishmania parasite through microscopy is the frequent method for diagnosis of this disease. However, this method is time-consuming and subject to errors. This study was aimed to develop an artificial intelligence-based algorithm for automatic diagnosis of leishmaniasis. Methods We used the Viola-Jones algorithm to develop a leishmania parasite detection system. The algorithm includes three procedures: feature extraction, integral image creation, and classification. Haar-like features are used as features. An integral image was used to represent an abstract of the image that significantly speeds up the algorithm. The adaBoost technique was used to select the discriminate features and to train the classifier. Results A 65% recall and 50% precision was concluded in the detection of macrophages infected with the leishmania parasite. Also, these numbers were 52% and 71%, respectively, related to amastigotes outside of macrophages. Conclusion The developed system is accurate, fast, easy to use, and cost-effective. Therefore, artificial intelligence might be used as an alternative for the current leishmanial diagnosis methods.

Histone Deacetylase (HDAC) Inhibitors for the Treatment of Schistosomiasis

Schistosomiasis is a major neglected parasitic disease that affects more than 240 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. Schistosomes display morphologically distinct stages during their life cycle and the transformations between stages are controlled by epigenetic mechanisms. The targeting of epigenetic actors might therefore represent the parasites’ Achilles’ heel. Specifically, histone deacetylases have been recently characterized as drug targets for the treatment of schistosomiasis. This review focuses on the recent development of inhibitors for schistosome histone deacetylases. In particular, advances in the development of inhibitors of Schistosoma mansoni histone deacetylase 8 have indicated that targeting this enzyme is a promising approach for the treatment of this infection.

Assessment of the Therapeutic Efficacy of Silver Nanoparticles against Secondary Cystic Echinococcosis in BALB/c Mice

Background: Cystic echinococcosis (CE) is a highly prevalent parasitic disease resulting from the hydatid cyst of Echinococcus granulosus. It is also described as a zoonotic disease and considered a neglected tropical infection. Aim: This study assessed the antiparasitic activity of silver nanoparticles (AgNPs), against E. granulosus infection in BALB/c mice. Methods: The green synthesis of AgNPs was accomplished using Zizyphus spina-christi leaves. AgNPs were orally administered to BALB/c mice for acute short-term toxicity evaluation, in doses of 50 mg, 100 mg, 200 mg, and 300 mg/kg, and observations for toxic signs were carried out at 24, 48 h, and 14 days, continuously. Moreover, a total of 20 mice divided into two groups were intraperitoneally administered with 1500 viable protoscoleces for secondary hydatidosis infection. Results: The results showed that AgNPs did not induce any adverse effects or signs and no death, in either group of mice. The histopathological findings in the liver, kidneys, and intestine of the mice administered with AgNPs revealed mild histological effects compared with the control ones. The treated-infected mice showed a change in the appearance of the liver hydatid cysts from hyaline to milky cloudy compared with the untreated infected mice. Conclusion: Biosynthesized AgNPs showed anti-hydatic effects and are suggested as anti-echinococcal cyst treatment.

Pelvic Hydatid Cyst with Hydroureteronephrosis: A Rare Case Report

Hydatid cyst is a parasitic disease caused by Echinococcus granulosus or Echinococcus multilocularis. Humans are accidentally infected with the parasite. The cyst is usually found in the liver and lungs and rarely occurs in other body parts. The present article describes a rare case of pelvic hydatid cyst in a young man who presented with nausea, vomiting, and right abdominal pain. Two large cystic masses were discovered during a CT scan in the patient’s pelvic region, resulting in right urinary tract hydroureteronephrosis. Additionally, the antibody index was used to confirm the presence of a primary hydatid cyst.

Effect of domestic freezing on the viability of Toxoplasma gondii in raw and dry-cured ham from experimentally infected pigs

Toxoplasma gondii is the causative agent of the parasitic disease toxoplasmosis, which is an important food borne zoonosis. Eating undercooked meat of infected animals has been considered the major transmission route of T. gondii to humans. The present study evaluates the efficacy of domestic freezing on the inactivation of T. gondii bradyzoites in raw and dry-cured ham. Meat (raw and dry-cured ham) of a pig experimentally orally inoculated with 4,000 oocysts of T. gondii VEG strain was subjected to domestic freezing of -20 ºC at different days. The effect was evaluated by bioassay in mice followed by qPCR. In raw ham and dry-cured ham, temperature of -20 ºC for 7 and 14 days respectively did not inactivate T. gondii . More studies are needed to find the right temperature and time needed to render the bradyzoites non-infectious for human. Meanwhile, the recommendations of freezing to inactivate T. gondii in raw or dry-cured meats must be revisited considered that it does not reduce the risk of infection.

microRNAs: Are they Important in the Development of Resistance in Leishmaniasis?

Leishmaniasis is an infectious and parasitic disease of great importance in public health. Numerous studies indicate that biochemical and molecular mechanisms are factors that contribute to the emergence of antileishmanial drug resistance. Currently, miRNAs have been identified as targets for the invasion of pathogens to control the immune response and imply resistance to treatments. Considering the alarming growth in drug resistance, new possibilities for controlling leishmaniasis have been emerging. Natural compounds originating from medicinal plants are being increasingly explored as promising antileishmanial alternatives. The chapter aims to provide a brief review on mechanisms of action associated with traditional agents used to treat leishmaniasis, focusing mainly on molecular bases associated with the resistance of Leishmania spp. to current drugs and identifying the possible miRNAs involved in this process. In addition, we seek to describe some of the promising plant molecules that can be used as potential antileishmanial agents and their possible mechanisms of action.

Potential molecular targets of Leishmania pathways in developing novel antileishmanials

The illness known as leishmaniasis has not become a household name like malaria, although it stands as the second-largest parasitic disease, surpassed only by malaria. As no licensed vaccine is available, treatment for leishmaniasis mostly relies on chemotherapy. Inefficiency and drug resistance are the major impediments in current therapeutics. In this scenario, identification of novel molecular drug candidates is indispensable to develop robust antileishmanials. The exploration of structure-based drugs to target enzymes/molecules of Leishmania which differ structurally/functionally from their equivalents in mammalian hosts not only helps in developing a new class of antileishmanials, but also paves the way to understand Leishmania biology. This review provides a comprehensive overview on possible drug candidates relating to various Leishmania molecular pathways.

A Rare Case of Cysticercosis Involving the Whole Spinal Canal

Background Cysticercosis is the commonest parasitic disease to affect the central nervous system (CNS). However, cysticercosis affecting the spine is extremely rare. We reported a rare case of cysticercosis involving the whole spinal canal in China. Case Presentation A rare case of cysticercosis involving the entire spinal cord, in a 52-year-old Chinese man, was detected in 2021. Epidemiological investigation, clinical and etiological examination was performed. Conclusion Since spinal cysticercosis is a rare but potentially life-threatening disease, clinicians should always consider the differential diagnosis of space-occupying lesions.