Latent activity of curcumin against leishmaniasis in vitro

In this study the anti-proliferative effect of curcumin (curcuma longa) that is the active ingredient of ground dried rhizome has been studied against three local and three reference leishmanial strains, Leishmania major, Leishmania tropica and Leishmania infantum (Pakistani isolate). Curcumin has shown an average IC50 of 5.3mM against promastigotes of various leishmanial strains which is much lower as compared with pentamidine that is one of the basic treatments against leishmaniasis. The main draw back attributed to these assays performed on promastigotes is the heterogeneity of results compared with those obtained with intracellular amastigotes or with in vivo effect. We also tested activity of curcumin against axenic amastigote like cells (AALC) of L. major strain (MHOM/PK/88/DESTO). Curcumin proves to be far more potent then pentamidine against AALC which further strengthens the fact about its leishmaniacidal activity

Identification of Small Molecule Lead Compounds for Visceral Leishmaniasis Using a Novel Ex Vivo Splenic Explant Model System

Visceral leishmaniasis is a life threatening parasitic disease present in several countries of the world. New drugs are needed to treat this disease because treatments are becoming increasingly ineffective. We established a novel system to screen for new anti-leishmanial compounds that utilizes spleen cells from hamsters infected with the parasite Leishmania donovani. The parasite strain we used was genetically engineered to emit light by the incorporation of the firefly luciferase gen. This laboratory test system has the advantage of reproducing the cellular environment where the drug has to combat the infection. The efficacy of the compounds is easily determined by measuring the light emitted by the surviving parasites in a luminometer after exposing the infected cells to the test compounds. The screening of more than 4,000 molecules showed that 84 (2.1%) of them showed anti-leishmanial activity and had an acceptable toxicity evaluation. Eighty two percent of these molecules, which had varied chemical structures, were previously unknown to have anti-leishmanial activity. Further studies in animals of these new chemical entities may identify drug candidates for the treatment of visceral leishmaniasis

In Vitro and In Vivo Efficacy of Ether Lipid Edelfosine against Leishmania spp. and SbV-Resistant Parasites

Leishmaniasis represents a major international health problem, has a high morbidity and mortality rate, and is classified as an emerging and uncontrolled disease by the World Health Organization. The migration of population from endemic to nonendemic areas, and tourist activities in endemic regions are spreading the disease to new areas. Unfortunately, treatment of leishmaniasis is far from satisfactory, with only a few drugs available that show significant side-effects. Here, we show in vitro and in vivo evidence for the antileishmanial activity of the ether phospholipid edelfosine, being effective against a wide number of Leishmania spp. causing cutaneous, mucocutaneous and visceral leishmaniasis. Our experimental mouse and hamster models demonstrated not only a significant antileishmanial activity of edelfosine oral administration against different wild-type Leishmania spp., but also against parasites resistant to pentavalent antimonials, which constitute the first line of treatment worldwide. In addition, edelfosine exerted a higher antileishmanial activity and a lower proneness to generate drug resistance than miltefosine, the first drug against leishmaniasis that can be administered orally. These data, together with our previous findings, showing an anti-inflammatory action and a very low toxicity profile, suggest that edelfosine is a promising orally administered drug for leishmaniasis, thus warranting clinical evaluation

Transfusion-Acquired <i>Plasmodium malariae</i> Infection in Two Premature Infants

Several diseases can be transmitted to infants via transfusion. The risk of acquiring an infection via transfusion is greatly increased in sick premature infants because they receive frequent transfusions. The full-term infant is not fully competent immunologically,15 and the premature infant is even less able to deal with infection.6,15 Ideally, the transfusion of infected blood, especially into immunoincompetent recipients, should not occur. However, because screening for malaria in nonendemic regions is not practical, physicians caring for sick premature babies should consider transfusion-acquired malaria as a possible cause of illness, especially when there is no response to antibacterial therapy.</jats:p

Encephalopathy associated with enteroinvasive Escherichia coli 0144:NM infection

Central nervous system manifestations typically occur with Shigella gastroenteritis and also in enteric Salmonella and Campylobacter infections. To date no association between enteroinvasive Escherichia coli infection and neurologic symptoms has been described. Two children with diarrhea caused by E. coli 0144:NM had otherwise unexplained encephalopathy manifested by profound stupor in one child and by obtundation and meningismus in the other one. These cases of infection occurred in northern Israel during a period of an unusually high rate of enteric infection caused by this organism. None of the microbiologic properties studied were uniquely attributable to the encephalopathic cases. The two encephalopathic as well as all eight nonencephalopathic isolates studied possessed the 140-MDa invasive plasmid. All 10 isolates examined produced small amounts of cytotoxin by the HeLa cell assay, all were nonmotile, and all had identical antibiograms. Eight of 10 of the isolates had identical plasmid profiles, while 2 isolates (from nonencephalopathic patients) had slightly different plasmid profiles. This is the first report of encephalopathy associated with enteroinvasive E. coli.</jats:p