ABSTRACT
Methylene blue (MB) is the oldest synthetic antimalarial. It is not used anymore as antimalarial but should be reconsidered. For this purpose we have measured its impact on both chloroquine sensitive and resistant Plasmodium strains. We showed that around 5 nM of MB were able to inhibit 50% of the parasite growth in vitro and that late rings and early trophozoites were the most sensitive stages; while early rings, late trophozoites and schizonts were less sensitive. Drug interaction study following fractional inhibitory concentrations (FIC) method showed antagonism with amodiaquine, atovaquone, doxycycline, pyrimethamine; additivity with artemether, chloroquine, mefloquine, primaquine and synergy with quinine. These results confirmed the interest of MB that could be integrated in a new low cost antimalarial combination therapy.
Subject(s)
Antimalarials/pharmacology , Malaria, Falciparum/drug therapy , Methylene Blue/pharmacology , Plasmodium falciparum/drug effects , Animals , Antimalarials/therapeutic use , Dose-Response Relationship, Drug , Drug Interactions , Drug Resistance , Drug Therapy, Combination , Humans , Inhibitory Concentration 50 , Methylene Blue/therapeutic use , Parasitic Sensitivity Tests , Treatment OutcomeABSTRACT
In French Guiana, Quassia amara L. (Simaroubaceae) leaf tea is a well-known widely used traditional antimalarial remedy. Impact of the vegetal sampling condition on in vivo and in vitro antimalarial activity was assessed. Traditional infusions were prepared with juvenile or mature leaves, both either fresh or dried. Results showed that growing stage and freshness of vegetal material exert a striking effect on antimalarial activity, both in vitro and in vivo. By far, leaf tea made from fresh juvenile (FJ) Quassia amara leaves was the most active. In vitro, active component (simalikalactone D) concentration correlates biological activities, although unexplained subtle variations were observed. In vivo, tea made with dried juvenile (DJ) leaves displays a peculiar behavior, meaning that some components may help simalikalactone D delivery or may be active in vivo only, therefore enhancing the expected curative effect of the traditional preparation.
Subject(s)
Antimalarials/pharmacology , Beverages , Desiccation , Malaria/drug therapy , Plasmodium falciparum/drug effects , Plasmodium yoelii , Quassia/growth & development , Animals , Antimalarials/chemistry , Antimalarials/standards , Antimalarials/therapeutic use , Chromatography, High Pressure Liquid , French Guiana , Malaria/parasitology , Mice , Parasitic Sensitivity Tests , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/growth & development , Quality Control , Quassia/chemistry , Quassins/analysisABSTRACT
In order to evaluate the antimalarial potential of traditional remedies used in French Guiana, 35 remedies were prepared in their traditional form and screened for blood schizonticidal activity in vitro on Plasmodium falciparum chloroquine re4sistant strain (W2). Some of these extracts were screened in vivo against Plasmodium yoelii rodent malaria. Ferriprotoporphyrin inhibition test was also performed. Four remedies, widely used among the population as preventives, were able to inhibit more than 50% of the parasite growth in vivo at around 100 mg/kg: Irlbachia alata (Gentiananceae), Picrolemma pseudocoffea (Simaroubaceae), Quassia amara (Simaroubaceae), Tinospora crispa (Menispermaceae) and Zanthoxylum rhoifolium (Rutaceae). Five remedies displayed an IC50 in vitro < 10 microg/ml: Picrolemma pseudocoffea, Pseudoxandra cuspidata (Annonaceae) and Quassia amara leaves and stem, together with a multi-ingredient recipe. Two remedies were more active than a Cinchona preparation on the ferriprotoporphyrin inhibition test: Picrolemma pseudocoffea and Quassia amara. We also showed that a traditional preventive remedy, made from Geissospermum argenteum bark macerated in rum, was able to impair the intrahepatic cycle of the parasite. For the first time, traditional remedies from French Guiana have been directly tested on malarial pharmacological assays and some have been shown to be active.
Subject(s)
Antimalarials/isolation & purification , Antimalarials/therapeutic use , Drug Evaluation, Preclinical/methods , Administration, Oral , Animals , Antimalarials/classification , Disease Models, Animal , Ethanol , Female , French Guiana/ethnology , Humans , Malaria, Falciparum/drug therapy , Mice , Phytotherapy , Plant Components, Aerial/chemistry , Plant Roots/chemistry , Plants, Medicinal/chemistry , WaterABSTRACT
Plasmodium kentropyxi n.sp. is described in the teiid lizard Kentropyx calcarata from north Brazil. Young asexual stages and gametocytes are at first polar in the erythrocyte but with elongation, move to a lateral position. Largest meronts seen contained from 30-40 nuclei and conspicuous greenish-black pigment granules located in a distinct vacuole. With growth the gametocytes eventually assume a smooth, curved cylindrical shape, with evenly rounded ends. Pigment is scattered or concentrated around a conspicuous vacuole which is slowly developed as the gametocytes mature. Mature male parasites measured 11.8 x 4.0 microns (9.6 x 4.2 - 13.2 x 3.6 microns), shape-index 2.9 (2.2 - 5.0), and females 13.5 x 4.5 microns (12.0 x 4.5 - 15.0 x 4.8 microns), shape-index 3.0 (2.2 - 3.8). Some larger meronts may slightly enlarge the erythrocyte, but most asexual stages and the mature gametocytes rarely do so. A second, P. tropiduri-like parasite encountered in K. calcarata possessed small rounded or fan-shaped meronts producing from 4-14 merozoites, and spherical to subspherical gametocytes of approximately 6.0 x 5.0 microns. The parasite was consistently polar in its position in the erythrocyte.
Subject(s)
Lizards/parasitology , Plasmodium/isolation & purification , Animals , Brazil , Female , Male , Plasmodium/classificationABSTRACT
A study of Plasmodium vinckei peterri sporogony was performed by experimental infection of Anopheles stephensi with gametocytes from infected mice. The study includes the description of the ookinete, complete evolution of oocysts and their final transformation to sporozoites. These were later used for intravenous infection of new mice, in order to study the exoerythrocytic schizogony. The morphology of exoerythrocytic schizonts was similar to that of other species of the same group. The minimal duration of the hepatic cycle was found to be of 61 hours. These data, along with other related to the hematic cycle characteristics, help to complete the information on the species, which can be recommended as a model for the study of human malaria.
Subject(s)
Anopheles/parasitology , Plasmodium/growth & development , Animals , Liver/parasitology , Male , MiceABSTRACT
A two-toed sloth (Choloepus didactylus) from French Guiana showed an erythrocytic parasite morphologically related to the Babesiidae family, and described as Babesia choloepi. It is the first Babesia species described in the Edentata order.