Biomedical subjects
Publications and source records attributed to I Landau.
The schizogonic rhythm of rodent malarias in the blood of mice varies from one species or subspecies to the other. Synchronous strains enable a precise study of the sensitive stage of the parasite to antimalarial drugs. Asynchronous strains are less sensitive than synchronous strains because of the delayed penetration of merozoites into red blood cells.
Protection against pre-erythrocytic stages of malaria is possible, as demonstrated by the resistance obtained by immunizing with irradiated sporozoites. However, the involved mechanisms are more numerous and intricate than previously believed. Recently, the hepatic stage, rather than the sporozoite stage, has been seen as the target of immune attack.
Antimalarial activity of arteether, a derivative of artemisinin (qinghaosu) against blood-induced infections of the highly synchronous Plasmodium vinckei petteri rodent species of malaria was evaluated in Swiss mice. A single subcurative dose of arteether of 2.2 mg/kg body weight was injected subcutaneously to mice, either during the prepatent period or during the patent infection, when different stages of the parasitic cycle were present in the blood. It was shown that rings and young trophozoites were the most susceptible stages to arteether. The drug had no effect on merozoites and little effect on mid-term trophozoites which is the stage most sensitive to chloroquine. The alcoholic solution (10% alcohol in sterile water) had an immediate effect while the oily solution (miglyol 840) was active between 3 and 21 hr after injection.
We report on a 19-year-old male patient who was operated on for an orbital tumor close to the trochlea. The microscopical examination showed a cartilaginous tumor classified as differentiation grade II. Because of the close topographic location to the trochlea the tumor is characterized as a chondroma. Its rare location does not give us any further information concerning the final dignity. Benign cartilaginous tumors of the orbital trochlea region are extremely uncommon.
Normal, splenectomized, and athymic Fischer rats were infected with Plasmodium chabaudi. In normal rat infections, acute-phase infection resolved rapidly and completely. In splenectomized rats, infection resulted in high parasitemia and ultimately death. In nude rats, parasite growth was reduced compared with normal rats, and a persistent parasitemia (between 20 and 45%) was observed for several months. Complete resolution of the infection was achieved after adoptive transfer of T lymphocytes, even when transfer occurred during the course of infection. These results indicated that an acquired, T-lymphocyte-dependent immunity was necessary for the complete recovery observed in normal rats. In normal rats, thrombocytopenia and splenomegaly occurred during infection. By contrast, in nude rats, both of these pathological manifestations were only observed after thymus grafting. Thrombocytopenia was also absent in the splenectomized animals. Despite an increase in platelet-associated immunoglobulin levels during the infection, thrombocytopenia was not transferred by injection of infected rat serum to normal recipients. It has been concluded that the nude rat infection can be regarded as a novel and useful model for studying the T-cell-dependent effector and pathological mechanisms and to investigate the anti-P. chabaudi immune response.
Chronotherapy is the science of the timing of drug application so as to achieve optimal therapeutic success for the treatment of disease. Here, Irene Landau, Alain Chabaud, Gilles Cambie and Hagai Ginsburg show how a suitable animal model can be chosen, how the stage of parasite development most susceptible to the drug can be identified, and how this can eventually be used for the improvement of drug treatment.
The cyclic nature of malarial fever in conjunction with the pharmacokinetic characteristics of antimalarial drugs, call for the conception of a chrono-therapeutic approach for the treatment of the disease. An experimental murine malarial model was devised using the highly synchronous species Plasmodium vinckei petteri to test this rationale. Sub-curative doses of chloroquine were injected sub-cutaneously to mice either during the prepatent period or during patent infection. Inspection of the effect of drug applied at different stages of the parasitic cycle, revealed that medium size trophozoites (MT) were the most susceptible stage to chloroquine, while ring and young trophozoite stages were refractory to the drug. Chloroquine given during these latter stages, affected the parasites when they developed into the MT stage. Drug treatment during the MT stage phase-shifted the schizogonic cycle by 18 hours. Hence, treatment with two consecutive injections given 18 hours apart, i.e. timed to the overwhelming presence of the MT stage in the circulation, gave the best therapeutic results.
In one case of human malaria imported from Gabon, abnormal forms of Plasmodium vivax are described; severe multiple infections of the host erythrocytes are noticed (up to 6 amoeboid trophozoites in a single red blood cell). Attention is drawn to the numerous morphologically abnormal intra-erythrocytic stages of P. vivax: severe multiple infections of red cells, parasites "ressembling" P. ovale, mature schizonts of small size, with reduced number of merozoites... The geographical distribution of P. vivax in Central Africa is discussed, with reflections on the factors allowing the importation of few P. vivax cases from this area.
The substitution of two deuterium atoms on the alpha-carbon of the primaquine side chain was found to produce a sevenfold decrease in the rate of conversion of primaquine to carboxyprimaquine by enzymatic oxidative deamination, but the deuterium substitution was found to have no significant effect on the in vitro antimalarial activity or on in vitro hepatocyte toxicity. Placing a single methyl group on the alpha-carbon was found to produce only a slight decrease in the rate of oxidative deamination. Although metabolic attack occurred adjacent to either the aniline nitrogen or the aliphatic amine, metabolic attack occurred primarily adjacent to the more basic nitrogen at the 1'-position, even when this position bore a methyl substituent. Primaquine, the alpha-dideutero analogue, and the alpha-methyl analogue were all found to have about the same in vitro antimalarial activity as determined in the liver hepatocyte assay.
Three patients are described showing corneal changes of unknown origin previously not described. The changes consist of discrete opacities mostly located in the epithelium of the cornea. The opacities are arranged in a continuous are originating from the limbus with the vertex extending towards the optic zone. The cornea inside and outside the arc was normal during the early stages of the disease. In two of the cases a progress of the changes were recorded and a stromal opacity developed inside the arc. The three cases were all unilateral. Bacterial and fungal cultures, virus isolation, several blood tests, serology and immunological tests have been negative. Light- and electron microscopy of biopsied material show intracellular specific epithelial cell changes in the form of perinuclear vacuoles. None of the treatments tried were successful.
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Freeze-thawing of blood infected with malaria parasites is a technique which brings about the destruction of all stages except the merozoites and makes possible investigations on the behaviour of these merozoites and the schizogonic rhythm of each species. Merozoites of Plasmodium y. yoelii remain in the blood during the 24 hrs. following inoculation; it is concluded that their penetration in the erythrocytes occurs gradually during this time. Synchronism is poor. Merozoites of P. vinckei petteri penetrate rapidly inside the erythrocytes independently of the time of inoculation. Infection is therefore synchronous and does not follow the circadian rhythm of the host. Penetration of merozoites of P. c. chabaudi is predominant at midnight when rodents are maintained with a normal circadian rhythm (light from 8 am to 8 pm) and predominant at noon when the rhythm of the host is inverted (light from 8 pm to 8 am). Infection is therefore synchronous and follows the host rhythm. The three species of plasmodia coexisting in Thamnomys rutilans from CAR show the same periodicity of 24 hrs. but, because of differences in the biology of the merozoites, they occupy three distinct niches. These notions have great practical implications in chronotherapy, as many data lead to the idea that merozoites are drug resistant.
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The splenectomy of a female Lemur macaco macaco, showing a scanty blood infection by Haemosporidians and a Trypanosome was followed by a dramatic increase of the rate of intra-erythrocytic parasitaemia. Three species of Plasmodium where then identified. The first species was unknown; it is described in this paper and named Plasmodium coulangesi n. sp. It is characterised by--the low (6). constant number of merozoites in mature schizonts,--the disposition of the pigment, well apart from the parasitic mass to which it is linked by a tiny wisp of cytoplasm,--the normal host erythrocyte, the shape, size and colour of which are unaltered. The second species was provisionaly designated as Plasmodium sp.; it was previously seen in the same host by Garnham and Uilenberg in 1975 and designated by these authors as Plasmodium girardi Buck, Coudurier et Quesnel, 1952. Only gametocytes of the last species were found; they are similar to those of Plasmodium lemuris Huff and Hoogstraal, 1963.
Lemur macaco macaco from Ambanja region was found polyparasitized by four different species of Plasmodium: --Plasmodium coulangesi recently described by lepers et al. (1989). --P. bucki n. sp.: its main differential characterisitics are the large numvber (32) of merozoites produced in mature schizonts and the stippling, resembling Maurer's dots, in an hypertrophied pinkish erythrocyte. --P. percygarnhami n. sp. (= P. girardi sensu Uilenberg, 1970 pro parte and sensu Garnham et Uilenberg, 1975 pro parte) producing 20 merozoites in mature schizonts and developing inside a deformed corpuscle (holly leaf-shaped or sometimes sea-urchin-shaped) which may also become decolourized when parasitized by older stages. --(?) Plasmodium lemuris: gametocytes are very large (11 microns x 7 micron); the parasitized erythrocyte is much hypertrophied (+/- 10 microns), distored and of a pinkish colour; one schizont only, possibly exo-erythrocytic, was found. The authors hypothesized this parasite to be a Haemoproteid. The analysis of published data led the authors to make the following modifications to the nomenclature previously established: --Plasmodium girardi Buck et al., 1952, sensu Garnham, 1966, sensu Uilenberg, 1970 parte and sensu Garnham and Uilenberg, 1975 pro parte, is refered to as Plasmodium sp., for stages developing in the blood of Lemur fulvus fulvus. The taxon P. percygarnhami is to be employed for stages developing in L. m. macaco and P. girardi Buck et al., 1952 for those developing in Lemur fulvus rufus. --Plasmodium foleyi Buck et al., 1952, sensu Garnham and Uilenberg, 1975 in L. f. fulvus is named Plasmodium uilenbergi n. sp., P. folleyi being a parasite of L.f. rufus. Excluding P. lemuris which probably does not belong to the genus Plasmodium, the morphological analysis led to individualize 7 species, in the three species of Lemurs studied. A phenomenon of "vicariance" thus appears, similar to what is known for the african Rodent Plasmodia, but with a more pronounced speciation. The vicariant species form a pair constituted of: --on the one hand a small species developing in a red blood cell of normal size, P. girardi in L.f. rufus, P. sp. in L.f. fulvus, P. percygarnhami, with also, P. coulangesi, in L. m. macaco; --on the other hand a large species determining an hypertrophy of the erythrocyte, P. foleyi in L.f. rufus, P. uilenbergi in L.f. fulvus and P. bucki in L.m. macaco.
Mice were fed a cholesterol-rich diet and then subsequently infected with chloroquine-sensitive strains of either Plasmodium berghei or P. chabaudi. Chloroquine therapy, which was started 24 hours post-infection and continued for 3-4 days, was significantly less effective in cholesterol-fed animals compared to controls. The consequences of these findings to the resistance of P. falciparum in man to chloroquine, are discussed.
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.
Twenty two birds belonging to the species Estrilda melpoda and E. astrild were studied. Nine birds were found infected by Trypanosomes. They belong to four different species: one is identified as Trypanosoma everetti, the other three are new species (T. chabaudi, T. davidmolyneuxi and T. gentilinii). Several mixed infections were found. Each species appears to be monomorphic in the circulating blood; it is suggested that the polymorphism of several Trypanosomes described in the literature is due to polyparasitic infections rather than to a true polymorphism.