Effects of the antimalarial drugs ferroquine and artesunate on Plasmodium yoelii yoelii gametocytegenesis and vectorial transmission.

Chemistry still has a role in the management of malaria, alongside the mosquito netting soaked in insecticide that is used increasingly, as we continue to await the long anticipated vaccine. During its cycle, the hematozoon parasite develops through three major periods. The first, malarial infection, corresponds to the intrahepatic development of infective forms from the mosquito vector; this period is not sensitive to treatment and is often asymptomatic. The period of erythrocytic schizogony is the most urgent, and treatment activity is primordial. Finally, the phase of sexual reproduction, when gametocytes develop within the erythrocytes ensures the perpetuation of the species when these reach the blood-feeding female anopheles mosquitoes. The aim of our work was to study the effect on gametocytes of drugs known to be effective on the asexual blood forms of the protozoan and thus the potential repercussions on malaria transmission. This experimental study was conducted with an animal model whose parasite cycle and modes of transmission are close to those of human malaria: Plasmodium yoelii, maintained on Swiss mice, with the Anopheles stephensi vector (maintained in an animal facility at the National Museum of Natural History in Paris). Two drugs were tested: ferroquine (a chloroquine derivative with a ferrocene molecule at the lateral carbon chain that restores its efficacy against chloroquine-resistant strains) and artesunate (a derivative of artemisinin, from ginghao, a Chinese plant also known as artemisia annua, or sweet wormwood), a treatment of choice in the combined therapies recommended by WHO. The efficacy of these drugs, prescribed at doses subcurative for the asexual forms, were tested against gametocyte production, quantitatively by counting them in the blood and qualitatively by counting the quantity of oocysts developed on the mosquito's midgut, which are indicators of gametocyte activity. The mice that were parasite-infected and then treated served as their own controls: lots of 30 mosquitoes fed on each mouse before treatment and then 90  minutes and 5  hours after treatment. Quantitatively, the comparison of the blood parasite level and the gametocyte index shows that treated mice had a higher level of circulating gametocytes than untreated parasite infested mice, regardless of drug or dose (5 or 10  mg/kg). For artesunate at 5  mg/kg, we noted that the blood gametocyte level was almost double that of the controls. On the other hand, qualitatively, the first results obtained with optical and electronic microscopy showed morphologic alterations of the circulating gametocytes (pigment clumping and lateralisation within red blood cells) and reduced infectivity of the gametocytes for the mosquitoes that fed at 1 and 5  hours after treatment. We were able to demonstrate statistically that the infectivity of gametocytes, measured by the quantity of oocysts counted in the mosquito midgut, was reduced by 70% for those treated with ferroquine and by 85% for those from mice treated by artesunate. Complementary studies will seek to specify the populations (age) of gametocytes damaged by treatment and the importance and nature of their morphologic alterations.

Molecular characterization of a new Tetratrichomonas species in a patient with empyema.

A new Tetratrichomonas species was identified by molecular and phylogenetic approaches in the pleural fluid from a patient with encysted empyema leading to dyspnea. This observation raised the questions of the real prevalence of pulmonary trichomonosis in humans, the zoonotic potential of trichomonads, and the existence of human-host-adapted strains.

[Emergence in humans of fascioliasis (from Fasciola gigantica) and intestinal distomatosis (from Fasciolopsis buski) in Laos]. / Emergence chez l'homme de fasciolose à Fasciola gigantica et de distomatose intestinale à Fasciolopsis buski au Laos.

Distomatoses due to Fasciola spp. and Fasciolopsis buski are very common in the developing countries of Southeast Asia. The flukes in Laos have not yet been completely studied and described, however. In 2004, we began screening for these two distomatoses in the province of Savannakhet, in southern Laos. Our initial results showed that the causal agent of fascioliasis in humans and animals is Fasciola gigantica. The infestation rate of fascioliasis in cattle in slaughterhouses ranged from 17 to 57%, with higher percentages in buffalo (75-100%) than in cows (0-25%). In Laotian villages, the prevalence of human fascioliasis reached 2.4 % after a stool examination and 13.8 % after systematic serology testing. The prevalence of intestinal distomatosis from F. buski was 33.7%. The rate of villagers with hepatobiliary and intestinal events exceeded 2% but the involvement of these two forms of distomatosis varied highly, ranging from 1.7% (stool diagnosis) to 16.4% (serodiagnosis) for F. gigantica and 11.2% for F. buski. We have described the first cases of fascioliasis and intestinal distomatosis from F. buski in Laos.

[Bilharziasis or schistosomiasis]. / Bilharzioses ou schistosomoses.

Schistosomiasis has been known and described since Antiquity. However, the pathogens were not clearly identified until the 19th century for Schistosoma haematobium, the 20th century for S. mansoni, S. japonicum, then S. intercalatum and S. mekongi. The lastest identified species is a hybrid between S. haematobium and S. intercalatum (Gabon, Cameroon). Given the frequent population exchanges with Southeastern Asia, schistosomiases caused by S. japonicum and S. mekongi are given more and more importance. Major migrations, dam and irrigation schemes and the various control programs modify the prevalence of the different types of schistosoma. In the foci where different species coexist, phenomena of competition and hybridization have been reported. For certain species, the definitive animal hosts have not all been identified, which constitutes an additional obstacle in disease control. The evocative clinical signs are not observed until the acme. Before this stage, the clinical diagnosis is difficult to establish and the signs are misleading. In the invasive phase, the laboratory diagnosis is made based on serology, showing hypereosinophilia, while at acme, the diagnosis is confirmed by the finding of eggs with a spine. Currently, only praziquantel is used in clinical practice, both for individual treatments and mass treatment campaigns, despite the development of a resistance to this molecule in well-defined foci. Other therapeutic protocols based on artemether are being used. Control programs aiming at decreasing the incidence of schistosomiasis are hampered by the implementation of irrigation schemes favorable to the development of mollusks and to disease transmission.

[Cysticercosis contracted in metropolitan France]. / Cysticercose contractée en France métropolitaine.

INTRODUCTION: All cases of cysticercosis diagnosed in France are thought to be imported. Our case report concerns a 48-year-old man who has never left Europe, in whom we diagnosed subcutaneous cysticercosis. CASE: Histologic examination of the subcutaneous nodule extracted from this patient's abdominal wall showed cysticercosis. He has never left Europe. Various imaging techniques showed no other localizations of this infection. Neither he nor any members of his family carried adult Taenia solium. DISCUSSION: We present an exceptional case of autochthonous cysticercosis. It is unlikely to be a larva of Taenia solium, since this adult tapeworm has not been seen in mainland France for a very long time. On the other hand, Taenia crassiceps cestodes parasitize the digestive tract of the fox in Auvergne and may occasionally cause cysticercosis in humans.

Two cases of opportunistic parasite infections in patients receiving alemtuzumab.

Two cases are reported of rare digestive opportunistic parasites in patients being treated with alemtuzumab for lymphoid haematological malignancies. In both patients, classical biological examinations were insufficient to reach the diagnosis. Only specific parasitological techniques enabled diagnoses of cryptosporidiosis and microsporidiosis, respectively. In both cases, cellular immune reconstitution was sufficient to eradicate these opportunistic infections. In this context, parasitological diagnosis is often underestimated by medical practitioners, so immunologists and oncohaematologists need to be aware of this kind of opportunistic pathogen.

Genotype of 88 Toxoplasma gondii isolates associated with toxoplasmosis in immunocompromised patients and correlation with clinical findings.

We report the genotyping analysis of Toxoplasma gondii isolates in samples collected from 88 immunocompromised patients, along with clinical and epidemiological data. Most of these samples were collected in France during the current decade by the Toxoplasma Biological Resource Center. Lack of specific anti-Toxoplasma treatment, pulmonary toxoplasmosis, and involvement of multiple organs were the 3 main risk factors associated with death for this patient group. Genotyping results with 6 microsatellite markers showed that type II isolates were predominant among patients who acquired toxoplasmic infection in Europe. Non-type II isolates included 13 different genotypes and were mainly collected from patients who acquired toxoplasmosis outside Europe. Type III was the second most common genotype recovered from patients, whereas type I was rare in our population. Three nonarchetypal genotypes were repeatedly recovered from different patients who acquired the infection in sub-Saharan Africa (genotypes Africa 1 and Africa 2) and in the French West Indies (genotype Caribbean 1). The distribution of genotypes (type II vs. non-type II) was not significantly different when patients were stratified by underlying cause of immunosuppression, site of infection, or outcome. We conclude that in immunocompromised patients, host factors are much more involved than parasite factors in patients' resistance or susceptibility to toxoplasmosis.