A brief history of malaria.

For millions of years, invertebrates and malaria parasites have coexisted and to date, malaria remains the most important human parasitic disease. This co-evolution had profound impacts on the movements of early hominids and on the genome of modern humans. Over the past two centuries, progress has been made with the discovery of the parasite, its transmission, and medicines, paving the way to the control of the disease and its elimination in some countries. However, the Plasmodium parasite is a formidable foe capable of developing resistance to drugs, and the mosquito vector has adapted to insecticides, foiling all attempts to eradicate the disease. Over recent years the economic and social costs of malaria have been recognized and more funds have been mobilized than ever before, however further efforts are needed. National programs, international institutions and researchers will need to do better if the preventable deaths of hundreds of thousands of mostly African children are to be averted.

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.

[Epidemiology of parasitic diseases, hypereosinophilia, IgE from tropical and European parasitological origins]. / Epidémiologie des parasitoses, hyperéosinophilies sanguines et IgE d'origines parasitaires en milieux tempérés et tropicaux.

Etiologic investigations of hypereosinophilia, often accompanied by IgE elevation, depends on the patient's geographic origin and travel history. In France, helminth diseases are the only parasitoses associated with hypereosinophilia. Some, such as oxyurosis in children, are frequent but generally mild. More severe but less frequent infections include distomatoses, trichinellosis, taeniasis, echinococcosis and visceral larva migrans. Among subjects originating from or having travelled to tropical areas with poor hygiene, eosinophilia may be due to early intense polyparasitism and has little etiologic value. In Gabon, a warm, humid country in equatorial Africa, schoolchildren harbor an average of three different parasites capable of inducing hypereosinophilia or serum IgE elevation. These children's eosinophil counts start to rise at very young age, after weaning and contact with soil, and continue to increase rapidly until adulthood. Average values across all age groups are 1580 eosinophils/mm3 and 3300 kU IgE/L. Direct diagnosis of chronic parasitic infections is often possible in this setting, and specific treatments can be prescribed. In contrast, hypereosinophilia has less etiologic significance in patients originating from or having travelled to the tropics and who present to European parasitology units. Direct examination is rarely positive, and the etiologic diagnosis will thus be guided by epidemiologic, clinical and serologic findings. These findings are sometimes sufficient to initiate probabilistic treatment with albendazole, ivermectin and praziquentel.

Immunoblot analysis of membrane antigens of Schistosoma mansoni, Schistosoma intercalatum, and Schistosoma haematobium against Schistosoma-infected patient sera.

Antigens present in aqueous n-butanolic extracts (BE) of Schistosoma mansoni (Venezuelan JL strain), Schistosoma intercalatum (Cameroon EDEA strain), and Schistosoma haematobium (Yemen strain) adult worm membranes were compared in immunoblot against sera of patients infected with S. mansoni, S. intercalatum, S. haematobium, Schistosoma japonicum, or Schistosoma mekongi looking for similarities (common antigens) and differences (species-specific antigens). About 17 S. mansoni BE polypeptides (M (r) approximately 8 to >80 kDa) were commonly recognized by S. mansoni-infected patient sera from Venezuela, Senegal, and Ethiopia. S. intercalatum-, S. haematobium-, or S. japonicum-infected sera were almost unreactive with S. mansoni BE. Nonetheless, S. mekongi-infected sera weakly cross-reacted with a approximately 10-15-kDa subset of S. mansoni BE. About 72.7% of S. intercalatum-infected patient sera reacted with a approximately 19-21-kDa complex in S. intercalatum BE and cross-reacted with a similar complex in S. haematobium BE. Conversely, all S. haematobium-infected patient sera reacted with a approximately 19-21-kDa complex in S. haematobium BE and cross-reacted with the approximately 19-21-kDa complex in S. intercalatum BE; S. mansoni- and S. japonicum-infected patient sera did not react with S. intercalatum or S. haematobium BE. Results showed the presence of a common membrane antigen between African schistosome species and species-specific antigens in S. mansoni BE that could be useful to discriminate between species and/or to detect Schistosoma infections.

[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.

Ivermectin and filariasis.

Ivermectin, a parasiticide that long ago proved its worth in veterinary medicine, became one of the most effective tools for control programs against human filarial diseases in the 1980s. It is provided at no cost, is effective against microfilariae (blocking their transmission) and can be administered annually as a single oral dose with virtually no side-effects: these considerations led the WHO to officially declare eradicable two endemic filarial diseases (among the major endemic diseases worldwide), onchocerciasis and lymphatic filariasis.