Isoenzyme analysis was conducted on the tachyzoite stage of 35 Toxoplasma gondii isolates. Fifteen enzyme systems were studied after isoelectrofocusing of tachyzoite extracts in polyacrylamide or agarose gels. Six enzyme systems showed variable electrophoretic patterns: aspartate aminotransferase (EC 2.6.1.1), glutathione reductase (EC 1.6.4.2), glucose phosphate isomerase (EC 5.3.1.9), amylase (EC 3.2.1.1), acid phosphatase (EC 3.1.3.2), and propionyl esterase. Their combination allows the description of 5 zymodemes among the 35 T. gondii isolates. Zymodeme 1 involves 6 isolates that are highly pathogenic to mice and for which oocysts could not be obtained. Isolates belonging to zymodemes 2, 3, and 4 are less pathogenic to mice and produced oocysts. Zymodeme 5 involves only 1 isolate, which was highly pathogenic to mice.
Nitric oxide (NO) is an important effector molecule of the immune system in eliminating numerous pathogens. Peritoneal macrophages fromTrypanosoma brucei brucei-infected mice express type II NO synthase (NOS-II), produce NO, and kill parasites in the presence ofl-arginine in vitro. Nevertheless, parasites proliferate in the vicinity of these macrophages in vivo. The present study shows thatl-arginine availability modulates NO production. Trypanosomes use l-arginine for polyamine synthesis, required for DNA and trypanothione synthesis. Moreover, arginase activity is up-regulated in macrophages from infected mice from the first days of infection. Arginase competes with NOS-II for their common substrate, l-arginine. In vitro, arginase inhibitors decreased urea production, increased macrophage nitrite production, and restored trypanosome killing. In vivo, a dramatic decrease inl-arginine concentration was observed in plasma from infected mice. In situ restoration of NO production and trypanosome killing were observed when excess l-arginine, but notd-arginine or l-arginine plusN ω-nitro-l-arginine (a NOS inhibitor), was injected into the peritoneum of infected mice. These data indicate the role of l-arginine depletion, induced by arginase and parasites, in modulating the l-arginine–NO pathway under pathophysiological conditions.
Human African trypanosomiasis (HAT), or sleeping sickness, is currently on the rise. HAT develops in two stages, the first involving the hemolymphatic system, and the second, the neurological system. Left untreated, HAT is invariably fatal. There have been no therapeutic advances in more than 40 years. Stage 1 can be treated with pentamidine and suramin, but stage 2 can only be treated with melarsoprol, a toxic arsenic derivative that has a 2-12% incidence of fatal side-effects (encephalopathy). Eflornithine has never achieved widespread use because it is difficult to administer under field conditions. Nifurtimox has been used successfully in the treatment of American trypanosomiasis, or Chagas disease, but only in small studies or as a compassionate use treatment. There is little research and development for new drugs in this area: only one prodrug is in the clinical development phase, a pentamidine analog that offers hope for the replacement of injectable pentamidine with an orally administered drug. Current efforts appear to be focused on reevaluating older drugs. A course of treatment with melarsoprol for 10 days at 2.2 mg/kg/day is now in the multicenter evaluation phase. Orally administered eflornithine is also slated for reevaluation. In addition, studies of drug combinations are recommended to determine possible combined or synergistic effects and find ways to reduce toxicity.
Major modifi cations of immune system have been observed in African trypanosomiasis. These immune reactions do not lead to protection and are also involved in immunopathology disorders. The major surface component (variable surface glycoprotein,VSG) is associated with escape to immune reactions, cytokine network dysfunctions and autoantibody production. Most of our knowledge result from experimental trypanosomiasis. Innate resistance elements have been characterised. In infected mice, VSG preferentially stimulates a Th 1-cell subset. A response of γ δ and CD8 T cells to trypanosome antigens was observed in trypanotolerant cattle. An increase in CD5 B cells, responsible for most serum IgM and production of autoantibodies has been noted in infected cattle. Macrophages play important roles in trypanosomiasis, in synergy with antibodies (phagocytosis) and by secreting various molecules (radicals, cytokines, prostaglandins,...). Trypanosomes are highly sensitive to TNF-α, reactive oxygen and nitrogen intermediates. TNF-α is also involved in cachexia. IFN-γ acts as a parasite growth factor. These various elements contribute to immunosuppression. Trypanosomes have learnt to use immune mechanisms to its own profi t. Recent data show the importance of alternative macrophage activation, including arginase induction. Lornithine produced by host arginase is essential to parasite growth. All these data reflect the deep insight into the immune system realised by trypanosomes and might suggest interference therapeutic approaches.
Summary: Purpose: Human cysticercosis is a direct consequence of infection by Taenia solium larvae (Cysticercus cellulosae). Results of studies on the impact of neurocysticercosis on epilepsy in Africa are inconsistent. The objective was to evaluate the role of cysticercosis in epilepsy in Burundi. Methods: A prevalent matched case–control design was used in the Kiremba area, Burundi, between March and April 2001. One case with epilepsy was matched to two control subjects, according to their age. Cases were subjects who had shown at least two unprovoked epileptic seizures within a 24‐h time range and who lived in the Kiremba area. The control subjects also lived in Kiremba and had neither neurologic illness nor kinship with the people with epilepsy. Seropositivity for cysticercosis was the exposure variable. Three hundred twenty‐four prevalent cases, with onset of epilepsy between 1950 and 2000, and 648 age‐matched controls were included. Results: This study found a link between cysticercosis infestation and the occurrence of epilepsy (odds ratio, 3.8; 95% confidence interval, 2.5–5.1). Conclusions: The study highlighted the importance of cysticercosis in the area of Kiremba, as 31.5% of the control subjects screened positive for this parasite. The attributable risk for cysticercosis was 50% (95% confidence interval, 42–57) in this population.
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