[Sciatica after return from Mali: case report of schistosomal myelopathy]. / Sciatique au retour du Mali.

INTRODUCTION: In spite of the high prevalence of schistosomiasis in Mali, few cases involving neurological complications have been described. The purpose of this report is to present a case associated medullary complications. CASE REPORT: A 29-year-old man was hospitalized for low back pain and difficulty in walking linked to dysesthesia. Five months earlier the patient had been trreated for schistosomiasis contracted during a trip to Dogon region of Mali. Based on radiological and laboratory findings and previous clinical history, the difinitive diagnosis was schistosomal myelopathy. DISCUSSION/CONCLUSION: Neuroschistosomiasis is a rare but serious complication of the schistosomiasis that can only be made after complete parasite identification and careful differential diagnosis. Treatment with antiparasitic agents in association with corticosteroids is mandatory but must only be initiated in state stage of the parasitic infection, i.e., after maturation of larvae into adults.

Evidence for absence of toxicity of T101 immunotoxin on human hematopoietic progenitor cells prior to bone marrow transplantation.

T101-ricin A-chain immunotoxin is a hybrid molecule made up of the T101 monoclonal antibody bound to the A-chain of ricin. It specifically destroys cells expressing the cell surface T65 antigen. We have designed a preclinical study to evaluate its possible use for the in vitro treatment of T-cell hematological cancers prior to autologous bone marrow transplantation. The data presented here show that conditions previously defined to produce high tumor cell killing, i.e., a 20-hr incubation at 37 degrees in the presence of T101-ricin A-chain immunotoxin up to 10(-7) M in a 10 mM ammonium chloride solution, do not affect the in vitro proliferative capacity of human hematopoietic stem cells studied by means of semisolid medium cultures (granulocyte-macrophage progenitors, burst-forming units-erythrocyte) and continuous liquid cultures (pre-granulocyte-macrophage progenitors). Therefore, autologous bone marrow transplantation with T101-ricin A-chain immunotoxin-treated graft should be feasible.

Hydrocephalus and racemose cysticercosis: surgical alternative by endoscopic third ventriculostomy.

BACKGROUND AND PURPOSE: Hydrocephalus is a frequent and potentially serious complication of neurocysticercosis. Its treatment often requires ventricular shunting. The complication rate is high due to obstruction or material infection, which may justify endoscopic third ventriculostomy (ETV). OBSERVATION: We report a case of obstructive hydrocephalus in a 46-year-old man in the context of racemose cysticercosis, presenting with headaches and transient disorders of consciousness. Imaging showed cystic lesions of the cisterna magna, responsible for hydrocephalus which was treated effectively by ETV. Treatment with albendazole decreased the volume of the cisterna magna cysts. RESULTS: The patient was followed for 6 years after ETV with no recurrence of hydrocephalus despite two more symptomatic episodes of the disease with extension of the cysts into the lumen of the fourth ventricle and into the perispinal subarachnoid spaces, effectively treated by albendazole each time. CONCLUSIONS: Treatment of obstructive hydrocephalus secondary to cerebral racemose cysticercosis by ETV seems to be an effective and safety technique. The role of ETV should be evaluated in this indication.

Experience with doxorubicin-bound polyisohexylcyanoacrylate nanoparticles on murine alveolar echinococcosis of the liver.

The parasiticidal properties of doxorubicin against the metacestode of Echinococcus multilocularis were investigated after binding of that drug to polyisohexylcyanoacrylate nanoparticles, a colloidal biodegradable drug carrier. A reduction of the hepatic parasite development and a reduced viability of the metacestode were observed in mice injected with 5 mg kg-1 body weight-1, but 7.5 mg kg-1 body weight-1 did not appear more efficient. Free doxorubicin or unbound nanoparticles had no antiparasitic activity.

In vitro quantitative assessment of Echinococcus multilocularis metacestode viability after in vivo and in vitro maintenance.

The aim of this study was to apply the enzymatic MTT (3,5 dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide--formazan colorimetry for quantifying the viability of Echinococcus multilocularis whole cysts, after maintenance in vivo or in vitro. The enzymatic activities of young cysts freshly removed from rodents were linearly correlated with the parasite cyst weight. A comparative evaluation of the MTT assay and the in vitro viability assessments showed that the number of animals used for drug-screening purposes would be reduced by 35.8%. In this way, the use of different parasite samples removed from the same host is required, because of their different ages and their subsequent different abilities to reduce MTT. Cysts removed from mice exhibited higher colorimetric values than those removed from jirds. Thus, small entire cysts obtained from mice were maintained in the CMRL 1066 culture medium. Their enzymatic activities were evaluated at different times. The results indicate that, in such conditions, the optimal period of time for testing the effect of drugs against the metacestodes is limited to the 10 days following their transfer from mouse to culture flasks. The MTT assay encourages further studies to improve the viability of the whole cysts in vitro, using other standardizable culture conditions.

Comparison of the viability and developmental characteristics of Echinococcus multilocularis isolates from human patients in France.

Alveolar echinococcosis, due to E. multilocularis, is usually a fatal disease in patients whether treated by benzimidazolecarbamates or not. However, aborted infections have been described, suggesting the existence of strains of parasites of varying pathogenicity. These observations led us to analyse the viability of larvae in 20 patients. After observation of human lesions, the viability of metacestodes was tested by intraperitoneal infection in two intermediate host species, Meriones unguiculatus and AKR inbred mice. Parasitic development was more frequent in mice than in M. unguiculatus, but in the latter, growth was more rapid and the larval mass produced was greater. Isolates which originated from patients undergoing treatment had an abortive growth; two others were characterized by a steady, though slow, development, producing a poorly budding larva; lastly there were some which were morphologically similar with a multivesicular appearance but differing development times. These results may serve as a guide for more basic studies leading to an understanding of the problem of intraspecific variations in E. multilocularis.

Lack of H-2 gene influence on mouse susceptibility to secondary alveolar echinococcosis.

To determine whether the development of hepatic Echinococcus multilocularis infection is influenced by major histocompatibility-linked genes, metacestode growth and host immune responses were compared in 4 C57BL/10 congenic murine strains of H-2b, H-2d, H-2k and H-2q haplotypes. Although the H-2q strain appeared slightly more resistant than the other strains, the 4 strains of mice developed comparable spleen cell proliferative response and Th1/Th2 cytokine production at 13 weeks p.i. A kinetic analysis, performed in 2 of these congenic strains, showed a similar pattern of parasite growth in these mice and failed to detect any significant difference in the production of parasite-specific IgM, IgG1 and IgG2, antibodies. Consequently, this study indicates that the control of secondary alveolar echinococcosis is not H-2 gene-linked.

Effects of cyclosporin A on the course of murine alveolar echinococcosis and on specific cellular and humoral immune responses against Echinococcus multilocularis.

The effects of cyclosporin A (CsA) on Echinococcus multilocularis (E. multilocularis) metacestode growth, and on the specific immune responses of the hosts, were examined in AKR mice. Mice were intra-peritoneally infected with a metacestode homogenate. CsA (40 mg kg(-1) day(-1)) was injected subcutaneously from the 45th day after infection (Group 1), and from the day before infection (Group 2) until the day of autopsy (days 125 and 80, respectively). Results showed that unlike ths situation with some other helminthiases, CsA had no antiparasitic effect, although it lengthened the maturation time of protoscoleces in Group 1. The parasitic burden, unmodified in Group 1, was significantly enhanced in Group 2. This enhancement was associated with a decrease in antibody levels, whereas the delayed-type hypersensitivity was decreased in the two groups. These results confirm the role of cellular immunity in controlling the first stages of the larval development of E. multilocularis and indicate the necessity for a careful follow-up of any recurrence of alveolar echinococcosis in patients treated with CsA after liver transplantation.

Development of an injectable formulation of albendazole and in vivo evaluation of its efficacy against Echinococcus multilocularis metacestode.

The loading of poly (D, L-lactide) nanoparticles with ABZ has led us to evaluate the potential of this new colloidal drug delivery system against E. multilocularis, using a murine model of hepatic alveolar echinococcosis. ABZ-loaded nanoparticles had a monodisperse size distribution between 100 and 150 nm. The efficiency of drug loading to nanoparticles was over 97%. In vitro, at an ABZ concentration of 1.0 microgram ml-1, the formulation had no toxicity for peritoneal macrophages harvested from uninfected mice. In vivo, the ABZ-loaded nanoparticles exhibited no signs of toxicity at any of the doses tested. Intravenous injections of 6 mg kg-1 of bound ABZ to infected mice had an equivalent antiparasitic effect on the metacestode growth to that of a treatment with 1500 mg kg-1 of orally administered free ABZ. The parasite hepatic superficial size as well as the peritoneal metastatic burden was significantly reduced by these 2 courses of treatment, as compared to those of untreated mice. Our results should encourage further study in order to explain the absence of dose-dependent efficacy of ABZ-loaded nanoparticles demonstrated in the present study.

Rapid technique for cryopreservation of Echinococcus multilocularis metacestodes.

Cysts of E. multilocularis were minced to prepare a crude homogenate and after addition of glycerol at a final concentration of 10%, cryopreservation was performed at a rate of 1 degree C min-1 in a controlled-rate freezer. The aliquots were subsequently stored in liquid nitrogen. All 22 isolates tested were successfully cryopreserved and their viability maintained.

Aspergillus fumigatus causes in vitro electrophysiological and morphological modifications in human nasal epithelial cells.

The role of the airway epithelium in the development of invasive aspergillosis in immunocompromised hosts has rarely been studied although patients at risk for this infection frequently have epithelial damage. We developed an in vitro model of primary culture of human nasal epithelial cells (HNEC) in air-liquid interface, which allows epithelial cell differentiation and mimics in vivo airway epithelium. We subsequently tested 7-day and 24-hour Aspergillus fumigatus filtrates on the apical side of HNEC to know whether A. fumigatus, the main species responsible for invasive aspergillosis, produces specific damage to the epithelial cells. The results were compared with those obtained with non-pathogenic filamentous fungi. Seven-day culture filtrates of A. fumigatus and Penicillium chrysogenum induced electrophysiological modifications whatever the fungus tested. In contrast, only 24-hour A. fumigatus filtrates induced a specific decrease in transepithelial resistance, hyperpolarization of the epithelium, and cytoplasmic vacuolization of HNEC compared with both A. niger and Penicillium chrysogenum. The inhibition of the A. fumigatus effects with amiloride suggests that the 24-hour fungal filtrate acts through sodium channels of HNEC. These early modifications of the epithelial cells could facilitate colonization of the airways by A. fumigatus. To know whether the molecules involved are specific to A. fumigatus or simply produced more rapidly than by other filamentous fungi warrants further investigation. In this perspective, the primary culture of HNEC represents a suitable model to study the interactions between airway epithelial cells and A. fumigatus.

Progress toward the development of vaccines against parasitic diseases: a review based on studies performed by participants of the Laveran seminar.

Although significant advances have been mode during the past 20 years, a better understanding of the orchestration of the immune response against a parasite candidate vaccine is still required for preparing vaccines which can induce the acquisition and the persistence of sterile immunity, without producing side effects in humans. This was, among others, one conclusion of the discussions between Thesis students and scientists. Only some aspects of the different steps of immune responses (recognition, protective effector mechanisms, cell regulation, cytokine activities, immunopathology, parasite escape mechanisms) are here reviewed. They are mainly related to malano and schistosomiasis, but also to other parasitic diseases, for which several experimental models have been developed.

[Alveolar echinococcosis in the French province of Ardennes: isolated case or new focus?]. / L'échinococcose alvéolaire dans le département français des Ardennes: cas isolés ou nouveau foyer?

The first three autochthonous cases of alveolar echinococcosis were diagnosed in the Ardennes area (France). This is the most occidental localization of this disease in Northern Europe. The authors discuss these cases with an epidemiological regard. They are looking for relationships with natural parasitic cycle in the neighbouring country Belgium and their consequences on local public health in the future.

Covalent cross-linking of liver collagen by pyridinoline increases in the course of experimental alveolar echinococcosis.

We report that covalent cross-linking of collagen molecules by pyridinoline increases significantly in liver in a murine model of alveolar echinococcosis. The highest amount of pyridinoline per collagen molecule (up to 3.5 fold the control values) is found in liver parasitic lesions. It is also increased, but to a far lesser extent, at distance from the fibrotic areas, in macroscopically normal zones of the liver, suggesting that the increase in mature collagen cross-linking occurring in the fibrogenesis due to Echinococcus multilocularis infection involves the whole liver. The comparison of these data with those we have obtained in another parasitic disease, murine schistosomiasis leading to a milder liver fibrosis, largely reversible following chemotherapy, supports a relationship between the liver pyridinoline level and the severity of liver fibrosis. Pyridinoline could be a tissular marker of chronic liver fibrosis in parasitic diseases.

Echinococcus multilocularis infection in mice: in vivo treatment with a low dose of IFN-gamma decreases metacestode growth and liver fibrogenesis.

As no antiparasitic drug is definitively efficient in patients with alveolar echinococcosis, the effects of exogenous IFN-gamma on murine Echinococcus multilocularis infection were assessed with regards to the parasite burden, parasite-specific immune responses, and the urinary level of the collagen cross-link pyridinolines. They were analyzed after 3-week treatments with 1 or 5 micrograms of IFN-gamma per day twice a week. The treatment with 1 microgram transiently reduced the liver metacestode load, and the metastase weight as far as 6 weeks after the end of treatment. It slightly increased Th 1-type T cell responses and reduced the excretion of pyridinolines. These results should encourage further study to assess whether the decrease in liver fibrosis leads to an improvement of the efficacy of albendazole therapy. In contrast, the treatment with 5 micrograms increased the liver metacestode load and was less efficient than that with 1 microgram in decreasing pyridinoline excretion. These results incitate to follow up carefully patients with alveolar echinococcosis who are treated with IFN-gamma.

[Alveolar echinococcosis in China: current data]. / L'échinococcose alvéolaire en Chine: données actuelles.

Very few information about alveolar echinococcosis in China is available outside the country. The aim of the authors is to give some precisions about the human cases and the infection in the natural animal hosts. It occurs in 3 distinct foci which comprise poor and remote rural areas. Approximately, 420 cases of human disease have been detected, and the most intense focus is Ningxia province in central China. In all areas, the adult tapeworm is frequently found in V. vulpes, V. corsac, and in the domestic dog. The intermediate hosts differ from an area to the others. Their infection rate is high in the central and the northern foci. More researches are needed for improving our knowledge about the epidemiology of the disease. But the actual major requirement is to apply control measures as health education and medical information.

[Alveolar echinococcosis: a dreadful orphan disease]. / L'échinococcose alvéolaire. Une redoutable orpheline.

A WIDESPREAD DISEASE: Significant progress in screening for alveolar echinococcosis has reduced the number of new cases observed in Europe. Health education and serodetection campaigns have allowed earlier diagnosis and more effective treatment. The disease cannot however be totally eradicated due to the widespread wild reservoirs, sometimes even in the center of large cities. THERAPEUTICS: Early diagnosed and treatment can inhibit the inevitable progression observed after clinical manifestations appear. Drugs can block disease progression and surgical excision can be most effective. Inversely, the hopes raised by liver transplantation in patients with advanced stage disease have not been fulfilled due to the more or less late-onset metastasis favored by immunosuppressive treatments. PERSPECTIVES: There has been considerable progress in our knowledge of this parasite disease, particularly in improved diagnostic techniques. They have also demonstrated that humans are poor hosts for the parasite which is often spontaneously ejected. We are beginning to better understand the mechanisms of this spontaneous cure. Practical consequences would be a definition of receptive patient profiles or "vaccine" or immunotherapeutic procedures.

[Mansonelliasis identified by a cervicovaginal smear at the university hospital center of Bobo-Dioulasso (Burkina Faso)]. / Frottis cervicovaginal révélant une mansonellose au centre hospitalier universitaire de Bobo-Dioulasso, Burkina Faso

INTRODUCTION: Mansonella perstans is a genus of filaria that is often asymptomatic or responsible for unspecific symptoms. M. perstans microfilariae are uncommon on cervicovaginal smears. CASE: We report the case of a woman with pruritis and eosinophilia. Microfilariae of M. perstans were observed on both cervicovaginal and blood smears. The patient was successfully treated with a combined single dose of 400 mg of albendazole and ivermectin (150 µg/kg). CONCLUSION: We described here an atypical and rare localization of M. perstans. The routine examination of cervicovaginal smears of women admitted to Bobo-Dioulasso Hospital for screening of cervical neoplasia should allow us to determine the frequency of this parasitosis and propose appropriate treatment.