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.
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.
Background & Aims: Hepatic alveolar echinococcosis (AE), caused by the larval growth of Echinococcus multilocularis, is one of the most lethal helminthic diseases with no satisfactory treatment. Advances in the understanding of the host's immune response (Th2 responses associated with a progressive form of AE), have driven the research towards immune stimulation as an alternative possibility to treat patients. We previously reported clinical stabilization associated with a shift from a Th2 to a Th1 cytokine profile in an AE patient treated with interferon (IFN)alpha. Methods: The effects of recombinant IFNalpha-2a were analyzed in the susceptible C57BL/6J E. multilocularis infected mice. Parasitic burden, macrophage functions, and specific T-cell responses were studied 15, 45, and 90 days postinfection. Results: After 90 days postinfection, 75% of infected IFNalpha-2a-treated mice had no hepatic lesions and half were fully protected. IFNalpha-2a treatment markedly decreased the abnormally elevated production of IL-10 in both Spleen cell cultures and peritoneal macrophage cultures from infected mice and restored phagocytosis and oxidative metabolism of macrophages. It also inhibited IL-6 and IL-13 antigen-induced secretions in spleen cell Cultures. Conclusions: Through its immunoregulatory properties, IFNalpha-2a may be effective in a helminthic liver infection and is a promising candidate for clinical application in AE.
ABSTRACT Alveolar echinococcosis (AE) is the most potentially lethal parasitic zoonosis of the nontropical areas in the northern hemisphere, where cystic echinococcosis (CE) is also endemic. Both AE and CE are highly endemic in China, and both serologic detection of echinococcosis, either AE or CE, and differentiation of AE from CE are crucial problems. Evaluation of Western blot analysis (WB) and enzyme-linked immunosorbent assay (ELISA) for the Em18 antigen, using affinity-purified and recombinant Em18, was carried out “blindly” using 60 human sera from patients diagnosed in France. The results were compared with those obtained using a commercially available Echinococcus WB immunoglobulin G (IgG) kit developed in France. The Em18 WB and Echinococcus WB IgG showed very similar results for detection of AE. Both affinity-purified Em18 or a recombinant Em18 WB and Echinococcus WB IgG seem useful for identification of AE, and the latter seems appropriate for both AE and CE, whereas affinity-purified Em18 ELISA and the newly developed recombinant Em18 ELISA appear to be suitable for detection of AE, especially for epidemiological surveys.
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.
Relationship between parasitic and allergic diseases has often been stressed. Parasitic diseases do offer a model to study the role of those events that may determine the final outcome of immune responses and the type of their effector stage. At first glance, the pathophysiological mechanisms involved in Echinococcus sp infections, hydatid cyst (cystic echinococcosis) and alveolar echinococcosis, appear quite different: IgE-dependent responses seem to be involved in the former and cell-mediated immunity in the latter However, an analysis of the cytokine profile in these two cestodoses shows that, in both cases, Th1 responses are protective, and are present in "abortive" forms of infection; conversely, Th2 responses characterised by IL-5 and especially IL-10 synthesis are the hallmarks of the "progressive" forms of infection, leading to the disease and its clinical complications. In patients, it seems that all known actors of the effector sell-mediated responses actually surround the parasitic cells but are somehow "paralysed", at least partially, by anti-inflammatory cytokines and other mediators such as nitric oxide: hence the chronic evolution of the disease and all complications related to fibrosis and necrosis. Both are the results of an inefficient immune response deviated by the parasite and favoured by immunogenetic characteristics of the host. The IgE synthesis that results from the Th2 immune response also participate in the occurrence of clinical complications. The comparison between parasitic and allergic diseases, through the "echinococcosis model" may be used to better understand the immune mechanisms involved both in the increase in allergic disorders in developed countries and in;mixed-type allergic lesions" which associate cellular immunity and IgE-dependent responses, such as atopic dermatitis. (C) 2001 Editions scientifiques at medicales Elsevier SAS.
Les relations entre les maladies parasitaires et les maladies allergiques ont souvent été soulignées. Les parasitoses offrent un modèle privilégié pour étudier le rôle des événements qui déterminent l’orientation finale des réponses immunitaires et les modalités de leur phase effectrice. Les échinococcoses, kyste hydatique et échinococcose alvéolaire, se présentent apparemment comme des maladies de mécanismes physiopathologiques opposés, privilégiant les réponses IgE dépendantes dans le premier cas et les réponses immunitaires cellulaires dans le second. Cependant, lˈanalyse du profil cytokinique dans ces deux infections à cestodes a montré que, dans les deux cas, la réponse Th1 était la véritable réponse efficace, qui se manifestait dans les formes « abortives » dˈinfection, alors que des réponses de type Th2, caractérisées par la synthèse dˈIL-5 et dˈIL-10, étaient à lˈœuvre dans les formes « progressives » dˈinfection, manifestées par lˈapparition de la maladie et de ses complications. Chez les malades, tout se passe comme si les acteurs de la réponse immunitaire cellulaire se mettaient en place autour des cellules parasitaires, mais se trouvaient, au moins partiellement, paralysés par lˈintervention de cytokines « anti-inflammatoires » et dˈautres médiateurs, comme le NO ; dˈoù la chronicité de la maladie et les complications en relation avec la fibrose et la nécrose induites par une réponse immunitaire pervertie par le parasite, à la faveur de caractéristiques immunogénétiques de lˈhôte. La synthèse dˈIgE induite par le climat cytokinique Th2 participe aussi aux complications. La comparaison parasitoses–allergie, inspirée par le modèle « échinococcose », est source d’enseignement tant pour la compréhension des mécanismes qui sous-tendent lˈaugmentation des maladies allergiques dans les pays développés que pour celle des maladies allergiques « mixtes » qui associent une composante dˈimmunité cellulaire et une composante IgE dépendante, comme la dermatite atopique.
A widespread disease: Significant progress in screening for alveolar echinococciasis 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.
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.
ABSTRACT The Echinococcus Western Blot IgG (LDBIO Diagnostics, Lyon, France), using a whole larval antigen from Echinococcus multilocularis , was evaluated for serodiagnosis and differentiation between two human parasitic infections of worldwide importance: cystic echinococcosis, due to Echinococcus granulosus , and alveolar echinococcosis, due to E. multilocularis . Fifty and 61 serum samples from patients with cystic and alveolar echinococcosis, respectively, were used for assessing diagnostic sensitivity. The sensitivity of the assay was compared with those of screening tests used for these applications. Sera used for assessing cross-reactivities were from 154 patients with other diseases, either parasitic or not. The assay allowed the detection of serum immunoglobulin G antibodies in 97% of Echinococcus -infected patients. It had a higher sensitivity than screening assays for the detection for each echinococcosis. The assay allowed us to correctly distinguish between E. granulosus - and E. multilocularis -infected patients in 76% of cases. It did not allow us to distinguish active from inactive forms of both echinococcoses. The occurrence of cross-reactivities with neurocysticercosis indicates the necessity for retesting sera with species-specific antigens, for rare patients with neurologic disorders. This study shows the usefulness of the commercially available Echinococcus Western Blot IgG for the serological confirmation of human echinococcosis.
The availability of mice carrying a deletion of LT‐α and tumour necrosis factor (TNF)‐α genes enabled us to investigate the role of the TNF during alveolar echinococcosis. We compared the growth rate of Echinococcus multilocularis in LT‐αTNF‐α +/+ mice to that of mice having either no or only one LT‐αTNF‐α functionnal allele. LT‐αTNF‐α−/− mice harboured a significantly higher parasite burden than did the other two populations at 5, 10, and 15 weeks of infection, and they did not survive thereafter. Liver metacestodes removed from these mice were alive and the dehydrogenase activities of peritoneal metacestodes were decreased. Liver lesions regressed in most wild‐type mice. Indeed, dead parasites were cordoned by granulomas containing numerous macrophages and lymphocytes leading to focal liver fibrosis at an early stage of infection. In contrast, most of LT‐αTNF‐α−/− mice harboured metacestodes interspersed with leucocytes, realising purulent abscesses with secondary extensive irregular fibrosis at a late stage of infection. Heterozygous mice had behavioural characteristics intermediate between homozygous mutants and wild‐type mice. Levels of E. multilocularis‐specific delayed‐type hypersensitivity and serum antibodies were slightly decreased in LT‐αTNF‐α−/− mice. This study shows that TNF‐α and/or LT‐α genes play an essential role in the immune protection mechanisms against E. multilocularis at the site of infection.
Using an experimental model of hepatic Echinococcus multilocularis infection in C57BL/6J mice, intraperitoneal administration of 0.8 μg of recombinant IL‐12 to mice with an established infection was shown to reduce the parasite burden as soon as two weeks after the end of treatment. At that time, in vitro Echinococcus multilocularis‐induced spleen T cell proliferative responses as well as IFN‐γ and IL‐5 production were higher in IL‐12 treated mice than in untreated mice. Administration of 0.8 μg of IL‐12 at the time of infection was shown to be without effect on the parasite establishment. However, this treatment greatly inhibited the subsequent metacestode development. Indeed, ten weeks after infection, it induced a complete healing in 37.5% of mice. At that time, the development of metastases was inhibited in 68.75% of IL‐12‐treated mice. This reduction of parasite burden was mainly associated with a strong proliferation of spleen cells to E. multilocularis antigen and with a high IFN‐γ production. Altogether, our results show that IL‐12 is of crucial importance in inhibiting the larval growth after the metacestode establishment in the liver and suggest that this cytokine could be of potential value in the treatment of human alveolar echinococcosis.
The aim of the study was to investigate the systemic and, for the first time, the intestinal humoral events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs. Thirty-one mice were divided into three groups; W-2, W-8 and control group. Each mouse of the W-2 and W-8 groups was orally infected with 1,500 E. multilocularis eggs, two weeks and eight weeks before sacrifice respectively. Control group mice received phosphate buffer saline. Measurement of anti-E. multilocularis and non-specific IgG, IgA and IgM, and of a transudation marker, albumin, were performed in serum and intestinal washings by a time-resolved immunofluorometric assay. These results were complemented by microscopic examination of the intestinal mucosa. This infection model is well-suited to the study of mucosal immunity during alveolar echinococcosis. It showed a major specific intestinal response in the early stage of the disease whereas the systemic response predominated later in the disease. Histopathological studies and calculation of the relative coefficient of excretion of Ig also confirmed that the presence of the parasite, even during a short period, was responsible for a local immunological and inflammatory response and for a change in mucosal permeability. Mucosal immunity could thus play a role in tolerance induction against E. multilocularis that could be a prerequisite for the subsequent development of the larvae in the liver, and for the occurrence of the parasitic disease, alveolar echinococcosis.
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.
The first three autochtonous 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.