Echinococcus multilocularis and Its Intermediate Host: A Model of Parasite-Host Interplay

Host-parasite interactions in the E. multilocularis-intermediate host model depend on a subtle balance between cellular immunity, which is responsible for host's resistance towards the metacestode, the larval stage of the parasite, and tolerance induction and maintenance. The pathological features of alveolar echinococcosis. the disease caused by E. multilocularis, are related both to parasitic growth and to host's immune response, leading to fibrosis and necrosis, The disease spectrum is clearly dependent on the genetic background of the host as well as on acquired disturbances of Th1-related immunity. The laminated layer of the metacestode, and especially its carbohydrate components, plays a major role in tolerance induction. Th2-type and anti-inflammatory cytokines, IL-10 and TGF-β, as well as nitric oxide, are involved in the maintenance of tolerance and partial inhibition of cytotoxic mechanisms. Results of studies in the experimental mouse model and in patients suggest that immune modulation with cytokines, such as interferon-α, or with specific antigens could be used in the future to treat patients with alveolar echinococcosis and/or to prevent this very severe parasitic disease

Alveolar echinococcosis: update 2016

L’échinococcose alvéolaire (EA) est une cestodose larvaire rare, due au développement dans le foie de la larve d’Echinococcus multilocularis. Sa progression s’apparente à celle d’un cancer à marche lente. En France, les caractéristiques épidémiologiques de l’EA se sont modifiées récemment. Les foyers endémiques restent localisés à l’Est et au Centre du Territoire, mais la limite occidentale de la zone d’endémie française dépasse désormais Paris et concerne également les zones urbaines. Le registre français des cas indique par ailleurs une augmentation de l’incidence annuelle. Elle est probablement surtout la conséquence d’une amélioration significative des techniques de diagnostic, en particulier de l’échographie, examen de première ligne pour le diagnostic de cette affection. Le développement de thérapeutiques immunosuppressives (chimiothérapie, biothérapie) pour diverses pathologies peut fournir une deuxième explication, avec l’observation croissante de cas d’EA découverts en situation d’immunosuppression. La maladie est repérée plus tôt dans son cours évolutif, très souvent à un stade asymptomatique. L’ictère qui, par le passé, révélait l’EA dans la moitié des cas, n’est aujourd’hui que très rarement présent au diagnostic. La chirurgie est restée jusque dans les années 1980, la seule et unique solution pour son traitement, souvent palliatif. Des options complémentaires, ou distinctes, sont apparues au cours de ces trente dernières années : administration d’albendazole exerçant un effet parasitostatique, radiologie interventionnelle, transplantation hépatique en cas d’EA évoluées. Toutes ces acquisitions, associées à un diagnostic généralement plus précoce, aux progrès des techniques d’imagerie et de la chirurgie hépato-biliaire ainsi qu’à une approche multidisciplinaire de cette prise en charge, ont permis d’améliorer considérablement le pronostic.Alveolar echinococcosis (AE) is a rare larval cestodosis infestation caused by the intra-hepatic development of Echinococcus multilocularis larva. Its progression in the liver is similar to a slow-growing cancer. Recently in France, the epidemiological characteristics of AE evolved. The endemic areas are still located in the East and in the Center of the territory, but the western limit of the French endemic zone now extends beyond Paris and includes other urban areas. The French Registry also indicates an increase of the annual incidence rate. Above all, this phenomenon is probably due to the major improvement of the diagnostic techniques – especially liver ultrasound exam, that proved to be the first line exam to diagnose this parasitic disease. This could also be explained by the development of immunosuppressive therapeutics like chemotherapy or biotherapy to treat various pathological conditions, which is linked with the growing observation of AE discovered in immunosuppressive situations. Today, the disease is detected earlier in its course, most of the time at an asymptomatic stage. By the past, jaundice, which usually reflect an advanced disease was the revealing symptom in half of the cases; it is now very rarely present at the time of diagnosis. Until the 1980s, surgery remained the only solution for its treatment – which was often part of a palliative care. Additional or alternative options appeared during the last 30 years: administration of albendazole having a parasitostatic effect, interventional radiology, liver transplantation in case of advanced AE. All these acquisitions, combined with an earlier diagnosis, the progress in imagery technology and in hepatobiliary surgery, and a multidisciplinary approach of the patient’s care, contributed to improve significantly AE prognosis

Indications and results of liver transplantation for Echinococcus alveolar infection: an overview

Background: Alveolar echinococcosis (AE) of the liver, caused by the larval stage of the fox tapeworm Echinococcus multilocularis, has the characteristics of a slow-growing liver cancer. It is one of the rare parasitic diseases for which a parasitolytic drug is not yet available, and AE is lethal in the absence of appropriate therapeutic management. Complete surgical resection of the parasite at an early stage of infection provides favourable prospects for cure, but, due to a long clinical latency, many cases are diagnosed at an advanced stage, so that partial liver resection can be performed in only 35% of patients. Benzimidazole (BZM) treatment is given in inoperable cases but these compounds are only parasitostatic, and lifelong therapy is required. During the past 20 years some centres have considered liver transplantation (LT) for the treatment of incurable AE. Methods: Our review summarizes the results of this experience based on a series of 47 European patients who received transplants between 1985 and 2002, tries to specify the real place of LT for AE, and underlines the measures that could be undertaken in the future to improve the results. Results: Five-year survival was 71%. Five-year survival without recurrence was 58%. Major technical difficulties related either to previous laparotomies or to the loco-regional involvement were observed. The nine early deaths concerned AE patients with a long past-history of symptomatic AE (iterative cholangitis, secondary biliary cirrhosis). Five late deaths were directly related to ongoing AE, located in the brain in three cases, a very rare AE location that was not investigated before LT in these patients. Conclusions: In general, the pre-LT screening for distant AE metastases appeared insufficient in this series. Heavy immunosuppressive schemes, absence or delayed re-introduction of BZM after LT have clearly played a role in this unfavourable course. This unique experience indicates that, despite major technical difficulties, LT for incurable AE is feasible and could be discussed in very symptomatic cases. Before LT, interventional radiology should be preferred to repeated laparotomies. Pre-LT and post-LT BZM treatment is mandatory. A careful evaluation of possible distant metastases should be done before the decision for LT is made. After LT, the possibility of an ongoing AE must be permanently kept in mind. This could be reduced by lightening the immunosuppressants, carefully following the specific circulating antibodies, and applying a systematic radiological evaluation, not only to the graft but also to the lungs and the brai

Alveolar echinococcosis in solid organ transplant recipients: a case series from two national cohorts

Alveolar echinococcosis (AE) is a severe parasitic infection caused by the ingestion of Echinococcus multilocularis eggs. While higher incidence and faster evolution have been reported in immunosuppressed patients, no studies have been performed specifically on AE in transplant patients. We searched for all de novo AE cases diagnosed between January 2008 and August 2018 in solid organ transplant (SOT) recipients included in the Swiss Transplant Cohort Study and the FrancEchino Registry. Eight cases were identified (kidney = 5, lung = 2, heart = 1, liver = 0), half of which were asymptomatic at diagnosis. AE diagnosis was difficult due to the low sensitivity (60%) of the standard screening serology (Em2+) and the frequently atypical radiological presentations. Conversely, Echinococcus Western blot retained good diagnostic performances and was positive in all eight cases. Five patients underwent surgery, but complete resection could only be achieved in one case. Moreover, two patients died of peri-operative complications. Albendazole was initiated in seven patients and was well tolerated. Overall, AE regressed in one, stabilized in three, and progressed in one case, and had an overall mortality of 37.5% (3/8 patients). Our data suggest that AE has a higher mortality and a faster clinical course in SOT recipients; they also suggest that the parasitic disease might be due to the reactivation of latent microscopic liver lesions through immune suppression. Western blot serology should be preferred in this population. Finally, surgery should be considered with caution, because of its low success rate and high mortality, and conservative treatment with albendazole is well tolerated

Benzimidazoles for the treatment of cystic and alveolar echinococcosis: what is the consensus?

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Une seule santé au milieu du gué ?

National audienceFace aux changements globaux (effondrement de la biodiversité, réchauffement climatique, épuisement des ressources, etc.), à la recrudescence des événements de santé dont la fréquence augmente depuis des décennies (pas seulement de nature infectieuse), et alors que l’origine écosystémique précise des grandes pandémies est très loin d’être élucidée, en mars 2022, l'OMS, l'OMSA (ex-OIE), la FAO et le PNUE ont conjointement plaidé pour un rééquilibrage des multiples composantes de One Health, incluant explicitement la notion d'équité entre secteurs et disciplines, et une vision plus clairement écologique de l'ensemble. L’approche One Health reconnait que la santé humaine, celle des animaux domestiques et sauvages, et celle des plantes et des écosystèmes sont étroitement liées et interdépendantes. Pour réussir ce changement transformateur, la recherche a besoin de renforcer les collaborations actuelles entre les disciplines et les secteurs professionnels, et d’en développer de nouvelles. Les financements, actuellement largement bénéficiaires aux soins et à la prévention strictement médicale, devraient aussi être considérablement rééquilibrés. Dans le cas contraire, "One Health" pourrait ne rester qu’une aspiration louable, nous laissant continuer à être perpétuellement impréparés à faire face aux enjeux sanitaires majeurs imposés par la démographie humaine combinée au réchauffement climatique et à l’effondrement de la biodiversité. Pour que ce ne soit pas qu’un vœu pieux, on peut se poser les questions suivantes : Les disciplines concernées (écologie, géographie de la santé, socio-anthropologie…) trouveront-elles un appui parmi celles concernant la santé humaine et vétérinaire, tant pour bénéficier des financements adéquats que pour mobiliser les compétences en santé pour une recherche collaborative ? Qui va plaider pour une structuration de la recherche qui permette l’indispensable double dimension spatiale et temporelle sur le long terme ? Les études médicales sont-elles assez ouvertes à ces problématiques ? Qui prendra l’initiative de former dès l’école des citoyens concernés, capables de s’engager dans une recherche participative sur les causes environnementales des maladies ? Nos réponses à ces questions seront déterminantes pour notre avenir

Une seule santé au milieu du gué ?

National audienceFace aux changements globaux (effondrement de la biodiversité, réchauffement climatique, épuisement des ressources, etc.), à la recrudescence des événements de santé dont la fréquence augmente depuis des décennies (pas seulement de nature infectieuse), et alors que l’origine écosystémique précise des grandes pandémies est très loin d’être élucidée, en mars 2022, l'OMS, l'OMSA (ex-OIE), la FAO et le PNUE ont conjointement plaidé pour un rééquilibrage des multiples composantes de One Health, incluant explicitement la notion d'équité entre secteurs et disciplines, et une vision plus clairement écologique de l'ensemble. L’approche One Health reconnait que la santé humaine, celle des animaux domestiques et sauvages, et celle des plantes et des écosystèmes sont étroitement liées et interdépendantes. Pour réussir ce changement transformateur, la recherche a besoin de renforcer les collaborations actuelles entre les disciplines et les secteurs professionnels, et d’en développer de nouvelles. Les financements, actuellement largement bénéficiaires aux soins et à la prévention strictement médicale, devraient aussi être considérablement rééquilibrés. Dans le cas contraire, "One Health" pourrait ne rester qu’une aspiration louable, nous laissant continuer à être perpétuellement impréparés à faire face aux enjeux sanitaires majeurs imposés par la démographie humaine combinée au réchauffement climatique et à l’effondrement de la biodiversité. Pour que ce ne soit pas qu’un vœu pieux, on peut se poser les questions suivantes : Les disciplines concernées (écologie, géographie de la santé, socio-anthropologie…) trouveront-elles un appui parmi celles concernant la santé humaine et vétérinaire, tant pour bénéficier des financements adéquats que pour mobiliser les compétences en santé pour une recherche collaborative ? Qui va plaider pour une structuration de la recherche qui permette l’indispensable double dimension spatiale et temporelle sur le long terme ? Les études médicales sont-elles assez ouvertes à ces problématiques ? Qui prendra l’initiative de former dès l’école des citoyens concernés, capables de s’engager dans une recherche participative sur les causes environnementales des maladies ? Nos réponses à ces questions seront déterminantes pour notre avenir

From Farming to Engineering: The Microbiota and Allergic Diseases

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Echinococcus spp.

International audienceThe tapeworms and their eggs are a risk to humans from dog feces thus the role of human excreta or sewage is generally not of concern. However due to the association with animals, particular dog excreta is an issue regarding hygiene and soil contamination where dogs are infected.The larval stages (metacestodes) of the helminth cestodes of the genus Echinococcus are the causes of echinococcoses. Until recently, the main two species recognized to cause diseases in humans were respectively E. granulosus, for ‘cystic echinococcosis’ (CE, formerly named ‘hydatidosis’, or ‘hydatid disease’ or ‘hydatid cyst’), and E. multilocularis, for alveolar echinococcosis (AE). The estimated minimum global human burden of human CE averages 285,500 disability-adjusted life years (DALYs) (more than 1 million if underreporting is taken into account), and AE, a rare but more severe disease, results in a median of 666,434 DALYs per year. At the beginning of the 21st century, based on genetic characteristics, E. granulosus sensu lato has been split into several species: E. granulosus sensu stricto (ex-sheep strain), E. felidis, E. equinus (ex-horse strain), E. ortleppi (ex-cattle strain), and E. canadensis (ex-camel, pig and cervid strains). E. oligarthrus and E. vogeli (only present in South America) cause diseases with a clinical presentation similar to that of CE and AE, respectively.The metacestodes consist of the germinal layer surrounded by the laminated layer. The germinal layer forms ‘buds’, then ‘vesicles’ (cysts), which are filled with a water-like liquid (‘hydatid/cyst/vesicle fluid’). Cysts may be single with little inflammatory reaction (typically for CE) or multiple and aggregated with an impressive granulomatous infiltrate, dense fibrosis, and necrosis of the central part of lesion (typically for AE).Both CE and AE are tumor-like diseases, most often located in the liver and also lungs for CE; dissemination may occur in any other organ/tissue. Echinococcosis may remain asymptomatic for a long period of time and spontaneous death of the metacestode occurs in many patients. Diagnosis relies on imaging, and incidental finding of an echinococcal lesion, especially in the liver, is not rare. Ultrasound (US) examination is the basis for diagnosis in patients with liver-related signs and symptoms and for mass screening.For CE, drug treatment includes 3-6 month albendazole for small cysts or, at the opposite of the spectrum, long-term albendazole (> 6 months) for disseminated non-operable CE. However, surgery remains the treatment of choice for most cysts. For AE, albendazole is the basis for care management in all patients, for a minimum of 2 years after radical surgical resection of the liver lesions; it must be administered for life, at least for decades, in all other cases; biliary complications and bacterial superinfection are treated by percutaneous or perendoscopic drainage and stenting.Infection of humans occurs through ingestion of Echinococcus eggs, excreted in the feces of definitive hosts. E. granulosus sensu lato is usually maintained by the domestic cycle (dog/domestic ungulates) and represents a persistent zoonosis in rural livestock-raising areas where humans cohabit with dogs fed on raw livestock offal in which the cysts are present. A cycle in wild animals allows E. multilocularis to occur in nature. It includes mostly voles of a number of different species and additionally lagormophs such as pikas in some areas, as intermediate hosts. Foxes, wolves and dogs are definitive hosts, and less commonly other carnivores. Environmental factors play a critical role in E. multilocularis infection in wild animals, resulting in a heterogeneous geographical distribution of the parasite and possibly influencing contamination of water. In many countries, dog and fox urbanization has considerably increased the human population at risk. Various types of association of CE and AE with water sources of the communities have been reported. Studies on the presence of infective eggs in the environment (including soil and plants/fruit/vegetables), using molecular tools, are just at their beginning. There are currently no published data on the presence of Echinococcus spp. eggs in sewage, sludge, surface waters, ground water, drinking water, soil or irrigation water. Echinococcus spp. eggs shed with carnivore feces are destroyed by heat (including water boiling) and desiccation but are very resistant to low temperature (until -70° C) and to all chemicals used for disinfection; they may be released into and are well preserved in water; they may also be dispersed in the soil through spreading of sludge from water treatment plants. Systematic studies on how various modalities of sewage treatment and sanitation may contribute to or conversely avoid human infection are needed

Les échinococcoses, des maladies parasitaires en expansion

International audienceDepuis quelques années, les ceintures et autres coulées vertes envahissent les villes et leurs abords, ramenant de la biodiversité dans des lieux où elle avait longtemps été négligée, voire combattue. S’il est agréable de vivre dans un tel environnement, et de le partager avec nos compagnons domestiques et des animaux sauvages, il faut avoir conscience que cela signifie aussi accepter de côtoyer les microbes dont ces derniers sont les hôtes.Or, la gamme d’organismes pathogènes qu’ils hébergent est très large, et certains sont susceptibles de passer à l’être humain, provoquant des maladies appelées zoonoses. L’une des plus célèbres est la maladie de Lyme, causée par une bactérie et propagée par les tiques. Mais d’autres zoonoses, beaucoup plus rares, sont moins connues. Elles n’en sont pas moins graves.C’est le cas des échinococcoses provoquées par les échinocoques, des vers plats parasites qui peuvent être propagés par les renards, certains rongeurs, voire nos chiens et chats domestiques. De quoi s’agit-il exactement, et comment s’en protéger