Human alveolar echinococcosis (AE), caused by the metacestode of the fox tapeworm Echinococcus multilocularis, is the most pathogenic zoonosis in temperate and arctic regions of the northern hemisphere. Prospective collection of human cases in some areas and mass screenings using ultrasound imaging and confirmation with serological techniques have markedly improved our knowledge of the epidemiology of the disease in humans during the past two decades. Transmission occurs when eggs of the tapeworm, excreted by the final hosts (usually foxes but also dogs, wolves and cats), are ingested accidentally by humans or during normal feeding by a variety of rodents and small lagomorphs. However, the species of host animals differ according to regional changes in mammalian fauna. This review mostly focuses on epidemiology of alveolar echinococcosis in those parts of the world where new and more accurate epidemiological data are now available, i.e. China and Europe, as well as on new epidemiological trends that can be suspected from recent case reports and/or from recent changes in animal epidemiology of E. multilocularis infection. The People's Republic of China (PRC) is a newly recognized focus on AE in Asia. Human AE cases were firstly recognized in Xinjiang Uygur Autonomous Region and Qinghai Provinces at the end of 1950s and infected animals were first reported from Ningxia in central China and north-east of Inner Mongolia in the 1980s. E. multilocularis (and human cases of AE) appears to occur in three areas: (1) Northeastern China (northeast focus): including Inner Mongolia Autonomous region and Heliongjiang Province (2) Central China (central focus): including Gansu Province, Ningxia Hui Autonomous Region, Sichuan Province, Qinghai Province and Tibet Autonomous Region and (3) Northwestern China: including Xinjiang Uygur Autonomous Region, bordered with Mongolia, Russia, Kazakhstan and Kyrgyzstan. The highest prevalence of the disease, up to 15 per cent of the population in some villages, is reached in China. In Europe, data from the European Echinococcosis Registry (EurEchinoReg: 1982–2000) show 53 autochthonous cases of AE in Austria, 3 in Belgium, 235 in France, 126 in Germany, 1 in Greece, and 112 in Switzerland, and 15 ‘imported’ cases, especially from central Asia; 14 cases were collected in Poland, a country not previously considered endemic for AE. Improved diagnostic technology, as well as a real increase in the infection rate and an extension to new areas, can explain that more than 500 cases have been reported for these 2 decades while less than 900 cases were published for the previous 7 decades. New epidemiological trends are related to an unprecedented increase in the fox population in Europe, to the unexpected development of urban foxes in Japan and in Europe, and to changes in the environmental situation in many countries worldwide due to climatic or anthropic factors which might influence the host–predator relationship in the animal reservoir and/or the behavioural characteristics of the populations in the endemic areas.
An area close to the Qinghai-Tibet plateau region and subject to intensive deforestation contains a large focus of human alveolar echinococcosis while sporadic human cases occur in the Doubs region of eastern France. The current review analyses and compares epidemiological and ecological results obtained in both regions. Analysis of rodent species assemblages within quantified rural landscapes in central China and eastern France shows a significant association between host species for the pathogenic helminth Echinococcus multilocularis, with prevalences of human alveolar echinococcosis and with land area under shrubland or grassland. This suggests that at the regional scale landscape can affect human disease distribution through interaction with small mammal communities and their population dynamics. Lidicker's ROMPA hypothesis helps to explain this association and provides a novel explanation of how landscape changes may result in increased risk of a rodent-borne zoonotic disease.
This unique experience indicates that LT is feasible for life-threatening AE. Specific management is needed to optimize the results: earlier decision for LT in incurable symptomatic biliary AE, pre- and post-LT BZM therapy, meticulous pre-LT evaluation to identify extrahepatic extension, and an immunosuppressive regimen kept to a minimum.
This review gives a critical update of the situation regarding alveolar echinococcosis (AE) in Europe in humans, based on existing publications and on findings of national and European surveillance systems. All sources point to an increase in human cases of AE in the "historic endemic areas" of Europe, namely Germany, Switzerland, Austria and France and to the emergence of human cases in countries where the disease had never been recognised until the end of the 20th century, especially in central-eastern and Baltic countries. Both increase and emergence could be only due to methodological biases; this point is discussed in the review. One explanation may be given by changes in the animal reservoir of the parasite, Echinococcus multilocularis (increase in the global population of foxes in Europe and its urbanisation, as well as a possible increased involvement of pet animals as definitive infectious hosts). The review also focuses onto 2 more original approaches: (1) how changes in therapeutic attitudes toward malignant and chronic inflammatory diseases may affect the epidemiology of AE in the future in Europe, since a recent survey of such cases in France showed the emergence of AE in patients with immune suppression since the beginning of the 21st century; (2) how setting a network of referral centres in Europe based on common studies on the care management of patients might contribute to a better knowledge of AE epidemiology in the future.
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 brain.
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% ofEchinococcus-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.
Between 1986 and 1991, 21 patients received liver grafts in our center for incurable alveolar echinococcosis (AE). The aim of this study was to analyze the long-term results in 15 of these 21 patients who survived more than 1 year after undergoing a liver transplantation (LT). The follow-up, mainly aimed at the diagnosis of recurrence, consisted of repeated radiological and specific immunological investigations. The role of pre- and post-LT benzimidazole (BZM) therapy was also evaluated. Among the 15 patients, 8 patients had a palliative LT related to previously known pulmonary AE metastases and/or inextirpable abdominal parasitic foci. In the 7 remaining patients, LT was considered curative. In June 1998, the mean follow-up duration was 96 months (range: 28-138 months). Five late deaths occurred, 2 of them were directly related to residual AE. A reinfection of the graft was observed in 4 patients. Preoperative BZM therapy seemed useful in preventing or delaying the parasitic recurrence. Post-LT BZM was able to stabilize and even to reduce residual AE. The anti-Em2 enzyme-linked immunosorbent assay (ELISA), which is the standard test used in patient follow-up after partial liver resection for AE, did not appear useful in detecting recurrence here; however, an ELISA, using a crude heterologous antigen (Echinococcus granulosus) allowed early diagnosis of residual AE. In conclusion, primary disease recurrence is not rare after LT for AE. Immunosuppressive therapy may favor larval growth in extrahepatic sites; therefore, an extensive extrahepatic radiological check-up has to be performed before LT. BZM therapy seems to stabilize residual foci. Anti-Eg immunoglobulin G (IgG) follow-up is the most useful test for early diagnosis of parasite recurrence.
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