Skin prick tests and specific IgE in 10-year-old children: Agreement and association with allergic diseases.

BACKGROUND: Accurate assessment of atopic sensitization is pivotal to clinical practice and research. Skin prick test (SPT) and specific IgE (sIgE) are often used interchangeably. Some studies have suggested a disagreement between these two methods, and little is known about their association with allergic diseases. The aims of our study were to evaluate agreement between SPT and sIgE, and to compare their association with allergic diseases in 10-year-old children. METHODS: Skin prick test, sIgE measurements, and assessment of allergic diseases were performed in children aged 10 years in the Protection against Allergy: STUdy in Rural Environments (PASTURE) cohort. The agreement between SPT and sIgE was assessed by Cohen's kappa coefficient with different cutoff values. RESULTS: Skin prick tests and sIgE were performed in 529 children. The highest agreement (κ=.44) was found with a cutoff value of 3 and 5 mm for SPT, and 3.5 IU/mL for sIgE. The area under the curve (AUC) obtained with SPT was not significantly different from that obtained with sIgE. For asthma and hay fever, SPT (cutoff value at 3 mm) had a significantly higher specificity (P<.0001) than sIgE (cutoff value at 0.35 IU/mL) and the specificity was not different between both tests (P=.1088). CONCLUSION: Skin prick test and sIgE display moderate agreement, but have a similar AUC for allergic diseases. At the cutoff value of 3 mm for SPT and 0.35 IU/mL for sIgE, SPT has a higher specificity for asthma and hay fever than sIgE without difference for sensitivity.

Landscape and climatic characteristics associated with human alveolar echinococcosis in France, 1982 to 2007.

Human alveolar echinococcosis (AE) is a severe hepatic disease caused by Echinococcus multilocularis. In France, the definitive and intermediate hosts of E. multilocularis (foxes and rodents, respectively) have a broader geographical distribution than that of human AE. In this two-part study, we describe the link between AE incidence in France between 1982 and 2007 and climatic and landscape characteristics. National-level analysis demonstrated a dramatic increase in AE risk in areas with very cold winters and high annual rainfall levels. Notably, 52% (207/401) of cases resided in French communes (smallest French administrative level) with a mountain climate. The mountain climate communes displayed a 133-fold (95% CI: 95-191) increase in AE risk compared with communes in which the majority of the population resides. A case-control study performed in the most affected areas confirmed the link between AE risk and climatic factors. This arm of the study also revealed that populations residing in forest or pasture areas were at high risk of developing AE. We therefore hypothesised that snow-covered ground may facilitate predators to track their prey, thus increasing E. multilocularis biomass in foxes. Such climatic and landscape conditions could lead to an increased risk of developing AE among humans residing in nearby areas.

Human cystic and alveolar echinococcosis in the Tibet Autonomous Region (TAR), China.

Human cystic echinococcosis (CE) is known to be endemic in the Tibet Autonomous Region (TAR), China; however, there is relatively little data from hospital records or community prevalence studies, and the situation regarding occurrence of human alveolar echinococcosis (AE) is unclear. Here we review the available reports about human echinococcosis in the seven prefectures of TAR. In addition, two pilot studies by mass screening using ultrasound (with serology) were undertaken (2006/7) in Dangxiong County of Lhasa Prefecture (north central TAR) and Dingqing County of Changdu Prefecture (eastern TAR). In Dangxiong County a prevalence of 9.9% (55/557) for human CE was obtained but no human AE cases were detected. By contrast, in Dingqing County (N= 232 persons screened), 11 CE cases (4.7%) and 12 AE cases (5.2%) (including one mixed CE and AE case) were diagnosed by ultrasound. Hospital records and published reports indicated that CE cases were recorded in all of seven prefectures in Tibet Autonomous Region, and AE cases in four prefectures. Incidence rates of human CE were estimated to range from 1.9 to 155 per 100,000 across the seven prefectures of TAR, with a regional incidence of 45.1 per 100,000. Incidence of AE was estimated to be between 0.6 and 2.8 cases per 100,000. Overall for TAR, human AE prevalence appeared relatively low; however, the pilot mass screening in Dingqing in eastern TAR indicated that human AE disease is a potential public health problem, possibly similar to that already well described in Tibetan communities bordering TAR in north-west Sichuan and south-west Qinghai provinces.

Specific IgE to allergens in cord blood is associated with maternal immunity to Toxoplasma gondii and rubella virus.

BACKGROUND: Various studies have found reduced prevalences of atopic sensitization and atopic diseases in children previously exposed to infections or living conditions with a high microbial burden, such as the farming environment. OBJECTIVE: We sought to determine the relationships of cord blood immunoglobulin E (IgE) with maternal health conditions before and during pregnancy. METHODS: Pregnant women living in rural areas in five European countries were recruited in the third trimester of pregnancy. Information on maternal health during pregnancy was collected from maternity records and by questionnaires (n = 497). Specific IgE for inhalant and food allergens was assessed in cord blood and peripheral blood samples of the mothers. RESULTS: Inverse associations of cord blood IgE to seasonal allergens with positive maternal records for Toxoplasma gondii (adjusted odds ratio = 0.37 [0.17-0.81]) and rubella virus (adjusted odds ratio = 0.35 [0.13-0.96]) were found. The previously described effect of prenatal farm exposure on IgE to seasonal allergens was partly confounded by a positive maternal record for T. gondii. The number of maternal siblings, maternal contact to cats during pregnancy or during her first year of life, predicted a positive maternal record for T. gondii. CONCLUSIONS: Maternal immunity to T. gondii and rubella may impact on atopic sensitization in the fetus. A positive T. gondii record explained the previously identified effect of prenatal farm exposure on IgE to seasonal allergens only to a minor extent.

Immunology of Alveolar and Cystic Echinococcosis (AE and CE).

Cystic and alveolar echinococcosis are severe chronic helminthic diseases caused by the cystic growth or the intrahepatic tumour-like growth of the metacestode of Echinococcus granulosus or Echinococcus multilocularis, respectively. Both parasites have evolved sophisticated strategies to escape host immune responses, mainly by manipulating and directing this immune response towards anergy and/or tolerance. Recent research studies have revealed a number of respective immunoregulatory mechanisms related to macrophages and dendritic cell as well as T cell activities (regulatory T cells, Tregs). A better understanding of this complex parasite-host relationship, and the elucidation of specific crucial events that lead to disease, represents targets towards the development of novel treatment strategies and options.

The Echinococcoses: Diagnosis, Clinical Management and Burden of Disease.

The echinococcoses are chronic, parasitic diseases that are acquired after ingestion of infective taeniid tapeworm eggs from certain species of the genus Echinococcus. Cystic echinococcosis (CE) occurs worldwide, whereas, alveolar echinococcosis (AE) is restricted to the northern hemisphere, and neotropical echinococcosis (NE) has only been identified in Central and South America. Clinical manifestations and disease courses vary profoundly for the different species of Echinococcus. CE presents as small to large cysts, and has commonly been referred to as 'hydatid disease', or 'hydatidosis'. A structured stage-specific approach to CE management, based on the World Health Organization (WHO) ultrasound classification of liver cysts, is now recommended. Management options include percutaneous sterilization techniques, surgery, drug treatment, a 'watch-and-wait' approach or combinations thereof. In contrast, clinical manifestations associated with AE resemble those of a 'malignant', silently-progressing liver disease, with local tissue infiltration and metastases. Structured care is important for AE management and includes WHO staging, drug therapy and long-term follow-up for at least a decade. NE presents as polycystic or unicystic disease. Clinical characteristics resemble those of AE, and management needs to be structured accordingly. However, to date, only a few hundreds of cases have been reported in the literature. The echinococcoses are often expensive and complicated to treat, and prospective clinical studies are needed to better inform case management decisions.

[Mixed infection of Echinococcus granulosus and Echinococcus multilocularis in dog].

OBJECTIVE: To identify mixed infection of Echinococcus granulosus and E. multilocularis in a dog from Xinjiang. METHODS: Thirty dogs from the pasture area were dissected and over 10,000 Echinococcus adult worms were found from one dog. Morphological observation revealed possible mixed infection of the two Echinococcus species. Further identification was made by amplification of the target gene DNA fragment (mitochondrial 12S rRNA gene). RESULTS: The adult worms of E. granulosus showed a relatively longer and larger gravid proglottid, its genital pore situated near or below the middle-side of the segment. The uterus was in a sacculate shape with irregular branches and approximately over 200 - 800 eggs in it. Morphology of the adult worms of E. multilocularis was similar to E. granulosus, slightly smaller, consisting of 4 to 5 proglottids. The uterus was not sacculate and with no branch. Its lateral genital pore often situated in the anterior part of the segment. Sequence analysis of mitochondrial 12S rRNA gene showed that amplification with the Eg1f/r primers shared complete identity with E. granulosus G1 genotype (GenBank accession no. AY462129), while that witht the EmH15/17 primers shared complete identity with E. multilocularis (GenBank accession no. AB031351). The presence of both E. granulosus and E. multilocularis was confirmed by microscopy and gene identification. CONCLUSION: Mixed infection of the two species of Echinococcus has been confirmed in the dog by morphological observation and PCR technique.

Brain metastasis of alveolar echinococcosis in a hyperendemic focus of Echinococcus multilocularis infection.

An unusual female case, with alveolar echinococcosis (AE) disseminated from the primary hepatic lesion to the brain by metastasis formation, was retrospectively identified during a community survey in Ningxia Hui Autonomous Region, northwest China in 2003. Among possible metastases of hepatic AE, locations to the brain are rare and usually fatal; and they have especially been assigned to concomitant immune suppression. An enhancing role of pregnancy, which may be suspected in this case, the favourable outcome after surgery and chemotherapy, and also a mental disability in a child following long-term intrauterine exposure to mebendazole, make the report particularly unique.

Clinical epidemiology of human AE in Europe.

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.

Polymeric Ig receptor expression in hepatocellular carcinoma.

The cellular localisation of the polymeric Ig receptor (pIg-R) and carcinoembryonic antigen (CEA), hepatic and biliary cell markers, were investigated in patients with hepatocellular carcinoma (HCC) and high serum levels of secretory component. Serum SC were increased 6-20-fold in 8 HCC patients compared with normal subjects. Serum free SC was positively correlated bilirubin (r = 0.95, P less than 0.04). In normal liver tissue, cytokeratin (CK) 8 and 18 were localised in hepatocytes and biliary cells while pIg-R and CK 19 expression was restricted to biliary cells. In tumoral liver tissue, malignant cells expressed CK 8 and 18 weakly; pIg-R and CK 19 were not detected in tumoral cells. CEA was expressed by biliary cells in normal and proliferating ducts. In peritumoral fibrosis, proliferating biliary cells were strongly stained by anti-cytokeratins and anti-pIg-R antibodies. In one case, pIg-R was localised in isolated cells close to fibrosis without co-staining of anti-CK 19. Thus increased serum SC is not associated with pIg-R expression by tumoral cells, and pIg-R may be considered an additional marker of biliary cells. High SC might be explained either by reflux from bile to serum and/or release of unbound SC from the vascular pole of non-functional, proliferating biliary structures.

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.

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.

Assessment of the epidemiological status of Echinococcus multilocularis in foxes in France using ELISA coprotests on fox faeces collected in the field.

The aim of this study was to estimate the relevance of Echinococcus multilocularis coproantigen detection in fox faeces collected in the field to identify different levels of endemicity for Echinococcus multilocularis on a large scale (n x 10 km(2)). Six study sites were selected in a high endemicity area and two study sites in a low endemicity area in eastern France on the basis of landscape composition. Sampling was undertaken in the winters of 1996-97, 1997-98 and 1998-99. At each site, (i) necropsy and intestine examination was undertaken on a sample of shot foxes (total number of foxes, 222), and (ii) fox faeces were collected in the field along road verges, and scored for degradation status (total number of faeces, 625). Fox faeces were also sampled in a control area (n=30) in western France in the summer of 1998. Intestines were examined according to the sedimentation method. Echinococcus multilocularis coproantigens were detected by using two ELISA tests: EM-ELISA and EmA9-ELISA. The necropsy prevalence in high and low endemicity areas was 63.3% and 19.4%, respectively, and the distribution of adult worms in the fox population was highly overdispersed (75.5% of the total biomass was harboured by 11.6% of foxes). Using the two ELISA tests, there was no difference in the detection of E. multilocularis coproantigens in field faeces, regardless of the degradation status. The medians of EM- and EmA9-ELISA OD values of field faeces in high endemicity area were significantly higher than in low endemicity area (P<0.001 for both ELISA). The distribution of EM-ELISA OD values in low endemicity area was significantly higher (P=0.002) than in the control area. Moreover, for the two ELISA, the observed ELISA OD value distributions in high endemicity area, low endemicity area and control area seemed representative of the distribution of adult worms in fox populations. These results indicate that E. multilocularis coproantigen detection in field faeces could serve for large-scale surveillance, as an alternative to necropsy.

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.

Seroepidemiologic screening of Echinococcus multilocularis infection in a European area endemic for alveolar echinococcosis.

In a serologic survey for Echinococcus multilocularis infection, we screened sera from 7,884 subjects from the Doubs Departement in France, an area endemic for alveolar echinococcosis (AE) of the liver. An enzyme-linked immunosorbent assay (ELISA) with a highly species-specific antigen (Em2) and an E. multilocularis crude antigen (Emc) was used for screening. An evaluation of the cost/benefit relationship of this screening, followed by therapeutic management of patients, was made and compared with the actual cost of the follow-up and treatment of the disease in symptomatic cases in this endemic area. Antibody reactions to Em2 and/or Emc made possible the detection of eight asymptomatic clinical cases (seroprevalence averaging 1/1,000), with typical lesions of active AE revealed by abdominal ultrasonography and computed tomography. All were seropositive using the Emc ELISA but two were seronegative using the Em2 ELISA. In five additional seropositive cases, the radiologic investigations revealed small calcified lesions similar to the lesions of abortive AE previously found in Alaska. The cost of this serologic screening program per screened subject and per diagnosed case averaged 50.00 French Francs (FF) (U.S. $8.60) and 60,000.00 FF (U.S. $10,909.00), respectively. The cost of diagnosis, follow-up and treatment of the patients was 5,086.00 FF (U.S. $929.00) per patient per month in the case of diseases diagnosed by the screening program and 7,086.00 FF (U.S. $1,288.00) per patient per month for patients with symptomatic AE. This survey indicates a high prevalence of AE in the target area; it confirms the long latency period of the larval growth in human AE and shows that abortive AE is present in Europe. The use of both the Emc and Em2 ELISAs seems to be better than using the Em2 ELISA alone. The cost of the hospitalization and treatment of the eight screened patients would appear to be relatively high. Even though two of them were asymptomatic, they had very severe forms of the disease. In fact, the total cost was much lower than the actual cost of the disease when diagnosed from clinical symptoms.

Combined eco-epidemiological and molecular biology approaches to assess Echinococcus granulosus transmission to humans in Mauritania: occurrence of the 'camel' strain and human cystic echinococcosis.

Mauritania lies between West-Central Africa where human cystic echinococcosis (CE) is considered extremely rare and West Maghreb where CE accounts for a real public health problem. Until 1992, Mauritania was considered as human CE-free even through CE seemed well known in livestock. In 1992, the introduction of ultrasonography led to the diagnosis of the first human CE cases. In 1997, a veterinary study revealed that dogs living around Nouakchott were commonly infected by Echinococcus granulosus. To assess E. granulosus transmission and to identify the most relevant animal reservoir responsible for human CE emerging in Mauritania, a simultaneous eco-epidemiological and molecular biology approach was performed. The fieldwork included sample collection and investigation of relationship between intermediate hosts, definitive hosts and humans. Typing of E. granulosus strains was performed using comparison of polymerase chain reaction (PCR)-amplified DNA sequences with one nuclear (BG 1/3) and 2 mitochondrial (COI, NDI) targets. Results show that the 'camel' strain is actually infectious to humans and circulates between intermediate hosts including camels and cattle. It is suggested that preventive measures at slaughtering places could reduce human contamination.

Analysis of immunoglobulin G subclass in the serum antibody responses of alveolar echinococcosis patients after surgical treatment and chemotherapy as an aid to assessing the outcome.

Immunoglobulin G (IgG) subclass-specific antibody responses were evaluated for the follow-up of alveolar echinococcosis (AE) patients. Seventy-four sequentially collected sera from 25 Chinese and French AE cases who underwent surgery including hepatectomy, liver transplant and/or chemotherapy were analysed quantitatively and qualitatively during the clinical follow-up period. These AE patients were classified in 4 groups--cured, improved, stabilized, or aggravated. Serum antibody levels of the subclasses IgG1 and IgG4 were significantly higher in the AE patients than in healthy controls. IgG1 and IgG4 isotypes in AE patients were the most sensitive IgG antibody response in an enzyme-linked immunosorbent assay (ELISA) and in binding to antigens of 44kDa, 35kDa, 21kDa and 17.5kDa in an Echinococcus multilocularis protoscolex extract after Western blotting. In AE cases classed as cured or improved, IgG subclass antibody levels tended to decrease earlier than total IgG levels, especially IgG4 antibody levels which became negative within one year after successful treatment. IgG4 antibody levels also decreased in most of the improved cases. Increasing or unchanged levels of IgG4 and IgG1 antibodies were demonstrated in both stabilized and aggravated AE cases using both ELISA and immunoblot assays. Reappearance of specific IgG4 antibodies was a strong indication of recurrence, especially in liver transplant patients. Combined quantitative and qualitative assessment of IgG1 and IgG4 antibodies may be potentially useful for the serological follow-up of human AE.

Classification, follow-up and recurrence of hepatic cystic echinococcosis using ultrasound images.

Ultrasound image and morphological structure of hepatic cystic echinococcosis (CE) were analysed in 277 human cases (385 hepatic hydatid cysts). These included 65 CE cases from community surveys carried out between 1995 and 2000 in 3 countries (China, Mongolia and Jordan) and 212 cases from a clinical hospital survey from Xinjiang, China. A new simplified WHO ultrasound classification for human CE was assessed, and considered useful. It is proposed that type, size and number in particular need to be included in the ultrasound classification of hepatic CE. For comparative purposes 6 categories of type were classified in the study as Type 0 to Type 5 (T0-T5): T0, univesicular without pathognomonic signs; T1, univesicular with pathognomonic signs; T2, cysts with sagging or floating laminated membrane; T3, cysts containing daughter cysts; T4, solid mass or mixed cysts; and T5, cysts with partial or full calcifications. This differs from the WHO classification wherein Type T3 cysts (daughter cysts present) are considered a pathological stage to occur in general prior to the sagging or floating membrane (T2) stage. Recurrent hydatid cysts in the liver were also studied based on morphological structures observed directly from surgical intervention. Case follow-up over 1-5 years since endocystectomy in the community surveys indicated 10% (2/10) recurrence of cysts in the residual surgical cavity. Recurrent CE included 2 (2/4) cases after percutaneous treatment.

Cystic echinococcosis in semi-nomadic pastoral communities in north-west China.

In order to determine the prevalence of human cystic echinococcosis (CE) in semi-nomadic traditional pastoralist groups in north-west China, 2 large community studies were undertaken in Altai and Tacheng Prefectures in 1990/91 and 1995/96, respectively. The Kekergash community (Altai) comprised mainly ethnic Kazakhs, whereas the Narenhebuke community (Tacheng) comprised mainly Mongolians. Populations were screened for CE by abdominal ultrasound scan (US) and serological tests. The total prevalence of confirmed human CE was higher in Narenhebuke (2.7%, 49/1844) than in Kekergash (0.9%, 17/1861; P < 0.01). Within each community there was no significant difference of CE prevalence between the Kazakh and Mongolian groups, although Han Chinese exhibited twice the rate of CE (4.9%) in Narenhebuke compared to the dominant Mongolian population. For each community, human CE prevalence increased with age and there was a greater risk associated with the practice of home slaughter of livestock. Dogs were screened for Echinococcus granulosus infection and re-infection levels using a highly specific coproantigen test. The proportion of dogs with positive coproantigen tests was significantly higher in Narenhebuke (36.0%, 50/139) compared to Kekergash (17.8%, 16/90). In Narenhebuke the re-infection levels of dogs, as determined by coproantigen positivity, were higher in the winter quarters (49.4%, 39/79) compared to the summer quarters (18.3%, 11/60; P < 0.01). Furthermore, coproantigen re-test positivity was 25% at 3 months and 29.2% at 7 months. Highest dog coproantigen positivity was obtained over the winter period.

An epidemiological and ecological study of human alveolar echinococcosis transmission in south Gansu, China.

Human alveolar echinococcosis (AE) is usually a rare, highly pathogenic zoonotic disease, transmitted across the northern hemisphere between fox and rodent hosts. In China the first cases were described in 1965; however very few epidemiological studies have been undertaken since. Following identification in 1991 of a serious focus of human AE in south Gansu province, detailed village-based community and ecological studies were carried out between 1994 and 1997. Hepatic ultrasound mass screening with serological testing (five tests) identified 84/2482 new AE cases (3%). An overall prevalence of 4.1% (135/3331) was recorded for the area when previous cases were also included. Based on a seropositive result only, without an ultrasound scan indication, no additional AE cases were identified. Of the evolutive AE cases, 96% were seropositive in at least one test, while up 15-20% of individuals who exhibited hepatic calcified lesions and 12-15% exhibiting hepatic nodular lesions were seropositive for specific Em2 or Em18 antibodies. Village (n=31) human AE prevalence rates varied from 0 to 15.8%. Questionnaire analysis indicated that total number of dogs owned over a period was a risk factor (P<0.006), but not a history of red fox hunting (P>0.6). Rodent ecology studies revealed an association between density indices of voles (Microtus limnophilus) and village AE prevalence rates, on the one hand, and village landscape characterised by a ratio of scrub/grassland to total area above 50% (P<0.005). Long-term transmission of Echinococcus multilocularis and risk of zoonotic infection of south Gansu farmers may be related ultimately to a process of deforestation driven by agriculture. This in turn probably results in creation of optimal peri-domestic habitats for rodents that serve as intermediate host species (such as M. limnophilus) and subsequent development of a peri-domestic cycle involving dogs.