S. Harraga

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.

Interactions between landscape changes and host communities can regulate Echinococcus multilocularis transmission

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. Lidickers 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.

Resistance/susceptibility to Echinococcus multilocularis infection and cytokine profile in humans. I. Comparison of patients with progressive and abortive lesions

To clarify the role of Th1‐ and Th2‐type cytokines in the various outcomes of human alveolar echinococcosis (AE), the cytokine immune response of self‐cured patients was studied and compared with those of progressive AE patients and healthy subjects. Self‐cured patients were divided into two groups according to the following clinical features: subjects who had positive Echinococcus multilocularis serologies and hepatic calcifications typical of AE were classified as ‘abortive AE’ patients, and those who had positive E. multilocularis serologies but no hepatic lesions or calcifications detectable by ultrasonography were classified as ‘positive serology’ subjects. Secretions of IL‐5, IL‐10 and interferon‐gamma, and expression of IL‐5 mRNA were evaluated in peripheral blood mononuclear cells (PBMC) stimulated in vitro with the mitogen phytohaemagglutinin‐C or specific E. multilocularis antigenic preparations. The cytokine profile of abortive AE patients was the opposite of that observed in progressive AE patients. An intermediate profile was observed in positive serology subjects. PBMC from abortive AE patients, whether non‐stimulated or stimulated with PHA and antigenic preparations, secreted significantly lower levels of IL‐10 than those isolated from progressive AE patients. Our observations seem to confirm the regulatory role of IL‐10 in the immunopathology of human AE.

IFNα-2a protects mice against a helminth infection of the liver and modulates immune responses

Abstract 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 hosts 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)α. Methods: The effects of recombinant IFNα-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 IFNα-2a-treated mice had no hepatic lesions and half were fully protected. IFNα-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, IFNα-2a may be effective in a helminthic liver infection and is a promising candidate for clinical application in AE.

Intestinal and systemic humoral immunological events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs

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.