(1/212) Vaccination with cathepsin L proteinases and with leucine aminopeptidase induces high levels of protection against fascioliasis in sheep.
The potential of different parasite proteinases for use as vaccine candidates against fascioliasis in sheep was studied by vaccinating animals with the cathepsin L proteinases CL1 and CL2 and with leucine aminopeptidase (LAP) purified from adult flukes. In the first trial, sheep were immunized with CL1 or CL2 and the mean protection levels obtained were 33 and 34%, respectively. Furthermore, a significant reduction in egg output was observed in sheep vaccinated either with CL1 (71%) or with CL2 (81%). The second trial was performed to determine the protective potential of the two cathepsin L proteinases assayed together, as well as in combination with LAP, and of LAP alone. The combination of CL1 and CL2 induced higher levels of protection (60%) than those produced when these enzymes were administered separately. Those sheep that received the cocktail vaccine including CL1, CL2, and LAP were significantly protected (78%) against metacercarial challenge, but vaccination with LAP alone elicited the highest level of protection (89%). All vaccine preparations induced high immunoglobulin G titers which were boosted after the challenge infection, but no correlations between antibody titers and worm burdens were found. However, the sera of those animals vaccinated with LAP contained LAP-neutralizing antibodies. Reduced liver damage, as assessed by the level of the liver enzyme gamma-glutamyl transferase, was observed in the groups vaccinated with CL1, CL2, and LAP or with LAP alone. (+info)
(2/212) Induced expression of CYP2A5 in inflamed trematode-infested mouse liver.
Trematode infections have long been associated with specific types of cancer. We investigated the ability of the liver fluke Fasciola hepatica to alter host enzymes in a manner that might provide insight into the phenomenon of biologically associated cancers. Our data demonstrate an increased activity of the CYP2A5 isozyme in male mouse liver infected with F.hepatica. Induction of this enzyme was further assessed immunohistochemically. The infection affected CYP2A5 distribution in hepatic tissue. Inflammation and proliferation in liver tissue were observed at the same time that CYP2A5 activity increased. This enzyme is known to participate in the metabolism of several carcinogens which are common contaminants in environments of developing countries where parasitic infections may be prevalent. (+info)
(3/212) Epidemiology of human fascioliasis: a review and proposed new classification.
The epidemiological picture of human fascioliasis has changed in recent years. The number of reports of humans infected with Fasciola hepatica has increased significantly since 1980 and several geographical areas have been described as endemic for the disease in humans, with prevalence and intensity ranging from low to very high. High prevalence of fascioliasis in humans does not necessarily occur in areas where fascioliasis is a major veterinary problem. Human fascioliasis can no longer be considered merely as a secondary zoonotic disease but must be considered to be an important human parasitic disease. Accordingly, we present in this article a proposed new classification for the epidemiology of human fascioliasis. The following situations are distinguished: imported cases; autochthonous, isolated, nonconstant cases; hypo-, meso-, hyper-, and holoendemics; epidemics in areas where fascioliasis is endemic in animals but not humans; and epidemics in human endemic areas. (+info)
(4/212) Short report: Diagnosis of human fascioliasis: detection of anti-cathepsin L antibodies in blood samples collected on filter paper.
We have developed an ELISA for the diagnosis of human fascioliasis based on the detection of IgG4 antibodies to Fasciola hepatica cathepsin LI cysteine protease. Use of this assay in the Bolivian Altiplano, a region with a high prevalence of the disease, was hampered by the reluctance of the indigenous population to provide blood. To overcome this problem, we have investigated the method of collecting small quantities of blood from the finger onto filter paper, followed by the elution of antibodies for use in the diagnostic assay. Serum samples and blood samples collected onto filter paper were obtained from 57 individuals living in the village of Cutusuma in 1987 and from 11 individuals in Chijipata in 1996. Analysis of the IgG4-ELISA results revealed that there is highly significant linear relationship (P < 0.001) between the two methods of sampling. Most importantly, a reliable diagnosis was made with the blood-filter samples from Cutusuma, which had been stored for 10 years at 40 degrees C. While some deterioration of the blood-filter samples from Cutusuma had occurred over the 10-year storage period, no deterioration occurred with the Chijipata samples, which were stored for one year. Therefore, the method of collecting blood onto filter paper should prove useful for large-scale epidemiologic studies on human fascioliasis in the Bolivian Altiplano and in other regions where this disease is prevalent. (+info)
(5/212) Short report: Immunodiagnosis of human fascioliasis using recombinant Fasciola hepatica cathepsin L1 cysteine proteinase.
Our laboratory recently developed a diagnostic test (ELISA) for human fascioliasis based on the detection of serum IgG4 antibodies reactive with Fasciola hepatica cathepsin L1 (CL1). In the present study, we have used recombinant CL1, generated by functional expression of the cDNA in Saccharomyces cerevisiae, in this immunodiagnostic test and compared its performance with native CL1. Sera obtained from 64 individuals living in Cutusuma village in the northern Altiplano of Bolivia, a region with a high prevalence of human fascioliasis, were analyzed by the IgG4-ELISA. A highly statistically significant correlation (r2 = 0.751, P < 0.001) was demonstrated between the absorbances obtained using the recombinant and native proteins. These assays showed that 38 (59%) of the individuals tested were seropositive for fascioliasis, whereas only 26 of them were coprologically positive for F. hepatica eggs. All seronegative patients were also coprologically negative. Serum from individuals infected with schistosomiasis mansoni, cysticercosis, hydatidosis, and Chagas disease did not contain antibodies reactive with the recombinant or native CL1. Therefore, recombinant CL1 shows excellent potential for the development of the first standardized assay for the sensitive and specific diagnosis of human fascioliasis. Finally, our data supports earlier reports on the high prevalence of human fascioliasis in the Bolivian Altiplano, which collectively suggest that the disease has been endemic there for more than a decade. (+info)
(6/212) Identification of circulating antibodies in fasciolosis and localization of 66 kDa antigenic target using monoclonal antibodies.
We identified three specific circulating antibodies in serum of cattle naturally infected with Fasciola gigantica. Two of the antibodies were found to react specifically to 97 and 66 kDa antigenic molecules of adult worm tegumental membrane extract. The third antibody was identified by the reaction with 26-28 kDa molecule of the excretory/secretory antigens. Monoclonal antibody against 66 kDa protein was developed and used for localization of its antigenic target in adult worm frozen sections. The experiment demonstrated that 66 kDa protein is a component on the outer surface membrane and on the membrane lining of the caecal epithelial of adult worm. The 66 kDa antigen was considered as a promising candidate for immunodiagnosis and vaccine. (+info)
(7/212) The Northern Bolivian Altiplano: a region highly endemic for human fascioliasis.
The worldwide importance of human infection by Fasciola hepatica has been recognized in recent years. The endemic region between Lake Titicaca and the valley of La Paz, Bolivia, at 3800-4100 m altitude, presents the highest prevalences and intensities recorded. Large geographical studies involving Lymnaea truncatula snails (malacological, physico-chemical, and botanic studies of 59, 28 and 30 water bodies, respectively, inhabited by lymnaeids; environmental mean temperature studies covering a 40-year period), livestock (5491 cattle) and human coprological surveys (2723 subjects, 2521 of whom were school children) were conducted during 1991-97 to establish the boundaries and distributional characteristics of this endemic Northern Altiplano region. The endemic area covers part of the Los Andes, Ingavi, Omasuyos and Murillo provinces of the La Paz Department. The human endemic zone is stable, isolated and apparently fixed in its present outline, the boundaries being marked by geographical, climatic and soil-water chemical characteristics. The parasite distribution is irregular in the endemic area, the transmission foci being patchily distributed and linked to the presence of appropriate water bodies. Prevalences in school children are related to snail population distribution and extent. Altiplanic lymnaeids mainly inhabit permanent water bodies, which enables parasite transmission during the whole year. A confluence of several factors mitigates the negative effects of the high altitude. (+info)
(8/212) Fasciola gigantica-specific antigens: purification by a continuous-elution method and its evaluation for the diagnosis of human fascioliasis.
Immunodominant antigens of an approximate molecular mass of 27 kD were obtained from an excretory-secretory product of adult Fasciola gigantica by a continuous-elution method. An indirect ELISA using the antigens obtained by this relatively simple procedure was developed for detecting specific antibodies from patients infected with F. gigantica. Sera from patients with other parasitic infections, healthy volunteers, and cholangiocarcinoma were also analyzed. The sensitivity, specificity, and positive and negative predictive values for this ELISA using the fractionated antigens were 100%. The data indicated a possible correlation of antibodies to F. gigantica with cholangiocarcinoma. (+info)