Improved serodiagnosis of alveolar echinococcosis of humans using an<i>in vitro</i>-produced<i>Echinococcus multilocularis</i>antigen

Müller, Norbert; Frei, Elisabeth; Nuñez, S.M.; Gottstein, Bruno

doi:10.1017/s0031182006002083

Cited by 42 publications

(40 citation statements)

References 34 publications

(85 reference statements)

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“…For preparation of E. multilocularis vesicular fluid, metacestode tissue was cultivated in vitro, resulting in the formation of metacestode vesicles, as described by Müller and colleagues [23]. Fertile E. granulosus cysts were collected from sheep in Kyrgyzstan.…”

Section: Parasite Isolatesmentioning

confidence: 99%

Serological diagnosis of echinococcosis: the diagnostic potential of native antigens

et al. 2011

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PURPOSE: Human alveolar (AE) and cystic echinococcosis (CE) caused by the metacestode stages of Echinococcus multilocularis and E. granulosus, respectively, lack pathognomonic clinical signs. Diagnosis therefore relies on the results of imaging and serological studies. The primary goal of this study was to evaluate the efficacy of several easy-to-produce crude or partially purified E. granulosus and E. multilocularis metacestode-derived antigens as tools for the serological diagnosis and differential diagnosis of patients suspicious for AE or CE. METHODS: The sera of 51 treatment-naïve AE and 32 CE patients, 98 Swiss blood donors and 38 patients who were initially suspicious for echinococcosis but suffering from various other liver diseases (e.g., liver neoplasia, etc.) were analysed. RESULTS: According to the results of enzyme-linked immunosorbent assays (ELISA), metacestode-derived antigens of E. granulosus had sensitivities varying from 81 to 97% and >99.9% for the diagnosis of CE and AE, respectively. Antigens derived from E. multilocularis metacestodes had sensitivities ranging from 84 to 91% and >99.9% for the diagnosis of CE and AE, respectively. Specificities ranged from 92 to >99.9%. Post-test probabilities for the differential diagnosis of AE from liver neoplasias, CE from cystic liver lesions, and screening for AE in Switzerland were around 95, 86 and 2.2%, respectively. Cross-reactions with antibodies in sera of patients with other parasitic affections (fasciolosis, schistosomosis, amebosis, cysticercosis, and filarioses) did occur at variable frequencies, but could be eliminated through the use of confirmatory testing. CONCLUSIONS: Different metacestode-derived antigens of E. granulosus and E. multilocularis are valuable, widely accessible, and cost-efficient tools for the serological diagnosis of echinococcosis. However, confirmatory testing is necessary, due to the lack of species specificity and the occurrence of cross-reactions to other helminthic diseases. Abstract Purpose Human alveolar (AE) and cystic echinococcosis (CE) caused by the metacestode stages of Echinococcus multilocularis and E. granulosus, respectively, lack pathognomonic clinical signs. Diagnosis therefore relies on the results of imaging and serological studies. The primary goal of this study was to evaluate the efficacy of several easy-to-produce crude or partially purified E. granulosus and E. multilocularis metacestode-derived antigens as tools for the serological diagnosis and differential diagnosis of patients suspicious for AE or CE. Methods The sera of 51 treatment-naïve AE and 32 CE patients, 98 Swiss blood donors and 38 patients who were initially suspicious for echinococcosis but suffering from various other liver diseases (e.g., liver neoplasia, etc.) were analysed. Results According to the results of enzyme-linked immunosorbent assays (ELISA), metacestode-derived antigens of E. granulosus had sensitivities varying from 81 to 97% and [99.9% for the diagnosis of CE and AE, respectively. Antigens derived from...

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Section: Parasite Isolatesmentioning

confidence: 99%

Serological diagnosis of echinococcosis: the diagnostic potential of native antigens

et al. 2011

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“…When the antigenic properties of EmHF cultured in vitro were investigated, some contradictions were observed. There was low antigenicity of EmHF obtained from the in vitro culture, and there was no reaction for low-molecular-mass proteins of Ͻ15 kDa (27). In contrast, an immunoblotting study revealed relatively strong antibody responses to Ͻ20-kDa proteins, although whether or not EmAgB3 was in those fractions was not determined (29).…”

Section: Discussionmentioning

confidence: 86%

“…Antibody responses became stronger over time. Several proteins, including those corresponding to molecular masses of 21 and 23 kDa, which showed prominent reactions (27) exhibited antibody responses 3 months postinfection. However, these proteins were cross-reactive with CE sera (Fig.…”

Section: Clinical Characteristics Of Ae Casesmentioning

confidence: 99%

An Echinococcus multilocularis Antigen B3 Proteoform That Shows Specific Antibody Responses to Active-Stage Alveolar Echinococcosis

et al. 2015

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e Alveolar echinococcosis (AE), caused by the Echinococcus multilocularis metacestode, represents one of the most frequently fatal zoonoses. Early diagnosis significantly reduces morbidity and mortality associated with AE. Diagnosis of AE largely depends on a combination of imaging and serological tests due to its minimal clinical manifestations. Several antigens derived from the whole worm and protoscolex have been targeted for AE serodiagnosis, while the antigenic properties of E. multilocularis hydatid fluid (EmHF) are unclear. We observed two AE-specific 6-and 8-kDa antigen proteoforms through an immunoproteome array of the EmHF. We identified these proteins as representing an E. multilocularis antigen B3 (EmAgB3) isoform, and the proteins were shown to be encoded by the same gene. We cloned the gene and expressed the recombinant EmAgB3 protein (rEmAgB3) in Escherichia coli. rEmAgB3 exhibited sensitivity of 90.9% (80/88 cases) and specificity of 98.5% (597/606 samples) by immunoblotting. The positive and negative predictive values were 89.9% and 98.6%, respectively. The protein did not show antibody responses to 33 AE sera collected during posttreatment follow-up monitoring. Mouse sera experimentally infected with AE protoscoleces began to demonstrate specific antibody responses to native and recombinant EmAgB3 6 months after infection. At that stage, fully mature metacestode vesicles that harbored the brood capsule, primary cell, and protoscolex were observed within an AE mass(es). The response declined along with worm degeneration. Our results demonstrate that the immune responses to this EmAgB3 isoform were highly correlated with worm viability accompanied with AE progression. rEmAgB3 is a promising biomarker for serological assessment of AE patients.A lveolar echinococcosis (AE), an infection caused by Echinococcus multilocularis metacestodes, is one of the most frequently chronic and fatal zoonoses (1-3). Epidemiological evidence has demonstrated that 0.5 to 6 of 100,000 inhabitants are infected in areas of endemicity of Europe and Central Asia (4, 5). In the Tibetan and Qinghai plateaus in China, the population at risk of infection is estimated to encompass 60 million (6).Two kinds of hosts are intimately involved in the life cycle of E. multilocularis. Domestic and wild canids (definitive hosts) harbor the adult tapeworm in their intestines. The worms produce numerous eggs, which pass out of the host with gravid segments. When wild rodents and humans (intermediate hosts) take in the eggs, oncospheres are activated in the small intestine; they then penetrate the intestinal wall and enter the circulation. They primarily lodge in the liver and grow slowly into multivesiculated metacestode vesicles, in which brood capsules, primary cells, and protoscoleces develop, resulting in AE (1, 7). AE usually presents with a complex of nonspecific liver manifestations that mimic cystadenoma, hepatocellular carcinoma, and liver cirrhosis (8, 9).Diagnosis of AE largely depends on a combination of imaging and serologi...

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“…Western Blot assays are already used for diagnostic investigations in other parasitic diseases like echinococcosis and cysticercosis in humans (Gekeler et al 2002;Muller et al 2007) or infections in cattle with Neospora caninum and Besnoitia besnoiti (Cortes et al 2006). For serological testing in humans for Trichinella spp., commercialized Western Blot assays are routinely used as a confirmatory test to distinguish between patients with Trichinella infections and other helminth infections (Robert et al 1996;Kociecka 2000;Yera et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Validation of a Western Blot for the detection of anti-Trichinella spp. antibodies in domestic pigs

et al. 2009

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Trichinellosis is a zoonotic disease in humans caused by Trichinella spp. According to international regulations and guidelines, serological surveillance can be used to demonstrate the absence of Trichinella spp. in a defined domestic pig population. Most enzyme-linked immunosorbent assay (ELISA) tests presently available do not yield 100% specificity, and therefore, a complementary test is needed to confirm the diagnosis of any initial ELISA seropositivity. The goal of the present study was to evaluate the sensitivity and specificity of a Western Blot assay based on somatic Trichinella spiralis muscle stage (L1) antigen using Bayesian modeling techniques. A total of 295 meat juice and serum samples from pigs negative for Trichinella larvae by artificial digestion, including 74 potentially cross-reactive sera of pigs with other nematode infections, and 93 meat juice samples from pigs infected with Trichinella larvae were included in the study. The diagnostic sensitivity and specificity of the Western Blot were ranged from 95.8% to 96.0% and from 99.5% to 99.6%, respectively. A sensitivity analysis showed that the model outcomes were hardly influenced by changes in the prior distributions, providing a high confidence in the outcomes of the models. This validation study demonstrated that the Western Blot is a suitable method to confirm samples that reacted positively in an initial ELISA.

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Improved serodiagnosis of alveolar echinococcosis of humans using anin vitro-producedEchinococcus multilocularisantigen

Cited by 42 publications

References 34 publications

Serological diagnosis of echinococcosis: the diagnostic potential of native antigens

Serological diagnosis of echinococcosis: the diagnostic potential of native antigens

An Echinococcus multilocularis Antigen B3 Proteoform That Shows Specific Antibody Responses to Active-Stage Alveolar Echinococcosis

Validation of a Western Blot for the detection of anti-Trichinella spp. antibodies in domestic pigs

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