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The use of Strongyloides ratti as heterologous antigen for serodiagnosis of strongyloidiasis is preferable to Strongyloides from humans due to the ease and safety of antigen preparation. In Southeast Asia where Opisthorchis viverrini coexists with Strongyloides stercoralis, there has been no report in using S. ratti for serodiagnosis of S. stercoralis. In this study, performance of an enzyme-linked immunosorbent assay (ELISA) based on S. ratti was compared with that based on S. stercoralis for diagnosis of strongyloidiasis in areas where O. viverrini is co-endemic in Thailand. Of the 107 individuals, 50 (46.7 %) were positive for S. stercoralis by agar culture method and by ELISA; 82 (76.6 %) and 81 (75.7 %) were seropositive using S. ratti and S. stercoralis antigens, respectively. The levels of parasite-specific IgG to S. ratti and S. stercoralis antigen were significantly proportionally correlated ( P < 0.001). Mixed infections with O. viverrini have little effect on diagnosis of strongyloidiasis. Of 42 subjects who were infected with other parasites, there were no cross-reaction with Angiostrongylus cantonensis, Taenia spp., hookworms, Paragonimus spp., Clonorchis sinensis, Ascaris lumbricoides except for Fasciola spp. (1 of 5), and Opisthorchis viverrini (5 of 20). In spite of cross-reactivities, the results suggest that the S. ratti antigen provides an useful option for diagnosis of strongyloidiasis in an endemic area of opisthorchiasis with high sensitivity comparable to the S. stercoralis antigen and provide a basis for effective control strategies for strongyloidiasis. [ABSTRACT FROM AUTHOR]

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and increasing risk of advanced fibrosis and bile duct cancer; for example, in age and sex adjusted analyses, individuals with the highest quartiles of plasma IL-6 had a 19 times greater risk of developing advanced periductal fibrosis and a 150 times greater risk of developing of bile duct cancer than individuals with no detectable level of plasma IL-6. Finally, we show that a single plasma IL-6 measurement has excellent positive predictive value for the detection of both advanced bile duct fibrosis and bile duct cancer in regions with high O. viverrini transmission. These data support our hypothesis that common mechanisms drive bile duct fibrosis and bile duct tumorogenesis from chronic O. viverrini infection. Our study also adds a unique aspect to the literature on circulating levels of IL-6 as an immune marker of hepatobiliary pathology by showing that high levels of circulating IL-6 in plasma are not related to infection with O. viverrini, but to the development of the advanced and often lethal pathologies resulting from chronic O. viverrini infection. Author Summary: O. viverrini is among the few parasites considered a Class 1 carcinogen because of its strong association with bile duct cancer (cholangiocarcinoma). Currently, more than 40 million people are infected with O. viverrini worldwide. Thailand has the highest prevalence of O. viverrini at 10 million people infected and also the highest incidence of Opisthorchis-associated bile duct cancer (cholangiocarcinoma) in the world. In the current study, we also show that levels of IL-6 in plasma are associated in a dose-dependent fashion with Opisthorchis-induced bile duct fibrosis (periductal fibrosis) and cholangiocarcinoma. More importantly, we show that O. viverrini infection alone does not elevate IL-6 levels in the plasma. It is only in the presence of these advanced pathologies (advanced fibrosis or cholangiocarcinoma) from chronic O. viverrini infection that significantly elevates plasma levels of IL-6 are observed. Moreover, we show that plasma IL-6 is an easily accessible biomarker for the detection of advanced periductal fibrosis and cholangiocarcinoma, which would be a critical advance for this region of Thailand and other countries in Southeast Asia, where the prevalence of O. viverrini infection can reach as high as 80% and the incidence of bile duct cancer is the highest in the world. [ABSTRACT FROM AUTHOR]

Abstract: Infection by Opisthorchis viverrini (liver fluke) is a major public health problem in southeastern Asia, resulting in hepatobiliary disease and cholangiocarcinoma. Fluke surface glycoconjugates are prominently presented to the host, thereby constituting a crucial immunological interface that can determine the parasite’s success in establishing infection. Therefore, N- and O-linked glycoprotein glycan profiles of the infective metacercarial stage and of the mature adult were investigated by nanospray ionisation-linear ion trap mass spectrometry (NSI-MS n ). Glycan immunogenicity was investigated by immunoblotting with serum from infected humans. Metacercariae and adult parasites exhibit similar glycan diversity, although the prevalence of individual glycans and glycan classes varies by stage. The N-glycans of the metacercaria are mostly high mannose and monofucosylated, truncated-type oligosaccharides (62.7%), with the remainder processed to complex and hybrid type glycans (37.3%). The N-linked glycan profile of the adult is also dominated by high mannose and monofucosylated, truncated-type oligosaccharides (80.0%), with a smaller contribution from complex and hybrid type glycans (20.0%). At both stages, complex and hybrid type glycans are detected as mono-, bi-, tri-, or tetra-antennary structures. In metacercariae and adults, O-linked glycans are detected as mono- to pentasaccharides. The mucin type core 1 structure, Galβ1–3GalNAc, predominates in both stages but is less prevalent in the adult than in the metacercaria. Immunogenic recognition of liver fluke glycoproteins is reduced after deglycosylation but infected human serum was unable to recognise glycans released from peptides. Therefore, the most potent liver fluke antigenic epitopes are mixed determinants, comprised of glycan and polypeptide elements. [Copyright &y& Elsevier]