PubMed · 8871399
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S Howell, P Crine. 1996. Type VI membrane proteins?. https://pubmed.ncbi.nlm.nih.gov/8871399/
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Neurocysticercosis, caused by infection with larval Taenia solium, is a major cause of epilepsy worldwide. Larval degeneration, which is symptomatic, results in inflammatory cell influx. Astrocytes, the most abundant cell type and major cytokine-producing cell within the CNS, may be important in orchestrating inflammatory responses after larval degeneration. We investigated the effects of direct stimulation and of conditioned medium from T. solium larval Ag (TsAg)-stimulated monocytes (CoMTsAg) on neutrophil and astrocyte chemokine release. CoMTsAg, but not control conditioned medium, stimulated astrocyte CCL2/MCP-1 (161.5 +/- 16 ng/ml), CXCL8/IL-8 (416 +/- 6.2 ng/ml), and CXCL10/IFN-gamma-inducible protein (9.07 +/- 0.6 ng/ml) secretion after 24 h, whereas direct astrocyte or neutrophil stimulation with TsAg had no effect. There was rapid accumulation of CCL2 and CXCL8 mRNA within 1 h, with somewhat delayed expression of CXCL10 mRNA initially detected 8 h poststimulation. Neutralizing anti-TNF-alpha inhibited CoMTsAg-induced CCL2 mRNA accumulation by up to 99%, causing total abolition of CXCL10 and up to 77% reduction in CXCL8 mRNA. CoMTsAg induced maximal nuclear binding of NF-kappaB p65 and p50 by 1 h, with IkappaBalpha and IkappaBbeta decay within 15 min. In addition, CoMTsAg induced transient nuclear binding of AP-1, which peaked 4 h poststimulation. In NF-kappaB blocking experiments using pyrrolidine dithiocarbamate, CoMTsAg-induced CCL2 secretion was reduced by up to 80% (p = 0.0006), whereas CXCL8 was inhibited by up to 75% (p = 0.0003). In summary, the data show that astrocytes are an important source of chemokines following larval Ag stimulation. Such chemokine secretion is NF-kappaB dependent, likely to involve AP-1, and is regulated in a paracrine loop by monocyte-derived TNF-alpha.
Fasciola hepatica has recently emerged as a major pathogen of humans from reports on areas of endemicity and hyper-endemicity for fascioliasis. This situation is aggravated by the lack of standard assays for the screen diagnosis of F. hepatica infection in humans living in endemic areas. Our laboratory has developed an enzyme-linked immunosorbent assay (Fas2-ELISA) based on the capture of IgG antibody by a purified protein Fas2, which is an adult fluke cysteine proteinase. Fas2-ELISA exhibited 95% sensitivity and 100% specificity in 38 individuals infected with F. hepatica diagnosed by finding eggs in stools and 46 serum samples from healthy volunteers. No cross-reaction was observed with 54 serum samples from patients with ten different parasitic infections including the trematodes Paragonimus westermani and Schistosoma mansoni. The high antigenicity of Fas2 is suggested by the fact that antibodies to Fas2 rise rapidly by 1-2 weeks of infection and rise until patency at 8 weeks of infection in experimentally infected alpacas. Field screening for human fascioliasis using Fas2-ELISA and coprology in three endemic locations of the Peruvian Andes resulted in 95.5% sensitivity, 86.6% specificity in a population of 664 children in an age range of 1 to 16 years old. These results provide evidence of the clinical potential of Fas2-ELISA to diagnose fascioliasis in humans exposed to liver fluke infection in endemic areas for this parasite. Fas2-ELISA is currently developed as a standard assay for both field screening for fascioliasis in people living in endemic areas and detecting occasionally F. hepatica infected patients in clinical laboratories.
BACKGROUND & OBJECTIVE: Although human paragonimiasis is known to occur in Manipur and Arunachal Pradesh, there is no indigenous immunodiagnostic test available in India. Sputum examination for detection of eggs is less sensitive method for diagnosis of paragonimiasis and unfortunately, the eggs are not always present in the sputum of infected individuals. Due to overlapping clinical manifestations and similarities between X-ray picture in pulmonary paragonimiasis and pulmonary tuberculosis, chances of diagnostic confusion can increase. Therefore, the objective of this study was to develop an ELISA test indigenously for diagnosis of paragonimiasis. METHODS: Somatic (S) and excretory-secretory (ES) antigens of adult trematodes belonging to genus Paragonimus were prepared. Serum samples were collected from 22 confirmed patients of paragonimiasis and from five groups of negative controls. The cut-off points for both types of antigens were calculated using receiver operating characteristic (ROC) curve analysis. The sensitivity, specificity, predictive values and efficiency of the ELISA tests were also calculated. RESULTS: IgG-ELISA test using either S or ES antigens were 100 per cent sensitive yet the utility of S antigen for diagnosis of paragonimiasis seemed to be less reliable because of low specificity (91.3%). On the other hand, ES antigen was more reliable with 100 per cent specificity as no false positive cases were recorded. INTERPRETATION & CONCLUSION: ES antigen can be effectively used for screening large populations for paragonimiasis. In areas where both paragonimiasis and tuberculosis are endemic, suspected subjects should be screened for both the diseases because of chance of mistaken diagnosis. Correct diagnosis will avoid unnecessary costly treatment.