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UBC Theses and Dissertations

An evaluation of cystic fibrosis screening programmes for implementation in British Columbia Scriabin, Jannie Martine


Four methods were investigated to determine their suitability for use in a CF screening programme for the province of British Columbia. A fecal trypsin method which measured trypsin activity by incubating dry stool samples on filter paper cards with the substrate p-tosyl-arginine methyl ester (TAME) and a pH sensitive dye was shown to be non-specific and therefore unsatisfactory. An attempt to combine a fecal albumin screen with a more specific quantitative immunodiffusion technique for albumin and alpha-1 antitrypsin was unsuccessful. A meconium albumin assay using the Boehringer-Mannheim Corporation (BMC) test-strip and a more specific fecal trypsin assay which uses the substrate benzoyl-arginine-p-nitroanilide (BAPNA) were incorporated into two pilot projects at Children's Hospital in Vancouver. The BMC test-strip was simple to use, reliable and inexpensive. Of 8,891 infants tested, 3 positives were diagnosed as suffering from cystic fibrosis and 1 CF patient tested negative. False positives were obtained on 1.3% of infants. The incidence of CF as determined by this screen was 1 in 2000. The meconium albumin screen was satisfactory as a local pilot project but the disadvantages of testing the unstable meconium specimens make the screen unsuitable for a province-wide application. The BAPNA fecal trypsin method devised by Crossley was used to test 4085 dry stool specimens collected in the hospital and at home. Out of a total number of 190 positive results, none was diagnosed as having CF, giving a false positive rate of 5.0% for the hospital collected specimens and 3.4% for the specimens collected at home. The false positive rate in the hospital collected specimens was due mostly to the large proportion of young infants (under 3 days). The false positive rate of the home collected specimens appeared to be due mostly to the thinner spread of stool sample on the card. Because the quantity of stool sample per test was significantly lower in the home than the hospital collected specimens a new cut-off point for the home collected specimens was considered. Its application/ however did not lower the false positive rate sufficiently. As a result, the high incidence of false positives and the difficulties encountered as a result of this incidence also makes the fecal trypsin screen unsuitable for the province of B.C. Difficulties encountered during the follow-up of positive results obtained in the two pilot projects are discussed and recommendations are made regarding the efficient and adequate implementation of a follow-up system.

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