Pseudomonas aeruginosa serological analysis in young children with cystic fibrosis diagnosed through newborn screening.
BACKGROUND
With newborn screening (NBS) for cystic fibrosis (CF), eradication of Pseudomonas aeruginosa (PA) is possible if PA detection occurs early. A serological response to infection likely precedes culture positivity in CF patients, so PA serological testing is very appealing in this population. However, controversies continue to exist about serology testing, titer cutoffs for enzyme-linked immunosorbent assay (ELISA) antibody tests, and their value in children with CF.


METHODS
This longitudinal, prospective study collected respiratory secretions as oropharyngeal swabs or expectorated sputum for culture and also sera over 6 years in 69 patients diagnosed by NBS. Serology assessed PA antibody titers against cell lysate, exotoxin A, and elastase. A novel statistical approach with weighted receiver operating characteristic (ROC) curves was used to determine best antibody titer cutoff values to predict subsequent PA positive cultures.


RESULTS
Using these weighted ROC curves, the order of sensitivity was found to be cell lysate, exotoxin A, and then elastase while age-specific cutoffs were better than fixed cutoffs previously used. Age-specific serological cutoffs both predict and detect PA respiratory infections with a higher sensitivity and specificity. Serological responses to the PA antigens determined that a response to cell lysate occurs significantly earlier than culture positivity.


CONCLUSIONS
Age-specific serological cutoffs rather than fixed values against common PA antigens improve early PA identification in infants and young children diagnosed with NBS. Regular serological assessment with age-specific cutoffs in these children appears to be a worthy diagnostic tool.
Hayes
D
D
Department of Pediatrics and Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Farrell
P M
PM
Li
Z
Z
West
S E
SE
D036002:ADP Ribose Transferases / Q000276:immunology; D000367:Age Factors; D001427:Bacterial Toxins / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications* / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005098:Exotoxins / Q000276:immunology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D015997:Neonatal Screening / Q000379:methods*; D010196:Pancreatic Elastase / Q000276:immunology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000150:complications / Q000175:diagnosis* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D037521:Virulence Factors / Q000276:immunology; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D007136:Immunoglobulins; D010196:Pancreatic Elastase; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A