Cystic fibrosis (CF) is an autosomal recessive disorder that affects 1 in 100,000 to 200,000 live births. CF results from mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). More than 350 different point mutations in the gene are described (638). These different mutations produce a disease spectrum ranging from malnutrition, chronic bronchitis, asthma, and infertility to fatal pulmonary disease. CFTR is the receptor for S. typhi and it is conceivable that heterozygosity of the CFTR allele is selected for in certain populations because it protects against the development of typhoid (639).

CF patients develop a well-defined epithelial abnormality because the mutant protein fails to perform its normal function. The CFTR mutation results in a chloride transport defect with relative chloride impermeability in ductal epithelium and inhibited sodium chloride reabsorption resulting in hypertonic secretions. When secretion falls below a critical minimum, thick mucus develops, blocking the ducts and leading to glandular swelling, cystic degeneration, and atrophy (640). The small intestinal mucosa shows a relatively high expression level of CFTR mRNA with a decreasing gradient of expression along the crypt-to-tip axis. Cells in Brunner glands also express high CFTR levels.