EVIDENCE FOR ZANAMIVIR RESISTANCE IN AN IMMUNOCOMPROMISED CHILD INFECTED WITH INFLUENZA-B VIRUS

Zanamivir, a neuraminidase inhibitor, has shown promise as a drug to c ontrol influenza. During prolonged treatment with zanamivir, a mutant virus was isolated from an immunocompromised child infected with influ enza B virus. A hemagglutinin mutation (198 Thr-->Ile) reduced the vir us affinity for receptors found on susceptible human cells. A mutation in the neuraminidase active site (152 Arg-->Lys) led to a 1000-fold r eduction in the enzyme sensitivity to zanamivir. When tested in ferret s, the mutant virus had less virulence than the parent; however, it ha d a growth preference over the parent in zanamivir-treated animals. De spite these changes, the sensitivity of the mutant virus to zanamivir assessed by a standard test in MDCK cells was unaffected. These data i ndicate that the current methods for monitoring resistant mutants are potentially flawed because no tissue culture system adequately reflect s the receptor specificity of human respiratory tract epithelium.