MICROBIOLOGY AND IMMUNOLOGY ON-LINE |
From the National Institute of Allergy and Infectious Diseases
Resistance to Popular Flu Drug May Be Higher than
Thought
If you come down with the flu, in addition to the added bed rest and fluids,
your doctor will likely prescribe one of two possible medications: an M2 ion
channel blocker or a neuraminidase inhibitor. The former prevents the virus from
making copies of itself inside the cell, while the latter prevents new viruses
from breaking free to infect other cells.
One of the benefits of neuraminidase inhibitors, such as zanamivir (Relenza) and
oseltamivir (Tamiflu), is they work against both influenza A and B, whereas M2
inhibitors are only effective against influenza A. Also, the influenza virus
appears to be less prone to becoming resistant to neuraminidase inhibitors than
to M2 inhibitors.
"True," says NIAID-supported researcher Yoshihiro Kawaoka, D.V.M., Ph.D., on the
subject of resistance, "but perhaps not as much as we'd originally thought." Dr.
Kawaoka, a renowned virologist who holds professorships at the University of
Wisconsin, Madison, and the University of Tokyo, recently studied the frequency
with which the H3N2 influenza virus developed drug-resistant mutations in 50
Japanese children taking oseltamivir.
Analyzing the virus's gene sequences before and throughout treatment with
oseltamivir, the researchers found mutations had occurred on the neuraminidase
gene in nine, or 18 percent, of the children studied. All of the mutants were
resistant to the effects of oseltamivir. Earlier clinical trials had
demonstrated oseltamivir-resistant mutations in only 4 percent of children ages
1 to 12 and in less than 1 percent of adults. (Resistance to the M2-inhibiting
drugs amantadine and rimantadine are much higher, occurring in roughly 30
percent of patients who take those drugs. In another study, Dr. Kawaoka has
shown that drug-resistant strains appeared in 80 percent of children taking
amantadine.)
The researchers also found that some children who did not experience drug
resistance continued spreading the flu virus, even after five days of treatment.
Dr. Kawaoka notes that younger children, who were probably exposed to influenza
for the first or second time, developed more drug-resistant viruses than older
children, who most likely possessed some pre-existing immunity against other
strains. Because this scenario resembles that found during a flu pandemic, these
findings could provide helpful insight into the use of neuraminidase inhibitors
if a new pandemic should arise, he says.