Two Vietnamese patients who were stricken with avian influenza died after their viruses repelled Tamiflu, casting doubts on the reliability of a medication being stockpiled worldwide.
Dr. Menno de Jong of the Hospital for Tropical Diseases in Ho Chi Minh City reports in Thursday's New England Journal of Medicine that four of eight patients treated with Tamiflu died, and that two had strains of the H5N1 flu virus that resisted the drug entirely.
Tamiflu, whose generic name is oseltamivir, is a type of drug known as a neuraminidase inhibitor, which means it blocks an enzyme crucial to viral function. Resistance to Tamiflu had been reported in the recent past. Two Japanese studies found drug resistant viruses in children with seasonal influenza who had taken lower Tamiflu doses than those given in the United States. Doctors in Ho Chi Minh City had given their patients standard doses.
"In contrast," de Jong said of the Japanese studies, "the viruses in our patients were isolated during or shortly after a course of oseltamivir at therapeutic twice-daily doses."
But while standard doses were administered to the patients, two young girls were infected with viruses that were able to repel the medication, allowing the viruses to flourish. Vietnamese scientists dubbed the resistant strains 274Y and found they predominated in both cases.
Drug resistance is a major public health concern and has been most widely documented with antibiotics, some of which are now impotent against powerful bacterial strains. Resistance occurs with the misuse, overuse and abuse of germ-killing drugs. When the drugs are not taken long enough or in the proper dosages to kill the infecting agent, hardy survivors remain in the body and rapidly mutate, gaining the genetic capacity to repel the medication.
Resistance against an antiviral, such as Tamiflu, is a growing public health concern because the drug is one of only two that can be used against superstrains of flu. Tamiflu, the newest of the influenza antivirals often cited because it is effective, can be taken in pill form and is not difficult to stockpile. The other antiviral, Relenza, must be inhaled in a mist.
Writing in a New England Journal of Medicine commentary, Dr. Anne Moscona, of New York-Presbyterian Hospital/Weill Cornell Medical Center in Manhattan, noted that people who are developing personal Tamiflu stockpiles pose more harm than good. Should a pandemic occur, resistance could quickly surface among self-dosers.
"This problem was actually predicted several years ago when scientists found that aspects of the chemical structure of Tamiflu were different than the structure of Relenza," and thus could facilitate resistance, Moscona said.