Resistance to treatment with Tamiflu (oseltamivir) and similar drugs in people who have the H7N9 flu virus has now been confirmed, according to new research published in The Lancet.
Described as one of the most detailed virological studies of the H7N9 virus to date, the study was led by Dr Zhenghong Yuang of the Shanghai Public Health Clinical Centre and School of Basic Medical Sciences, Shanghai Medical College of Fudan University, China, and Dr Malik Peiris, of the University of Hong Kong, China.
The investigators examined 14 patients who were treated at Shanghai Public Health Clinical Center with confirmed H7N9 infection in April. They calculated their viral load – the quantity of virus in their body as a sign of virus severity – throughout the path of their infection and treatment.
After the expected course of H7N9 infection, all patients contracted pneumonia. Seven of them needed mechanical ventilation, while three later became so critically ill that they needed extracorporeal membrane oxygenation (ECMO) – a procedure that gives oxygen to the blood from outside the body when the lungs cannot do their job.
Two of these patients died, while the third was still reliant on ECMO to survive at the time the paper went to press.
By examining the patients’ viral loads, the investigators revealed that for the majority of patients, treatment with a class of antiviral known as neuraminidase inhibitors – this includes Tamiflu and is the only treatment option available currently for H7N9 – caused a decrease in the viral load found on throat swabs and was linked to clinical recovery.
For the three patients who became extremely sick, antiviral treatment did not decrease their viral load, hence the researchers believe that the H7N9 virus had become resistant to the antiviral drugs in these cases.
This was verified by genetic testing of the viruses taken from the patients, where the investigators found a genetic mutation characteristic of resistance to neuraminidase inhibitors. This mutation has been seen in one other virus strain in an earlier study of H7N9, however, its clinical relevance is questionable.
The current paper includes the first research to associate clinical cases of resistance to neuraminidase inhibitors with this genetic mutation in the H7N9 virus to negative clinical outcome.
After examining the viral load in all patients, the investigators found traces of viral RNA in all areas in some patients. While the viral RNA found is not necessarily infectious, they authors say that further studies are required to determine whether H7N9 is able to spread beyond the respiratory tract.
The authors reiterate that early intervention with antivirals provides the best treatment currently possible. However they add:
“The apparent ease with which antiviral resistance emerges in A/H7N9 viruses is concerning; it needs to be closely monitored and considered in future pandemic response plans.”
Earlier this month, it was reported that the H7N9 virus may be human transmissible. But it has not been shown compellingly yet to be human transmissible, the experts noted.
A new vaccine is currently being developed for H7N9 that will protect against multiple strains of the disease, according to the World Health Organization.
MIT scientists reported in the journal Cell (June 2013) that the H5N1 and H7N9 bird flu virus strains need just one or a few genetic changes to become easily human transmissible, which would raise the likelihood of there being a flu pandemic.
Written by Kelly Fitzgerald