Dr. Aeron Hurt, who works at the WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, Australia, explained that the H1N1 strain's ability to spread from human-to-human and develop oseltamivir (Tamiflu) resistance increases the risk of a public health emergency.
What is H1N1pdm09?The former seasonal H1N1 virus - in 2008, there was a H1N1 virus strain in circulation that developed resistance to Tamiflu. It spread globally and is known today as the 'former seasonal H1N1 virus'.
The H1N1pdm09 virus - a year later, in 2009, the "swine flu" pandemic occurred. It was caused by a different H1N1 strain, which is known as 'H1N1pdm09' (pdm stands for pandemic). When H1N1pdm09 emerged, the 'former seasonal H1N1 virus' became extinct. One of the good things H1N1pdm09 did was to destroy the previous Tamiflu-resistant virus that was in circulation.
Since 2009, levels of Tamiflu-resistant H1N1pdm09 have remained steady at between 1% and 2%. The only exception is in Newcastle, New South Wales, Australia, where the percentage of resistant strains exceeded 10%. Even so, within these resistant strains, a growing number are being found in people who never took Tamiflu.
According to WHO, the Swine Flu pandemic infected nearly one in every five people worldwide and close to half of all schoolchildren. It is thought to have caused the death of almost 200,000 people.
From Adamantantes drugs to Neuraminidase inhibitorsDr. Hurt explained that two different antiviral medications have been used for treating influenza. Adamantantes drugs are no longer used because all influenza virus strains, including H1N1pdm09, have become resistant.
Neuraminidase inhibitors, another class of drugs, include:
- Tamiflu (oseltamivir)
- Relenza (zanamivir)
What does 'fit' or 'fitness' mean? - if a virus strain is fit, it means it can effectively transmit from one person to another. If a virus loses its 'fitness', it loses its ability to spread.
Dr. Hurt and team analyzed circulating H1N1pdm09 strains and discovered that:
- Resistance to Tamiflu was fairly low. Only about 2% of the H1N1pdm9 strains tested were resistant.
- More and more of these Tamiflu-resistant viruses are being found in patients who are not taking Tamiflu (oseltamivir). This suggests the emergence of a "fit" strain that is Tamiflu-resistant.
A widespread cluster of Tamiflu resistanceIn 2011, Dr. Hurt and team found a widespread cluster of oseltamivir-resistant influenza in Newcastle, NSW, Australia. They say this represents "the most widespread outbreak of oseltamivir resistant H1N1pdm09 viruses".
The World Health Organization is concerned that these resistant, fit strains could spread abroad.
Resistant strains have been found in Europe, but only single random cases or very tiny clusters, not widespread clusters. In the United Kingdom, in Wales in 2009, there was evidence that a Tamiflu resistant strain had spread from person-to-person in a hospital - five patients were diagnosed with H1N1pdm09 resistant to Tamiflu.
Dr. Hurt added:
"However the trend observed in Australia of a greater proportion of resistant cases being detected in untreated community patients is also being observed both in the USA and Europe."
Animal studies carried out by Hurt and team now confirm that these Tamiflu-resistant virus strains are much fitter than the previous H1N1pdm09 resistant strains.
This means that when resistant virus strains emerge in patients who are taking Tamiflu, there is a serious risk that they may spread widely to other patients.
Dr Hurt said "The greatest concern is that these resistant viruses could spread globally, similar to that seen in 2008 when the former seasonal H1N1 virus developed oseltamivir resistance and spread worldwide in less than 12 months."
Relenza (zanamivir) is still effectiveNone of the Tamiflu-resistant viruses that Hurt and team have detected are resistant to zanamivir. The researchers believe it is because the medications were designed differently, and also that zanamivir is used much less than oseltamivir.
Dr. Hurt said "Sustained global monitoring for the emergence of resistance is important to underpin public health and guidance for clinical management. Surveillance schemes should assess frequency of resistance in the community and in specific patient groups receiving treatment, such as severely immunocompromised, seriously ill patients in hospital, and patients not responding to antiviral therapy. Further studies to better understand influenza-virus infections in these patients and to improve antiviral treatment strategies are needed."
Saving lives depends on speed and cooperationAny resistance needs to be detected rapidly, Hurt emphasized. Specimens need to be shipped and tested promptly, and the results communicated immediately to the medical and scientific community to make sure resistance is detected quickly, so that treatment guidelines may be decided upon in time - only then can we save more lives.
Dr. Hurt added "We also need to increase our understanding of what is making some of these strains fitter for transmission. The widespread transmission and circulation of oseltamivir-resistant H1N1pdm09 viruses remains a risk in the future. Close monitoring of resistant viruses in both treated and community patients remains important."
Written by Christian Nordqvist