South African scientists have dismissed predictions of a possible public health emergency following reports from Australia that a small number of swine flu patients were resistant to the first-line treatment, Tamiflu.

Resistance is carefully monitored in South Africa and globally and in South Africa resistance remains at very low levels, according to Dr Cheryl Cohen, Head of Epidemiology at the Centre for Respiratory Diseases and Meningitis (CRDM).

A report in this week’s The Lancet journal details a small percentage of Australian patients not previously treated for swine flu (H1N1), who are showing increased resistance to the first-line treatment, Tamiflu.

This information has prompted some to predict that it could raise the risk of an international public health emergency if the resistant strains spread.

The new Australian research was presented today (MONDAY) at the Annual Scientific Meeting of the Australasian Society for Infectious Diseases (ASID) in Canberra, Australia.

Two different classes of antivirals drugs are currently approved for treatment of influenza (in Australia). The adamantantes class of drugs is no longer suitable for patient treatment, since virtually all strains of influenza (including H1N1pdm09) show resistance to these drugs.

The other class, neuraminidase inhibitors, contains the drugs widely publicised during the 2009 pandemic (zanamivir, trade name Relenza; and oseltamivir, trade name Tamiflu). Resistance to neuraminidase inhibitors has so far been limited. Furthermore, most strains that become resistant also lose their ability to spread as effectively (their ‘fitness’).

In this study, Dr Aeron Hurt of the World Health Organisation Collaborating Centre for Reference and Research on Influenza, in Melbourne, analysed circulating swine flu (H1N1pdm09) strains and found that although the overall frequency of oseltamivir resistance was relatively low (approximately 2% of H1N1pdm09 strains tested) an increasing proportion of these viruses are being detected from patients not being treated with oseltamivir, suggesting a fit strain could be emerging since it must be being transmitted to these patients never treated with that drug.

A widespread cluster of influenza cases of oseltamivir-resistant influenza in Newcastle, NSW, in 2011 detected by surveillance conducted by Hurt and colleagues, represents the most widespread outbreak of oseltamivir resistant swine flu viruses and generated significant concern that these strains may spread outside of Australia.

Similar resistant strains have since been detected in Europe but at this stage only on an ad hoc basis. “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,” says Hurt.

Professor Marietjie Venter, Director of the National influenza Centre added that World Health Organisation surveillance data confirmed that there were very low levels of resistance.

In South Africa Venter and colleagues do resistance testing by genetic and phenotypic test. In 2011, which was an Influenza A(H1N1(pdm09) season they tested 294 isolates from that year and all were sensitive to Oseltamivir.

IN 2012 which was an Influenza H3N2 and Influenza  B season, they tested 127/142 H3 isolates, all were sensitive to Oseltamivir, and 31 Influenza B strains that were also all sensitive.

She said the cases in Australia were a cluster of cases already described in 2011.

“So far they have not spread further as far as we know. The Influenza season has not yet started in the Southern hemisphere, so we will have to see what happens in Australia this year,” she added.

Studies in animal models conducted by Hurt’s team have now confirmed that these oseltamivir-resistant viruses are fitter than previous swine flu oseltamivir-resistant strains. This finding means that when resistant viruses arise in patients undergoing treatment, there is now an increased chance that these viruses may spread widely to other patients.

Hurt notes that “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.”

All of the oseltamivir-resistant viruses detected by Hurt remain sensitive to the alternative drug zanamivir, probably due to both drug design differences and the fact that zanamivir has been generally used less than oseltamivir.

“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,” says Hurt.

“Further studies to better understand influenza-virus infections in these patients and to improve antiviral treatment strategies are needed.”

He adds that it is essential that specimens should be rapidly shipped and tested, and results communicated as rapidly and widely as possible to ensure resistance is detected quickly, enabling treatment guidelines to be revised in a timely manner, and, ultimately, more lives saved.

* In 2008 there was a H1N1 strain circulating that became oseltamivir-resistant and spread globally (this strain is now known as the ‘former seasonal H1N1 virus).

In 2009 when the ‘swine flu’ pandemic occurred a different H1N1 strain emerged this is now known as ‘H1N1pdm09’. The emergence of the H1N1pdm09 resulted in the extinction of the former seasonal H1N1 virus, and therefore the one positive to come from the pandemic is that it got rid of an oseltamivir-resistant strain that was circulating. Since the H1N1pdm09 virus has been circulating (i.e. since 2009) the levels of oseltamivir resistance have remained at 1-2%, except for in Newcastle, NSW in 2011, where the percentage of resistant strains exceeded 10%. Yet within these resistant strains, more are coming from persons not previously treated with oseltamivir.