Calming the storm…while killing the virus

A couple of months ago Pro-Test blogged about some interesting research that may lead to new drugs that to prevent the lethal “cytokine storm” that was responsible for most deaths in the SARS outbreak.

However SARS is not the only virus that kills by inducing an excessive immune response; the threat posed by the  H5N1 strain of bird flu is of grave concern to many public health officials http://www.cdc.gov/flu/avian/. With an observed mortality rate of between 45% and 80% in infected humans here is little doubt that if it was to mutate into a form that was highly contagious in humans it could pose a great risk to the population, and possibly cause a pandemic on the scale of the 1918 Spanish flu. During outbreaks it has been observed that although some anti-viral medicines can kill the virus they did not reduce mortality rates, probably because they were administered too late to stop the virus from provoking the cytokine storm.

A study published online in Proceedings of the National Academy of Sciences of the United States of America (PNAS) this week (1) by Prof. Kwok-Yung Yuen and colleagues at the University of Hong Kong shows that it should be possible to both kill the virus and prevent the cytokine storm.  Working with mice infected with the H5N1 virus compared administering the anti-viral drug zanamivir alone or in combination with anti-inflammatory drugs. A key element in their study was a decision to delay treatment for 48 hours after infection in order to mimic the real world clinical situation where the illness may not be diagnosed until some time after infection.  Their results confirmed that zanamivir alone did not reduce mortality when compared to an untreated control group, and even though viral levels were a lot lower than in the control group only 13% of mice survived.  In contrast when zanamivir was combined with the anti-inflammatory drugs celecoxib and mesalazine 53% of the mice survived, a very significant improvement, without compromising the ability of zanamivir to kill the virus.
Since all the drugs this study are already approved for human use this result should make a real difference to how we respond to any future H5N1 outbreaks, and indeed to outbreaks of other viruses that kill in the same way.  It is sobering to reflect that even with this improved treatment the mortality rate was still frighteningly high, more research is clearly needed to help develop better drugs for the treatment of virus induced cytokine storms.

Cheers

Paul Browne

1) Zheng B.-J. et al. “Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus” Proc. Natl. Acad. Sci. USA, Published online on June 3, 2008 DOI:10.1073/pnas.0711942105

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