Confronting an influenza pandemic with inexpensive generic agents: can it be done?
Avian influenza A H5N1 presents a serious and possibly imminent pandemic threat. In such an event, adequate supplies of affordable vaccines and antiviral agents will be unavailable to most people in the world. In view of the overwhelming need for effective alternatives, generic agents that target the host immune response or the pandemic virus should be considered. Many scientists doubt the effectiveness of these agents. Nonetheless, several studies suggest that statins improve outcomes in patients with bacteraemia and pneumonia and might be similarly effective against influenza. An experimental study has shown that the fibrate gemfibrozil, a peroxisome proliferator-activated receptor (PPAR) alpha agonist, reduces mortality in H2N2 influenza virus-infected mice. There is substantial molecular cross-talk between statins and PPAR agonists, and their clinical effects are additive in patients with cardiovascular diseases. Chloroquine increases endosomal pH, impairing influenza virus release into the cytosol. Statins, fibrates, and chloroquine are produced as generic medications in developing countries. They are inexpensive, could be stockpiled, and would be available on the first pandemic day. With a lack of realistic alternatives for confronting the next pandemic, research is urgently needed to determine whether these and other generic agents could mitigate the effects of what might otherwise become an unprecedented global public-health crisis.
Fedson
David S
DS
dfedson@wanadoo.fr
D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use; D004196:Disease Outbreaks / Q000517:prevention & control*; D015248:Gemfibrozil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology* / Q000517:prevention & control
D000998:Antiviral Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007155:Immunologic Factors; D002738:Chloroquine; D015248:Gemfibrozil