Antivirals

This week the Proceedings of the National Academy of Sciences (PNAS) published a paper about a new antiviral drug that fully protected mice against virulent bird flu virus (H5N1). I don't usually pay a lot of attention to papers announcing new flu antivirals that work in animals. It's a long way from there to use in humans. But this drug, called T-705 (also known as favipiravir) seems different in several respects. The work was mainly supported by the Japanese government (with some support from the US NIH) and was led by Yoshihiro Kawaoka, one of the world's leading flu scientists (University…

Red wine has been touted for its health benefits but these don't seem to extend to warding off swine flu. The virology laboratory in Bordeaux in the southwest of France tested via RT-PCR over 1200 nasopharyngeal swabs between May 1 and the first week in October and found 186 positive for the new pandemic strain. They looked at five of these cases more closely, monitoring them for duration of viral shedding. Two of the five kept shedding for 2 to 4 weeks (paper in Eurosurveillance by Fleury et al., v. 14, #49, December 10, 2009). The first case was a non-obese previously healthy male in his…

The other day the British Medical Journal (BMJ) published a clutch of articles about whether Tamiflu was as useful a drug as some have touted. I read the main article, another one of the Cochrane Collaborative meta-analyses of the studies they deem useful about any particular subject, and it didn't seem to make much news. It confirmed what their previous review had said about the neuriminidase inhibitor antivirals for influenza (Tamiflu and Relenza): these drugs work but their effect is modest. We've been saying the same thing for years here, not because we did a fancy meta-analysis, but…

Frequent readers here know we are fascinated with the similarities between computer viruses and real viruses. Both use their unwittingly infected hosts (computers or host cells) to make copies of themselves and in the process can cause varying degrees of sickness. It's hard to give any solid criteria which will differentiate one as qualitatively different than the other (except perhaps one is purely carbon based). But now you don't have to choose. You can have both at once: A new malware campaign uses faked e-mails that appear to inform of H1N1 vaccination programs from the Centers from…

It seems swine flu is full of surprises that turn out not to be surprises. Or so it's claimed. Or not. Here is CDC's Dr. Anne Schuchat, the agency's chief health officer and spokesperson on swine flu, responding to NPR's Melissa Block's question about what has been her biggest surprise: Dr. SCHUCHAT: I shouldn't have been surprised, but I have been surprised about this disproportionate toll that it's taking in pregnant women. I think I'd never lived before a pandemic before, and I actually hadn't seen the really sorry and just the tragic stories of healthy pregnant women coming down with such…

We've gotten the question here fairly frequently: If antivirals (Tamiflu, Relenza) for swine flu work best when given early but shouldn't be given to people who aren't really that sick, how do you balance waiting for them to get sick and have the drugs not work well with giving it when you don't need to? There is no absolutely right answer to this difficult question. Early in the pandemic antivirals were being given prophylactically to stop spread, then they were being given only when a diagnosis of swine flu was confirmed. Then only to the sickest patients. We're all on a learning curve. The…

There is no way to keep up with all the flu news, so we pick and choose, usually based on some kind of point we want to make. That's both the good and the bad of this blog: the news comes with a point of view. But so does most news, and we try to make ours both explicit and scientifically as accurate as we can with the information at hand. Today is a typical example. Bloomberg is reporting that any swine flu virus resistant to oseltamivir (trade name Tamiflu), the only antiviral pill effective at all for the infection, transmits less well than swine flu that's sensitive to Tamiflu. The source…

Yesterday (today as I am writing this) the British Medical Journal published another Cochrane meta-analysis on the efficacy of neurimminidase inhibitor antivirals (the only two in use now, being oseltamivir [Tamiflu] and zanimivir [Relenza]). Their conclusions have made the news, so I guess I should cast my baleful eye on their handiwork. I think there is less here than meets the eye, but first let's look at what meets the eye. This is a meta-analysis, that is, an analysis of other analyses, the other analyses in this case being drug trials of Tamiflu or Relanza in children. So it's an…

There have been three reported oseltamivir (Tamiflu) resistant isolates of H1N1 swine flu (added: and now a fourth in Canada) but with those exceptions all others have been sensitive to this oral antiviral. This is in marked contrast to the other H1N1 strain, the seasonal variety which is almost entirely resistant. The spread of Tamiflu resistance in the seasonal strain happened with dramatic suddenness in the winter of 2007 - 2008 and came as an unhappy surprise. People assume that a rapidly mutating virus would inevitably become resistant, but based on several laboratory studies there were…

For reasons not revealed to anyone I know, WHO is saying the Tamiflu resistance in a Danish swine flu isolate is "isolated case." Could be, but I'd sure like to know why they think so, other than they don't have any other examples. Meanwhile WHO and CDC continue to advise prompt use of Tamiflu (oral oseltamivir) for treatment of swine flu in high risk patients. Which brings up the question of side effects. The most common Tamiflu side effect is nausea and vomiting. When my daughter was seen at the local hospital ER for swine flu symptoms and a positive rapid test for influenza A at a time…

Currently the only antiviral drugs effective against the swine flu (novel H1N1) virus are the two neuriminidase inhibitors, oseltamivir (trade name Tamiflu) and zanamivir (trade name Relenza). Relenza is in active form at the outset and cannot be absorbed orally. It must be inhaled, leading to asthmatic reactions in some, ineffective dosage in those with breathing difficulties, and no drug at sites beyond the respiratory tract. Despite these drawbacks, it has so far produced little or no viral resistance. Tamiflu is absorbed orally and converted by the liver into the active form, so it gets…

CDC guidelines for antiviral therapy for swine flu infection: This swine influenza A (H1N1) virus is sensitive (susceptible) to the neuraminidase inhibitor antiviral medications zanamivir and oseltamivir. It is resistant to the adamantane antiviral medications, amantadine and rimantadine. (CDC) What are these antiviral drugs and how do they work? Over the years here we've discussed this pretty often, so I went back and retrieved one of our older posts (from 2007). I've done some editing but it's pretty much the same as when I wrote it about bird flu. Same principles. Oseltamivir (which we…

The news of a new antiviral comes at a Press Conference. That could either mean a blockbuster breakthrough or an unwarranted device to get attention for some otherwise decent but not blockbuster science. Unfortunately, the news that "Experts Identify Compound That May Fight Bird Flu" is of the second type: Scientists in Hong Kong and the United States have identified a synthetic compound which appears to be able to stop the replication of influenza viruses, including the H5N1 bird flu virus. The search for such new "inhibitors" has grown more urgent in recent years as drugs, like oseltamivir…

I'm not sure what to make of the report that scientists in Boston, California and the CDC in Atlanta have made monoclonal antibodies that protect mice against many different flu subtypes. Monoclonal antibodies are antibodies made by the descendants of a single immune cell (that is a single clone, hence monoclonal). Thus unlike natural antibodies, these are also monospecific, i.e., they are directed against one specific target. Our natural immune system "sees" a protein on the surface of the virus called hemagglutinin (HA), of which there are 16 broad subtypes and many, many variations within…

If there's an influenza pandemic in the near future all bets are off when it comes to unplanned for consequences. Well, maybe not all bets. Right now the only oral antiviral likely to have any effectiveness in a pandemic is oseltamivir (Tamiflu), although how effective and how long it would retain any effectiveness is in question. But there's a lot of it out there and it will be taken in high volume and, either in its capsule form [oseltamivir ethylester-phosphate (OE-P)] or its active form [oseltamivir carboxylate (OC)], excreted into the sewer system in massive quantities (discussed here…

So Roche Pharmaceuticals now has sufficient productive capacity to make their influenza antiviral Tamiflu (oseltamivir) meet demand. More than enough, it appears, since they now have come up with a new scheme to unload some of their inventory before its 3 year shelf life expires and to keep turning over the inventory year after year, whether or not there is a demand in any particular year: With an endorsement from US health officials, Roche, maker of the antiviral drug oseltamivir (Tamiflu), today unveiled a program to encourage more businesses to stockpile the drug to protect employees in…

First Tamiflu (oseltamivir), now Relenza (zanamivir): Health officials [in Canada] are investigating whether Relenza - a drug provinces have stockpiled in case of a pandemic flu outbreak - can be linked to fatal reactions or abnormal behaviour in children. [snip] The investigation is a response to recently updated safety warnings issued by the U.S. Food and Drug Administration (FDA) or Relenza. In March, pharmaceutical giant GlaxoSmithKline updated Relenza's safety labels after children in Japan were reported to suffer from delirium, hallucinations. Some died after injuring themselves. A…

I'm an advocate of using computer models to help us think about what might or could happen during various pandemic flu scenarios, but it is a technique with drawbacks. For one, it can suggest that some things might be possible that are either very difficult to do or aren't feasible. This happened in 2005 when some models were published in Science and Nature that suggested a pandemic could be nipped in the bud before it started. Most people thought that what was required was unrealistic but it put WHO in a bind. They had to marshal their resources to show they were willing to try or go down…

There are a lot of open questions about the influenza antiviral drug oseltamivir ("Tamiflu"), among them whether it works at all for bird flu (highly pathogenic influenza A/H5N1), and if it does, whether resistance will develop making it ineffective. But all the questions have a common assumption: that the patient is actually taking Tamiflu. How would you know if you were or not? Because the bottle says so? Not necessarily. In December 2005 U.S. Customs and Border Protection (CBP) Officers seized 51 shipments they said were counterfeit Tamiflu pills at their air mail facility in San Francisco…

Press releases are the way a lot of scientific information is released today. Straight to the public, no peer review. This has advantages and disadvantages. The advantages are speed and directness. No filtering through reviewers, journal editors, colleagues. And of course that's the disadvantage, too, especially when the news comes from an interested party as it usually does in a press release. This is part of the interpretation of data these days. All that being said, the maker of Tamiflu, Hoffman - La Roche, has released data they have gathered from physicians treating cases of H5N1 in…