Antivirals
revere | February 17, 2008When my colleagues announced early afternoon on Friday he was headed home because he was sick, I knew the flu had finally arrived on my doorstep. It was already here, of course. The emergency rooms are jammed, clinics have long waits and hospital admissions for flu are up -- way up. The flu situation was the page one column eight story in Saturday's Boston Globe:
The flu virus is rampaging across New England, spawning waves of coughs and fevers, causing patients to flood doctors' offices, and raising questions about the effectiveness of flu shots given to tens of millions of Americans.
During…
revere | February 8, 2008We've discussed this already, but now CIDRAP News also has a story (which they got from AP) that this year's flu vaccine is not perfectly matched to the all the circulating viruses (of course we had it first, but hey, who's keeping track?). The data that are used to prepare vaccines for the next flu season come from predictions based on what is seen during the current season as determined by a global surveillance network (the same network at issue in the refusal of Indonesia to share H5N1 isolates, although this mismatch has nothing to do with the Indonesian situation). The circulating…
revere | November 15, 2007If you are in the "older age group" (as those of us in that group prefer to be called) you are at increased risk of dying from seasonal influenza (pandemic strains seem to target the young), but you are also less likely to be helped by a flu shot because you don't mount as fast and effective an immune response. At least that's what we think on the basis of current evidence. Like everything else about flu, it's subject to change.
Like the idea that you have a 48 hour window for the use of antiviral neuraminidase inhibitors like tamiflu. After 48 hours, we believed, they don't do any good.…
revere | November 9, 2007Influenza A/H5N1 (bird flu) bubbles away this year much as in past years and public health professionals continue to wait with bated breath for the other shoe to drop. It could happen this year, next year or not at all. That's the way the world is. Betting on "not at all" isn't considered prudent by most people in public health, despite the fact that it's possible. So given the uncertainty, what is the best strategy?
It is a bit disconcerting to see that the overwhelming preponderance of resources to pandemic preparedness resources are going into influenza-specific counter-measures,…
revere | June 24, 2007There's been a bit of a buzz about a paper by Australian researcher Jennifer McKimm-Breschkin at the Toronto flu meetings last week. McKimm-Breschkin told the gathering of 1500 flu obsessed scientists just what they didn't want to hear: that she and her colleagues had evidence from the laboratory that clade 2 H5N1 avian influenza virus isolated from birds in Indonesia were becoming resistant to the only oral antiviral effective against the virus, oseltamivir (Tamiflu). In comparison to clade 1 (southeast asian) virus from a few years back, the sensitivity was 20 to 30 times less.
We'll have…
revere | June 21, 2007The prospect of a influenza pandemic has concentrated the minds of vaccine makers. There has been a lot of new research and development on newer, faster and cheaper ways to make flu vaccines. The antiviral field hasn't been quite as active, although now things seem to be picking up. Until now the antivirals (all four of them!) have been in two main classes, the old M2 inhibitors (adamantanes) and the newer neuraminidase inhibitors (oseltamivir, zanamivir; and waiting in the wings, peramivir). Now we are hearing about new drug targets:
One of the promising things about the work is that the…
revere | April 5, 2007[A series of posts explaining a paper on the mathematical modeling of the spread of antiviral resistance. Links to other posts in the series by clicking tags, "Math model series" or "Antiviral model series" under Categories, left sidebar. Preliminary post here. Table of contents at end of this post.]
This is the last in a long series attempting to explain a recent paper by Lipsitch et al. on mathematical modeling of the effects on influenza control of antiviral resistance, published in PLoS Medicine in January 2007. Modeling is a valuable technique but for most readers, even most scientists…
revere | April 4, 2007[A series of posts explaining a paper on the mathematical modeling of the spread of antiviral resistance. Links to other posts in the series by clicking tags, "Math model series" or "Antiviral model series" under Categories, left sidebar. Preliminary post here. Table of contents at end of this post.]
We have now gone through the entire paper on modeling the impact of antiviral resistance in an influenza control program, by Lipsitch et al., published in PLoS Medicine. Since a number of assumptions were made, we take some time to consider what effects they have on the model's results. In the…
revere | April 4, 2007Just as we are preparing to wind up our marathon series of posts on a mathematical model of antiviral resistance, a new paper has appeared in the Journal of the American Medical Association (JAMA) with data on antiviral resistance from Japan, the country that uses more Tamiflu and Relenza (the two available neuraminiase inhibitor antiviral drugs) than any other. It turns out the accompanying Editorial in JAMA specifically mentions the modeling paper and its results as a key to understanding the significance of this work. So all our labor has not been in vain. Here's more.
Our eye was caught…
revere | April 3, 2007[A series of posts explaining a paper on the mathematical modeling of the spread of antiviral resistance. Links to other posts in the series by clicking tags, "Math model series" or "Antiviral model series" under Categories, left sidebar. Preliminary post here. Table of contents at end of this post.]
We conclude our section by section examination of the mathematical modeling paper by Lipsitch et al., published in PLoS Medicine. We have finally arrived at the final section, Discussion (starting on page 8 of the .pdf version). In the second post we said many scientists read only the Abstract,…
revere | April 2, 2007[A series of posts explaining a paper on the mathematical modeling of the spread of antiviral resistance. Links to other posts in the series by clicking tags, "Math model series" or "Antiviral model series" under Categories, left sidebar. Preliminary post here. Table of contents at end of this post.]
In this post we explain the remaining results presented in the paper by Lipsitch et al. in published in PLoS Medicine (the subsections headed, "Effects of resistance on epidemic size" and "Dependence of outcomes o fitness cost and intensity of control" on page 6).
These sections and the…
revere | April 1, 2007[A series of posts explaining a paper on the mathematical modeling of the spread of antiviral resistance. Links to other posts in the series by clicking tags, "Math model series" or "Antiviral model series" under Categories, left sidebar. Preliminary post here. Table of contents at end of this post.]
We now take a look at what happens in the model when we vary the intensity of prophylaxis and treatment. The model treats the fraction of those prophylaxed, fp, and those treated, fT, separately, but for illustrative purposes the paper sets these two figures at the same number. In the previous…
revere | March 31, 2007[A series of posts explaining a paper on the mathematical modeling of the spread of antiviral resistance. Links to other posts in the series by clicking tags, "Math model series" or "Antiviral model series" under Categories, left sidebar. Preliminary post here. Table of contents at end of this post.]
We've spent a long time in the previous posts looking inside the black box of a mathematical model for the spread and consequences of antiviral resistance to Tamiflu (described in the paper by Lipsitch et al., published in PLoS Medicine). From the last post you will recall the authors assume it…
revere | March 30, 2007[A series of posts explaining a paper on the mathematical modeling of the spread of antiviral resistance. Links to other posts in the series by clicking tags, "Math model series" or "Antiviral model series" under Categories, left sidebar. Preliminary post here. Table of contents at end of this post.]
Now we are almost ready to run the model described in the paper, "Antiviral resistance and the control of pandemic influenza," by Lipsitch et al., published in PLoS Medicine. If you have been following up to this point, you will know the model described in the Methods section is a homogeneous…
revere | March 30, 2007Tamiflu side effects have been much in the news and we have concurrently been posting our mega-series on modeling antiviral resistance in influenza control. The two subjects are related in two ways, one obvious (Tamiflu is the main antiviral being stockpiled for influenza control) and one not so obvious: both topics are related to the fact that million, tens of millions or hundreds of millions of doses are contemplated. For antiviral resistance this means even very rare mutations producing a fully transmission-competent resistant virus can spread widely through the population (you will see…
revere | March 20, 2007Tomorrow we begin a blog experiment, one we already judge has failed. In January Marc Lipsitch and his team at the Harvard School of Public Health published a splendid paper using a mathematical model to investigate the spread of antiviral resistance in the control of pandemic influenza. When we read it our first thought was to write a substantial blog post about the results. The paper was published in PLoS Medicine almost the same week as another mathematical model on spread through the air traffic system by Colizza et al. and the Colizza paper seemed to get most of the newswire notice. But…
revere | November 15, 2006Over a year ago reports from Japan began to circulate that the influenza antiviral, Tamiflu, which is prescribed there often for uncomplicated seasonal influenza, was causing abnormal behavior, most worrisomely delirium and suicidal behavior in children. The drug is approved for adults and children over a year old. At that time the FDA decided the evidence was insufficient but planned to revisit the issue in a year. Now the year is up and FDA has apparently decided the evidence is stronger. They are now recommending patients who take Tamiflu be "monitored" for abnormal behavior. It isn't…