Cox was at the center of the storm in many respects: April 23, the day she learned that the single H1N1, first found in the US and also identified by CDC been spreading in Mexico, lightning struck his house and all but burned to the ground. Still, Mother's Day, May 10, Cox spoke with Science Insider length on ongoing studies at the CDC. She explained how scientists there sound the autopsy tissues, the immune system of those who received the vaccine against swine flu in 1976, older cases of swine flu infect humans, and how people manage currently infected infection. CDC researchers are also trying to develop improved diagnostics for the influenza A (H1N1) and to assess the potential value of the seasonal vaccination against this strain more closely, and the ability of the virus to evade antiviral drugs. Cox said the propensity of a specific influenza virus to combine with his parents and create a new strain-all this is a "triple reassortant" of humans, pigs and birds can have a coating of money because it could pick up genes from a parent that our immune systems have encountered and how to overcome
This is a condensed transcript of the interview, edited for clarity
Q: .. What research priority issues for you and your group
NC:. We will look at animal models and also autopsy of deceased patients tissues that have this disease to watch the pathogenesis
Q: What specifically you look
NC: We will compare the image that you see in the lungs of people infected with this virus with pictures of lungs of people who have died from seasonal flu to see if there are differences, and also to see if there is virus in the extra fabric where you would not normally find in people who have died from seasonal flu
Q :. there is evidence from previous 50 cases reported in the literature of swine flu in humans that different lung compartments are infected than in human influenza
NC: There have been so few deaths in the cases and no autopsy I know. There are additional cases. We just had a [ The ] New England Journal of Medicine Article 11 cases, and a number of unpublished cases we have to CDC of the past. But they also have, in general, are not very interesting
Q :. You are also looking at the antibodies in the blood of people vaccinated in 1976 against the swine flu. What you are looking
NC:. We will look to see if there is cross-reactivity of the antibodies of people given the swine flu vaccine in 1976 with the current virus
Q: You are looking for their today or samples stored antibody
NC: This stored samples. We do not have the ability to trace the 45 million people who are vaccinated
Q: .. You could probably find 100 of them
NC: Well, I'm one of them. I was a brand new postdoc here at CDC and of course I volunteered.
We expect that the antibodies induced by the vaccine against swine flu has decreased over the years, but there would be memory there. This question is one of the centers of interest and scientific courses of interest if you have been involved in the vaccination campaign against swine flu 1976 to see if there is some residual benefit. Regarding our current response, we would not say, "OK guys, if you had the vaccine in 1976, you will not receive the vaccine for it," assuming it is developed
[ Q: are you saying that you could see a certain level of protection in this older age group who received the vaccine 33 years ago
NC :. Correct
Q: Although early studies suggested that the seasonal vaccine provides no protection against H1N1 flu, you are looking at the possibility that this might not prevent infection, but still reduce the severity of disease
NC: We are looking very, very carefully serum panels from individuals who received different seasonal vaccines from various manufacturers and successive years what we. see is that the older you get, the more likely you are to have what we call cross-reactive antibodies to the new virus. We are not saying that this is a protective antibody. But we are looking very, very carefully the data.
We try to make the spectrum of ages that you would need to make recommendations on the use of seasonal vaccine. What is absolutely clear and confirmed by many groups is that for children 6 months to 9 years say, there is no pre-vaccination of cross-reactive antibodies or after vaccination with the vaccine against seasonal influenza
Q :. Is there evidence that anyone in Mexico or the United States who had a serious illness has been vaccinated
NC: All teams are looking very carefully at this. You'd be surprised how hard it is to track back and whether a person is vaccinated. Some people think we should be able to snap your fingers and have that data. And we do not do.
I assure you before giving you an answer that I go through the latest data I have, and I work on other emerging issues.
Q: I understand. I can not imagine that those who are
NC: .. You would not know
[On 13 May, Nancy Cox said CDC knew the vaccination status of 40 people hospitalized because of a confirmed H1N1 infection. Of these, nine reported having received the seasonal flu vaccine, but seven had underlying medical conditions that could have predisposed them to severe disease from influenza. "We're really not able to draw conclusions about vaccine effectiveness," she cautioned.]
Q: Shortly after the new strain has been detected, the CDC has developed and distributed a test that uses real-time analysis of polymerase chain reaction (PCR) to detect. But this is not the ideal rapid test, is it?
N.C. No, it's not. It takes 3-4 hours for a response to the real-time PCR
Q :. There are quick tests on the market today. What are their limitations?
N.C. All rapid tests that are commercially available now that you say so is influenza A or B or just the flu. And there is variability between rapid tests commercially available to do so. Some of these, commercial approved rapid tests have become less sensitive to pick up seasonal influenza viruses A, and in addition, some of them seem to be less sensitive to pick up this new virus as influenza A.
Q: But how do you use these because they are not sub-type at all? You can not say that it is this new H1N1 virus.
NC: No, but in the face of an epidemic where you have very high attack rate, say in a school, you can use these rapid tests to determine, yes there is influenza A, we're having here, and you would be able to take samples from a subset of these children and sending them to the health department of the state for diagnosis with real time PCR.
Q :. This helps explain what happened in Mexico
N.C. Exactly, exactly. Because they used standard tests available, and immunofluorescence, and of course, they are not able to determine what it was because there is simply not the sensitivity. Now that they have the real-time PCR test is, they are able to test a large number of specimens.
Q: What about looking at how many people infected with the virus occur, viral shedding studies? What are you and what do you hope to learn from them?
N.C. We would like to know how long people could be infectious. So we seek both the amount of virus and duration so that we can try to understand the period in which people will be able to transmit the virus
. Q: And what is the average for influenza A
NC: This varies by population group, and that's what makes this so difficult. The children throw higher titers of virus for longer periods. Immunocompromised people throw higher titers of virus which can be very long periods of time. Normal, healthy adults probably shed the virus for 3 or 4 days
Q :. What about children
N.C. Children can shed the virus 10 days or more ?. But the excretion of virus transmission equal. You must be shedding large amounts enough virus to actually infect someone
. Q: How do you test for viral shedding? Is this a nasal swab every day? It seems complicated.
N.C. is complicated. You must have buffers series and try to make semiquantitative PCR or plaquing studies so you're measuring quantities of virus. And it is difficult to establish a standard method of sampling for they are equivalent daily
Q :. And you do not have Marcus Welbys door-to-door visiting people who have flu. How do you do? People are sick arrive?
N.C. We have field teams to do the studies, and they are very difficult to do. It is difficult to find infected people are willing to do and hard to put these studies into place. But they are important, and the National Institutes of Health is working on natural history studies as well. And you're more likely to do this kind of study for the most serious patients, for hospital patients
Q :. This H1N1 has not genotypic mutations known to cause resistance to drugs that inhibit neuraminidase [the "N" in H1N1]. But have you grown the virus in cultures and looked to see if the isolates could still have a resistance to these drugs, the so-called phenotypic testing
NC: With the neuraminidase inhibitors, we know not even the full range of mutations that can confer resistance. So to be sure we do not lack anything, we phenotypic testing
Q:.? Have you seen even isolates that are resistant
NC: No
Q: It is inevitable in the minds of some people that we will see co-infections with the new H1N1 other flus "seasonal", including human H1N1 currently circulating that is resistant to neuraminidase inhibitors. Can they restock as the new strain develops resistance to drugs
NC: co-infections occur frequently enough that we could very well be the emergence of an H1N1 virus with the seasonal N1, which is resistant, and hemagglutinin [the “H”] of this new virus. But the population would have some antibodies against the N1 seasonal virus that could reduce the severity of infection, providing a degree of cross-protection against the disease
. Q: reassortment may have opposition in the head end of the world scenario than the current strain could become resistant to all drugs. Do you still detected coinfections?
N.C. Not us. We are very, very carefully heterogeneity at each nucleotide position. So we would see the heterogeneity at different nucleotide positions if we see coinfections
Q :. What other studies are you that you think are really interesting, even if they are not as important from a point of view of public health
NC: The various theories of the origins of these viruses explored in detail. We are looking very carefully any additional data that is entered in the database that may give us additional clues about the interim we are looking for missing links. We also examine very carefully how viruses change once the avian influenza virus are introduced into pigs and humans. And we began to look hemagglutinin [glycoprotein], and there are some very interesting models that we will explore. We structural biology studies looking at what parts of the molecule change, trying to understand our observations that might mean in terms of the physiology of the host.
These studies help us understand not only what the virus are most likely to jump from species to species, but once they are in a new host, what types of changes are likely to produce. This can also help us determine how long the virus was in that particular host
Q :. I am interested in the Canadian swine herd. Canadians apparently have not completed the sequencing of the virus in pigs. The assumption that a carpenter working at the infected farm pork is not based on experimental evidence, and according to his own description, he swapped some vents to a barn and has no direct contact with pigs. It would be interesting to make a phylogenetic analysis of the virus in pigs and see if it is younger or older
NC: .. Exactly
Q: did this happen
NC: this is the veterinary people, the Canadian food inspection Agency, they are sequence analysis, and the last time I talked to my counterpart Canadian on the human side, Frank Plummer, was last Friday and his colleagues had not finished making the movie. He thought they would have the complete sequence in the coming days. And he, and everyone was really interested in looking at the sequences of these viruses. But from what he knew of his colleagues, the sequence similarity was very large. Of course, to see where he is phylogenetically interesting. Could it be a precursor or is it just clearly part of this epidemic
Q :? So you have not excluded the possibility that the pigs were infected first
NC: no, I'm not completely exclude anything. Until you see the data, you can not rule anything
Q :. Because the CDC is speed sequential measurement of isolates and position data in GenBank, you seem particularly able sequencing of these viruses. Have you asked Canadians to isolate this pig?
N.C. Before this outbreak, we have had experience with the triple reassortant swine that had infected humans, we had our primers and probes already ready to go. Our machine was already oiled and ready to go. We just had to do tweaking.
But we did not ask this isolate because we felt it was well in hand. And human disease is our disease pathways and animals is the way the US Department of Agriculture (USDA). As we work to the animal-human interface, and we work very closely with our colleagues from the USDA, we try to stay in our lane and use the data generated by those working on the side of the animal health.
Q: But in this case, you made the triple reassortant who moved from pigs to humans before. And there is this confusion of the lines, it seems to me that you are the perfect place to do it.
N.C. Correct, right. We are always happy, I mean, we never turn samples
Q :. Do you think the epidemic will grow from the current phase 5 to phase 6, a full pandemic -scale? There was a time when it seemed imminent and everyone said yes, and now it is
NC "Who knows, perhaps, not be ." L World health Organization is looking very, very carefully the spread to Europe to see if transmission and sustained community outbreaks. It is a sort of cape in this direction, but it is not there yet
Q:.? Are you surprised it's not there yet
NC: What we have been able to verify is that in the United Kingdom and Spain, they had advanced warning. By the time we had the disease, it was broadcast in the United States, spread really quickly. Europeans were able to screen travelers returning from Mexico or the United States, followed by ensuring that had a flu-like illness, put on Tamiflu [oseltamivir], to their contacts on Tamiflu. Some countries that have done this and not have very many cases to start have been able to really dampen disease
Q :. I also heard about your home, and that is the terrible moment.
NC :. If this were my only headache I would be happy at this point in time
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