Microbiologist Celia Alpuche heads the laboratory in Mexico that has become ground zero of the outbreak of the country's swine flu. Alpuche spoke to Science yesterday from his office at the Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE) in Mexico City.
Many people have raised questions about whether Mexico could have detected the outbreak earlier and contained before it spreads elsewhere. But as Alpuche explains InDRE was a confusing situation because the virus has surfaced in the middle of the flu season - and it may not have originated in Mexico anyway. Alpuche also sets out the facts about why it took several weeks to link the epidemic with symptoms first case, a 4 year old boy from La Gloria in Veracruz state. And she frankly described the limits of its own laboratory.
InDRE worked closely with the Public Health Agency of Canada and the US Centers for Disease Control and Prevention (CDC) to identify the virus as the cause of the epidemic, and Mexico continues collaborate to test suspected samples. May 1, Mexico had 156 confirmed cases and nine deaths, more than any other country in the world. Mexico has identified another 1,918 suspected cases, as described in the years CDC Morbidity and Mortality Weekly Report ( MMWR ) yesterday and InDRE rushes to sort how many are actually swine flu .
flu is caused by two strains A and B, as well as several different subtypes that are designated by the two proteins that mark the viral surface, hemagglutinin and neuraminidase, followed by a number. The epidemic is caused by an influenza A virus subtype H1N1
The interview follows after the jump ...
Science :. There have been many questions about the origin and timing. When is it an indication that there was an unusual number of cases of respiratory disease
Alpuche :? April 7, we learned that the National Institute of Respiratory Diseases was particularly serious cases of pneumonia in young adults who were previously healthy. Immediately, we started to get the data around this cluster. We also started doing a retrospective analysis of influenza data we had.
We looked at all the data we had on the detection of influenza since January until this month and also compared to the last flu season. In addition to SARS, we started having rumors there were other cases that are not pneumonia, it was like a respiratory disease, flu-like illness.
Science : Have you seen anything from your analysis of influenza trends that tell you anything
Alpuche : the first thing he told us we were still detect flu in the country, not only in Mexico city. It was about the same as we see every year, except that it was an extension of the flu season. Then we analyzed the subtypes of influenza strains, and one of the unusual things we saw was that in this season, we had the first peak in the latter part of November and December and another in February. During the season, we started to have more influenza B that we had last year.
Science :. This has nothing to do with this epidemic
Alpuche nothing to do with it. He was very confused. We found that 37% were B and the year before, we find up to 15% were B. Then, we examined the data they have the flu to CDC surveillance system to see if anything unusual occurring. We also saw in the United States something kind of similar - a prolonged period of influenza and increasing the strain B. So, we thought we had something related to the flu, and we were still concerned by pneumonia. We returned immediately to look all influenza outbreaks we had in the country since the season started to see if it was more related to the prolonged flu or there was something else we see. We had small outbreaks in some states in the central part of Mexico, Tlaxcala, and the last outbreak we had was in the state of Veracruz, in the town of La Gloria, near Perote. It was during the last 2 weeks of March
Science :. Why did not it trigger concern in the last 2 weeks of March
Alpuche : There was a flu-like illness, no deaths and no cases of pneumonia. This outbreak has been deeply studied with epidemiologists from the state. The Secretary of Health of Veracruz did a great job during the epidemic in the last 2 weeks of March
Science :. What capacity do they have to type subtypes?
Alpuche : influenza, laboratory surveillance network in Mexico using immunofluorescence - which is the screening test, and uses antibodies against A and B. This is what the laboratory public health is doing.
Science : So they do not have the subtype tests and had to send the samples to you
Alpuche : Yes. Not now, because if there is anything unusual, they expect to get accumulated cases and then send to the national reference center. One of the interesting things in this epidemic is that they were testing, but the onset of symptoms was after 4 or 5 days. The sensitivity of the immunofluorescence test is low after 72 hours. Most of the tests, which were nasopharyngeal samples were negative
Scienc e :. You made later sampling over La Gloria, right?
Alpuche : In the last part of the outbreak in La Gloria, the children began to have symptoms April 1. They took samples April 3. They sent samples the laboratory of the state of public health, and they were treated 4. April they arrived in my laboratory on April 8.
science :? What were the positive aspects
Alpuche : They have identified three influenza strains at the end of the period. A proven to be H3N2. The other was, but it was not encouraging. Here in our lab, we considered that this could be H1, but she seemed indeterminate. To be honest, we are not able to enter it. And then we got a B.
Science : The one that you are not able to type, have you sent anywhere else? Did you fear that you can not type
Alpuch e:. At this point, we have no information about the A nontypable they have seen in the children of California
science . in the monitoring program here in California, if you can not type, you send it to CDC
Alpuche : That's what we do. Our collaboration center is CDC. We have three different time to the accumulation of samples sent to the CDC during the season. When we had the first permanent strain of La Gloria, we were not worried. Right now, the epidemic has been controlled.
Science : On April 12, Mexico notified the Pan American Health Organization, in accordance with the International Health Regulations regarding the outbreak of influenza Veracruz. First, do you have that these cases resemble flu
Alpuche :? Our initial thinking, as we reported in accordance with International Health Regulations, was that we were in the process of intensification and extension of the influenza period. We thought outbreaks of Tlaxcala and Perote were nothing unusual in terms of pneumonia. It is later, then we started to consider that there was anything unusual
Science :. On April 17, Mexico began to increase its surveillance of influenza. What triggered the switch to improve active surveillance
Alpuche : We had a notification of an isolated case, a 37-year-old diabetic who is death due to respiratory disease and pneumonia in Oaxaca. The woman had onset of symptoms April 4. There was no connection to Perote. We obtained samples, and it was a lung biopsy because the parents did not allow an autopsy. They studied intensively contacts around the deaths. They found some with respiratory diseases, but no deaths. Nothing unusual, right? They were tested and all were negative for influenza and other viruses.
Science :? When did you first contact Frank Plummer, head of Canada's Public Health Agency National Microbiology Laboratory
Alpuche : I contacted April 17 by e- mail and he replied immediately. He wanted to know more about it, and we had a long conversation Saturday, April 18.
Science Frank told me he not originally thought flu. He thought it would be an unknown pathogen
Alpuche :. Exactly. And we discussed with Dr. Plummer. In fact, I'm the one who called him because I am the person laboratory. I met him through the Action Group for global health security. And we talked about different collaborations, and immediately when we started discussing it and epidemiology, we wanted to exclude all we could
Science .: Why did you contact him?
Alpuche : Canada has a lot of experience with the screening of severe acute respiratory syndrome, SARS, of unknown pathogenesis.
Science : When did you learn of the first two cases of swine flu in California that have been reported in MMWR April 21
Alpuche : CDC sent me a preprint. I do not know exactly when
Science .? When you have samples sent to Canada and CDC
Alpuche : April 21. We have asked for help both simultaneously. The CDC is my collaborating center in the WHO network. They always help us make the quality assessment for us, giving us the reagents, do training, technology transfer. But to do the shipping for each of them, it was a bit difficult. It was a bit delayed to get all the US authorities
Science : Was your decision to send him to Canada also because the US authorities held your samples?
Alpuche : No, not at all. I sent these samples to the CDC because they are my collaboration center. Here's how to do it. We get all the help we need the CDC
Science :. But I think it's important for the United States to learn from that. How long your samples were held in place and why
Alpuche : It was just a difference of 1 day. I can not tell you if it is because it is more difficult to send things from Mexico to the United States rather than Canada. To be honest, I can not explain.
Science : I guess you were frustrated by the delay
Alpuche :. Yeah, but we knew we were going to get the help we needed, and we got it. He was just a little difference
Science .? When have you heard back from Frank Plummer on your samples
Alpuche : We got the preliminary results April 22. Dr. Plummer received the samples at 3:00 in the afternoon and at midnight he called me to say that we had influenza A. Some of the samples that I sent him, we knew they were swine flu this week, we started to see the A and we have started to change our mind that influenza B prolongation of seasonal flu.
Science : When did you know they were positive for a new virus of swine flu?
Alpuche : I learned that it was swine Frank Plummer; that was in the afternoon of April 23. And later that night Dr. Nancy Cox [of CDC] on a conference we had with Mexican experts, we discussed it and she gave us the preliminary results we have some pig strains, those who just arrived that day at CDC
science :. what do you think of the criticism that Mexico has not made early enough to catch it? It comes from the Mexican press and the international press
Alpuche . There will always be to be something to find fault in everything. This is a new unknown virus. We have grown both in terms of diagnosis and epidemiological surveillance recently. We still have limitations, for sure. We really have to accept. And we work very hard to overcome these limitations. We, and all health authorities, has done everything possible to try to define as soon as possible.
We work so hard to try to control it. And we were very open from the beginning. When I received the confirmation of Dr. Frank Plummer, I was immediately in contact with my superior Dr. Mauricio Hernández, and he spoke immediately with Secretary Córdova and was essentially open.
Science : Many laboratories in Mexico that I have visited are very sophisticated. What are the limits that have prevented your lab to identify the new H1N1 virus? What CDC and Canada only you do not have
Alpuche : The only place in Mexico doing subtyping is this lab here. We are able to sequence and subtype, but we are overwhelmed by samples of the flu and other things around the country. It is a bit slower than in the US or Canada
Science .? But what are the limits of your laboratory for virus isolation and sequencing
Alpuche Since this week, we have experts from CDC and Canada helping us develop a PCR live [polymerase chain reaction] technology to test swine H1N1 directly.
Science : Is your lab the only lab in the country at this point who can do the confirmatory test with the real-time PCR machine
[?Alpuche : at this point, yes, but we work with the CDC and Canada to form molecular biologists in different institutions in six different states in Mexico. We have two PCR machines in real time, we were able to immediately - we borrowed from each company. And now, we purchased 10 more machines. We are working full-time to accelerate diagnostics
Science .? How many samples do you have waiting to be tested
Alpuche : right now we have a backlog of about 1,000 tests that we will rush to make it in time . We will have three quarters of people who work in the morning, afternoon and night
Science :. You have 1000 samples waiting to be tested, but there are almost 2,000 suspected cases.
Alpuche had not all cases that have been tested in hospitals samples that were submitted to us. . And not all the 1000 samples we have are suspected cases
Science : Are you always send samples to the CDC and Canada
Alpuche : Yes, we sent several samples to Canada this week, and we just organize one here with the CDC to send more samples to the CDC. We want to exclude all these samples into us so that we can continue with the new
Science :. Many Mexican press and now press outside of Mexico wrote about the Gloria and the large pig farm near Perote, Granjas Carroll. There are all these allegations and even conspiracy theories.
Alpuche :. I do not know, there are so many rumors
Science : What about the boy in La Gloria, which has received much attention
Alpuche :. It was a mild disease, no problem
science : Is it correct that it is the index case
Alpuche :? We're not sure. By the onset of symptoms, it is the first that we see in our database, which is all
Science : .. What is the start for him
Alpuche : April 1.
science : There were all these stories as Perote the epicenter, or sender. Do you believe that
Alpuche : We asked the agriculture authorities, and they have assured us that they do not detect any problems with outbreaks with animals on these farms near Perote. And the farm is located 80 kilometers from La Gloria.
Science : So, it is very far
Alpuche :. Even away to someone who works there to make the trip. But we are studying it. We epidemiological surveillance. And we asked other authorities, and there was virtually nothing wrong
Science .? Is there a confirmed case any employee of Granjas Carroll
Alpuche :. Not that I know to date
science : One of the theories is that this origin in the US or elsewhere and a human being came to Mexico, may -being a migrant. The assumption that he was a big pig could be very misleading
Alpuche :. Perhaps. This is the same thought that we have. We need more data to prove it. One of the interesting things is we see these isolated cases in Oaxaca and Perote, they are well known for migration. And also the other state that we see many cases today when active outbreak is San Luis Potosi, and it is like the migration corridor. It is hard to believe that it will be associated to this farm, but I know that the authorities thoroughly investigated, it
Science :. Do you think if it resurfaces elsewhere that Mexico would have been contained, or the flu just go too fast anyway
Alpuche : Considering it was the end of the season, maybe confused done a little something else might grow, but probably the flu moves too fast anyway.
Science The US cases detected early, and the US has not been able to contain it. He said that the virus is smarter
Alpuche : Yes, for sure
Science :. One. last thing. How many hours a night do you sleep
Alpuche : .. [laughter] At the two
Science . This has been going on for 2 weeks now
Alpuche : Yeah, so some days we get 2 hours and then a nap half an hour. And there Latte. double strokes. . Espresso
Science : Anything you need, anything at present the international community
Alpuche : We 're all right now in the way we work and our employees. But at some point, if we need it so I'll ask. But now, we agree.
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