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Compiled by Kristen Cole   Date: 4/27/09 Bookmark and Share

Q & A with Rob Dorit: the Lowdown on Swine Flu

Rob Dorit (on right) examines cells with a student in the lab.

With the news about the swine flu first reported in Mexico spreading as quickly as the virus, Robert L. Dorit, Smith associate professor of biological sciences, shares his knowledge about what is known and unknown at this point.

“The influenza virus is a notorious shape-shifter,” says Dorit, who is an expert on molecular evolution, antibiotic design and resistance. “This strain has picked the lock of human-to-human transmission quickly.”

Gate: What do we know about the swine flu?

Rob Dorit: In addition to humans, many species can be infected by the influenza virus. We refer to the other species that can harbor influenza as animal reservoirs.  As a general rule, influenza viruses are specifically adapted to infect and thrive within a single host species--thus, pig influenza viruses are best able to infect pigs, and bird influenza strains do best in birds. Occasionally, however, influenza viruses can make a cross-species jump, and infect humans. There have been previous examples of a swine flu infecting humans, but it has generally been confined to individuals that come into extensive and frequent contact with pigs. Once inside a human host, the swine strain can be reshaped by evolution into a strain that can thrive in the new host.

Gate: What don't we know about the flu? How does that impact the public health response?

RD: The initial reports from Mexico suggest that this influenza A (H1N1) strain of swine flu has infected a large number of individuals (>1400), most of whom have not been in recent contact with pigs. This suggests the possibility that this strain was either already capable of infecting humans (a fortuitous consequence of the similarity between the human and pig immune systems), or else has quickly evolved the capacity for human-to-human transmission. This strain appears to be responsible for more than 100 deaths in Mexico so far. There are now sporadic reports of possible infection with this strain in the U.S. and Canada, as well as in Spain, France, Israel, Brazil and the South Pacific.

But this situation is in rapid flux, and there are many things we do not yet know. We do not, for instance, have confirmation that the deaths in Mexico are all the result of this strain, or may represent an amalgamation of several lethal respiratory infections. Similarly, the strain responsible for the cases being reported outside of the 
Americas is still unconfirmed. The confirmed cases in the U.S. are characterized by quite mild symptoms, raising important questions about the differences in disease severity between the cases in Mexico and those in the U.S. Finally, the infectivity of this strain is still not well understood, and the possibility that the enormous density and environmental degradation in Mexico City may be contributing to the spread of the virus (and the severity of symptoms) cannot be dismissed.

The public health response to date has been impressive. In Mexico, public health authorities have responded quickly and effectively, largely by engaging citizens in a series of measures meant to reduce the transmission of this virus: schools are closed, large gatherings discouraged, and individuals exhibiting symptoms are being encouraged to report to clinic and minimize contact with uninfected individuals.  Outside of Mexico, the response, for now, involves additional surveillance for possible unexpected influenza outbreaks, as well as reminders of some common sense measures, such as the importance of washing hands, avoiding contact with infected individuals and reporting to your health care practitioner if you suspect you may have the flu.

Gate: How does a new flu arise?

RD: New influenza strains arise all of the time, both as a result of the biology of the virus and the ecology of hosts. The influenza virus is a notorious shape-shifter, and it accomplishes this feat by virtue of its high rate of mutation and its ability to occasionally sequester versions of the genes that encode its surface proteins from other species. The influenza virus is, in effect, constantly sending out a swarm of variants, or versions, to test the defenses of actual and potential hosts. Most of these scouts fail in their mission. But occasionally, a variant strain will enter a host whose immune system cannot recognize the surface proteins of the virus. Although the immune system of the host will mount a defense, this takes time, and the virus takes advantage of this lull to establish a foothold in the new host.

The ecology of hosts also plays a role. In the case of human influenza, the high population density in certain urban areas, the limited access to primary care, and the frequent burden of co-infection with other infectious diseases may all be playing a role in the spread of this strain in Mexico. For non-human hosts, the spread and intensification of industrial agriculture with the consequent confinement of very large numbers of animals (pigs) or birds (chickens, ducks) in small spaces, may also be promoting the emergence of new strains.

Gate: What makes this one more or less scary than any other flu?

RD: Three aspects of this outbreak are causing significant concern:

1) This strain of swine flu appears capable from the outset of human-to-human transmission. While other swine flu strains do occasionally enter the human population, the outbreaks tend to be self-limiting, precisely because the individuals that first acquire the infection cannot easily pass it on to other humans. This strain has picked the lock of human-to-human transmission quickly.

2) The deaths being attributed to this H1N1 swine flu strain are occurring among otherwise healthy children and young adults. While other flu strains can be lethal, they usually fell individuals from immunologically vulnerable groups, including the very young and the elderly. This strain is killing individuals that would normally be  able to fend off the infection. The deaths early in the most devastating pandemic of influenza (the 1918 pandemic) also occurred among healthy young adults.

3) The world has become a smaller and more deeply interconnected place, and the flow of people through Mexico is very high. As a result, a strain emerging in a cosmopolitan and well-connected world capital such as Mexico City can be spread around the world by travelers in a matter of days. All of the confirmed cases reported outside the U.S. involve individuals who had traveled in Mexico in the last two weeks.

There are, however, some reassuring aspects to this outbreak:

1) The strain appears to be sensitive to currently available antivirals, provided these are administered early in the course of infection. Strains that are resistant to antivirals have been reported in the past, and an outbreak of such a strain would significantly complicate control and treatment. Extensive stockpiles of these antivirals exist and are being effectively distributed in the U.S. and around the world should they be needed.

2) The international response appears to be well-coordinated and transparent. Over the past decade, a number of mechanisms have been put in place to allow for the rapid dissemination of information about and the coordinated response to disease outbreaks. National and international organizations appear to be collaborating effectively to monitor the progress of the outbreak, to mount an effective response, and to remind the public of some common-sense measures that can reduce viral transmission.

3) In part as the result of the concern surrounding possible bird flu outbreaks over the past three years, the public appears to be aware of the risk of transmission of influenza, and is reacting calmly and reasonably.

4) While this virus appears to be highly transmissible, the milder symptoms being reported in cases outside of Mexico suggest it may be somewhat less dangerous than initially feared.



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