WHO will redefine pandemic

pandemic-influenzaThe World Health Organization, whose duties include directing and coordinating authority for health within the United Nations system, will soon be writing science textbooks.

That statement isn’t true, of course. But it was my reaction to reading the latest announcement from Geneva:

Bowing to pressure, the World Health Organization announced Friday that it would rewrite its rules for alerting the world to new diseases, meaning the swine flu circling the globe will probably never be declared a full-fledged pandemic. Dr. Keiji Fukuda, the deputy director general making the W.H.O. announcement, said that he could not predict exactly what the new rules would be but that criteria would include a “substantial risk of harm to people,” not just the geographic spread of a relatively benign virus.

Apparently members of the United Nations don’t like the fact that WHO has been using ‘pandemic’ to describe the global spread of the new H1N1 influenza strains. They feel that the word pandemic implies that the virus is lethal and capable of causing many deaths – like the 1918 strain of influenza. Problem is, the new H1N1 strain isn’t any more lethal than seasonal strains of the virus. Apparently using the p-word gets everyone frightened as pandemic preparedness plans shift into gear.

According to the virology textbooks (one of which I wrote), the word pandemic means ‘global epidemic’. Even wikipedia has a benign definition: “A pandemic (from Greek παν pan all + δήμος demos people) is an epidemic of infectious disease that spreads through populations across a large region; for instance a continent, or even worldwide.”

I can already see how the WHO edict will influenza future versions of textbooks. For example, the current edition of  Clinical Virology states “Over the past 300 years, at least six pandemics of influenza have probably occurred, including three well-characterized ones in the 20th century”. In the next edition, this will have to be rewritten: “Until recently, at least six pandemics of influenza have probably occurred, including three well-characterized ones in the 20th century. In 2009, a new strain of H1N1 influenza emerged and spread globally, but it was not considered a pandemic by the new WHO rules”.

WHO redefining pandemic is absurd. Pandemic is an epidemiological definition that has nothing to do with virulence. A pandemic of influenza occurs when a new viral strain emerges to which the population has little or no immunity. Although pandemic is most frequently associated with influenza virus, other infectious agents may cause worldwide epidemics. The world is currently in the midst of an AIDS pandemic, one of the worst in history.

WHO should leave textbook writing to others. To paraphrase Andre Lwoff, a pandemic is a pandemic. The word implies nothing about virulence – and has little to do with politics.

Swine influenza A/Mexico/2009 (H1N1) update

reassortment-swineHere is an update on the global swine flu situation as of 29 April 2009.

There are now 257 laboratory confirmed cases, with 7 deaths, in 11 countries. In the US there are 109 cases  in 11 states. There are many more suspected cases; together the statistics indicate widespread dissemination of the new H1N1 influenza virus. I no longer doubt that this is the next pandemic strain. WHO will probably soon raise the level of influenza pandemic alert from phase 5 to phase 6. Important questions include whether spread will continue in the northern hemisphere through the summer, or stop very soon, as is the case with most influenza virus outbreaks. Unfortunately the southern hemisphere seems in for an extended flu season. Will antivirals be useful in reducing morbidity and mortality? Will the virus returns to the north in a more virulent form in the fall? Can a vaccine be prepared in time?

Viral RNA sequences from 12 new isolates were deposited at NCBI, bringing the total to 32. Conspicuously missing are sequences from Mexican isolates. In a Science Magazine interview, Ruben Donis, Chief of the molecular virology and vaccines branch at CDC, indicated that strains from Mexico and elsewhere are “very, very similar. Many genes are identical. In the eight or nine viruses we’ve sequenced, there is nothing different.” It’s still not clear why these sequences have not been released; clearly the work has been done. In any case, his statement confirms what we have suspected from examining other isolates, that the Mexican strains are not sufficiently different to explain their apparent higher pathogenicity.

I highly recommend reading the interview with Dr. Donis, as it contains a wealth of information about the new H1N1 virus. Much of it will be difficult to understand for those without familiarity with influenza virus, but you can send your questions to virology blog. One interesting aspect concerns the statement last week that the new virus was composed of genes from pig, human, and avian sources. Examination of the sequences in the past week has revealed the virus to be composed of RNAs solely from swine viruses. Here is what Dr. Donis said:

Q: Is it of swine origin?

R.D.: Definitely. It’s almost equidistant to swine viruses from the United States and Eurasia. And it’s a lonely branch there. It doesn’t have any close relatives.

Q: So where are avian and human sequences?

R.D.: We have to step back [to] 10 years ago. In 1998, actually, Chris Olsen is one of the first that saw it, and we saw the same in a virus from Nebraska and Richard Webby and Robert Webster in Memphis saw it, too. There were unprecedented outbreaks of influenza in the swine population. It was an H3.

The PB1 gene, that was human. H3 and N2 also were human. The PA and PB2, the two polymerase genes, were of avian flu. The rest were typical North American swine viruses. Those strains were the so-called triple reassortants.

I’ll post an entry this weekend on the history of swine viruses, which should help clarify Dr. Donis’ explanation.

On Friday, 1 May I will be holding a FAQ session on swine flu with Marc Pelletier of Futures in Biotech. A video stream of our conversation will be broadcast live at 4:00 PM EST at live.twit.tv. Send us your questions via twitter to @profvrr.

Swine influenza H1N1 update

pandemic-phase-42Here are some updates on the global status of swine influenza H1N1.

As of Monday, 27 April, the US has reported 40 laboratory confirmed cases of swine influenza H1N1 infection in California, Kansas, New York City, Ohio, and Texas. Mexico has confirmed 26 human cases with seven deaths,  Canada reports six cases, and Spain one case. The first two cases of the illness in the UK were reported in Scotland. These statistics were obtained from ProMED-mail, WHO, and CDC.

You might find higher numbers from other sources. The difference is that the numbers in the preceding paragraph are laboratory confirmed cases – meaning that the virus has been isolated from the patient and identified as swine influenza H1N1 (or A/California/07/2009 (H1N1), in the influenza virus nomenclature). Many suspected cases are being reported – in these the disease appears to be influenza, but confirmation of infection with A/California/07/2009 (H1N1) has not been confirmed by laboratory tests. For example, the suspected death toll in Mexico is 149, with 1995 hospitalizations. There are also suspected cases in England and Australia.

As a consequence of the continuing spread of the virus, the WHO Director-General has raised the level of influenza pandemic alert from phase 3 to phase 4. According to WHO, “This phase is characterized by verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause community-level outbreaks.” A complete explanation of pandemic alert phases can be found at the WHO website. In Mexico, health authorities have closed schools in the entire country until 6 May. In the US, CDC activated its Emergency Operations Center to coordinate the agency’s response, and the Secretary of the Department Homeland Security has declared a public health emergency. These actions will allow the release of funds to support the public health response.

Because a vaccine is not yet available for A/California/07/2009 (H1N1), antiviral compounds (Tamiflu and Relenza) must be used to curb epidemics. The use of such compounds may save many lives at the expense of selecting for drug resistant viruses. If such variants emerge before immunization can be carried out they will limit our ability to control the infection.

Here are my answers to some questions posted to virology blog:

Q: Do you have any theories as to why the mortality rate (apparently) is higher in Mexico than it is elsewhere?

A: I have two theories. One involves the possibility that infection with the current circulating human H1N1 strain might confer some protection, in the form of milder disease, to infection with the swine H1N1 virus. If this is true – and it might not be – then one could speculate that individuals in Mexico City were less immune to human H1N1, and consequently experienced more severe disease when infected with the swine strain.

The other theory is more vague – because Mexico City is extremely densely populated, the virus may spread more quickly, infecting more people, leading to selection of more virulent viral variants.

Q: Are viruses more likely to get more or less pathogenic as time goes on?

A: It could go either way. Viruses need living hosts in which to multiply – if they kill the host quickly, or debilitate the host so it cannot interact with others (to spread the infection), then the virus will not endure. On the other hand, you can imagine how increased virulence leading to more coughing and sneezing could help spread the infection. This topic is hotly argued among virologists, which means that both sides probably are correct.

Q: Should we be saving our Relenza and Tamiflu if this does become highly pathogenic?

A: Save them for the fall, in case the virus returns then. Flu season is basically over in the US, and with the increasing heat and humidity (over 90° today in NYC) virus transmission should soon stop. However, if A/California/07/2009 (H1N1) takes hold in the southern hemisphere in the coming months – their flu season is still beginning – it is likely to return to the northern hemisphere in the fall. Unfortunately, by then extensive antiviral use in the southern hemisphere is likely to have produced drug-resistant variants.

Q: I keep thinking about the Great Influenza book – that in an era with no planes, the virus traveled around the world three times. Given our capacity for travel now, is quarantine even possible?

A: No. The CDC has already said quarantine is futile. Check out the transcripts of their press conferences; they are a good read (or listen).

Q: Will our over vigilance in treating this lead to its becoming resistant quicker?

A: If you mean treating the infection with antivirals, then the answer is a resounding yes. Many people have likely been saving Relenza and Tamiflu, and they will take them at the first sign of a respiratory illness.

Q: Should this be considered a prime candidate for next winters flu season?

A: It depends on what happens in the southern hemisphere. In the next week or two we will know whether A/California/07/2009 (H1N1) spreads in the lower half of the globe and causes epidemics of disease. If it does, then it is highly likely that the virus will return here in the fall. If the virus fails to spread, then everyone can go back to worrying about H5N1.

Send your questions to virology blog (virology@virology.ws) and I will post my answers each day.

Polio returns to Minnesota

amishPoliovirus has been isolated from a patient who died last month in Minnesota. Is this incident related to the outbreak of polio in an Amish community in the same state four years ago?

Here are the facts about this case that have been released by the Minnesota Department of Health: the patient, an adult, had paralytic polio, but it is not known if this played a role in death. Apparently the patient had multiple health problems, including a weakened immune system. The virus isolated from this patient is related to the infectious, orally administered poliovirus vaccine, OPV. They speculate that the patient was infected with OPV over nine years ago, because the use of this vaccine in the US was discontinued in 2000.

The fact that OPV use was discontinued 9 years ago in the US does not prove that this patient was infected with a vaccine virus at that time. The only way to answer this question would be to determine the nucleotide sequence of poliovirus isolated from the patient. From this information the number of years that the vaccine-derived virus has been replicating in humans could be determined. However, no sequence information has been reported by the Department of Health. It is likely that the patient was infected with poliovirus at any time in the last 9 years. If in fact the patient had an immunodeficiency, then infection could have persisted for at least nine years, as has been reported in other immunodeficient patients. However, it seems unlikely that the virus would replicate for 9 years in this individual, and then cause paralytic disease only recently.

I believe this individual was a member of a Minnesota Amish community and was therefore not immunized with OPV as an infant. The patient was probably infected recently with a strain of poliovirus derived from OPV. Because OPV has not been used in the US since 2000 and in Canada since 1995-96, the infecting virus was either imported from another country, where OPV is still used, or shed by an immunodeficient individual in the US. Such patients excrete poliovirus for years in the absence of clinical symptoms. A similar scenario has been invoked to explain poliovirus infection in 2005 of children in a Minnesota Amish community.

We will find out whether this speculation is correct when the Centers for Disease Control and Prevention release the complete data on this case.

You might be wondering why poliovirus has been isolated on two separate occasions in Minnesota. It so happens that the former Minnesota State epidemiologist was Dr. Harry Hull,  who previously worked on the polio eradication campaign at the World Health Organization. When he arrived in Minnesota after his WHO stint, he installed an excellent polio surveillance system in the state which remains in place to this day.

Odoom, J., Yunus, Z., Dunn, G., Minor, P., & Martin, J. (2008). Changes in Population Dynamics during Long-Term Evolution of Sabin Type 1 Poliovirus in an Immunodeficient Patient Journal of Virology, 82 (18), 9179-9190 DOI: 10.1128/JVI.00468-08

Poliovirus

Poliovirus by Jason Roberts

Poliovirus is the etiologic agent of the paralytic disease known as poliomyelitis. It’s also the virus I’ve worked on for most of my career. The World Health Organization is in the midst of a massive effort to eradicate the disease, an undertaking that has encountered a number of obstacles. In coming posts I’d like to discuss the polio eradication effort, but first we need some background on poliovirus.

Poliovirus is a member of a family of viruses called the Picornaviridae. Viruses are classified into families, and then genera, based on many criteria, including physical and biological properties. The Picornaviridae includes many other human pathogens, such as Coxsackieviruses, echoviruses, enteroviruses, hepatitis A virus, and rhinoviruses (which cause the common cold). The International Committee for the Taxonomy of Viruses is responsible for virus classification and maintains the Universal Virus Database, where you can find information about most known viruses.

Poliovirus is a rather small and simple virus. It is composed of a shell, or capsid, made of protein, as shown.

The poliovirus capsid is about 30 nanometers in diameter. Within the capsid is the information to make new virus particles – a single molecule of ribonucleic acid, or RNA. In the image, part of the capsid has been cut away to reveal the viral RNA. When the virus infects a cell, the RNA genome enters the cell and programs it to make new virus particles. These virus particles are released from the cell and go on to infect new cells.

In humans, poliovirus is ingested, and replicates in cells of the gastrointestinal tract. Newly synthesized virus particles are released into the intestine and shed in the feces. Transmission of poliovirus to another human occurs through contact with virus-containing feces or contaminated water. After multiplying in the gastrointestinal tract, poliovirus may enter the spinal cord and brain. Destruction of motor neurons by the virus leads to limb paralysis.

Poliomyelitis became a common disease at the turn of the 20th century. Two vaccines were developed in the 1950s that can effectively prevent the disease – inactivated poliovaccine (IPV, developed by Jonas Salk) and live, oral poliovaccine (OPV, developed by Albert Sabin). In 1988 the World Health Organization announced that it would eradicate poliomyelitis from the globe by the year 2000. We’ll discuss that goal, and obstacles that might prevent it from being attained, in subsequent posts.