Influenza surveillance in the US

A network of ~150 laboratories in the United States participate in virological surveillance for influenza. The results of these analyses are publicly available, and provide extremely interesting characterization of the pandemic spread of the new H1N1 strain. During week 22, 6,664 samples were submitted for testing, of which 2,681 were positive for influenza virus. Of these, 2,071 (89%) were identified as the new H1N1 strain. The previous seasonal influenza A (H1), A (H3), and B viruses continue to co-circulate. These observations are summarized on this graph:

influenza-week-22

I have noted previously the unusual upsurge in influenza activity during weeks 17 and 18, which coincided with the emergence of the new H1N1 virus. The number of virus-positive specimens dropped during week 19, but has since risen. More importantly, the percent positive specimens – the black line – continues to rise. This observation suggests that the new H1N1 virus will continue to circulate, at least for the next month. Increased sampling by clinicians in the face of a pandemic probably also contributes to the rising numbers of influenza positive specimens.

Also of interest is the declining circulation of the two influenza virus strains of the previous season – H3N2 and H1N1. Of the 2,681 influenza positive samples in week 22, 9 were identified as the previous seasonal H1N1 strain, and 22 as the H3N2 strain. The circulation of these seasonal influenza viruses into June is probably not abnormal. Because of the pandemic H1N1 strain, more samples are being tested than is usual. Clinicians stop testing for influenza virus at the end of May as the ‘flu season’ wanes. CDC stops its influenza surveillance in May, and resumes in the fall. This year CDC will probably keep up the influenza reporting through the summer. According to Dr. Anthony Fiore, a medical epidemiologist at CDC,

Now people who don’t normally look for flu are looking more than they ever have. We’re seeing that some of the respiratory illnesses that occur even late in the season may be due to seasonal flu viruses that we didn’t appreciate in the past. I guess we don’t know that anything different is occurring right now with seasonal flu viruses. This is an artifact of clinicians looking very hard for flu viruses at a time they don’t normally look.

The textbooks have always said that influenza viruses can be isolated from large northern hemisphere cities throughout the summer. The increased surveillance this year will provide a more detailed picture of the extent of influenza virus spread.

I’m also looking forward to reviewing influenza surveillance data from the southern hemisphere in the coming months. The Department of Health and Ageing of Australia provides similar data as the CDC, but their information has not been updated since 22 May and consequently the impact of circulation of the new H1N1 strain is not evident.

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

CDC influenza RSS feed

455572466_19166858d6_oThe Centers for Disease Control and Prevention has added a new RSS feed called ‘CDC Flu’. This feed will keep track of any new or updated documents posted anywhere on the CDC Flu Website. This website has a great deal of useful information about influenza, including weekly activity reports, recommendation on immunization and antivirals, and notification of upcoming events. It’s a terrific resource for scientists or anyone who wants to learn more about this respiratory infection.

You can subscribe to the CDC Flu RSS feed here.