Incidence of death for 2009

On August 9, 2009, I provided a list of countries with the highest incidence of death expressed as the number of deaths per 100,000 people. The following is a similar list which includes all countries with data for the year 2009. Countries are listed in descending order.

1. Saint Kitts and Nevis – 3.8
2. Marshall Islands – 1.6
3. Argentina – 1.5
4. Sao Tome and Principe – 1.2
5. Latvia – 1.2
6. Canada – 1.2
7. Malta – 1.2
8. Barbados – 1.2
9. Bahamas – 1.2
10. Samoa – 1.1
11. Israel – 1.1
12. Oman – 1.1
13. Costa Rica – 1.0
14. Mongolia – 1.0
15. Uruguay – 1.0
16. Tonga – 1.0
17. United States – 0.9
18. Kuwait – 0.9
19. Chile – 0.9
20. Australia – 0.9
21. Brazil – 0.8
22. Paraguay – 0.8
23. Montenegro – 0.8
24. Mexico – 0.8
25. Estonia – 0.7
26. Peru – 0.7
27. Moldova – 0.7
28. Ecuador – 0.7
29. Macedonia – 0.7
30. Finland – 0.7
31. Portugal – 0.7
32. Turkey – 0.6
33. Qatar – 0.6
34. Slovenia – 0.6
35. Iceland – 0.6
36. Libya – 0.6
37. Greece – 0.6
38. Mauritius – 0.6
39. Palestinian Territories – 0.6
40. Luxembourg – 0.6
41. Norway – 0.6
42. Spain – 0.6
43. Bolivia – 0.6
44. Saint Lucia – 0.6
45. Serbia – 0.6
46. Slovakia – 0.6
47. Croatia – 0.5
48. Czech Republic – 0.5
49. Hungary – 0.5
50. El Salvador – 0.5
51. United Kingdom – 0.5
52. Syria – 0.5
53. Ireland – 0.5
54. Saudi Arabia – 0.5
55. Lithuania – 0.5
56. Denmark – 0.5
57. New Zealand -0.5
58. Bulgaria – 0.5
59. Ukraine – 0.4
60. Colombia – 0.4
61. Venezuela – 0.4
62. Singapore – 0.4
63. Suriname – 0.4
64. Cyprus – 0.4
65. Trinidad and Tobago – 0.4
66. Cuba – 0.4
67. France – 0.4
68. South Korea – 0.4
69. Maldives – 0.3
70. Netherlands – 0.3
71. Poland – 0.3
72. Panama – 0.3
73. Italy – 0.3
74. Thailand – 0.3
75. Malaysia – 0.3
76. Romania – 0.3
77. Sweden – 0.3
78. Jamaica – 0.3
79. Jordan – 0.3
80. Brunei – 0.2
81. Russia – 0.2
82. Georgia – 0.2
83. Dominican Republic – 0.2
84. Honduras – 0.2
85. Belarus – 0.2
86. Iran – 0.2
87. Nicaragua – 0.2
88. Solomon Islands – 0.2
89. South Africa – 0.2
90. Albania – 0.2
91. Bahrain – 0.2
92. Bosnia and Herzegovina – 0.2
93. Tunisia – 0.2
94. Sri Lanka – 0.2
95. Germany – 0.2
96. Morocco – 0.2
97. Belgium – 0.2
98. Switzerland – 0.2
99. Taiwan – 0.2
100. Egypt – 0.1
101. Iraq – 0.1
102. Algeria – 0.1
103. United Arab Emirates – 0.1
104. Guatemala – 0.1
105. Lebanon – 0.1
106. Yemen – 0.1
107. Armenia – 0.1
108. Japan – 0.1
109. India – 0.1
110. Afghanistan – 0.1
111. Vietnam – 0.1
112. China – 0.1

Namibia, Cambodia, Austria, Phillippines, Azerbaijan, Laos, Madagascar, Sudan, Nepal, Mozambique, Pakistan, Indonesia, Ghana, Bangladesh, Tanzania and Burma reported an incidence of death of less than .05.

The following countries have reported cases of pandemic H1N1, but no deaths: Andorra, Angola, Antigua and Barbuda, Belize, Bhutan, Botswana, Burundi, Cameroon, Cape Verde, Cote d’Ivoire, Democratic Republic of the Congo, Djibouti, Ethiopia, Fiji, Gabon, Grenada, Guyana, Haiti, Kazakhstan, Kenya, Kiribati, Lesotho, Liechtenstein, Malawi, Micronesia, Monaco, Nauru, Nigeria, North Korea, Palau, Papua New Guinea, Republic of the Congo, Rwanda, Saint Vincent and the Grenadines, Senegal, Seychelles, Swaziland, Tajikistan, Tuvalu, Uganda, Vanuatu, Zambia, and Zimbabwe.

The following countries have not reported any pandemic H1N1 cases: Central African Republic, Chad, Comoros, Equatorial Guinea, Eritrea, Gambia, Guinea, Guinea-Bissau, Holy See, Kyrgyzstan, Liberia, Mali, Mauritania, Niger, Sierra Leone, Somalia, Timor-Leste, Togo, Turkmenistan and Uzbekistan.

Future blogs will discuss the significance of this data in more detail.

Incidence of Death in US States – December 31, 2009

I last posted a list of the US States with incidence of death per 100,000 on September 9, 2009. Not surprisingly, the numbers have gotten much worse in the following months. Here is the current list, in descending order:

1. South Dakota – 2.9
2. New Mexico – 2.5
3. Arizona – 2.0
4. Oregon – 2.0
5. Montana – 2.0
6. Wyoming – 1.0
7. Alaska – 1.7
8. American Samoa – 1.7
9. Nevada – 1.6
10. Utah – 1.6
11. California – 1.5
12. Iowa – 1.3
13. Idaho – 1.3
14. Maine – 1.3
15. Rhode Island – 1.2
16. Washington – 1.2
17. Colorado – 1.2
18. Guam – 1.2
19. West Virginia – 1.1
20. Oklahoma – 1.1
21. Florida – 1.1
22. Minnesota 1.0
23. Puerto Rico – 1.0
24. US Virgin Islands – 0.9
25. South Carolina – 0.9
26. Louisiana – 0.9
27. Kansas – 0.9
28. Hawaii 0.9
29. North Carolina – 0.8
30. Kentucky – 0.8
31. Alabama – 0.8
32. Wisconsin – 0.8
33. Connecticut – 0.8
34. New York – 0.8
35. Tennessee – 0.8
36. Texas – 0.8
37. Nebraska – o.8
38. Michigan – 0.7
39. Maryland – 0.7
40. Arkansas – 0.7
41. New Hampshire – 0.7
42. Illinois – 0.6
43. Pennsylvania – 0.6
44. Indiana – 0.6
45. Delaware – 0.6
46. Mississippi – 0.5
47. Vermont – 0.5
48. North Dakota – 0.5
49. Virginia – 0.4
50. New Jersey – o.4
51. Georgia – 0.4
52. Massachusetts – 0.4
53. Ohio – 0.3
54. Missouri – 0.2
55. District of Columbia – 0.2

The overall incidence of death per 100,000 people in the United States is 0.9.

One of the striking results from this list is the wide range in the reported incidence of death due to H1N1 in the different States and Territories. The reported incidence of death is 10 times higher in South Dakota than in Ohio, Missouri and the District of Columbia. Does this represent a true difference or is it due to variations in competency and/or honesty of public health officials? For example, Ohio health officials appear to have covered up clusters of H1N1 cases in that State. Comparisons of reported pandemic H1N1 deaths with overall pneumonia and influenza deaths as well as maternal and child deaths may allow an analysis of how honesty and/or competency of various State public health officials has affected reporting of pandemic deaths.

Although reporting errors likely account for some of the variation among States and Territories, the presence of Western/Northern Tier States among the top 10 is striking. One explanation for this may be due to relatively large numbers of Native Americans who have been disproportionately affected by this pandemic.

Although the number of reported new cases of H1N1 has been dropping in the United States, the pandemic is not over. Many observers are concerned that there will be another surge in cases in January and February of 2010.

Time will tell.

Chan kills the WHO?

In the latest bizarre media output from the Director-General of the WHO, Margaret Chan takes on anti-vaccine conspiracy theorists. Or does she?

From an interview in The Canadian Press with Helen Branswell:

And in wild and wacky reaches of the Internet – fertile ground for those who sow seeds of speculation and conspiracy – there are even accusations that the WHO colluded to create and unleash the new virus on an unsuspecting world.

“I can understand all these suspicions and conspiracy thinking, but I must emphasize there’s no basis for that. Absolutely no basis,” Chan insisted.

Asked if she really does understand how people could conclude the agency she heads had a hand in starting a pandemic, Chan’s tone changed.

“If indeed that conspiracy, if there is any evidence and basis to it, I want to see that (evidence), number 1,” she said.

If there is any solid proof, “I will personally kill the organization,” she said.

I’m not sure what the context is for the passage about the “wild and wacky reaches of the internet”. Was this the de rigeur denunciation of “those crazy people on the internet” by a MSM reporter or did Chan bring up the idea of the WHO conspiracy by herself? Chan’s response to this apparent question is bizarre. As Director-General of the WHO, she should know whether or not her organisation caused a pandemic. Hence, the presumed response should be that such rumors are completely false, period. Her request for evidence and promise to kill the WHO if any is found is odd. It suggests that such evidence might be found and that she, personally, has the power to destroy a United Nations organisation.

What would be the best way for the Director-General of the WHO to give aid and comfort to anti-vaccine advocates? Why, by disclosing that she herself has not been vaccinated.

From the AFP

World Health Organization chief Margaret Chan revealed Tuesday that she has yet to be vaccinated against the swine flu virus, which has killed over 11,500 people world-wide.

“I have asked my medical service to enquire where I can go to get my vaccination,” she told reporters in Geneva, pointing out that she has just returned from leave.

The WHO director-general stressed that she would “of course” get vaccinated and that “many of my staff” at the WHO have already taken their jabs against the A(H1N1) virus.

The Director-General of the WHO doesn’t know where she can get a flu shot? Really? The excerpt above will be used over and over again on anti-vaccine sites to create suspicion about the vaccine. Something Dr. Chan and her handlers cannot possibly not know.

For the record, I am a vigorous opponent of the anti-vaccine conspiracy sites on the internet (some of which include prominent flu forums with excellent relationships with the MSM). I don’t think the WHO created pandemic H1N1. But it is not crazy to wonder if pandemic H1N1 was created by someone in some way. After all, “seasonal” H1N1 most likely came from a Chinese laboratory.

What crazy internet conspiracy site did I get that one from?

The New York Times. What a bunch of wackos.

Pandemic H1N1 greatly increases the death rate among pregnant women – The California study

Pregnant women died at much greater rates during previous pandemics than other people. The 2009 pandemic is no exception.

From The New England Journal of Medicine

Eight patients in this series died…None of the eight received antiviral agents within 48 hours after symptom onset…

[snip]

Over the 4-month study period, the cause-specific maternal mortality ratio for 2009 H1N1 influenza was estimated at 4.3 in California. The maternal mortality ratio for death from any cause was 19.3 in California in 2005 and 13.3 in the United States in 2006. More than two thirds of maternal deaths in the United States each year are directly related to obstetrical factors, and maternal deaths due to influenza have been rare. The high 2009 H1N1 influenza–specific maternal mortality suggests that this pandemic has the potential to notably increase overall maternal mortality in the United States in 2009.

It is worth noting that none of the 8 patients who died with confirmed H1N1 had been treated with Tamiflu within the recommended 48 hours of symptoms. Given that approximately 50% of the pregnant women had received Tamiflu within 48 hours of symptoms, it is highly likely that Tamiflu greatly reduced the death rate among pregnant women.

Again, the stories suggesting pandemic H1N1 are no worse than seasonal flu are at variance with the truth. 2009 will likely go down in American history as one of the years with the highest recorded number of deaths among pregnant women, despite the advanced medical care most women received. In countries where Tamiflu and advanced medical care is not readily available, very large numbers of deaths among pregnant women is likely.

Reference

Louie et al. (2009) Severe 2009 H1N1 Influenza in Pregnant and Postpartum Women in California. New England Journal of Medicine. December 23.

Pandemic H1N1 10 times more lethal to children than seasonal flu – The Argentinian study

One of the great falsehoods promulgated about the current influenza pandemic is that the new H1N1 virus is no worse than seasonal flu. This statement is based on comparing seasonal death rates among the elderly, which assume excess deaths in the winter are due to influenza, without testing, with lab-confirmed deaths due to pandemic flu. Such comparisons are not legitimate because we don’t know for sure that all the elderly deaths are due to influenza, not everyone who has died of pandemic flu is recorded due to inadequate testing and the current pandemic is not over yet. However, the most important reason why these comparisons are not valid is due to the ages of the people who die in a normal flu season versus this pandemic. The vast majority who die of seasonal flu are elderly. The vast majority of those who have died of the new H1N1 have been middle-aged and younger.

A recently published study in the New England Journal of Medicine attempts to quantify the mortality rate of the new H1N1 virus with seasonal flu on children in Buenos Aires. Here is what they found:

Pandemic 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza in previous years.

This is likely an underestimate of the true lethality of the new H1N1 virus relative to seasonal flu. Although Argentina was slow to close their schools, once the burden on emergency rooms became too great, they did engage in extensive social distancing measures including school and business closures. These actions likely reduced the number infected and, consequently, the number of children who would otherwise have died from pandemic flu. Such extraordinary steps were not taken during normal flu seasons.

The antivrial drug oseltamivir (Tamiflu) is rarely prescribed in Argentina for seasonal flu. However, as the deaths mounted in Argentina, this drug was prescribed with increasing frequency. There is reason to believe that people who received it promptly were more like to survive. From the study:

Of the 13 patients who died, 5 were hospitalized within 48 hours after the onset of symptoms; none received timely oseltamivir.

Without Tamiflu, the number of deaths among children in Argentina might have been much higher.

The American CDC was in close contact with Argentinian authorities during their outbreaks this summer. Further, they were likely well aware of the results of this study months ago. Yet, the Director of the CDC, Thomas Frieden, saw no reason to close American schools until a vaccine was ready. Further, the CDC was slow to encourage the use of Tamiflu to treat patients, despite clear evidence that children were dying due to lack of access.

The failure of the CDC to warn American parents that their children would be 10 times more likely to die of pandemic flu than seasonal flu is inexcusable. Many American children likely died because of CDC policies on school closure and Tamiflu prescription.

Reference

Libster et al. (2009) Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1) in Argentina. New England Journal of Medicine. December 23.

Turkey goes silent

The government of Turkey has announced that they will now censor coverage of the spread of the pandemic within that country. Specifically, they will hide data relating to deaths. [hat-tip, Oric].

From ANSAmed, December 23, 2009

Turkey’s Health Ministry will no more make public death toll from swine flu, as Turkish daylies Milliyet and Vatan report today. The ministry was expected to release the toll today but it announced that routine statements would not be made anymore as the World Health Organization, or WHO, has not recommended such a practice.

The implication of the excerpt above is that the decision to hide pandemic deaths in Turkey is made on the recommendation of the WHO. This would be strange advice from a body that is supposed to be guarding public welfare, but, sadly, would not be out of character for the current Director-General, Margaret Chan.

Countries do not withhold good news. So, it is safe to assume that the death toll in Turkey has reach alarming levels. So alarming, that the government of Turkey, and perhaps the WHO, find it necessary to suppress this information.

What has caused this alarming increase in deaths in Turkey? At this point, we don’t know. There are many potential explanations including lack of access to Tamiflu and other medical care.

Turkey is of especial interest because in 2005 there was a large outbreak of H5N1 that resulted in a cluster of cases consistent with human-to-human transmission. Although this outbreak was extinguished and no new human cases of H5N1 have been reported in Turkey recently, the willingness of the Turkish government to suppress H1N1 pandemic deaths makes one wonder if they have also been suppressing H5N1 cases. The nightmare scenario would be human to human transmission of H5N1 and H1N1 at the same time. That would be alarming indeed.

Once governments take the decision to censor bad news, it is only natural to speculate why. If they don’t like the speculation, too bad. They’ve left us no alternative.

H1N1 and Gaza – Empircal evidence that movement restrictions are effective in a pandemic

Egypt and Israel both reported their first deaths due to the new H1N1 in July. Yet, the first pandemic H1N1 death in the Gaza Strip did not occur until 5 months later in December. Given that the Gaza Strip borders both Israel and Egypt, how is this possible?

The answer is simple: movement restrictions.

From Reuters, December 6, 2009

With Egypt’s help, Israel began restricting the flow of goods into Gaza in 2006 after Hamas won a legislative election.

[snip]

Restrictions on who could enter and leave the Gaza Strip were tightened in 2007 when Hamas seized full control of the territory.

[snip]

H1N1 swine flu has finally reached the Gaza Strip, the health ministry said on Sunday, worrying Palestinians who had credited Israel’s blockade of the territory with keeping the virus at bay.

And how did the virus finally get in?

Also from Reuters:

Palestinians had been concerned that several thousand pilgrims who recently returned from the annual haj pilgrimage in Saudi Arabia might bring the virus back to Gaza with them.

Movement restrictions protected Gaza from the new H1N1. Relaxation of movement restrictions for the Haj let it in.

This should not be a surprise. Movement restrictions are the only measure which has ever been shown to be completely effective in stopping the spread of pandemic influenza. Such evidence is extensive and well-documented. See Empirical Evidence for the Effectiveness of Movement Restrictions for examples and references.

Some epidemiologists, including those running the WHO and the CDC, have claimed that movement restrictions would not work. They were, quite obviously, completely and utterly wrong. The “studies” they cite consist of “models”, ie made-up scenarios, which are carefully tweaked to guarantee that the p0litically “correct” answer is arrived at – that movement restrictions should not be attempted because they won’t work. The ample empirical data demonstrating the effectiveness of movement restrictions is ignored.

It is particularly impressive that H1N1 was kept out of the Gaza Strip because it shares two land borders with countries that have had infections for over 5 months. The success in keeping H1N1 out of the Gaza Strip was likely dependent on the use of the military. They know how to control the movement of people.

The lesson is clear, if other countries wish to protect their citizens from pandemic flu, especially one that may become even more lethal, they need to close their borders.

And don’t give the job to epidemiologists. They don’t know what they are doing.

Give it to the military. It’s their job.

Rare Mutation in Matrix Gene Invalidates RT-PCR Assay for Pandemic H1N1?

There are 8 genomic segments in the Influenza A genome. The matrix (M) gene is usually highly conserved, that is, mutations accumulate more slowly in it than the other genomic segments. This is presumably because mutations would interfere with the function of the two proteins it encodes. The relatively stable sequence of the M gene makes it an ideal target for RT-PCR assays used to detect the presence of influenza. This is because mutations can cause mismatches with PCR primers that could result in false negatives, ie, failure to detect a flu infection.

A recent publication by Zheng et al. in J. Clin. Microbiol. raises the possibility that a mutation in the pandemic H1N1 M gene has occurred which invalidates at least one RT-PCR assay used to test for H1N1 in patients. To summarise their findings, a nasopharyngeal sample taken from a 4 year old girl initially tested negative using the ProFlu+ assay (Gen-Probe). This assay relies on RT-PCR with primers specific to the M gene of influenza. Perhaps because the girl exhibited classic pandemic flu symptoms and was positive with a rapid flu test (Binax), further RT-PCR tests were done. These included RT-PCR tests for the NP gene and HA gene of pandemic H1N1. These tests were positive. A RT-PCR test to the M gene produced by another company, EraGen Biosciences, was also positive. Although the sequences of the primers used to detect the M gene by Gen-Probe and EraGen Biosciences are not provided, they are presumably different.

One possible interpretation of these results is that there is a mutation in the M gene that results in a mismatch with Gen-Probe primers but not the EraGen primers. The authors indicate that sequencing of the isolate that gave anomalous results may be underway but do not report them in this paper.

From the paper:

We believe that this is the first report of a sample that may indicate a mutation in the influenza A virus matrix gene. At this time, although it seems to be very rare, the true prevalence of this variant among all 2009 H1N1 viruses is unknown until more data are available. Because of the implication of misidentification with a single assay, this case underscores the need for cautious interpretation and additional testing when a negative RT-PCR result does not seem to fit clinical presentation.

This result highlights the need for rapid, ongoing and extensive sequencing of pandemic H1N1 isolates. As the virus mutates, RT-PCR assays are going to fail, at least some of the time. Without sequencing, it will be impossible to be certain that an assay that clinicians are relying on is still valid.

Reference

Zheng et al. (2009) Unique Finding of a 2009 H1N1 Influenza Virus Positive Clinical Sample Suggests Matrix Gene Sequence Variation. J. Clin. Microbiol.

Not a mosquito bite – Cover up in Trinidad and Tobago?

We all depend on honest reporting of cases of pandemic flu to alert us that a more virulent virus has evolved. Unfortunately, many politicians view H1N1 deaths as “bad press” that they’d rather not acknowledge. This creates a clear conflict of interest for public health authorities who are usually appointed by politicians. Do they do what is best for the public or what their politician-bosses tell them to do? Sadly, it’s usually the latter.

This dangerous drama may be playing out in Trinidad and Tobago.

From Trinidad Express, December 17, 2009:

THE NUMBER of swine flu-related deaths is continuing to rise, but the Ministry of Health refuses to come clean about the pandemic, says Opposition MP Subhas Panday.

Addressing members of the media at a briefing at the Office of the Leader of the Opposition in Port of Spain yesterday, Panday insisted that, since October, at least 18 people have died at the San Fernando General Hospital from flu-like symptoms, but the Health Ministry has yet to say why or even confirm what their blood samples show.

’These people died from swine flu, but the ministry is not saying that and they have the doctors fighting to save their jobs because they afraid to come out and tell anybody what really happening at that hospital,’ he said.

Panday admitted that he did not know what was happening at the other health facilities, but the death of his niece provided him with the opportunity to get inside the San Fernando General Hospital and question medical officials about the pandemic.

’Nobody wants to talk, they did not even want to talk to me. But I went in there, I went through the system and I asked them everything about this,’ he said while waving around the list he acquired of people who died since October.

The list, which predominantly names people of East Indian descent between the ages of 22 and 52, outlines the age, area and cause of death. And while it was not an official document, Panday said he was able to get the list legally through the Ministry of Legal Affairs.

[snip]

The doctors have not chosen me as their mouthpiece, but people in this country have a right to know … they listing all these deaths as pneumonia. This is not like a mosquito bite. How could so many people die in one month from the same symptoms?’

Of course, the government denies that it is covering up anything.

From the Trinidad Express, December 17, 2009

Medical Director of San Fernando General Hospital, Dr Anand Chatoorgoon, said last night that the hospital does not have information that 18 patients died at the institution from swine flu.

[snip]

Chatoorgoon told the Express that ’deaths from bronchial pneumonia as shown on Mr Panday’s list are not necessarily caused by the swine flu’.

He said, ’All patients showing symptoms of the swine flu are admitted to the institution. In some cases, they are sent to the ICU when they are having a breathing problem.’

Chatoorgoon noted that ’it is customary for patients to develop pulmonary embolism simply because they are confined to a bed and blood clots could develop’.

He added, ’The blood tests taken from patients are sent directly to the Ministry of Health in keeping with PAHO’s policy.’

Without the results of real time PCR tests, it is hard to know what is going on in Trinidad and Tobago. However, if an unusually large number of people younger than 65 are dying of a respiratory disease, it is highly likely that pandemic flu is the cause.

Trinidad and Tobago is a small country (population 1,339,000). The 18 deaths are all from one hospital. If there are more deaths in other hospitals, it is important that these be reported as well. If an unusually large number of people are dying, we need to know. It may be the only warning we get that a more dangerous virus is circulating.

The polymerase basic protein 1 (PB1) gene of pandemic H1N1

The second genomic segment of the influenza A virus encodes the polymerase basic protein 1 gene (PB1). This is the second longest genomic segment and is sometimes labeled “segment 2″. This gene produces three proteins: PB1 (sometimes referred to as PB-F1), PB1-F2 and N40.

When the BLAST program is used to align A/California/04/2009(H1N1) PB1 with sequences from GenBank, the nucleotide sequence was most similar to A/Wisconsin/10/98 (H1N1) – 96% identical. This strain was apparently isolated from a man in Wisconsin in 1998. The best protein match for A/California/04/2009(H1N1) PB1 was also A/Wisconsin/10/98 (H1N1). However, several isolates from North American birds had an identical protein sequence to A/Wisconsin/10/98 (H1N1), including: A/northern pintail/South Dakota/Sg-00126/2007(H3N2), A/mallard/South Dakota/Sg-00127/2007, A/mallard/South Dakota/Sg-00128/2007(H3N2), A/mallard/South Dakota/Sg-00125/2007(H3N2). The PB1 protein from A/California/04/2009(H1N1) was 98% identical to A/Wisconsin/10/98 (H1N1) and the four avian virus proteins.

The PB1 subunit works with PB2 and PA subunits to create the viral polymerase. This polymerase is responsible for the transcription and replication of the viral genome.

N40 is a newly described protein of influenza A virus from the PB1 gene (Wise et al., 2009). It does not appear to be necessary for replication, but failure to produce it appears to impair the replication, under certain conditions.

PB1-F2 is unusual in that this protein is coded by a subset of the nucleotides that code for PB1. This is due to the use of a different reading frame (+1). Thus, the PB1 and PB1-F2 proteins are completely different in sequence (Lamb and Takeda, 2001; Chen et al. 2001). They also appear to be completely different in function. While PB1 is involved transcription and replication, PB1-F2 may play a role in the virulence of influenza strains (Zamarin et al. 2006). PB1-F2 has been implicated in the severe symptoms and high death rate associated with the 1918 virus (Kash, et al. 2006). PB1-F2 is thought to kill cells by interfering with the function of mitochondria. These organelles are the energy power plants of cells. If these structures fail, a cell will die. It has been suggested that PB1-F2 is especially lethal to immune system cells (Chen et al. 2001).

The 2009 pandemic influenza H1N1 does not produce a full length PB1-F2 protein. The new H1N1 virus PB1 gene codes for an 11 amino acid peptide instead of a 90 amino acid protein for PB1-F2 due to mutations which create stop codons (Ramakrishnan, 2009, Trifonov et al. 2009). Thus, a few nucleotide mutations in the pandemic H1N1 PB1 gene could create a functioning PB1-F2 protein. This, in turn, might cause an instant increase in the lethality of this virus.

References

Wise et al. (2009) A Complicated Message: Identification of a Novel PB1-Related Protein Translated from Influenza A Virus Segment 2 mRNA. J. Virol. 83: 8021-8031.

Trifonov et al. (2009) The contribution of the PB1-F2 protein to the fitness of influenza A viruses and its recent evolution in the 2009 influenza A (H1N1) pandemic virus. PLoS Currents: Influenza. 2009;22

Ramakrishnan (2009) A Serine12Stop mutation in PB1-F2 of the 2009 pandemic (H1N1) influenza A: a possible reason for its enhanced transmission and pathogenicity to humans. J. Vet. Sci. 10: 349-351

Wanitchang et al. (2009) Enhancement of reverse genetics-derived swine-origin H1N1 influenza virus seed vaccine growth by inclusion of indigenous polymerase PB1 protein. Virus Res. Oct. 30.

Conenello et al. (2007) A Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence. PLoS Pathogens. 3: e141.

Zamarin et al. (2006) Influenza A Virus PB1-F2 Protein Contributes to Viral Pathogenesis in Mice. J Virol. 80: 7976–7983.

Kash et al. (2006) Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus. Nature. 443: 578–581.

Obenauer et al. (2006) Large-scale sequence analysis of avian influenza isolates. Science. 311:1576-80.

Holmes (2006) Comment on “Large-Scale Sequence Analysis of Avian Influenza Isolates”. Science. 313: 1573.

Zamarin et al. (2005) Influenza Virus PB1-F2 Protein Induces Cell Death through Mitochondrial ANT3 and VDAC. PLoS Pathog. 1: e4

Chen et al. (2001) A novel influenza A virus mitochondrial protein that induces cell death. Nature Medicine. 7: 1306 – 1312.

Lamb and Takeda (2001) Death by influenza virus protein. Nature Medicine 7, 1286 – 1288.