USA

Recombinomics Commentary 22:50
March 27, 2012 The CDC has released five sets of H3N2 from recent collections in Maryland.  All five sequences were generated directly from the clinical samples, strongly suggesting that all five were linked to the recent death cluster. 

Three of the samples (A/Maryland/04/2012, A/Maryland/05/2012, A/Maryland/06/2012) were from March 5 collections, the date of death for two of the siblings.  The other two, A/Maryland/08/2012 and A/Maryland/09/2012, were from collections on February 21 and February 20 respectively.  Although the ages and gender of the index case and three children involved in the Maryland death cluster have been cited in media reports, the CDC withheld the age and gender for all five sequences. 

Thus, the assignment of each of the five samples was not possible from the public data released by the CDC.  However, all five H3 sequences were virtually identical and related to the drift variant, A/Brisbane/299/2011, which has S199A, as noted for prior sequences designated as low reactors by the CDC. 

A reassortant of A/Brisbane/299/2011 (designated A/Brisbane/299/2011 X-215) has been generated as a potential H3N2 vaccine target because it is a variant that produces a low reaction when tested against the current vaccine, which is directed against A/Perth/16/2009.

Thus, the sequence data confirmed that the Maryland cluster were from a drift variant and were unlikely to react well with the current vaccine, in contrast to the CDC comments and internet rumor.

Sad news out of Maryland, and a reminder of how devastating MRSA, methicillin-resistant Staphylococcus aureus, can be when it combines with flu infection. According to the Maryland Department of Health and Mental Hygiene, the Washington Post and ProMED, five members of a family have fallen ill and three have died from MRSA pneumonia that took hold in lungs inflamed by flu infection.

The dead are Ruth Blake, 81, and her children Lowell, 58, and Vanessa, 56. Another child, Elaine, also fell ill and was hospitalized, and Ruth Blake’s sister has been hospitalized also. They had all contracted one of the seasonal flu strains circulating this year: H3N2. According to the Post, Ruth Blake was vaccinated against flu this season; her children were not. The assumption is that both flu and MRSA spread from the mother to the children.

 From the Post:

Calvert health officials said in a statement Wednesday that the cases were isolated to a single family and that “there are currently no other affected individuals.” Local health-care providers, they said, are not reporting any significant increase in patients with flulike symptoms.

David Rogers, the county’s health officer, said health officials suspect that Blake also had the flu and then suffered a serious lung infection that turned into pneumonia.

“In older people, that can often be fatal,” he said.

Blake had a flu shot, he said. None of the others were vaccinated.

What’s unusual, he said, is that the infection spread from the mother to three children, probably at her bedside. Most likely, the mother’s coughing spread the virulent organisms into the air, and her caregivers, two of whom also had the flu, breathed them in and became infected, he said. (Byline: Annys Shin and Lena H. Sun)

MRSA pneumonia is fast-acting and lethal; it is often called “necrotizing pneumonia” for the way it simply kills lung tissue. Exactly why it has that effect is still disputed — MRSA has so many cellular toxins at its disposal that there could be a number of culprits — but there is no dispute that it is a very serious disease.

MRSA post-flu pneumonia isn’t well-understood because it has been a concern only recently. The first cases to alert the United States this might be a problem were in Baltimore in the flu season of 2003-04. The four patients were all seen at Johns Hopkins University Medical Center, and physicians there wrote the cases up afterward. Over two months, there was a 31-year-old woman who was in the hospital for four weeks; MRSA ate holes in her lung, the largest of which was 1 by 1.5 inches. Two other women, 20 and 33 years old, were each hospitalized for three months. The 20-year-old’s heart stopped, and her blood clotting grew so disordered that doctors had to amputate one leg below her knee; the 33-year-old lost both lower legs. The fourth patient was a 52-year-old man, a two-pack-a-day smoker, who died.

Other reports came into the Centers for Disease Control and Prevention over the course of that flu season. When the CDC counted up the following summer, there had been 15 cases of severe MRSA pneumonia in 9 states. Four of them died. CDC personnel wrote another article warning of the dangers of MRSA and flu two years later, after clusters of cases in Louisiana and Georgia during the 2006-07 flu season. They said: “Secondary S. aureus pneumonia is a potentially catastrophic complication of influenza… MRSA [community-acquired pneumonia] often affects young, otherwise healthy persons and can be rapidly fatal.”

Pneumonia that follows on flu is a seriously under-appreciated danger of flu infection: An analysis from 2010 points out that, in 2007, there were 457 deaths from flu in the US and 52,847 deaths from post-flu pneumonia. There is no reliable way to protect yourself against MRSA, since there is no vaccine, and the bacterium can live on the skin undetected for an unpredictable period of time. Hypothetically, if you prevent flu infection you lessen the likelihood of this pneumonia occurring — but as the mother’s case illustrates, flu vaccine doesn’t confer perfect protection, especially not in the elderly whose immune systems are not robust enough to begin with.

It’s a very sad story, and another illustration of how perilous and destructive MRSA can be.

http://www.wired.com/wiredscience/2012/03/flu-mrsa-pneumonia/

Recombinomics Commentary 18:45
March 7, 2012

"State health officials say today that lab tests confirm that two of the members of a Calvert County family who died early this week of severe respiratory illness had Influenza H3, a strain of the flu that has been going around this season".

The above comments confirm the Recombinomics commentary published this morning on the H3 sero-type of the HA from the fatal Calvert County, Maryland cluster.  However it is unlikely to be the “strain” of flu that has been going around this season. 

Recombinomics called the Calvert County Health Department as well as the Maryland Department of Health and Mental Hygiene, and the US CDC to get a clarification on the testing that led to the report that the influenza A was seasonal flu, since the CDC has reported an explosion of H3N2 low reactors in the week 7 and week 8 FluView reports.  The antigen characterization data indicated an new H3 had replaced the H3N2 strain that had been circulating earlier this season.

The CDC did not comment on this explosion and therefore it was unclear if the low reactors were a drift variant of the current seasonal H3N2 vaccine target, Perth/16, or were widespread H3N2v, which would also generate a low reactor result.

Moreover, the CDC PCR test distributed to state labs can identify H3N2v under ideal conditions, but most confirmed H3N2v cases gave negative, inconclusive, or seasonal H3 results, and H3N2v was confirmed by CDC sequencing.

The cluster in Maryland was determined to be H3 by the Maryland state lab, which was used for this morning’s announcement by Calvert County.  Media at the Maryland state lab suggested I e-mail the specific testing questions, and also noted that the best source of information would be the CDC, who had already been asked via cell phone and e-mail about testing and the relationship between the H3 result generated by the Maryland state lab and the low reactors reported by the CDC, which may be H3N2v.

As of this commentary, neither agency has responded to the e-mailed questions, and the relationship between the H3 in the death cluster, the low reactors reported by the CDC, and H3N2v remains unclear, but the likelihood that the H3 “strain” in the Maryland death cluster matches the seasonal H3N2 dominant in the US in 2011 and early 2012 is extremely small.

Recombinomics Commentary 16:30
March 7, 2012

"Initial testing of two of four family members in Lusby, three of whom have died, suggests that that the serious lung infection suffered by all four was a complication of seasonal flu. A fourth family member remains hospitalized at Washington Hospital Center and is improving".

The above comments from the latest update from the Calvert County Health Department website indicate the Calvert County, Maryland death cluster was linked to seasonal influenza.  A call to the health department indicates the state lab obtained an H3 serotype.  However, it remains unclear if the H3 is Perth/16-like and recognized by the current H3N2 vaccine or a "low reactor” as described in the week 8 FluView.

Moreover, it remains unclear if this is a Perth/16 variant or an H3N2v which gives and H3 positive on the CDC PCR test.  H3N2v has D225G, which is associated with patients coughing up blood.

More detail on the PCR testing and sequences from the CDC would be useful

Recombinomics Commentary 17:30
March 6, 2012

"The first patient, an 83-year-old woman, became sick on Feb. 23. Three of her children, a son and two daughters all in their 50s, arrived on Feb. 28 to take care of her.

The mother died on March 1. One daughter, 56, and her son, 58, both died on Monday while a third daughter, 51, remains at Wash Hospital Center in critical condition".

The above comments describe a death cluster in Calvert County, Maryland.  Anecdotal reports also describe a fifth victim, the funeral director who had contact with the bodies.  These reports also indicate fatal cases were coughing up blood and the funeral director was hospitalized with breathing difficulties.

More information on testing would be useful.

Recombinomics Commentary 16:00
January 6, 2012 HHS has contracted with pharmaceutical companies Novartis and Sanofi Pasteur to develop investigational lots of the vaccine. Novartis will produce its supply using cell-culture technology at its plant in Holly Springs, North Carolina, and Sanofi Pasteur will grow the vaccine in chicken eggs (a slower method of production) at its plant in Swiftwater, Pennsylvania.

The influenza virus being targeted is a variant of the A(H3N2) virus found in pigs.

The above comments describe preparations for spring clinical trials for an H3N2v pandemic vaccine.  These developments are not a surprise.  In August the CDC released sequences of vaccine constructs of A/Minnesota/11/2010, which was followed by a WHO September 29, 2011 report on vaccines, showing that the sera against the above target was effective against the first H3N2pdm11 isolate, A/Indiana/08/2011.
 
Although December media reports cited the creation of a seed vaccine, the real drivers for the clinical trials were the H3N2pdm11 cluster at the daycare center in Iowa, followed by the trH3N2 sustained cluster in the daycare center in Mineral County, West Virginia (which has a novel N2 which has acquired seasonal polymorphisms via recombination.

The West Virginia cluster was alarming, with 23/70 contacts of the index case exhibiting ILI (influenza-like illness), which led to a CDC request to all states to increase surveillance, especially in children.  Multiple states issued advisories or alerts, including Marin County, California, which also cited a new H3N2v case in a Napa county resident in its week 50 report.

Today the CDC published the December 23 early release MMWR, which described the West Virginia cluster, which made it clear that transmission was sustained for a month at the daycare center, but failed to note that 23 contacts had ILI.  In December the CDC also held a 50 state conference call.

An explosion of H3N2v cases and clusters is expected this month.

Recombinomics Commentary 05:00
January 5, 2012 More recently, investigation of a case in West Virginia has identified a possible outbreak, with 23 out of 70 contacts of the case reporting ILI; all have recovered.

The above comments are in the California Department of Public Health December 15 H3N2v advisory.  The West Virginia cluster was described in the CDC early release MMWR, but the 23 ILI cases were not mentioned.  Instead the report said there were several contacts of the index case, A/West Virginia/06/2011, which initially tested as negative.  trH3N2 was isolated from a contact, A/West Virginia/07/2011, which initially tested as inconclusive and was reported as an influenza A case.  The partial sequence of HA and NA were virtually identical to the index case, and both had a novel N2 that was easily distinguished from the first 10 cases in 2011 (H3N2pdm11).

Thus, the vast majority of cases at the day care center were not reported, and the two confirmed cases had serious testing issues.  The numbers cited in the California advisory indicate the attack rate was high, and the transmission was sustained for almost a month, but the CDC maintains that there is no sustained or community transmission of H3N2v.  None of the cluster members have reported contact with swine.

A pediatric case in Napa County, California has also tested positive for trH3N2 and is under investigation.  Anecdotal reports indicate ILI is widespread in pediatric cases in northern California, but most are mild and not tested.  As seen in the West Virginia cluster, testing is a serious issue, allowing the trH3n2 to silently spread.

An explosion of cases and clusters is expected this month.

by Agencies

04:45 AM Nov 28, 2011

//

WASHINGTON - Flu experts are gearing up their response planning, after an odd new flu virus has been detected, a senior official of the World Health Organization (WHO) said.

The virus is currently jumping from pigs to people in parts of the United States, and experts are "figuring out what needs to be done if the virus continues to spread and a global response is required", Dr Keiji Fukuda, assistant director-general for Health Security and Environment, was quoted as saying by The Toronto Star.

The virus is influenza A of the H3N2 subtype, a distant cousin of H3N2 viruses that circulate in humans.

Since the virus was first spotted in July, 10 cases have been confirmed in Maine, Indiana, Pennsylvania and Iowa.

All the victims were children under 10, with an exception - a 58-year-old adult.

Flu expert Malik Peiris, chairman of the Department of Microbiology at the University of Hong Kong, said exposure to contemporary H3N2 viruses might provide some protection against these swine viruses.

"It is important to see the serological data to see how much vulnerability or susceptibility there is in the human population," he was quoted by the paper.

The WHO's desire to be ready without causing alarm comes after its failure to communicate uncertainties about the H1N1 swine flu pandemic in 2009.

Critics said the WHO had created panic about the swine flu virus, which turned out to be moderate in its effect, and caused governments to stockpile vaccines that went unused.

http://www.todayonline.com/World/EDC111128-0000016/New-flu-virus-has-WHO-gearing-up-to-respond

Some of the media reports above reference the current flu vaccine as a good preventative measure for trH3N2. This is not true. That strain is not included in this year's trivalent flu shot.

Recombinomics Commentary 17:30
November 26, 2011
 "We have received disturbing information on the WHO alert system that the U.S. two people the virus H3N2: a seven-month child in Illinois and 46-year-old man in Pennsylvania, "- told Interfax Rospotrebnadzor head Gennady Onishchenko.
 
The WHO wants to be ready to make recommendations and issue guidance to countries if the need arises — though Fukuda stressed at this point it is far from certain there will be that need.

"We're very aware that we don't want to over-play or under-play. We're trying to get that right," says Fukuda, a leading influenza expert.

"(We're) trying to make sure that we're ready to move quickly, if we have to move quickly, but also trying not to raise alarm bells."

The desire to be prepared without raising alarm is a legacy of the 2009 H1N1 pandemic. The WHO was heavily criticized in Europe for declaring that event a pandemic when the outbreak turned out to be far milder than originally feared.

But what exactly the agency — and the world — might need to prepare for now is very unclear. With the public relations problems of the 2009 outbreak fresh in the minds of health officials, no one is using the "p" word these days.

Yet in some respects the parallels to 2009 are striking.

The above comments are from the response to the WHO pager alert (in blue), issued almost exactly one year ago, and the latest media report (in red) of current WHO pandemic plans.

The alert issued in November, 2010 cited two trH3N2 isolates (A/Wisconsin/12/2010 and A/Pennsylvania/14/2010), but WHO and the CDC were probably aware of a third case (A/Pennsylvania/40/2010) who developed symptoms less than a week prior to the Wisconsin case (cited as an Illinois cases in the alert).

If the WHO and CDC didn’t know about the second Pennsylvania case when the alert was issued, within days they knew of that case, as well as a case from Minnesota (A/Minnesota/11/2010) and symptomatic contacts.  When the CDC released the sequences from these cases, there was clear cause for concern, as seen in slide 7 from the CDC (Nancy Cox) presentation in February, 2011 (at the FDA vaccine advisory committee meeting). 

The H3 sequences from cases in Wisconsin, Pennsylvania, and Minnesota were clustering, indicating the H3 for all three cases were remarkably similar and distinct from trH3N2 swine isolates.  Moreover, the sequences from the Wisconsin case and the Pennsylvania case that was not mentioned in the alert, were virtually identical, creating striking parallels between the trH3N2 data and the initial cases in southern California at the start of the H1N1 pandemic in 2009.

However, the absence of the sequences from the second case allowed the CDC to offer assurances that there was no human transmission because of sequence differences between the two cases in the alert, which were isolated 6 weeks apart.  The announcement of the second case in Pennsylvania was delayed until February 5, because the case was initially classified as seasonal H3N2, but sequence data showed that the case was clearly trH3N2.  That sequence was used in slides 7 and 8 in the CDC February 25, 2011 presentation, but the sequence was not released until Sunday, April 17, 2011 at GISAID without comment.
As seen in slides 7 and 8, the PA/40/2010 sequence was virtually identical to WI/12/2010 and this identity extended to all 8 gene segments.  Moreover the two cases developed symptoms within a week of each other, even though they were not epidemiologically linked.  Thus, the only significant difference between the trH3N2 matches in 2010 and the trH1N1 matches in 2009 was the claim of “swine exposure” for the trH3N2 cases.

However, this “exposure” was listed in the CDC slide as a “visit to a local animal fair”.  Since the Wisconsin case was only seven months old at the time, the extent of “contact” was likely limited, and no trH3N2 was reported at any of the swine at the fair.  Similarly, the Pennsylvania case (3F) was only 3 years of age, and swine contact at the fair was also likely limited, and no trH3N2 matching the human cases has been reported from either state.  Similarly, the other case from Pennsylvania (PA/14/2010) had no reported exposure to swine, although he lived in a rural area (and closely related sequences to this case were subsequently identified in Pennsylvania swine).

Thus, the red flag raised over a year ago in the WHO pager alert signaled the start of a series of events which left little doubt that the trH3N2 had begun in 2010, and gained significant speed in 2011.  In week 21 of 2011 trH3N2 was lab confirmed (serologically) in the daughter of the Minnesota case and her lack of swine exposure led to the CDC concession that the case represented limited human to human transmission.

This concession was made again for the first 2011 trH3N2 case (A/Indiana/08/2011), who also had no swine contact.  However, the caretaker of the patient had swine exposure, so the case was said to have “indirect swine exposure” even though the caretaker and swine were asymptomatic and not trH3N2 was identified in either case.

Similarly, the first 2011 case from Pennsylvania (A/Pennsylvania/09/2010) also visited an agricultural fair (Washington county) but no symptomatic swine was identified at the fair, which included the market hogs exhibited by the second Pennsylvania case.  The third case also visited the fair and a friend who exhibited swine, but there was no evidence that any of the three cases were infected by trH3N2 in swine at the fair, and the sequences from the 2nd and 3rd Pennsylvania case (A/Pennsylvania/10/2011 and A/Pennsylvania/11/2011) were virtually identical to the Indiana case.

Thus, the matches between cases that were not epidemiologically linked as seen in late 2010, was repeated in the initial cases in 2011, although this sequence had evolved from the 2010 sequences by acquiring an NA gene matching the other Pennsylvania case (PA/14/2010) and an M gene segment from 2011.

This constellation and lineage has now been found in all 2011 human cases, including the Iowa cluster, which had no swine contact and involved three confirmed cases and two symptomatic family members of the index case.

Thus, the “swine exposure’ link, which generated the more advanced testing at the CDC required to confirm trH3N2, was absent from the Iowa cluster, leaving little doubt that the novel trH3N2 was spreading in humans and was orders of magnitude higher than the ten confirmed cases from four states (Indiana, Pennsylvania, Maine, Iowa) as well as one novel trH3N2 swine isolate from New York, A/swine/NY/A01104005/2011.

Consequently, WHO is planning for the trH3N2 pandemic, without using the “P” word.

Currently, the CDC is watching the development of a novel strain of influenza A H3N2 identified as S-OtrH3N2 [Swine-Origin, triple reassortant (H3N2)]. Triple reassortant H3N2 was first identified in pigs in 1998 (link) and a few years later found to be endemic in pigs and turkey populations in the USA with evidence of interspecies transmission (link). The first reported possible human case of trH3N2 was a farm worker from Ontario Canada in 2005 (link).

Since 2009 there have been sporadic scattered human cases in the USA, most from apparent interspecies transmission.

2009-2010 Influenza Season

http://www.cdc.gov/mmwr/preview/mmwr...cid=mm5929a2_w

2010-2011 Influenza Season

http://www.cdc.gov/mmwr/preview/mmwr...cid=mm6021a5_w

2011-2012 Influenza Season

Since July 2011, 10 additional human trH3N2 cases have been reported in the USA, all carrying the M gene from the pH1N1 virus. The virus is now officially referred to as S-OtrH3N2. The first seven of these 10 cases appear to have resulted from interspecies jump from swine to humans on different occasions.

http://www.cdc.gov/mmwr/preview/mmwr...m60d1123a1.htm

Of these seven cases 2 are from Indiana, 2 from Maine, and 3 from Pennsylvania.

Indiana (2):
1. http://www.cdc.gov/mmwr/preview/mmwr...cid=mm6035a6_w
2. http://www.in.gov/isdh/files/Week43-2011.pdf

Maine (2) : http://www.maine.gov/tools/whatsnew/...id=318365&an=2

Pennsylvania (3)
1. http://www.cdc.gov/mmwr/preview/mmwr...cid=mm6035a6_w
2. http://www.cdc.gov/media/haveyouhear...b_testing.html
3. http://www.cdc.gov/media/haveyouhear...b_testing.html

Human to Human Transmission – Iowa

Yesterday, The CDC published an MMWR report on three new S-OtrH3N2 human infections from Iowa (link). These three reported cases are all children who attended the same day care center. The staggered onset dates suggests that one of the children infected the others. And none of the children were reported to have contact with swine. In addition, another sibling and parent of the children also exhibited ILI symptoms but were not tested. These 5 individuals perhaps represent the first reported human cluster of S-OtrH3N2 infection resulting from human-to-human (H2H) transmission. These cases represent intraspecies transmission of S-OtrH3N2; the threat of this novel virus as a pandemic virus has increased.

Discussion and Implications

So far, human infections with S-OtrH3N2 have not resulted in any deaths, but several of the cases have been hospitalized. Children under 10 years are the most commonly infected individuals, suggesting that previous exposure to earlier strains of H3N2 may provide some cross-protective immunity. The ultimate virulence of this novel strain as it continues to infect human is unknown. The CDC has already developed and submitted a sample strain of this virus for potential inclusion into future influenza vaccines (link).

http://www.flutrackers.com/forum/showthread.php?t=177008

Recombinomics Commentary 22:45
November 23, 2011
 Prior to the three cases in Iowa, most human infections with this virus were associated with exposure to swine. In Iowa, however, no swine exposure has been identified. At this time, it appears that unsustained human-to-human transmission may have occurred.

The above comments are from the November 22 “Have You Heard?”, a CDC backgrounder for the media.  The latest Iowa cluster leaves little doubt that the novel trH3N2 with the H1N1pdm09 M gene is transmitting in a sustained manner.  The CDC maintains its “unsustained” claim by limiting testing.

Since the trH3N2 virus has a human H3 and N2, it frequently tests positive for seasonal H3N2.  This mis-classification can be corrected in the newly approved CDC PCR test, which has two swine genes from H1N1pdm09, but low abundant RNA samples can test negative for these markers to produce a false positive for seasonal H3N2, as was reported for a case from 2010 (A/Pennsylvanai/40/2010), as well as the second case from Maine (A/Maine/07/2011).  Therefore sequencing is required to conclusively classify the H3N2 positive case as seasonal H3N2 or trH3N2.

The CDC has released 14 sequences collected from adolescent samples that were influenza A positive since July 20, 2011.  9 of the 10 confirmed trH3N2 cases in 2011 were from patients aged 1-9.  Thus, only 5 seasonal H3N2 sequences have been identified in public sequences which include the patients age and gender, as updated below.  trH3N2 cases are in bold.

As seen below, 64.2% of the US cases were trH3N2, and the percentage for those under 10 years-of-age is 75%.  Moreover, for cases in the four states where trH3N2 has been detected, 90% of the cases have been trH3N2 confirmed (all have the H1N1pdm09 M gene and all eight gene segments are from the same lineages). 

Other than the 9 cases from children, one novel trH3N2 case was from an adult, A/Indiana/10/2011, and one case was identified in swine, A/swine/NY/A01104005/2011 .

Thus, trH3N2 is common and transmitting, and cases will explode if the CDC begins serious testing, including sequencing of influenza A positive samples from children under 10 years of age.

A/Iowa/09/2011                11/14 2M
A/Iowa/08/2011                11/14 1M
A/Iowa/07/2011                11/14 3F
A/Maine/07/2011              10/24 8M
A/Maine/06/2011              10/10 8M
A/Indiana/09/2011             10/03 1M
A/Washington/17/2011      09/14 10F
A/Pennsylvania/10/2011 08/26 9F
A/Florida/24/2011               08/25 1M
A/Pennsylvania/11/2011 08/25 9F
A/Pennsylvania/09/2011 08/20 2F
A/Louisiana/06/2011          08/16 13F
A/Florida/20/2011               08/05 8M
A/Indiana/08/2011              07/27 2M

Three children in Iowa have come down with a new type of flu virus previously linked to pigs, but this time the bug appears to have been spread by people.

The children, who live in rural Webster and Hamilton counties, did not become seriously ill, said Dr. Patricia Quinlisk, medical director for the Iowa Department of Public Health. But the detection of the virus known as swine-origin A/H3N2 in patients who hadn't had contact with animals raises concerns about potentially greater spread of a new type of flu.

"We have pretty good evidence of person-to-person spread," Quinlisk said. "None of the children or anyone around them had exposure to swine, turkeys or other sources."

Officials with the Centers for Disease Control and Prevention had previously detected seven cases of people with the new H3N2 virus that appears to have acquired a gene that may make it more transmissible from H1N1, the flu that sparked the so-called swine flu pandemic in 2009. Flu viruses often swap genetic parts. Officials say the new virus was probably formed when a pig became infected with the H3N2 virus and the H1N1 virus at the same time.

The new bug has components of human, avian, H1N1 and swine flu viruses, all mixed together in what scientists call a recombinant virus.

The first new H3N2 case was identified in a child in Indiana in July, and has been followed by cases in Pennsylvania, Maine and, now, Iowa.

In the previous cases, however, the patients either had direct exposure with pigs, or exposure to a person who'd been around pigs. In the new cases, it appears that one of the children transmitted the flu to the other two, and none of them had any animal exposure, Quinlisk said. She declined to identify the children or their ages, saying only they were younger than 18. No further cases have been identified in the past week, she said.

The Iowa cases are nothing to panic about, health officials emphasized. The H3N2 flu causes symptoms similar to the regular seasonal flu, including fever, cough, fatigue, body aches and loss of appetite. 

"People need to be most concerned about the regular, everyday seasonal flu," Quinlisk said.

But Iowa health officials are now testing samples of people with flu-like illness to detect further spread of the new bug. And CDC officials have asked states across the country to be vigilant in looking for it, said Dr. Joe Bresee, the agency's influenza and epidemiology branch chief.

The current seasonal flu vaccine being offered by doctors and clinics was not developed to protect against the H3N2 virus. It contains some antigens similar to a flu virus that circulated in the 1990s, so some people who had the flu then or were vaccinated could have some immunity, but it's not clear how much, Quinlisk said. The Iowa children apparently had not been vaccinated, she added.

With the new cases, CDC officials have confirmed 31 cases in the U.S. of the new swine-origin virus since 2005, including 10 with the H3N2 virus that carries the M gene from the 2009 H1N1 virus.

The best prevention for the new flu, as with any flu, is to wash hands frequently, cover coughs and sneezes and limit spread of germs by staying home when you're sick, health officials said.

http://vitals.msnbc.msn.com/_news/2011/11/23/8977636-new-flu-virus-in-three-iowa-kids-raises-concern-about-wider-spread

Recombinomics Commentary 14:00
November 23, 2011
Iowa has increased flu surveillance state-wide. And Cox said the CDC has asked bordering states to enhance their surveillance efforts as well.

The three children attended a small day-care together. They live in adjacent counties, Webster and Hamilton, in the centre of the state.
One became sick first and appears to have infected the other two. Quinlisk said it's not clear how the first child got infected.

Another child who is a contact of the first child was ill with what may have been influenza prior to the first child's infection, she said. But by the time laboratories had confirmed the cases, that other child had recovered.

The above comments on the trH3N2 cluster in Iowa leaves little doubt that the novel virus has spread across the United States, yet the CDC continues to deny the extent of the spread and is increasing surveillance in “bordering states”.

The trH3N2 has already been confirmed in children in Indiana, Pennsylvania, Maine, and now Iowa, in addition to a pig in New York.  Surveillance remains abysmal in spite of rates of 100% in confirmed cases in children in Maine and Pennsylvania, and 50% in Indiana.  All seven of the prior isolates match in all 8 gene segments, which also match the swine isolate in New York, signaling a jump from human back to swine.

The CDC has maintained a “swine exposure” narrative, leading to a request for samples with “swine exposure” when the first two cases were announced in the early release MMWR.  The denial of human transmission was maintained in the Maine CDC advisory claiming that all prior 2011 cases had a swine exposure, which was not true for the case in Indiana, and the cases in Pennsylvania had limited exposure to asymptomatic swine at a state fair (and only one had direct contact).  Moreover, the Maine state epidemiologist claim “no thought” of human transmission, and these agency claims were propagated by media and ProMED reports, and remarkably, this narrative on swine exposure is still be propagated by CIDRAP in its report in the Iowa cluster.
The upcoming MMWR on the cluster in Iowa should demand an increased surveillance throughout the country to get a true estimate of the extent of spread and the number of hospitalized cases.

The silent spread of a trH3N2 pandemic two years after the trH1N1 pandemic raises serious concerns about influenza surveillance in the United States and worldwide.

Recombinomics Commentary 14:00
November 9, 2011
Swine-Origin Influenza A(H3N2)
Swine influenza A(H3N2) viruses are enzootic in swine herds of North America and other parts of the world. Characterisation of recent A(H3N2) viruses from swine in North America indicates that their HA genes have evolved from the human virus precursors that circulated in the mid-1990s. Isolation of swine-origin influenza viruses (SOIV) A(H3N2) from humans has been reported infrequently. The United States of America reported eight infections due to A(H3N2) SOIV between January 2005 and 15 February 2011.

A(H3N2) SOIV infections from 16 February 2011 to 19 September 2011
There have been four human infections with A(H3N2) SOIV in the states of Indiana (1) and Pennsylvania (3), United States of America, in this period. The HA and neuraminidase genes of these four viruses were similar to those of swine viruses that circulate in the United States of America. Sequencing data indicated that the matrix genes of these viruses were acquired from an A(H1N1)pdm09 virus, unlike SOIV isolates from previous human cases.

The above comments are from the WHO update on pandemic influenza vaccine targets.  The update appears to have taken some of the information from the CDC website on SOIV in humans since 2005.  That website presented very fuzzy data on the history of US cases (which has been recently clarified), which then was extended and misrepresented in the above WHO comments. Although the first triple reassortant case in the US was in 2005, all 13 H1 cases (twelve H1N1 and one H1N2) were prior to the 2009 swine flu pandemic.  The first US (SOIV)H3N2 case was in 2009 (A/Kansas/13/2009), which was followed by a second case in 2009 (A/Iowa/16/2009) and 6 cases in 2010 (A/Minnesota/09/2010, A/Pennsylvania/40/2010, A/Wisconsin/12/20110, A/Pennsylvania/14/2010, A/Minnesota/11/2010, daughter of A/Minnesota/11/2010).  Thus, the 8 cases were in a period of just more than one year, and not the 6 years cited above.  Reporting of the first Pennsylvania case was delayed 5 months and the reporting of the sequence was delayed 6 months.  The reporting of daughter of the Index case for the Minnesota cluster was delayed 6 months, and was after The February 15, 2011 cited above.

Similarly, the first reported case with an M gene from H1N1 was from an infection in late July, so the 2011 cases were reported over a 2 month time period prior to the report, and there were 3 more October cases, bring the total number of reported cases to seven over a three month period. Moreover, the first 2011 case had no swine exposure.  The CDC speculated that the case was infected by his caretaker, who had swine exposure, but neither the caretaker nor associated swine had symptoms, and no SOIV has been reported in either.

Thus, the first three cases reported in 2011 supported human to human transmission.  The Pennsylvania sequence matched the Wisconsin sequence in all 8 gene segments.  The Minnesota case lab confirmed human to human transmission in the cluster, and suggested the symptomatic contacts who tested “inconclusive” were also trH3N2 infected.  The first trH3N2 case in 2011 had no swine exposure and was acknowledged to be due to human to human transmission.  Moreover, the constellation of flu genes had never been reported in swine, and was matched by the next six trH3N2 cases in 2011.  Thus, all seven 2011 cases have the same constellation of genes which has never been reported in swine.

In spite of the overwhelming evidence for human to human transmission, the CDC early release MMWR requested samples from cases with a swine exposure, further biasing the testing for trH3N2.  This bias was extended by the Maine CDC who claimed that all 2011 trH3N2 cases had a swine exposure (which was in the advisory associated with the first October case in Maine).  Similarly, the Indiana DoH claimed that there was no novel influenza circulating in Indiana, even though the only PCR confirmed cases in week 43 was trH3N2, and this isolate was only the second confirmed flu cases in the first month of the 2011/2012 flu season (weeks 40-43).  Thus, the trH3N2 case represented 100% of the PCR confirmed cases in Indiana week 43, and 50% of confirmed cases in the 2011/2012 season.

The WHO summary also does not note the relationship of the 2011 isolates to the 2010 sequences.  However, Table 7 lists the ability of the four trH3N2 antisera (A/Kansas/13/2009, A/Wisconsin/12/2010, A/Pennsylvania/12/20110, and A/Minnesota/11/2010) to recognize the first trH3N2 from 2011, A/Indiana/06/2011.  The recognition is high because the H3 is closely related to the targets from Wisconsin and Minnesota, while the N2 is closely related to the isolate from Pennsylvania.
 
The September publication confirmed that Minnesota/11/2010 was the pandemic H3N2 vaccine target, as suggested by the release of sequences in August, and the September report was e-mailed to WER subscribers on October 21 (but was not updated to reflect the three confirmed October cases.

The two most recent October cases were the subject of reports in the media and ProMED, which noted the development of seed stocks, which were largely ignored, due in part to the representations in the CDC and WHO reports, which focused on swine exposure minimized the significance of the sequence matches, the Minnesota cluster, the lack of swine exposure in the first reported 2011 trH3N2 case, and the absence of the human contagion constellation in swine.

An outbreak of an usually mild form of pneumonia has been reported among school-age children in Shelby County, southeast of Indianapolis.

Several of the children, primarily in elementary and middle schools, have been hospitalized, the Shelby County Health Department reports.

"At least 20 students have shown a similar chest x-ray pattern, and several have required hospital admission and treatment with intravenous antibiotics," said a news release from Shelby County health officials. "The affected students are distributed throughout Shelby County, and thus the disease is not associated with any one school or other specific location or activity."

The exact cause is unknown, but it is believed to be a type of "walking pneumonia," which comes from specific bacteria that does not respond to drug treatments including penicillin and cephalexin. The bacteria can be fought with drugs including erythromycin (also known as Z-Pak), fluoroquinolones (also known as Cipro, Levaquin), and tetracyclines.

Typical symptoms include fever, cough, bronchitis, sore throat, headache and tiredness, according to the Indiana State Department of Health's epidemiology resource center, which said walking pneumonia usually is mild and rarely requires hospitalization. Infections of the middle ear

also can result.

Symptoms may persist for a few days to more than a month, according to the state center. Symptoms begin 15 to 25 days after exposure and generally develop slowly, over a period of two to four days.

The State Department of Health provided local physicians with testing kits for the bacteria mycoplasma to help determine if it is the cause of the ailment, Shelby County authorities said. The bacteria are transmitted via droplets from coughs or other contact with saliva.

There are no vaccines to prevent mycoplasma pneumonia, the state reports.

Children with the ailment should stay home from school, the health department said.

"If your children have a cough and any of the symptoms above, please keep them home from school and seek evaluation from your primary care physician," the release said. "As always, cough into your sleeve, wash your hands frequently or use antibiotic hand gel, and dispose of tissues properly."

http://www.indystar.com/article/20111108/LIVING01/111080396/Pneumonia-breaks-out-among-Shelby-County-children?odyssey=mod|newswell|text|IndyStar.com|s

Atypical Pneumonia in Indiana Children Raise trH3N2 Concerns
Recombinomics Commentary 19:45
November 8, 2011
"Every time it went away it would always come back, and it was 102," said parent Kim Dickmann.

Her son Luke, 6, has pneumonia.

"When you start seeing chest X-rays with infiltrates, fluid in the lungs, you know this is more than just your typical illness," said Dr. Paula Gustafson, a Shelby county pediatrician.

Gustafson said she saw 15 possible cases of pneumonia last week and upward of five possible cases on Monday.

"We've had some of them complain about intense cough, tightness in their chest, they've been on a couple rounds of antibiotics, and they aren't getting better," she said.

The above comments describe an atypical pneumonia in elementary and middle school students spreading throughout Shelby County, Indiana.  The Shelby County health department is treating the outbreak as Mycoplasma, but as seen above, cases have a high temperature and are not responding to antibiotics and there has been no lab confirmations reported.  Moreover, at least five of the more than 25 symptomatic students have been hospitalized.

The age demographic matches that of most confirmed trH3N2 cases this year (six of the seven were 9 years of age or younger), of which two were in Indiana.  Media reports do not suggest these patients have been tested for influenza.

More information on testing would be useful.

Recombinomics Commentary 12:40
October 28, 2011

*** CDC discontinued reporting of individual confirmed and probable cases of 2009 pandemic influenza A (H1N1) virus infections on July 24, 2009. During 2009, four cases of human infection with novel influenza A viruses, different from the 2009 pandemic influenza A (H1N1) strain, were reported to CDC. The four cases of novel influenza A virus infection reported to CDC during 2010, and the seven cases reported during 2011, were identified as swine influenza A (H3N2) virus and are unrelated to the 2009 pandemic influenza A (H1N1) virus. Total case counts are provided by the Influenza Division, National Center for Immunization and Respiratory Diseases (NCIRD).

The above comments from the week 42 MMWR confirm that the novel influenza listed in the provisional table was trH3N2, and is almost certainly the last reported case (8M) from Maine, A/Maine/06/2011.  The seven cases confirmed in 2011 strongly support human to human (H2H) and contradict the CDC narrative citing a very loose “swine exposure” as a source of the infections.

The first case confirmed in 2011 is from a 2010 infection in a case, A/Pennsylvania/40/2010. who was symptomatic on Sept 6, 2010, a week prior to the Wisconsin case, A/Wisconsin/12/2010, and 7 weeks prior to Pennsylvania case, A/Pennsylvania/14/2010, which were the subject of the WHO pager alert.  That alert noted the Wisconsin and Pennsylvania cases and assurance were then issued by the CDC that the two cases had sequence differences indicating that the infectiones were not from a common source. 

However, the sequence from the first Pennsylvania case was virtually identical to the Wisconsin case, but the reporting of the first Pennsylvania case delayed 5 months due to technical issues linked to the growth and isolation of the virus.  However, the CDC has a PCR tested for swine H3, which can quickly identify trH3N2 in samples directly.  Similarly, the CDC can sequence from the clinical sample without virus isolation.  These abilities were clearly demonstrated in the Maine case.  The state agency notified the CDC of an influenza A positive, subtype inconclusive case, on October 14.  The CDC confirmed trH3N2 on October 16, and released full sequences for all eight gene segments on October 17, using the clinical sample collected in Maine on October 10.  Thus, cases that support the CDC can be analyzed and reported in a few days, not 5 months.

A long delay was also associated with the second trH3N2 reported in 2011.  This was another 2010 case who was the daughter of a case (31M) confirmed in 2010, A/Minnesota/11/2010.  She had no swine contact and her trH3N2 was confirmed serologically.  Other symptomatic family members were “inconclusive” for trH3N2, suggesting many family members were infected by A/Minnesota/11/2010, and the CDC has used this isolate to create an H3N2 pandemic vaccine.  This cluster represented the first acknowledged H2H transmission of trH3N2.

However, the five trH3N2 cases infected in 2011 provide compelling evidence that this new human contagion is widespread in humans.  In 2010 most of the human cases shared most of the flu trH3N2 genes, but in 2011 this clustering evolved into identities where all 5 2011 cases match each other in all five gene segments, including an M gene from H1N1pdm09, which was critical for the jump of H1N1 from swine to humans.

The first 2011 case, A/Indiana/08/2011, had no swine contact.  His caretaker had swine exposure, but the caretaker and swine were asymptomatic and no SOIV has been reported.  Moreover, enhanced surveillance of swine in the United States and swine worldwide has failed to identify the constellation present in all five human cases.

Moreover, the next three cases attended the Washington County Fair in Pennsylvania and two of the sequences, A/Pennsylvanai/10/2011 and A/Pennsylvania/11/2011, were virtually identical to the Indiana, infected a month earlier, while the third case in Pennsylvania, A/Pennsylvania/09/2011, was a drift variant, signaling a second source for the Pennsylvania, but the constellation of gene segments was the same.

The most recent case from Maine, A/Maine/06/2011, is also a drift variant.  It began to diverge from the 2010 sequences at an earlier date, adding support for a widespread distribution of this human contagion.

However, all five of the confirmed 2011 trH3N2 have a loose association with swine exposure raising concerns that case with no swine exposure have not been disclosed because they are still being investigated for a swine exposure, leading to bizarre reporting of unsubtypables, which resemble a shell game, with clear examples of “now you see it / now you don’t”.

Recombinomics Commentary 17:30
October 24, 2011

"The acquisition of the M gene likely occurred as a result of swine being co–infected with the swine influenza A (H3N2) virus and the human 2009 H1N1 virus".

The above comments are from the latest CDC “Have You Heard” which discusses the most recently reported trH3N2 cases (8M), A/Maine/06/2011.  This isolate increases the overwhelming evidence for the transmission of trH3N2 in humans, yet the CDC continues to cite swine involvement, which is not supported by data.

The sequence data provides compelling evidence for human transmission, and the evidence was initially made public in November, 2010 when the CDC released the sequence data on trH3N2 cases. The sequences were released just after the WHO issued a pager alter on two trH3N2 patients and the sequences (A/Wisconsin/12/2010 and A/Pennsylvania/14/2010) raised concerns. Many of the internal genes from cases were clustering phylogenetically, signaling adaptation to humans. However, the CDC put out its first “Have You Heard” on trH3N2, which suggested the two cases did not represent human transmission because of differences between the two sets of sequences.

Shortly after these assurances were given, another case was reported.  This case was in Minnesota and the sequences, A/Minnesota/11/2010, were closely related to the Wisconsin case, providing more evidence for human transmission.  This sequence data was strengthened by 2011 reports on additional 2010 cases.

The first data set came from the report of a second Pennsylvania case, A/Pennsylvania/40/2010, who developed symptoms less than a week prior to the Wisconsin case.  However, the sample was initially classified as seasonal H3N2, and additional analysis / reporting was delayed because of technical difficulties in growing the virus.  In week 4 of 2011 the case was reported as another trH3N2 case, and the sequence was closely related to the Wisconsin case, demonstrating clear clustering of sequences from human trH3N2.

The concern that this clustering signaled human transmission was confirmed in week 21, when the daughter of the Minnesota case was confirmed to have also been trH3N2 infected, even though she had no swine contract.  The CDC then acknowledged limited human transmission (additional family members were also symptomatic, but trH3N2 confirmations were reported as “inconclusive), and selected the isolate from the father as a pandemic H3N2 vaccine target.

However, the sequence data for human transmission was significantly strengthened, when sequences from the first 2011 trH3N2 case (2M), A/Indiana/08/2011, were released at GISAID without comment, other than a note mentioning the presence of an M gene segment from pandemic H1N1 (H1N1pdm09). The acquisition of the M gene was a concern because an independent reported cited the M gene as being critical for the jump of H1N1pdm09 from swine to humans.  Therefore, this acquisition could drive the jump of trH3N2 from swine to humans.  The sequences of the other genes also increased concerns.  5 gene segments (PB2, PA, HA, NP, NS) including H3 matched the most common 2010 human trH3N2 sequences, while the NA was closely related to the second Pennsylvania isolate (PA/14/2010) and the PB1 was related to two other human cases, A/Ohio/01/2007 and A/Ohio/02/2007, linked to the Huron County outbreak.  This, all seven of the trH3N2 gene segments matched prior human isolates, adding to the evidence of human adaptation.

The release of the Indiana sequence was followed by an early release MMWR which described the Indiana case (2M) as well as a 2011 case (2F), A/Pennsylvania/09/2011, who was from Schuylkill County in eastern Pennsylvania, but attended the Washington County agricultural fair in western Pennsylvania.  The Indiana case had no swine contact, but his caretaker contact with swine was cited as a potential trH3N2 source leading to limited human to human contact.  However, the caretaker and associated swine were asymptomatic, so no true link was established.  Similarly, the Schuylkill resident attended an agricultural fair, but no symptomatic swine was identified.  The MMWR also cited sequence differences between the Indiana and Pennsylvania cases, suggesting the infections did not come from a common source.  However, both sets of sequences had the same constellation of genes, including the M gene from H1N1pdm09, as well as matches for all 7 trH3N2 gene segments.

The early release MMWR was followed by another “Have You Heard” which described two addition cases (both 9F), A/Pennsylvania/10/2011 and A/Pennsylvania/11/2011, which had the identical set of gene segments.  These three cases from the same county fair represented the largest number of trH3N2 isolates from a single location.  However, the investigation, which the CDC characterized as “intensive”, failed to identify a source for any of the 2011 cases.

The release of the sequences from the 2011 trH3N2 cases in Pennsylvania strongly supported human transmission.  Although the sequences from PA/09/2011 signaled a different source, the sequences from the other two cases, PA/10/2011 and PA/11/2011, were virtually identical to each other as well as IN/08/2011, even though the Indiana case was a month earlier and at a location 100’s of miles away.  The sequence identity between these three cases, which were not epidemiologically linked, strongly supported sustained transmission, and the identical constellation of genes in the third Pennsylvania case strong supported human adaptation.

The support was increased with the report of the 5th trH3N2 case (8M), A/Maine/06/2011, which also had the M gene from H1N1pdm09.  The sequences confirmed that the identical constellation of genes was involved, although several gene segments began evolving away from the 2010 human trH3N2 sequences at an earlier data, strongly suggesting that this novel trH3N2 represented a new human contagion, and represented sustained transmission.

The CDC has denied sustained transmission based on epidemiological data, which was generated using the same approach that failed to identify a source for any of the 5 2011 trH3N2 cases.  The linkage to swine was based solely on the pseudo linkages, which led to trH3N2 testing, which is only done by the CDC and is limited to samples received, which are flagged due to pseudo linkage to swine, including the Indiana case which had no direct linkage, and the other four cases who had attended fairs where asymptomatic swine were exhibited.

However, no symptomatic swine have been identified at these fairs, and no swine have been identified with the constellation of genes found in all five human cases from three states (Indiana, Pennsylvania, and Maine).

Thus, in spite of this lack of any real data linking human trH3N2 to trH3N2 infected swine, the CDC continues to statements such as the one quoted above, which are based on hopes and dreams, and lack any real data.

Recombinomics Commentary 23:15
October 21, 2011

CDC has confirmed the fifth case of human infection with a swine–origin influenza A (H3N2) virus that carries the M gene from the 2009 H1N1 virus. This virus was first detected in a child in Indiana in July. Subsequently three additional cases of human infection with swine–origin influenza A (H3N2) viruses carrying the same genetic change were detected in Pennsylvania. Though rare, human infections with swine–origin influenza viruses can occur, usually after close contact with infected swine.

While we know the M gene plays a role in influenza virus infection, assembly and replication, the significance of this change in these swine–origin influenza A (H3N2) viruses is unknown at this time. CDC continues to investigate the implications of this genetic change.

The above comments are from the latest “have you heard” put out by the CDC.  The statements represent an agency in the state of denial with regard to the human transmission of trH3N2.  They confuse reported trH3N2 with actual trH3N2 infections.  The association with swine is directly linked to the CDC trH3N2 testing which is largely limited cases with some kind of pseudo-link to swine.

The report acknowledges that the 5 trH3N2 in 2011 all involve the same trH3N2 virus which has an M gene from pandemic H1N1, but ignores the data indicating the M gene of pandemic H1N1 is critical for human transmission.

The CDC has yet to provide any direct evidence for human trH3N2 infections from swine in 2011.  The first case (from Indiana) has no known swine contact, and the CDC has acknowledged likely human to human transmission, which has also been acknowledged for the two most recent 2010 trH3N2 cases (father and daughter from Minnesota represent by A/Minnesota/11/2010 isolated from the father).

For the four most recent trH3N2 cases (in Pennsylvania and Maine) no link has been established between SOIV infected swine and the four cases.  The three Pennsylvania cases attended an agricultural fair (which is why they were tested for trH3N2), but no swine with symptoms or trH3N2 swine infections have been identified.  The same is true for the Maine fair in Cumberland County.  Moreover, no swine anywhere at any time have been identified with the human constellation, even though swine surveillance in 2010 and 2011 has been dramatically increased in the US.

Similarly, the CDC has failed to demonstrate that trH3N2 is rare in recent human H3N2 cases.  They have released sequences from 15 US H3N2 cases infected since July, and 5 of the 15 were trH3N2.

Thus, the CDC is relying solely on its heavily biased testing to claim the swine linkage.

Distribution of trH3N2 PCR kits to state labs is long overdue. 

Such state testing will determine the true extent and transmission of trH3N2 in humans in the US in the 2011/2012 season.

PORTLAND, Maine (AP) — An unusual strain of swine flu has infected five young children in Maine, Pennsylvania and Indiana, health officials said Friday.

A young boy of 7 or 8 from Cumberland County, Maine became the latest case when he came down with flu symptoms in early October, not long after being exposed to pigs at an agricultural fair, the Maine Center for Disease Control and Prevention said. He and the other four children have recovered, health officials said.

The H3N2 swine-origin strain was confirmed by the U.S. Centers for Disease Control as the same strain identified earlier in three cases in Pennsylvania and one case in Indiana, according to Maine's state epidemiologist Stephen Sears.

The three infected children in Pennsylvania had all attended an agricultural fair in August where pigs were exhibited, the CDC said. The Indiana child had not been exposed to pigs, but is thought to have been infected in late August by another person who had recently been exposed to pigs, but who did not have flu symptoms.

Unusual strains of influenza pop up virtually every year, health officials said, and there's nothing to suggest that this H3N2 strain is being widely transmitted from person to person. The infected boy in Maine was treated by a family doctor and is back up and playing, Sears said.

"We're taking a prudent public health approach to this," Sears said. "This is an unusual virus, but it doesn't appear to be spreading in people, so we don't think it's a major issue."

The first case of H3N2 was reported to the federal CDC in late August after a boy under 5 from Indiana experienced a fever, cough, shortness of breath, diarrhea and a sore throat. The boy was hospitalized for treatment and has since recovered.

Like humans, pigs can become infected with influenza viruses and suffer the same symptoms people do. Pigs can become infected not only with swine flu viruses, but with human and avian influenza viruses as well, the CDC says. On rare occasions, humans can become infected with swine flu viruses; the CDC says fewer than two dozen cases have been documented in the last five years.

The H3N2 virus contains a gene picked up from H1N1 swine flu virus that resulted in global pandemic in 2009, the first combination virus to turn up in people since the pandemic, according to the CDC. It is a hybrid of viruses that have infected pigs over the last decade.

Influenza viruses are constantly changing and picking up genes from other viruses, and the H3N2 strain represents a step in the evolutionary process of a virus taking on new genetic properties, said federal CDC spokesman Tom Skinner.

"Right now we don't see any widespread person-to-person transmission and that's the key when it comes to influenza cases," Skinner said.

Meanwhile, seasonal influenza activity remains low around the country with the arrival of seasonal flu season, the CDC says. The agency said earlier that this year's vaccine, the same as last year's, likely would not protect against the new swine strain.

http://www.southbendtribune.com/news/sbt-new-swine-flu-virus-sickens-5-children-in-3-states-20111021,0,3133475.story

Recombinomics Commentary 01:30
October 18, 2011
The latest trH3N2 set of sequences, A/Maine/06/2011, released by the CDC match the 2011 trH3N2 sequences from Indiana, A/Indiana/08/2011, and Washington County (A/Pennsylvania/09/2011, A/Pennsylvania/10/2011, A/Pennsylvania/11/2011), confirming human to human transmission.  The sample was collected October 10, 2011 from an 8M in Maine and the CDC is commended for the rapid release of this set of sequences. However, the detection of this case in Maine suggests a lack of swine contact.

The Indiana case had no swine contact, and the latest comment from the CDC, in week 40 FluView, only states that the three Pennsylvania cases attended a county fair that exhibited swine.  There was no statement claiming swine contact (and there have been no reports of symptomatic swine at the Washington County fair and no reports of any influenza infections in swine). 

In contrast, all five human cases in 2011 have the identical constellation of flu genes including a PB1 that lacks E618D, an NA that is similar to A/Pennsylvania/14/2010, and an MP that matches pandemic H1N1.

The CDC claim of no sustained transmission merely reflects the limitations in the CDC sample collections and testing, which failed to find a source for any of the cases, including the caretaker of the Indiana case. The pseudo-linkage to swine drives trH3N2 testing of cases infected prior to the start of the flu season.  Details on the present case have not been released, but in contrast to earlier locations for 2011 trH3N2 cases in states that have high levels of swine, the location of this case, Maine, is not noted for swine farms or fairs.

The circumstances associated with the detection of the current case in unclear, but the bizarre reporting on unsubtypables raises concerns that testing for influenza A and/or seasonal H3 is a less than ideal approach for detecting human trH3N2 cases.

The CDC should distribute swine H3 PCR kits to the state labs to determine the true level of human trH3N2 infections and transmission in the United States.

Maine trH3N2 Sequences Signal Human Transmission
Recombinomics Commentary 20:40
October 21, 2011

One case of human infection with a novel influenza A virus was reported by the Maine Center for Disease Control and Prevention. The patient was infected with a swine origin influenza A (H3N2) virus. Testing performed at Maine’s Health and Environmental Testing Laboratory on October 14, 2011 indicated a likely swine origin influenza A (H3N2) virus and this result was confirmed at CDC on October 16, 2011. The patient reported attendance at an event where pigs were present in the week preceding symptom onset on October 7, 2011, did not require hospitalization, and continues to recover. No illness has been identified in family members or close contacts, but the investigation is ongoing.

Swine-origin triple reassortant Influenza A (H3N2) viruses have been circulating among North American swine herds since the late 1990's. Human infections with these viruses are detected sporadically, and cases usually occur following direct or indirect contact with pigs.

The above comments are from today’s (week 41) CDC FluView, which highlights the rapid generation and release of sequences from this case (8M).  The confirmation was two days after Maine tests, and a full set of sequences were made public (at GISAID) the following day (and made available at Genbank 2 days later).

However, the CDC has not addressed the significance of the 2011 trH3N2 sequences, which provide compelling data for human to human transmission.  Instead the CDC recites its standard comment on triple reassortants, and ignores the fact that all five isolates from 2011 have the same constellation of genes, which goes beyond the more general composition of 7 gene segments from trH3N2 cases and an M gene segment from pandemic H1N1.

The human trH3N2 sequences, release on November, 2010 had obvious clustering, which increased as additional cases were identified.  WHO issued a page alert on two of these cases, A/Wisconsin/12/2010 and A/Pennsylvania/14/2010 and offer assurance of o transmission based largely on significant differences in the sequences from these two isolates.  However, when those assurances were presented, another Pennsylvania case, A/Pennsylvania/40/2010 (PA/40/10), was being analyzed.  That patient developed symptoms less than a week prior to the Wisconsin case, but the PA/40/10, was initially designated seasonal H3N2 and was reported to be trH3N2 in 2011, five months after infection, and the sequence was virtually identical to the Wisconsin case. 

Moreover, just after the pager alert another case was identified in Minnesota, A/Minnesota/11/2010, and most of the gene segments, including H3, were closely related to the Wisconsin and Pennsylvania cases.  In addition, the daughter of the Minnesota was subsequently trH3N2 confirmed (serologically), increasing the number of confirmed trH3N2 cases infected between September and November 2010 to five, and four of the five had gene segments, including H3 that were closely related, signaling human adaptation.

This adaptation was significantly increased in the 2010 isolates.  The early release MMWR report by the CDC described the first two cases, A/Indiana/08/2011 and A/Pennsylvania/09/2011, and noted that both had an M gene from pandemic H1N1.  Again assurances were offered based on sequences differences because although both isolates had the same constellation of genes, the Pennsylvania isolate was a drift variant and a few of the genes had evolved further from the 2010 sequence than the Indiana isolate.  However, two additional cases were identified in Pennsylvania (A/Pennsylvania/10/2011 and A/Pennsylvania/11/2011) which were virtually identical to each other as well as the Indiana case.  Thus, these three cases not only had the same constellation of genes, but the sequences of all 8 gene gene segments were virtually identical, even though infections in Indiana and Pennsylvania were a month apart and not link epidemiologically, supporting human to human (H2H) transmission.

The H2H transmission was further supported by the Maine sequence, A/Maine/06/2011, which had the same constellation of genes as seen in the four earlier 2011 cases, but evolution from the 010 sequences was slightly different.  The Maine genes branched off the 2010 sequences earlier, and consequently were more closely related to several of the 2010 gene than the IN/PA cases even though the ME case was infected more recently.

This earlier divergence indicates human trH3N2 infections have more heterogeneity than seen in the five sets of sequences released, and this earlier divergence highlights the significance of the lack of the detection of this constellation in swine isolates, which has not been reported in any swine, including a high number of 2011 isolates collect as recently as July, 2011.

This, the identity in the overall constellation of flu genes in all five 2011 human cases and its absence in all swine cases signals H2H transmission, as does the acquisition of the M gene segments from pandemic H1N1, and the close relationship to the 2010 human trH3N2 sequences.

In contrast to the public data supporting human to human transmission, the CDC focuses of linkage to direct or indirect swine exposure based largely on selective testing of patients with a swine linkage for trH3N2.  To date the CDC has released H3N2 sequences from 15 US cases collected since July 2011, and 5 of the 15 cases have been trH3N2.

This high frequency, coupled with the sequence identities in these five cases, indicates the number of trH3N2 cases in the US is orders or magnitude higher than the five cases reported to date, and PCR test kits for swine H3 should be distributed to all state labs as soon as possible.