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04:45 AM Nov 28, 2011

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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 12:30
November 23, 2011
"It appears the seasonal influenza vaccine currently available may offer some protection against this novel strain,” said IDPH Medical Director, Dr. Patricia Quinlisk.

The above comment on the cross reactivity between the current seasonal H3N2 vaccine, which targets A/Perth/16/2009, and the novel trH3N2 spreading across the country ignores the recent WHO data in its recent update on pandemic vaccines.

The report noted that production of a vaccine against A/Minnesota/11/2010 had started, and various activities were released in table 7, Antigenic properties of a recent A(H3N2 SOIV).  The A/Perth/ 16/2009 (Perth/09) anti-sera had a titer of 640 against A/Perth/16/2009, but the level dropped to 10 for A/Indiana/08/2011, the first novel trH3N2 isolated.

All seven 2011 trH3N2 sequences are closely related to each other (and the sequences from the three Iowa cases are expected to be similar), and titer will be similar.

A titer of 10 is not protective and the current seasonal H3N2 vaccine will be of little value.  Moreover, the cases in Indiana and Pennsylvania (as noted in MMWR early release on first two trH3N2 cases in 2011) had been vaccinated previously with the current tri-valent vaccine.

The H3 and N2 in trH3N2 is linked to seasonal H3N2 infection of swine in the early 1990’s, but the trH3N2 has evolved significantly from the H3N2 circulating in the 1990’s (as seen in phylogenetic trees in CDC report to FDA vaccine advisory committee), and as seen by the WHO data, the current seasonal vaccine will have little utility for the trH3N2 spreading throughout the United States.

Recombinomics Commentary 14:00
November 10, 2011
International Travel epidemic

The United States - H3N2 swine flu

Source: WHO Event Information Site for IHR National Focal Point, 2011/11/2

U.S. 11 / 1 reported two cases of swine-derived H3N2 influenza cases, prior to the onset had a history of contact with pigs. 1 case of 8-year-old boy, the incidence of 10/22, 10/24 medical treatment; the other 1 case of 58-year-old male veterinarian, the incidence of 10/20, 10/21-10/24 hospital. The United States this year, total 7 cases swine-derived H3N2 influenza cases so far in 2005 total of 15 cases.

Relevant countries and regions:

The above translation is from the Taiwan CDC website which warns of travel to all 50 US states and District of Columbia due to the two most recent trH3N2 cases described at the WHO password protected site (IHR National Focal Point) for the reporting of diseases covered by International Health Regulations.

As seen above, like the WHO update on pandemic vaccine target, the 15 trH3N2 confirmed cases are reports as beginning in 2005, although the first US case was reported in August. 2009.  Thus, the concentration of cases is far higher than indicated on the WHO website designed for submission and reporting of a variety of cases including those infected by a novel influenza, such as trH3N2.

Although media and ProMED are reporting these cases as “sporadic” jumps from pigs to people, all 7 cases from the US, including the two cases cited above, have the identical constellation of flu genes which has never been reported in swine.

The finding of the 3 or more identical constellation of genes in triple reassortant cases, other than those infected with H1N1pdm09, is without precedent and clearly signals human transmission. Thus far reported 2011 trH3N2 cases have been limited to Indiana, Pennsylvania, and Maine, the 7 cases represent 70% of influenza cases reported by these states since July, 2011.

There has been limited and biased testing in the US, due in part to the CDC request for samples in the early release MMWR describing the first two 2011 cases, which limited samples to cases with a swine exposure.

The CDC should announce a modified request for pediatric samples from cases with flu-like symptoms and/or those that are influenza A positive.  These cases cannot be tested for trH3N2 by state agencies and samples must be tested by the CDC at this time, but an expanded testing of samples without swine exposure, such as the atypical pneumonia cases in Shelby County Indiana, is long overdue.

Asymptomatic Swine Linked To Indiana Veterinarian With trH3N2
Recombinomics Commentary 12:30
November 10, 2011

1 case of 58-year-old male veterinarian, the incidence of 10/20, 10/21-10/24 hospital.

The above translation is from the travel warning issued by the Taiwan CDC regarding trH3N2 in the United States.  The warning sourced the above information to the WHO Event Information Site for IHR National Focal Point dated 11/2.

The above dates and description of the trH3N2 case matched the characterization sheet associated with the sequences released by the US CDC for A/Indiana/10/2011 and subsequently reported by the Indiana State DoH and the US CDC.

Therefore, Recombinomics contacted Dr Bret Marsh, State Veterinarian at the Indiana State Board of Animal Health, who investigated the case.  He noted that all of the swine contacted by the veterinarian prior to symptoms had been asymptomatic for at least a month prior to contact, reducing the likelihood that these swine were the source A/Indiana/10/2011.

Similar results had been reported for the caretaker for the first 2011 trH3N2 case (2M) from Indiana.  The case had no swine contact and the caretaker ,as well as the swine linked to the caretaker, were asymptomatic.

Similarly, the swine presented at the Washington County fair in Pennsylvania were asymptomatic and the disease onset dates for the two Maine cases reduces the likelihood of a swine origin for these case.  The first case (8M) was from Cumberland county and he developed symptoms on October 7 (sample collected October 10).  He attended a agricultural fair in the week prior to symptoms, which was almost certainly the Cumberland County fair, which ended October 2.  The five day gap between the end of the fair and the disease onset dates reduces the likelihood that the swine were at source of A/Indiana/06/2011.  The second case was also exposed to swine at an agricultural fair and since the second case lived in the vicinity of the first, he (also 8M) his “exposure” was also associated with the Cumberland County fair, but he developed symptoms two weeks later (sample collected October 22) significantly reducing the likelihood that the swine at the fair were a source of his infections.  Moreover, there have been no reports of symptomatic swine at the fair in Maine.

The absence of linkage to any symptomatic swine by any of the 7 confirmed cases is consistent with the sequence analysis of the isolates from the human cases, which share the same constellation of genes with each other, including an M gene from H1N1pdm09, which has never been reported in swine anywhere in the world in spite of increased swine surveillance, including SOIV sequences from swine in Indiana and Pennsylvania collected in 2010 and/or 2011.

Moreover, the trH3N2 cases dominate the confirmed cases in the above states.  The two trH3N2 cases in Maine represent the only two reported cases since July 2011.  Similarly, the Indiana cases represent 2 of the 3 influenza cases in Indiana, while the Pennsylvania cases represent 3 of the 5 confirmed influenza cases in Pennsylvania.

Thus, the swine “exposure” is more closely linked to sample collection and testing than transmission from swine, which highlights the need for aggressive testing of cases without swine exposure, such as the atypical pneumonia cases in Shelby County, Indiana.

Recombinomics Commentary 17:45
November 2, 2011

Maine confirmed a second case of swine origin novel influenza A virus. The first case was confirmed on October 17th, and the second case was confirmed October 31st. Both cases had multiple exposures to pigs.

The above comments are from the Maine week 43 influenza surveillance report, and extends the number of 2011 trH3N2 cases with swine “exposure” to six, and it is likely that the seventh case (59M) will also have some sort of “exposure” raising concerns that the absence of cases without an exposure represents a charade which withholds such cases pending results of ongping epidemiological investigations.  All seven of the 2011 cases reported to date have the same constellation of flu genes, which has never been reported in swine in spite of increased swine surveillance and public sequences from swine isolates as recent as July, 2011.

The emergence of a trH3N2 human contagion was predicted by sequences from 2010 isolates, which were released after WHO issued a pager alert on two cases (in Illinois and Pennsylvania).  The pager alert created some concern, especially in eastern Europe, but the CDC noted that although both cases were H3N2 triple reassortants, sequence differences indicated the trH3N2 was not transmitting in humans.
However, the release of the sequences (at GISAID) revealed clustering of sequences and linkage to sequence isolate from a trH1N1 outbreak in Huron County, Ohio in 2007.  This outbreak yielded isolates from a presenter and her father (A/Ohio/01/2007 and A/Ohio/02.2007), which included internal genes which were precursors to the genes in the trH3N2 isolates.  Moreover, two dozen Huron fair attendees had flu-like symptoms, which are uncommon in August in Ohio, suggesting the trH1N1 spread well beyond the two confirmed cases.

The first trH3N2 case in the United States was from an infection two years after the Huron County outbreak.  The Kansas case, A/Kansas/13/2009, was followed by a case in Iowa, A/Iowa/16/2009, and one in Minnesota in early 2010, A/Minnesota/09/2010.  The isolates from the two cases in the pager report were A/Wisconsin/12/2010 and A/Pennsylvania/14/2010.  Just after the pager alert, a second case in Minnesota, A/Minnesota/11/2010 was reported, and additional cases in Minnesota were under investigation. The H3 sequence in the Minnesota isolate was closely related to the Wisconsin sequence, as were most of the other genes, which extended the clustering.

This trend was accelerated by the first two cases confirmed in 2011, which were cases that experienced significant reporting delays.  The first case (also from Pennsylvania) had developed symptoms less than a week prior to the Wisconsin case, but had been initially characterized as seasonal H3N2 and confirmation of trH3N2 was delayed due to technical issues linked to virus isolation.  Consequently, the case was reported 5 months after infection, and the sequence, A/Pennsylvania/40/2010, was closely related to the Wisconsin sequence, voiding the CDC assurances that followed the WHO pager alert.

The assurances were also voided by the second case reported in 2011, which was the daughter of the Minnesota case.  trH3N2 infection was lab confirmed by serological studies, which led to a six month delay in reporting.  The daughter had no swine contact, and represented the first lab confirmed examples of human transmission of trH3N2.  Like the Huron outbreak, the number of infections was likely markedly higher than the lab confirmed cases, because additional Minnesota family members had symptoms, but lab results were “inconclusive”.

Thus, the first two cases reported in 2011 strongly suggested that trH3N2 was transmitting based on sequence similarities between the cases in Pennsylvania, Wisconsin, and Minnesota, as well as lab confirmation of the Minnesota cluster.

However, the sequence data supporting human transmission was increased dramatically by the 2011 infections.  The first case reported was in Indiana and that case, A/Indiana/08.2011 also had no swine contact.  However, his caretaker had swine contact, but neither the caretaker nor the associated swine were symptomatic, and no evidence of SOIV infection has been reported.  The sequences from this case were novel.  Five of the gene segments, including H3, were closely related to the dominant sequence from 2010 (A/Pennsylvania/40/2010, A/Wisconsin/12/2010, A/Minnesota/11/2010, and the daughter of the Minnesota index case).  The NA gene however was closely related to the N2 of the other human case from late 2010, A/Pennsylvania/14/2010, while the PB1 gene was closely related to the sequence from the two confirmed 2007 cases in Ohio.

Of most interest however, was the M gene segment, which was acquired from H1N1pdm09, and this acquisition was of significant concern because a recent study indicated that the M gene was critical for the jump of H1N1pdm09 from swine to humans.  Moreover, this constellation of genes had not been reported in swine.

Concerns increased when the CDC issued an early release MMWR, which included the Indiana case as well as a case from Pennsylvania, A/Pennsylvania/09/2011, which had the same constellation of genes.  It was a drift variant, so the CDC noted that the same source for the Indiana and Pennsylvania was unlikely because of minor sequence differences.  However, these assurances were voided by two more cases from Pennsylvania, who like the first case had attended the Washington County fair.  These sequences matched each other, as well as the Indiana case, supporting human transmission.  Moreover, although swine were exhibited at the fair, there were no reports of symptomatic swine or identification of SOIV infection.

The emergence of a new human contagion was supported further by the first case in Maine (8M), which had a matching constellation of genes a seen in A/Maine/06/2011.  Swine exposure at an agricultural fair (likely the Cumberland County fair) was again cited, but no symptomatic swine were reported.  That case was followed by another case from Maine, A/Maine/07/2011, and Indiana, A/Indiana/11/2011 which were also from patients infected in October by trH3N2 related to each other and the first Maine case.

Thus, all seven 2011 cases have the same constellation of genes which has not been reported in any swine.  In spite of this strong evidence of human transmission, all reported cases have a loose “swine exposure” component, suggesting cases without a swine exposure are being withheld pending epidemiological investigations.
trH3N2 cases without some sort of swine exposure, would confirm widespread human transmission and the start of a new pandemic, and this announcement has been delayed by the charade that releases sequences from cases with a swine exposure, and delays confirmation of cases without an exposure.

Details on suspect trH3N2 cases under investigation are long overdue.