h3n2v

 This is a two-year-old girl, in Duoc, Long An and is now cured. For years, our country has recorded cases of infection with influenza virus A (H3N2) in humans, also known as regular seasonal flu, while flu patients is derived from pigs.

Recombinomics Commentary 13:15
February 15, 2012

The national flu monitoring system detected this case in April 2011. A two-year-old female baby in Long An province contracted the disease and was treated successfully at the Children’s Hospital No 1. in HCM City. The A/H3N2 flu virus she had originated from pigs.

The test results of the HCMC Pasteur Institute were confirmed on January 10, 2012, by the WHO laboratory at the US Centres for Disease Control and Prevention (CDC).

The above comments provide additional clarity on the dates surrounding the confirmed H3N2v case in Vietnam, but still leave many questions unanswered.  It is likely that this case was initially classified as seasonal H3N2 in 2011.  The H3N2v cluster in Iowa in November led to an alert issued by WHO, largely because the three confirmed cases had no swine exposure.  That alert was followed by a media report in Vietnam that described the US cases and increased surveillance in Vietnam.  Those reports incorrectly described the US H3N2v cases as H3N1.
Last week media reports in Vietnam again issued a warning about H3N2v cases, but only provided detail on the cases in the United States and again described the cases as H3N1, and a follow-up report claimed no H3N2v cases in Vietnam in 2012 (carefully parsed to avoid acknowledgement of the 2011 case).

Today, reports from Vietnam described the above case (age, gender, and location) and the English language reports clearly indicated this was a 2011 case that was confirmed over a month ago by the US CDC.

This raises several important questions, which have not been answered. None of the reports have cited a swine exposure by the confirmed case.  Similarly, the CDC has not released the sequences at GISAID, as was done for the 2011 variant cases in the United States (H3N2v, H1N2v, H1N1v).  Moreover, WHO has not announced the confirmed case, in spite of lab confirmation by a WHO regional center, although it is unclear if the WHO has announced this case at its password protected site.
Thus, a month after confirmation, all of the above questions remain unanswered by public data, although the sequence would clearly distinguish between a linkage to Asian or North American swine lineages.

The lack of transparency by WHO and the CDC continues to increase pandemic concerns.

Recombinomics Commentary 09:15
February 15, 2012

As reported by the National Influenza Center - Pasteur Institute of Ho. Ho Chi Minh, influenza surveillance system key southern countries found cases of A/H3N2 flu originated from pigs.

This is a new 2-year-old female patients in Duoc, Long An influenza have been treated at Children's Hospital 1 and then cured. Samples of these patients have been tested in a laboratory at the CDC standard WHO official - the United States and has been confirmed.

Yang said, this is the first case reported in Vietnam A/H3N2 flu originated from pigs. This slight movement of cases and no evidence of transmission from person to person.

The above translation describe the first case (2F) of H3N2v in Vietnam (Duoc, Long An).  In contrast to earlier reports, which described similar cases in the United States, this report describes a PCR confirmed case in the Mekong Delta region in southern Vietnam.

As noted earlier, there are 6 sets of public sequences from H3N2v in swine, isolated in 2010 (A/swine/Binh Duong/03_06/2010, A/swine/Binh Duong/03_08/2010, A/swine/Binh Duong/03_09/2010, A/swine/Binh Duong/03_10/2010, A/swine/Binh Duong/03_13/2010, A/swine/Binh Duong/03_14/2010). All six isolates are closely related and have human H3 and N2 genes, with swine internal genes that are generally more closely related to H3N2v swine sequences in Asia (South Korea and Hong Kong).

However, Hong Kong has released 3 sets of sequences from Guangxi and Hong Kong (A/swine/Guangxi/NS2783/2010, A/swine/Hong Kong/2503/2011, A/swine/Hong Kong/NS2439/2011) , which have similar H3 and N2 human genes surrounding six internal genes from H1N1pdm09. In the United States, all 12 of the H3N2v sequences in humans in 2011 have an H1N1pdm09 M gene. Prior H3N2v cases in the United States have PB1 E618D, which is not in the swine isolates from Vietnam, but is in the new sequences from Hong Kong and China, since E618D is in virtually all H1N1pdm09 PB1 sequences.

The above report does not cite swine contact, so the origin of the infection is far from clear.  H3N2v in Vietnam is readily distinguished from H3N2v in the United States.

Information on the constellation of genes in the case in Vietnam 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.