Recombinomics Commentary 14:15
January 25, 2012

 Now, allegations of similar cases are also found in West Jakarta, where a boy aged three years initials RV, a resident of RT 15/07 Cengkarengtimur Village, District Cengkareng , died on Monday (23 / 1) around 06.00 after previous intensive care at Friendship Hospital, East Jakarta.

Regarding the victim's body is covered a coffin and not allowed to open, say Parwathi, it was according to the procedure as a form of anticipation of the hospital for suspected cases of bird flu. Despite the negative results of bird flu, disclosed Parwathi,

The above translation describes the death of a suspect H5N1 case (3M) in Cengkareng, Indonesia, which is adjacent to Tangerang, where another suspect H5N1 case (18M) also died after testing negative for H5N1.  These two cases had bird flu symptoms and were buried in a sealed coffin, which is customary for H5N1 cases.

The failure to detect H5N1 in these two fatal cases in adjacent areas on the west side of Jakarta is in addition to the suspect case in Bekasi, on the east side of Jakarta, as well as the confirmed cluster in North Jakarta, where the second case initially tested negative for H5N1.

These five cases in the Jakarta area raise concerns that H5N1 is being more efficiently transmitted as it evolves away from the sequences being used in the H5N1 PCR test.

Recombinomics Commentary 12:45
January 25, 2012

Patient suspect bird flu, Rohmat (18), resident of RT 09/03, Ciodeng Village, Village Blooms Jaya, District Panongan, Tangerang regency, died after being treated for five days in critical condition in RSU Tangerang District, on Wednesday.

Previously the patient's condition was critical since it first entered isolation space bird flu," said Public Relations RSU Tangerang Regency Ahmad Muchlis when confirmed on her cell phone. According Muchlis, until now is still not clear whether Rohmat died from bird flu or not. "There is no certainty. But the results of observations in the home environment Rohmat by the Health Department yesterday was negative bird flu," he said. He added that the next will Rohmat shrouded corpse in the mortuary. Chances are, he said, Rohmat not take home to his family home. "The possibility is not taken home, but immediately buried," explained Muchlis.

The above translation describes the death of a suspect H5N1 case (18M) in Tangerang, Indonesia, which is on the northwest side of Jakarta.  The death follows a confirmed H5N1 cluster in North Jakarta, as well as suspect fatal cases in Cengkareng, which is adjacent to Tangerang, as well as Bekasi, which is on the east sided of Jakarta. 

Although the three most recent cases have not been H5N1 confirmed, the second case (5F)  in the North Jakarta cluster tested negative multiple times before H5N1 confirmation at autopsy, raising concerns about the sensitivity of the H5N1 for the bird flu currently circulating in Indonesia.
False negatives in Indonesia are common because patients are tested after the start of Tamiflu treatment, which lowers the RNA level.  Patient who recover continue to test negative and are not reported as confirmed cases, while those who die have increasing H5N1 RNA levels, which eventually test positive.  This testing procedure accounts in part for the high case fatality rate, which ha been near 80% in Indonesia since the first confirmed cases were reported in 2005.

However, at least two the three cases adjacent to Jakarta have tested negative, even though the patients have died with H5N1 symptoms, and have been quickly buried, per protocol for confirmed H5N1 cases.
These recent fatalities and the failure to link the cases to infected poultry, has raised concerns that the H5N1 in Indonesia is being transmitted more efficiently, as seen in the confirmed cluster in North Jakarta as well as the Bali cluster.

Sequences from the Bali cluster included receptor binding domain changes (D187N, A188G, R193M), as well a clear examples of recombination.  Moreover, these chnages are likely to lead to immunological escape.

Release of sequences from the North Jakarta cluster would be useful.

Blue dot postmark is confirmed poultry. Blue postmark is suspected poultry. Red is human:

Back in October, 2011, the Chickens started to die in the Bone Regency. We reported it on Nov. 25th. Article found here:

16/10/2011 10:04

Liputan6.com , Bone: Hundreds of chickens died suddenly in the Village Ponceng, Bone regency, South Sulawesi. Allegedly the chickens died of bird flu that is circulating in the area. Dead chickens salivate.

On January 11, we previous reported a family of 6 in S. Sulawesi. 3 Family members were dead, and the other 3 were put in ICU, along with 15 others. Article(s) can be found here, here, here, here, and here.
Our details are below.

Date of article 1/10/12 

3 Family Members Died in house with Same Complaints 

Below: Father, Mother, 11 yo 

Name: Risnawati or Nismawati (16) 

Name: Nurbaya 

Name: Arsil

Name: Wahid

From: Relemba, Tombolopao Dist., Gowa

Sym’s: high fever, sore throad

Adm: RSU Wahidin (a referral hospital for bird flu)

Notes: All live in same home. All had same complaints. Health Department went in to village, 1/7. Family & neighbors taken blood samples. 15 people were brought to Wahidin Hosp. Suffering from severe clinical symptom’s.

 

Adm: 14 civilians in Intensive Care, RSU Wahidin

 

Deaths:
3 Brothers

Name: Zul Asril (6)

Adm: 12/20 - Pustu Health Ctr.

Sym’s: high fever sore throad/bleed when spitting

Diagnosis: tonsillitis pharyngitis/acute inf. Resp. tract.

DOD: 12/26/11

 

Name: Amiruddin (17)

Adm: None. Brought to Traditional Healer.

Sym’s: same as brother Zul

Onset: 12/25

DOD: 12/30/11

 

Name: Nurmiati (14)

Adm: none

Sym’s: sore throat

Onset: (?) Drastic decline on 12/31.

DOD: 1/3/12 Died on way to health center

 

On 1/20, Residents were brought to the hospital in N. Sulawesi located here.
Excerpt:

Shocking, bird flu virus (H5N1) that is very deadly if contracted in humans, was endemic in the region Kanonang Kingdom, Western District Kawangkoan, Minahasa regency. A number of residents who allegedly exposed to the virus was rushed to hospital and 2740 chickens and ducks dimusnahan, Friday (01/20/2012).
"The incidence of chickens died suddenly had occurred from late December 2011. Until now there are chickens that died suddenly," he said
Head Distanak North Sulawesi Province, Johanis Palenewen said, according to procedures for handling bird flu, if there is one area of ​​bird flu infected poultry, all poultry population in the area must be destroyed.
"Culling of poultry has been within the rules. We found no positive poultry infected with bird flu, poultry populations so that all must be destroyed. This is done to break the spread of bird flu virus," he said.

In an article, 1/20, 2 boys are hospitalized, suspected of bird flu, posted here and here:

Unexpected Observations Diskes Minahasa boy Bird Flu, Friday, January 20, 2012 16:59 pm "But we will continue to observe its development. We are concerned lest the later symptoms appear several days after the sudden death of poultry at the scene," he said. Manado (North Sulawesi Reuters) - North Sulawesi Provincial Health Office observe the two boys suspected bird flu in the village of Kanonang, District Kawangkoan, Minahasa regency, North Sulawesi Province.

"There are two three-year-old boy and 12 years, but both had to go home to his village. We are still observing to see the development of a sequel," said Head of Controlling Health Problems (FMD) Diskes North Sulawesi Province, dr Lampus Jemmy, in Manado, on Friday.

He said the two boys was observed after feathered friends around him died suddenly and unexpectedly have a fever.

Article dated January 21, that tells of the poultry dying with absolutely NO symptoms.
Excerpt:

Hundreds of chickens owned by residents of Environmental Makammu 2, Village Bulukunyi, District of South Polongbangkeng, in an instant died suddenly, Friday, January 20.

The incident shocked the owner of the chicken. Worried about bird flu, chickens that died immediately annihilated by dumped and buried. Residents later reported the incident to the related department.

"There is no previous symptoms. But before dying chickens bowed his head bowed. After five minutes later, the chicken is dead," said one resident, Dg Nuntung. Until yesterday afternoon, his ten chickens died.
Neighbors Nuntung Dg, also experienced the same event. Fourteen of his chickens, died suddenly.
"One chicken bangkok kasian I die, too. Now live chicks remaining," said Dg Nanring.

Do not want to take risks, a number of teams from the field of Animal Husbandry Takalar immediately took to the field. They took samples of dead chickens and chickens live who are ill to be examined the scene.

"The chickens are infected with virus positive ND (newcastle disease), not the bird flu. ND virus is not contagious to humans, but its spread to other chicken fast enough," explains Head of Livestock Department of Agriculture and Forestry Takalar Ghani Muhammad Ridwan.

He also suggested to conduct spraying disinfectant on the chickens are still alive. Ridwan also said, live chickens infected with ND virus can still be consumed as long as it is cooked to perfection.

"To destroy this virus is rather difficult. Control can only be done by way of vaccination. It is common place, as it related to weather factors. So that affect the health of chickens that are easily infected with ND virus of this disease," he explained.

To obtain more complete results, it also brought some samples to be tested in depth in the laboratory.
http://tinyurl.com/7847moc

source: http://pandemicinformationnews.blogspot.com/2012/01/indonesia-commentary-on-sulawesi-h5n1.html

Click map to enlarge
We have had 5 deaths.
An additional death (part of a family cluster) on December 31st.

In Indonesia, we have a cluster of 6 Family members, 3 alive (last we knew); 3 dead. 14 in ICU No information as to their diagnosis.

In Indonesia, we have another confirmed by the Director of the Hospital, but not yet by the Health Minister.

Source:

Thanks to Commonground

http://pandemicinformationnews.blogspot.com/2012/01/summary-map-of-2012-confirmed-human.html#links

Recombinomics Commentary 16:45
January 23, 2012

"A man died in southern China on Sunday from the H5N1 bird flu virus, the Health Ministry reported. It was China’s second such death in less than a month.

On Sunday, Chinese censors generally blocked Internet users from reading reports of the latest death."

The above comments describe censorship of news on the H5N1 case (39M) from Guiyang, Guizhou who had no reported contact with poultry, suggesting that the case would be linked to clade 2.3.2.1 as seen in the recent case from Shenzhen, who also had no reported contact with poultry.  The sequences from the Shenzhen case, A/Guangdong-Shenzhen/1/2011, were released less than a week after collection, and the HA sequence had a number of receptor binding domain changes.  The two changes reported in the Gharbia cluster, V223I and M230I, were present, as expected.  However, the sequence also had S227R as well asQ196K, raising concerns that the combination of changes could be approaching the five changes reported in the paper censored by Science. 

That paper described five changes on two genes and four of the five changes have already been found in published sequences.  One of those changes is PB1 E627K, which was not in the Shenzhen clade 2.3.2.1, but was present in the most recent H5N1 sequence from cases in Cambodia, where all 8 of the cases in 2011 have died, as has the only case in 2012.  That case also had S227N, which is likely to be one of the HA changes in the aerosol version of H5N1 that transmits in ferrets.

The co-circulation of the above changes raises concerns that new combinations may be generated by recombination, leading to enhanced transmission, which may or may not match the changes described in the censored paper at Science.

It is unclear if the censorship of news on the most recent case will impact release of sequences from the Guizhou case.  Similarly, Indonesia quickly released sequences from the Bali cluster, which also had receptor binding domain changes.  That cluster was followed by a cluster from North Jakarta. And sequences from that cluster have not been released, raising concerns that the censorship of the papers and nature and Science will have a chilling effect on transparency and lead to more hidden sequences, as it becomes increasingly clear that H5N1 currently in circulation is very close to efficient transmission.

The natural versions pose a far greater hazard than some unnamed rogue state or terrorist who are said to benefit from the release of the five changes describe in the Science paper.  Since it is already known that 4 of 5 changes are already in circulation in a published sequence, the creation of a transmissible H5N1 is a trivial task, although the value of such bioweapon is far from clear, since influenza cannot be controlled, and effects on rogue nations would be significant.

Thus, the censorship by Nature and Science continues to endanger the world’s health, and the lack of understanding of influenza evolution by the NSABB is glaring.  Therefore replacement of the current board with one more knowledgeable about influenza evolution should be actively pursued.

China announced today the second death because of bird flu in this country, in less than a month, following the death of a person in Vietnam and a child in Cambodia.

Officials said the last patient died today in Guizhou Province in southwest China, after being taken to hospital on 6 January.

Tin said the 39-year-old man who has no direct contact with poultry.

In December last year, a bus driver had died of avian flu in Guangdong Province.

Avian influenza virus is usually spread to people who have direct contact with infected birds have.

Some scientists fear the H5N1 virus could change into a form that can spread easily between people with each other, and thus potentially causing millions of deaths.

Sequences from Shezhen case were promptly reelased. No sequences yet on Guizhou case.

Same denial cited for Shenzhen:

The victim developed a fever on December 21 and was sent to hospital on December 25 with severe pneumonia. On Saturday he was confirmed to have H5N1.

The center said earlier that Chen regularly visited the wetland at Waterlands Resort for morning exercise.

About 120 people who had close contact with him have not developed any abnormal symptoms, health authorities said.

The Guangdong Department of Agriculture announced on Saturday that no epidemic of bird flu among poultry has been reported in the province.

Hong Kong infectious diseases specialist Lo Wing-lok criticized the center's report as "confusing" and "nonsense."

Lo said: "They cannot say that the virus is similar to that found in wild birds and say Chen may have contracted the virus from wild birds.

"There is no evidence in the whole world that suggests people contract H5N1 through wild birds. It is always through poultry.

"Does that mean the virus simply fell from the sky?"
http://www.thestandard.com.hk/news_prin ... 18460&sid=

 Mr. Xu owned a car rental company, which is interesting since the previous H5N1 human case in Shenzhen was also in the transportation business. He was probably well known and a visible person in the community.

It also appears he received the antibody treatment but died anyway.

machine translation -

Guizhou bird flu killed a 71 contact no abnormal
Posted 2012年01月23日16:33 China News

　　BEIJING, January 23 Xinhua Guiyang (Chao Zhao Gang) reporter from Guizhou Province Health Department Emergency Response Office was informed that, January 22, Guiyang City, Guizhou Province, a man treat bird flu patients died, 71 were close contacts are is not unusual, closing at 14:00 on the 23rd, 12 close contacts have been observed to lift the remaining 59 people in the medical observation.

　　Reporters from Guizhou Province Health Department Emergency Response Office learned that patients Liao Xu, male, 39, is a car rental company owner Guiyang,

January 6 after the onset of the Fourth People's Hospital of Guiyang stay, 19 into the Guiyang Medical College Affiliated Hospital, Guizhou Province, by the CDC after a preliminary judge for suspected bird flu. Guizhou Province Center for Disease Control to 21 virus samples sent to China CDC for review by the Ministry of Health confirmed bird flu. On the same day, Guizhou Provincial Health Office for the Coordination Ministry of Health, three experts, to carry the avian virus serum to Guiyang inductance for treatment of patients, at 12:35 on the 22nd, sicker patients, blood pressure, sudden ventricular fibrillation, died.

　　According to the Guizhou Provincial Health Department Emergency Office director Chen Zhongguo, currently the world who has not yet appeared avian influenza virus infection of human cases, so 71 were close contacts with the patient in isolation, living a normal life, only for medical observation. Currently no one fever and respiratory symptoms, 12 of whom had been lifted observation, and the remaining 59 people still continue to observe them. At present, the source of virus infection in patients is still under investigation.

more..

Zhttp://news.sina.com.cn/c/2012-01-23/163323840187.shtml

It appears:

January 6 - admitted into Fourth People's Hospital of Guiyang
January 19 - transferred to Guiyang Medical College Affiliated Hospital
January 21 - blood sample sent to China CDC for analysis
January 21 - H5N1 confirmed by China CDC
January 21 - antibody serum treatment begun
January 22 - death

Source: flutrackers.com

Recombinomics Commentary 16:30
January 19, 2012

" Because of his condition continued to decline, eventually the patient died on January 16, 2012 at around 2:00 pm.

Bird flu actually detected on her 5-year-old woman with the initials U.S. in Tanjung Priok, North Jakarta, Jakarta Province. This is confirmed by the Ministry of Health Directorate General of Disease Control and Environmental Health. New cases of H5N1 have also been confirmed by the Center for Basic Biomedical and Health Technology, Health Research Agency".

The above translation describes another fatal case (5F) in Tanjung Priok in North Jakarta who was the sister of a WHO confirmed case (23M who died January 7) who raised pigeons.  The 9 day gap in dates of death raises concerns that the cluster was due to human to human transmission. 

This Indonesian cluster follows a cluster in Bali, which involved a mother and her son and daughter.  Those sequences which had multiple receptor binding domain changes (D187N, A188G, R193M) were released almost immediately, and release of sequences from this cluster would be useful.

These receptor binding domain chnages continues to increase concerns that the multiple chnages in circulation will recombine to produce combinations similar to those censored at Nature and Science which produced efficient transmission in a ferret model.

Recombinomics Commentary 23:45
January 18, 2012

"It is for the first time that it has been found in the country, Mishra said. “We have compared it to the strains from Vietnam, Indonesia and other places in Asia and found similarities with the Vietnam strain,” added Mishra.

The NIV had received samples that included four crows from among those that had died in several areas of Jharkhand, including Jamshedpur, Bokaro and Hazaribagh. The process of characterisation of the virus is underway and it is a different strain of the avian influenza virus, NIV scientists said.

The strain belongs to Clade 2.3.2.1 while the H5N1 strain that was reported in the country in 2006 belonged to Clade 2.2."

The above comments confirm that clade 2.3.2.1 has migrated into south Asia, as expected.  In the past, clade 2.3.2.1 was largely confined to southern China and southeast Asia.  Hong Kong surveillance would identify the sub-clade in dead wild birds identified each year, generally between December and February.  However, in the spring of 2008 there was a major expansion of this sub-clade to wild birds in northern Japan as well as poultry in South Korea and poultry and wild birds in southeastern Russia.  These confirmed cases suggested that the Fujian clade 2.3.2 would be competing with Qinghai clade 2.2 due to infections in wild birds that share large flyways that overlap in Mongolia and Russia.

In 2008 one culler was infected and H5 PCR confirmed.  However, virus was not isolated and the human case was denied.  The denial included comments that human cases had involved the Fujian sub-clade 2.3.4 and not 2.3.2 even though the internal genes of the 2.3.2 were 2.3.4.  Fatal human cases involving 2.3.2 were subsequently confirmed in China and Hong Kong.  These cases were of concern because two receptor binding domain changes V223I and M230I were fixed in clade 2.3.2.  Many of the recent wild bird sequences had an additional receptor binding domain change S227R, and the recent fatal case in Shenzhen had the three changes above as well as Q196K raising concerns that many of the receptor binding domain changes use to create a more transmissible H5N1 in ferrets were recombining in wild birds and evolving in more transmissible H5N1 without the aid of scientists or terrorists.

It is likely that the recent H5N1 outbreaks in northeastern India as well as Bangladesh also involved clade 2.3.2.1 containing two or more of the above changes, increasing the likelihood of human infections.  Recently released sequences from 2011 isolates from Japan and South Korea share polymorphisms with clade 2.2.1 isolates in Egypt, including sub-clade 2.2.1 G, (see list here and here) which has PB2 E627K as well as sequences from seasonal and pandemic H1N1 (H1N1pdm09).  Moreover, these sequences include identities with H3N2v sequences in United States cases.

Full sequences from the H5N1 in India and Bangladesh would be useful, in addition to full sequences from human cases in Egypt.

Similarly, release of the receptor binding domain changes described in the censored papers at nature and Science is overdue.  The withholding of this information by Nature and Science continues to be hazardous to the world’s health.

Recombinomics Commentary 17:20
January 17, 2012

"the patient resides District, Dar ash next to the hospital, and the sister was younger, and at the age of 22 years may She died a week ago affected infected with the same symptoms, and remains one of his relatives suffer from the same symptoms at home."

The above translation describes a suspect H5N1 cluster in Fayoum, Egypt.  The index case (22F) has died with bird flu symptoms.  Here brother (30M) is hospitalized, and any family member has symptoms.

This clusters follows a number of recent confirmed fatal cases in Egypt.  The past three confirmed adult cases have died in December (42M Menofia Dec 22; 29M Dakahlia Dec 19; F Dakahlia Dec 3) and the November case was in critical condition and on a ventilator (31F Dakahlia Nov 16).  The most recent child was the daughter of the Dakahlia case who died on Dec 3).

The high frequency of severe and fatal adult cases (all four of the most recent confirmed cases) is in marked contrast to cases in late 2009 /, early 2010, where almost all were young children who recovered, lowering the case fatality rate in Egypt to less than 10%.  All of the earlier cases were clade G, which had a 3 base pair deletion (133del) and gave bioinformatic profiles similar to seasonal H1N1.

At that time a vaccine resistant H5N1 was identified in poultry, and no human cases have been reported.  However, the last human H5N1 sequence from Egypt was from March of 2010, raising concerns that the severe and fatal adult cases reflect a host range expansion of the vaccine resistant sub-clade F to humans.

These concerns were increased by recently released sequences from 2010 poultry in Egypt, which were PB1 and PB2 recombinants which had acquired seasonal H1N1 and pandemic H1N1 gene sequences, as well as wild bird sequences which matched recent H3N2v, H1N2v, and H1N1v cases in the United States

Concerns have been increased further by a lack of transparency by NAMRU-3 regarding release of sequences.  Three years ago NAMRU-3 promptly released sequences from the Gharbia cluster (largest confirmed cluster to date in Egypt), as well as fatal cases in early 2007 and milder cases in the spring of 2007.  NAMRU-3 was then designated a WHO regional center, and release of sequences has slowed significantly.  The lat series of sequences were in 2010, and included sequences from cases confirmed a year earlier. 

However, the latest sequences are now almost 2 years old moving Egypt from the most transparent to the least transparent for human H5N1 sequences.  Indonesia recently released full sequences for thye Bali cluster prior to official confirmation, and the same was done for a December fatal case in Shenzhen, China.  In addition, sequences from 2011 fatal cases in Cambodia have been released.

In contrast, the sequences from Egypt have been withheld, even though the case fatality rate has increased dramatically, and the issues associated with the similarities between H5N1 clade G cases with seasonal H1N1 as well as the clade F vaccine resistance remains, while the recent internal gene sequences (especially PB1 and PB2) demand an immediate release of full sequences by NAMRU-3 and/or the US CDC.

Recombinomics Commentary 23:30
January 13, 2012 St Jude has released full sequences (at Genbank) from four H5N1 avian isolates from Egypt.  The PB1 and/or PB2 sequences from three of the isolates (A/chicken/Egypt/Q1182/2010, A/chicken/Egypt/Q1185/2010, A/chicken/Egypt/Q1011/2010) have extensive regions of identity with seasonal H1N1, seasonal H3N2, or H1N1pdm09, raising serious concerns regarding sequences in internal genes from human H5N1 cases.

NAMRU-3 has not released any H5N1 sequences from any human case since March, 2010. 

Full sequences on human H5N1 should be generated and released as soon as possible. 

The recombination with human sequences seen in the avian isolates strongly suggests serious recombination in human H5N1 cases.

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.

January 4, 2012 — Taking no chances, the US Centers for Disease Control and Prevention (CDC) is laying the groundwork for a possible vaccine against a novel strain of a swine influenza virus that has surfaced in 5 states and sickened 12 individuals, mostly children, since July 2011, an agency official told Medscape Medical News Tuesday.

The strain, designated A(H3N2)v, is a variant of the A(H3N2) virus that circulates among humans on a seasonal basis. What makes it a variant is a gene from the pandemic 2009 influenza A(H1N1) virus that codes for matrix proteins found in the viral shell.

In Indiana, Pennsylvania, and Maine, the virus appeared to have spread from pigs to humans, according to the CDC. In Iowa and West Virginia, however, the evidence suggests limited human-to-human transmission. In general, the novel virus is no more severe than ordinary seasonal influenza, and all the people infected with it have recovered.
The CDC is encouraging public health agencies and clinicians to collect more nasopharyngeal swabs from patients presenting influenza-like illness for testing to determine whether the novel virus may be spreading on a sustained basis.
CDC spokesperson Thomas Skinner told Medscape Medical News that the agency already has prepared a "seed virus" obtained from A(H3N2)v specimens that drug manufacturers can use to develop a vaccine if needed. Preparing a seed virus involves genetically manipulating specimens to incorporate preferred features.
Because the new virus is different enough from the seasonal viruses now in circulation, the seasonal influenza vaccine for 2011-2012 "is not expected to provide significant protection" against the newcomer, according to a Morbidity and Mortality Weekly Report that the CDC published on December 23. The trivalent seasonal vaccine is formulated to protect against the 2009 pandemic virus, the regular A(H3N2) virus, and an influenza B strain.
CDC Could Be Preparing for 2012-2013 Influenza Season
So far, the evidence does not suggest that the A(H3N2)v strain is spreading freely through communities, which would create the need for a vaccine. The bug could fizzle out, according to Christine Layton, PhD, MPH, a public health researcher and influenza pandemic expert at RTI International in Research Triangle Park, North Carolina.
"There have been past instances where a novel virus comes up and then goes back down," Dr. Layton told Medscape Medical News. "There may be something about the virus that [prevents] sustained human-to-human transmission."
If the A(H3N2)v virus ever takes off, she said, drug manufacturers would have a tough time turning out a corresponding monovalent vaccine "at the drop of a hat." Influenza vaccines are still mass-produced, for the most part, by being grown in chicken eggs. Together with testing and licensing a vaccine, this process easily can last 3 to 4 months.
A more likely scenario, said Dr. Layton, would be incorporating an A(H3N2)v strain in the trivalent seasonal vaccine for 2012-2013, assuming the novel virus becomes that much of a threat. Each February or so, an advisory panel of the US Food and Drug Administration (FDA) recommends 3 strains of influenza that should make up the seasonal vaccine for the coming fall on the basis of what it expects to see circulating then. The CDC then develops the seed viruses for these 3 strains, which the FDA distributes to vaccine makers. 

http://www.medscape.com/viewarticle/756348

Recombinomics Commentary 16:30
January 4, 2012

" In order to investigate the escape process and to enable predictions of escape, we serially passaged influenza A H5N1 virus in vitro 100 times under immune pressure. The generated escape viruses were characterized phenotypically and in detail by full genome deep sequencing. Mutations already found in natural isolates were detected, evidencing the in vivo relevance of the in vitro induced amino acid substitutions".
 
The above comments are from an upcoming publication, “Highly Pathogenic Avian Influenza Subtype H5N1 escaping neutralization: more than HA variation” which describe the identification of escape mutants which are present as a minor species in the original sample.  P198S was identified in a swan clade 2.2 (Qinghai strain) isolate from Germany, A/cygnus cygnus/Germany/R65/2006, using this approach, and it was also in a clade 2.2 swan isolate from Russia, A/Cygnus olor/Caspian Sea/2006, confirming it was in circulation in clade 2.2 in Europe in 2006.

P198S was in the recently released sequence from the fatal case in Shenzhen, China, A/Guangdong-Shenzhen/1/2011, which had a large number of HA changes, including the adjacent change Q196K, which is in clade 2.2 isolates in Egypt, Germany, and Kuwait (see list here).

The Shenzhen sequence is clade 2.3.2.1 (Fujian strain) also has another receptor binding domain change, S227R, but was generated via novel coding that was distinct from S227R in clade 2.3.2.1 in Hokkaido and Fukushima.  The coding found in the Shenzhen sequence is found in H5 sequences from wild birds.

H5N1 is frequently found in wild birds in Hong Kong at this time of year, due to migration patterns.  In 2008  clade 2.3.2 was found Japan, South Korea, and Primorsky (southeastern Russia) in poultry and wild birds, which create expansion concerns.  Clade 2.3.2 was subsequently identified in Mongolia, followed by Romania, matching the wild bird path that brought clade 2.2 to Europe, the Middle east, and Africa.

The movement of clade 2.3 into the clade 2.2 flyway created an environment for co-infections and recombination, leading to the acquisition of clade 2.2 polymorphisms in poultry and wild birds in Europe, the Middle East, and Africa.

These interactions lead to rapid evolution as seen in the large number of HA changes in the fatal case in Shenzhen, China.

Recombinomics Commentary 21:20
January 1, 2012 CDC experts found that the patients infected with the virus is 2.3.2.1 sublines highly pathogenic avian influenza virus to humans is highly pathogenic…..

the results show that virus is adamantane class of drugs are more sensitive but resistance to Tamiflu, the role of drugs still under study
 
The above translation indicates the H5N1 from the fatal case In Shenzhen, China is clade 2.3.2.1, which is common in wild birds.  Between December and February, Hong Kong typically finds clade 2.3.2.1 in wild birds.  A clade 2.3.2.1 case was identified in Hubei last year, and WHO has selected that isolate, A/Hubei/1/2010 as a pandemic vaccine target.  Last November an H5N1 case was also identified in Hong Kong, A/Hong Kong/6841/2010).  Both isolates are in the phylogenetic tree in figure 3 in the WHO vaccine update.  As seen in the top 100 matches for the Hubei isolate (here) or the Hong Kong isolate (here), wild bird isolate are closely related, although the Hong Kong isolate is closer to sequences from Laos.

Both of the human isolates from 2010 had receptor binding domain changes V223I, D225G, M230I, which are common in wild bird sequences in eastern Asia, and were also in the Gharbya cluster in Egypt in 2006.

The 2010 cases in China were wild type at positions 274 (275) and 294 in NA and therefore susceptible to Tamiflu (oseltamivir).

Although the translation suggests the latest case is wild type at HA positions 226 and 228, but changes at positions 223, 225, and 230 raise concerns that more efficient transmission can be achieved by changes at additional positions. 

Release of the sequences from the Shenzhen cases, as well as those that led to airborne transmission in ferrets would be useful.

A man in southern China died of bird flu on Saturday, a week after being admitted to hospital, although he apparently had not been in contact with poultry. It has been the country’s first deadly case in more than a year, state media reported.

AP - A Chinese bus driver who tested positive for the H5N1 bird flu virus died Saturday in a city bordering Hong Kong, health officials said, in the country’s first reported case of the disease in humans in 18 months.

The man surnamed Chen died in the wealthy southern city of Shenzhen, provincial health officials said. Shenzhen is separated by a small river from Hong Kong, where thousands of birds have been slaughtered after two were confirmed to have the virus last week.

During the month prior to his fever, Chen, 39, apparently had no direct contact with poultry and did not travel out of Shenzhen, a metropolis of 10 million people.

H5N1 rarely infects humans and usually only those who come into close contact with diseased poultry. But among those infected, nearly 60 percent die, and scientists are closely watching the virus for any signs it is becoming more easily transmissible from human to human.

Chen developed a fever on Dec. 21 and was hospitalized on Dec. 25, city and provincial authorities said in a statement. Health Ministry experts confirmed on Saturday that he was infected with H5N1, the provincial health department said.

The Guangdong health department also said 120 people who had close contact with Chen have not developed any abnormal symptoms.

The Ministry of Health has informed the World Health Organization about the case, local authorities said.

WHO says globally there have been 336 human deaths from 573 confirmed bird flu cases since 2003. Of these, 40 cases were in China, 26 of which were fatal.

Chen’s death comes a week after two dead birds tested positive for the virus in Hong Kong.

More than 19,000 birds at a Hong Kong market were slaughtered and imports and sales of live poultry were banned for three weeks after a chicken carcass tested positive for H5N1. Lab tests later confirmed that an Oriental magpie robin found dead on Dec. 17 was also infected.

China’s last reported human case of H5N1 was in June 2010. A pregnant 22-year-old woman from central Hubei province died after being exposed to sick and dead poultry.

http://www.france24.com/en/20111231-bird-flu-kills-china-H5N1-health-poultry

Recombinomics Commentary 22:45
December 30, 2011  A CHP spokesman said the patient was a 39-year-old man living in Shenzhen. He developed symptoms on December 21 and was admitted to a hospital on December 25 because of severe pneumonia. He is now in critical condition. The man had no travel history or contact with poultry before the onset of symptoms.

The above comments describe a confirmed H5N1 case in critical condition in Shenzhen, which is in Guangdong province and adjacent to Hong Kong and Fujian Province.  The absence of poultry contact heightens concerns on human transmission which can be most effective addressed by the sequences of the H5N1.

Sequence data has been of note lately because of recent experiments which achieved airborne transmission through the introduction of five changes in two genes as well as selection via passage in ferrets.  Publication of this critical information is long overdue.

The timing of this controversy with the above case and location is of note.  The first cases of H5N1 in humans were in Hong Kong in 1997, and one of the key pieces of information centered on the role of PB2 E627K, which has been researched by one of the labs that generated airborne H5N1, which almost certainly involves PB2 E627K as one of the changes.

Hong Kong was also the center of two additional outbreaks.  One began in Guangdong province in late 2002 and then spread internationally from the Metropole Hotel in Hong Kong by an infected physician who had treated Guangdong cases and came to Hong Kong for a wedding.  He infected those on the 9th floor when he vomited outside his room (911) and guest and visitors to the ninth floor the spread the mystery virus to Hong Kong, Singapore, Hanoi, and Toronto.  An international team of investigators identified the SARS coronovirus as the etiological agent and published sequences at their websites, which led to the rapid development of diagnostic test to monitor the spread.

In early 2003 there was a smaller by instructive cluster of H5N1 in a Hong Kong fanily who travel to Fujian province.  The daughter died in China, while the father and sone returned to Hong Kong where H5N1 was isolated from each.  The father also died but the son survived and both sets of sequences were identical and had the HA receptor binding domain change S227N, which is aother likely change leading to enhanced transmission.  Other adjacent changes are already circulating in clade 2.3.2 in the area.  These changes, V223I and M230I are also of concern, as are changes at positions 226 and 228, all of which are well known and are additional candidate, as are changes flanking positiin190.  These changes are also well known and studied by the labs who achieved the efficient transmission in ferrets.

On a somewhat related note, the movie Contagion also involved an infectious agent that jumped species in Guangdong province and the isolates were stored in liquid nitrogen adjacent to SARS CoV and H1N1pdm09, which are well know pathogens which have been sequenced thousands of times.

Thus, the release of the sequences from the above patient, as well as key changes associated with airborne H5N1 should be released or published immediately.