Recombinomics Commentary 19:00
March 5, 2012

Detection of three new human infections with the deadly H5NI strain of bird flu in a week has set alarm bells ringing as scientists have found evidence of the virus in the live-bird market in crowded Dhaka.

The above comments describe three confirmed H5N1 cases in wet market workers in Dhaka, Bangladesh.  The first case has been WHO confirmed and has recovered, but the three 2012 cases has doubled the number of H5N1 confirmed cases in Bangladesh.  This significant up tick is almost certainly due to clade 2.3.2.1 which has now expanded its geographic spread and was confirmed in crows in India earlier this season.  New sub-clade migrate into India and Bangladesh each season, which are closely related to each other.

The first human clade 2.3.2 was described in media reports in the spring of 2008 when a culler (soldier) developed symptoms and was H5 PCR confirmed.  However, South Korea denied the culler was infected with clade 2.3.2 because prior human infections in China were clade 2.3.4.  Moreover, South Korea used the failure to isolate the H5 virus as an excuse for not filing a report.  However, the sequence had V223I and M230I, which were in the Gharbya cluster and fatal clade 2.3.2.1 cases were subsequently reported in China, including the recent case from Shenzhen who had no reported poultry contact (but had wild bird exposure).

The appearance of clade 2.3.2 in south Asia raised concerns of additional human cases, and the three confirmed cases in Bangladesh are likely confirmation of the realization of such concerns.

World Press and Vietnam again caused a stir and organizational control disease prevention (CDC) confirmed three more American young people in Iowa mutate flu virus infects a new A (H3N2) derived from pig . As from January 8.2011, the CDC has recorded 12 cases scattered in five northeastern states of the United States. The samples after the tests to detect genetic decoding in the variable new strains of genetic reassortment between H3N2 is circulating in pigs in the United States with M genes of H1N1 pandemic strain in 2009, is S-OTR called H3N2 (swine-origin H3N2 triple reassortant).

Why does the medical world feared H3N2 S-OTR?

Influenza A viruses, including subtypes (subtypes) based on a combination of two proteins, hemagglutinin (H) and Neuraminidase (N). . There are 16 H antigens and nine antigen N.  In nature, each H and N antigens are often distributed in a certain species of animals.  Currently only three H antigen subtypes (H1, H2, H3) and two subtypes N antigens (N1, N2) is regularly circulated in humans. The other subtypes found mostly in animals. Wild birds are natural hosts of the virus.

The most important characteristics of the virus is likely to change frequently antigenic structure through the phenomenon of mutation and genetic recombination.  Meanwhile, strains "new" would escape recognition by the immune system, easily cause major outbreaks and high mortality risk to the community without resistance. History has proven each pandemics were caused by a new virus appears to mutate.

Back at the North American case, which flu strains are circulating in pigs rarely causes human disease.  Since 2005, only 35 cases reported in the United States, but production levels have increased in 2011.  When different strains co-infection in a host body, the genetic material can exchange and create a new strain variables.

At the conference Fourth European Influenza held in Malta (May 9.2011), a scientific discovery has been global shocked Dr. Ron Fouchier and colleagues at Erasmus Medical Center Rotterdam (Netherlands) announced . In the laboratory, they have successfully tested the mutant strains caused by H5N1 virus introduced directly into the respiratory tract to cause infection experiment repeated on civet.  With only five through ten mutant virus experimental phase, they have gained new H5N1 strain can spread easily through the airways from civet to others. Biologically, this means the ability to spread from person - people with respiratory!

A similar result was also published later by Ruben O. Donis and colleagues from the CDC Atlanta, USA mutagenic when carrying sialic acid receptors on antigen H and N antigens on the H5N1 virus.

H5N1 threat there

H5N1 bird flu virus circulating in migratory birds, infected poultry, but no symptoms (especially in species of aquatic birds).  Due to different antigenic structure should only pathogenic H5N1 virus for some people with close contact (slaughter poultry diseases) and not be able to spread from person to person. Diseases caused by H5N1 in humans begins with the outbreak in 1997 in Hong Kong. Up to date 08/02/2012, the world's total was 584 cases with 345 deaths (59%). In Vietnam, since the first cases detected in the hospital as soon 11/01/2004 tropical disease, now has a total of 121 cases (the third highest in the world after Indonesia and Egypt), 61 deaths ( 50%).  After nearly two years absence from the H5N1 Swine Flu, the health ministry announced two deaths from H5N1 in January 1.2012 in Kien Giang and Soc Trang.  Ministry of Agriculture and Rural Development is published on the H5N1 poultry in the provinces of Thanh Hoa, Ha Nam, Hai Duong, Quang Tri, Soc Trang and Kien Giang.

As translated in poultry, the risk of H5N1 infection when exposed and not protected very high and the cases will continue to happen ...

Worst case scenario and how to deal

When infected people continue to have variable influenza virus strains circulating in human capital (such as avian influenza H5N1, H3N2 swine flu ...), viral conditions regular exercise over how to penetrate the human body, the ability to turn adaptive genetic change will have many opportunities to occur and to a certain time, a new varieties with the ability to spread from person - who will appear (this time in natural conditions, repeat the process "of make " was successful in the lab)!

Imagine a new pandemic scenario for the appearance of a human influenza virus can mutate damage the strength of the H5N1 (mortality 50%) combined with the ability to spread from person - person via the respiratory tract of H1N1 each 2009 pandemic (worldwide spread in just three months)!

Before a flu pandemic threat is happening in the future, the medical community should be prepared for questions: when would appear? Any complications? Responding to like? ...

First of all, have solved the bird flu. Spread to humans by blocking the implementation of biosecurity measures in animal husbandry, food processing line clean. Implementation of effective vaccination for poultry and humans. Monitoring, detection and early treatment of cases to be dispersed in the community.

Hopefully, mankind continues to win the race for survival with competing microbial world, which took place millions of years and continues increasingly fierce.

Red Dot: Positive Human Case. Red Only: Suspected Human Case

West Java

2/21/12

Name: 19 yo (F)

From: Tangerang

Adm: 2/12

Onset: 2/8 - fever

Notes: Health Team surveyed home & neighborhood, can't determine source.

Confirmed: Positive

DOD: 2/13

Bali

2/21/12

Name: WM (12) (M)

From: Badung

Adm: 2/21 Denpasar Sanglah Hospital

Recon: 2/16 Surya Husada

Notes: Family took him home after death.

DOD: 2/21

Confirmed: Positive based on PCR

Central Kalimantan

Name: M (49)

From: Desa Muroi, Kapuas Tengah, Palangkaraya, Kabupeten Kapuas

Onset: 2/17; day after eating dead poultry

Adm: 2/18 Rumah Sakit Umum Daerah (RSUD) Doris Sylvanus Palangkaraya

Recon: 2/18 Muhammadiyah hospital

Notes: Had 12 chickens, 3 died. Then they cut more chickens to make family dishes. 2/21: chickens tested positive for New Castle. Negative for H5N1. Patient improving health.

South Sulawesi

Gowa

5 Members of Single Family

2 Adults, 3 children

From: Gowa Reg., Pallangga Dist., panaikang Village

Adm: 2/21 Dr. Wahidin Sudirohusodo Hosp. Makassar

Recon: 2/16 Hospital Sheikh Yusuf

Name: Surti (32)

Name: Suci Maharani (3 months)

Name: M. Agung (6)

Name: Nephew of Surti, Suci Ramadani(7 months)

2/19: 5th person was treated at Sheikh Yusuf, w/sym's high fever & flu.

Notes: Friend: Daeng Kenang (40) said hundreds of chickens died suddenly in his home.

I also have another 5 Suspected in East Java from February 17th:

East Java

2/17/12

5 Suspected People

Name: Ponimah (50) Husband

Name: Karju (52) Wife

From: Petamanan Village, District of South Bugul, Makati City

[Jalan Wahidin Selatan, RT 2, RT3 / RW III Kelurahan Petamanan, Dist.: Bugul Kidul, City Pasuruan.]

Onset: 2/12 (according to quote from brother below)

Adm: Ponimah Saiful Anwar Hospital (RSSA) Malang 2/18

Reconciled: Ponimah to Soedarsono Hospital on 2/18.

Name: Jacob, brother Ponimah ""My brother suffered from fever, coughs and colds. This, since 5 days ago. Moreover, before he was suffering from a sore throat,"

Notes: "There were five people suspected of being infected and we took blood samples to be tested," said Kartika, officers Flu Pasuruan Bird Animal Husbandry Department, Friday (02/17/2012).

"4 other suspects monitored from their homes" (2/18).

Thanks to Commonground's: http://pandemicinformationnews.blogspot.com/2012/02/commongrounds-indonesia-case-list-map.html

Recombinomics Commentary 16:00
February 21, 2012

Denpasar Bird flu virus still a threat, a boy with the initials WM (12) died of the H5N1 virus is. WM is the origin of Badung, Bali
"Based on the PCR, he's positive, "he said. case of death of this child is the fifth death from bird flu virus that occurred in Bali.

The above translation describes lab confirmation of another fatal H5N1 case (12M) in Bali.  Earlier, sequences from a Bali cluster of three were released.  The sequence from the mother was a recombined sequence derived from the sequences from her children.  The sequences had multiple receptor binding domain changes, which may have been present in the Indonesian clade 2.1 H5N1 used in the Ron Fouchier transmission experiments, which began with three changes and acquired two additional changes.  The five changes in two genes represented previously reported polymorphisms, which were used in ferret transmission experiments.  The death of all 40 exposed ferrets has raised concerns that a lethal transmitting H5N1 could emerge in the near term.

The recent clusters in Indonesia and Egypt have raised concerns that the withholding of the details in the Fouchier and Kawaoka experiments continues to be hazardous to the world’s health.

Absence of Poultry Contact for H5N1 Bali Indonesia Fatality
Recombinomics Commentary 18:00
February 21, 2012

Of the interrogation Sanglah party, according to Ken, could not be ascertained whether the WM had contact with poultry. "The family is still denying that the victims had contact with poultry. We are therefore of bird flu team is digging deeper than where the victim of a virus," explains Ken. But from the VCR in Sanglah examination showed that the victim was positive for influenza WM birds. Due to the bad condition when taken to the hospital Sanglah, WM can only last for five hours and finally died at 03.00 pm, Tuesday (21/2) yesterday.

The above translation, describing the recent fatal case near Bali, Indonesia notes the lack of a reported bird contact.  This case follows a cluster of three with disease onset dates which supported human to human transmission, which was also supported by the recombinant H5N1 sequence from the mother (39M) of the first two cases (5F, 10M).
These lab confirmed cases increase concerns that the H5N1 in Indonesia is evolving toward efficient transmission.  Clade 2.1 was the source for the H5N1 used by Ron Fouchier.  After 10 passages in ferrets the virus had 5 chnages in 2 genes and 4 of the 5 changes have been found in published sequences.

This alarming development has been overshadowed by concerns of bioterrorism and an NSABB recommendation to withhold details.  This recommendation has been rejected by scientisis meeting in Geneva last week, who were given the details on the tranmssion studies.

The relative ease in the creation of a transmitting H5N1 or an H5 reassortant highlights the lack of preparation for a transmitting H5N1.
The current vaccine program has largely stockpiled older isolates, and although newer targets have been selected. Pandemic preparedness lags, and the only clade 2.1 vaccine target is the 2005 isolate from the initial Tangerang cluster.

Recombinomics Commentary 14:30
Bruce Alberts says that the research shows that it is very easy for lethal bird flu to develop and it should act as a "real wake up call to the world".

He added: "This is likely to happen at some point in the wild because these viruses are mutating very actively in the wild."

Kudos to Science for cutting to the chase on the H5N1 transmission issues.  The two papers are game changes with regard to the understanding of the risk of a natural and evolving H5N1.  Prior “experts” had claimed that H5N1 would never transmit in humans because it is an “avian” virus, and had not jumped to humans, in spite of many opportunities since the outbreaks in Hong Kong in 1997, and rapid expansion in Asia in 2004, and throughout Europe, the Middle East, and Africa in 2006.

However, two different groups using two distinct sub-clades had achieved efficient transmission in a ferret model involving a small number of natural changes, highlighting the near term potential for efficient transmission.

Although the NSABB has the right to request limitations, they have not made a scientifically valid argument.  Instead, public comments have revealed a serious lack of understand of the scientific literature and the abilities of others to reproduce and improve the transmission based on papers published prior to the acceptance of the papers at Nature and Science.

Both groups have published extensively in the past, and media reports describe the overall findings.  The Science paper uses a clade 2.1 isolate from Indonesia with three changes, which was passed in ferrets to select two additional changes.  All five changes in the two genes have been described previously, although all five have not been reported in the same isolate, although published sequences include four of the five is a single isolate.  The Nature paper uses a different sub-clade (2.3.4.2) from Vietnam, but only the H5 is used.  It is on an H1N1 background, and the sub-clade and construct have been described previously.

Thus, any serious program targeting an H5 that transmits efficiently in mammals would already have sufficient information to reproduce and improve the censored results, since there is little doubt that transmission is not limited to the two examples described in the Nature and Science papers.

H5N1 however, remains a poor choice as a bioweapon because it can’t be controlled once it has been released, although interest in a transmitting H5N1 will likely increase due to the attention and concerns expressed by the NSABB.

The concerns have also detracted from the game changing result, as noted in the above quote, which is why the papers should be immediately published in full, so a true discussion of the significance of these results can begin, which includes enhanced surveillance and counter measures such as an extensive H5N1 vaccination campaign to protect against a naturally evolving H5N1.

Suspect H5N1 Cluster In East Java Indonesia
Recombinomics Commentary 14:30
February 17, 2012

Outbreaks of bird flu again attacked chickens in residential Wahidin Road South, RT 2, RT3 / RW III Petamanan Village, District of South Bugul, Makati City.

At least 80 chickens died suddenly from a week ago. In addition to attacking the chicken, the bird flu outbreak is believed to have infected a number of residents in these settlements. A total of five people are known to suffer from the disease with symptoms of fever, bone pain, and shortness of breath.

As experienced Ponimah (52). Since three days ago, he felt the symptoms of shortness of breath, cough, runny nose, watery eyes, and bone pain.

The above translation describes a suspect H5N1 cluster near Pasuruan, south of Surabaya in East Java, Indonesia.  Addition reports indicate the poultry associated with the suspect cases has tested positive for H5N1.
Symptoms in 5 residents in area raise concerns of increased transmission. 

The report being delayed at Science from the Ron Fouchier lab in the Netherlands used a clade 2.1 sequence from Indonesia to generate a transmissible H5N1 in a ferret model, which maintained its lethality.  After ten passes in ferrets, the transmitting H5N1 had 5 changes in two genes.

Release of five changes in this manuscript is long overdue. 

Friday, 02/17/2012 22:32

The avian influenza virus was genetically engineered into the new virus is highly virulent, contagious and resistant to vaccines. While Vietnam does not have A/H5N1 flu vaccine on humans

While bird flu continues to spread to many provinces, the deadly virus have been many changes detrimental to the prevention and treatment measures in poultry. More worrying when the death rate from influenza A/H5N1 in humans is 100% of cases are detected.

Resistant virus vaccine

On 17-2, Hoang Van Nam, Director of Animal Health authority (Ministry of Agriculture - Rural Development), said from the beginning of this year has 11 local detection of avian influenza including Thanh Hoa, Quang Tri, Soc Trang, Ha Nam, Hai Duong, Thai Nguyen, Kien Giang, Bac Giang, Ha Tinh and Hai Phong and Quang Nam.

Not yet quarantined poultry still be comfortable buying and selling, slaughtering in Hanoi

There were nearly 20,000 birds, mostly ducks to be destroyed. The bird flu is complicated, spread in all 3 regions. If loose slaughtering operations management, transportation and trade of poultry, the risk of widespread outbreaks is huge.

Risk of spreading bird flu, today (18-2) National Steering Committee for prevention of avian influenza will have an emergency meeting to discuss measures to cope. Meanwhile, Mr. Diep Kinh Tan on 17-2, Deputy Minister of Agriculture - Rural Development, said it had written to the Prime Minister requests the State budget of 13 billion contract to buy 50 million doses of H5N1 vaccine Re-vaccination strains fifth round of 1-2012 for timely enclosure, stamping out.

According to Tan, 2012 is expected to need 327 million doses of vaccine given to poultry, but due to bird flu virus in the northern provinces with the change, the vaccine strain H5N1 Re-5 protection levels households is not high. Meanwhile, in the southern provinces, not bird flu virus is modified to use H5N1 vaccines imported from China, so immediate permission to import 50 million doses.

The risk to humans is very large

According to experts, the bird flu virus may be genetically caused the surveillance becomes more difficult. Department of Animal Health representative said before, there are 3 branches Vietnam H5N1 virus has been detected. A branch in the south, north branch and the branch 2.3.4 7 capable of highly infectious.

However, recently in the northern provinces, discovered a new bird flu virus branch, symbol 2.3.2 branch. More worryingly, had discovered the virus 2.3.2 branch into 2 groups. With a group of old virus, vaccine against bird flu meets only 75%, while the new virus, vaccines are currently using does not work. Therefore, the risk of spreading the virus in poultry and humans is very large. What is more dangerous than professional bodies continue on raising waterfowl flocks, sold in many places but no signs or symptoms but still carry the virus H5N1.

Dr. Nguyen Hong Ha, deputy director of Tropical Diseases Hospital Central, concerned with the weather hot and humid climate are favorable for growing influenza virus. Moreover, with the normal seasonal flu viruses such as influenza B, H1N1, H3N1, H5N1 ... the risk is present, the virus strains combine or mutate to create new influenza virus virulent more dangerous is huge. Currently, flu vaccines are being used in Vietnam is just common flu as influenza A (H3N1, H3N2, H1N1) and there is no vaccine against A/H5N1 flu in humans.
100% mortality rate

According to Dr. Tran Thanh Duong, deputy director of the Department of Preventive Health (MOH), A/H5N1 flu spread from birds, waterfowl infected with influenza A/H5N1 virus to humans is strongly virulent virus, the mortality rate very high. At this point, the rate of death from influenza A/H5N1 in humans is 100% of cases were detected. Two cases were patients who died despite antiviral treatment.

http://nld.com.vn/20120217102740382p0c1002/virus-h5n1-bien-doi-vacxin-bat-luc.htm

H5NI virus or commonly known as bird flu has mutated over the nature of change or development time, this is further strengthened by reports of a number of areas.  Even so, not yet ascertained the impact of the change.
  It is feared the virus could be more dangerous than ever before.  Further research is needed to ensure the fatality rate of the new virus.
  Head of Animal Husbandry and Health of Central Java Province, Semarang District Whitono reveals, some poultry that died of bird flu now has features that are not as usual, ie no black or bluish spots on the comb or body part that is not hairy.
 Meanwhile, Head of Animal Health Animal Husbandry and Animal Health in Central Java, Eko Sutarti revealed, though not sure about the new virus, characteristics of birds that died of bird flu part shifted.
  Usually the birds that died of bird flu are marked with blue or black spots on the comb or body parts that are not covered in fur.  Now the poultry that died suddenly without these spots were found positive for bird flu.
  Of Brebes, Central Java, reportedly, the body's defense system against virus attacks poultry in the region changed when compared with previous years. This is evident from the clinical symptoms found in cases of chicken deaths in the region last week.
 Head of Animal Health and Veterinary Public Health Veterinary Services Bradford, Jhoni Murahman say, around 2003, when he first outbreak of bird flu virus in Bradford, clinical symptoms of bird deaths at that time happened very quickly and in large quantities.  Physical signs in birds that died of bird flu is also very clear, that the body was black, very much saliva, swollen heads and blue crest on the head.

  However, at present, clinical symptoms are not very visible. Poultry deaths tend to be in unison, but one by one.  Body of dead birds as well just turn blue with not a lot of saliva and the head is not swollen.

25 Tail Poultry Sudden Death 
  London continues to increase alertness, following the discovery of 25 birds that died suddenly in some districts during 2012. . However, after checking through the rapid test, avian bird flu was declared negative.
   Bandung, Maria Dewi in Soreang, Sunday (12/02/2012) says, from the beginning of January 2012 to Sunday, it received reports of about 25 birds died suddenly.
  "There have been reports from some districts, namely Cimaung, Rancaekek, Nagreg and Soreang who reported any poultry that died suddenly. But after we checked, it turns out negative bird flu," he explained.
  It is said, if there are reports of dead birds suddenly, direct action by the parties Disnakan spraying disinfectant around the discovery of the dead birds.
 "In particular for this disinfectant we have not been scheduled. But there are reports of each case, we immediately move and do a rapid test. With the rapid test, in 20 minutes can be found out whether the results are positive or negative. In addition, we also do spraying disinfectant," he said .
  Although not yet found a positive poultry bird flu this year, but continue to increase vigilance Disnakan. Moreover, the previous year was found positive poultry bird flu in eight villages. Only when compared to the year 2010, that number has decreased.
  Maria further said, to prevent bird flu cases in the District does not happen again.  Bandung, it will continue to take preventive vaccination of pets, especially birds and the provision of disinfectants.
http://translate.google.com/translate?hl=en&ie=UTF8&prev=_t&rurl=translate.google.com&sl=id&tl=en&twu=1&u=http://esq-news.com/2012/berita/02/14/waspada-virus-flu-burung-mutasi.html

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.

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 16:30
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.