Cluster

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

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

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

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

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

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

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

 From the Post:

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

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

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

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

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

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

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

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

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

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

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

Recombinomics Commentary 18:45
March 7, 2012

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

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

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

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

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

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

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

Recombinomics Commentary 16:30
March 7, 2012

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

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

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

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

Recombinomics Commentary 17:30
March 6, 2012

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

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

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

More information on testing would be useful.

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.

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. 

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

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 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.