RECOMBINOMICS

[dothedd]

Commentary
Nigeria Index Matches Ebola Sub-Clade In Guinea & Sierra Leone
Recombinomics Commentary 17:15
August 11, 2014

The lab in LUTH under Prof Omilabu received samples on July 22nd and the next day provided results of a pan-FILOVIRUS family diagnosis, that is evidence of presence of a virus belonging to the family of Ebola virus (including Marburg, Ebola-Zaire, Ebola-Sudan Bundibugyo virus, Reston virus, and Taï Forest virus).

Samples were also sent to Prof. Happi’s lab at the Redeemer’s University (RUN), late on July 23. The Happi team worked and tested and confirmed that the virus was the specific Ebola-Zaire type virus early on July 25, 2014. All these happened before confirmation came in from Dakar. I understand the RUN lab will commence sequencing studies pretty soon. My congratulations to our colleagues in LUTH and RUN for a great job.

The lab at LUTH (Lagos University Teaching Hospital) has released a 239 BP sequence, LIB/NIG 01072014, from the Nigeria index case, Patrick Sawyer. The RNA polymerase (L gene) sequence is identical to all 2014 Ebola virus (EBOV) at Genbank (3 from March collections in Guinea and 95 June collections from Sierra Leone), in contrast to all earlier Ebola sequences..

The index case arrived in Lagos on July 20 from Monrovia, Liberia (via planes from Monrovia to Accra, Ghana and Accra to Lagos, with a stop in Lome, Togo) but denied contact with Ebola patients (even though he had close contact with his sister, Princess Nyuennyue, who was Ebola lab confirmed and died in early July). He was tested for Malaria and HIV, but was not tested for Ebola until July 22 (and the sample was used to PCR confirm a filovirus, as noted above, as well as generate the 239 BP sequence).

The delay in confirmation of Ebola has led to the infection of a large number of contacts, who are largely health care workers (HCW) and media reports indicate additional patients at First Consultant Hospital Obalande (including a pregnant patient), where the index case was treated.

Thus, the recently released sequence represents Ebola circulating in Nigeria and Liberia, which matches sequences from Sierra Leone and Guinea, confirming that the outbreaks in all four countries are linked to a single introduction, which appears to be a 2 year old boy in Guinea and late 2013 (he died December 6, 2013).

The most recent WHO update of August 8 on cases through August 6, cites 13 cases in Nigeria (which included 7 probable cases, which were those lab confirmed in Nigeria). However, none are listed as confirmed because of delays in transporting a sample to the WHO regional center in Senegal. As noted above, the index case has been confirmed by at least two labs in Nigeria by PCR, as well as sequence confirmation that the Ebola is the novel Zaire sub-clade described previously.

[dothedd]

Liberia Spike In Ebola Cases & Deaths Raises Concerns
Recombinomics Commentary 18:15
August 15, 2014

The latest Ebola WHO update (reporting case between August 12-13) shows a dramatic jump in new cases in deaths (116 and 58, respectively). These numbers dwarf those from Liberia in the same period (27 and 14, respectively) and suggest that yesterday’s WHO announcement that “Staff at the outbreak sites see evidence that the numbers of reported cases and deaths vastly underestimate the magnitude of the outbreak” may have a significant relationship to the deteriorating situation in Liberia in general and Monrovia in particular.

Recent reports indicate that efforts to limit movement from heavily impacted rural regions in Liberia have not prevented flow of cases into Monrovia. Moreover, recent reports have cited bodies in the streets of two of Monrovia’s slums, West Point and Clara Town, which may represent a fraction of infected and/or fatal cases in these densely populated regions.

WHO has noted barriers to control, which included infections and deaths of a large number of health care workers and closing of hospitals, resulting in bed shortages and treatment limitations.

These recent developments raise concerns of a literal “death spiral”.

[dothedd]

Commentary
Liberia Ebola Case Fatality Rate At 84%
Recombinomics Commentary
September 23, 07:00

So far, nearly 2,500 suspected cases have been reported in what the WHO says is the worst known outbreak of the disease.
However, the WHO's website says the survival rate for people with Ebola in this outbreak has been 47%, which is a substantial improvement over the disease's survival rate, historically.

There is a 47% survival rate with this outbreak.

Approximately 300 infected patients have survived Ebola treatment in Liberia since the outbreak here from March to September, Assistant Health Minister for Preventive Services, Tolbert Nyenswah, has announced.

The above comment (in dark red) is from an August 26 media report noting that 47% of Ebola cases in the current outbreak survive, in spite of the fact it is the worst known outbreak of Ebola. The same figure is currently cited on the Canadian Infection Prevention and Control site on Ebola (in light red).

This survival number is from the WHO Ebola website, which had listed three bold headings characterizing Ebola in the current outbreak. The first headline, “H2H” reflected the fact that virtually all cases were due to human to human transmission. The second headline “2 to 21 days” reflect the wide range of reported incubation times. The third headline “47% survive” was followed by a claim that the survival rate was higher than most prior outbreaks (this headline was removed last week).

A link to the prior outbreaks list (by WHO) was provided, and the corresponding 53% CFR (case fatality rate) was lower than any of the 8 largest Zaire strain outbreaks (more than 50 cases each), which had CFR’s ranging from 60%-90%. Moreover, the 53% matched the two Sudan outbreaks (Sudan in 1976 and Uganda in 2000), and only the two Bundibugy outbreaks (51% for DR Congo in 2012 and 25% for Uganda in 2007) had a lower CFR.
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However, the CFRs for the prior outbreaks were based on outcomes (all reported cases had either died or had recovered), while the 47% survival used by WHO in the current outbreak represented cases who had recovered, as well as those hospitalized, those housed at holding centers, and those who had been sent home because all beds at hospitals and holding centers were full. Thus, the 47% survival rate would only be accurate if all of the live patients who had not been discharged subsequently recovered, for which there was no scientific or historic basis.

As seen above (in blue), less than 300 cases in Liberia have survived, based on the September 18 comment by the Assistant Health Minister in Liberia. The September 17 report from the Liberia Ministry of Health cited 3022 cases and 1578 deaths in Liberia (which were also cited in the latest WHO Road Map). Thus, although Liberia reported 1444 live Ebola cases as of September 17, less than 300 represented recovered cases. The more than 1144 active live cases included approximately 300 in hospitals receiving treatment and less than 100 in holding centers. Thus, more than 744 cases had been identified as Ebola cases, but had been sent home because all available beds were full.

The Ebola CFR based on outcomes (1578 deaths and 300 recovered cases) is 84% (1578/1878), which is among the highest reported Ebola CFRs (only the 90% for the 2003 outbreak and the 88% for the 1976 outbreaks in the DR Congo were higher).

The low frequency of recovered cases among the live Ebola cases in Liberia highlights the problems associated with the lack of beds. Most of the identified cases are in the community, posing a threat of further spread. Moreover, WHO has estimated that the true number of Ebola cases is 2-4 times the reported numbers, suggesting 1000-3000 additional cases were not being treated and were further spreading the virus in Liberia, in addition to such cases in Sierra Leone and possibly Guinea.

The absence of reports on recovered Ebola cases in WHO reports is glaring. Although they have removed the claim of a 47% survival rate from their website, the number of recovered cases should be include in updates, including road map reports.

[dothedd]

Media Myth On Ebola Convalescent Antibodies
Recombinomics Commentary
Octoerber 14, 2014 21:00

The patient’s 103-degree fever might warrant “a little more investigation,” Adalja said. A chart showed he did not arrive with a fever but left with one.

By Duncan’s second ER visit, the care was “impeccable,” the doctor said. Dallas physicians immediately signaled concern about Ebola and “spared no measure to try to keep him alive.”

After it became clear that Duncan was suffering from Ebola, another option would have been to give him a transfusion from an Ebola survivor in the hopes that antibodies in the blood could help him fight the disease.  But Duncan did not receive a transfusion because the blood types did not match, the hospital said.

Dr. Kent Brantly, the first American flown back to the U.S. for treatment of Ebola, confirmed that account, saying he spoke with a doctor caring for Duncan and was willing to donate blood. But their blood types were incompatible, he said Friday in an interview with Abilene Christian University’s alumni magazine.

The above account on the failure to treat Duncan with convalescent plasma is alarming. The WHO has cited the use of convalescent blood or plasma to treat patients and posted a detailed 2014 report on its Ebola website entitled “Use of Convalescent Whole Blood or Plasma Collected from Patients Recovered from Ebola Virus Disease for Transfusion, as an Empirical Treatment during Outbreaks”. The report addresses ABO mismatches:
When it is not possible to test the patient’s ABO group or if ABO matched CWB/CP is not available then:
and recommends using whole blood if the donor is type O (universal donor) and to use plasma if the donor is type AB, A, or B (since plasma has had the blood cells removed).

Indeed, Kent Brantly was treated with convalescent antibodies from a recovered case (14M) in Liberia and he was the donor for three cases treated in Nebraska (Rick Sacra and Ashoka Mukpo) was well as the health care worker in Texas, Nina Pham. Media reports characterize one or more of these treatments as a plasma infusion, suggesting an ABO mismatch (which would preclude a whole blood transfusion, but not a plasma transfusion).

This failure to treat with convalescent antibody follows a failure to admit when Eric Duncan made his initial visit to Texas Health Presbyterian Hospital on the evening of September 25. Although he had a low grade fever when he arrived, when he left 4 hours later he had a fever of 103 F (and was sent home with antibiotics and Tylenol).

Texas Health Presbyterian Hospital has been cited for the past three years for having a high frequency of ER discharges which returned within 30 days, and Eric Duncan fit that pattern when he returned on September 28 after a contact called 911, which led to ambulance transport. By then Eric Duncan also had diarrhea and vomiting but his blood was not sent out for Ebola testing until the next day, Monday, September 29 (and media reports indicated his nephew call the CDC on Monday due to a lack of progress).

Although Eric Duncan was lab confirmed on Tuesday, September 30 by the CDC in Atlanta and the Texas State Lab in Austin, he was not treated with convalescent antibodies even though Kent Brantly was willing to donate. Moreover, experimental drug treatment was delayed until Duncan suffered organ failure and was placed on life support (involving intubation and dialysis).

The withheld antibodies and late treatment may have contributed to the patient’s deterioration, which was likely associated with an increased viral load, which may have played a role in the infection of Nina Pham.

More detail on the apparent failure to follow WHO advise on the use of convalescent plasma on recipients which do not match the donor and why the treatment of Eric Ducan was characterized as “impeccable” would be useful .

[dothedd]

More Farms Infected in Canada - H5N8 Increasingly Likely (12/04/14 02:00)

More Farms Quarantined In Canada - H5N8 Increasingly Likely (12/03/14 23:45)

Fujian H5N8 In Fraser Valley Canada Increasingly Likely (12/03/14 22:00)

Egypt Confirms 7 H5N1 Cases In 3 Days (12/03/14 20:00)

Did H5N8 Fly Into Fraser Valley Canada? (12/03/14 14:00)

Three H5N8 Introductions in Europe & Netherlands = Wild Birds (12/02/14 07:15)

H5N8 Wild Birds Are Not Victims (11/29/14 19:45)

H5 Confirmed In Dead Ducks In Kerala India - H5N8 Likely (11/25/14 03:30)

Japan H5N8 Matches Germany Netherlands England (11/23/14 11:30)

H5N8 Spread In Europe Mimics H5N1 In 2005 (11/21/14 17:30)

Wild Bird H5N8 Transmission from Asia to Europe (11/20/14 20:30)

Novel Enterovirus D68 Sub-Clade Linked To Flaccid Paralysis (11/10/14 22:00)

LINK FOR DETAILS ON THE ABOVE ARTICLES:
www.recombinomics.com/whats_new.html

[dothedd]

More Farms Quarantined In Canada - H5N8 Increasingly Likely
Recombinomics Commentary
December 3, 2014 23:45

@paulvieira: Canada food watchdog says in phone briefing 2 more poultry farms closed due to avian flu, adds it is "possible" other farms could be hit

@citytvnews: CFIA says 2 more farms in the Fraser Valley have been placed under quarantine in the Avian flu outbreak.

@helenbranswell: #CFIA says 2 more farms under quarantine in British Columbia after discovery of an H5 avian #flu virus. No results yet on pathogenticity.

The newly quarantined farms are located in Abbotsford and Chilliwack between two farms where avian flu was announced Tuesday. All the birds at both farms will be destroyed, and the farmers will be compensated.

[dothedd]

Commentary
More Farms Quarantined In Canada - H5N8 Increasingly Likely
Recombinomics Commentary
December 3, 2014 23:45

@paulvieira: Canada food watchdog says in phone briefing 2 more poultry farms closed due to avian flu, adds it is "possible" other farms could be hit

@citytvnews: CFIA says 2 more farms in the Fraser Valley have been placed under quarantine in the Avian flu outbreak.

@helenbranswell: #CFIA says 2 more farms under quarantine in British Columbia after discovery of an H5 avian #flu virus. No results yet on pathogenticity.

The newly quarantined farms are located in Abbotsford and Chilliwack between two farms where avian flu was announced Tuesday. All the birds at both farms will be destroyed, and the farmers will be compensated.

The above tweets and comments indicate more farm quarantines in Fraser Valley in British Columbia, Canada (see map). The spread and lethality of the H5 strongly suggests it is H5N8 (Fujian clade 2.3.4) which is currently circulating in Asia (primarily in wild birds in Japan) and Europe (Germany, Netherlands, and England).

Sequence data of H5N8 outbreaks supporting multiple introductions leaves little doubt that the spread in Asia and Europe are due to wild birds, and the outbreaks in multiple farms in Fraser Valley also implicate wild birds.

Canada has never reported HPAI H5, although the gosling deaths on Prince Edward Island were almost certainly due to the Qinghai strain (clade 2.2) of H5N1. However, that sub-clade is largely confirmed to Egypt at this time, and wild bird H5 is largely the Fujian strain (either clade 2.3.2 or 2.3.4).

The H5N8 is clade 2.3.4 and confirmation in Fraser Valley would represent the first report of that clade in poultry in the Americas.

Canada undoubtedly knows the sub-clade, which would be obvious from the sequence of the PCR insert.

A new testing facility is processing samples in Fraser Valley, and deaths were first reported over the weekend, so sequence data is known.

Release of these sequences would be useful.



Commentary
More Farms Infected In Canada - H5N8 Increasingly Likely
Recombinomics Commentary
December 4, 2014 02:00

The two farms continue to be under quarantine to control disease spread, and two additional farms in the Fraser Valley have been placed under quarantine today. These farms were determined to be at high risk since they received birds from one of the original farms. Birds on these new farms were also showing signs of illness.

The above comments from a Canadian Farm Inspection Agency (CFIA) indicate that the two additional quarantined farms are also H5 infected base on broiler chicken symptoms. This spread is expected because the H5 is clearly highly pathogenic and easily spread.

This is the first reported outbreak of HPAI H5 in Canada, raising concerns that the H5 is from wild birds carrying the Fujian H5N8 which is spreading in wild birds in Japan and wild birds and poultry in Europe (Germany, Netherlands, England). Although the sequences in Europe are most closely related to the wild bird sequences from Japan, the differences in the sequences in the three European countries indicate infections are due to three independent introductions, which is also true for the first three farms confirmed in the Netherlands.

In Frazer Valley, the first two farms reporting dead poultry also were not connected, suggesting infection by wild birds. Confirmation of Fujian H5N8 would represent this reported expansion of this strain to North America.

These infections may signify a more northern route for H5N8, which eluded detection in Russia / Mongolia and spread to northern Europe through western migration, and British Columbia via eastern migration.

Both of these locations raise concerns of further migration to the south, expanding H5N8 into the Middle East and Africa by the birds in Europe, and to regions in the southern United States by birds in British Columbia.

These serious possibilities may be the reason for the delay in the acknowledgement that the Fraser Valley outbreak is due to H5N8 that matches the sequences in Asia and Europe.

[dothedd]

H5N8 Wigeons In Netherlands = Independent Introductions 

Recombinomics Commentary  

December 4, 2014 17:15 

The Erasmus Medical Center (EMC) has released nearly complete H5 and N8 sequences (at GISAID) from two wigeon fecal samples (A/eurasian wigeon/Netherlands/emc-1/2014 and A/eurasian wigeon/Netherlands/emc-2/2014) collected on November 24, 2014 between Kamerik and Kockengen (see map). EMC is commended for the rapid release of these important sequences.

As noted by recent comments, the sequences are closely related to the November sequences in Europe (A/turkey/Germany-MV/R2472/2014, A/duck/England/36254/14, A/chicken/Netherlands/14015526/2014 and A/chicken/Netherlands/14015531/2014) and wild birds in Japan (A/duck/Chiba/26-372-48/2014 and A/duck/Chiba/26-372-61/2014). Although the wigeon sequences are closely related to the public sequences, they have unique markers indicating they are not linked to the above markers and represent an independent introduction.

Public sequences support independent introductions into each of the European countries, and at least 3 introductions into the Netherlands, firmly supporting wild bird sources.

Similarly, the H5N8 sequence data from Europe or wild birds in Japan suggests that the two outbreaks in Fraser Valley are also due to H5N8 from wild birds. Like the Netherlands outbreaks, the outbreaks were in unlinked farms and produce a high mortality in chickens and turkeys.

The delay in announcing the N8 in Canada or the sequence similarities with Fujian H5N8 also supports a serious spreading outbreak in Canda, which will have implications throughout the Americas.

[dothedd]

Is H5N2 In Fraser Valley Canada Fujian Clade 2.3.4? 

Recombinomics Commentary  

December 4, 2014 17:15 

A source to News1130 has confirmed the type of avian flu strain that is affecting four farms in the Fraser Valley.

It’s called H5N2

The above comments suggest that the H5 HPAI in Fraser Valley is H5N2. However, it remains unclear if the H5 is a North American strain, or is Fujian clade 2.3.4 which is circulating in Asia as multiple serotypes, including H5N1, H5N2, H5N5, H5N6, and H5N8.

H5N8 has attracted considerable attention because of the massive outbreak in South Korea in early 2014, as well as its presence in November outbreaks in Europe (Germany, Netherlands, and England) as well as Japan. These November confirmations include wild birds in German (teal), Netherlands (wigeon), and Japan (Tundra swan, ducks, white naped crane).

North American H5 has been widely reported in Canada, but these isolates were low path, in contrast to the high path in Fraser Valley. In 2004 H7N3 began as low path, but evolved into high path on farms which then devastated the poultry population. However, the change from low to high path takes time, but the OIE report on the 2014 H5 outbreak in Fraser Valley suggests that both outbreaks began at the end of November, with high mortality on December 1, suggesting the infections were due to high path H5 from wild birds.

The difference between Asian and North American H5 can be easily determined with the insert sequence generated in the PCR test.

Release of the sequences of the H5 insert or a larger segment would be useful.

[dothedd]

H5 Confirmed In Four Fraser Valley Canada Farms 

Recombinomics Commentary  

December 5, 2014 04:00 

Harpreet Kochhar, DVM, PhD, Canada's chief veterinary officer, said in a press briefing today that test results on turkeys at a farm in Abbotsford and on chickens at a farm in Chilliwack confirmed highly pathogenic H5N2. Two other farms, also in Abbotsford and Chilliwack, that received chickens from the first Chilliwack farm have birds that tested positive for H5

"We think that it's about a 3- to 5-day incubation period. And we also know that if it hits, the [poultry] producer isn't going to miss it."
the outbreak at the initially affected farm in Chilliwack was restricted to one of three barns. In the affected barn, all 700 of the 24-week-old chickens died from H5N2.

Pritchard said that at the Abbotsford turkey farm, the "vast majority" of 11,000 turkeys died from H5N2.

The above comments provide additional detail on the HPAI H5N2 outbreak in Fraser Valley in British Columbia (see map). The first two farms (Abbotsford turkeys and Chilliwack chickens were not linked but developed a highly pathogenic H5N2 in the same time frame strongly suggesting infection by wild birds. The OIE report suggested the outbreak began on November 30 and mortality was very high, as noted above and in media reports that noted significant numbers of deaths on December 1. This time frame suggests that the infectious agent (in the wild birds) already was highly pathogenic.

Canada has never reported an HPAI H5N2 outbreak. The three prior H5N2 outbreaks were low path and effectively managed through culling.

Both high and low path outbreaks are reportable for H5 and H7 because of reports of low path evolving into high path on infected farms. This type of evolution happened for H7N3 in 2004. Initial cases were low path, but over time a high path version emerged, which led to the culling of 17 million birds in Frazer Valley.

The absence of reports of an initial low path outbreak in Fraser Valley in 2014 raises concerns that high path H5N2 is circulating in wild birds.

Although high path H5N2 has never been reported in wild birds or poultry in Canada, such isolates have been reported in Asia, including isolates with a Fujian clade 2.3.4 H5. This H5 has been found in multiple serotypes (H5N1, H5N2, H5N5, H5N6, H5N8), raising concerns that the H5N2 in Fraser Valley is from the Asia lineage.

An Asian linage would be a significant concern, because wild birds have developed immunity to this H5, which has a lethality in poultry similar to the numbers described above. The Fujian H5N8 has captured a great deal of attention because of recent isolates in asymptomatic wild birds in Germany (teal), Netherlands (Eurasian wigeon) and Japan (Tundra swan, ducks, white naped crane), which are lethal in domestic turkeys, chickens, and ducks (see map).

The Asian lineage has never been reported in the America, so a Fujian H5N2 would represent a serious development.

The lineage can be easily determined through sequence analysis.

Release of the H5 PCR insert or large pieces of the H5N2 genome would be useful.

[dothedd]

H5N2 Spreads To Aldergrove In Fraser Valley Canada 

Recombinomics Commentary  

December 6, 2014 23:45 

News1130 @news1130radio

EXCLUSIVE: A fifth farm in the Valley tests positive for Avian Flu. Sources confirm it's a turkey farm on the Aldergrove-Abbotsford border.

The above tweet indicates the fifth farm with H5N2 in Fraser Valley is in Aldergrove (see map). A press conference today indicated the turkey farm was near Abottsford and had two barns with a capacity of 30,000 turkeys each. Each farm had three age groups of turkeys and H5 was confirmed in a group of 10,000 nine-week old turkeys, suggesting the two barns were at or near capacity. These 60,000 turkeys are in addition to the 80,000 birds which are being culled on the first four farms.

The owner of the latest farm noted that birds began dying on Thursday. Friday the matrix gene was PCR confirmed and H5 was confirmed today, indicating H5N2 will be confirmed in Winnepeg. The latest farm is west of Abottsford and more outbreaks are likely.

The possibility of wild or migratory birds was cited, which once again raises the question of lineage. Canada has never reported a high path H5 in wild birds or poultry. In contrast, high path H5 is common in Asia.

Although H5N8 has received attention because of its recent detection in wild birds in Japan, Germany and Netherlands as well as poultry outbreaks in Germany, Netherlands, and England (due to wild birds), Fujian clade 2.3.4 H5N2 has been reported in China in 2014, raising concerns of migration to North America.

Release of sequences from the H5N2 outbreak in Fraser Valley would be useful.

[dothedd]

Deafening Silence From Winnipeg On Fraser Valley H5N2 Lineage  

Recombinomics Commentary  

December 7, 2014 05:15 

The confirmation of H5 on a fifth farm in Fraser Valley. which is in Aldergrove, 13 miles from the nearest prior H5N2 farm (see map) raises additional concerns on the lineage of the H5N2. This issue has not been addressed by Canada's Winnipeg National Lab, even though they have now received samples from at least 4 farm sources and have determined that the serotype is H5N2.

Canada has never reported high path H5N2 in wild birds or poultry. Since the fifth farm, like the relationship between the first and second, had no linkage to any of the other farms, it is likely that the infections are due to wild birds carrying high path H5N2.

The comments at yesterday’s press conference also suggests that additional farms have symptomatic poultry, and it is likely that these new outbreaks will be announced today and/or Monday, and the new farms will also not be linked to prior farms. Additional unlinked farms would further suggest that the outbreaks in Fraser Valley are due to wild birds, which were also cited in today’s press conerence. Comments also noted the wild bird spread of H5N8 in Europe, which involves a Fujian clade 2.3.4, which is currently circulating in wild birds in Japan.

Although high path H5N2 has never been reported in wild birds in Canada, it has been reported in wild birds and poultry farms in China (see map for 2014 oubreaks), and the H5 has been the Fujian lineage, raising concerns that the H5N2 in Fraser Valley is this Asian strain.

Distinguishing Asian H5 from North American H5 is done by comparing sequences, which can be done in seconds, and by now Winnipeg undoubtedly has enough sequence data to make that determination, but they have been alarmingly silent.

If this H5N2 was a North America lineage, Winnipeg would have offered assurances that the lineage in Fraser Valley is similar to the low path that has been responsible for prior outbreaks in Canada.

The silence from Winnipeg is deafening, and raises serious concerns that the H5N2 in Fraser Valley is Asian in origin.

[dothedd]

H7N9 showing signs of increasing adaption to humans
Novel H7N9 Hong Kong Ex-Shenzhen - H7 Human Adaptations

Recombinomics Commentary
December 30, 2014 23:00

The sequences from the first confirmed H7N9 case (68F) in Hong Kong in the 2014/2015 season, A/Hong Kong/8194273/2014, raised concerns due to evidence of human adaptation in four recently acquired internal genes. [[ The "internal genes" are the genes other than the two surface genes, H and N ]] The PB2 sequence is most closely related to avian H9N2 sequences, except it has the human adaptation E627K. In addition, two other internal genes (PB1 and NP) are closely related to the human H9N2 case (86M) in late 2013, A/Hong Kong/308/2014, while the PA sequence is closely related to the human H10N8 sequence, A/Jiangxi-Donghu/346/2013 (73F, also from late 2013).

However, the H7 sequence also has evidence for human adaption. Two changes, T160A and Q226L, were present in the initial cases in early 2013. However, cases from late 2013 and early 2014 were found in geographic or familial clusters, especially those in Guangdong Province. Although sequences from initial cases were made public, subsequent sequences were withheld, and most sequence data was from cases exported to Hong Kong, as was the case for the first case in the 2014/2015 season.

The H7 sequence belongs to a sub-clade that includes the three most recent sequences from the prior season (A/Hong Kong/8122430/2014, 85F collected 4/13; A/Hong Kong/5731/2014, 82F collected 4/8; A/Hong Kong/5581/2014, 65M collected 4/3) as well as A/Hong Kong/4495/2014, 0.5F collected 3/1; and A/Malaysia/228/2014, 67F collected 2/11).

This subclade has three non-synonymous changes that are almost exclusively limited to human cases. E113K is present in the six human H7 sequences above, as well as A/Hangzhou/17-1/2014 and A/chicken/Jiangxi/SD001/2013). L177I is in the six above, plus 2 more human sequences (A/Taiwan/1/2014 and A/Taiwan/2/2014), while N276D is in the six above, plus A/Huizhou/01/2013, A/Guangdong/1/2013, A/shanghai/05/2013, and A/Shanghai/1/2013. The presence of all three of these polymorphisms in the six member subclade, as well as addition isolates which are almost exclusively human, raises concerns that these three H7 polymorphisms represent further human adaptation.

The first Hong Kong case in 2014/2015 was from Shenzhen, where the first case (35F) in Guangdong province was just reported. No poultry link was cited for either case, and both have symptomatic contacts, raising concerns that the number and size of clusters this season will be markedly
---------------------------
This will keep considerable pressure on to get a vaccine stockpile, even if the number of cases isn't very high. If the number of cases is also high this "season" then the pressure for a vaccine will be considerably higher than it was before.

Because 1) it spreads so easily AND 2) because the incubation period is much shorter AND 3) because it can be spread before symptoms are apparent AND 4) because the early symptoms are the same as some other very common conditions, H7N9 is far more of a pandemic threat than Ebola, even despite that there are current partially efective treatments for H7N9 and none for Ebola and the H7N9 mortality rate is lower than Ebola, H7N9 is more of a danger than Ebola, IMHO.

[dothedd]

65 Taiwan Farms With Suspect Fujian H5N8 and H5N2 (01/13/15 09:30)

Taiwan Fujian H5N8 and Novel H5N2 Signal Global Expansion (01/12/15 14:00)

Fujian H5N8 and Novel H5N2 Migrate To Taiwan (01/11/15 13:30)

Did Fujian H5N8 Migrate To Kano Nigeria? (01/10/15 14:00

California Location of Fujian H5N8 Gadwall Not In US OIE Report (01/09/15 18:00)

Fujian H5N8 In White Crane Rostock Germany Zoo (01/08/15 14:00)

Fujian H5N2 Spread To Richland Washington (01/07/15 10:30)

Fujian H5N2 Confirmed In Benton City Washington (01/06/15 23:45)

Fujian Fills Flyway - H5N8 Paciic (01/06/15 11:30)

Fujian H5N8 Migrates To Butte County California (01/05/15 23:00)

Fujian H5N8 US Spread Raises Surveillance Concerns (01/05/15 21:00

Fujian H5 Backyard Farm Near Benton Washington (01/03/15 03:15)

Fujian H5N8 Diversity Raises Surveillance Concerns (01/01/15 12:00)

Fujian H5N8 Diversity In Kagoshima Japan and North America (12/31/14 23:00)

Novel H7N9 Hong Kong Ex-Shenzhen - Human H7 Adaptations (12/30/1 23:00)

Novel H7N9 Hong Kong Ex-Shenzhen - Human H9N2 & H10N8 (12/30/14 12:00)

www.recombinomics.com/whats_new.html

[dothedd]

Fujian H5N2 Wild Bird Clonal Expansion In The United States
Recombinomics Commentary
February 21, 2015 11:30

The USDA has released three sets of Fujian clade 2.3.4.4 H5N2 sequences (A/chicken/Washington/61-9/2014, A/domestic duck/Washington/61-16/2014, A/turkey/Washington/61-22/2014) from December 30 collections on the index farm in Benton County, Washington are closely related to each other, as well as sequences from the index farm December 2 collection in Fraser Valley, British Columbia, Canada (A/turkey/BC/FAV10/2014) and a wild bird December 8 collection from Wiser Lake in Whatcom County, Washington (A/Northern_pintail/Washington/40964/2014).

These similarities signal clonal expansion of this constellation (with North American wild bird sequences in PB1, NP, and N2) by migratory birds.The sequence matches in Benton County in December 30, 2014 collections was followed by H5N2 confirmation in 6 hunter killed wild birds (3 Wood Ducks and 3 Northern Shovelers) in the Umatilla Wildlife Refuge, which is about 25 miles southwest of the Benton Country farms (see H5N2 map).

These January 3, 2015 collections in Morrow County likely match the Benton County sequences Similarly, the H5N2 in a mallard from the Fern Ridge Wildlife area near Eugene, Oregon in collected January 7 also likely matches the Washington sequences as well as the H5N2 in a Mallard in the same area in Lane County collected earlier, or the Northern Pintail collected later. In addition, H5N2 was also found in hunter killed wild birds (2 Mallards and 1 Pintail) in Columbia County collected January 5.

The sequence data supporting clonal expansion of H5N2 by wild birds in the United States is in addition to H5N8 sequence data showing clonal expansion of the parental Fujian serotype and the OIE report on H5N1 in Fraser Valley appears to match the H5N1 sequence in Whatcom County (A/American_green-winged_teal/Washington/195750/2014).

All three serotypes in North America have an H5 that is closely related to the crane in Kagoshima, Japan (A/crane/Kagoshima/KU1/2014), which is also found in the three serotypes in Taiwan (H5N2 A/Goose/Taiwan/0104/2015, H5N3 A/Goose/Taiwan/01042/2015, and H5N8 A/Goose/Taiwan/0103/2015).

The spread of Fujian clade 2.3.4.4 in wild birds in the United States may lead to a new wave of outbreaks as the migratory birds in the US begin to fly north to Canada in the upcoming weeks.




Fujian H5N8 Wild Bird Clonal Expansion In The United States
Recombinomics Commentary
February 23, 2015 16:00

The USDA has recently released a full set of Fujian clade 2.3.4.4 sequences from backyard poultry in Benton County, Washington (A/chicken/Washington/61-9/2014, A/domestic duck/Washington/61-16/2014, A/turkey/Washington/61-22/2014). The sequences matched each other, as well sequences from the index farm in Fraser Valley, British Columbia (A/turkey/BC/FAV10/2014), and the first confirmed Fujian H5N2 case in the United States (A/Northern_pintail/Washington/40964/2014), confirming the H5N2 clonal expansion in the United States.

The USDA also released full sets of H5N8 sequences from a backyard farm in Douglas County, Oregon (A/guinea fowl/Oregon/41613-1/2014 and A/chicken/Oregon/41613-2/2014), which matched each other as well as the first confirmed H5N8 case (A/gyrfalcon/Washington/41088-6/2014), confirming that H5N8 is also expanding clonally in the United States. This expansion is also supported by the above H5N2 sequences, which have a 5/3 ratio between H5N8 sequences and North American wild birds, which contribute PB1, NP and N2 to the H5N2 constellation, or a 4/4 ratio between H5N8 and H5N1 sequences (A/American green-winged teal/Washington/195750/2014) where wild bird origins are found for PB1, PA, N1, NS.

Thus, the clonally expanding H5N8 is the parental sequence for the other two serotypes identified in North America, H5N1 and H5N2. However, the North American H5N8 is most closely related to the crane sequence from Japan, (A/crane/Kagoshima/KU1/2014). That sequence is also closely related to the sequences in Taiwan, where the number of H5 confirmed farms has increased to 841. In Taiwan the H5N8 has acquired two gene segments from wild birds in Asia (PB1 and PA), while H5N2 has 1 4/4 ratio, while H5N3 has only two gene segments from H5N8, N5 and MP (H5N2 A/Goose/Taiwan/0104/2015, H5N3 A/Goose/Taiwan/01042/2015, and H5N8 A/Goose/Taiwan/0103/2015).

Thus, in Taiwan and North America, and H5N8 parental clade has produced two additional serotypes via ressortment with local wild birds. In North America the three serotypes has clonally expanded as indicated by sequence data for H5N8 and H5N2, or an OIE description of H5N1 in Fraser Valley. The H5N8 has been widely reported in the United States (see H5N8 map), while H5N2 has been limited to Fraser valley and three northwestern states (Washington, Oregon, and Idaho – see H5N2 map), and H5N1 has been found in Washington and Fraser Valley – see H5N1 map).

However, the frequencies for each serotype may have expanded over the winter and impacts may be significantly higher in the spring as wild birds migrate back to Canada and Alaska.

[dothedd]

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