RECOMBINOMICS

[dothedd]

MERS and SARS Similarities Increase
Recombinomics Commentary 18:00
November 28, 2013

The critical remaining question about this virus is the route by which humans are infected. A large portion of the human cases that did not have an apparent human source of their infection, also did not have direct camel exposure. Specifically, the remaining questions include 1) the specific behaviors and exposures that bring humans into contact with sources of the virus, 2) whether camels are a part of the chain of transmission to humans or whether they are coincidentally infected, and 3) whether other animals may also play a role in transmission or act as a reservoir.

The above comments from the November 22 WHO update once again invites comparisons between MERS and SARS. MERS is looking increasingly like a slowly emerging SARS outbreak based on epidemiological and sequence data. The media reports citing the announcement of sequence data this week from a case (43M) and camel in Jeddah, Saudi Arabia, as well as PCR and sequence confirmation in 3 asymptomatic camels linked to two confirmed cases in Qatar raises the strong possibilities that more similarities between MERS and SARS will emerge soon.

The first confirmed cases of SARS were in late 2002 (samples confirmed in 2003). These early cases were in Guangdong province (population almost 100 million). However, super spreader events (SSE) were reported in the city of Guangzhou (population almost 10 million) in early 2003, with reported cases increasing to 50 per day peaking in early February. A nephrologist, who had treated patients Guangzhou, traveled to Hong Kong for a wedding and checked into room 911 in the Metropole Hotel (Hotel M) on February 21. An SEE occurred on the 9th floor leading to the infection of multiple guests, who subsequently traveled to Vietnam, Singapore, Canada and the United States, which was followed by SSEs in Vietnam, Singapore, Canada, and Hong Kong (linked to former guests of hotel M).

The number of reported cases increased dramatically in March and April, but quickly declined in May. Intermediate hosts were identified in live markets in Shenzhen, and sequences were closely related to the initial cases in Guangdong Province. However, sequences from cases in Guangzhou and Hotel M had a 29 BP deletion, which was present in the vast majority of subsequent sequences. Moreover, this deletion (as well as larger deletions found in human clusters), where not detected in animal sequences.

There was extensive culling and such animals (most notably masked palm civets, aka civet cats) were banned. However, after the lifting of the ban in the fall of 2003, SARS-CoV was again detected in live markets. This later version also lacked the deletions found in the prior cases, but was easily distinguished from the sequences from isolates in late 2002 and early 2003. Moreover, human cases were subsequently found in late 2003, which matched these more evolved sequences. The sequences in the human isolates led to massive culling in Hong Kong and subsequent human cases were not detected. However, testing of animals in farms supplying the live markets failed to detect SARS-CoV, so the source of these later sequences remains unclear.

A subsequent search for a natural host for SARS-CoV focused on bats, and although SARS-like CoVs were identified, these sequences were decades or centuries away from the human / live market sequences. The search noted that many different coronavirus were hosted by bats, including beta coronavirus that were similar to OC43 (a human cold virus serving as the prototype for 2a), SARS-CoV, representing 2b, as well as additional sequences representing 2c and 2d.

The universal probes used to identify these various bat coronavirus were also used to identify MERS-CoV in the first two confirmed cases, which were most closely related to the bat beta2c sequences. The initial bat beta2c sequences were from Guangdong and were centuries away from the MERS-CoV sequences. However, testing of bat sequences from Europe and Africa identified more closely related beta 2c sequences which were more closely related to MERS-CoV, but these sequences were still decades or centuries away from the human sequences.

However, a short (203 BP) sequence from a bat in Bisha exactly match one of the sequences from the first confirmed MERS case (who lived in Bisha but was diagnosed and died in Jeddah). Thus, this sequence was more closely related to the human EMC sequence than any other human MERS sequence. However, the species harboring this bat sequence had a very limited geographic reach in Saudi Arabia (and was more widespread in India, Sudan and Egypt).

Testing in camels suggested MERS-CoV may be widespread in the Middle East and northeastern Africa. Beta 2c antibodies where detected at high frequencies and titers in racing camels in Oman. Similar results were also reported for camels imported to Egypt from Sudan for slaughter.

The strongest data hover comes from recent PCR results (and associated sequence data) for a symptomatic camel in Jeddah (owned by a confirmed critical MERS case, 43M) and three asymptomatic camels in Qatar (owner or linked to two recovered cases, 61M and 23M).
The latest camel data has much in common with live animals in Guangdong Province or Hong Kong linked to SARS cases in 2002 and 2003. As was seen for recent MERS cases (which are significantly more commonly reported inside and outside the Middle East in 2013 than 2012), most cases are not linked to animal sources and super spreader events have produce nosocomial outbreaks in Jordan and Saudi Arabia, the animal links may spark outbreaks.

However, elimination of an animal source for MERS may be significantly more difficult than for SARS.

[dothedd]

Detail On MERS Asymptomatic Camels Cluster In Qatar
Recombinomics Commentary 16:30
November 29, 2013

Epidemiological comments The health authority in Qatar notified the presence of a confirmed human MERS-CoV (Middle-East Respiratory Syndrome Coronavirus) case. A joint team from both health and veterinary authorities was sent to the patient farm to investigate the health status of animals and the contact person. A farm worker proved to be positive for MERS-CoV and samples were collected from the 14 existing camels in addition to one sheep, some pigeons and chickens and some environmental samples (water, soil, animal food and grass) and all were sent to the Netherlands for testing. All animals were kept under observation and quarantine and all were apparently healthy.

The above comments are from the OIE report on the three PCR confirmed camels in Shahanya, Rayyan in Qatar (see map). This information supplements the October 18, 2013 WHO report on the index case (61M) who was hospitalized on October 11, three days prior to the OIE designated start of the above outbreak. The WHO report noted that the initial tests on the farm animals were negative.

Media reports have cited collection of nasal swabs for the PCR and sequence confirmations, which conclusively indicated the three camels were infected with MERS-CoV. Since the index case and a farm worker (23M) survived, it is likely that extensive sequence data will be forthcoming for one or both of the cases as well as one or more camel. It is likely that these sequences will be virtually identical (>99.9%).

However, media reports citing positive antibody results may signal earlier infections, especially if samples collected on October 10 are positive.

The 14 camels offer an opportunity to further characterize MERS-CoV infections in animals, since the PCR data signaled active infections at the time of sample collection. Detail on antibody and RNA levels in sequential collections may offer insight into the direction of the interspecies transmission, as well as potential intra-species transmission in camels, as well as similarities with the 2003 SARS outbreak..

[dothedd]

ProMED Confusion On Qatar MERS Camel Tests
Recombinomics Commentary 19:15
November 29, 2013

[As rightly indicated in the official report of the Qatar health authority (item 1 above), "the presence of the MERS-CoV [antibodies?] is newly recognized among animals, and currently there is neither a clear scientific case definition nor enough information as to the role animals may play in transmitting and spreading the disease." This is also the current view of the OIE, namely: "Serology tests for MERS-CoV have not yet been validated in animals and may not be reliable. If these tests, which may not be sufficiently specific, are used in animals, there is a risk that 'false positive' results will occur because it may not be possible to differentiate antibodies to MERS-CoV from antibodies to other coronaviruses, commonly found in animals. That is why tests in animals should focus on isolating and identifying the virus itself" (see ProMED-mail 20131119.2064239).

As apparent from item 2 above, the discovery of the 3 camel "cases" in Qatar is based upon serological tests; more specifically, "3 different tests" applied by the Dutch investigators. Further details of the techniques applied and on their respective validation status will be helpful.

On 12 Nov 2013, Saudi Arabia's Ministry of Health notified the 1st time that a camel related to a human case had tested positive for MERS-CoV by PCR (see ProMED-mail 20131112.2051424). Reportedly, further testing was ongoing to sequence the patient's and the camel's viruses and compare genetic similarity levels to conclude causality. The results of these tests are not yet available. - Mod.AS\

The above comments in a ProMED RFI on the detection of MERS-CoV in the 3 camels in Qatar represents a gross misrepresentation of the facts presented yesterday by Qatar and a large number of media reports.

The detection of MERS-CoV was based on a MERS PCR test, which is one of the three tests cited in the quoted media report. Other reports made it clear that both antibody tests and sequencing were done in addition to the PCR testing. The assumption that the MERS-CoV was solely based on antibody testing is curious. The limitations of such testing are well known and the official announcement, as well as associated media reports, made it clear that the camel testing went well beyond antibody assays.

The media reports were followed by reports by WHO, OIE, and ECDC that confirm the significance of the PCR result. There was no doubt that the camels were infected with MERS-CoV and there was interspecies transmission between the two MERS confirmed cases and the camels, but the direction of the transmission was still under investigation.

The MERS PCR test, in contrast to the universal PCR conoravirus, is designed to limit a positive result to MERS-CoV because confirmation requires positive results for two or more regions, which target MERS-CoV. Thus, the positive result in Qatar camels was similar to the positive result for the Jeddah camel, which also supported interspecies transmission since the owner of that camel was also MERS confirmed.

The universal PCR test, in contrast, requires follow-up sequence data to determine the type and sub-clade of coronavirus. This test was used to find SARS-related sequences in bats in China. It was then used to find additional coronavirus sequences, including beta2c sub-clades in Europe and Africa, which were more closely related to MERS sequences. However, only the BIsha bat sequence is close enough to MERS to resent a candidate for recent jumps to humans.

However, the recent MERS PCR data in camels signals MERS CoV which will be very closely related to the Jeddah and Qatar human sequences in the owners of these camels.

The Qatar camel data should offer additional insight into MERS in camels, since the Jedda and Qatar camels were tested during active infection, and sequences from their owners should also be generated and released soon.

[dothedd]

Jordan UAE ex-KSA MERS Cluster Raises Concerns


Recombinomics Commentary 20:30
November 30, 2013

The director of health care at the Ministry of Health, Dr. Bassam Hijjawi that the tests conducted by the Public Health Authority in Abu Dhabi proved wounding three Jordanians residing there Corona virus, they are the same family (father, mother and child, 9 years old).
He said in a statement to «opinion» that the wife was hit in multiples of being pregnant and went into a coma as a result of the corona virus that causes respiratory syndrome,

Hijjawi said that contacts revealed that the patients went through Saudi Arabia before traveling to the UAE expected to be infected during their stay in Saudi Arabia

The above comments provide detail for a MERS confirmed cluster in United Arab Emirates (UAE) involving a Jordanian family who traveled through the Kingdom of Saudi Arabia (KSA) prior to hospitalization in Abu Dhabi (see map). The two adults were announced by UAE state media and were cited in many reports (in Arabia and English), but the reports on the third family member (9M), the status of the wife (in a coma), and travel history (through KSA) are limited two a few local media reports.

The travel through KSA increases concerns that the number of KSA cases is significantly higher than those reported. This concern began to rise at the end of Ramadan. Although KSA failed to any MERS cases in pilgrims performing Umrah in KSA during Ramadan, a traveler (59M) returned to Qatar and was MERS confirmed (as were subsequent contacts in Qatar). Although the traveler was not performing Umrah, he was infected in Medina, where additional local cases were reported by KSA, but these cases were also not cited as pilgrims.

Similarly KSA failed to report MERS in any pilgrims attending the Hajj, but two pilgrims returned to Madrid, Spain and were MERS confirmed. The index case (61F) developed symptoms shortly after arriving in Mecca from Medina. She subsequently sought medical attention in Mecca and was pneumonia confirmed by X-ray, but she refused treatment in KSA and flew to Madrid from Jeddah. A travel companion was also confirmed. But details on the second case were limited, although the recovery of both cases was reported.

The reports of these two pilgrims was followed by a report of MERS in a Jeddah resident (43M), which was followed by reports of MERS confirmation in a symptomatic camel owned by the Jeddah case. This cluster, like the cluster in Medina following Ramadan raised concerns that these cases were directly or indirectly linked to traveling pilgrims.
These events linked to western KSA were followed by reports in countries adjacent to eastern KSA. Oman reported its first confirmed case, who had contact with relatives who had just returned from the Hajj. Another Omani sought treatment in UAE, where he was MERS confirmed. Kuwait then reported its first two confirmed cases and at least one had returned from KSA.

The travel through KSA by the Jordanian family hospitalized in UAE raises concerns that the export of MERS from KSA is increasing following the Hajj.

[dothedd]

Qatari Camel MERS Sequences Re-Confirmed

Recombinomics Commentary 16:15
December 2, 2013

The scientists confirmed the result by sequencing a fragment of the virus. "Based on the length of the sequence we are absolutely certain that this is MERS," says Marion Koopmans, chief of virology at the National Institute for Public Health and the Environment in the Netherlands, who was involved in the work.

Osterholm praises Qatar for its efforts. "The public health officials in Qatar deserve a great deal of credit for their aggressive actions in investigating this situation and involving the relevant international laboratory partners," he says. "This could have been done in Saudi Arabia months ago."

The above comments on MERS sequences in a Qatar camel confirm that the PCR test identifies MERS-CoV. This identification was expected because of the specificity of the MERS PCR test, but the camel cluster has generated significant confusion, including statements about MERS-like antibodies found in camels in Oman and Egypt. Although the antibody data only suggests that the coronavirus infections were due to beta2c, the PCR result in Qatar and Saudi Arabia increase the likelihood that the earlier antibody results were in fact due to prior MERS-CoV infections.

The additional comments on progress in the Kingdom of Saudi Arabia (KSA) highlight concerns that testing of camels in KSA has been lacking. Recently a symptomatic camel owned by a MERS confirmed Jeddah case was PCR confirmed. Sequences from the camel and case were expected last week, but the identity between the two sets of sequences is expected to be close to 100% (>99.9%). The identity between the KSA sequences or sequences from the Qatari camels and linked confirmed human cases (61M & 23M), will confirm interspecies transmission, but will not determine the direction.

The direction of transmission is largely dependent on more serious surveillance in KSA and throughout the Middle East. The index case of a cluster in Batin had cared for a symptomatic camel, but there are no reports on the testing of the camel. Dr Ziad Memish had defended that lack of animal testing due to the absence of a protocol from WHO. However, media reports noted that the PCR confirmation of the camels in Qatar (who were either asymptomatic or had mild symptoms) used a nasal swab, which could be collected by veterinarians and testing would follow the protocol used for swabs from humans.

The presence of MERS in camels throughout the Middle East (as indicated by antibody positives in Oman and Egypt or MERS PCR positive in KSA or Qatar) raises serious concerns because of the potential for ongoing jumps from camels to humans and subsequent adaptation to humans. The lack of serious surveillance has delayed a determination of the extent of MERS spread throughout the camel population and the ability to control this potentially significant reservoir.

[dothedd]

Hong Kong H7N9 Case(s) Raise Concerns
Recombinomics Commentary 23:30
December 2, 2013

The 36-year-old patient is in a critical condition in Queen Mary Hospital, Pok Fu Lam, with severe pneumonia and breathing with the help of an artificial lung.

The live-in helper works for a couple with two children, and all four were said to have minor flu symptoms and were under observation in quarantine at Princess Margaret Hospital.

Health officials are looking for a second person who accompanied the helper to Shenzhen on November 17.

The helper developed flu symptoms four days later. She was first treated at Tuen Mun Hospital, but was transferred to Queen Mary last Wednesday.

Ko said two earlier tests for the virus came back negative, but a third test last night confirmed she had contracted H7N9.

The above comments describe the first confirmed H7N9 bird flu case (36F) in Hong Kong. The live-in helper had traveled to Shenzhen (see map) to buy a chicken. She developed flu symptoms, but tested negative twice. However, after her condition worsened (including breathing difficulties) she was hospitalized and tested positive for H7N9.

The case raised concerns since she tested negative twice and it is unclear if milder cases will be detected. The four contacts in the home have mild symptoms, while status of the person who also traveled to Shenzhen is currently unknown.

This is the third H7N9 case originating in Huizhou in Guangdong province since August (collected Aug 10). A full set of sequences, A/Guangdong/1/2013, was released for the first case (51F). Although the external gene segments (H7, N9, MP) and NP were closely related to the cases from the spring (largely centered around Shanghai), the internal gene segments (PB2, PB1, PA, NS) were most closely related to H9N2 sequences found in southern China (largely Hong Kong).

Sequences from a more recent case (3M), which was also from Guangdong Province (Dongguan) have not been released. However, the Hong Kong case also traveled to Guangdong Province (Shenzhen) raising the possibility that all three cases have a similar constellation of genes which is distinct from the sequences from northern China.

The second case was also linked to symptomatic family members, but they tested negative for H7N9. The initial negative tests for the current case raise concerns that mild H7N9 cases, including contacts, will also test negative.

[dothedd]

Commentary
H1N1pdm09 Louisiana Tamiflu Resistance Cluster Grows
Recombinomics Commentary 20:30
December 3, 2013

Recently released H1N1pdm09 sequences by the CDC identified two cases (25F and 56F) in Louisiana with the oseltamivir resistance marker, H274Y (A/Louisiana/07/2013 and A/Louisiana/08/2013). The detection of two cases in the same state at the same time (collected Oct 7 & 9) raised concerns since the two cases matched the total number of cases for the 2012/2013 season (A/Pennsylvania/01/2013 (collected Jan 18 and A/Tennessee/03/2013 collected Mar 26).

The CDC release sequences for all eight gene segments, which showed that the two isolates were virtually identical. The Louisiana Department of Health indicated the CDC requested additional samples, which led to the identification of a third case (the first 2 cases were cited in week 44 FluView and the third case was in week 45) and all three cases were unlinked.

The CDC recently released sequences for all eight gene segments of the third case 25F, A/Louisiana/10/2013 from a sample collected on October 21. That set of sequences matched the first two, extending the clonal expansion. The CDC also released two sets of sequences (A/Louisiana/11/2013 and A/Louisiana/12/2013) which were oseltamivir sensitive, but these sequences were also closely related to the three resistant sequences.

This similarity raises concerns that the sensitive cases are mixtures, with H274Y present in lower concentration. The possibility of a mixture in the Louisiana sequences is support by newly released sequences from a resistant case (14F) in Utah, A/Utah/10/2013, which has almost equal levels of H274Y and wild type, but is also closely related to the Louisiana sequences.

[dothedd]

Louisiana H1N1 Tamiflu Resistance Expands To Utah
Recombinomics Commentary 23:45
December 3, 2013

The CDC released another series of recent H1N1pdm09 sequences, which included the third Louisiana sequence, A/Louisiana/10/2013, with H274Y. Like the first two cases, A/Louisiana/07/2013 and A/Louisiana/08/2013, all eight gene segments were sequenced and the match signaled clonal expansion. The CDC also released full sequences from two additional Louisiana patients, A/Louisiana/11/2013 and A/Louisiana/12/2013, which were Tamiflu sensitive, but were closely related to all 8 gene segments of the three resistant cases, raising concerns that the sensitive samples included a subset that included H274Y.

Those concerns were increased by a fourth sequence with H274Y, which was from a Utah patient (14F, A/Utah/10/2013). That sequence gave a mixed signal for position 274, but was also closely related to all 8 gene segments in the above Louisiana sequences, suggesting that H274Y was far more widespread than indicated by the four sequences with H274Y.

This concern was increased by the latest FluView (week 47), which cited two more H1N1pdm09 cases that were Tamiflu resistance. The spread of this clone to Utah, and the announcement of two more cases in the week 47 report, raise concerns that the number of cases will continue to increase for the current season, where the vast majority of flu cases are influenza A, and the vast majority of influenza A cases are H1N1pdm09.

[dothedd]

Novel Hong Kong H7N9 Constellation
Recombinomics Commentary 19:00
December 4, 2013

The Center for Health Protection in Hong Kong has released a full set of sequences, A/Hong Kong/5942/2013 (at GISAID), from a November 30, 2013 collection from the recently (see map) confirmed case (36F). The CHP is to be commended for the rapid release of these important sequences.

As expected, these sequences have much in common with sequences, A/Guangdong/1/2013, from the August case in Huizho (51F collected August 10, 2013). That sequence was easily distinguished from the H7N9 sequences from cases in northern China (A/Zhejiang/22/2013 and A/Zhejiang/DTID-ZJU10/2013). Although four gene segments (H7, N9, MP, NS) were related to the northern China sequences, the other four gene segments were most closely related to H9N2 sequences circulating in southern China (mostly from poultry sequences from Hong Kong or Guangdong Province).

A/Hong Kong/5942/2013 also had same relationship with H7, N9, MP, and NS, including the presence of Q226L in H7. In addition, the H7 sequence had T131A, which was also uniquely found in A/Guangdong/1/2013. Similarly, the PB2 had E627K and was closely related to the PB2 in A/Guangdong/1/2013. However, the other three internal genes (PB1, PA, NP) were related to H9N2 sequences circulating in southern China (largely Hong Kong), but were distinct from the A/Guangdong/1/2013 sequences.

Thus, A/Hong Kong/5942/2013 represents an independent introduction into humans, which reflects a constellation circulating in southern China that is distinct from the August H7N9 from Guangdong Province. This sequence data indicates H7N9 circulating in southern China is readily distinguished from the former and recent sequences in northern China, and there is significant heterogeneity in the southern sequences signaling widespread H7N9 in poultry in southern China.

[dothedd]

Another Hong Kong ex-Shenzhen H7N9 Case
Recombinomics Commentary 18:00
December 6, 2013

The patient, with underlying medical condition, lives in Shenzhen. He was admitted to a hospital in Shenzhen for management of his chronic illness from November 13 to 29.

On December 3, he arrived in Hong Kong with his three family members via Shenzhen Bay Port Border Control Point (SBP BCP) and subsequently took a taxi there in the afternoon to the Accident and Emergency Department (AED) of Tuen Mun Hospital (TMH) where he was admitted for further management of his chronic illness on the same day.

The patient had no fever upon admission. However, he developed fever this morning and was put under isolation immediately. His nasopharyngeal swab was tested positive for the avian influenza A(H7N9) virus upon laboratory testing by the Public Health Laboratory Services Branch of the CHP today.

The patient will be transferred to Princess Margaret Hospital for isolation. His current condition is stable.

The above translation, from the Government of Hong Kong press release provides detail on the second confirmed H7N9 case (80M) at the Tuen Mun hospital (see zoomed map), which had a travel history in Shenzhen. This second case raises concerns that there is a significant number of unreported cases in Shenzhen.

The Guangdong CDC has promptly released a full sequence, A/Hong Kong/5942/2013, from the first case (36F), which has much in common with the sequence, A/Guangdong/1/2013 (GD/1), from August case (51F - see map). Both sequences are easily distinguished from the H7N9 cases last spring, which had internal H9N2 gene segments related to avian sequences circulating in northern China. The recent cases had four internal genes (PB2, PB1, NP, NS) which were related to H9N2 sequences circulating in southern China (Guangdong and Hong Kong) and both sequences also had H7 T131A, which also distinguishes the southern H7 sequences from the spring sequences.

However, the recent Hong Kong sequence was novel due to the relatedness of three of these gene segments (PB1, PA, NP) to H9N2 lineages that were distinct from GD/1, which can be used to determine the relatedness of the two Hong Kong sequences to each other.

Rapid release of the latest H7N9 sequences would again be useful.

[dothedd]

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Commentary
Nosocomial H7N9 Transmission at Tuen Mun Hospital HK?
Recombinomics Commentary 19:30
December 6, 2013

On December 3, he arrived in Hong Kong with his three family members via Shenzhen Bay Port Border Control Point (SBP BCP) and subsequently took a taxi there in the afternoon to the Accident and Emergency Department (AED) of Tuen Mun Hospital (TMH) where he was admitted for further management of his chronic illness on the same day.

The patient had no fever upon admission. However, he developed fever this morning and was put under isolation immediately.

The above translation from the Hong Kong press release raises concern that the latest confirmed case (80M) was H7N9 bird flu infected at Tuen Mun Hospital, which is where the first case (36F) was treated (see zoomed map). The development of symptoms 2-3 days after admission is consistent with nosocomial transmission. Multiple contacts of the index case have flu-like symptoms, but have tested negative on the rapid test. However, the index case twice tested negative on the rapid test prior to PCR confirmation.

The full sequence, A/Hong Kong/5942/2013, from the index case (36F) has been published and it is novel (easily distinguished from cases in northern China as well the August case in Guangdong Province).

If the latest case (80M) is due to nosocomial transmission, the sequences should match. The full first sequence was promptly released and sequences from most of the internal gene segments would allow for assessment of likely nosocomial transmission.

Immediate release of the sequences from the latest case would be useful.

[dothedd]

Commentary
Hangzhou and Hong Kong H7N9 Clusters Raise Concerns
Recombinomics Commentary 14:00
December 7, 2013

Inform the PRC Zhejiang Provincial Health Department on December 6, 1 new cases of human infection in Zhejiang Province H7N9 avian flu cases . At risk patients, male, 30 years old. On December 5 confirmed, first affiliated hospital of Zhejiang University School of medicine now.
This reporter learned that, the infection H7N9 avian flu virus risk, was in a hospital of Zhejiang University last Wednesday the 57 confirmed Mr Chang's son-in-law.

The above translation describes the two most recent H7N9 bird flu confirmed cases (57M and 30M) in Hangzhou in Zhejiang Province (see map). WHO has not yet acknowledge these two cases in northern China or the two recent cases in Hong Kong (36M and 80M) who were both treated in Tuen Mun Hospital (see map).

These two sets of clusters raise serious human to human transmission issues. Sequences from one of the four above cases, A/Hong Kong/5942/2013, have been released, which are novel and distinct from spring H7N9 cases due to the presence of 5 of the 8 gene segments (PB2, PB1, PA, NP, NS) which are most closely related to H9N2 sequences circulating in southern China (largely from Hong Kong). Two independent labs have released sequences from an October case, 35M, in Zhejiang, A/Zhejiang/22/2013 and A/Zhejiang/DTID-ZJU10/2013, which are closely related to H7N9 cases from the spring.

Thus, although H7N9 constellations in northern China and southern China are readily distinguished from each other, the presence of familial and hospital clusters raises serious human transmission concerns.

Release of sequences from the two cases from Hangzhou, as well as the most recent case in Hong Kong, would be useful.

[dothedd]

Commentary
Curious ProMED Comments On H7N9 Human Transmission
Recombinomics Commentary 16:00
December 8, 2013

It remains uncertain whether the 2nd (imported) case in Hong Kong contracted H7N9 virus infection before or after arrival in Hong Kong. Clarification is awaited. In both of the new H7N9 cases described above, there is no evidence of human-to-human transmission of infection....
- Mod.CP

The above comments from a ProMED H7N9 update on the two most recent cases (80M in Hong Kong and 30M in Hangzhou) are curious. The above Hong Kong case (80M) developed symptoms three days after admission to Tuen Mun Hospital (TMH), supporting nosocomial transmission, which is further supported by the earlier admission of the first confirmed H7N9 case (36F) in Hong Kong, who was also treated at TMH (which is midway between Palatial Coast home of the family served by the index case and Shenzhen – see map). There has been no evidence of exposure to H7N9 poultry in chickens in Shenzhen, but the family served by the index case was symptomatic, and both confirmed H7N9 birdflu cases in Hong Kong were treated at TMH.

Similarly, the only known H7N9 exposure of the most recent case (30M) in Hangzhou, Zhejiang is his father-in-law (57M), who has been H7N9 confirmed. The gap in hospitalization dates suggests the younger case (30M) was infected by his father-in-law (57M).

The circumstantial epidemiological data can be strongly supported or refuted by sequence data. The sequence for the Hong Kong index case, A/Hong Kong/5942/2013, has been published. It has a novel constellation which includes five gene segments (PB2, PB1, PA, NP, NS) which are most closely related to H9N2 sequences circulation in Hong Kong, which includes three gene segments (PB1, PA, NP), which are easily distinguished from the August H7N9 sequence, A/Guangdong/1/2013. Thus, a match between sequences from the first two confirmed cases (treated at TMH) would strongly support nosocomial (human to human) transmission. Similarly, a match between the sequences from the two family members in Hangzhou (57M and 30M), which are more likely to match the October sequences from Zhejiang (A/Zhejiang/22/2013 and A/Zhejiang/DTID-ZJU10/2013), would also support H2H transmission between the family members.

Release of sequences from the three recently confirmed cases in Hong Kong (80M) and Zhejiang (57M and 30M), would be useful.

[dothedd]

Commentary
Curious ProMED Comments On H7N9 Human Transmission
Recombinomics Commentary 16:00
December 8, 2013

It remains uncertain whether the 2nd (imported) case in Hong Kong contracted H7N9 virus infection before or after arrival in Hong Kong. Clarification is awaited. In both of the new H7N9 cases described above, there is no evidence of human-to-human transmission of infection....
 Mod.CP

The above comments from a ProMED H7N9 update on the two most recent cases (80M in Hong Kong and 30M in Hangzhou) are curious. The above Hong Kong case (80M) developed symptoms three days after admission to Tuen Mun Hospital (TMH), supporting nosocomial transmission, which is further supported by the earlier admission of the first confirmed H7N9 case (36F) in Hong Kong, who was also treated at TMH (which is midway between Palatial Coast home of the family served by the index case and Shenzhen – see map). There has been no evidence of exposure to H7N9 poultry in chickens in Shenzhen, but the family served by the index case was symptomatic, and both confirmed H7N9 birdflu cases in Hong Kong were treated at TMH.

Similarly, the only known H7N9 exposure of the most recent case (30M) in Hangzhou, Zhejiang is his father-in-law (57M), who has been H7N9 confirmed. The gap in hospitalization dates suggests the younger case (30M) was infected by his father-in-law (57M).

The circumstantial epidemiological data can be strongly supported or refuted by sequence data. The sequence for the Hong Kong index case, A/Hong Kong/5942/2013, has been published. It has a novel constellation which includes five gene segments (PB2, PB1, PA, NP, NS) which are most closely related to H9N2 sequences circulation in Hong Kong, which includes three gene segments (PB1, PA, NP), which are easily distinguished from the August H7N9 sequence, A/Guangdong/1/2013. Thus, a match between sequences from the first two confirmed cases (treated at TMH) would strongly support nosocomial (human to human) transmission. Similarly, a match between the sequences from the two family members in Hangzhou (57M and 30M), which are more likely to match the October sequences from Zhejiang (A/Zhejiang/22/2013 and A/Zhejiang/DTID-ZJU10/2013), would also support H2H transmission between the family members.

Release of sequences from the three recently confirmed cases in Hong Kong (80M) and Zhejiang (57M and 30M), would be useful. 

[dothedd]

Nosocomial H7N9 Sequences at Tuen Mun Hospital HK?
Recombinomics Commentary 04:00
December 9, 2013

The 80-year-old male patient lives in Fu Yong Xin He District in Shenzhen

The above translation from the Centre for Health Protection (CHP) Department of Health December 8 Epi update indicates the recent H7N9 case lives in northwestern Shenzhen (see map), which is also the location of the Fuyong People’s Hospital where the case initially sought treatment for chronic diabetes and cardiac problems. After discharge, he traveled from Shenzhen to Tuen Mun Hospital (TMH) on December 3 where he was admitted for treatment for his chronic conditions. Three days later, on December 6 he developed a fever and was tested for H7N9, which was confirmed. Thus, the development of flu-like symptoms three days after admission is consistent with nosocomial transmission.
The possibility of H7N9 nosocomial transmission is increased by the prior treatment of the first confirmed H7N9 case (36M) at the same hospital. A sample collected by the CHP on November 30 was the source of a complete sequence, A/Hong Kong/5942/2013 (HK/5492), which was released at GISAID on December 4.

A similar turn-around time for the second confirmed case, would produce a public sequence on December 9, which would address the issue of nosocomial transmission, because the recent sequence was novel and easily distinguished from recent H7N9 sequences from a case in Zhejiang Province (A/Zhejiang/22/2013 and A/Zhejiang/DTID-ZJU10/2013 - see map) as well as an August case in Huizhou (see map), which produced the A/Guangdong/1/2013 (GD/1) sequence.

Both sets of sequences from cases in southern China were easily distinguished from the northern China sequences, which were similar to the poultry and human H7N9 sequences from the spring. The southern China sequences had internal genes which were most closely related to H9N2 sequences circulating in southern China (largely from Hong Kong). GD/1 had four such internal gene segments (PB2, PB1, PA, NS),
HK/5942 was easily distinguished from GD/1 because the Hong Kong sequence had an additional gene segments (NP), which matched H9N2 Hong Kong sequences, and two additional gene segments (PB1 and PA) matched southern China lineages that were distinct from those found in GD/1. Thus, these significant differences between GD/1 and HK/5942 strongly suggest that H7N9 in chickens in distinct regions of Shenzhen would have easily distinguished sequences.

The Hong Kong index case (36F) was employed at a resident in the Palatial Coast complex, which is 5 miles south of TMH (see map) suggesting that the market in Shenzhen that she visited to buy a chicken was near the Hong Kong border. In contrast, the chicken that the second case ate was likely from northwestern Shenzhen, and H7N9 from these two regions would be distinct.

In contrast, if the second case was infected after admission to TMH and that infection was linked to the prior admission of the index case, the two sequences would be closely related in all 8 gene segments.

Therefore, the prompt release of the full sequence from the recent Hong Kong case would be useful.

[dothedd]

Familial H7N9 Cluster In Hangzhou Zhejiang
Recombinomics Commentary 14:45
December 10, 2013

The patient became ill on November 20 and was admitted to a local hospital on November 22 for treatment. He is currently in critical condition. His sample tested positive for the avian influenza A(H7N9) virus upon testing by the relevant health authority of Hangzhou.

Yu a November 29 onset, mainly fever, cough, fever immediately to a hospital in Zhejiang outpatient treatment. "After November 27 Moumou confirmed, because the risk of a no symptoms, and no sampling checks. Nov. 29, after he had a fever, we immediately sampling tests, the results were negative until December 5 sicker, the first Secondary test results were positive, he was diagnosed infected with H7N9 avian influenza. "

The above translations describe a Hangzhou (see map) familial cluster involving an index case (57M) who developed symptoms on November 20 and his son-in-law (30M) who developed symptoms on November 29. The disease onset dates and relationship between the two cases is cited in the WHO December 10 H7N9 update, which also includes the two cases in Hong Kong (36F and 80M). WHO notes in the update, as well as numerous tweets, that there is no evidence of sustained human to human (H2H) transmission, which is distinctly different from the curious ProMED comments citing no evidence of H2H transmission.

When contacts develop symptoms that have a significant gap in disease onset days (like the 9 days cited above), it is likely that the index case infected the contact, especially when the contact cared for the index case, as happened in Hangzhou, Zhejiang.

A small number of familial clusters were cited in the spring, so familial H7N9 clusters are not new. However, the cluster in Hangzhou and the linkage of the two cases in Hong Kong to the same hospital (Tuen Mun) has raised concerns that the frequency of such clusters may be on the rise, and the size and number of such clusters may be limited by false negatives.

The above detail on the second case notes that he tested negative when he initially developed symptoms on November 29, and continued to test negative until December 5. Initial negative results were also reported for the index case in Hong Kong. The testing protocol in Hong Kong used the rapid test for monitoring, which is then followed by antiviral treatment and additional testing if the patient’s flu-like symptoms worsen. Thus, milder cases who initially test negative and recover are not lab confirmed, which leads to fewer clusters and a higher case fatality rate, but masks the H2H transmission.

The sequences, A/Hong Kong/5942/2013) from the index case in Hong Kong were released 5 days after collection, Confirmation of the three other cases cited above were confirmed using samples collected more than five days ago.

Prompt release of these sequences and more aggressive testing of symptomatic contacts would be useful.

[dothedd]

More MERS Clusters In KSA Raise Concerns
Recombinomics Commentary 23:45
December 10, 2013

The first case is for a 73-year-old female citizen in Riyadh, who had been suffering from various chronic diseases. She passed away….
The second case is for a 65-year-old male citizen in Al-Jouf, who has been suffering from various chronic diseases. Recently, he has been transferred to the IC unit in Riyadh region; to carry on his treatment

The first case is for a 26-year-old female citizen, working in the health sector in Riyadh, who was in contact with a confirmed case of the virus, and the disease symptoms were not shown in her cases.
The second case is for a 51-year-old female citizen in Al-Jouf, who has been suffering from various chronic diseases. Recently, she has been transferred to the IC unit in Riyadh region; to carry on her treatment.

The above comments from the Kingdom of Saudi Arabia Ministry of Health (KSA-MoH) MERS website describe two MERS clusters. The November 19 announcement (in red) describes a fatal case (73F) in Riyadh, as well as the first confirmed case (65M) in Al-Jouf. The December 6 announcement (in blue) describes a second Riyadh case (26F) who is an asymptomatic health care worker who is a contact of a confirmed case. The announcement also cites a second case (51F) in Al-Jouf, raising concerns that the second case is part of a cluster, even though the announcement is silent on the relationship between the two Al- Jouf cases.

The wording, other than age and gender, is identical for both cases, citing underlying disease as well as transfer to an ICU in Riyadh. The transfers raise concerns that the hospital(s) in Al-Jouf do not have the resources to properly care for the two confirmed cases.

However, recent local media reports raise concerns that there are several additional suspect or confirmed cases which include relative(s) of the confirmed case(s) and hospital employees in Sakaka (see map). Additional reports cite a 40 year old expatriate from India, as well as another case (37M) who has been in a coma for 12 days and has been MERS confirmed.

More information on the confirmed and suspect cases in Sakaka, Al-Jouf, including relationships and disease onset dates, would be useful.

[dothedd]

H7N9 Sequences At Two Longgang Shenzhen Wet Markets
Recombinomics Commentary 23:30
December 11, 2013

An infected blood sample came from a chopping board at a stall selling live poultry at the Henggang Henggang market. The other two were found in chicken excrement and a plucking machine from a stall at the Kangqiao market in the Nanwan neighbourhood.

The above comments describe three H7N9 samples collected in the Longgang District in Shenzhen in Guangdong Province, which were near the flat of the Hong Kong index case (36F) who had exposure to a live chicken (see map). The presence of H7N9 in two different wet markets in Shenzhen raises concerns that H7N9 is widespread.

The two positive wet markets are about 15 miles east of the home and location (see map) of the second Hong Kong case (80M), who did not have contact with live poultry. He did eat chicken that was stored in his freezer and was asymptomatic when he was admitted to Tuen Mun hospital, where the index case was also treated prior to his admission. He developed symptoms three days after admission, raising nosocomial transmission concerns.

Although the sequence, A/Hong Kong/5942/2013, from the index case was promptly released, the release of the sequence from the second case has been delayed.

Release of that sequence as well as sequences from the two Shenzhen wet markets would be useful.

[dothedd]

Fenggang H7N9 Case Raises Transmission Concerns
Recombinomics Commentary 16:00
December 15, 2013

After preliminary investigation, the patient started on December 6 with fever, headache and fatigue and discomfort, did not improve after the self-medication, he worked in a local clinic, Fenggang town, the 11th to Fenggang hospital treatment, 13 patients with dyspnea was progressively increased transferred to ICU treatment.

The above translation describes the most recent H7N9 confirmed case in China. This case (39M) is also in Guangdong Province who lives in Fenggang town in Dongguan (see map). The above claim that he “worked in a local clinic” in Fenggang town raises concerns that he was infected by another case. H7N9 was recently confirmed in two wet markets in the Longgang district which are 7-8 miles south of Fenggang town.

The index case in Hong Kong (36F) had handled live poultry in the Longgang district (also depicted in map). In contrast, the second case in Hong Kong (80M), lived about 20 miles west of the Longgang district. He did not have contact with live poultry, and developed symptoms 3 days after admission Tuen Mun Hospital (see map), where the index case was also treated and hospitalized.

The sequence from the index case, A/Hong Kong/5942/2013, was promptly released. It had acquired internal genes that had been circulate\ng in H9N2 poultry in southern China, which were easily distinguished from cases (A/Zhejiang/22/2013 and A/Zhejiang/DTID-ZJU10/2013) in northern China (in the spring and fall), which had internal genes related to H9N2 circulating in northern China. Moreover, the August sequence from southern China, A/Guangdong/1/2013 had fewer southern H9N2 genes and was easily distinguished from the Hong Kong sequence.

The sequence from the second Hong Kong case has not been released. If he was ibfected to nosocomial transmission linked to the first case at Tuen Mun, the two sets of sequences should be virtually identical. Similarly, these sequences should also be closely related to sequences from live markets in the Longgang district. These sequences, which are from samples collected more recently, also have not been released.

The release of sequences from the second Hong Kong case, the positive samples in the Longgang district, and the most recently case, should be released immediately.

[dothedd]

SORRY, I DON'T HAVE TIME TO LIST THIS INDIVIDUALLY.  YOU CAN CLICK ON THE LINK IF YOU ARE INTERESTED. 

Michigan pH1N1 EMCO Machines Maxed Out (01/03/13 20:30)

Silent Spread of H1N1 RBD Change L194I (12/30/13 23:34)

H1N1 Tamiflu Resistance Spread In Sapporo Japan (12/29/13 23:45)

D225G and Q226R Driving H1N1 Deaths? (12/27/13 01:15)

H1N1 Q226R In Mississippi (12/26/13 21:45)

Austin H1N1 ECMO Machines Maxed Out (12/26/13 12:00)

CDC Issues H1N1 Advisory (12/25/13 20:30)

H1N1 Swine Flu Tamiflu Resistance Spreads To Mississippi (12/23/13 13:15)

H1N1 swine Flu Levels Approach 100% In Texas and US (12/23/13 04:00)

Texas Issues Influenza Health Alert (12/21/13 16:30)

Explosion In Houston H1N1pdm09 Deaths Expected (12/21/13 15:00)

Houston Fatal and Severe H1N1pdm09 Cases Increase (12/21/13 12:00)

Houston Fatal and Severe H1N1pdm09 Cases Confirmed (12/20/13 20:00)

H1N1pdm09 Confirmed Again In Montgomery Co Texas (12/19/13 23:45)

H7N9 Longgang Shenzhen Case Confirmed In Guangdong (12/19/13 12:30)

H1N1pdm09 Confirmed As Mystery Fatal Disease In Texas (12/18/13 23:45)

JiangCheng Yangjiang H7N9 Cluster In Guangdong China (12/18/13 15:00)

Texas Rapid Flu Tests Raise Serious Concerns (12/18/13 13:45)

H1N1pdm09 Is Likely Mystery Fatal Disease In Texas (12/18/13 06:30)

H1N1pdm09 Louisiana Tamiflu Resistance Cluster Expands (12/18/13 02:00)

Yangjiang H7N9 Case Expands Guangdong Reach (12/16/13 16:15)

www.recombinomics.com/whats_new.html

[dothedd]

Commentary
Tamiflu Resistance Driving Severe California pH1N1 Cases?
Recombinomics Commentary 08:00
January 5, 2014

If patients continue to do poorly on oral oseltamivir, investigational intravenous zanamivir is available under an emergency investigational new drug (EIND) request to the Food and Drug Administration (FDA). To request an EIND, contact: (8:00AM - 4:30PM EST): 301-796-1500

The California Department of Public Health (CDPH) issued a pH1N1 health advisory earlier this week. Like advisories from Texas and the CDC, the CDPH advisory warned of severe and fatal pH1N1 cases in previously health young and middle aged adults, as well as the lack of sensitivity in rapid tests, and the utility of starting antiviral treatment based on clinical presentation rather than test results from rapid tests or PCR re-testing. Although the CDPH report is considerably longer that the advisories from Texas and the CDC the above comments and detail on the use of IV Relenza via an EIND raises concerns that Tamiflu resistance is creating problems.

Boots on the ground reports have suggested that cases in Texas (see map) and northern California have not been responding to Tamiflu treatment, and a blast FAX was sent to physicians in northern California. Earlier sequences released by the CDC included those with H274Y which had clonally expanded in Louisiana (see map), and were also identified in Mississippi as well as Utah. Similarly, NIID in Japan had released sequencing supporting H274Y clonal expansion of another sub-clade in Sapporo.

This week media reports have described ICU and fatal H1N1 cases in California, which a heavy concentration in the Bay Area (see map). More detail from California (and Texas) on antiviral testing would be useful.

[dothedd]

Commentary
Texas pH1N1 Deaths Explode
Recombinomics Commentary 23:45
January 5, 2014

The flu outbreak is growing and so is demand for vaccine, according to officials. Dallas County is now reporting eight deaths due to the flu, and another nine additional suspected flu deaths.

The Beaumont health director tell us two more people died at Christus St. Elizabeth from the virus, bringing the total to eight deaths.
They range in age from 24 to 73 from Jefferson, Jasper and Hardin counties plus one from the San Antonio region.

The above comments describe a large number of reported pH1N1 deaths in Dallas County (in red – see map) and in one hospital in Beaumont (blue – see map). However, over 60 deaths have been reported in the state (see map), and these reported cases only represent a fraction of the deaths, raising concerns that significant increases will be reported in the upcoming weeks.

Adult deaths from influenza are not reportable. Although a Texas report covering the emergence of pH1N1 from April 2009 to January 2010 details 240 cases which were concentrated in those under 65, the actual number of flu deaths in Texas are not known. The recent deaths are also concentrated in young and middle aged adults, many of whom were previously healthy.

The number of reported cases in Texas is grossly under-represented in part due to widespread use of rapid tests (more than 60% of confirmed flu cases in Texas are confirmed by a rapid test), which have a low sensitivity for pH1N1, as indicated in advisories by Texas, the CDC, and California. Moreover, almost all of the cases listed in the maps cited above are delineated in media reports. Thus, while there are 17 cases cited in Dallas County, there is only one case cited in adjacent Fort Worth (Euless in Tarrant County). Other large cities are also glaringly missing cases, while others such has Hidalgo County (see map) have reported 6 confirmed cases out of a total of 24 (with more than half hospitalized or dead).

Thus, the cases shown in the above maps are only a fraction of the fatal cases, and the large number of hospitalized cases indicates these numbers will increase significantly in the upcoming weeks.

[dothedd]

Eight pH1N1 Pittsburgh Patients On ECMO Machines
Recombinomics Commentary 22:45
January 6, 2014

Officials at Allegheny General Hospital said four patients are hospitalized at the North Side facility. All became so sick that they had to be hooked to a special machine to help their lungs and hearts function.

At UPMC Presbyterian in Oakland, the treatment machine known as extracorporeal membrane oxygenation, or ECMO, has been used on four patients, said Dr. Donald Yealy, UPMC's chief of emergency medicine.

Yealy said patients treated with the machines are experiencing “the most serious complications short of death.”

At least five other patients at UPMC were critically ill but did not require treatment with ECMO machines.

The above comments describe the status of 13 H1N1 cases at two Pittsburgh hospitals, where one additional patient (62F) has died (see map) This high number of critically ill patients is being reported two weeks after the number of confirmed cases in Pennsylvania has begun to rise. Allegheny county has reported 149 confirmed H1N1 cases and the ILI level for Pennsylvania in the week 52 FluView was moderate (6 on a scale of 10). In spite of these relatively low numbers, 14 cases are either dead (1), on ECMO machines (8), or critically ill (5). Moreover, the fatal case (62F) was described as “an older woman” suggesting most or all of the above hospitalized are young or middle aged adults.

The high frequency of severe and fatal cases raises concerns that the death toll will dramatically increase in upcoming weeks, raising concerns the quasi-species of receptor binding domain changes (D225G/N, Q226R, and L194I) or oseltamivir resistance (H274Y) is common (see map), leading to have viral loads in the lungs of these patients (and others in the US, see Texas map, and Canada), leading to unfavorable outcomes.

[dothedd]

FDA Announces Shortage of Children's Tamiflu
Recombinomics Commentary 21:00
January 7, 2014


Genentech is experiencing temporary delays in manufacturing of Oral suspension. A brief shortage of Oral Suspension is expected in early--‐mid January.

Please check with authorized Genentech distributors and retailers for product availability. Genentech expects to have additional supply of Tamiflu for Oral Suspension mid-January 2014.

The above comments are from the FDA website, citing a shortage of children’s (oral suspension) of oseltamivir (Tamiflu). The website gives detail, including product number and company access, as well as compounding remarks. The reason for the shortage is demand.

Similar shortages arose in 2009, when pH1N1 dramatically spread. The current shortage highlights the public’s concern driven in part by media coverage.

However, most of the reported deaths have been in middle age adults, where the level of H1N1 is beginning to rise, raising concerns that the death toll, as well as demand for children’s and adult oseltamivir will increase significantly.

Details on supplies and production of adult oseltamivir would be useful.

[dothedd]

Fatal H5N1 Encephalitis In Edmonton Canada ex-Beijing
Recombinomics Commentary 23:15
January 8, 2014

Dr. James Talbot, chief medical officer for Alberta, said the person was admitted to hospital on Jan. 1 with high fever and “decreasing CNS consciousness” (meaning extreme lethargy). There was no cough or other signs of respiratory illness, which is usually the case with influenza, but not always with H5N1. Dr. Talbot said the patient died of meningoencephalitis, or swelling of the brain.

The above comments describe the clinical presentation of the first confirmed H5N1 case in the Americas. The patient (female?) developed symptoms on an Air Canada 030 flight from Beijing on December 27. The case is reported export of H5N1 via commercial airline.

The export signals a high level of H5N1 in humans in northern China. However, human avian influenza in China has been dominated by reports of H7N9, including cases reported today in northern China (Ninjing, Jiangsu – see map), southern China (Foshan, Guangdong – see map), and Hong Kong (see map).

Enhanced surveillance in mainland China as well as Taiwan has led to the identification of H6N1, H10N8, H9N2 cases in 2013, but there have been no reports of human cases of H5N1.

The unusual clinical presentation raises concerns that high levels of H5N1 in cases in China are being missed due to a focus on cases with more traditional bird flu symptoms including breathing difficulties and pneumonia.

Aggressive testing of encephalitis cases in Beijing and Toronto would be useful, as would release of complete H5N1 sequences from this case.

[dothedd]

Fatal H5N1 Encephalitis Cluster Raises Concern
Recombinomics Commentary 04:00
January 9, 2014

There was no cough or other signs of respiratory illness, which is usually the case with influenza, but not always with H5N1. Dr. Talbot said the patient died of meningoencephalitis, or swelling of the brain.

These cases have important clinical, scientific, and public health implications. In both cases, the clinical presentation led to diagnoses of gastrointestinal infection and acute encephalitis, which alone or in combination are common clinical syndromes in southern Vietnam.

Patient 1 had no respiratory symptoms and a normal chest radiograph less than 24 hours before she died. Although Patient 2 showed signs of pneumonia during the last day of his life, a respiratory illness was not considered his most relevant clinical problem.

The above comments (in red) describe the first exported H5N1 case reported to date. The Canadian developed symptoms during a flight from Beijing to Vancouver and was subsequently hospitalized in Edmonton, where she died, after presenting as indicated above.

The above comments (in blue) are from a New England Journal of Medicine paper describing a cluster in Vietnam involving siblings who both developed encephalitis. These two fatal H5N1cases raised concerns that similar cases would go unnoticed because of a focus on cases with respiratory symptoms.

The 2014 case raises similar concerns because China did not report any H5N1 cases in northern China in 2013. Enhance surveillance for H7N9 in China and Taiwan led to the first human case of H6N1, the first fatal case of H10N8, and the detection of an H9N2 case, which is also rare. The failure to detect any H5N1 cases during this surveillance raises concerns that H5N1 is presenting with symptoms similar to the three H5N1 cases described above, and such cases are common, based on the export of H5N1 from China to Canada.

[dothedd]

Fatal H5N1 Export By China Raises Surveillance Concerns
Recombinomics Commentary 13:45
January 9, 2014

The minister, Rona Ambrose, and several public health officials, insisted that the death was an isolated case and posed little or no risk to the general public. They said that the victim did not appear to have contracted the H5N1 virus from human contact during a trip to Beijing last month and was unlikely to have passed it along when returning to Alberta.

The above comment on H5N1 transmission in humans in general or the above case in particular is based on negative data from a country that has just exported H5N1 via a commercial airline passenger infection for the first time in recorded history. These statements raise serious concerns about media reports functioning as propaganda machines.

The above case had an unusual presentation (encephalitis in the absence of significant respiratory symptoms) which apparently is not being effectively monitored in China, which has not reported any human H5N1 cases since February 2013 (in Guizhou Province in southern China). The first reported export of H5N1 via airline passenger infection suggest human cases of H5N1 in the exporting county are common, and the failure to report any such cases in almost a year signals an unreliable surveillance system, which is being used to generate negative data to support the claim of little or known human transmission.

Examples of coronavirus export from Hong Kong in 2003 or Saudi Arabia in 2013 were associated with human to human transmission as well as nosocomial transmission associated with significant numbers of lab confirmed cases, which signaled a more significant transmission in milder cases which were not lab confirmed.

For influenza, export has preceded the declaration of a pandemic, for which the 2009 H1N1 pandemic is the most recent example. Although there is no suggestion that H5N1 is transmitting at pandemic levels, claims of limited human transmission in an H5N1 exporting country does not have a scientific basis, and such claims are little more than propaganda.

[dothedd]

Commentary
California Week1 H1N1 Hospitalizations Spike Higher
Recombinomics Commentary 23:45
January 13, 2014

LINK ON TO VIEW THE CHART: www.recombinomics.com/News/01131401/H1N1_PI_CA_Wk1.html

The above graph from the California Week 1 flu report tracks pneumonia and influenza (P&I) cases as a percentage of hospital admissions in Kaiser Permanente Hospitals in northern California. Like the CDC’s P&I death rate for the entire county, the levels oscillate throughout the year and pear at the height of flu season. Like the CDC graph, the displayed data represents five flu seasons, and the above graph shows tha dramatic spike in recent weeks to a level higher than the past five seasons, even though the jump just began in the past few weeks.

The rate did get above the epidemic threshold last season when the dominant serotype was H3N2, which aggressively attacked the elderly, who usually account for >95% of flu deaths. The dominance of H3N2 last season also led to a dramatic rise in the death rate for the entire country, which reached 9.8% of all deaths at its peak in early 2013. This death rate, like the hospitalization rate in the above graph, was higher in the 2012/2013 season than 2009/2010, when pH1N1 emerged.

The death rate in 2009/2010 was blunted because pH1N1 spared the elderly because they have cross protection from seasonal H1N1 which circulated decades ago, when it was more closely related to swine H1N1. As a result, flu deaths in the elderly were very low in 2009/2010, which is also true for the current season.

However, this season the current pH1N1 is causing a dramatic spike in the hospitalization percentage, even though the age groups hit hardest are young and middle aged adults. This dramatic spike is also seen in Table 2 in the week 1 report from Dallas County in Texas, where cases increased several weeks ahead of California. The Dallas report tracks hospital and ICU admissions for the current season, as well as 2012/2013, and like the above graph shows a dramatic uptick in cases which have already surpassed last season, even though the current pH1N1 attacks younger patients.

This dramatic increase in severe and fatal cases in young and middle aged adults is likely due to receptor binding domain changes which target human lung. Changes such as D225G, Q226R, and L194I were noted in early case this season and additional examples were seen in new sequences released by the CDC from cases in late November or early December. These changes were most easily seen in egg isolates, and all recently released egg isolates had these changes, highlighting the need for release of more sequences from eggisolates collected from more recent cases, such as those depicted in Texas and California.

[Aman A.K.A. Ahamburger]

At what point did they start to close air traffic during the SARS outbreak b?

[dothedd]

H1N1 Tamiflu Resistance Spreading In Mississippi (01/17/14 16:00)

US P&I Death Rate Crosses Epidemic Threshold (01/16/14 22:30)

China H1N1 Sequences Target Lung (01/16/14 19:30)

Dallas County Severe H1N1 Cases Spike Higher (01/15/14 23:45)

BELOW IS THE LINK TO READ THE ARTICLES: 

www.recombinomics.com/whats_new.html