RECOMBINOMICS

[dothedd]

H1N1pdm09 PA In Ohio ex-Virginia H3N2v Case
Recombinomics Commentary 20:45
August 1, 2013

The CDC has released a full set of sequences, A/Ohio/05/2013, from an Ohio resident who developed flu-like symptoms after attending an agricultural fair in northwestern Virginia (likely the Fauquire County Fair).

H3N2v was confirmed by the Ohio Department of Health laboratories in Reynoldsburg and the sample was forwarded to the CDC for confirmation and sequencing. The sequences from a July 22 sample included H3 N145R, which was present in the sequences from the Indiana Hancock County Fair (A/Indiana/14/2013, A/Indiana/15/2013, A/Indiana/16/2013, A/Indiana/17/2013, A/Indiana/18/2013) as well as the most recent H3N2v sequence from Indiana, A/Indiana/10/2013 (see map). N145R has not been reported in any swine sequence.

The earlier sequences in Indiana (from attendees of the Grant County Fair) had N145K, which also had not been previously reported in human cases, although this polymorphisms did appear in early 2013 swine H3N2v sequences. The presence of N145R in all of the above recent human cases (associated with agricultural fairs in Indiana and Virginia) raises concerns of human adaptation.

The latest sequence from the Ohio DoH sample also has a novel constellation of genes, which includes H1N1pdm09 PA, which also has never been reported in humans (or swine). Five of the gene segments (PB2, H3, NP, N2, MP) are closely related to the 2013 Indiana H3N2v cases. However, the other three gene segments (PB1, PA, NS) have been circulating in recent H3N2v swine (which have internal genes closely related to human sequences from 2011) and two of the genes (PB1 and NS), are closely related to the sequences from 2012 Minnesota H1N2 cases.

The acquisition of three gene segments in 2013 is similar the genetic changes which produced the constellation of genes seen in the human cases in 2011. That constellation had 5 gene segments matching 2010 human cases (PB2, PA, H3, NP, NS), but acquired the other three gene segments (PB1, N2, MP) from H1N2 swine, which included am H1N1pdm09 MP gene segment.

The time frame for the appearance of the novel constellation in 2013 is similar to the appearance of the novel constellation which included H1N1pdm09 MP in 2011.

The new constellation in 2013, coupled with the acquisition of N145R, raises concerns for a larger number of H3N2v human cases in 2013.

[dothedd]

H1N1pdm09 PA In Illinois and Indiana H3N2v Cases
Recombinomics Commentary 23:45
August 14, 2013

The CDC has released a full set of H3N2v sequences from the first 2013 confirmed cases in Illinois, A/Illinois/03/2013, as well as the most recent case in Indiana, A/Indiana/11/2013 (14th 2013 Indiana confirmed case). As was seen in the case in Virginia (Ohio resident who visited an agricultural fair in northwestern Virginia), A/Ohio/05/2013, both of the newly released sequences included an H1N1pdm09 PA gene segment (in addition to a H1N1pdm09 M gene segment). Moreover, the two most recent PA sequences were identical and differed from the Virginia sequences at two positions (the three human PA sequences were much more closely related to each other than any reported H1N1pdm09 PA sequence in swine).

Thus, the three most recent human H3N2v cases have H1N1pdm09 PA, increasing the total number of gene segments with a recent history of efficient transmission in humans to five. In the early 1990’s three human genes (H3, N2, PB1) were identified in swine. All human H3N2v sequences (first case was in 2009) have H3 and N2 that trace back to seasonal H3N2 circa 2003. The acquisition of H1N1pdm09 M gene in 2011 and PA in 2013 create a majority for human lineage genes in human H3N2v isolates.

These acquisitions signal further human adaptation that increase pandemic concerns.

[dothedd]

2013 Human and Swine H3N2v Sequence Discordance
Recombinomics Commentary 23:45
August 15, 2013

The USDA released the first July, 2013 H3N2v sequences (H3, N2, and MP from Ohio and Minnesota), and the sequences matched the sequences from 2012 human cases. The July sequences were similar to earlier 2013 swine H3N2v sequences. A/swine/Ohio/A01351573/2013 (collected July 10) was closely related to swine sequences such as A/swine/Ohio/A01349485/2013, and the USDA released a full set of sequences from this earlier isolates confirming matches with all 8 gene segments from the 2012 human cases. Virtually identical H3 sequences were seen in 2013 collections on March 29, 22, 22, 12, 12 (A/swine/Ohio/A01349615/2013, A/swine/Ohio/A01349495/2013, A/swine/Ohio/A01349485/2013, A/swine/Ohio/A01349305/2013, A/swine/Ohio/A01349302/2013, respectively), but no human H3N2v cases have been reported in Ohio in 2013.

The only Ohio resident with confirmed H3N2 in 2013 had visited a agricultural fair in northwestern Virginia just prior to disease onset.

Similarly no cases have been reported in Minnesota this year although the July 11 isolate, A/swine/Minnesota/A01351603/2013, also matched 2012 human cases.

In contrast to the frequent detection of 2013 swine matches with 2012 human cases, only one swine sequence, A/swine/Illinois/A01432795/2013, isolated in June is closely related to the 2013 human cases, which all have a closely related H3 which has either N145K or K145R (the Illinois swine has N145K). Thus, there is significant discordance between swine sequences, where there is just one closely related to the human sequences, while all 16 human cases in 2012 are closely related even though they are linked to fairs and farms in Indiana, Virginia, and Illinois.

Moreover, the three most recent human cases (A/Ohio/05/2013, A/Illinois/03/2013, and A/Indiana/11/2013) all have an H1N1pdm09 PA gene segment (as well as an M gene segments) which is identical in the isolates from Illinois and Indiana and are virtually identical to the sequence from Virginia (diagnosed and confirmed in Ohio).

This discordance again suggests that humans are infecting swine, which is why the human sequences share changes that are rarely found in swine collections made prior to the fair season.

[dothedd]

Qatari MERS-CoV Case Raises Ramadan Concerns
Recombinomics Commentary 08:15

August 21, 2013

The Supreme Council of Health in Qatar Tuesday for the registration of new cases of Corona virus that causes respiratory syndrome Middle East, a patient diagonal at the age of 59 years. The council said in a press statement Tuesday that "the patient was out of the country and felt symptoms before coming to the state, and upon arrival it was detected and diagnosed with the disease in the National Influenza Laboratory." And, the statement said, "that the patient receives appropriate treatment currently is in stable condition."

The above translation describes the first MERS-CoV case (59M) identified in Qatar.

However, the above case is the third Qatari to be MERS-CoV confirmed. The first case (49M) developed mild symptoms while performing Umrah in the Kingdom of Saudi Arabia (KSA) during Ramadan, almost exactly one year ago. He and companions developed mild symptoms while in KSA and his symptoms resolved after returning to Qatar. However, symptoms returned 2 weeks after resolution and worsening symptoms led to transport to England via air ambulance. The sequences from this case (England1) were 99.5% identical to the first confirmed (60M), EMC/12, confirmed a novel human coronavirus which was evolutionarily distinct from beta 2c coronavirus identified in prior and subsequent bat sequences.

The second confirmed Qatari (45M) was also confirmed in 2012 and also was diagnosed in Europe. He had not traveled outside of Qatar in the days prior to symptoms and the sequences (Essen, Germany) were most closely related to England1, suggesting both cases were infected in Qatar.

However, the above 2013 cases was diagnosed in Qatar, but developed symptoms while outside of the country, raising the possibility that his infection was linked to Ramadan pilgrims who would have been exiting KSA.

Detail on the travel history of the above case and disease onset dates would be useful.

[dothedd]

Identity Between Bisha Bat and First MERS-CoV KSA Case
Recombinomics Commentary 18:30

August 21, 2013

Virus from 1 bat showed 100% nucleotide identity to virus from the human index case-patient.

The above comments from the EID paper, Middle East Syndrome Respiratory Virus in Bats, Saudi Arabia, indicate a reservoir for the MERS-CoV sequences found in human cases has been identified.

Although the sequence generate from Taphozous perforatus is only 181 BP and within a highly conserved gene (positions 15068-15249 of RNA dependent RNA polymerase), the 100% identity, which includes T15196C, which is uniquely found in EMC/12, strongly suggests that the entire genome will be very closely (>99.5%) related to the human sequences (especially the sub-clade represented by EMC/12 and Jordan-N3) representing a source for the fatal infection of the first confirmed case (60M), who developed symptoms in June, 2012 and died on June 14. The bat sequence was from a sample collected in Bisha ruins (<12 km from the home of the 60M fatal case) and is much more closely related to the human sequences than prior bat beta2c sequences from samples outside of KSA.

Although the sequence data are limited (likely due to the holding of samples at 25 C for 48 hours at US customs), this identity raises the strong possibility of multiple introductions into the human population in Saudi Arabia and throughout the Middle East.

[dothedd]

Bisha Bat Signals Multiple Species / Human MERS Introductions
Recombinomics Commentary 04:45

August 22, 2013

Sequence fragments for five bat samples collected in 2012 and 2013 in on Kingdom of Saudi Arabia (KSA) have been released at Genbank (see sequences here, here, here, here, and here) in association with the EID paper on KSA bat coronavirus sequences. The four samples collected in 2013 included three from Bisha and one from Riyadh, but only the 2012 sample from Bisha (Taper/CII_KSA_287/Bisha/Saudi Arabia/2012 collected October 14) matched the human MERS-CoV sequences.

The EID paper presented a phylogenetic tree representing positions 15068-15249 of the EMC/12 sequence, which demonstrated identity between the bat and human sequence. However, the bat sequence at Genbank was 203 BP representing positions 15057-15259 and was also identical to EMC/12. As noted earlier, this region included T15196C, which is uniquely found in EMC/12, which is from the first confirmed MERS-CoV case (60M) who lived in Bisha <12 km from the location of the bat, who was nesting in Bisha ruins.

The presence of T15196C in the bat sequence suggests that the role of the bats in the Bisha infection is recent. The bat species (Taphozous perforatus) is more common in Africa and India (see map here) and the distribution in KSA is limited to a small area encompassing Bisha (which is near Jeddah, where the patient was treated and died). The Bisha sequences are most closely related to the sequences from Jordan (Jordan-N3), raising concerns that the MERS-CoV sequences are in multiple bat species.

The Bisha/Jordan sequences are distinct from the other human MERS-CoV which form two distinct branches, with England1/Essen forming one branch and England2/Al Hasa forming the other branch. These two additional groups suggest there are multiple introductions into humans which may involve multiple bat species which may impact humans via intermediary hosts.

21 additional human MERS-CoV sequences are expected to be released in the next few days, which may define additional sub-groups and additional animal species.

[dothedd]

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Commentary

Another Qatari MERS-CoV Case Raises Ramadan Concerns
Recombinomics Commentary 23:45
August 26, 2013

Qatari Health Higher Council registered Monday a new case of the deadly coronavirus after a Qatari man was diagnosed with flu and other symptoms a few days back.
The 29-year-old was diagnosed in the national center for flu, and samples were sent to laboratories abroad for confirmation, the health authority said in a press statement.
The man is in "critical condition," and he is currently under observation at the intensive care unit, the statement added.

The above comments describe the second MERS-CoV confirmed case in Qatar in the past week. Like the earlier case (59M), this case is reported almost exactly one year after another Qatari (49M) developed flu-like symptoms while performing Umrah in the Kingdom of Saudi Arabia (KSA) during Ramadan. The 2012 case recovered after returning to Qatar, but symptoms returned after 2 weeks and his condition deteriorated. He was transported to England by air ambulance, where he was MERS-CoV confirmed (he was the second confirmed case). He was placed on life support and was hospitalized for 9 months prior to his death.

The case who was diagnosed in the past week was said to have developed symptoms prior to returning to Qatar, and local media indicate he also developed symptoms in KSA while performing Umrah during Ramadan.

Few details have been released for the latest case, who is the second case diagnosed by Qatar. The time of this case also raises concerns that the infection is linked to Ramadan pilgrims such as the recent confirmed case or contacts or other pilgrims who recently returned fro KSA.

More detail on travel history of the latest cases, as well as links to the recent case or contacts would be useful.

[dothedd]

Qatari MERS-CoV Ramadan Links Raise Concerns
Recombinomics Commentary 12:15
August 27, 2013

Informed sources revealed the « Arab »that the Qatari national, who proved his HIV Corona virus syndrome Middle East respiratory feet from Saudi Arabia, where most likely he was doing Umrah, and is currently in the room isolate Hospital Hamad General, where receives follow closely, in parallel with make statements and medical monitoring of the health status of his family and those close to him, who he met after his return to the homeland.

The above translation suggests that the first MERS-CoV case (59M) identified by Qatar surveillance had been practicing Umrah in the Kingdom of Saudi Arabia (KSA) during Ramadan when he developed symptoms, which was also true for the first confirmed Qatari (49 M confirmed in England), who died in June after being on life support for 9 months. The most recent case (29M) also developed symptoms in August raising concerns of a direct or indirect link to pilgrims returning from KSA after Ramadan. Only one of the confirmed Qatari MERS cases (45M confirmed in Germany) had a disease onset which was not in August.

The latest case is the second Qatari in the past week, raising concerns that the number of Umrah / Ramadan linked cases is significantly higher than the two prior Qatari cases, and the number of cases in Qatar may continue to increase.

More information on the travel history and contacts for the two recent cases would be useful.

[dothedd]

Bisha Bat Match Raises MERS-CoV Concerns
Recombinomics Commentary 19:00
August 27, 2013

Reusken notes that the study authors could sequence only a 190-nucleotide-long segment of the 30,000-nucleotide coronavirus genome. Studies have suggested that sequences of at least 800 nucleotides are necessary to accurately determine how closely viruses are related.

The above comments on the recently described 203 nt fragment from a bat in Bisha in the Kingdom of Saudi Arabia, Taper/CII_KSA_287/Bisha/Saudi Arabia/2012, cites a 2010 study which was written prior to the discovery of MERS-CoV or the publication of large segments of the MERS-CoV genome generated from samples from 10 patients. Sequences from nine of the cases are complete (each over 30,000 nt) as well as a larger partial sequence (over 5,000 nt), which are in addition to much shorter segments from 4 additional cases.

All of the human sequences are closely related to each other and are >99.5% identical to the consensus sequence, and are easily distinguished from prior bat sequences, which were <92.5% identical, even when short conserved regions were compared. Thus, distinguishing these earlier bat sequences from all human sequences was straight forward.

In contrast, the 203 nt sequences is identical to the human sequence, EMC/12 from Bisha, clearly signaling a common origin for the two sequences. Comments from Ian Lipkin, strongly suggest the identity is not an artifact, since the sequence was generated prior to the acquisition of the human EMC/12 samples and repeated testing of other bat samples have been uniformly negative.

The identity between the Bisha bat and human sequences is significant. The human sequences can be clearly divided into two sub-clade. The two earliest sequences (Jordan-N3 from an ICU nurse, 40F, in Jordan and EMC/12 from the first confirmed case, 60M, from Bisha) form one subclade, which differs from the consensus sequence due to clustered polymorphisms in the RNA dependent RNA polymerase (RdRp) gene, most of which are shared by the two earliest sequences. However, in addition to these shared polymorphisms in RdRp, each sequence has a number of unique polymorphisms. In contrast, the remaining sequences which are largely from cases in the east (Al Hasa in KSA, Al-Hasa_1, Al-Hasa_2, Al-Hasa_3, Al-Hasa_4), as well as case from Qatar and United Arab Emirates).

The Bisha bat sequence is in RdRp (positions 15057-15259) and each of the two early sequences has a unique polymorphism in this region (T15196C for EMC/12 and C15229T for Jordan-N3). In contrast, all of the other eight human sequences exactly match the consensus for positions 15057-15259). Like EMC/12, the Bisha bat sequence has one polymorphism in this region, which is T15196C. Thus, the sharing of this unique polymorphisms by the human case from Bisha and the bat sequence from Bisha signals a common geographic origin, which has significant implications.

The species for the Bisha bat, Taphozous perforates, has a very limited geographic reach in KSA (which is largely limited to the area surrounding Bisha). In contrast, this species is far more common in Egypt and Sudan in Africa, as well as India in Asia, raising the possibility that related MERS-CoV cases are grossly under-reported in these countries (none have reported a MERS-CoV case within their borders). Moreover the exact match between the Bisha sequences suggest that many additional bat sequences have sequences closely related to the human cases, which signal multiple independent introductions.

However, the 10 published sequences represent a small percentage of the confirmed cases and the diversitry may be significantly higher. 21 additional human sequences are expected to be released in the near term, and are said to be diverse and signal more independent introductions.

These published and soon to be released sequences suggest that there should be a greater effort targeting bat droppings, which have a high concentration of coronavirus RNA,, and were the source of the match in the Bisha bat. In the past coronavirus sequences have been identified in collections represent 1000’s or tens of 1000’s samples of bat droppings, which can be efficiently collected to determine the diversity of closely related MERS-CoV sequences in bats in KSA.

Those sequences can be used with the expanded sequence database from human cases to determin the role of bats in the “sporadic” cases, and follow up studies which include bat captures and wing punches can be used to link the diverse sequences to specific bat species and geographic distribution.

[dothedd]

Qatari MERS-CoV Ramadan Cluster Raises Concerns
Recombinomics Commentary 23:45
August 27, 2013

The Supreme Council of Health (SCH) has reported a new Middle East Respiratory Syndrome corona virus case.

The patient is a 29-year-old Qatari citizen who has a exposure to a confirmed case and suffers from asthma and several risk factors.

The above comments indicate the latest MERS-CoV case (29M) in Qatar is linked to a confirmed case, which presumably is the 59M who developed symptoms while abroad, which appears to be linked to Umrah ln Kingdom of Saudi Arabia (KSA) during Ramadan.

Thus, apparently both confirmed MERS-CoV cases in Qatar are linked to travel to KSA during Ramadan.

[dothedd]

H3N2v In Michigan With H1N1pdm09 PA & MP?
Recombinomics Commentary 21:45
August 29, 2013

Today, August 29, 2013, the Michigan Departments of Community Health (MDCH), and Agriculture and Rural Development (MDARD), along with the Berrien County Health Department (BCHD) have identified one case of an H3N2 variant (H3N2v) in a child who was a swine exhibitor at the recent Berrien County Youth Fair, which took place August 12-17, 2013.

The child, who was not hospitalized, is reported to have contracted H3N2v after exposure to swine at the fair. In addition, a sick pig from the fair tested positive for Influenza A H3N2 at the National Veterinary Services Laboratories in Ames, Iowa. MDCH, MDARD, and BCHD are working with the Berrien County Youth Fair (BCYF) board to reach out to swine exhibitors who attended the fair to identify additional illnesses.

The above comments from a MDCH press release describe the first H3N2v case in Michigan this year and the seventeenth 2013 case reported in the United States. The three most recent cases prior to the above case were infected by H3N2 with H1N1pdm09 PA and MP genes. The first sequence with this combination, A/Ohio/05/2013, was from an Ohio resident who had visited an agricultural fair in north western Virginia prior tp disease onset. All prior human H3N2v had a signature change at position 145 (H3 numbering) which was N145K in the intial cases in Indiana and K145R in the subsequent case that were identified prior to the Ohio/ Virginia case. A/Ohio/05/2013 had K145R. However, the next two sequences, A/Illinois/03/2013 and A/Indiana/11/2013, had an H1N1pdm09 PA gene that exactly matched each other and differed from A/Ohio/05/2013 at two positions. The Illinois and Indiana sequences had N145K.

The proximity of the Michigan fair to Indiana and Illinois locations (see map) suggests that the Michigan case will have N145K as well as H1N1pdm09 PA and MP genes.

Although the characterization sheets for the three prior cases with H1N1pdm09 PA clearly note that the cases have H1N1pdm09 MP and PA genes, the CDC has not addressed this development or the fact that none of the published swine H3N2v sequences match the most recent human sequences (the only closely related sequences are from an Illinois swine, A/swine/Illinois/A01432795/2013, which had N145K and was closely related to the initial Indiana sequences, which also did not have H1N1pdm09 PA.

The CDC update on H3N2v spread at agricultural fairs notes that H3N2v can transmit from swine to humans as well as humans to swine, but the emphasis remains on transmission from swine to humans, even though swine sequences collected prior to the start of the agricultural fair season show discordance with subsequent human sequences.

[dothedd]

Michigan H3N2v With H1N1pdm09 PA & MP
Recombinomics Commentary 23:45
September 3, 2013

The CDC has released a full set of H3N2v sequences from the Michigan case (6M) who exhibited swine at the Berrien County Fair in southwestern Michigan (see map). The case was diagnosed in Indiana and named A/Indiana/21/2013. As expected, the sequence was closely related to the three most recent sequences (A/Ohio/05/2013, A/Illinois/03/2013, A/Indiana/11/2013) and had H3 N145K as well as H1N1pm09 PA and MP gene segments.

Thus, all four of the most recent cases (with collection dates between July 21 and August 22) have an H1N1pdm09 PA gene segment which is virtually identical to each other. These four cases are linked to agricultural fairs in Virginia, Illinois, Indiana, and Michigan.

However, the CDC has not addressed in the presence of H1N1pdm09 PA gene in the four most recent cases, although its presence is noted in the characterization sheet for each of the four cases. The presence of H1N1pdm09 PA signals further human adaptation and raises concerns regarding limited surveillance and sub-typing of summer influenza A cases not linked to swine or agricultural fairs.

[dothedd]

More H3N2v Cases In Michigan With H1N1pdm09 PA & MP?
Recombinomics Commentary 17:15
September 6, 2013

One additional infection with influenza A (H3N2) variant (H3N2v) virus was reported to CDC during week 35 from Michigan. A total of 18 H3N2v cases have been reported this summer (Illinois [1], Indiana [14], Michigan [2], and Ohio [1]). So far during 2013, one person has been hospitalized as a result of H3N2v illness;

The above comments from the CDC week 35 FluView cite a second confirmed H3N2v case in Michigan. Recombinomics was referred to the Berrien County Department of Health for more information, since the second case was linked to Barrien County (see map). However, there is also appears to be an Ingham County case, so it is unclear if the second case resides in Ingham County or there are now three cases in Michigan.

The CDC has released full sequences from the first Michigan case (designated A/Indiana/21/2013 because Indiana collected the sample and made the diagnosis), which like the three prior cases had change at position 145 and had H1N1pdm09 PA and MP gene segments. The linkage to Barrien County suggests the second case in Michigan will also have H1N1pdm09 PA and MP genes, extending the number of human cases with that constellation to five (and extending the number of 2013 H3N2v cases with N145K or K145R to 18 - all cases confirmed in 2013).

The increasing number of human cases with H1N1pdm09 PA and MP genes and the absence of this constellation in H3N2v swine sequences, including collection in July, 2013, have not been addressed by the CDC.

[dothedd]

MERS Outbreak In Riyadh Military Hospital (09/12/13 01:00)

Suspect MERS Cluster In Trabzon Turkey ex-Riyadh KSA (09/10/13 23:45)

Bat Beta2c Coronavirus Recombination Signals MERS Evolution (09/10/13 07:30)

Batin KSA Camel Contact Raises Surveillance Concerns (09/10/13 03:00)

Camel MERS Antibodies Raise Surveillance Concerns (09/09/13 16:45)

www.recombinomics.com/whats_new.html

[dothedd]

Vague KSA-MoH & WHO Reports Confuse MERS Blogosphere
Recombinomics Commentary 22:00
September 14, 2013

NEJM MERS Transmission




We previously reported two cases of MERS-CoV infection in health care workers,2 one of which was fatal.

The above comment from the introduction in the New England Journal of Medicine (NEJM) paper describing mild MERS in health care workers (HCWs) in the Kingdom of Saudi Arabia (KSA) confirms the death of the HCW in critical condition in the NEJM paper on the outbreak in Al Hasa. Although this case (45M) is the first reported death of a HCW in the KSA, and was well covered in the literature (see figure above) and media reports, the failure of the KSA Ministry of Health (MoH) or WHO to re-cite his HCW status when his death was reported has caused considerable confusion in the MERS blogosphere.

The two first confirmed HCWs in KSA were reported on May 14 by the KSA-MoH, which noted that both cases were in the eastern province. The following day WHO provided additional information by noting that one case (45M) had developed symptoms on May 2 and was in critical condition, while the second HCW (43F) developed symptoms on May 8 and was in stable condition.

The confirmation of MERS in two HCW was well covered by local media, and one publication included the patient’s name (Ismail mystic), nationality (Jordanian), and location (Aramco Hospital in Dhahran).

More detail was provided by the NEJM paper on the MERS outbreak in the eastern region. The detailed report included a figure (above) on the transmission between two probable cases (index case and super spreader) as well as 23 confirmed cases (which included the two HCWs represented above by hexagons). The milder case (R infected by index case A) was listed as a 42F who developed symptoms on May 8, was hospitalized on May 12, and was discharged on May 23. The more severe case (V infected by K who was infected by F who was infected by the super spreader, C) was designated as a 45M who developed symptoms on May 2, was hospitalized on May 3, and was transferred to the ICU on May 9, where he was ventilated. When the paper went to press on May 23 he was still ventilated in the ICU. The paper also noted that he was in hospital D, which was Aramco. Also noted (in supplement) was his interaction with a probable case, which was described as “face to face contact with the symptomatic but untested relative of another case patient.”

The untested relative was described in media reports as the unconfirmed son (26M) of the index case, who was hospitalized in Aramco (with media photo). Another son (33M) of the index case was patient O, who was infected by the index case. The index case (56M, Mohammed al-Sheikh) and his two sons were well covered in local media (print, photo, and videos) as well as Reuters, which was described in ProMED.

Thus, the critical HCW was well covered by the KSA-MoH, WHO, local media, and high profile (NEJM) peer reviewed publications.

However, when the patient died, the reports by KSA-MoH and WHO did not re-cite the fact that one of the prior cases was the previously confirmed HCW. The KSA-MoH report on June 16 cited the deaths of four prior cases (and did note that two were from Taif and two were from the eastern region). The WHO report on the next day simply said that “four previously laboratory-confirmed cases have died.”

This lack of detail in the KSA-MoH and WHO reports on his death created confusion in the MERS blogosphere, but the deaths were covered in the local media, and the paper that gave details in May when the confirmed case was announced gave the same details on his death, noting his name, nationality, and hospital, as well as the fact that he was a cardiologist.

Moreover, the more recent NEJM paper (quoted above) notes that there were two confirmed HCWs in the Al Hasa outbreak and one had died. Since the earlier paper had reported the discharge of the milder case, it was clear that the more severe case (45M represented as patient V) had died.

However, more detail in KSA-MoH and WHO reports on MERS clusters, including HCWs, would be useful.

[dothedd]

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Commentary

Bisha_1 Recombinant Unwinds MERS Molecular Clock
Recombinomics Commentary 02:15
September 18, 2013

The Kingdom of Saudi Arabia Ministry of Health (KSA-MoH) has released 45 sequences (accession numbers KF600612-KF600656) from MERS cases in 2012 and 2013 (see list here), which includes 13 full sequences (each of more than 30,000 BP). The sequences reveal dramatic examples of recombination lead to rapid MERS evolution and adaption.

The earliest sequence, Bisha_1_2012, is from the first confirmed case (60M), which was also the source for EMC/12. Bisha_1/2012 was from a sample collected June 19, 2012, while EMC/12 was from a sample collected June 13, 2012. Although both samples were from the same patient and collected less than a week apart, the sequences were dramatically different. The EMC/12 sequence was the first sequence made public and was related to the sequence from the earliest sequence, which was from a nurse in Jordan, Jordan-N3. These two sequences for a distinct sub-clade that had shared polymorphisms clustered in the ORF1ab gene signaling recombination. The other public sequences were easily distinguished from this sub-clade, and these differences were used to general a molecular clock suggesting MERS was evolving quickly and had recently infected humans.

However, this type of analysis assumes that the polymorphisms are acquired at a steady rate, but the clustering suggested the differences were due to recombination and therefore not useful for calibrating a molecular clock and predicting an interspecies jump to humans. The Besha_1/2012 sequence however was closely related to the more recent sequences, suggesting the patient was infected by at least two very distinct MERS coronavirus.

Moreover, the Bisha sequence had clear evidence supporting additional recombination within this second sub-clade. The polymorphisms in the 5’ end of the genome (positions 11492-22790) had 7 polymorphisms found in England1 (from Qatari, 49M. who was transported to England by air ambulance and placed on life support for 9 months prior to death), while the 3’ end of the genome (positions 23648-29850) had 9 polymorphism found in the first four sequences from Al Hasa (Al Hasa_1, Al Hasa_2, Al Hasa_3, Al Hasa_4).

The clustering of these shared polymorphism signals evolution by homologous recombination.

However, the sequences from a case in Al Batin (Hafr-Al-Batin_1_2013), collected on June 4, 2013 had even more dramatic examples of recombination, including clustered polymorphisms from Jordan-N3 (positions 542-1833) as well as additional clusters involving polymorphisms from Al Hasa, UAE, and England 1).

The examples of extensive recombination in Al Batin, raises serious concerns about the rate of evolution involving multiple parental sequences.

[dothedd]

Riyadh_1 Recombinant Destroys MERS Molecular Clock
Recombinomics Commentary 06:45
September 18, 2013

The Kingdom of Saudi Arabia Ministry of Health (KSA-MoH) released 45 MERS-CoV sequences, including full sequences from 13 cases. One of the sequences, Bisha_1_2012 was from the same patient (60M) as the first public sequence, EMC/12. However, the two sequences were from easily distinguished sub-clades indicating the first confirmed MERS case was infected by at least two distinct MERS coronvairuses. Moreover, the Bisha_1 sequences had clear evidence for recombination, with the 5’ end donated by England1 –like parent and the 3’ end from an Al Hasa –like parent. The recombination events, as well as the clustering of polymorphisms shared by EMC/12 and Jordan-N3 in ORF1ab, signaled additional recombination which would serious damage a near term molecular clock.

Another full sequence released by KSA-MoH was Riyadh_1_2012 which was collected on October 23, which would correspond to the hospitalization date for the first reported MERS-CoV case from Riyadh, a 45M gym teacher who fully recovered (after a month in the hospital which included kidney failure and dialysis). The collection date was more than 4 months after the collection date for Bisha_1_2010 (June 19), but the more than 30,000 BP sequences were virtually identical (Riyadh_1 had A75T). This identity included a 17 BP deletion at position 26561. Thus, the identities between the two sequences from samples collected 4 months apart at well separated locations, also seriously limits the use of a molecular clock for the determination of a near term jump of MERS to humans.

Similarly, the identical cross-over points for the recombination signals clonal expansion of recombinants, which are commonly found in human MERS-CoV sequences.

[dothedd]

Extensive Recombination In Human Hafr Al Batin MERS
Recombinomics Commentary 10:00

September 18, 2013

The Kingdom of Saudi Arabia Ministry of Health (KSA-MoH) released 45 MERS-CoV sequences, including full sequences from 13 cases. The Bisha_1_2012 sequence was from the same patient (60M) as the EMC/12 sequence, but each sequence represented easily distinguished sub-clades indicating the patient was infected by two or more MERS coronaviruses.

The Bisha_1 sequence was an obvious recombinant, and the sequence was virtually identical to Riyadh_1_2012, which was collected 4 months after the Bisha case, signaling faithful replication and evolution via homologous recombination.

However, the most dramatic example of recombination was in the Hafr-Al-Batin_1_2013 sequence which was collected on June 4, 2013. The sequence had clear clustering of polymorphisms from four different parents. Positions 542-1833 had 5 polymorphisms shared with Jordan-N3. The sequence between positions 3276-19418 then switch to an Al Hasa sequence with 8 polymorphisms shared with Al Hasa 1-4. The sequence then changed again with 3 UAE polymorphisms between 20848 and 22895. The sequence then switched back to Al Hasa with 6 polymorphisms between 23648 and 24740. The 3’ end of the genome had 6 England1 polymorphisms between positions 25052 and 29853.

This switching from one human MERS parent to another across the entire genome raises concerns that the level of human MERS is markedly higher than reflected in the confirmed cases. The two distinct sequences from the first confirmed case in KSA in June, 2012 and the extensive recombination in a sequence from a June 2013 case signal rapid evolution and adaptation by human coronaviruses, which highlights the need for more active surveillance and sequences in KSA and adjacent countries.

[dothedd]

Egypt MERS Recombinant Raises Surveillance Concerns
Recombinomics Commentary 22:00

September 19, 2013

The Kingdom of Saudi Arabia Ministry of Health (KSA-MoH) has recently released 45 MERS-CoV sequences. Most were from patients in the Al Hasa outbreak (7 full sequences and 32 partial sequences from 9 additional patients), which were virtually identical to the earlier four sequences from Al Hasa. Moreover, two of the recent sequences from other locations (Riyadh_2_2012 and Buraidah_1_2013) were also related to the Al Hasa sequences.

However, the other four sequences had clear evidence of evolution via homologous recombination. Two of the sequences (Bisha_1_2012 and Riyadh_1_2012) were virtually identical to each other (differed a 1 position) and had polymorphisms shared with England1 / UAE in the 5’ end and Al Hasa polymorphisms in the 3’ end. A more complex pattern was seen in Hafr-Al-Batin_1_2013, which had clusters of polymorphism from four different parents. The fourth sequence, Riyadh_3_2013, also has clear evidence of recombination with a cluster s of polymorphisms including four (T2456A, C3320T, T4847C, and T6332C) shared with EMC_12 / Jordan-N3 , which are downstream from the four Jordan-N3 / EMC-12 polymorphisms (A542G, T623C, T1514C, C1883A) found in Hafr-Al-Batin.

Riyadh_3_2013 also has a cluster of 7 polymorphisms found in England1 / UAE (C11492T, A11534G, G19075A, C20848A, C22790T, T24299C, G24515C) with the first five of these polymorphisms also present in Riyadh_1 / Bisha_1.

Riyadh_3_2013 was from a sample collected on February 5, 2013, which corresponds to a patient (61F) who developed symptoms while traveling in Egypt, suggesting the sequences represents unreported MERS circulating in Egypt, which is supported by antibodies found in camels raised in Egypt for slaughter.

The Riyahd_3 sequence highlights the need for more aggressive MERS surveillance in countries adjacent to KSA.

[dothedd]

Recombination and 45 New MERS Sequences
Recombinomics Commentary 22:45

September 19, 2013

The Kingdom of Saudi Arabia Ministry of Health has recently released 45 MERS sequences from 21 patients. Previously, full sequences had been made public from nine patients, which included four sequences from Al Hasa (Al-Hasa 1, 2, 3, 4), which were virtually identical, confirming the clonal expansion spread of MERS in the Al Hasa outbreak (the sequences were >99.99% identical with 0-2 differences with the Al Hasa consensus). The recent sequences included seven more full sequences from Al Hasa (Al Hasa 12, 15, 16, 17, 18, 19, 21) as well as 32 partial sequences from 8 more Al Hasa patients (Al Hasa 7, 8, 9, 10, 11, 13, 14, 22), which are also virtually identical to the four Al Hasa sequences released previously.

Thus, the newly released 45 sequences had 6 new full sequences not previously represented in the public data base. Although the new sequence data sheets did not include the age and gender of the patients, the collection date and location allowed for likely assignments, which may be clarified in the upcoming paper in Lancet. Bisha_1, collected on June 19, 2012 is likely from the same patient (60M) as EMC/12 (although the two sequences were from very distinct sub-clades). Riyadh_1, collected October 23, 2012, is from the gym teacher (45M) who fully recovered (although he was hospitalized for a month and was on hemodialysis due to kidney failure). Riyadh_2, collected October 30, 2012, is likely from the fatally infected son (39M) in the first family cluster in Riyadh. Riyadh_3, collected on February 5, 2013 is likely from the fatally infected case (61F) who developed symptoms while in Egypt. Baraidah_1, collected on May 13, 2013, is from the fatally infected case (63M). Hafr-Al-Batin_1, collected on June 4, 2013, is also from a fatally infected case.

Two of the sequences (Riyadh_2_2012 and Baraidah_1) have polymorphisms that are shared with the Al-Hasa sequences. However, the other four sequences (Bisha_1_2012 and Riyadh_1_2012, which are virtually identical, Riyadh_3_2013, and Hafr-Al-Batin_1_2013, which has the most complex acquisition pattern) have clear examples of recombination.

The presence of two very distinct sequences in the first confirmed case, indicates MERS is widespread and generates dual infections, which facilitate recombination. The virtually identity in Bisha_1 and Riyadh_1, collected 4 months apart) signals high fidelity in RNA replication, supporting rapid evolutionary change via recombination. Moreover, the complex acquisition pattern in Hafr-Al-Batin indicates infections by multiple beta2c coronaviruses are common.

Thus, the recently released sequences suggests that the number of MERS-CoV infections in the Middle East is markedly higher than the modest number of confirmed cases.

[dothedd]

Curious Clade A Comments On MERS
Recombinomics Commentary 21:30

September 24, 2013

The EMC/2012 sequence was obtained after extensive cell culture passage to establish a virus isolate;26 there are 76 single nucleotide differences between EMC/2012 and the root of the clade B lineage. EMC/2012 and Jordan-N3 share 44 nucleotide changes not present in any other known MERS-CoV genome. Because of the lack of reported technical details for the Jordan sequence, the tissue culture adaptation of EMC/2012, and the shared polymorphisms despite large difference in geographical origins of clade A, we focused our analysis on sequences obtained directly from patient material, namely those in clade B. Importantly, genome Bisha_1_2012 (figure 2, in light green) was obtained with direct sequencing of nasopharyngeal swab material from the same patient reported as the source of the EMC/2012 virus (figure 2, in light green).26

The above comments from The Lancet paper on newly released MERS sequences are curious. Clade A (EMC & JOR) are easily distinguished from clade B due to the 39 polymorphisms listed below (cited as 44 polymorphisms above). Prior to the release of the new sequences in the above paper these 39 polymorphisms were limited to clade A. However, two of the newly released sequences share six of these polymorphisms, which are clustered. The Al Batin (BAT1) sequence shares 3 tightly cluster polymorphisms (A542G, T624C, T1514C), while three additional polymorphisms (T2456A, C3320T, T6632C) are shared with Riyadh_3 (RY3).

The sharing of these six polymorphisms, which were identified via direct sequencing, strongly indicates these polymorphisms are not due to tissue culture artifacts. Moreover, these shared polymorphisms cluster within the sequences listed below, and 39 clade A polymorphisms are concentrated in ORF 1a. This clustering strongly supports acquisition by recombination in areas across the Middle East.

Similarly, the Bisha sequence (BIS1) provides more evidence for widespread MERS. In it’s a clade B sequence, but was isolated from the same patient as the clade A sequence, EMC, signaling heavy concentrations of coronavirus. Moreover, BIS1 is virtually identical to Riyadh_1 (RY1) even though the samples were collected more than 4 months apart and in geographically distinct areas (and both sequences have the same 17 BP deletion).

Thus, the hard data supports a genetically distinct clade A. co-infection by clade A and B sequences, and clonal expansion over an extended time period and spread into geographically distinct area, curious comments notwithstanding.

A542G BAT1
T624C BAT1
T1514C BAT1
A2040G
T2318C
T2456A RY3
T3134C
T3277C
C3320T RY3
T3442C
A4034G
T4388G
A4995G
A4996G
A5427C
G5516A
C6059T
C6293T
T6332C RY3
T6619C
T8207C
T8258C
T8333C
C8546T
T8617C
G9516A
T10505C
T10835G
C10982T
C11984T
T12684C
A12707G
T13022C
T17794C
C18415A
T25926T
T26716C
C26806T
C28772T

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MERS Migration Into Riyadh KSA
Recombinomics Commentary 02:00
September 25, 2013


MERS Patients

Geographical locations of the ancestral viruses were co-estimated along with the phylogeny, to assess the spatial evolution of the virus. These results suggest the circulating virus in Saudi Arabia is centred around Riyadh, with sporadic excursions to other centres; the most probable geographical location for all of the internal nodes, except for the Al-Hasa outbreak, is in Riyadh

CHART ON WEBSITE:  www.recombinomics.com/News/09251301/MERS_Riyadh_Migration.html

Although the above comments are modified in the Lancet paper discussion, the evidence for Riyadh as the center of the MERS-CoV outbreak is largely lacking. Earlier commentaries, based on sequence data which included collection dates, accurately identified the three cases from Riyadh, as confirmed in the above table (also from the Lancet paper).

Riyadh_1 (RY1) was from a gym teacher (45M) who was the first confirmed case in Riyadh. His daughter had a “mild cold” and was the likely source of his infection. The RY1 sequences formed a node with Bisha_1 (BS1), which was collected from the first confirmed case in Saudi Arabia (who was co-infected with EMC/12 (EMC). The RY1 and BS1 sequences were virtually identical and both had the same 17 BP deletion, signaling clonal expansion. However, the BS1 case was infected four months prior to RY1, suggesting the sub-clade migrated to Riyadh and did not create an excursion from Riyadh, as cited above.

Riyadh_2 (RY2) was from a fatal infection of the son (39M) of the index case for the first confirmed cluster in Riyadh. RY2 formed a second node, which contained most of the clade B sequences. However, the RY2 sequence had a cluster of polymorphisms (T23648T, T23756C, C24191T, C24191T, C24251T, A24514G, G24740C, C25926T, C27092T, T29851C) that were shared with the BS1/RY1 sequences, suggesting RY2 also had origins tracing back to Bisha (home of BS1), which was due to an infection 4 months earlier, raising the possibility that RY2 also involved a parent that was involved in an excursion to Riyadh.

The Riyadh_3 (RY3) case was not detailed in a prior publication and the Lancet paper and characterization sheet withheld the patient’s age and gender, but the collection date (February 5) was during the hospitalization of another fatal case (61F) who developed symptoms while in Egypt (which is supported by a cluster of polymorphisms (T2456A, C3276A, C3320T, T6332C) shared by JOR and EMC, suggesting that RY3 also migrated to Riyadh.

Thus, while Riyadh may now have a large concentration of MERS-CoV cases, represented by the three Riyadh related nodes, these early cases appear to have origins outside of Riyadh and the diversity may be largely due to the size of the city’s population base.

Moreover, all three Riyadh sequences have clear evidence of recombination, limiting the utility of traditional phylogenetic analysis and geographic tracing.
 

[dothedd]

MERS WHO and KSA Transparency Concerns Increase
Recombinomics Commentary 23:30
September 25, 2013


MERS Patients

NOTE CHART ON WEBSITE: www.recombinomics.com/News/09251302/MERS_KSA_WHO_Transparency.html

MERS-CoV=Middle East respiratory syndrome coronavirus.
* Proportion of genome obtained compared with a full genome value of 30 119 nucleotides.
† Code used in figure 2; single letter codes refer to patients from Assiri and colleagues.16
‡ Patient described by Albarrak and colleagues.24
§ Patient described by Memish and colleagues.25
¶ Same patient providing sample for van Boheemen and colleagues.26

19 September 2013 - WHO has been informed of an additional 18 new laboratory-confirmed cases including three deaths with Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Saudi Arabia.
The patients are reported from Hafar Al-Batin, Medina and Riyadh. Their ages ranging from three to 75 years old. These cases were announced by the Ministry of Health in Saudi Arabia on 1, 5, 8, 10 and 11 September 2013.

The above table and legend (in red) and the WHO September 19 MERS-CoV update (in blue), demonstrate serious concerns about Kingdon of Saudi Arabia Ministry of Health (KSA-MoH) and WHO transparency on cases.

The KSA-MoH updates rarely give dates associated with patients, and age/gender information is uneven. In the past, WHO updates provided key pieces of information such as dates for disease onset, hospital admission, and discharge / death, in addition to age and gender. As seen in the September 19 update above, this information has been withheld for the 18 KSA cases cited.

However, as seen in the above table, the withholding of key information has been extended to peer reviewed papers, including the recent Lancet paper on sequences or the New England Journal of Medicine (NEJM) paper on the Al Hasa outbreak. The above table does not list the age and gender of the patients, which is critical for linking the cases to WHO updates. However, the initial cases in the table have been described in publications so age and gender is known for the confirmed cases in Al Hasa as well as the first confirmed case in KSA (60M in Bisha – BS1), the first confirmed case in Riyadh (45M gym teacher – RY1), and a case from the first confirmed cluster in Riyadh (39M son of index case – RY2).

However, the more recent cases are not described in publications, and identification requires matching of the sample collection date with the dates of hospitalization. This analysis indicates RY3 was from a fatal case (61M) who developed symptoms while traveling in Egypt. Although this case died in early 2013, details on travel and disease onset are lacking. However, the sequence includes clustered polymorphisms shared by sequences from Bisha (EMC) and Jordan (JOR) supporting an origin outside of Riyadh. Although this case was used to suggest that MERS was radiating out from Riyadh, the match of RY1 with BS1 and the likely origin of RY3 from Egypt impacts one of the main points of the paper (which requires some background on RY3, which was not given in the paper.

Similarly, the NEJM paper on the Al Hasa outbreak failed to give information on the probable cases, other than the two key cases (index and super spreader) and the admission dates and location (which indicated the vast majority of the probable cases were dialysis patients). The outcomes for the cases (other than the fatal outcomes for the index and super spreader), and their positions in the transmission graph, also affected interpretation of the data regarding fatality rates in these probable cases as well as the length and number of transmission chains.

The September 19 WHO report, as well as earlier reports on the Al Hasa cases which withheld age, gender, disease onset, hospital admission, and date of death or discharge further limits the analysis of the cases and clusters, and raises serious transparency concerns by KDS-MoH and WHO, which will likely increase as more pilgrims fly in and out of KSA before and after the Hajj.

[dothedd]

CDC Cites Authorization For MERS Isolation & Quarantine
Recombinomics Commentary 12:15
September 27, 2013

CDC has determined that federal isolation and quarantine are authorized for MERS-CoV under Executive Order 13295

The above comments are from today’s CDC update in the week 38 MMWR. The above executive order was put in place for the control of SARS-CoV in 2003, which is listed on the CDC page of quarantinable diseases. The determination that MERS-CoV falls under the order for SARS-CoV recognizes the similarities between the two virus and its clinical effects. SARS and MERS are beta coronaviruses (2b and 2c, respectively) and produce similar clinical presentation in older cases, especially those with underlying conditions. WHO had initially maintained that MERS was unique because of the high frequency of renal failure in initial cases. However, SARS also caused renal failure in approximately 5% of confirmed cases, which was associated with a poor prognosis.

The high frequency of renal failure in MERS was largely based on surveillance. Probable cases in Jordan were identified epidemiologically and/or via lab confirmation of MERS antibodies and none of the probable cases developed renal failure and the milder cases did not develop pneumonia. Similarly, more aggressive testing of contacts (family and health care workers) has led to PCR confirmation of cases which did not develop pneumonia or renal failure. These milder cases recovered quickly without treatment and many were asymptomatic.

However, the cases identified because of severe pneumonia with no known etiology have an case fatality rate that is higher than SARS and it is these more severe MERS cases that are likely to be subjected to the above executive order.

The latest MMWR reflects growing concerns that the upcoming Hajj may facilitate the spread of MERS to countries sending pilgrims to Saudi Arabia and many countries have increased surveillance of symptom travelers who arrive from the Middle East.

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FROM THE CDC WEBSITE:

Due to the lapse in government funding, only web sites supporting excepted functions will be updated unless otherwise funded. As a result, the information on this website may not be up to date, the transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted.

Updates regarding government operating status and resumption of normal operations can be found at www.usa.gov.

Updated Information on the Epidemiology of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Guidance for the Public, Clinicians, and Public Health Authorities, 2012–2013

Weekly
September 27, 2013 / 62(38);793-796


The Middle East respiratory syndrome coronavirus (MERS-CoV) was first reported to cause human infection in September 2012 (1). In July 2013, the World Health Organization (WHO) International Health Regulations Emergency Committee determined that MERS-CoV did not meet criteria for a "public health emergency of international concern," but was nevertheless of "serious and great concern" (2). This report summarizes epidemiologic information and provides updates to CDC guidance about patient evaluation, case definitions, travel, and infection control as of September 20, 2013.

As of September 20, 2013, a total of 130 cases from eight countries have been reported to WHO; 58 (45%) of these cases have been fatal (Figure 1). All cases have been directly or indirectly linked through travel to or residence in four countries: Saudi Arabia, Qatar, Jordan, and the United Arab Emirates (UAE) (Figure 2). The median age of persons with confirmed MERS-CoV infection is 50 years (range: 2–94 years). The male-to-female ratio is 1.6 to 1.0. Twenty-three (18%) of the cases occurred in persons who were identified as health-care workers. Although most reported cases involved severe respiratory illness requiring hospitalization, at least 27 (21%) involved mild or no symptoms. Despite evidence of person-to-person transmission, the number of contacts infected by persons with confirmed infections appears to be limited. No cases have been reported in the United States, although 82 persons from 29 states have been tested for MERS-CoV infection.

Potential animal reservoirs and mechanism(s) of transmission of MERS-CoV to humans remain unclear. A zoonotic origin for MERS-CoV was initially suggested by high genetic similarity to bat coronaviruses (3), and some recent reports have described serologic data from camels and the identification of related viruses in bats (4–6). However, more epidemiologic data linking cases to infected animals are needed to determine if a particular species is a host, a source of human infection, or both.

To date, the largest, most complete clinical case series published included 47 patients; most had fever (98%), cough (83%), and shortness of breath (72%). Many also had gastrointestinal symptoms (26% had diarrhea, and 21% had vomiting). All but two patients (96%) had one or more chronic medical conditions, including diabetes (68%), hypertension (34%), heart disease (28%), and kidney disease (49%). Thirty-four (72%) had more than one chronic condition (7). Nearly half the patients in this series were part of a health-care–associated outbreak in Al-Ahsa, Saudi Arabia (i.e., a population that would be expected to have high rates of underlying conditions) (8). Also, the prevalence of diabetes in persons aged ≥50 years in Saudi Arabia has been reported to be nearly 63% (9). It remains unclear whether persons with specific conditions are disproportionately infected with MERS-CoV or have more severe disease.

CDC Guidance

Evaluating patients. CDC has changed its guidance to indicate that testing for MERS-CoV and other respiratory pathogens* can be conducted simultaneously and that positive results for another respiratory pathogen should not necessarily preclude testing for MERS-CoV. Health-care providers in the United States should continue to evaluate patients for MERS-CoV infection if they develop fever and pneumonia or acute respiratory distress syndrome (ARDS) within 14 days after traveling from countries in or near the Arabian Peninsula.† Providers also should evaluate patients for MERS-CoV infection if they have ARDS or fever and pneumonia, and have had close contact§ with a recent traveler from this area who has fever and acute respiratory illness.

CDC continues to recommend that clusters¶ of patients with severe acute respiratory illness (e.g., fever and pneumonia requiring hospitalization) be evaluated for common respiratory pathogens and reported to local and state public health departments. If the illnesses remain unexplained, particularly if the cluster includes health-care providers, testing for MERS-CoV should be considered, in consultation with state and local health departments. In this situation, testing should be considered even for patients without travel-related exposure. Additional information about CDC's interim guidance regarding who should be evaluated for MERS-CoV infection is available at www.cdc.gov/coronavirus/mers/interim-guidance.html.

Case definitions. Although CDC has not changed the case definition of a confirmed case, confirmatory laboratory testing now requires a positive polymerase chain reaction of at least two, instead of one, specific genomic targets or a single positive target with sequencing of a second. CDC's definition of a probable case has been changed so that identification of another etiology does not exclude a person with an illness meeting this definition from being classified as having a probable case. Additional information about CDC's case definitions is available at www.cdc.gov/coronavirus/mers/case-def.html.

Travel guidance. The peak travel season to Saudi Arabia is July through November, coinciding with the religious pilgrimages of Hajj and Umrah. CDC encourages pilgrims to consider recommendations from the Saudi Arabia Ministry of Health regarding persons who should postpone their pilgrimages this year, including persons aged ≥65 years, children, pregnant women, and persons with chronic diseases, weakened immune systems, or cancer (http://www.moh.gov.sa/en/coronanew/news/pages/news-2013-7-14-001.aspxExternal Web Site Icon). WHO advises that persons with preexisting medical conditions consult a health-care provider before deciding whether to make a pilgrimage (http://www.who.int/ith/updates/20130725/enExternal Web Site Icon).

CDC continues to recommend that U.S. travelers to countries in or near the Arabian Peninsula protect themselves from respiratory diseases, including MERS-CoV, by washing their hands often and avoiding contact with persons who are ill. If travelers to the region have onset of fever with cough or shortness of breath during their trip or within 14 days of returning to the United States, they should seek medical care. They should tell their health-care provider about their recent travel. More detailed travel recommendations related to MERS-CoV are available at wwwnc.cdc.gov/travel/notices/watch/coronavirus-arabian-peninsula.

Infection control. With multiple health-care–associated clusters identified (8,10), infection control remains a primary means of preventing and controlling MERS-CoV transmission. CDC has recently made checklists available that highlight key actions that health-care providers and facilities can take to prepare for MERS-CoV patients (http://www.cdc.gov/coronavirus/mers/preparedness/index.html). CDC's infection control guidance has not changed. Standard, contact, and airborne precautions are recommended for management of hospitalized patients with known or suspected MERS-CoV infection.

CDC has determined that federal isolation and quarantine are authorized for MERS-CoV under Executive Order 13295 (http://www.cdc.gov/quarantine/aboutlawsregulationsquarantineisolation.html).** At this time, CDC is not restricting the movement of travelers with respiratory illness (that is not confirmed or probable MERS-CoV infection) arriving from the Arabian Peninsula. However, persons with illness meeting CDC's definition of a confirmed or probable case of MERS-CoV infection should remain in isolation until they are no longer considered to be contagious according to current guidance. Those who do not adhere to isolation requirements, or who intend to travel, may be subject to additional public health measures. CDC does not recommend quarantine of asymptomatic persons who were exposed to confirmed or probable cases. CDC generally recommends that persons with febrile respiratory illness delay travel until their symptoms resolve.

CDC has issued new guidance for care and management of MERS-CoV patients in the home and guidance for close contacts of these patients (http://www.cdc.gov/coronavirus/mers/hcp/home-care.html). Persons who are confirmed, or being evaluated for MERS-CoV infection, and do not require hospitalization for medical reasons should be isolated in their homes as long as the home is deemed suitable for isolation. CDC currently recommends MERS-CoV patients should be isolated at home until public health authorities or a health-care provider determine that they are no longer contagious. Persons who might have been exposed†† to MERS-CoV should be monitored for fever and respiratory symptoms for 14 days after the most recent exposure. Asymptomatic exposed persons do not need to limit their activities outside the home. If persons exposed to MERS-CoV have onset of symptoms, they should contact a health-care provider as soon as possible and follow the precautions for limiting possible exposure of other persons to MERS-CoV.

More detailed MERS-CoV–related interim guidance about patient evaluation, case definitions, travel, and infection control is available at www.cdc.gov/coronavirus/mers/index.html. This guidance might change as CDC learns more about the epidemiology of MERS-CoV. CDC will continue to post the most current information and guidance on its MERS-CoV website. State and local health departments with questions should contact the CDC Emergency Operations Center at 770-488-7100.

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Recombinomics Commentary 

THIS WEBSITE Affected by a Government Shutdown  

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What's Affected by a Government Shutdown?

Below, find an overview of some of the government services and operations that will be impacted until Congress passes a budget to fund them again. For detailed information about specific activities at Federal agencies, please see federal government contingency plans.

Vital services that ensure seniors and young children have access to healthy food and meals may not have sufficient Federal funds to serve all beneficiaries in an extended lapse.

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Work to protect consumers, ranging from child product safety to financial security to the safety of hazardous waste facilities, will cease. The EPA will halt non-essential inspections of chemical facilities and drinking water systems.

Permits and reviews for planned energy and transportations projects will stop, preventing companies from working on these projects. Loans to rural communities will be halted.

Hundreds of thousands of Federal employees including many charged with protecting us from terrorist threats, defending our borders, inspecting our food, and keeping our skies safe will work without pay until the shutdown ends.

Hundreds of thousands of additional federal workers will be immediately and indefinitely furloughed without pay.

[dothedd]

Services That Will Continue During the Government Shutdown

Social Security beneficiaries will continue receiving checks.

The U.S. Postal Service will keep delivering mail.

Active military will continue serving.

Air traffic controllers, prison guards, and border patrol agents will remain on the job.


NASA Mission Control will continue supporting astronauts serving on the Space Station.

[dothedd]

Commentary

H7N9 Case Confirmed in Shaoxing Zhejiang
Recombinomics Commentary 19:00
October 15, 2013

patients Liu XX, male, aged 35, a company employee, now living in Shaoxing County. October 8 in Shaoxing County township first diagnosed, Shaoxing, now a hospital for treatment.

the patient's condition has been severe, there has been coma, edema, pulmonary symptoms of low blood oxygen saturation. According to the history and CT changes, etc., the patient's condition and February this year he was first discovered in Shanghai Minhang H7N9 cases are very similar.

 Through to the family learned that the patient engaged in painting, copying aspects of the work, often outside the sketch.

The above translation describes the first confirmed H7N9 case in the 2013/2014 flu season in the northern hemisphere. The vast majority of prior cases were confirmed in the winter/spring of 2013 and most cases were in northern China, including the first cases in the Minhang District in Shanghai in February. As noted above the symptoms in the current case matches those observed in cases in the spring, when the largest number of confirmed cases was identified in Zhejiang province.

This case, in Shaoxing, is also in Zhejiang province, although the source of the infection is far from clear, since there is no occupational exposure.

The most recent case prior to the current case, was in Guangdong province. The full sequence, A/Guangdong/1/2013, was recently released by the Guangdong CDC. Although the N9 sequence was identical to earlier cases and the H7 was closely related, the Guangdong sequence represented a reassortant which contained four internal gene segments (PB2, PB1, NP, NS) which were most closely related to H9N2 genes from southern China (in contrast to the earlier cases which had H9N2 internal genes closely related to sequences from northern China).

Moreover, recently releases H7N9 sequences from Hunan province (A/Changsha/1/2013 and A/Changsha/2/2013) from cases from last spring have gene segments closely related to the earlier cases, including H7 Q226L. However, the PB2 sequences from these two cases do not have adaptive changes which were seen in all prior PB2 sequences from patient (which was dominated by E627K). The two Hunan sequences exactly match avian PB2 sequences at the protein level, signal additional diversity in human H7N9 sequences.

Although, H7N9 cases in the fall have been expected, the confirmation of the first cases increases concerns that many additional cases will follow in the near term.

Release of sequences from the latest case would be useful.

[dothedd]

Qatar MERS Case Raises Hajj Concerns
Recombinomics Commentary 19:15
October 17, 2013

The Supreme Council of Health said the new patient at the age of 61 years old and suffering from chronic diseases, but he did not travel outside the country in the two weeks prior to his injury, as he did not in touch Bmassaben. The council was announced on the seventh of September

The above translation describes an new MERS-CoV confirmed case (61M) in Qatar. This case follows a cluster confirmed last week which was linked to travel to Medina by the index case (59M). Although the traveler did not visit the Grand Mosque, he developed symptoms the day of his return from Medina, where multiple other cases were confirmed. Contacts of the Qatar subsequently developed symptoms in Qatar, signaling onward transmission. This cluster raised concerns that unreported cases linked the Qatari and other confirmed cases in Medina to pilgrims performing Umrah during Ramadan.

The current case raises concerns of unreported cases in Qatar as well as additional cases in pilgrims traveling from the Kingdom of Saudi Arabia in association with the Hajj, although the KSA-MoH has denied confirmation of any MERS cases in pilgrims.