dothedd
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Post by dothedd on Nov 18, 2012 15:39:49 GMT -5
Egypt H5N1 Matches In Fatal 2011 Cases Raise Concerns Recombinomics Commentary 21:30 November 15, 2012
The CDC has released a series of H5N1 sequences from cases in Egypt. Full sets of sequences were released for cases through the end of 2011. The three most recent sets were from fatal cases who died in December, 2011. The first case (F), A/Egypt/N11126/2011 was 24 weeks pregnant and developed symptoms on November 26 (which was also true for her young child, who was also H5N1 confirmed, but survived). The mother died on December 3 (the sample was collected on December 1, when the mother was admitted) and was from Dakahlia Governorate. The second fatal case (29M), A/Egypt/N11470/2011, was also from Dakahlia. He developed symptoms on December 8 and died December 19 (the sample was collected on December 15, when he was admitted). The third fatal case (42M), A/Egypt/N14976/2011, was from Menofia Governorate. He developed symptoms on December 16, and died on December 22 (the sample was collected on December 21, when he was admitted).
Although the cases were from two distinct governorates, and from cases that developed symptoms more than three weeks apart, all three sequences were virtually identical. Sequences for PA and NS were identical in all three patients. Five other genes (PB2, HA, NP, NA, MP) where identical in the two male patients, and the female sequence had one nucleotide difference in each of the five genes. The PB1 sequence was also closely related in all three cases and mapped on the same branch in phylogenetic analysis.
The near identity in all three cases (which would almost certainly be closely related to the child who was also H5N1 confirmed, raises concerns that H5N1 is evolving toward more efficient transmission in humans in Egypt. The adaptations had been noted previously, since all recent human cases have been from the same sub-clade, which has the 3 BP deletion in HA.
More information on relationships between these three cases, as well as sequences from 2012 H5N1 cases would be useful.
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dothedd
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Post by dothedd on Dec 8, 2012 12:47:46 GMT -5
Novel Beta Coronavirus HCW Clusters Raise Concerns (12/03/12 19:00) Fatal Novel Beta Coronavirus HCW Cluster In Jordan (12/03/12 10:00)More WHO Novel Beta Coronavirus Reporting Issues (12/01/12 20:30)
Week 47 Iowa H3N2v Child With No Swine Exposure (11/30/12 23:55)
Identical Novel Beta Coronavirus Sequences Signal H2H (11/30/12 21:00)
Jordan Fatal Novel Beta Coronavirus Cluster Confirms H2H (11/30/12 19:00)
WHO Corrects Novel Beta Coronavirus Guideline Errors (11/30/12 15:00)
WHO Acknowledges Milder Novel Beta Coronavirus Cases (11/29/12 23:30)
Massive H5N1 Wild Bird Outbreak In Krasnodar (11/29/12 18:15)
WHO Confirms Third Fatal Novel Beta Coronavirus Case (11/29/12 15:30)
Widespread Novel Beta Coronavirus Alerts Issued (11/29/12 02:00)
Qatar Novel Beta Coronavirus Case In Mecca For Umrah Week (11/28/12 21:15)
Novel Beta Coronavirus Mecca Linkage Raises Concerns (11/28/12 20:00)
ECDC In Denial of Novel Beta Coronavirus Human Transmission (11/27/12 22:30)
Curious Coronavirus Comments By Saudi Arabia MoH (11/26/12 23:55)
Concerns On WHO SARS-like Coronavirus Reporting Delays (11/24/12 19:15)
Media Myth On Betacoronavirus Nomenclature (11/24/12 16:30)
Disease Onset Gap Signals Betacoronavirus H2H Transmission (11/24/12 07:45)
Renal Failure In Riyadh Betacoronavirus Fatal Cluster (11/24/12 05:45)
Betacoronavirus Sequences In Saudi Arabia and Qatar Match (11/24/12 04:15)
WHO Suggests Broader Betacoronavirus Testing (11/23/12 22:00)
Betacoronavirus Cluster Raises Pandemic Concerns (11/23/12 18:30)
4th Betacornavirus Case Raises Pandemic Concerns (11/23/12 16:15)www.recombinomics.com/whats_new.html
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dothedd
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Post by dothedd on Apr 15, 2013 12:28:30 GMT -5
Beijing H7N9 Cluster Raises Pandemic Concerns Recombinomics Commentary 12:00 April 15, 2013 The boy, surnamed Zhu, was tested positive for H7N9 flu virus by the Beijing Center for Disease Control and Prevention Sunday evening.
Zhu has so far shown no flu symptoms and is receiving medical observation in Beijing Ditan Hospital.
Local health officials said a neighbor of the boy had bought chicken from the family whose seven-year-old girl became Beijing's first H7N9 case.
The carrier was discovered after local disease control authorities tested 24 people who raise poultry in a village of Cuigezhuang township, Chaoyang District.
The above comments provide information on the relationship between the first confirmed H7N9 case (7F) in Beijing, and the second (4M), who is asymptomatic. Both are being treated and/or observed in the same hospital in northeastern Beijing area (see map), further suggesting they both live in the same neighborhood. This cluster raises serious pandemic concerns.
The WHO statements on the absence of sustained H7N9 transmission is based on limited detection of H7N9 in contacts of confirmed cases. Two familial clusters in Shanghai have been acknowledged. One cluster involved the first confirmed H7N9 case (87M). Two of his sons (69M and 55M) were hospitalized for pneumonia and one, 55M, died (as did the index case). However, the two sons tested negative. The second cluster involved a husband and wife. The index case (64F) also died and her husband initially tested negative. A subsequent sample from the lower respiratory tract was positive. Both of the clusters raise serious lab detection issues. Moreover, media reports suggests that most of the contacts of confirmed cases are being monitored via phone interviews, which may not identify milder cases. Thus, the WHO claim of no sustained transmission is based on negative data generated by highly suspect methodologies.
The two cases in Beijing are relatively mild (one is asymptomatic and the other has been transferred out of the ICU). The current case fatality rate for H7N9 is 93% because 14 of the 15 outcomes of confirmed cases have been fatal. The two cases In Beijing will lower that rate when discharged, but the majority of cases have been reported as critical or severe. Moreover, the most recent death was for a case that was initially reported as stable, raising concerns that some cases WHO has classified as mild will also be fatal.
Sequences from four fatal cases have been released and all have PB2 E627K. In contrast, E627K was not found in the three avian sequences made public. However, the avian sequences have Q226L, which is a receptor binding domain change that increases affinity for receptors in the human upper respiratory tract. Thus, it is possible that some human cases have an H7N9 infection lacking E627K.
However, E627K increases the polymerase activity at lower temperatures, leading to higher levels of virus in the upper respiratory tract and the Beijing screening primarily involved samples collected from the upper respiratory tract, suggesting that the asymptomatic case described above has E627K.
Release of sequences from the Beijing cases would be useful. The presence of E627K would raise serious questions about the WHO claim of no sustained H7N9 transmission and would increase pandemic concerns.
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dothedd
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Post by dothedd on Apr 30, 2013 10:29:49 GMT -5
H7N9 Zaozhuang Shandong Cluster Raises Concerns Recombinomics Commentary 03:15 April 29, 2013 Patients Zhang, male, 36 years old, who lives in Zaozhuang City, and engaged in the work of building materials wholesale. Fever, cough 6 days, hold breath after 1 day the Zaozhuang City hospital on the evening of April 21, admitted to hospital with severe pneumonia In Shandong, experts confirmed an H7N9 bird flu case in the city of Zaozhuang on Sunday. The patient, a four-year-old boy surnamed Zhang, developed a fever on Saturday. The above translation (in red) describes the first confirmed H7N9 case (36M) in Zaozhuang, Shandong Province, who developed symptoms on April 15 (see map). The comments (in blue) describe the confirmation of H7N9 in his son (4M), who developed symptoms on April 27. The 12 day gap in disease onset dates strongly signals human to human transmission. Similar time gaps exist for family members in other H7N9 bird flu clusters, including the Minghan familial cluster where disease onset dates between son and father was 8 days (both cases died). Although the disease onset date gaps provided compelling evidence of human to human (H2H) transmission, the evidence for sustained H2H transmission is the identity in three genes found on A/Hangzhou/1/2013 and A/Jiangsu/01/2013, which included L226I
The dramatic spread of confirmed cases in recent days (see map) also supports widespread H2H transmission.
H7N9 Zaozhaung Shandong Cluster Raises Concerns (04/29/13 03:15)
H7N9 L226I Spread Raises Pandemic Concerns (04/28/13 11:30)
H7N9 Q226L Spread In Poultry and Humans (04/28/13 08:00)
H7N9 Spread To Hunan Province (04/27/13 13:30)
H7N9 Spread To Fujian Province (04/26/13 13:00)
H7N9 Spread To Nanchang Jiangxi (04/26/13 12:00)H7N9 Taiwan Case Ex-Huzhou Jiangsu (04/24/13 14:00)
H7N9 Spread To Zaozhuang Shandong Confirmed (04/24/13 08:00)
H7N9 Human PB2 Changes Raise Pandemic Concerns (04/22/13 20:00)
H7N9 Zhejiang Chicken Sequence (04/20/13 14:00)
PB2 D701N in H7N9 Zhejiang Critical Case (04/19/13 22:45)
Absence of E627K in H7N9 Zhejiang Critical Case (04/18/13 20:10)
H7N9 Minhang Familial Cluster Confirmed (04/17/13 21:00)
H7N9 Minhang Confirmed Cluster Grows To Six (04/17/13 08:30)
H7N9 Minhang Family Cluster of Three Confirmed? (04/16/13 23:30)
E627K In First Confirmed Hangzhou Case (04/15/13 19:00)
www.recombinomics.com/whats_new.html
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dothedd
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Post by dothedd on Apr 30, 2013 10:33:20 GMT -5
SORRY I DON'T HAVE TIME TO POST ALL THE IMPORTANT LINKS, BUT I HIGHLY RECOMMEND THAT WHEN YOU HAVE TIME TO PERUSE THE "WHAT'S NEW"... AND READ AT YOUR LEISURE.
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dothedd
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Post by dothedd on Apr 30, 2013 10:46:48 GMT -5
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Post by dothedd on Apr 30, 2013 10:53:28 GMT -5
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dothedd
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Post by dothedd on Apr 30, 2013 12:41:40 GMT -5
Per Dr. Niman on the recording ... Human Genetics/The Science confirm there is human-to-human spread of H7N9. By next week there will be a lot of suspect cases with all the holiday travel this week.
My recommendation is to listen to Recombinomics, Inc April 29 interview ... thing are getting out of hand in china with H7N9...
www.recombinomics.com/whats_new.html
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dothedd
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Post by dothedd on May 10, 2013 20:32:59 GMT -5
H7N9 Cluster In Fuzhou Fujian Province Grows Recombinomics Commentary 10:30 May 5, 2013
Patients Wie, male, 69 years old, Fuzhou, Fuqing City, Town farmers. April 29 patients palpitations, chest tightness reasons unknown origin "to stay at the Fujian Provincial Hospital April 30 after cardiac surgery, recurring fever accompanied by cough, lung infection after anti-infective therapy is still progress. May 2 sample and send Fuzhou Center for Disease Control detection, re-examination by the Fujian Provincial Center for Disease Control in the afternoon of May 4, report the cases of specimens of human infection of H7N9 avian influenza virus nucleic acid positive. In the evening of May 4, the provincial-level expert group based on the clinical performance, results of laboratory tests and epidemiological data, the diagnosis of human infection of H7N9 avian influenza confirmed cases. At present, the case is under active treatment. After investigation, as of the close contacts of the cases of 9, to take timely measures of medical observation, were not unusual.
Up to now, the province reported a total of four cases of human infection with the H7N9 avian influenza confirmed cases were in active treatment and no deaths. Distribution of cases (n = 3) in Fuzhou, Longyan (1) two municipalities and districts in three counties (cities, districts).
The above translation describes a new H7N9 bird flu case in Fuqing City, Fuzhou, Fujian Province, which is near two other recent cases (see map), one that was also in Fuqing City, and the other in Cangshan District, Fuzhou (click on map markers for detail). These cases, as well as the fourth case in Fujian Province, mark the leading southern spread of H7N9 (see map)..
Although the reporting of cases has slowed markedly in the past week, this change appears to be largely linked to testing / reporting. H7 was confirmed in poultry in Guangdong province, leading to extensive culling, but the announcement of the confirmation of H7N9 has been delayed. There have also been rumors that reporting of cases has been limited to two per day, and reports of spread have been banned or discouraged. Instead, emphasis has been placed on cases discharged and the absence of cases after culling.
However, the number of poultry sequences with PB2 sequences with mammalian adaptation markers at position 627 or 701 remains at 0% (0/5), while the number of PB2 human sequences with E627K or D701N remains at 100% (10/10). Moreover, the 10 human PB2 sequence from 8 patients is heavily weighted toward E627K (7 of 8 cases) signaling clonal expansion in humans, supported by identity in sequences from cases linked to Jiangsu Province, but not each other (A/Hangzhou/1/2013 and A/Jiangsu/01/2013). Thus, the role of H7N9 in poultry in any of the recent human cases remains to be demonstrated by sequence matches.
The H7N9 reporting delays and anomalies continue to increase pandemic concerns.
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dothedd
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Post by dothedd on May 11, 2013 16:46:26 GMT -5
WHO Cites Hospital Linked MERS-CoV Clusters (05/10/13 18:30)
MERS-CoV Cluster In France Increases To Four (05/10/13 12:45)
MERS-CoV Cluster In France Raises Pandemic Concerns (05/09/13 23:45)
MERS-CoV Spreads from Dubai UAE to Douai France (05/08/13 14:15)
Beta2c Coronavirus Cluster in Al Ahsa Hospital Grows (05/06/13 14:00) www.recombinomics.com/whats_new.html
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dothedd
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Post by dothedd on May 22, 2013 17:44:03 GMT -5
Fatal MERS-CoV Confirmed In Tunisia ex-KSA/Qatar (05/20/13 18:15)
MERS-CoV Fatal Infections In Children In Eastern KSA (05/16/13 23:00)
Health Care Workers MERS-CoV Confirmed In KSA (05/15/13 14:30)
Adolescent MERS-CoV Cases Raise Transparency Concerns (05/14/13 12:30)
MERS-CoV Community Transmission In Al Hofuf? (05/14/13 10:00)
MERS-CoV and SARS-CoV Similarities Raise Concerns (05/12/13 13:30)
MERS-CoV Transmission In France Confirmed (05/12/13 02:00)
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dothedd
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Post by dothedd on May 23, 2013 13:06:48 GMT -5
H7 G228S Raises H7N9 Pandemic Concerns Recombinomics Commentary 23:45 May 22, 2013
Both isolates had potentially functional amino acid sites related to mammal- or human-adapting substitution T189A, Q226L, and G228S (H3 numbering) in the receptor-binding site of hemagglutinin.
The above comments from a New England Journal of Medicine paper, Live-Animal Markets and Influenza A (H7N9) Virus Infection, cite the second key receptor binding domain change in H7, G228S in A/Nanjing/1/2013 and A/environment/Nanjing/2913/2013.
The NEJM quote is INCORRECT. The above links were activated by Genbank today and G228S is NOT present in either sequence. The combination of Q226L and G228S was present in the 1957 H2N2 pandemic and well as the 1968 H3N2 pandemic, and both changes were introduced into two of the three H5N1 bird flu transmission experiments (the other experment used N224K and Q226L and the recently released sequence, A/Shanghai/patient1/2013, has N224I and Q226L).
The appearance of these changes in H7N9 may be facilitated by the H9N2 internal genes.
However, the presence of Q226L and G228S in the above case (45F) raises serious pandemic concerns.
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dothedd
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Post by dothedd on Jun 12, 2013 18:14:34 GMT -5
26th MERS-CoV Death In KSA Raises Concerns (06/10/13 23:00)
Mild MERS-CoV Onward Transmission Raises Concerns (06/10/13 12:30)
MERS-Cov Asymptomatic Cases Raise More Testing Concerns (06/04/13 22:45)
MERS-CoV Asymptomatic Cases Raise Testing Concerns (06/04/13 15:15)
MERS-CoV Asymptomatic Health Care Workers In Italy (06/04/13 12:45)
MERS-CoV Asymptomatic Cluster In Florence Italy (06/03/13 23:00)
MERS-CoV Cluster In Italy ex-Jordan (06/01/13 16:30)
French MERS-CoV Sequences Identical To England2 (05/30/13 19:30)
MERS-CoV Morocco Case ex-Middle East (05/30/13 15:00)
Another MERS-CoV Hospital Outbreak In Eastern KSA (05/30/13 12:45)
More MERS-CoV Cases and Deaths in Eastern KSA (05/29/13 14:00)
Emergence of H7N9 R292K Tamiflu Resistance (05/28/13 18:30)
H7 G228S Raises H7N9 Pandemic Concerns NOT (05/23/13 13:30)
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dothedd
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Post by dothedd on Jun 17, 2013 17:51:49 GMT -5
MERS-CoV UAE/KSA Seqs Signal Human Transmission Evolution Recombinomics Commentary 23:45 June 12, 2013 Recently released full MERS-CoV sequences (see map) from fatal cases in the United Arab Emirates (UAE) and the Al Hasa region of the Kingdom of Saudi Arabia (KSA) fully support human transmission of the novel coronavirus in the Middle East, as well as evolution via homologous recombination. The sequence from the fatal case (73M) from Abu Dhabi, UAE (MUNICH/AbuDhabi/2013), who had links to racing camel and was transported to Munich, Germany for treatment, has been made available at the Institute for Virology in Bonn. Similarly, researchers affiliated with the KSA Ministry of Health have released four full sequences via Genbank (Al Hasa 1/2013, Al Hasa 2/2013, Al Hasa 3/2013, Al Hasa 4/2013). They are to be commended for the rapid release of these important sequences (see map for patient assignment and location).
Prior to the release of these five full sequences, similar sequences were available for four prior cases (the earliest case confirmed by PCR - 40F from ICU outbreak in Zarka – Jordan-N3/2012, the first confirmed case – 60M from Bisha – EMC/2012, the second confirmed case – 49M from Qatar ex-KSA – England1/2012, the index case for first confirmed onward transmission – 60M from England ex-KSA – England2/2012).
These four sequences were closely related to each other (>99.5% identity with consensus) and clear fell into two sub-clades due to clustered changes in the ORF-1ab gene. The two earlier sequences (Jordan-N3/EMC) formed one sub-clade, while the two more recent sequences (England1 and England2) formed a second sub-clade. The clustering of the majority of the defining polymorphisms signaled evolution via homologous recombination.
In addition to the four full sequences, partial sequences were published from four cases (first case confirmed in Riyadh -45M – Riyadh sequence, Qatari treated in Germany– 45M – Essen sequence, French tourist ex-UAE -73M - French index sequence, French hospital roommate – 51M – French contact sequence. These partial sequences (2 regions for each patient) matched the full sequences (Riyadh was identical to consensus, Essen had one polymorphisms in common with England1, French sequences matched each other and England2. Thus, the sequences from the eight prior cases fully supported MERS-CoV evolution in humans.
Human evolution was strongly supported by the five recently released full sequences.
The sequence from UAE, MUNICH/AbuDhabi/2013, is in the England1/2 sub-clade. England1 and England2 formed separate branches within this sub-clade and AbuDabi was clearly on the England1 branch. Earlier analysis had noted the importance of position 1060 in the spike protein. A Q was at position 1020 in both sequences in the Jordan/EMC sub-clade, but England1 had Q1020H while England2 had Q1020R. AbuDabi had G24515C, which encoded Q1020H and had 6 additional polymorphisms which were specific for England1. Four of these polymorphisms (G19075A, C20848A, C22790T, T24299C) clustered with G24515C in the S gene or the 3’ end of the adjacent upstream ORF 1ab gene. The other two polymorphisms (C11492T and C11534T) clustered with each. Similarly, and additional polymorphism, C24740G was also in the S gene and was shared with England1 as well as Jordan-N3, which is in the other sub-clade. The clustering of these polymorphisms as well as sharing with a different sub-clade are associated with recombination and the presence of these shared polymorphisms in human isolates supports evolution during human transmission.
Human transmission was also supported by the four sequences from Al Hasa. All four sequences were greater than 30,000 BP yet only had a single difference at most with the consensus sequence for these isolates. This level of identity signal clonal expansion and nosocomial transmission in the hospital in Al Hofuf. This cluster is similar to the ICU cluster in Jordan last year, but the Al Hasa outbreak was more lethal and more similar to SARS-CoV outbreaks in 2003.
The four Al Hasa sequences were closely related to England2 (and all had Q1020R), signaling further evolution in humans. These sequences will be described in detail in an upcoming commentary.
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Post by dothedd on Jun 17, 2013 18:03:53 GMT -5
CONTINUED:
MERS-CoV KSA Western Spread Raises Ramadan Concerns (06/15/13 12:15) MERS-CoV Nosocomial Spread In Al Hofuf KSA (06/15/13 15:45) MERS-CoV KSA Clonal Expansion Raises Concerns (06/15/13 22:45)
MERS-CoV Death Increases KSA Death Total To 29 (06/16/13 01:00) MERS-CoV Taif Death Increases KSA Death Total To 29 Recombinomics Commentary 01:00 June 16, 2013 Died today in a hospital of King Abdul Aziz Specialist Hospital in Taif Saudi elderly at the age of 65 years after being infected with the "Corona", the deceased was suffering from chronic diseases.
The sources pointed out that there are other cases infected with Corona Hospital, another Saudi woman at the age of 68 years and is currently lying in intensive care and are subject to medical follow-up
The above translation provides an update for the two recently confirmed MERS-CoV cases in Taif (see map). One case (65F) has died, increasing the death toll in the Kingdom of Saudi Arabia (KSA) to 29.
Although there are currently 46 confirmed cases, only 7 have recovered, while 10 remain hospitalized on life support. The case fatality rate (CFR) for cases with outcomes is now at 81%. This rate is markedly higher than MERS-CoV onward transmission cases outside of the Middle East. Three of the cases (1 in England and 2 in Tunisia) have recovered without treatment or hospitalization, while two in Italy recovered after a brief hospitalization. The only death had a serious underlying condition (brain tumor), and one case in France) remains hospitalized.
The dramatic difference in the CFR for cases with outcomes in the KSA, and those were infected in England, France, Tunisia, and Italy, raises concerns that KSA testing is largely focused on hospitalized cases, and milder cases, including contacts, are largely missed.
The above two cases in Taif are near Mecca and raise serious concerns about the influx of pilgrims into western KSA while performing Umrah during Ramadan, which begins July 9. Milder cases may not be detected and may spread MERS-CoV worldwide via commercial airline as was noted for exported cases in England, France, Tunisia, and Italy as well as SARS-CoV in 2003.
MERS-CoV Geographic Spread Raises Ramadan Concerns (06/16/13 23:45) MERS-CoV Geographic Spread Raises Ramandan Concerns Recombinomics Commentary 23:45 June 16, 2013 The first citizen in the eastern region at the age of 42 years and receiving treatment in the hospital and suffers from chronic asthma, and the second case of a citizen in the area of Riyadh at the age of 63 years and is receiving treatment in intensive care and suffer from multiple chronic diseases. The third case is a child in Jeddah at the age of two years, and suffers from a chronic disease of the lungs and receiving treatment in intensive care. This brings the total number of confirmed cases of 49 cases.
It also announces four deaths of previously recorded cases, including two deaths in the province of Taif and two in the eastern region
The above comments are from the Kingdom of Saudi Arabia Ministry of Health (KSA-MoH) website on MERS-CoV cases. The three new cases increase the number of confirmed cases to 49 and the four new fatalities increase the number of deaths to 32. However, there have only been 7 cases discharged, so the case fatality rate (CFR) for cases with outcomes has increased to 82%
However, the new cases have significantly increased the spread of MERS-CoV within KSA. Previously, new cases were largely limited to two nosocomial outbreaks in the eastern region. The KSA-MoH had offered assurance for pilgrims planning on performing Umrah during Ramadan, which begins July 9 because cases were in the eastern region and Mecca and Medina were in the west.
New cases unlinked to the two nosocomial outbreaks began to be announced earlier this week with a death in Hafar Al Batin which was in the eastern region, but over 200 miles northwest of the nosocomial outbreaks (see map). That case was followed by three cases much closer to Mecca. One was significantly south of Riyadh, but within Riyadh province in central KSA, while two cases were in Taif just east of Mecca (see map).
As noted above, the two recent cases in Taif have now died, but now there is a case in Jeddah, which is just west of Mecca, as well as a case in Riyadh.
Media reports raise concerns that there are many additional hospitalized cases which have not yet been confirmed. One report cited a dialysis patient in Riyadh, raising concerns of another nosocomial outbreak in Riyadh. Another report cited additional suspect cases and at least one death in Riyadh province raising concerns that there is a nosocomial infection south of Riyadh. Another media report cited 7 cases in Taif, including two health care workers (HCWs) raising concerns that there was a nosocomila outbreak ion Taif near Mecca. Yet another media report cited the death of a cardiologist in Dhahran, in eastern KSA. The reports of infections of HCWs in multiple locations associated with multiple nosocomial outbreaks have striking similarities with the spread of SARS-CoV in 2003.
Moreover, the dramatic spread of MERS raises serious concerns that the influx of pilgrims performing Unrah for Ramadan, which begins July 9 will lead to a dramatic spread of MERS-CoV worldwide.
Eight More MERS-CoV Cases Confirmed In Jordan ICU (06/17/13 23:15) MERS-CoV Taif Cluster Raises Ramandan Concerns Recombinomics Commentary 14:45 June 17, 2013 the presence of 7 cases infected with Corona in the King Abdul Aziz Specialist Hospital in Taif.
The information indicated injuring two nurses - one Filipino and one Indian - were accompanied by one of the infected cases, which was announced before yesterday, as the case died yesterday morning
The above translation cites additional suspect MERS-CoV cases in Taif, which is just east of Mecca. The Kingdom of Saudi Arabia Ministry of Health (KSA-MoH) announced two confirmed cases in Taif (65 and 68F) on June 14. WHO followed with a June 15 announcement but gave the age of one as 45M (and the other as 68F). Media reports had indicated the two cases were in separate hospitals and a follow-up report indicated the 65 year old had died, while the 68F was still in critical condition. The most recent MoH reported cited two deaths in Taif, which would have been the two confirmed cases since the number of cases in Taif did not increase.
However, media reports raised questions regarding the nationality of the Taif cases, which is likely linked to reports like the one above which noted that two health care workers (HCWs) were infected, including one from India and another from the Philippines. The report of 7 cases, including two HCWs, raises concerns that the cluster may be linked to a nosocomial outbreak similar to outbreaks cited for at least two hospitals in eastern KSA. The increasing number of hospial clusters, including infection of HCWs, has striking similaroties with the SARS coronavirus outbreaks in 2003.
Such an outbreak in hospital(s) in Taif would raise serious concerns regarding the upcoming influx of pilgrims for Ramadan, since hospitals in Taif are used to screen Mecca pilgrims. Hospitals in Jeddah are also used, but a case (2 year old) in Jeddah was cited in the latest MoH report, raising concerns that local infections will lead to nosocomial outbreaks in hospitals flanking Mecca (see map).
Audio:Apr29 May2 May16 MAP Commentary Eight More MERS-CoV Confirmed Cases In Jordan ICU Recombinomics Commentary 23:15 June 17, 2013 1 25 M 3/21 4/04 4/25 Student Deceased Confirmed 2 30 M 3/30 4/08 4/23 Apr Nurse Alive Probable 3 40 F 4/02 4/09 4/19 Nurse Deceased Confirmed 4 60 M 4/02 Refused admission – Physician,internist Alive Probable 5 29 M 4/11 4/15 4/21 Nurse Alive Probable 6 33 M 4/12 4/14 4/21 Nurse Alive Probable 7 28 M 4/13 4/17 4/21 Nurse Alive Probable 8 45 M 4/14 4/17 4/24 Road tech (brother of case 3) Alive Probable 9 46 M 4/15 4/16 4/21 Nurse Alive Probable 10 25 M 4/15 4/18 4/21 Nurse Alive Probable 11 53 M 4/18 4/21 4/23 Physician, internist Alive Probable 12 28 F 4/19 Refused admission – Nurse Alive Probable 13 60 F 4/26 5/01 5/05 Housewife (mother of case 2) Alive Probable The above list from EMRO supplement provides age, gender, and disease onset dates for the 13 confirmed or probable MERS-CoV cases linked to an ICU outbreak in Jordan over a year ago. The recent release of this data raises serious transparency issues, and confirms the clear human to human (H2H) over a year ago. The gaps in disease onset dates among the health care workers (HCWs), as well as their contacts, was expected from contemporary media reports, which described a large ICU outbreak of a SARS-like illness.
HCWs complained of a lack of protective masks, which were denied due to concerns that patients would be alarmed. The HCW concerns and complaints increased markedly when the second death was announced. The HCWs referred to the fatal cases as a student, as well as a colleague, suggesting he had a relationship with the ICU HCWs. The report describing the above case was from an epidemiological investigation that happened long after the fact, and interviews were not made with relatives of either of the confirmed / fatal cases, although the lack of use of gloves was noted (which was also due to concerns that patients would be alarmed). Similarly, the linkage of the second death to the earlier cases was denied because of cardiac involvement, which was not present in the other cases. However, they all had pneumonia, and the cases who recovered had a wide spread in hospitalization days.
The outbreak was reported by ECDC in May of 2012, which cited the death of the nurse as well as involvement of 1 doctor and 7 nurses. However, attempts to identify the etiological agents failed, and new cases were not reported after the early May case cited above, so interest waned until a novel coronavirus was identified in the fall. Retesting by NAMRU-3 confirmed MERS-CoV in the two fatal cases, but due to limited samples, the surviving cases were not confirmed. WHO issued an update and classified the cases linked to the confirmed cases as probable and noted that the infections of the two family members was likely due to human to human (H2H) transmission.
However, the number of probable cases was not released and the data displayed above was withheld. The disease onset dates clearly supported extensive H2H transmission beginning in March with the student, leading to infection of a subset of HCWs followed by a gap and a second extended wave of infections in the ICU. The length of the second wave supported infection of the later cases by the earlier cases, and the family member at the end of the transmission change represent further onward transmission. The multiple transmission events in an ICU were similar to SARS-CoV HCW outbreaks in 2003. However, this type of transmission was not described in the WHO reports, which was hidden by the withholding of the disease onset dates. Release of the above data in 2012 would have muted the various story lines claiming no H2H transmission and sporadic cases due to animal exposures.
The Jordan cluster had no linkage to animals and was clearly due to H2H transmission, although WHO has repeatedly claimed that a common source could not be excluded. However, none of the disease onset dates supported a common source other than the index case or other HCWs. Similarly, ECDC produced a risk analysis that claimed there were no mild MERS-CoV cases because all cases were sporadic and due to animal exposure. When the Jordan fatal cases were confirmed, ECDC largely ignored the probable cases, which thoroughly refuted the basic foundation of their risk analysis. They started a list of confirmed cases, which represented the Jordan outbreak with 2 fatal cases.
However recently Jordan sent to the US CDC serum samples from 124 people linked to the ICU outbreak. Media reports note that there were 8 additional positives (in addition to the 2 previously confirmed cases). The 8 newly confirmed cases include 6 who were symptomatic as well as a health care worker and a contact. Since all of the probable cases were symptomatic, it seems that the 6 cases were from the above list and the 2 asymptomatic cases would represent new cases which were neither confirmed nor probable. Alternatively, the 6 symptomatic cases may have been other patients who were not identified by the epidemiological study and the 2 cases which were HCWs or contacts were included in the above list.
Clarification of the relationship of the 8 newly confirmed cases with the probable cases listed above would be useful.
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dothedd
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Post by dothedd on Jun 19, 2013 17:07:17 GMT -5
Mild and Asymptomatic MERS-CoV Cases Confirmed Recombinomics Commentary 22:15 June 19, 2013
At least two people who were thought to have been cases in this cluster were not tested.
Of the eight newly confirmed cases, six people — all health-care workers — were known to have been sick at the time of the outbreak.
A seventh health-care worker, who had not been identified as part of the cluster at the time, tested positive. He or she reported having been sick, though not sick enough to require hospitalization,
The eighth case was a household contact of a confirmed case. When asked, the person did not recall having been sick
Testing continues on seven more individuals who are currently designated "indeterminate
The above comments provide more detail on the MERS-CoV ICU outbreak in Jordan in the spring of 2012. In addition to the 2 confirmed cases, WHO designated 11 additional cases as “probable” based on linkage to the confirmed cases and each other. Disease onset dates strongly supported transmission among the health care worker s (HCWs) as well as transmission to their contacts. 9 of the 11 probable cases were HCWs, and they represented a wide range of presentations ranging from two cases who recovered without hospitalization or treatment to severe cases who were hospitalized for approximately 1 week.
These probable cases, as well as other HCWs and contacts, were tested using new antibody tests. Two confirmed cases had not been identified previously because they had not been hospitalized and had mild or no symptoms. Six additional positives were health care workers, while seven more cases were positive on one of two antibody tests. They will be tested further and will likely be confirmed after further adjustments of the test. In addition, two of the probable cases were not tested.
It is likely that three of the seven cases who were positive on one of the antibody tests were among the probable case and the four additional patients who were positive represent more mild cases who were not hospitalized because symptoms were minimal or absent.
Thus, of the 19 cases who were confirmed (10), probable but not tested for antibodies (2), or positive on one antibody test (7), 8 recovered without hospitalization, and 2 were hospitalized for 2 or 3 days. For the 9 more serious cases, 2 died.
The results for the Jordan ICU cluster are similar to results for onward transmission cases outside of the Middle East. There have been 7 such cases reported in four countries (England, France, Tunisia, Italy). Five cases were apparently healthy when infected and all quickly recovered. Three recovered without treatment or hospitalization, while two were briefly hospitalized. They were discharged a few days after hospitalization because they were PCR negative. Thus, these milder cases were only PCR positive for a few days and if tested a few days after disease onset they would have been negative. Two of the onward transmission cases not well when infected. The fatal was had been diagnosed with a brain tumor, while the case that remains hospitalized was infected while hospitalized because of a heart attack.
The disease severity and outcomes for the Jordan ICU cluster and onward transmission cases were similar to each other, but markedly different than the confirmed cases in the Kingdom of Saudi Arabia )KSA). 32 of the 49 confirmed cases have died, and 10 more remain hospitalized. Only 7 of the 49 cases have been discharged. Thus, the case fatality rate (CFR) for KSA confirmed cases with outcomes is 82%.
These differences are related to testing. In KSA most confirmed cases were seriously ill and hospitalized when tested. Details on testing of contacts is limited, but if samples are collected after index cases are confirmed, it is likely that symptomatic contacts will have recovered and most samples will be collected at sub-optimal times (may days after disease onset) or from sub-optimal sites (upper respiratory tract), leading to false negatives for milder cases.
The confirmation of milder cases in Jordan by antibody tests as well as onward transmission cases outside of the Middle East by PCR highlights the wide range of clinical presentation of MERS-CoV infected cases and the CFR for these cases is markedly different than those reported in the KSA.
Thus, the Jordan outbreak is much like outbreaks reported for SARS coronavirus in 2003, and the CFR is similar to the 10% CFR reported for SARS-CoV.
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dothedd
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Post by dothedd on Jun 27, 2013 14:27:28 GMT -5
MERS SARS-CoV-like Outbreaks In Al Hasa Hospitals Recombinomics Commentary 04:15 June 20, 2013 Nosocomial Transmission
The above transmission map is Figure 2 from the New England Journal of Medicine paper “Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus” which details the MERS-CoV spread in Al Hasa (see map) in the Kingdom of Saudi Arabia (KSA). This large outbreak has striking similarities with SARS-CoV nosocomial outbreaks in 2003 which involve super spreaders and multiple transmission chains, which are readily seen in the above figure. Dispalyed are 23 confirmed cases, as well as two probable cases (the index case represented by dotted circle A and the super spreader represented by dotted circle C). The index case infected one of his sons (box O) and was the likely source for a health care worker (hexagon R) and the super spreader.
The super spreader infected 6 patients (circles D-I) in the dialysis unit, as well as one (J) in the ICU. Three of those infected by the super spreader were the source for two more rounds of transmission. Thus, there were three sets of H2H2H2H2H transmission chains and sequences were published from isolates from four members of these chains (patient K, A/Al Hasa 4/2013, infected doctor V, A/Al Hasa 1/2013 and both sequences were identical, while sequences from patient J, A/Al Hasa 2/2013, and patient I, A/Al Hasa 3/2013 were virtually identical).
The paper clear demonstrates multiple transmission rounds, but only describes a subset of the cases. There were 11 probable cases which were not detailed (other than the index case and super spreader) and are not included in the KSA MoH or WHO tallies. The index case was part of a 4 member family cluster, as described in multiple media reports and videos, as well as a detailed English language report, which was also carried on ProMED. The index case (56M, Mohammed al-Sheikh) was not tested, but his older son (33M) was confirmed. Another son (26M) was hospitalized and both brothers were pictured in media and video reports, including stories and videos on their discharges. A younger sister was symptomatic but tested negative and was not hospitalized. Thus, out of the four likely cases, only one was confirmed and listed in the KSA / WHO total.
The confirmed case is one of the seven discharged MERS-CoV cases in KSA, although two other family members were almost certainly infected and had mild cases. Thus, even though these were family members of the index case for this large nosocomial outbreak which was written up in NEJM spawning multiple media reports, which clearly placed MERS-CoV in the SARS-CoV threat level, only one case in the familial cluster has been confirmed.
Although the index case is listed as having acquired MERS-CoV in the community, family members cite the hospital as the origin. The levels of MERS-CoV circulating in humans is orders of magnitude higher than the confirmed cases, which is also supported by the export of cases from the Middle East to England, France, Tunisia, and Italy.
Thus, this cluster helps explain why the case fatality rate is 82% in KSA. The biased testing of hospital cases and limited detection of milder cases has produced a CFR that is markedly higher than the Jordan ICU outbreak or the onward transmission cases in England, France, Tunisia, and Italy.
Similarly, the multiple transmission chains support sustained transmission, which WHO describes as "seemingly sporadic".
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dothedd
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Post by dothedd on Jun 27, 2013 14:29:27 GMT -5
Audio:May2 May16 Jun20 MAP RSS Feed twitter News Now
Commentary
MERS SARS-CoV-like KSA Surveillance Concerns Recombinomics Commentary 15:30 June 20, 2013
Description of the Outbreak Between April 1 and May 23, 2013, a total of 23 confirmed cases of human infection with MERS-CoV were identified in the eastern province of Saudi Arabia (Fig. S1 in the Supplementary Appendix). All confirmed cases and 11 probable cases were part of a single outbreak involving four health care facilities (Figure 1)
The above comments are from a New England Journal of Medicine paper which details a nocosomial MERS-CoV outbreak involving at least four hospitals in Al Hasa in eastern Kingdom of Saudi Arabi (KSA) – see map. The detail in the paper contains many elements that are strikingly similar to nocosomial outbreaks linked to the SARS coronavirus in 2003 including infections of patients and health care workers (HCWs) by super spreaders which lead to extended transmission chains in multiple hospitals.
In the Al Hasa outbreak the index case (Patient A, 56M) is the likely source of infection of the super spreader (Patient C, 55M), who was hospitalized in an adjacent room, as well as one of his sons (patient O, 33M) and a nurse (patient R, 42F).
The super spread is the likely source for the infection of 7 patients in the dialysis unit (patient D, 59M; patient E, 24M; patient F, 87M; patient G, 77M; patient H, 62F; patient I, 58M) or ICU (patient J; 94M). Five of these seven cases were the source of onward transmission involving 13 additional confirmed cases in four different hospitals (as depicted in Figure 2).
Although the confirmed cases described above define the spread of MERS-CoV between patients and HCWs in four hospitals, there were at least 9 additional cases which were classified as probable and not lab confirmed (as indicated above). Although these cases are represented in Figure 1, which includes disease onset date and hospital, the relationship of these 9 cases with each other and the confirmed cases is far from clear, so the hospital transmission chains may be longer than represented in Figure 2 (which had three H2H2H2H2H chains).
Patients A and B are listed as cases which were infected in the community (see Figure 2 and supplement). However, both cases had been hospitalized for 4 or 6 days, respectively, prior to disease onset, suggesting that they were infected in the hospital by unknown patients or HCWs, which would have extended the hospital transmission chain.
Moreover, neither case A or C were lab confirmed, even though both infections were fatal and case A was in the ICU for 7 days after disease onset (including intubation for the final 5 days) and case C was hospitalized for 8 days after disease onset, including 5 days in the ICU where he was intubated. Thus, if these two key cases were not linked to additional pneumonia cases, it is likely that they would have never been reported, even though they were fatally infected with MERS-CoV.
In addition to the detail in the paper, more information on the index case and his older son (who was lab confirmed) were available from many media reports and videos (see CNN/Reuters clip in first 26 seconds), including an English language report covered by ProMED. The confirmed son (Hesham Mohamed Al Bin Sheik) indicated is father (the index case, Mohamed Al Sheik) was infected in the hospital and the son developed symptoms 3 days after his father’s death. A second son (Abdullah Mohamed Al Bin Sheik) also developed symptoms and was also hospitalized. Media reports included pictures of both sons in their hospital beds, as well as news conferences when each was discharged. Media reports indicated a daughter was also symptomatic, but she tested negative and recovered without hospitalization. Thus, the transmission chain was longer than the linkage between the index cases and his confirmed son, and the number of recovered cases was higher than the one confirmed case.
The older son is one of only seven confirmed MERS-CoV KSA cases who has been discharged. KSA has reported 32 deaths, which includes the vast majority of confirmed cases from the Al Hasa outbreak, which produces a case fatality rate of 82% for confirmed cases with outcomes (10 of the confirmed cases are hospitalized, but most are in critical condition and on life support). The two milder unconfirmed cases in the family of the index case would lower this rate if they were confirmed, which is also likely for additional suspect cases cited in the paper.
However, in addition to the cases in the paper, they are likely many more infected cases among the hundreds or thousands of cases which have tested negative because the collection times of the samples were sub-optimal, or collections were limited to the upper respiratory tract, where viral RNA levels may be below detection limits.
The paper clearly shows that MERS-CoV is readily transmitted to patients and HCWs and the number of infected contacts is markedly higher than the small number of confirmed cases. Many of these additional cases would be identified through antibody testing, as was seen in the Jordan ICU outbreak, which would also significantly lower the CFR, which is much higher in KSA than the Jordan ICU cluster or onward transmission cases outside of the Middle East.
The paper provides dramatic evidence for similarities between the spread of MERS-CoV and SARS-CoV in 2003, and raises serious concerns about potential infections and spread linked to Umrah associated with Ramadan beginning July 9, as well as the Hajj in KSA in October. Media Link
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dothedd
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Post by dothedd on Jun 27, 2013 14:31:45 GMT -5
MERS PCR Confirmed In Asymptomatic HCWs In Taif KSA Recombinomics Commentary 22:45 June 22, 2013
The other three cases are female health care workers aged 29, 39 and 45 from Taif governorate who cared for two previously confirmed MERS-CoV cases and were detected as part of the outbreak investigation and contact tracing. Two of these three cases were asymptomatic and all three tested weakly positive by PCR.
The above comments from the June 22 WHO update represents the first reported PCR confirmed MERS-CoV infections in asymptomatic contacts. The reporting of “weak positives” as confirmed MERS-CoV represents a sea change in MERS-CoV surveillance.
This report is likely due to a series of recent reports which highlighted serious MERS-CoV detection failures using prior approaches, and the finding of weak positives in mild or asymptomatic cases. These developments should help end media myths which overweight negatives generated by highly suspect assays and discount positives on asymptomatic contacts, such as one report that assumed the positives in Italy were false and the negatives were true, as well as another report that called the antibody positive data in asymptomatic or mild contacts in Jordan “anomalies”.
The sea change began with testing of asymptomatic contacts of the MERS-CoV index case in Italy. 8-10 contacts, including at least five health care workers gave weak PCR positives. Re-testing by a second lab, using different primers, failed to confirm the positive results, so the cases remained suspect (while at least one media report called the weak positives false).
The weak positives in Italy were followed by antibody testing of contacts linked to an ICU outbreak in Jordan in the spring of 2012. Retrospective testing confirmed MERS-CoV in the two fatal cases (one by antibody and the other by PCR and sequencing). Testing in 2012 (for SARS coronavirus and other known human respiratory viruses) had exhausted swab samples, but serum sample were collected in 124 contacts and tested with two antibody targets. This testing re-confirmed the two fatal cases as well as 8 contacts. 6 were from the testing of 9 contacts which had been classified as probable cases based on clinical presentation and contact with the two fatal cases. However two cases were confirmed who had not been previously classified as suspect because one had mild symptoms and was not hospitalized, while the other was asymptomatic. The confirmation of the asymptomatic case was the first confirmation of MERS-CoV in an asymptomatic case. Moreover, 7 additional cases tested positive with one of the two antibody test. Further refinements will likely confirm the 7 additional cases. CIDRAP called the positive antibody tests anomalies, since the cases were mild or asymptomatic.
In addition to the above positive data on mild and asymptomatic contacts, the recent New England Journal of Medicine report on the significant nosocomial outbreak in four hospitals in th eastern region of the Kingdom of Saudi Arabia highlighted detection failures in serious and fatal cases, which were classified as probable based on clinical presentation and linkage to one or more confirmed cases.
The reporting of mild PCR cases as confirmed cases may reflect a lowering of the cut-off level, or confirmation of weak positives through sequencing of inserts (both of which are long overdue). However, the PCR detection of MERS-CoV in asymptomatic contacts suggests confirmed cases will increase significantly, which will be accompanied by a drop in the case fatality rate.
These weak positives will also impact the monitoring of pilgrims coming to KSA to perform Umrah during Ramadan and demonstrate the sustain transmission of MERS-CoV in humans.
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dothedd
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Post by dothedd on Jun 27, 2013 18:05:48 GMT -5
8 MERS PCR Confirmations In Asymptomatic HCWs & Children Recombinomics Commentary 22:45 June 23, 2013
The Ministry of Health that through investigation epidemic disease virus Corona new (MERS-CoV) has been monitoring the virus in four of the contacts of confirmed cases in the areas of Riyadh and the eastern region between the ages of 7 and 15 years old, did not show them any symptoms of the disease, all in good health.
The ministry also announced monitor virus in عاملتين of صحيتين in the eastern region and Hasa and they show no symptoms also,
The above translation from the June 23 Kingdom of Saudi Arabia Ministry of Health (KSA-MoH) update describes six more asymptomatic confirmed MERS-CoV cases. Two of the cases are health care workers (HCWs) from nosocomial outbreaks in Al Hasa, as well as a second location in the eastern province. These are in addition to the two asymptomatic HCW cases in Taif, which is in the western region of KSA and adjacent to Mecca (see map). The asymptomatic cases in Taif are in addition to a mild MCW case and two fatal cases in sisters (65F and 68F) in Taif, signaling a nosocomial outbreak in the west.
In addition, the four confirmed MERS-CoV cases in asymptomatic children who are contacts of cases in Riyadh and the eastern region are the first such cases reported. The reasons for the dramatic increase in confirmed asymptomatic cases is unclear.
WHO reported the asymptomatic and mild HCW cases in Taif as “weak positives”, which was the terminology used to describe PCR positives in asymptomatic contacts in Italy, which included at least five HCWs A second lab failed to confirm the weak positives, but different primers were used, raising the possibility that the first set of primers was more sensitive, leading KSA to switch primers.
A NEJM publication of the large nosocomial outbreak in the eastern region described a super spreader and multiple long transmission chains similar to those reported for SARS coronavirus in 2003. However, the NEJM report also cited 11 probable cases who developed pneumonia and were contacts of confirmed cases but were not confirmed (either because they were not tested or tested negative one time). The failure to detect MERS included fatal cases that included the index case and the super spreader, signaling serious sensitivities issues. This may have prompted a change to more sensitive PCR primers and the detection of the asymptomatic cases.
Alternatively, the NEJM paper included full sequences of four of the nosocomial cases generated through a collaboration between the Welcome Trust and the KSA-MoH. This relationship may have led to sequencing of inserts from PCR tests which proved that the weak positives were true positives, leading to an explosion of confirmed asymptomatic cases which increased the total from 0 to 8 in the past two days.
As expected these new cases led to a plummet in the case fatality rate for cases with outcomes, which has fallen from 82% (32/39) to 63% (34/54).
More detail on KSA-MoH PCR testing would be useful.
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dothedd
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Post by dothedd on Jun 27, 2013 18:07:40 GMT -5
H3N2v Confirmed In 4 Attendees of Indiana Grant County Fair Recombinomics Commentary 02:30 June 27, 2013
State health officials are encouraging Hoosiers to take steps to protect themselves at county and 4H fairs around the state this summer following detection of four cases of variant influenza A (H3N2v). All individuals visited the Grant County Agricultural Fair, June 16-22, prior to illness, and at least two had contact with swine The above comments from the Indiana State Department of Health (ISDH) press release describe 4 confirmed cases of H3N2v in attendees of the Grant County Agricultural Fair in Marion, Indiana. H3N2v was also detected in 13 swine at the fair (see map here).
Recently the USDA released 2013 H3N2v sequences from Indiana swine with collection dates as recent as April 30. Sequences (H3, N2, MP) from six isolates (A/swine/Indiana/A01260252/2013, A/swine/Indiana/A01260254/2013, A/swine/Indiana/A01260261/2013, A/swine/Indiana/A01260276/2013, A/swine/Indiana/A01260280/2013, A/swine/Indiana/A01260284/2013) were closely related to sequences from 2012 cases, which had an N2 that was closely related to sequences ( A/West Virginia/06/2011) from a West Virginia day care center in late 2011.
That sub-clade accounted for the vast majority of human cases in 2012 (see BLASTS here).
The detection of four cases, including two without reported contact with swine, raise concerns that the number of 2013 H3N2v cases will exceed 2012. The first fair related cases in 2012 were in LaPorte, Indiana, which were reported in late July.
Release of 2013 human sequences would be useful.
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dothedd
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Post by dothedd on Jun 27, 2013 18:09:44 GMT -5
Sequence From Taiwan H6N1 Case Has G228S Recombinomics Commentary 15:15 June 27, 2013
The patient, who lives in central Taiwan and works at a breakfast shop, developed mild pneumonia in early May and was hospitalized on May 5, Yang said.
"The patient was discharged from the hospital on May 11 after recovering from her illness," Yang said.
According to Yang, the patient had never been abroad and had no history of contact with poultry.
The CDC later found that 36 people had come into contact with the patient, and four of them had flu-like symptoms.
"But after examining them, we found that none were infected with the H6N1 virus," Yang said.
The above comments describe the first reported H6N1 case (20F). Although the patient was discharged on May 11, the case was reported on May 20, so investigation of the symptomatic contacts was unlikely to yield a positive H6N1 or influenza A result, since contacts would have recovered prior to sample collection.
The Taiwan CDC recently released a full sequence, A/Taiwan/2/2013 (at GISAID from a May 7 collection), which was most closely related to chicken H6N1 sequences from Taiwan. The Taiwan CDC is to be commended for the prompt release of full sequences from this case. The sequences had some evidence of reassortment within this serotype, but in several instances the most closely related sequences were collected 8-11 years ago.
However, the Animal Health Research Institute released a full set of bird flu sequences (at GISAID) from a healthy chicken, A/chicken/Taiwan/A2837/2013, collected May 15 and they are also commended for the rapid release of these important sequences. These sequences were much more closely related to the human sequences, but some segments were still evolutionarily distant, signaling an absence of a robust database representing the human sequences.
Both sequences, as well as the most closely related sequences from earlier collections, had key H6 changes that would enhance binding to mammalian receptors in the upper respiratory tract, including the absence of a glycosylation site at position 158, and the presence of receptor binding domain changes E189V and G228S.
The presence of G228S is of concern because it was present in H2N2 in the 1957 pandemic as well as H3N2 in the 1968 pandemic and it was introduce in H5 sequences used in transmission studies. Q226L was also in the H2N2 and H3N2 pandemic sequences, as well as H7N9 sequences in human cases in the Shanghai area, and a traveler to Taiwan (represented by A/Taiwan/1/2013).
Thus, the presence of Q226L in Taiwan/1/2013 and G228S in Taiwan/2/2013 is of concern.
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dothedd
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Post by dothedd on Jun 27, 2013 18:13:29 GMT -5
NOTE: www.recombinomics.com/News/06271303/MERS_Al_Hasa_Dialysis.html ****TRANSMISSION MAP****
All Confirmed Hospitalized Al Hasa MERS-CoV Dialysis Cases Died Recombinomics Commentary 20:00 June 27, 2013
Nosocomial Transmission
The above transmission figure from the New England Journal of Medicine report on the MERS-CoV nosocomial outbreak at 4 hospitals in the Eastern Region of Saudi Arabia clearly demonstrates the role of the index case and super spreader in the infection of 23 confirmed cases. However, in addition to the 23 confirmed cases, the authors identified 11 probable cases, who were defined as pneumonia cases linked to confirmed cases, but who were not laboratory confirmed because no sample was available or only one negative test was run.
Two of the probable cases are depicted in the graph (as cases A and C), in part because of their key roles in the spread of MERS-CoV in the hospital. Case A was the index case for the outbreak. He infected his son (Case O), a health care worker (Case R), and the super spreader (case C). Case C infected 6 patients receiving dialysis (cases D-I) as well as one patient in the ICU (case J). However, the other 9 probable cases are not in the figure, even though each had pneumonia and was linked to one or more confirmed cases. The 9 probable cases were listed in Figure 1, which showed the 34 cases by disease onset dates and classified cases by location site of infection. A comparison of the cases in Figure 1 with the 25 cases in supplement Figure 2, which provided detail on the 25 cases in Figure 2, indicated that 8 of the 9 probable cases not represented in Figure 2 were dialysis patients.
The confirmed dialysis cases did not fare well. One patient had a mild case and was not hospitalized. However, all 8 of the cases who were hospitalized died. The status of patients was updated on June 12. For the 23 confirmed cases, 15 had died and 6 had been discharged (including the case who was not hospitalized). 2 cases were still hospitalized in critical condition on June 12, but have since died. The two probable cases in supplement figure 2 also died. Thus, for the 25 cases with public outcomes (23 confirmed and 2 probable - index case and super spreader), 19 died and 6 survived to produce a case fatality rate of 76%. The survivors were concentrated in the cases who were previously healthy. All three of the family members (patient M, O, and S) who were linked to three confirmed cases (patient G, S, and A) survived, as did the nurse (patient R) infected by the index case.
However, it remains unclear as to why the 11 suspect cases were not confirmed, since most were dialysis case and all eight of the confirmed dialysis cases died and the unconfirmed cases developed symptoms in the same time frame as the confirmed cases.
The dramatic spread of MERS-CoV in the Al Hasa hospitals raised concerns that more such spread would be seen, which was confirmed by reports of additional cases in the eastern region which were at unnamed hospitals in unnamed cities. More recently MERS-CoV has been confirmed in health care workers in Taif (in western KSA), as well as Riyadh (also west of the eastern region), but 4 of the health care workers (2 in Taif and 2 in Riyadh) were asymptomatic.
Thus, it is unclear why MERS-CoV was not confirmed in fatal and serious pneumonia cases in Al Hasa, but MERS-CoV was detected in asymptomatic HCWs and children in the most recent KSA reports.
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dothedd
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Post by dothedd on Jun 27, 2013 18:25:35 GMT -5
Original Article
THE NEW ENGLAND JOURNAL OF MEDICINE
Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus
Abdullah Assiri, M.D., Allison McGeer, M.D., Trish M. Perl, M.D., Connie S. Price, M.D., Abdullah A. Al Rabeeah, M.D., Derek A.T. Cummings, Ph.D., Zaki N. Alabdullatif, M.D., Maher Assad, M.D., Abdulmohsen Almulhim, M.D., Hatem Makhdoom, Ph.D., Hossam Madani, Ph.D., Rafat Alhakeem, M.D., Jaffar A. Al-Tawfiq, M.D., Matthew Cotten, Ph.D., Simon J. Watson, Ph.D., Paul Kellam, Ph.D., Alimuddin I. Zumla, M.D., and Ziad A. Memish, M.D. for the KSA MERS-CoV Investigation Team
June 19, 2013DOI: 10.1056/NEJMoa1306742 Respiratory viruses are an emerging threat to global health security and have led to worldwide epidemics with substantial morbidity, mortality, and economic consequences. Since the severe acute respiratory syndrome (SARS) pandemic in 2003–2004,1-3 two additional human coronaviruses — HKU-1 and NL-63 — have been identified, both of which cause mild respiratory infection and are distributed worldwide.4,5 In September 2012, the World Health Organization (WHO) reported two cases of severe community-acquired pneumonia caused by a novel human β-coronavirus, subsequently named the Middle East respiratory syndrome coronavirus (MERS-CoV).6-8 Since then, MERS-CoV has been identified as the cause of pneumonia in patients in Saudi Arabia,7,9 Qatar,7,10 Jordan,11,12 the United Kingdom,13,14 Germany,15 France,16 Tunisia,17 and Italy.17 Phylogenetic analysis shows that the MERS-CoV defines a novel lineage C, making this coronavirus a lineage C β-coronavirus known to infect humans.18,19
The natural host and reservoir of MERS-CoV remain unknown. We describe human-to-human transmission of MERS-CoV in a health care setting, estimate the incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission), and describe the clinical features of the disease. CONTINUED:www.nejm.org/doi/full/10.1056/NEJMoa1306742?query=featured_home
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dothedd
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Post by dothedd on Jul 18, 2013 20:53:10 GMT -5
Hancock County Indiana H3N2v Cases Acquired N145R (07/13/13 13:15)
Grant County Indiana H3N2v Cases Acquired N145K (07/12/13 22:15)MERS Confirmed In Abu Dhabi United Arab Emirates (07/12/13 15:15)WHO Acknowledges Possible Sustained MERS Transmission (07/09/13 19:45)WHO Forms MERS Emergency Committee (07/08/13 17:45)2013 H3N2v Cases Spread To Hancock County Fair In Indiana (07/04/13 21:00)
MERS-CoV Essen Sequence Matches England1 (06/29/13 01:15)
2013 Grant Co Indiana H3N2v Matches 2012 Cases & Swine (06/28/13 22:15)
2013 Grant County Indiana H3N2v Matches 2012 Cases (06/28/13 18:15)
Indiana H3N2v Outbreak Raises Concerns (06/27/13 21:30)www.recombinomics.com/whats_new.html
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dothedd
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Post by dothedd on Jul 18, 2013 20:54:34 GMT -5
Asir Mild MERS Cluster Raises Pandemic Concerns Recombinomics Commentary 16:30 July 17, 2013
The first case is for a 26-old-year Saudi male in Asir, who was in contact with one of the confirmed cases. The second case is for a 42-year-old female resident working at the health sector in Asir. Both cases have mild symptoms that not required admitting to hospital.
The above description from the Kingdom of Saudi Arabia Ministry of Health (KSA-MoH) website cites the two most recent confirmed MERS-CoV cases, a contact of a confirmed case and an associated health care worker (HCW). Both cases are mild and recovered or are recovering without treatment of hospitalization. These cases extend a recent trend in KSA of confirmation of mild or asymptomatic contacts (which frequently included HCWs) of confirmed cases which have been reported throughout KSA (see map).
This latest cluster began with a confirmed case (66M) in a military hospital in Asir (see map). Media reports noted that there were three additional suspect cases in the area, and the above report confirms MERS-CoV in two. These two confirmed cases raise the official KSA numbers to 68 confirmed and 38 fatal cases, but these numbers are largely meaningless and are used to put out press reports for media stories which grossly misrepresent the true MERS-CoV distribution in the Middle East. MERES-CoV has attainedsustain community transmission throughout the region, which strong parallels with the SARS outbreak in 2003.
An announcement by a MERS emergency committee is expected today, to attempt to restore some credibility to WHO comments on the situation (and move beyond "seemingly sporadic"). Recently WHO has acknowledged the obvious (possible sustained community transmission), but has not formally confirmed community transmission.
The latest cases support community transmission since almost all confirmed cases are associated with onward transmission, which largely involves mild symptoms in contacts. KSA acknowledged these mild cases indirectly in the spring, when they noted that most of the mild cases were in Jeddah, when the only confirmed case was the first confirmed case, who was a resident of Bisha who was diagnosed and died in Jeddah in July of 2012. The only confirmed Jeddah case since the mild cases were announced was a child (2M) in a military hospital who also died. Thus, to date there have been no confirmed mild cases in Jeddah, although the KSA-MoH was well aware of the mild cases in the spring.
The recent mild and asymptomatic cases signal earlier gaming of the system, and invalidate WHO claims of no sustained community transmission.
It will be interesting to see if the emergency committee acknowledges the sustained transmission, or merely extends the WHO fairy tale on community transmission.
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dothedd
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Post by dothedd on Jul 18, 2013 20:57:21 GMT -5
Mild UAE HCW MERS Cluster Raises Pandemic Concerns Recombinomics Commentary 19:30 July 18, 2013
In the UAE, the four cases are health care workers from two hospitals in Abu Dhabi who took care of an earlier laboratory-confirmed patient. Of these, two cases, a 28-year-old man and 30-year-old woman, did not develop symptoms of illness. The other two cases, both women of 30 and 40 years old, had mild upper respiratory symptoms and are in stable condition.
The above comments from the latest WHO MERS coronavirus update describe two more hospitals involved in onward MERS-CoV transmission. The index case (82M) was the first case identified by the United Arab Emirates, and the above cases bring the total number identified by the UAE (see map) to 5, which is in addition to the case (65M) exported to France or the case (73M) treated in Germany.
The above four confirmed cases in health care workers (HCWs) follows a report of two mild Asir cases in the Kingdom of Saudi Arabia (KSA) described yesterday and confirmed by WHO today. That cluster was in Asir and also involved a HCW, which extends a trend in onward transmission throughout KSA involving mild cases (family contacts and/or HCWs). These milder cases have a case fatality rate of zero, because many are not hospitalized, while others are briefly hospitalized until, they test negative for MERS-CoV. These cases do not develop pneumonia and are not treated.
These mild cases were initially noted by KSA officials who commented in the spring that MERS-CoV was producing flu like symptoms in cases that did not require hospitalization of treatment. Since these officials noted that most of the mild cases were in Jeddah, when no mild cases had been confirmed, the comments strongly suggested that KSA was identifying and monitoring these cases using lab results that fell shy of the WHO definition of a confirmed case. Although it was unclear if these cases were just below the official cut-off, or were not confirmed in subsequent test due to sample degradation, or more stringent testing requirements, It was clear that the cases were being lab confirmed because mild cases would share symptoms with a wide variety of respiratory infections (and these cases were not "seemingly sporadic").
When the CDC identified (via MERS-CoV antibodies) mild and asymptomatic cases in the Jordan ICU outbreak and Italy identified asymptomatic cases via aggressive PCR testing, KSA followed suit by citing mild and asymptomatic contacts of confirmed cases. Although WHO initially described these cases as “weak positives” these cases were included in the confirmed cases category, dramatically lowering the case fatality rate (CFR).
This lower CFR in previously healthy contacts (family members or HCWs) was also seen in onward transmission cases in England, Tunisia, and Italy, indicating MERS-CoV was transmitting in sustained manner by the milder cases not linked to severe hospitalized index cases. There is no ongoing surveillance for these milder cases. The mild and asymptomatic reported above are cases linked to severe cases which are identified in surveillance of hospitalized cases.
In WHO’s recent press conference, they denied knowledge of the number or significance of the mild and asymptomatic cases, and have no plans to acknowledge the sustained community transmission of MERS-CoV.
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dothedd
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Post by dothedd on Jul 30, 2013 16:57:03 GMT -5
South African Bat Beta2c Distinct From Human MERS-CoV Recombinomics Commentary 22:15 July 25, 2013
To obtain better phylogenetic resolution, we extended the 398-nt RdRp fragment generated by the screening PCR to 816 nt, as described (5). PML/2011 differed from MERS-CoV by only 1 aa exchange (0.3%) in the translated 816-nt RdRp gene fragment.
The above comments are from an EID paper describing a beta2c isolate, PML/2011/Neozul/RSA/2012, which is the bat sequence that is most closely related to human MERS-CoV sequences. Although the actual sequence at the above link has not been released, it is likely that it is marginally more related to the human sequences than the three bat sequences from Europe (UKR-G17/Pipnat/UKR/2011, 8-691/Pipnat/ROU/2009, 8-724/Pippyg/ROU/2009) based on the phylogenetic tree of a 138 nt segment from the spike gene.
There currently are nine full sequences from human MERS-CoV sequences which are closely related to each other, but are decades or centuries away from the bat sequences, including the isolate from South Africa. The human sequences form two major sub-clades composed of the 2 earliest sequences (Jordan-N3 and EMC) in one subclade and the 7 more recent sequences in a second clade, which can be further divided into two sub-grioups involving England1 and the UAE sequence on one arm, with England2 and the four sequence from Al-Hasa (Al-Hasa_1, Al-Hasa_2, Al-Hasa_3, Al-Hasa_4) on the other arm. The differences between the two subclades are clustered in the polymerase gene, signaling evolution by recombination, but all of the human sequences have an identity of at least 99.6% with the human consensus sequence, based on the nucleotide sequence.
The above comment on the South African bat sequence, like the earlier paper on the European bat sequence, largely ignores the significant nucleotide difference between the bat and human sequences and instead uses the predicted protein sequence of a highly conserved region of a highly conserved gene to highlight similarities between the bat and human fragments.
The human sequences however, demonstrate the superior value of the data provided by the nucleotide sequences, which is greater than 30,000 positions for each of the human isolates. The four Al Hasa sequences differ from each other by 3 nucleotide or less, yielding an identity greater than 99.99%. Similarly, the identities between th e 7 more recent sequences is approximately 99.9%, once again showing the strong nucleotide conservation between sequences from cases in Saudi Arabia and Qatar, while the 99.6% extends the conservation to 2012 sequences from Jordan and Saudi Arabia.
The differences between the bat and human sequences are easily seen using the short segments described in the recent papers on the bat sequences. The 816 nt segment of the polymerase gene (RdRp) described above is identical in all 7 of the most recent human sequences and has 1 difference with Jordan-N3 and 2 differences with EMC. In contrast the most closely related bat sequence, UKR-G17/Pipnat/UKR/2011, has 101 differences (87.6% identity). Similarly the spike sequence of 138 nucleotides is identical in all 9 human sequences, but there are 30 differences (78.3% identity) in the most closely bat sequence from Europe.
Although the South African sequences have not been released yet, the RdRp identity is likely to be near 90% while the spike fragment is likely to be near 80%, indicating the South African bat sequence, like the European bat sequences, is decades or centuries away from the human sequences, signaling the absence of any recent jumps to humans to produce the public MERS-CoV sequences.
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dothedd
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Post by dothedd on Jul 30, 2013 16:58:44 GMT -5
Virginia H3N2v Case Raises Concerns Recombinomics Commentary 23:30 July 26, 2013
An additional case of H3N2v infection has been confirmed in a non-Virginia resident who had close and prolonged contact with pigs at a fair in the northwest region of the state
The above comments from a Virginia Department of Health July 26 press release describe the first H3N2v case linked to a Virginia agricultural fair. The above location and exposure date correspond to the Fauquire County Fair, which ran from July 16-July 23 and is located in northwest Virginia (see map). The attendee is a resident of Ohio and was diagnosed in Ohio, so the patient is cited as an Ohio case in today’s CDC FluView and H3N2v case count. The early appearance of an H3N2v case in Virginia, coupled with the 13th 2013 H3N2v case in Indiana, raises concerns that the 2013 total may top the record number of confirmed H3N2v cases in 2012, when the first cases linked to fairs were cited exactly one year ago for the LaPorte County Fair in Indiana. It is not clear if the latest case from Indiana is again linked to that fair, but the CDC has released the sequence, A/Indiana/10/2013, from a July 16 collection, and the H3 sequence has N145R and is viritually identical to the 2013 cases linked to the Hancock County Fair (see map).
www.recombinomics.com/News/07261301/H3N2v_VA.html
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dothedd
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Post by dothedd on Aug 5, 2013 23:23:05 GMT -5
Illinois Swine H3N2v Matches Grant County Indiana Cases Recombinomics Commentary 14:45 July 27, 2013
The early appearance of H3N2v clusters in Indiana has increased concerns over the status of similar sequences in swine. The USDA has recently released sequences, and the most recent sequence (H3, N2, and MP from a June, 2013 collection), A/swine/Illinois/A01432795/2013, has N145K and is closely related to the human sequences linked to the Grant County Fair (see map).
Five sequences (A/Indiana/04/2013, A/Indiana/05/2013, A/Indiana/06/2013, A/Indiana/07/2013, A/Indiana/08/2013) were closely related to each other and human sequence from the 2012 outbreaks, but has also added H3 N145K, which was present in the Fujian strain which dominated the 2002/2003 season. The season flu was virulent and the large number of adolescent deaths led to regulations requiring the reporting of all lab confirmed adolescent flu deaths in the United States. The above human sequences were the first reported cases with N145K and the above swine sequence is the first sequence set closely related to the human sequences (Michigan swine sequence set, A/swine/Michigan/A01432678/2013, collected on May; or Iowa swine sets, A/swine/Iowa/A01432529/2013, collected in March, or A/swine/Indiana/A01432300/2013 collected in January) also have N145K and lineages matching the 2012 human cases, but are not as closely related to the 2013 human sequences as the Illinois swine). Thus, the Illinois swine sequence raises concerns that sequences similar to the Indiana sequences will be found in human cases in Illinois.
However, the human sequences in Indiana have evolved further, leading to K145R, which was present in the sequences linked to the Hancock County fair (A/Indiana/14/2013, A/Indiana/15/2013, A/Indiana/16/2013, A/Indiana/17/2013, A/Indiana/18/2013). K145R has not been reported in any of the swine sequences and raises concerns that H3N2v is adapting to humans, which could lead to a record number of cases in 2013.
This concern was increased by the report of the 13th case in Indiana, as well as the sequence of A/Indiana/10/2013, which also had K145R even though it was collected more than two weeks after the earlier sequences, and likely represents an independent outbreak (because the CDC generated a full set of original sequences).
The confirmation of H3N2v in an attendee of a Virginia County Fair (likely the Fauquire County Fair) which is the first case linked to a fair in Virginia. This case (which was reported as an Ohio case since the attendee was an Ohio resident and the patient was H3N2v confirmed in Ohio), represent another earlier case, which also signals infections outside of Indiana.
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