Live Markets & Novel Flu Risks In The United States

  

 

#10,377

 

Last week’s FluView report on 1 Novel (H3N2v) Flu Case Reported In Minnesota marked the 375th known swine variant flu infection of a human over the past decade in the United States.  As surveillance and testing is very limited, this number likely represents a small fraction of actual infections (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).

 

During the 2012 outbreak, associated with attendance of state and county fairs in the Midwest, more than 300 cases were detected.  Most were mild, and none of these viruses maintained transmission in the community (see EID Journal: H3N2v Swine To Human Transmission At Agricultural Fairs – 2012).

 

Although it hasn’t happened often - in 2009, we saw a swine-origin H1N1 virus, after kicking around in swine herds for a decade – adapt well enough to human physiology to spark the first pandemic in more than 40 years. While not a particularly severe pandemic, this event showed that pigs can generate a pandemic virus as well as birds.

While avian flu viruses are of great concern – particularly because of the observed high mortality rates in humans when infected with certain H5 and H7 strains – most of them fall between the H4 to H16 subtypes – none of which are known to have sparked a pandemic in the past.  

 

There are some who wonder  whether a non-H1, H2, or H3 virus has the `right stuff’ to spark a pandemic (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?).

 

Going back 125 years, only H1, H2 & H3 subtypes have sparked major epidemics, subtypes that typically circulate most often in humans and pigs (there are H1, H2, & H3 avian viruses as well).

125 Years of Pandemics – Credit ECDC

While this doesn’t preclude an H5 or an H7 avian virus from adapting enough to spark a pandemic, it is generally thought that novel or variant H1, H2 and H3 viruses have less of an evolutionary `leap’ to make.  Which puts pigs high on our suspect when it comes to novel flu strains.

 

Since pigs can be infected by more than one flu virus at the same time, it is also possible for two viruses to swap genetic material (reassort), resulting in a new hybrid strain. 

 

Here in North America we’ve been watching the evolution of several swine variant viruses (H1N1v, H1N2v, H3N2v) over the past few years, all of which have reassorted with - and picked up the M gene segment from – the 2009 H1N1 virus (see Keeping Our Eyes On The Prize Pig). 

 

Not only are pigs excellent hosts and `mixing vessels’ for influenza, they tend to have a fair amount of contact with humans; on the farm, at county and state fairs, and at live markets. Places where humans can either pass their flu viruses onto pigs (reverse zoonosis), or catch swine variant viruses and potentially carry them into the community.

 

Hence the development of this year;s CDC Interim Guidance for Workers who are Employed at Commercial Swine Farms: Preventing the Spread of Influenza A Viruses and last year’s  Measures to Minimize Influenza Transmission at Swine Exhibitions, 2014[189 KB, 6 pages].

 

All of which serves as prelude to a study, appearing this week in Clinical Infectious Diseases, that looks at the risks of swine variant flu transmission at live markets in the state of Minnesota.   First a link, and some excerpts from the abstract, then a look at CIDRAP’s report on this last night.

 

Live animal markets in Minnesota: a potential source for emergence of novel influenza A viruses and interspecies transmission

Mary J. Choi1,*, Montserrat Torremorell2,*, Jeff B. Bender2, Kirk Smith3, David Boxrud3, Jon R. Ertl2, My Yang2, Kamol Suwannakarn2, Duachi Her3, Jennifer Nguyen3, Timothy M. Uyeki1, Min Levine1, Stephen Lindstrom1, Jacqueline M. Katz1, Michael Jhung1, Sara Vetter3, Karen K. Wong1, Srinand Sreevatsan2, and Ruth Lynfield3

 

Abstract

(EXCERPT)

Results. Nasal swabs from 11 (65%) of 17 employees tested positive for IAVs by rRT-PCR; seven employees tested positive on multiple occasions and one employee reported influenza-like illness. Eleven (73%) of 15 employees had baseline hemagglutination-inhibition antibody titers ≥40 to swine-origin IAVs, but only one demonstrated a 4-fold titer increase to both swine-origin, and pandemic A/Mexico/4108/2009 IAVs. IAVs were isolated from swine (72/84), air (30/45) and pen railings (5/21). Whole genome sequencing of 122 IAVs isolated from swine and environmental specimens revealed multiple strains and subtype codetections. Multiple gene segment exchanges among and within subtypes were observed, resulting in new genetic constellations and reassortant viruses. Genetic sequence similarities of 99%–100% among IAVs of one market customer and swine indicated interspecies transmission.

Conclusions. At markets where swine and persons are in close contact, swine-origin IAVs are prevalent and potentially provide conditions for novel IAV emergence.

 

This summary from CIDRAP’s News scan.

 

Flu viruses found in workers, animals at fairs

(EXCERPT)

 

Researchers from the CDC and Minnesota obtained samples from two markets that were epidemiologically linked to people with infections of variant swine-origin flu. Nasal swabs from 11 of 17 employees (65%) tested positive for influenza A, and 7 tested positive multiple times. Also, 11 of 15 workers (73%) had baseline hemagglutination-inhibition antibody titers of 40 or higher to swine-origin flu, and 1 had a fourfold titer increase to both swine-origin and 2009 H1N1 flu.

In addition, influenza A viruses were isolated from 72 of 84 swine (86%), from 30 of 45 air samples (67%), and from 5 of 21 railings (24%). Whole-genome sequencing of viruses isolated from swine and environmental specimens revealed multiple strains and subtype co-detections, with multiple gene segment exchanges.

Finally, genetic sequencing of viruses from a market customer and from swine indicated pig-to-human transmission or vice versa. The authors conclude that live-animal markets may provide conditions for novel flu viruses to emerge.

(Continue . . . )

 

We’ve been fortunate that since the end of 2012 we’ve seen fewer human swine variant infections reported.   Swine viruses continue to circulate and evolve (see last year’s USDA IAV-S Surveillance Program Detects Novel H3N1 In US Swine), however, and so the threat has not gone away.

 

 

 

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WHO: World On Verge Of An Effective Ebola Vaccine

Credit WHO

 

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Fresh off of its 12:00 GMT embargo, we have an article appearing in The Lancet detailing the results of a a Phase III clinical trial of the rVSV-ZEBOV candidate Ebola vaccine - and while preliminary - the results are very encouraging.

 

Utilizing a `ring vaccination’ strategy – where relatives and neighbors of known Ebola cases are vaccinated to halt further transmission -  early results suggest a high rate of protection.  

 

Of the contacts who were vaccinated immediately after a case emerged– none developed the disease after more than 10 days post vaccination. While of contacts who received a delayed vaccination 3 weeks after the first case was detected, 16 fell ill.

 

We’ve some excerpts from the abstract and a link to a full report in The Lancet,  followed by a press release from the World Health Organization. 

 

Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial

Ana Maria Henao-Restrepo, Ira M Longini, Matthias Egger, Natalie E Dean, W John Edmunds, Anton Camacho, Miles W Carroll, Moussa Doumbia, Bertrand Draguez, Sophie Duraffour, Godwin Enwere, Rebecca Grais, Stephan Gunther, Stefanie Hossmann, Mandy Kader Kondé, Souleymane Kone, Eeva Kuisma, Myron M Levine, Sema Mandal, Gunnstein Norheim, Ximena Riveros, Aboubacar Soumah, Sven Trelle, Andrea S Vicari, Conall H Watson, Sakoba Kéïta, Marie Paule Kieny*, John-Arne Røttingen*

ABSTACT

Findings Between April 1, 2015, and July 20, 2015, 90 clusters, with a total population of 7651 people were included in the planned interim analysis. 48 of these clusters (4123 people) were randomly assigned to immediate vaccination with rVSV-ZEBOV, and 42 clusters (3528 people) were randomly assigned to delayed vaccination with rVSV-ZEBOV.

In the immediate vaccination group, there were no cases of Ebola virus disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100% (95% CI 74·7–100·0; p=0·0036). No new cases of Ebola virus disease were diagnosed in vaccinees from the immediate or delayed groups from 6 days post-vaccination.

At the  cluster level, with the inclusion of all eligible adults, vaccine effectiveness was 75·1% (95% CI –7·1 to 94·2; p=0·1791), and 76·3% (95% CI –15·5 to 95·1; p=0·3351) with the inclusion of everyone (eligible or not eligible for vaccination). 43 serious adverse events were reported; one serious adverse event was judged to be causally related to vaccination (a febrile episode in a vaccinated participant, which resolved without sequelae). Assessment of serious adverse events is ongoing.

Interpretation The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy.

 

News Release WHO/ 37
31 July 2015

World on the Verge of an Effective Ebola Vaccine

Geneva, 31 July 2015 – Results from an interim analysis of the Guinea Phase III efficacy vaccine trial show that VSV-EBOV (Merck, Sharp & Dohme) is highly effective against Ebola. The independent body of international experts - the Data and Safety Monitoring Board – that conducted the review, advised that the trial should continue. Preliminary results from analyses of these interim data are published today in the British journal The Lancet.

 
“This is an extremely promising development,” said Dr Margaret Chan, Director-General of the World Health Organization. “The credit goes to the Guinean Government, the people living in the communities and our partners in this project. An effective vaccine will be another very important tool for both current and future Ebola outbreaks.”

While the vaccine up to now shows 100% efficacy in individuals, more conclusive evidence is needed on its capacity to protect populations through what is called “herd immunity”.  To that end, the Guinean national regulatory authority and ethics review committee have approved continuation of the trial.

  
“This is Guinea’s gift to West Africa and the world,” said Dr. Sakoba Keita, Guinea’s national coordinator for the Ebola response. “The thousands of volunteers from Conakry and other areas of Lower Guinea, but also the many Guinean doctors, data managers and community mobilisers have contributed to finding a line of defence against a terrible disease.”

“The “ring” vaccination method adopted for the vaccine trial is based on the smallpox eradication strategy,” said John-Arne Røttingen, Director of the Division of Infectious Disease Control at the Norwegian Institute of Public Health and Chair of the Study Steering Group. “The premise is that by vaccinating all people who have come into contact with an infected person you create a protective “ring” and stop the virus from spreading further.  This strategy has helped us to follow the dispersed epidemic in Guinea, and will provide a way to continue this as a public health intervention in trial mode.”

The Guinea vaccination trial began in affected communities on 23 March 2015 to evaluate the efficacy, effectiveness and safety of a single dose of the vaccine VSV-EBOV by using a ring vaccination strategy.  To date, over 4 000 close contacts of almost 100 Ebola patients, including family members, neighbours, and co-workers, have voluntarily participated in the trial.

The trial stopped randomisation on 26 July to allow for all people at risk to receive the vaccine immediately, and to minimize the time necessary to gather more conclusive evidence needed for eventual licensure of the product.  Until now, 50% of the rings were vaccinated three weeks after the identification of an infected patient to provide a term of comparison with rings that were vaccinated immediately.  This now stops.  In addition, the trial will now include 13 to 17-year-old and possibly 6 to 12-year-old children on the basis of new evidence of the vaccine’s safety.

“In parallel with the ring vaccination we are also conducting a trial of the same vaccine on frontline workers,” said Bertrand Draguez, Medical Director at Médecins sans Frontières.  “These people have worked tirelessly and put their lives at risk every day to take care of sick people.  If the vaccine is effective, then we are already protecting them from the virus.  With such high efficacy, all affected countries should immediately start and multiply ring vaccinations to break chains of transmission and vaccinate all frontline workers to protect them. ”

The trial is being implemented by the Guinean authorities, WHO, Médecins sans Frontières (MSF) and the Norwegian Institute of Public Health, with support from a broad partnership of international and national organizations.

“This is a remarkable result which shows the power of equitable international partnerships and flexibility,” said Jeremy Farrar, Director of the Wellcome Trust, one of the funders of the trial. “This partnership also shows that such critical work is possible in the midst of a terrible epidemic. It should change how the world responds to such emerging infectious disease threats. We, and all our partners, remain fully committed to giving the world a safe and effective vaccine. ”

“This record-breaking work marks a turning point in the history of health R&D,” said Assistant Director-General Marie-Paule Kieny, who leads the Ebola Research and Development effort at WHO.  “We now know that the urgency of saving lives can accelerate R&D.  We will harness this positive experience to develop a global R&D preparedness framework so that if another major disease outbreak ever happens again, for any disease, the world can act quickly and efficiently to develop and use medical tools and prevent a large-scale tragedy.”

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USGS: New Madrid Simulation Shows Risks For Memphis & Little Rock

Seismic Hazard Map – Credit USGS

 

#10,375

 

In 2011 – during the bicentennial of the four great New Madrid earthquakes of 1811-12 – FEMA and other federal agencies mounted the largest National Level Exercise (NLE) to that date, revolving around a catastrophic earthquake occurring in the New Madrid Seismic Zone (NMSZ) that would involve eight Central U.S. States: Alabama, Arkansas, Kentucky, Illinois, Indiana, Mississippi, Missouri, and Tennessee spread across 4 FEMA regions (IV, V, VI, and VII).

 

While sparsely populated 200 years ago during the last big seismic event, a similar quake today would endanger millions of people living in the central United States, and likely cause severe economic and social disruption across an even wider area of the nation.

 

This National Level Exercise tested initial incident response along with disaster recovery plans. According to FEMA’s NLE fact sheet, the exercise was designed to validate the following capabilities:

• Communications
• Critical resource logistics and distribution
• Mass care (sheltering, feeding and related services)
• Medical surge
• Citizen evacuation and shelter-in-place
• Emergency public information and warning
• Emergency operations center (EOC) management
• Long term recovery

 

While large quakes in the middle of the country are rare, the USGS, in Earthquake Hazard in the New Madrid Seismic Zone Remains a Concern, warns:

Continuing Preparedness Needed

The geologic record of repeated large earthquakes, the historical accounts of the 1811–12 large earthquakes, and the continuing earthquake activity in the area are compelling evidence that the New Madrid region has high earthquake hazard. The preponderance of evidence leads us to conclude that earthquakes can be expected in the future as frequently and as severely as in the past 4,500 years. Such high hazard requires prudent measures such as adequate building codes to protect public safety and ensure the social and economic resilience of the region to future earthquakes.

 

Complicating matters, earthquakes in the central and eastern part of the nation are generally felt over a much wider area than those on the west coast, due to differences in their underlying bedrock.  In 2012’s USGS: Eastern Earthquakes - Rare But Powerful, we looked at this phenomenon.

 

The following shake map from the USGS shows the areas reporting shaking from two recent quakes, a 6.0 in Central California, and the recent 5.8 Virginia quake. By an incredibly large margin, the smaller eastern quake was felt over a much bigger area.

 

All of which serves as prelude to yesterday’s release from the USGS that shows that computer simulations indicate a future New Madrid quake could produce major, prolonged ground shaking in metropolitan areas across several states, including Memphis, TN, Paducah, KY, Evansville, IN, and Little Rock, AR.

 

New Simulations of 1811-1812 New Madrid Earthquakes Show Strong and Prolonged Ground Shaking in Memphis and Little Rock

Released: 7/30/2015 2:00:00 PM

Computer simulations of earthquake shaking, replicating the quakes that occurred in 1811-1812 in the New Madrid seismic zone (NMSZ), indicate that future large earthquakes there would produce major, prolonged ground shaking. The 1811-1812 events were some of the largest in the United States since its settlement by Europeans, and the NMSZ spans portions of seven states: Illinois, Indiana, Missouri, Arkansas, Kentucky, Tennessee and Mississippi.

Scientists from the Universidad Nacional Autónoma de México, the U.S. Geological Survey, San Diego State University, AECOM (formerly URS Corporation), and the University of Memphis simulated a set of 20 hypothetical, yet plausible earthquakes located along two currently active faults in the NMSZ. The hypothetical earthquake scenarios range in magnitude from 7.0 to 7.7, and consider various possible epicenters.

”Based on our simulations, were the 1811-1812 earthquakes to repeat today, more than 8 million people living and working near the New Madrid seismic zone would experience potentially damaging ground shaking at modified Mercalli intensities ranging from VI to VIII,” said Leonardo Ramirez-Guzman, lead author of the paper that appears in the July 30 edition of the Bulletin of the Seismological Society of America.

“Strong ground shaking in the greater Memphis metropolitan area could last from 30 seconds to more than 60 seconds, depending on the magnitude and epicenter of a potential seismic event,” said Ramirez-Guzman, a professor at Universidad Nacional Autónoma de México and former USGS contract scientist.

The simulations also demonstrate the importance of fault rupture directivity (seismic energy focused along the direction of faulting), especially when combined with the wave channeling effects of the Reelfoot rift, a buried, northeast-southwest trending geologic valley in the NMSZ. In particular, future large earthquakes on the approximately 80-mile long NMSZ fault show strong shaking at vibration frequencies that pose a risk for mid-rise to high-rise buildings and tall bridges. This fault is thought to be responsible for the December 16, 1811 magnitude 7-7.7 earthquake. Some of the earthquake simulations showed strong shaking focused to the northeast as far as 100-200 miles away near Paducah, Kentucky and Evansville, Indiana, and to the southwest 150 miles toward Little Rock, Arkansas. An example of this earthquake shaking focusing effect can be seen here.

While it’s not possible to know which direction a fault will rupture once an earthquake starts, knowing that there is an increased chance of strong shaking along these geologically-defined corridors is a valuable aid in better characterizing seismic hazard and minimizing earthquake risk.

Earthquakes pose a significant risk to nearly 150 million Americans. The USGS and its partners in the multi-agency National Earthquake Hazard Reduction Program are working to improve earthquake monitoring and reporting capabilities via the USGS Advanced National Seismic System (ANSS). More information about ANSS can be found on the ANSS website.

Peak ground-motion variability for a magnitude 7.7 earthquake. Warmer colors indicate stronger ground motions. The stronger ground motions are extended further northeast and southwest caused by the channeling effect of the Reelfoot rift (RFR) The fault is displayed as a thick black continuous straight line, with the epicenter indicated by the triangle. (high resolution image 1.3 MB)

 

From my 10 years of living in the mostly rural Bootheel of Missouri, I know that most local residents are aware of the seismic history of the region, and are – in general – a fairly resilient lot.  As farmers and ranchers, they tend to be a bit more self sufficient than those who live in surrounding cities.

But as mentioned above, a rupture of the New Madrid fault could have serious effects on cities 100-200 miles away.

 

Areas where millions of people live and work in structures that were not designed with earthquake safety in mind, and where severe disruptions of essential services (water, power, EMS) – particularly during the winter – could make life extremely difficult.

 

All of which makes participating in this year’s Great Central U.S. Shakeout, and preparing your home and family for an earthquake, all the more important.  Those who live in other seismically active regions (worldwide) will want to visit Shakeout.org for information on your region’s activities.

 

 

For more recent blogs on earthquakes, and earthquake preparedness, you may wish to revisit:

 

OSU: Pragmatic Action - Not Fatalism - In Order To Survive The `Big One’

Shakeout.Org Twitter Chat On Earthquake Preparedness

USGS/OGS Joint Statement On Increased Earthquake Threat To Oklahoma

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Defra: Preliminary Analysis Of Germany’s HPAI H7N7 Outbreak

Credit Defra 

 

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The announcement earlier this week of highly pathogenic H7N7 Reported At Emsland Poultry Farm comes on the heels of several low path (LPAI) H7N7 detections in recent months in Germany, the Netherlands, and the UK. Of particular interest, this latest HPAI outbreak was detected less than a kilometer away from a farm that had reported LPAI H7N7 less than 3 weeks ago.

 

LPAI H7 viruses are often found in wild and migratory birds, and are viewed as the principal vector of the virus to domesticated poultry. 

 

The concern with these LPAI H5 and H7 viruses is that when they are not controlled - they have the potential to mutate into highly pathogenic strains. HPAI viruses have been generated in the lab by repeated passage of LPAI viruses through chickens (cite FAO) but exactly how and why this occurs naturally is poorly understood (see JVI  Emergence of a Highly Pathogenic Avian Influenza Virus from a Low Pathogenic Progenitor). .

While it hasn’t been documented often, the risk is considered great enough that all LPAI H5 and H7 outbreaks must be reported to the OIE, and immediate steps must be taken to contain and eradicate the virus. 

 

All of which brings us to a Defra preliminary analysis of last week’s HPAI H7N7 outbreak, that has buried in it sneak peek from a yet-to-be published report about the UK’s  most recent HPAI H7N7 outbreak.

 

. . on the 6th July, the UK reported an outbreak of H7N7 HPAI in laying hens. Investigations into this outbreak have revealed a mutation event occurred within the poultry premises, following an incursion of LPAI. The most likely source of infection was contact with wild birds, given the presence on the farm of nesting wild waterfowl and two ponds

 

As this report points out, this is a rare event:

 

In the last 10 years, there have been only four such documented events of mutation from LPAI to HPAI occurring all within chicken layers in Europe: UK in 2008, Spain in 2009 (SCoFCAH, 2010), Italy in 2013 and UK in 2015; all involved H7N7.

The question –  still under investigation - is whether this latest HPAI H7N7 outbreak in Germany has any connection with the LPAI outbreak earlier this month on a farm a kilometer away.  

 

If it turns out to be true - and we have really had two such `rare’ events in the span of a couple of weeks - it then begs the question as to whether these sorts of LPAI to HPAI `conversions’ are becoming more common . . .and why?.

 

 

Preliminary Outbreak Assessment
Highly Pathogenic Avian Influenza H7N7 in poultry in Germany

29 July 2015 Ref: VITT/1200 HPAI H7N7 in Germany

Disease Report Germany has reported an outbreak of highly pathogenic avian influenza, H7N7 in poultry in North West Germany (Lower Saxony) (European Commission, 2015; OIE, 2015). The holding was comprised of over 10,000 laying hens and clinical signs were first reported on 24/7/2015. Disease control measures are in place, including 3km and 10km protection and surveillance zones in line with Directive 2005/94/EC. The birds have been depopulated.

The outbreak was located less that 1km from a premises which had reported H7N7 LPAI on June 11th 2015 and this new IP tested negative in the course of disease investigations into LPAI. Further analyses may reveal the relationship if any between the two events.

Situation assessment In the last few months there have been several reported outbreaks of H7N7 avian influenza viruses in poultry in Europe. The UK had a low pathogenicity strain in February, Netherlands had two outbreaks of LPAI in March and April while Germany had two outbreaks of LPAI in both March and June. The June outbreak in Germany was in the same region as the latest HPAI incident.

Meanwhile on the 6th July, the UK reported an outbreak of H7N7 HPAI in laying hens. Investigations into this outbreak have revealed a mutation event occurred within the poultry premises, following an incursion of LPAI. The most likely source of infection was contact with wild birds, given the presence on the farm of nesting wild waterfowl and two ponds. The full epidemiology report will be available soon at www.gov.uk

It is of no surprise that H7 LPAI viruses have been detected this year, as these viruses are continually circulating in wild waterfowl and therefore there is a constant low risk of incursion of these viruses into poultry. However, the mutation of LPAI to HPAI viruses is a rare event.

Several factors may drive these mutation events: a “jump” from Anseriform birds into Galliform poultry; adaptation to Galliform poultry; repeated passage through the poultry; spread within the poultry (free range birds as opposed to caged birds where mixing between birds is reduced) that acquire LPAI virus immunity that then acts to exert selective pressure and possibly the age of the birds.

In the last 10 years, there have been only four such documented events of mutation from LPAI to HPAI  ccurring all within chicken layers in Europe: UK in 2008, Spain in 2009 (SCoFCAH, 2010), Italy in 2013 and UK in 2015; all involved H7N7. In the case of the UK mutation event in 2008, mallard ducks present at the premises and in contact with free range laying hens seemed to be the source for the LPAI incursion with subsequent mutation following sustained transmission within the flock. In Spain, the incursion of LPAI was believed to be from wild waterfowl on a nearby reservoir which was the water source for the farm and the mutation consequently occurred in one of four sheds of laying hens (SCoFCAH, 2010). In Italy the virus was introduced to free range hens as LPAI and mutated to HPAI during transmission within the flock.

It remains to be seen if the same event has occurred in Germany, but given the circulation of LPAI demonstrated recently, this would seem highly probable. Surveillance sampling in the event of an outbreak only gives a level of confidence for finding over a certain prevalence, therefore occasionally there may be a possibility that additional cases which have gone undetected if incursion at the time of sampling is relatively new.

(Continue . . . )

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WHO MERS Update – Saudi Arabia July 29th

 

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The World Health Organization has published a new MERS update describing eight recent MERS cases, and their likely route of infection (if known).  All but one are from Riyadh City (#8 is from Hofuf), and three of the cases are listed as contacts or family members of known cases.  A fourth case (#3) is listed as a possible nosocomial infection.

Possible camel exposure is cited for three cases (including the Hofuf case), although only one case is listed as having actual camel contact.

 

Although it may well be probative, exposure to camels or camel products in the 14 days prior to onset of illness does not automatically lock that in as the actual source of infection. Despite growing Evidence for Camel-to-Human MERS-CoV Transmission, how often that actually happens is unknown.

 

Previously, we’ve seen estimates that only 3% of cases are caused by direct zoonotic infection (see Dr. Tariq Madani: 97% Of MERS Cases From Human-to-Human Transmission).Assumptions and numbers that must be taken with a sizable grain of salt, as we’ve yet to see the kind of case-control study to support them.

 

While repeated promises have been made regarding this type of study (see KSA Announces Start To Long-Awaited MERS Case Control Study), for whatever reason, we’ve yet to see the results.

 

Last May, in WHO EMRO: Scientific Meeting Reviews MERS Progress & Knowledge Gaps we examined some of the glaring deficits in our understanding of this disease, a full three years after it first emerged in a Jordanian hospital.

 

Here then is the latest WHO update:

 

Middle East Respiratory Syndrome coronavirus (MERS-CoV) – Saudi Arabia

Disease outbreak news
29 July 2015

Between 16 and 25 July 2015, the National IHR Focal Point for the Kingdom of Saudi Arabia notified WHO of 8 additional cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including 1 death.

Details of the cases

• A 30-year-old male from Riyadh city developed symptoms on 22 July and was admitted to the hospital on the same day. The patient, who has no comorbidities, tested positive for MERS-CoV on 24 July. Currently, he is in stable condition in a negative pressure isolation room on a ward. The patient is a contact of a laboratory-confirmed MERS-CoV case (case n. 7 - see below). Investigation of history of exposure to other known risk factors in the 14 days prior to the onset of symptoms is ongoing.
• A 28-year-old, non-national male from Riyadh city developed symptoms on 22 July and was admitted to the hospital on 23 July. The patient, who has no comorbidities, tested positive for MERS-CoV on 24 July. Currently, he is in stable condition in a negative pressure room. The patient is a contact of a laboratory-confirmed MERS-CoV case (case n. 7 - see below). He has no history of dealing with or consumption raw camel meat. Investigation of history of exposure to other known risk factors in the 14 days prior to the onset of symptoms is ongoing.
• A 54-year-old, non-national male from Riyadh city developed symptoms on 20 July while admitted to hospital since 20 July due to unrelated chronic medical conditions. He tested positive for MERS-CoV on 22 July. Currently, the patient is in critical condition in ICU. Investigation of possible epidemiological links with laboratory-confirmed MERS-CoV cases who were hospitalized in the same hospital (case n. 5 – see below; case n. 2 – see DON published on 24 July) or with shared health care workers is ongoing.
• A 52-year-old female from Riyadh city developed symptoms on 17 July and was admitted to hospital on the same day. The patient, who had comorbidities, tested positive for MERS-CoV on 21 July and passed away on 22 July. She was a family member of a laboratory-confirmed MERS-CoV case (case n. 5 – see below).
• A 56-year-old male from Riyadh city developed symptoms on 13 July and was admitted to hospital on 15 July. The patient, who has comorbidities, tested positive for MERS-CoV on 19 July. Currently, he is in critical condition in ICU. The patient has a history of frequent contact with camels and consumption of their raw milk.
• A 60-year-old female from Raniah city developed symptoms on 12 July and was admitted to hospital on 19 July. The patient, who has comorbidities, tested positive for MERS-CoV on 21 July. Currently, she is in stable condition in a negative pressure isolation room on a ward. The patient lives in an area with several camel farms; however, she has no history of contact with camels or consumption of raw camel products. Investigation of history of exposure to other known risk factors in the 14 days prior to the onset of symptoms is ongoing.
• A 32-year-old, non-national male from Riyadh city developed symptoms on 15 July and was admitted to hospital on 19 July. The patient, who has no comorbidities, tested positive for MERS-CoV on 20 July. Currently, he is in critical condition in ICU. Investigation of history of exposure to known risk factors in the 14 days prior to the onset of symptoms is ongoing.
• A 93-year-old male from Hofuf city developed symptoms on 12 July and was admitted to hospital on the same day. The patient, who has comorbidities, tested positive for MERS-CoV on 16 July. Currently, he is in stable condition in a negative pressure isolation room on a ward. The patient owns a camel farm; however, he has neither a history of contact with camels nor consumption of their raw milk. Investigation of history of exposure to other known risk factors in the 14 days prior to the onset of symptoms is ongoing.

Contact tracing of household and healthcare contacts is ongoing for these cases.

The National IHR Focal Point for the Kingdom of Saudi Arabia also notified WHO of the death of 2 MERS-CoV cases that were reported in previous DONs on 24* July (case n. 4) and on 23 June (case n. 2).

Globally, since September 2012, WHO has been notified of 1,382 laboratory-confirmed cases of infection with MERS-CoV, including at least 493 related deaths.

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CDC Study: Pathogenesis & Transmissibility Of HPAI H5 In Mice & Ferrets

 

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Its effects on poultry are well established, but determining the pathogenesis (progression of disease) and degree of transmissibility of our recently arrived HPAI H5 viruses among mammals is a  high priority.  While it’s been encouraging that we’ve seen hundreds of poultry outbreaks over the past 18 months without seeing any human cases, a more precise measurement of their pandemic potential is needed.

 

Despite this lack of human cases, we have seen reports of dogs being infected with H5N8 (see MAFRA: H5N8 Antibodies Detected In South Korean Dogs (Again)).   The ability to infect canines does not automatically make it a human threat, but it does raise some concerns (see Study: Dogs As Potential `Mixing Vessels’ For Influenza).

 

Earlier this year, in Virology: Pathogenesis Of Avian A/H5N8 In Ferrets, we saw that that ferrets intranasally inoculated  with the Korean H5N8 strain suffered no mortality or serious respiratory symptoms, but that ferrets intratracheally infected showed `dose-dependent mortality’.

 

Yesterday the CDC published a new study in the Journal of Virology (the bulk of which, alas, is behind a pay wall) that further explores both the pathogenicity (in mice) and transmissibility (in ferrets) of both the North American H5N8 and H5N2 viruses.

  

The CDC has provided a lengthy summary, and for the most part the news remains good.  Some highlights:

• The severity of disease in inoculated mice was dose dependent, with severe disease only in mice given a very high dose of the virus.  And while the virus was detected in the lungs, laboratory mice experienced a less severe, more moderate disease than seen when exposed to the Asian H5N1 virus.
• Illness in ferrets was described as mild, and the virus did not spread to flu naïve ferrets placed in the same cage as infected ferrets, suggesting the risk of human-to-human transmission is low.
• H5Nx viruses replicated in human lung and airway cell cultures - but not as vigorously as with the Asian H5N1 virus – comparable to what is seen with seasonal H1N1.

 

While none of this precludes the possibility that human infection with one of these viruses might occur, this does reinforce the CDC’s assessment that these viruses currently pose a low risk to human health.   Influenza viruses are always changing, however, and new reassortants could appear, so ongoing vigilance is required.

 

More from the CDC below:

 

New CDC Laboratory Study Suggests U.S. H5 Bird Flu Viruses Currently Pose Low Risk to People

A new CDC study describes findings from a series of CDC laboratory experiments designed to improve understanding of the human health risk posed by two H5 bird flu viruses detected in birds in the United States: H5N2 and H5N8. Findings of this study indicate that the H5N2 and H5N8 bird flu viruses detected in the United States were less lethal in mammals and replicated (made copies of themselves during infection) at a lower level than the H5 bird flu viruses from Asia that have caused infections, serious illness and deaths in people. Overall findings suggest that these new U.S. bird flu viruses are unlikely to easily infect or spread between people in their current form and are likely to be associated with mild to moderate illness compared to the more severe illness associated with Asian H5 viruses. These U.S. bird flu viruses would need to undergo additional changes in order to pose a pandemic health risk to people.

This study, published today in the Journal of Virology, involved a combination of laboratory tests, some of which included animals and others that involved human lung cells grown in the laboratory via cell culture. CDC often uses such tests to infer how newly detected flu viruses can impact human health. These studies are part of a routine public health risk assessment process that CDC undertakes whenever a new virus with pandemic potential is identified.

Experiments conducted in this study include the following: tests in mice to determine the severity of disease associated with these viruses, tests in ferrets to determine characteristics of how these viruses spread between mammals and within the body, and tests using cell culture to measure the ability of these viruses to grow in human airway/lung cells (specifically human airway epithelial Calu-3 cells) in a laboratory setting.

Results in mice showed that mice infected with these viruses did not experience severe disease unless given very high doses of the virus. Virus was detectable in the lungs of mice, though, which is a characteristic that can be associated with more serious illness. However, compared to Asian H5 viruses, these U.S. H5 bird flu viruses demonstrated less severe, more moderate disease characteristics. Health researchers consider mice to be a reliable model for how disease associated with H5 bird flu viruses develops and progresses in mammals.

Transmission experiments involving ferrets showed that these U.S. H5 bird flu viruses did not spread between flu naïve ferrets (i.e., ferrets that had never been exposed to flu viruses previously) placed in the same cage as infected ferrets. This indicates that the virus is unlikely to spread efficiently among people, if they were to become infected by close contact with H5N2- or H5N8-infected poultry. Also, illness in the infected ferrets was generally mild, and the viruses did not spread systemically to multiple organs, which is a characteristic associated with more severe disease. These results are consistent with previous studies of H5N8 bird flu viruses in South Korea, which also showed low to moderate virulence in mammals. Ferrets are considered an excellent model for studying flu transmission and they also exhibit signs of disease that are similar to people infected with the flu.

Researchers also evaluated the ability of these bird flu viruses to replicate in human lung cells in laboratory experiments involving cell culture. The ability of a virus to infect human lung and airway cells is a trait that can be associated with more severe illness. These tests showed that H5N2 and H5N8 viruses replicated in human lung and airway cells at significantly lower levels compared to the Asian H5N1 viruses that have caused human deaths in Asia and elsewhere. While replication did occur, it was at a level comparable to human seasonal H1N1 flu virus.

Outbreaks in birds of H5N2, H5N8 and a new H5N1 bird flu virus were detected in the United States first in late 2014. Both of the bird flu viruses involved in this study were detected in Washington State: the H5N8 bird flu virus was obtained from an infected gyrfalcon and the H5N2 virus was obtained from a northern pintail duck. Most of the U.S. poultry outbreaks reported this year have been associated with the H5N2 virus, resulting in the loss of nearly 50 million chickens and turkeys on over 200 farms since the virus was first identified in December 2014. No human infections with these viruses have been detected at this time.

These findings reaffirm CDC’s current assessment that these viruses pose a low risk to the general public. CDC will continue to closely monitor and assess the risk of these viruses to human health as part of its routine pandemic preparedness responsibilities and activities.

 

 

 

Pathogenesis and transmission of novel HPAI H5N2 and H5N8 avian influenza viruses in ferrets and mice

Joanna A. Pulit-Penaloza, Xiangjie Sun, Hannah M. Creager, Hui Zeng, Jessica A. Belser, Taronna R. Maines and Terrence M. Tumpey

A novel highly pathogenic avian influenza (HPAI) H5N8 virus, first detected in January 2014 in poultry and wild birds in South Korea, has spread throughout Asia and Europe, and caused outbreaks in Canada and the United States by the end of the year. The spread of H5N8 and the novel reassortant viruses, H5N2 and H5N1 (H5Nx), in domestic poultry across multiple states in the U.S. pose a potential public health risk. To evaluate the potential of cross-species infection, we determined the pathogenesis and transmissibility of two Asian-origin H5Nx viruses in mammalian animal models. The newly isolated H5N2 and H5N8 viruses were able to cause severe disease in mice only at high doses. Both viruses replicated efficiently in the upper and lower respiratory tracts of ferrets; however clinical symptoms were generally mild and there was no evidence of systemic dissemination of virus to multiple organs. Moreover, these influenza H5Nx viruses lacked the ability to transmit between ferrets in a direct contact setting. We further assessed viral replication kinetics of the novel H5Nx viruses in a human bronchial epithelium cell line, Calu-3. Both H5Nx viruses replicated to a level comparable to a human seasonal H1N1 virus, but significantly lower than a virulent Asian-lineage H5N1 HPAI virus. Although the recently isolated H5N2 and H5N8 viruses displayed moderate pathogenicity in mammalian models, their ability to rapidly spread among avian species, reassort, and generate novel strains underscores the need for continued risk assessment in mammals.

(Continue . . .)

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RESEP CUMI ASIN KECAP PEDAS SAUS TERIYAKI

Resep cumi asin kecap pedas enak dan praktis dengan tambahan bumbu saus teriyaki. Olahan cumi asin atau cumi yang dikeringkan atau diawetkan ini bisa menjadi salah satu menu hidangan favorit keluarga. Cara memasak cumi asin yang enak dengan bumbu yang sederhana bisa menggunakan resep praktis di bawah ini dengan bumbu kecap pedas dan saus teriyaki.

Tips mencuci asin cumi, merendam air panas serta memasaknya dengan singkat merupakan cara mudah agar cumi asin tidak keras dan alot serta mengurangi rasa asin. Untuk rasa pedas yang spesial menggunakan cabe gendot atau bisa menggunakan cabe lainnya seperti cabe hijau atau sesuai selera.

RESEP CUMI ASIN KECAP PEDAS
Bahan dan bumbu :

• 150 gram asin cumi
• 3 buah cabe gendot atau cabe lainnya dipotong kecil-kecil
• 3 butir bawang merah diiris tipis
• 2 siung bawang putih diiris tipis
• 2 sendok makan saus teriyaki
• 2 sendok makan kecap manis
• 1/2 sendok teh garam atau sesuaikan selera
• 1/2 sendok teh merica
• 1/2 sendok teh kaldu bubuk atau penyedap
• 100 ml air
• minyak untuk menumis secukupnya

CARA MEMASAK CUMI ASIN KECAP PEDAS

1. Cuci bersih dengan air mengalir kemudian rendam asin cumi pakai air panas yang baru dididihkan, diamkan sejenak sekitar 10 menit.  Setelah itu cuci bersih kembali dan potong-potong sesuai selera.
2. Panaskan minyak secukupnya, tumis bawang merah, bawang putih dan cabe gendot hingga harum. Masukkan potongan cumi lalu tuang air, garam, merica dan kaldu bubuk sambil aduk rata.
3. Setelah mendidih, masukkan kecap dan saus teriyaki lalu aduk rata dan masak sebentar hingga matang menyerap dan kuah agak menyusut. Angkat masakan tumis cumi asin dan siap untuk disajikan.

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