EID Journal: Geographic Distribution of MERS-CoV among Dromedary Camels, Africa

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Six years ago this week, Dr. Ali Mohamed Zaki - an Egyptian virologist working in Saudi Arabia - collected blood and sputum samples from a 60 year old Saudi male hospitalized with with pneumonia and acute renal failure and began testing to determine the pathogen involved (see Nature Middle East The story of the first MERS patient).

Although he was able to isolate and culture a virus, his laboratory lacked the facilities to sequence its genome. He decided to send a sample to Dr. Ron Fouchier, at the Erasmus Medical Centre in the Netherlands, who had the equipment to do a proper analysis.

Two months later, Dr. Zaki emailed ProMed Mail (see Sometimes They Come Back), announcing the discovery of a new `SARS-like' coronavirus. Dr. Zaki's eventual `reward’ was that he was fired by the Saudis for going public with his discovery, proving once again that no good deed goes unpunished.  

Roughly one year - and 91 confirmed cases MERS Cases later - dromedary camels were pegged as the likely zoonotic conduit of the virus to humans (see Lancet: Camels Found With Antibodies To MERS-CoV-Like Virus).

At first the Saudis were slow to accept the idea that camels - a beloved symbol of their country - could carry a deadly disease (see Saudi Health Minister denies relation between camels, Mers).

In the face of mounting evidence, however, (see EID Journal: MERS Coronaviruses in Dromedary Camels, Egypt & The Lancet: Identification Of MERS Virus In Camels), in May of 2014 the Saudi Ministry Of Agriculture Issued Warnings On Camels, urging breeders and owners to limit their contact with camels, and to use PPEs (masks, gloves, protective clothing) when in close contact with their animals. 

Once camels in KSA were implicated, researchers began testing camels in other regions of the Middle East and Africa. Looking for, and finding, evidence of carriage of the MERS coronavirus going back many years.

EID Journal: MERS Antibodies In Camels – Kenya 1992-2013

Kuwait Tests Camels - Finds 6% Positive For MERS-CoV

EID Journal: Three Decades Of MERS-CoV Antibodies In Camels

Last year, in MERS-CoV In Camels: The Gift That Keeps On Giving, we saw a study that demonstrated that camels can be reinfected by the MERS virus, despite having substantial antibody titers.  A finding that may significantly complicate vaccine creation.

One of the (many) mysteries surrounding MERS-CoV is that while camel infection appears common on the Arabian peninsula, Saudi Arabia accounts for roughly 90% of known human MERS infections in that part of the world.

Even further afield, in early 2017 we saw EID Journal: Serologic Evidence Of MERS-CoV Infection in Pakistani Camels, and in 2015 Eurosurveillance: MERS-CoV In Nigerian Camels, yet South Asia and Africa have never reported a human infection.

Today we can add another study, published in the EID Journal, that further expands the geographic range of MERS-CoV in African camels, and shows its prevalence to be very high.   

I've only posted some excerpts, so you'll want to follow the link to read it in its entirety.  I'll have a bit more when you return. 

Volume 20, Number 8—August 2014
Dispatch
Geographic Distribution of MERS Coronavirus among Dromedary Camels, Africa

Chantal B.E.M. Reusken1 , Lilia Messadi1, Ashenafi Feyisa1, Hussaini Ularamu1, Gert-Jan Godeke, Agom Danmarwa, Fufa Dawo, Mohamed Jemli, Simenew Melaku, David Shamaki, Yusuf Woma, Yiltawe Wungak, Endrias Zewdu Gebremedhin, Ilse Zutt, Berend-Jan Bosch, Bart L. Haagmans, and Marion P.G. Koopmans

Abstract

We found serologic evidence for the circulation of Middle East respiratory syndrome coronavirus among dromedary camels in Nigeria, Tunisia, and Ethiopia. Circulation of the virus among dromedaries across broad areas of Africa may indicate that this disease is currently underdiagnosed in humans outside the Arabian Peninsula.

A novel betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), was identified as the cause of severe respiratory disease in humans during 2012 (1). In August 2013, dromedary camels (Camelus dromedarius) were implicated for the first time as a possible source for human infection on the basis of the presence of MERS-CoV neutralizing antibodies in dromedaries from Oman and the Canary Islands of Spain (2).

Since then, the presence of MERS-CoV antibodies in dromedaries has been reported in Jordan (3), Egypt (4,5), the United Arab Emirates (6,7), and Saudi Arabia (8,9). In October 2013, analysis of an outbreak associated with 1 barn in Qatar (10) found dromedaries and humans to be infected with nearly identical strains of MERS-CoV.

Further proof of widespread circulation of MERS-CoV among dromedaries was provided by studies from Egypt and Saudi Arabia (5,9). These findings have raised questions about the geographic distribution of MERS-CoV among camel populations elsewhere. Here, we report our assessment of the geographic distribution of MERS-CoV circulation among dromedaries in Africa by serologic investigation of convenience samples from these animals in Nigeria, Tunisia, and Ethiopia.

        (SNIP)

A question raised by these findings is whether human cases occur outside the Arabian Peninsula and if such cases are currently underdiagnosed in Africa. In addition, for the whole region, the possibility exists that MERS-CoV illness occurred before its discovery in 2012 and that such infection has been overlooked in the areas with evidence for virus circulation among animals during the past 10 years. Retrospective studies of cohorts of humans with respiratory illnesses of unknown etiology should address this notion.

Alternative explanations for the lack of cases in Africa could be the following: a different risk profile, for instance, related to demographics and local practices; or subtle genetic differences in the circulating virus strain.

Full-genome sequencing, virus isolation, and phenotypic characterization of viruses circulating outside the Arabian Peninsula will resolve this issue. Meanwhile, awareness of MERS-CoV infections should be raised among clinicians in Africa.

(Continue . . . )

While it may seem unlikely than any significant number of clinical MERS cases could go undetected in Africa, it isn't as far-fetched of an idea as it may sound.

Despite years of reporting outbreaks of H5N1 in Sub-Saharan African poultry, only one human infection with the virus has ever been confirmed there by the WHO (see 2007’s Nigeria Confirms Human Bird Flu Case).

There were three other suspected cases at the time  - including the mother of the confirmed case in Lagos – but testing was `inconclusive’.

According to local media reports at the time (see The Nigerian Paradox), the only reason we have the one confirmed case is because the husband/father of the two related victims paid for a private autopsy and lab testing when his daughter died two weeks after his wife. 

The reality is, in Nigeria (pop. 175 million) - the average life expectancy is about 53 years - and roughly 6,000 people die each and every day.  Many are never  afforded medical care, and testing for exotic diseases like H5N1 or MERS-CoV is rarely - if ever - done.

According to the CDC, the top 10 causes of death in Nigeria are:

Deaths from lower respiratory infections in Nigeria, which can cover a lot of territory – including novel influenza or MERS-CoV – are second only to malaria.

The story is much the same in many other African nations where MERS has been detected in camels, with lower respiratory infections claiming 4% of lives in Egypt, 10% in Ethiopia, 5.4% in Tunisia, and while good data is hard to come by, at least 10% in Sudan.

Even in Saudi Arabia, where decent medical care is available, and the threat of MERS is well recognized, we've seen estimates that many - perhaps even most - MERS cases go undetected.

• In November of 2013, we looked at a study published in The Lancet Infectious Diseases, that estimated for every case identified, there are likely 5 to 10 that go undetected.
• In 2015, when Saudi Arabia had recorded fewer than 1200 MERS cases, a seroprevalence study (see Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study by Drosten & Memish et al.,) suggested nearly 45,000 might have been infected. 
• And a 2016 study (see EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016) suggested that as much as 60% of severe Saudi MERS cases go undiagnosed.

In 2016, in EID Journal: MERS-CoV Antibodies in Humans, Africa, 2013–2014, we looked at the results of a seroprevalence study conducted in Kenya, which produced remarkably similar results to what Drosten & Memish et al found in KSA;  

1.52% vs. 1.43% positivity by rELISA and 0.15% vs. 0.18% positivity by PRNT for Kenya vs. Saudi Arabia, respectively.

Whether the MERS virus carried by African dromedaries pose the same human health risks as those on the Arabian peninsula remains an open question - but given the limits of surveillance and testing in the region - we’d be remiss in excluding that possibility simply because we haven't seen any confirmed cases.

Clinical & Epidemiological Characteristics of A(H9N2) Infection In A Young Child - China, 2017

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At first glance, H9N2 - a ubiquitous (at least in Asia and the Middle East, and recently reported in Africa), low pathogenic avian influenza (LPAI) virus that  generally produces mild symptoms in poultry - appears fairly tame. 

We've seen no large outbreaks in humans - only a few dozen widely scattered, usually mild infections over the past 20 years - mostly reported from China, Egypt, and Bangladesh (see FluTrackers Global Cumulative H9N2 Partial Case List 1998-2017).

Despite all of that, H9N2 is regarded as having at least some pandemic potential (see CDC IRAT SCORE), and so several candidate vaccines have been developed over the years.

Avian H9N2 virus occupies a special spot in our bird flu coverage because - while so far only an LPAI virus in poultry - its internal genes routinely make up the backbone of many of the HPAI viruses (including H5N1, H5N6, and H7N9) that pose the greatest risks to both poultry, and human health.

H9N2's reach extends beyond just avian flu subtypes, as we've also seen evidence of it reassorting with other influenza viruses, including A Canine H3N2 Virus With PA Gene From Avian H9N2 - Korea and PNAS: Reassortment Of H1N1 And H9N2 Avian viruses.

In 2014, in PLoS Path: Genetics, Receptor Binding, and Transmissibility Of Avian H9N2 researchers found evidence of Chinese H9N2 viruses binding preferentially to alpha 2,6 receptor cells -  the type commonly found in the human upper respiratory tract - rather than to alpha 2,3 receptor cells which are found in the gastrointestinal tract of birds.

Also in 2014  The Lancet carried a report entitled Poultry carrying H9N2 act as incubators for novel human avian influenza viruses  where  researchers warned that `reassortment between the prevalent poultry H9N2 viruses (providing genetic segments) and the influenza virus from wild birds could make the influenza evolve to adapt to domestic hosts.'

Earlier this year, in H9N2 Adaptation In Minks, we saw even more evidence of mammalian adaptation of H9N2, in a study that found H9N2 influenza virus isolated from minks has enhanced virulence in mice.

While relatively few human infections have been reported, we've seen a decided uptick in the past few years.  Although this is likely due to better surveillance, its (generally) mild presentation probably means most cases go undetected. 

We've a case report of a 2017 infection from China - one which was reported by the WHO in their 27 September 2017 Monthly Risk Assessment - albeit without much in the way of details:

Since the last update, one laboratory-confirmed human cases of A(H9N2) virus infection was reported to WHO from China. The patient is a child who had mild illness onset of 18 September, received outpatient care and had no apparent exposure history to live poultry.

Today we learn more about the case, along with some surprising statistics  about just how spotty surveillance is in China when it comes to detecting mild, novel flu virus infections.   I've only included some excerpts, so you'll want to download the PDF to read the report in its entirety.

Clinical and epidemiological characteristics of a young child infected with avian influenza A (H9N2) virus in China

First Published June 13, 2018 Case Report

Download PDF

ABSTRACT
Three cases of the avian influenza A (H9N2) virus have been documented in Changsha, which is a large city that has nine districts and a population of 7.04 million in central South China. Among these patients, one was a girl and two were boys. The ages of the patients were 9 months, 2 years, and 15 years. Two cases of H9N2 were detected in September, 2015 and one was detected in 2017.

Two patients were children who had not reached the age for kindergarten and one was a student. These three cases were all mild and were detected in a sentinel hospital of the Chinese Influenza Surveillance System. We describe the clinical and epidemiological features of the youngest patient with H9N2 in 2017 and the surveillance results of the H9N2 virus in live poultry markets in Changsha.

From January 2014 to December 2017, 4212 samples were collected in live poultry markets in Changsha, among which 25.81% (1087/4212) were H9N2-positive. Public health concerns should be addressed for emerging H9N2 virus infection, and more strategies should be performed before this virus mutates to be more transmissible and highly pathogenic.

        (SNIP)

       CASE REPORT

The patient, who lives in a six-person family in District A in Changsha, was a 9-month- old boy with no vaccination history of influenza vaccine and no other disease history. The boy had symptoms of fever (no temperature measurement was taken at this time) and was sneezing at 4:00 h on 18 September, 2017. Several hours later, with an auxiliary temperature of 39.5 C, he was sent to the paediatric emergency department of a sentinel hospital of the CISS system. 

A routine blood examination showed that the white blood cell count was 10.31 Â 10 9 /L and neutrophils represented 45.9% of blood cells. A throat swab sample was collected at the emergency department for pathogenic detection. Influenza virus antigen detection showed a positive result for influenza A.

Consequently, he was diagnosed with influenza and treated with oseltamivir and ibuprofen. However, the patient’s symptoms did not improve after treatment. He returned to hospital three times since 16:00 h on 18 September to 15:00 h on 20 September. Besides oseltamivir and ibuprofen, he was then prescribed oral medi-
cine, including Bifidobacterium and a Chinese traditional medicine (Xiao’er Chiqiao Qingre Keli), as well as intravenous medicine, including andrographolide injection, vitamin C, amino acids, potassium chloride, and a paediatric electrolyte supplements injection. No symptoms were observed after 15:00 h on 20 September.

The result of a throat swab sample (collected on 18 September) was H9N2-positive by using polymerase chain reaction, which was performed in the influenza surveillance network laboratory in Changsha Center for Disease Control and Prevention on 22 September. Another throat swab sample that was collected on 23 September was H9N2-negative when tested on 24 September.

        (Continue . . . )



While this child did not have recent poultry exposure, his parents both worked at a retail market where poultry was sold, and his father and sister both reported mild, non-specific symptoms in the days leading up to his illness. Again from the report:

The patient’s elder sister developed a mild fever, which rapidly disappeared between 16 and 17 September. She did not receive any medical treatment during these days. The patient’s father had mild nasal obstruction, which rapidly disappeared on 18 September. The other family members did not have any symptoms of the upper respiratory tract or influenza-like illness before the patient’s illness onset date.

Blood samples were pulled from the father and sister on the 23rd, but came back negative for H9N2.  There is no mention of additional testing for H9N2 among the remainder of the 36 close contacts identified, none of whom were reportedly symptomatic.

From the discussion section of the case report, we get a much better idea of the limits of routine testing of flu samples in China.  

Because of the mild symptoms, children infected with H9N2 and other subtypes of avian influenza virus were commonly detected by sentinel hospitals of the CISS system. However, a large amount of hospitals are not covered by this system. In Changsha, there are more than 50 hospitals, excluding private clinics and health care centres, but only two hospitals are included in the CISS system.

The authors conclude by writing:

Although no environmental surveillance evidence of our case was provided to show a full transmission chain, the positive rates of H9N2 were high in live poultry markets in nine districts of Changsha. Owing to the high prevalence of H9N2 virus in live poultry markets, more H9N2 viral infections might be missed in China. Therefore, public health concerns should be addressed for emerging H9N2 virus infection, and more strategies should be performed before this virus mutates to be more transmissible and highly pathogenic.

Whether H9N2 ever poses a direct pandemic threat or not, it continues to aid and abet in the creation of new, potentially deadly, bird flu viruses. That alone makes it worthy of our attention, although any substantial increase in human infection would be of concern as well.

Unfortunately, the two regions of the world where these human infections tend to occur (China & Egypt) are also among the least likely to publicize their existence.
 

DAERA: H5N6 Confirmed In Wild Bird In Northern Ireland

Credit DAERA

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Although the summer is traditionally the slow season for avian flu reports in the Northern Hemisphere, over the past couple of days we've seen outbreaks from both Russia and Bulgaria, and today DAERA is reporting on the discovery of a dead goose recently recovered in County Armagh that has tested positive for HPAI H5N6.

A reminder that while poultry outbreaks have been greatly reduced this past winter and spring, that the virus continues to circulate in wild birds.

Avian Influenza confirmed in a wild bird in Co Armagh

Date published: 15 June 2018

The Department of Agriculture, Environment and Rural Affairs today confirmed that a wild greylag goose, found in Lurgan Park, Co Armagh, has tested positive for H5N6 Avian Influenza.

The goose was reported to DAERA as part of its dead wild bird surveillance programme, and was submitted for testing at the Agri-Food and Biosciences Institute (AFBI), where initial testing has indicated avian influenza, sub-type H5N6. This is the same strain as confirmed in a wild buzzard in Co Antrim in March this year.

The Chief Veterinary Officer for Northern Ireland, Dr Robert Huey, said: “This is the second case of H5N6 in a wild bird in Northern Ireland this season and is not unexpected given that avian influenza continues to circulate in wild birds across Europe.

It further emphasises the requirement for all bird keepers to remain vigilant and to critically review their biosecurity measures, for example, feeding and watering birds under cover to help reduce the risk of their poultry coming in contact with wild birds. It is important that flock keepers report early any suspicions of disease.

“While the risk of an avian influenza incursion in wild birds remains, the risk to poultry is low. However, it is essential that we take the necessary steps to protect our poultry industry, international trade and the wider economy.

“I continue to encourage strongly all bird keepers to register their flocks. This will ensure they receive the latest information from the Department and also allow them to be contacted in an avian disease outbreak enabling them to protect their flock at the earliest opportunity. I would also encourage bird keepers to subscribe to the Avian Influenza text service by simply texting: ‘BIRDS’ to 67300”

Advice from the Public Health Agency is that the risk to public health from the virus is very low, however the general public is advised to take appropriate biosecurity precautions before touching or picking up birds that are dead, or appear to be sick or dying. Further advice can be found on the DAERA website.

The Food Standards Agency has confirmed that Avian Influenza does not pose a food safety risk for UK consumers. Thoroughly cooked poultry and poultry products, including eggs, are safe to eat.

Members of the public are encouraged to report dead waterfowl (swans, geese or ducks) or gulls, or five or more dead wild birds of other species in the same location, to the DAERA helpline on 0300 200 7840, Mon-Fri 9am to 5pm).

If you are concerned about the health of your birds you should seek advice from your veterinary surgeon. If you suspect that your birds are showing signs of the disease you should immediately report it to your nearest Department Veterinary Office.

More On the Bulgarian Avian Flu Outbreak In Dobrich

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The Bulgarian Agency For Food Safety has posted another update on their website on the avian flu outbreak reported yesterday (see Bulgarian Food Safety Agency Reports Avian Flu At Poultry Farm In Dobrich), and we are beginning to get more details from the local press. 

At this point the full subtype has not been announced, although we've seen outbreaks of HPAI H5N8 in this region over the past several months. 

First, we have the following (translated) statement on the Food Safety website:

Take measures following the detection of an outbreak of avian influenza in. Donchevo m. Dobrich 

14.06.2018
 
On 06/13/2018 Bulgarian Agency for Food Safety confirmed an outbreak of highly pathogenic avian influenza in the holding of rearing laying hens in. Donchevo m. Dobrich. Immediately after the establishment of the disease NVS ordered to take measures in accordance with Decree № SG-103 of 21 August 2006 on measures for prevention, control and eradication of avian influenza (flu) influenza including:

1. Forced humanely killed and destroyed under official supervision of the corpses laying hens in a manner precluding spread of the disease;
2. Performing multiple mechanical cleaning and disinfection of premises for poultry, equipment, vehicles, and yards and roads in and around the poultry facility.
3. They are defined protection zone, which includes the settlements within a radius of three kilometers and a surveillance zone within a radius of ten kilometers around the outbreak of the disease. The measures in these areas are:

• a ban on trade and movement of poultry, wild, other birds and eggs for breeding;
• ban on organizing and conducting fairs, markets and exhibitions for poultry;
• a ban on releasing of birds renewal of game reserves;
• conducting a census, registration and daily clinical examinations of birds kept in settlements located in the protection and surveillance zones;
• carrying out periodic clinical examinations of birds kept in the villages on the territory of Dobrich;
• sampling for laboratory testing in any doubt about avian influenza;
• doing research and tracking over the past three weeks, which covers movements of poultry and other birds, eggs, products and animal by-products derived therefrom feed for poultry and means of transport associated with the process in the protection and surveillance zones ;
• verification for the implementation of biosecurity measures at poultry sites in Dobrich. The owners of the objects that have not adopted biosecurity measures will be penalized.
• Control the entry of people in and from farms where the birds are kept;
• strict control over the production, processing and marketing of poultry meat products from poultry meat and eggs in Dobrich.

Not mentioned in either of the two official reports we've seen, but being reported by local media, is that the affected farm is supposedly the largest egg producer in the country, where more than 550,000 birds are housed.

So far, only two barns -  involving about 35,000 birds - are reported to be  affected.  This from TVN News.

Bird flu struck the biggest Bulgarian company for production of eggs

Author: June 15, 2018 Video

Only two weeks after the secondary outbreak of bird flu in the village of Stefanovo in Dobrich kindled a new outbreak.

Is smitten largest enterprise for production of eggs in Bulgaria, which is located in the village Donchevo. It raised 550 000 laying hens, so far struck two warehouses in commodity laying hens. A destruction of 35,000 birds, as hopes of owner Ivan Ivanov have this limit contagion.

He informed the Regional Directorate for Food Safety on Tuesday, but yesterday issued an order for the destruction of dead birds flu, it has not really begun.

The owner rejected versions of deliberately infecting with the aim of favoring by insurance or benefits. According to him, they would not be enough to restore production. The farm bred 350 000 200 000 hens and breeding hens produce around 150 million. Eggs per year. Now gives bread to over 200 families.

The main reason for the emerging country outbreaks of avian ban the EC to vaccinate birds and too little spacing of 200 meters between farms categorically Ivanov. The village people today have not yet been notified.

Mayor Donchevo accidentally found out about the situation of the extraordinary session of Dobrich Municipality yesterday, which ironically was convened for the untimely disclosure of the outbreak in the village Stefanov. Official document is not received. Both epizootic commissions - regional and municipal met behind closed doors.

All commercial establishments were sent letters - eggs infected in the last two weeks, to be harvested by commercial halls and be disposed of in the shops themselves.

Determined is a 3-km protection zone, which includes the villages Bogdanovo, Donchevo and Opanets. The marketing and movement of poultry and wild birds and eggs for breeding.

Experts will monitor poultry farms in the 10-kilometer zone. They will be constantly checked by veterinarians.

Regular readers will recall that just over a year ago H5N8 contaminated poultry products shipped from a single infected turkey farm in the Rostov region of Russia sparked a massive months-long operation to remove potentially tainted products from their food chain.

A few blogs on that incident include:

Rosselkhoznador Investigation Into HPAI Contaminated Meat Distribution & Sale

Rosselkhoznador: HPAI Contaminated Poultry Shipped To At Least 9 Regions Of Russia

Russia: Rosselkhoznadzor Finds More HPAI Contaminated Meat In Retail Stores

The concern then was less about human infection with the H5N8 virus - which has never been documented - and more about preventing the inadvertent spread of the virus to farms or to wild birds in other regions of the country.

And those are essentially the same concerns today in Bulgaria, as orders have gone out to destroy all eggs recently shipped from the afflicted farm.  

This (translated) report from Topnovini.bg.

Imposed a prohibition on eggs produced on a farm in. Donchevo


Outlined measures to suppress the outbreak of bird flu in Dobrich farm

Imposed a prohibition on eggs produced on the farm in the village of Dobrich Donchevo where there has been an outbreak of influenza. Letters were sent to all outlets, charge the eggs from the facility in the past two weeks, forbidden to sell products will be disposed of in stores, the press office of the regional government.

At a meeting of the Regional epizootic commission has identified measures to suppress the outbreak of avian influenza in. Donchevo, Dobrich region.

Holdings is located in 10 km zone defined on occasion found fireplace for the second time on a farm in. Stefanovo, said Dr. Kamenov in his report. Holding in. Donchevo is divided into different sectors.

Sunday evening veterinarian farm noticed increased mortality in one sector. On Sunday, there was again a large number of dead birds than usual. This gave rise to the veterinary specialist to a signal for increased mortality in the subject, were immediately taken and sampled.

Their results have confirmed the presence of influenza type H5 while awaiting the results of the second part of the virus, added Dr. Kamenov. Increased mortality was recorded in the production halls, where there is a total of about 320 thousand. Birds. Throughout holding birds are total 551 300 units.

According to the regulations and the regulations are taken immediate action. The object is divided into sectors introduced is increased biosecurity. Today we move on to the humane killing of birds in two of the rooms, as in every one of them has about 16 thousand. Number of birds. In parallel, monitor the condition of hens in other rooms. Imposed a foreclosure and produced eggs. Letters were sent to all outlets stocked eggs otfermata over the past two weeks.

Dr. Anelia Andonova clarify that these eggs are forbidden for sale and will be disposed of in commercial establishments on the ground. The very birds on the farm will be liquidated in the incinerator site, which is expected within today be delivered.

        (Continue . . . )


While likely not a human health concern - given the damage to Europe's poultry industry from their record setting H5N8 2016-17 epizootic - these measures are quite understandable.

Stay tuned.

Rosselkhoznadzor & OIE: HPAI H5 Reported In Kursk Oblast

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Things have been pretty quiet on the avian flu front in Russia the past few months - with the last OIE notification coming in the last week of December from Kostromskaya Oblast - which reported an unusual outbreak of HPAI H5N2 that resulted in the loss of more than 600,000 birds.

Last month's ESA Epidemiological Update described that event as:

An H5N2 virus detected in Russia

On 29th December 2017, Russia reported an outbreak of HPAI H5N2 in a poultry farm of more than 660 000 birds, in the region of Kostroma in the Northeast of Moscow (OIE report 29/12/2017). This outbreak was initially notified as H5N8 three days prior.

This is the first report of HPAI H5N2 virus in Russia and the last outbreak of HPAI H5N2 reported in Europe dates back to January 2017 with three outbreaks reported in poultry farms in France.

Regarding the origin of this virus, two hypotheses can be formulated:

• the mutation of a LP H5N2 virus in domestic birds, into a HP virus (as was the case in 2015 with H7N7 in the United Kingdom and Germany, or with H5N1 and H5N2 in France),
• a reassortment between HP H5N8 which circulated in Europe in 2016-2017 with a LP Eurasian strain, as for the H5N6 virus currently circulating in Europe. Indeed, viruses from clade 2.3.4.4 have a strong mutation potential, as illustrated by the emergence of H5N6 and H5N5 viruses following the circulation of H5N8 in Europe in 2016-2017.

Whatever the case may be, further analyses are needed to identify the origin, the link and the genetic composition of these new viruses, and the evolution of the epidemiological situation in Europe should be closely monitored.

Today, we've an OIE report and a statement from the Kursk Oblast office of Rosselkhoznadzor, of what appears to be at least two outbreaks of an HPAI H5 virus (full subtype not yet identified) in Kursk Oblast.

First, a screenshot from the OIE report, followed by excerpts from the official statement.

About Avian Influenza registration in Kursk region

June 14, 2018

Office of Rosselkhoznadzor for the Orel and Kursk regions announces the registration of avian influenza in the territory of Kursk region. As a result of laboratory tests FGBU "ARRIAH" 10/06/2018 identified the genetic material of the avian influenza virus type A subtype H5 in pathological material taken from:

- fallen poultry (chickens and ducks) contained in private farms in the village of N. Grayvoronka Soviet district of the Kursk region,.

- carcasses of poultry (chickens), found in the forest belt Ryshkovskogo to / from the Kursk region Kursk region.

Currently, the disadvantaged section are specialists gosvetsluzhby Kursk region under the control of the Territorial Office of Rosselkhoznadzor. Measures are taken in accordance with the rules to combat bird flu, approved by Order of the Ministry of Agriculture of Russia from 27.03.2006 number 90.

Although the OIE report only details the backyard poultry outbreak, the above statement and the (following) TASS news report reference a second location, involving carcasses of poultry found in a forested area of another district, suggesting there may be more to this event than the initial report might indicate.

In two districts of the Kursk region, quarantine was introduced due to an outbreak of avian influenza
June 14, 16:25 UTC + 3


The veterinary department of the Ministry of Agriculture sent an application for allocation of 50 thousand doses of vaccine to the region

KURSK, June 14th. / TASS /. The governor of the Kursk region, Alexander Mikhailov, signed a decree on the introduction of quarantine on the territory of two regions of the region due to an outbreak of avian influenza. This was reported to the regional administration on Thursday.

As previously reported, experts for the first time detected the avian influenza virus in the Kursk region in pathological material selected from the dead hens and ducks in the private farm in the village of Nizhnyaya Graivoronka of the Sovetskiy district, as well as in the forest belt of the Ryshkovo village Soviet.

"By the decisions of the Kursk Oblast Governor in the Soviet and Kursk regions, quarantine for avian influenza has been introduced, and control over all poultry farms operating in the" closed type "mode, as well as the number of birds kept in personal subsidiary plots, has been strengthened," the regional administration noted.

In addition, an application was sent to the Veterinary Department of the Ministry of Agriculture of the Russian Federation on the allocation of the Kursk region 50 thousand doses of the vaccine against bird flu.

Avian influenza is an infectious disease that affects the digestive organs, breathing and leading to the death of birds. As a rule, the carriers are wild individuals. Most strains of the disease for people are not dangerous.

While HPAI H5N8 or H5N6 are the most likely culprits, last winter's outbreak of HPAI H5N2 several hundred miles to the North and East of Kursk - and the promiscuous nature of HPAI H5 clade 2.3.4.4 viruses in general - means we'll be waiting with considerable interest to learn what virus is driving this latest outbreak.

KLRD1 : A Biomarker For Predicting Influenza Susceptibility?

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When we talk about  about `high risk’ influenza patients, it is generally where their age and/or co-morbidities (COPD, Asthma, pregnancy, etc. ) can lead to a greater chance of infection and/or complications. 

But there may be other factors at work as well.

In the past we've looked at some fascinating research on the role of host genetics and certain biomarkers that might determine whether certain people are more (or less) susceptible to severe influenza infection than others.

In 2008, in the Journal of Infectious Diseases, we saw a study that suggested there might be a heritable susceptibility to death from the influenza virus:

Evidence for a heritable predisposition to death due to influenza.

Albright FS, Orlando P, Pavia AT, Jackson GG, Cannon Albright LA.

While interesting, that study didn’t provide us with a smoking gene.

In 2009 (see The Best Defense) we inched a bit closer, with research from Harvard Medical School and the Howard Hughes Medical Institute, that identified the IFITM3 protein as capable of inhibiting the replication of influenza, and other viruses, such as West Nile and Dengue. 

We revisited the IFITM3 story again in early 2012, in Luck Of The Draw, when we looked at research from the Wellcome Trust Sanger Institute, that found that people who carried a particular variant of the IFITM3 gene - (SNP rs12252-C) - were more likely to be hospitalized with severe influenza

In 2013, a study by Professor Peter Doherty (see PNAS: Genetic Marker & Cytokine Levels Linked To Severity Of Human H7N9 Infection) linked IFITM3 CC gene variant (aka C/C Genotype)  to hypercytokinemia (aka a `Cytokine Storm’), and severe outcomes in H7N9 infections.

This genetic marker– while comparatively rare in Caucasians - is far more common in Han Chinese, and may (partially) account for some of the particularly high mortality rates we’ve seen with novel influenza’s in Asia. 

And in 2015, in A Genetic Predisposition To Severe Flu Infection, we looked at a study published in Science Express that identified yet another (rare) genetic marker -  a mutation of the IRF7 gene -  linked to a lack of interferon production which can lead to a more severe influenza infection.

And just last year, in New IFITM3 Genetic Marker May Help Identify High Risk Flu Patients, researchers from St. Jude Children's Research Hospital  found patients who carried a particular inherited variation in the  IFITM3 gene were `more than twice as likely to develop severe, life-threatening flu symptoms as those who carried the protective version of the gene'.

As you can see, there are multiple avenues of inquiry into host susceptibility to influenza infection, and while progress continues to be made, the final answer is unlikely simple or even limited to one gene.

To this growing list we can add a new study, published today in Genome Medicine by researchers at Stanford University, that identifies a gene called KLRD1 as a potential biomarker for influenza susceptibility.

First a snippet from the press release, and then a link to the open-access study.

Stanford scientists discover biomarker for flu susceptibility

Scientists at Stanford are believed to be the first to have discovered a biomarker that can predict who will be most susceptible to influenza.

Jun 13 2018

Researchers at the Stanford University School of Medicine have found a way to predict whether someone exposed to the flu virus is likely to become ill.

Purvesh Khatri, PhD, associate professor of medicine and of biomedical data science, and his team used a computational approach to pinpoint a blood-based genetic biomarker to determine an individual’s susceptibility to the disease.

“We’ve been after this for about four years,” Khatri said. “To our knowledge, it’s the first biomarker that shows susceptibility to influenza, across multiple strains.”

The biomarker is a gene called KLRD1, and it essentially acts as a proxy for the presence of a special type of immune cell that may be a key to stamping out nascent flu infection. Put simply: the more of this cell type found in a person’s blood, the lower their flu susceptibility. The research even hints at new avenues for pursuing a broadly applicable flu vaccine.

A paper describing the work will be published online June 14 in Genome Medicine. Khatri is the senior author. Graduate student Erika Bongen is the lead author.

(Continue . . . )

The actual study is lengthy, at times technical, and far too complex to summarize here.  The abstract provides the gist, but you'll probably want to follow the link to read it in its entirety.

When you return I'll have a short postscript.

KLRD1-expressing natural killer cells predict influenza susceptibility

Erika BongenView ORCID ID profile,  Francesco Vallania, Paul J. Utz and Purvesh KhatriEmail author
Genome Medicine201810:45

https://doi.org/10.1186/s13073-018-0554-1

© The Author(s). 2018

Abstract
Background

Influenza infects tens of millions of people every year in the USA. Other than notable risk groups, such as children and the elderly, it is difficult to predict what subpopulations are at higher risk of infection. Viral challenge studies, where healthy human volunteers are inoculated with live influenza virus, provide a unique opportunity to study infection susceptibility. Biomarkers predicting influenza susceptibility would be useful for identifying risk groups and designing vaccines.

Methods

We applied cell mixture deconvolution to estimate immune cell proportions from whole blood transcriptome data in four independent influenza challenge studies. We compared immune cell proportions in the blood between symptomatic shedders and asymptomatic nonshedders across three discovery cohorts prior to influenza inoculation and tested results in a held-out validation challenge cohort.

Results

Natural killer (NK) cells were significantly lower in symptomatic shedders at baseline in both discovery and validation cohorts. Hematopoietic stem and progenitor cells (HSPCs) were higher in symptomatic shedders at baseline in discovery cohorts. Although the HSPCs were higher in symptomatic shedders in the validation cohort, the increase was statistically nonsignificant. We observed that a gene associated with NK cells, KLRD1, which encodes CD94, was expressed at lower levels in symptomatic shedders at baseline in discovery and validation cohorts. KLRD1 expression in the blood at baseline negatively correlated with influenza infection symptom severity. KLRD1 expression 8 h post-infection in the nasal epithelium from a rhinovirus challenge study also negatively correlated with symptom severity.

Conclusions

We identified KLRD1-expressing NK cells as a potential biomarker for influenza susceptibility. Expression of KLRD1 was inversely correlated with symptom severity. Our results support a model where an early response by KLRD1-expressing NK cells may control influenza infection.

(Continue . . . )

Like all research, this study was subject to a number of limitations (see below), and so the findings - while impressive -  may not be quite as clear cut as the lede of the press release would suggest. 

As the conclusion of the abstract states, they identified `KLRD1-expressing NK cells as a potential biomarker for influenza susceptibility.'

Press releases, after all, do tend to emphasize the positives.  From the DISCUSSION section of the study. 

        (Snippet)

Our study was limited due to our dependence on publicly available challenge study data. Arguably, the number of samples in the challenge studies used here were low. A post hoc statistical power analysis indicated we had sufficient power to detect NK cell and HSPC immune cell proportion differences [38]. We only included symptomatic shedders and asymptomatic nonshedders in our analysis. It is unclear whether our results are applicable to symptomatic nonshedders and asymptomatic shedders. Participants across all challenge studies were healthy young adults. Our results may not be applicable to children or the elderly and need to be investigated in these groups. Furthermore, we only had access to transcriptomic data. Additional studies should confirm whether symptomatic shedders have lower proportions of NK cells at baseline and whether high expression of KLRD1 in the blood directly correlates with greater numbers of CD94+ NK cells via flow cytometry.

While I suspect we are still a long way from knowing all of the gene variants and  biomarkers linked to influenza susceptibility, researchers continue to expand their watch list, and more importantly, their understanding of how they work.