Friday, August 17, 2018

WHO Ebola Update - DRC August 17th

http://www.who.int/csr/don/17-august-2018-ebola-drc/en/
















#13,459


The World Health Organization has published their weekly DON (Disease Outbreak News) summary of the the ongoing Ebolavirus outbreak in the DRC, with the sobering news that 8 more HCWs have been diagnosed with the  virus.
The only good news is that reports earlier this week of suspected cases outside of the DRC - including in Uganda - have all tested negative for the virus.
That said, the potential for exporting cases to other regions remains a genuine concern. I've only posted some excerpts from a much longer report, so follow the link to read it in its entirety.

Ebola virus disease – Democratic Republic of the Congo

Disease outbreak news
17 August 2018

On 1 August 2018, the Ministry of Health (MoH) of the Democratic Republic of the Congo declared a new outbreak of Ebola virus disease (EVD) in the town of Mangina, Mabalako Health Zone, North Kivu Province. Confirmed cases have since between reported from Beni and Mandima health zones, Ituri Province; however, all confirmed exposures and transmission events to date have been linked back to the outbreak epi-centre, Mangina. North Kivu and Ituri are among the most populated provinces in the country, share borders with Uganda and Rwanda, and experience conflict and insecurity, with over one million internally displaced people and migration of refugees to neighbouring countries.

As of 15 August 2018, 78 EVD cases (51 confirmed and 27 probable), including 44 deaths, have been reported.1 Since the DON published on 9 August, 34 new confirmed cases have been reported: seven from Ituri Province (Mandima Health Zone) and 27 from North Kivu Province (one in Beni and 26 in Mabalako health zones). The 78 confirmed or probable cases reside in five health zones in North Kivu and one health zone in Ituri. The majority of cases (39 confirmed and 21 probable) have been reported from Mangina in Mabalako Health Zone (Figure 1). As of 15 August, 24 suspected cases are currently pending laboratory testing to confirm or exclude EVD.

Eight new confirmed cases among health care workers have been reported, bringing the total number of infected health care workers to 10 (nine confirmed and one probable deceased case).
These health care workers were likely exposed in clinics, not Ebola treatment centres (ETCs), many of which may have been infected before the declaration of the outbreak. WHO and partners are working to increase awareness of Ebola among health care and other frontline workers, and to strengthen infection prevention and control (IPC) measures.

The MoH, WHO and partners continue to systematically monitor and rapidly investigate all alerts in other provinces and in neighbouring countries. Since the last DON was published, alerts in several provinces of the Democratic Republic of Congo as well as in Uganda, Rwanda, and the Central African Republic were investigated; EVD was ruled out for all.

For more information, see:

Ebola situation reports: Democratic Republic of the Congo

(Continue . . . )

Russia Notifies OIE Of A Second HPAI H5N2 Outbreak In Kostroma Oblast

Kostroma Oblast - Credit Wikipedia













#13,458


Amid dozens of reports of HPAI H5 (presumably H5N8) in Western Russia over the past two months we have a new report of HPAI H5N2 - the second reported from Russia - once again from Kostroma Oblast.
Roughly 8 months ago, in OIE: Outbreak In Kostroma, Russia Now Identified As HPAI H5N2, we learned of the first appearance of this HPAI H5N2 virus in Russia, where it forced the culling of 600,000 birds. 
Today the OIE is reporting a second outbreak in Kostroma Oblast, affecting a poultry farm with nearly 500,000 birds.   This report also confirms that this virus is of clade 2.3.4.4. - which suggests this may be a relatively new reassortment - likely from either HPAI H5N8 or HPAI H5N6.

http://www.oie.int/wahis_2/public/wahid.php/Reviewreport/Review?page_refer=MapFullEventReport&reportid=27576
Source of the outbreak(s) or origin of infection    

    Unknown or inconclusive

Epidemiological comments
    


The virus isolate was identified as H5N2 subtype by PCR and nucleotide sequencing. The comparative analysis of the obtained nucleotide sequences of the H gene and N gene fragments revealed that the isolate belongs to the Asian genetic lineage of highly pathogenic avian influenza (Clade 2.3.4.4.) which spread in the Russian Federation as well as in Asian, European, Middle Eastern and African countries in 2016-2018. The hemagglutinin cleavage site has a –REKRRKRGLF- structure, characterizing the virus as potentially highly virulent.

Clade 2.3.4.4. H5 viruses have proven themselves to be highly promiscuous, reassorting readily with other flu viruses, and generating a number of viable hybrids. Last year we saw the emergence and spread of HPAI H5N6 (see Tottori University: Shimane HPAI H5N6 A New Reassortment) while the year before a new H5N5 virus was spreading in parts of Europe.  
Going back even farther, in 2014-2015 we saw a reassorted clade 2.3.4.4. HPAI H5N2 virus help spark the largest avian epizootic in North American history (along with HPAI H5N8), affecting at least 15 states and parts of Canada.
This second appearance of HPAI H5N2 in Kostroma Oblast suggest this reassorted virus is likely circulating in wild or migratory birds - and while we don't know much how this particular reassortment behaves  - this will raise fresh concerns over this fall's bird migration into Europe, the Middle East and Africa.


Thursday, August 16, 2018

China MOA Confirms 2nd Outbreak Of African Swine Fever - Henan ex Heilongjiang Province

http://www.fao.org/3/i8805en/I8805EN.pdf















#13,457



For the second time in two weeks China's MOA has confirmed an outbreak of African Swine Fever (ASF) among commercial pigs, this time originating in Heilongjiang Province.
Thirteen days ago, in China MOA: 1st Reported Outbreak Of African Swine Fever, we saw the report of the long anticipated, but dreaded first arrival of ASF to China among pigs in Liaoning Province, which borders North Korea.
This discovery prompted the Chinese MOA To Hold An Emergency Meeting On African Swine Fever (ASF) last week, where the Ministry announced a major offensive against this threat.
While not a human health concern, ASF could severely impact pork production in China, which provides much of the animal protein for the dietary needs of 1.4 Billion Chinese.
Within the past few hours China's MOA confirmed a second detection, this time at a Henan Province slaughterhouse, among pigs recently transported from Heilongjiang Province.

Heilongjiang transferred to Zhengzhou, Henan Province, pigs were diagnosed with African swine fever

Date: 2018-08-16 15:42 Author: Source: Ministry of Agriculture and Rural Press Office 

The news office of the Ministry of Agriculture and Rural Affairs was released on August 16th. A pig swine epidemic occurred in a slaughterhouse of a food company in Zhengzhou Economic Development Zone, Henan Province.

On August 14, a pig in a slaughterhouse of a food company in Zhengzhou Economic Development Zone of Henan Province died of unexplained deaths, with 260 heads, 30 diseases and 30 deaths. The quarantine certificate showed that the pigs came from Tangyuan, Jiamusi City, Heilongjiang Province. County Heli Town Trading Market. In the early morning of August 16, it was confirmed by the National Center for Animal Diseases and Diseases of the National Center for Animal Health and Epidemiology of China, and the epidemic was caused by the African swine fever.

After the outbreak, the Ministry of Agriculture and Rural Affairs immediately dispatched supervisory components to Henan and Heilongjiang. In accordance with the requirements, Henan has launched an emergency response mechanism and adopted measures such as blockade, culling, harmless treatment and disinfection to prohibit all pigs and susceptible animals and products from being transported into or out of the blockade. Heilongjiang Province has carried out investigations and epidemiological investigations. At present, the epidemic has been effectively controlled.

Considering that ASF was confirmed less than 24 hours prior to this announcement, the assurances that  `Heilongjiang Province has carried out investigations and epidemiological investigations. At present, the epidemic has been effectively controlled.' are probably best taken with a sizable grain of salt. 

  Meanwhile, the OIE has published the official notification (see below).

http://www.oie.int/wahis_2/public/wahid.php/Reviewreport/Review?page_refer=MapFullEventReport&reportid=27568&newlang=en 
Source of the outbreak(s) or origin of infection 

Legal movement of animals 

Epidemiological comments 
Strict blockade, disinfection, and movement control measures were conducted in the slaughterhouse. The local government launched the African swine fever contingency plan and emergency response according to the Standard & Protocol for African swine fever. All live pigs and animal products were prohibited to enter and exit the area. Epidemiological survey and screening have been initiated in the Heilongjiang province.
Technically, this outbreak is in Henan Province, although the infected pigs were recently transported from Heilongjiang province. Last March, the FAO issued a Rapid Risk Assessment on the potential for seeing ASF in China, where they wrote:
The most likely regions for ASf spread are the northeast (Heilongjiang), followed by the central eastern area (Henan, Shanxi, Ammui, and Hubbei) and the southeast (Hunan). Surveillance for swine diseases in this region should be heightened.
While one outbreak might be dismissed as happenstance, a second outbreak in another province within two weeks is a pretty solid sign that ASF has already established a beach head in China.

One which has the potential to become a major economic, and societal problem for China in the months ahead.

Evaluation of a Visual Triage for the Screening of MERS-CoV Patients














#13,456


With the Hajj scheduled to begin in 3 days time, and with more than 2 million religious pilgrims from around the globe gathering in the Holy Cities of Saudi Arabia, the way that the Saudi MOH screens for potential MERS-CoV cases is of particular interest.
As we've seen previously, respiratory infections are the most commonly reported illness among religious pilgrims (see  EID Journal: ARI’s In Travelers Returning From The Middle East).
This study also found that  `Pneumonia is the leading cause of hospitalization at Hajj, accounting for approximately 20% of diagnoses on admission.’
Four years ago, in EID Journal: Respiratory Viruses & Bacteria Among Pilgrims During The 2013 Hajj, we looked at another study that examined a small group of French pilgrims (n=129) both before and after attending the Hajj, and compared nasal swabs.  They found: 
. . .  that performing the Hajj pilgrimage is associated with an increased occurrence of respiratory symptoms in most pilgrims; 8 of 10 pilgrims showed nasal or throat acquisition of respiratory pathogens. 
It is against this confusing backdrop that medical authorities must evaluate, and hopefully accurately identify and isolate, potential MERS cases among hundreds of thousands of symptomatic travelers presenting with a variety of respiratory symptoms.
While laboratory tests are available, they generally take between 24-48 hours to get the results,  and it usually requires two negative tests - 24 to 48 hours apart - to rule out MERS, during which time the patient should be isolated. 
Doable when you are dealing with a few dozen suspected cases, but impractical on a much grander scale.  Instead, the Saudi MOH has developed a scoring system - based on visible symptoms, and exposure history - to decide who to isolate and test as a potential MERS case.
The $64 question is:  Does it work?
The answer, as provided by prolific MERS researcher and former KSA Deputy Minister of Health,  Ziad Memish, MD et al.,  in a new analysis published this week in NMNI, is not particularly well.
 
Evaluation of a Visual Triage for the Screening of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Patients

Sarah H. Alfaraj, MBBS, Jaffar A. Al-Tawfiq, MD, Philippe Gautret, MD, Mishal Ghazi Alenazi, MBBS, Ayed Yahya Asiri, MBBS, Ziad A. Memish, MD

Open Access


DOI: https://doi.org/10.1016/j.nmni.2018.08.008
 

Introduction
The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in September 2012 in Saudi Arabia had attracted the attention of the global health community. Recently in the beginning of 2017, the Saudi Ministry of Health released a visual triage system with scoring to alert healthcare workers in emergency departments and hemodialysis units for the possibility of occurrence of MERS-CoV infection in their patients.

Patients and Methods


This is a retrospective analysis of the visual score of the Saudi Ministry of Health to determine its sensitivity and specificity. The study included all cases from 2014 to 2017 in a MERS-CoV referral center in the city of Riyadh, the capital of Saudi Arabia.

Results

During the study period, there were a total of 2435 suspected MERS cases. Of these cases 1823 (75%) tested negative and the remaining 25% tested positive for MERS-CoV by PCR assay. The application of the visual triage score revealed a similar percentage of MERS-CoV and non-MERS CoV patients with each score from 0 to 11.
The percentage of patients with the cut-off score of > 4 was 75% in patients with MERS Cov infection and 85% in patients without MERS-CoV infection (P =0.0001). The sensitivity and specificity of this cut off score for MERS-CoV infection were 74.1% and 18.6%, respectively.

Conclusion

The sensitivity and specificity of the scoring system was low and further refinement of the score is needed for better prediction of MERS-CoV infection.
The two main measures of the accuracy of any diagnostic test are sensitivity and specificity.
  • Sensitivity is defined as the ability of a test to correctly identify individuals who have a given disease or condition.
  • Specificity is defined as the ability of a test to exclude someone from having a disease or illness.
This visual scoring system failed to identify more than 25% of MERS cases, and at the same time more than 80% of `tagged' patients were negative for the virus.

The authors provide two strategies to improve screening:
Firstly, revise the case definition after careful review of the data available to the MoH for 5 years and secondly invest in developing a highly sensitive and specific point of care (POC) testing in the EDs and haemodialysis units where the results will be available in 1-2 hours [24–26].
The authors were particularly blunt in their assessment (bolding mine) of the current system.
The  current  study  conducted  on  a  large  number  of  patients  shows  that  clinical  scoring  is not predictive  of  MERS  infection. 
Our  results  are  robust  and  confirm  that  MERS  cannot  be distinguished from other respiratory infections based on  risk factors  and clinical features.  Thus all  patients with  non-specific  symptoms  in  a  MERS  endemic  area  will  have  to  be  isolated  until MERS can be ruled out by rapid PCR testing.
All of which adds weight to the notion that a substantial number of MERS cases may be going undiagnosed in Saudi Arabia, and elsewhere in the world.  We've seen estimates that many - perhaps even most - MERS cases go undetected.

While we've been lucky in the past, with no large MERS outbreaks linked to the Hajj, the possibility of seeing one or more infected pilgrims returning to their home countries while silently incubating the virus remains a genuine concern.

All of which will have public health officials around the world particularly on alert for the next 30 days.

California: CDFA Expands Quarantine For Virulent Newcastle Disease (VND)

Updated Quarantine Order





















#13,455


Five weeks after the California's Department of Food and Agriculture (CDFA) ordered a poultry Quarantine In 2 Counties (San Bernardino & Riverside) due to outbreaks of Virulent Newcastle Disease - amid rising case counts and a surge in Los Angeles County - the agency has issued a second, follow-up quarantine order.
August 14, 2018 - California Area Quarantine Notice #2: Los Angeles and San Bernardino County Areas
 The operative part of the new order reads:
You are hereby notified that the State Veterinarian has imposed a Quarantine pursuant to Food and Agricultural Code, Section 9562 on the following population of animals and animal products:

Description of Population of Animals and Animal Products: Poultry species (including chickens, turkeys, ducks, geese, partridges, pheasants, quail, guinea fowl, peafowl (peacocks), doves, pigeons, grouse, swans, and ratites), poultry products including eggs, manure/fertilizer, and used equipment or other items that could be contaminated due to exposure to poultry or poultry manure.


Present Location: In those areas of Los Angeles and San Bernardino Counties as described above.


Reason for Quarantine:
This Quarantine is imposed because the population of animals and animal products described above may be infected with virulent Newcastle disease virus (VND) or may have been exposed to VND and can transmit an illness that could kill or seriously damage other birds, or may be at risk for such exposure.


Required Action: Pursuant to California Food and Agricultural Code Section 9562 and Title 3, California Code of Regulations, Section 1301 et seq., require the following:

  • Hold the population of animals and animal products described above on the premises where it is now located.
  • Segregate and Isolate the population of animals and animal products described above from other animals or products no later than: 5:00 PM on August 15, 2018.
  • The method of isolation shall be confinement to one premises in a pen, cage or other means that prevents poultry from moving off the premises.
  • No poultry or hatching eggs shall be moved onto the premises and no poultry, poultry products, used poultry equipment or other items that could spread disease due to contact with poultry or poultry manure shall be moved off the premises until this quarantine is rescinded or revised; or unless the owner has signed a compliance agreement with the California Department of Food and Agriculture (CDFA) and such movement is made using a CDFA or United States Department of Agriculture (USDA) movement permit.
  • All owners shall immediately report any clinical signs suggestive of VND (described on CDFA website at https://www.cdfa.ca.gov/go/VND) and any unexpected decreases in egg production or increase in mortality (above expected rate for strain and age) by phone to the sick bird hot line at (866) 922-2473 or California State Veterinarian at (916) 900-5000.
  • Euthanize and Dispose of the population of poultry that cannot be isolated as described above. Due to the high risk of exposure to VND in the above designated disease control areas, CDFA or USDA will assist with euthanasia if poultry are free roaming and not isolated as described by 5:00 PM on August 16, 2018.

All outbreaks, so far, have been limited to backyard exhibition poultry. No commercial poultry operations have been affected yet. The last poultry outbreak in the United States was reported in 2003 (described below), although sporadic detections in wild birds have continued around the country.

This from the California Dept. of Food & Agriculture (Note: VND was called END - Exotic Newcastle Disease in 2003). 

The 2002-03 END outbreak, originally confirmed in backyard poultry in Southern California, spread to commercial poultry operations in California and backyard poultry in Arizona, Nevada and Texas.  The Governor of California declared a State of Emergency, the Secretary of the United States Department of Agriculture (USDA) declared an Extraordinary Emergency, and local emergencies were declared in San Diego, Riverside, Los Angeles, and San Bernardino Counties.
A USDA and the California Department of Food and Agriculture (CDFA) Task Force was formed that involved over 7,000 individuals rotating in and out over the course of the outbreak.  Trade restrictions resulting from the disease had negative impacts on California and U.S. poultry and egg producers.  The outbreak, from discovery to eradication, lasted eleven months.  The outbreak response led to the depopulation of 3.16 million birds at a cost of $161 million.
In 1971, an outbreak that began in Southern California led to the culling of 12 million birds and a loss of tens of millions of dollars.
We won't get a new weekly report until sometime tomorrow, but as of last weekend CDFA had reported - since May 18th - 93 cases of VND in backyard birds in California; 73 in San Bernardino County, 8 in Riverside County and 12 in Los Angeles County.
While there is a very slight risk of human infection, illness is generally mild and usually presents as conjunctivitis. The real threat is to the poultry industry, should the virus find its way again into commercial flocks.

Stay tuned.

Wednesday, August 15, 2018

Sci. Repts.: Characterization Of Avian Influenza Virus Attachment Patterns To Human & Pig Tissues
















#13,454


RBD's or receptor binding domains, are that part of the virus that allows it to attach to receptor cells in a host's body. Different viruses are attracted to different types of cells, which explains why some viruses that affect man, don't affect other species, and why we don't get influenza in our elbow or thumb.

Receptor cells have stalks of sugar (carbohydrate) molecules on their surface. These carbohydrate molecules - called `glycans' - form a dense sugary coating to all animal cell membranes. The composition of these stalks varies between types of cells and hosts, but the right combination can provide attachment points for some types of viruses.
When the right virus meets a compatible receptor cell, they bind, and assuming there are no other barriers in place, infection can ensue. 
Avian influenza viruses, like H7N9 and H5N1, bind preferentially to the alpha 2,3 receptor cells found in the gastrointestinal tract of birds, while `humanized’ flu viruses - like H3N2 and H1N1 - have an affinity for the alpha 2,6 receptor cells most commonly found in the human respiratory system. 
While greatly outnumbered by alpha 2,6 receptor cells, humans do have some of these avian-like alpha 2,3 receptor cells, which probably explains why some avian viruses have jumped directly to humans.
There are certainly other factors involved in a successful infection.  For example, avian flu viruses tend to replicate better at the higher temperatures found in the gastrointestinal tract of birds, rather than those present in the upper airway of humans.
But host adaptation mutations - like the PB2 E627K amino acid substitution - enable influenza viruses to replicate at lower temperatures (roughly 33C).
And we've seen growing evidence of avian viruses developing HA G186V and Q226L/I amino acid substitutions, which are linked to switching the virus from binding preferentially to avian (a2,3) receptor cells to mammalian (a2,6) receptor cells (see Cell: Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4).

Despite these adaptations, human infection by avian influenza viruses remains relatively uncommon, while pigs - which carry both alpha 2,6 alpha 2,3 receptor cells - are susceptible to a wide variety of human, swine, and avian flu viruses and are viewed as likely `mixing vessels' for influenza. 


Which begs the question: Do avian viruses require an intermediate (i.e. swine) host in order to jump to humans?
Attempting to answer this, we have a lengthy and quite detailed study - published today in Scientific Reports - where researchers using four different AIVs (Mallard H3N2, Mallard H6N1, Ruddy Turnstone H12N5, and Black Headed Gull H16N2) explored their ability to bind to a variety of human and pig tissues.
The answer they reveal is, while pigs are indeed susceptible to many avian viruses, in general `. . . . AIV attachment was more abundant to human tissues than to pig tissues.'

The full report is available at the link below, and I can't possibly do it justice here, so follow the link to read it in its entirety.   I've excerpted the abstract, and some sections from the discussion below:
Characterization of avian influenza virus attachment patterns to human and pig tissues 
Per Eriksson,Cecilia Lindskog, Ebbe Engholm, Ola Blixt, Jonas Waldenström, Vincent Munster, Åke Lundkvist, Björn Olsen, Elsa Jourdain & Patrik Ellström
Scientific Reports volume 8, Article number: 12215 (2018) | Download Citation

Abstract

Wild birds of Anseriformes and Charadriiformes are natural reservoirs of influenza A viruses (IAVs). Occasionally, IAVs transmit and adapt to mammalian hosts, and are maintained as epidemic strains in their new hosts. Viral adaptions to mammalian hosts include altered receptor preference of host epithelial sialylated oligosaccharides from terminal α2,3-linked sialic acid (SA) towards α2,6-linked SA.
However, α2,3-linked SA has been found in human respiratory tract epithelium, and human infections by avian IAVs (AIVs) have been reported.

To further explore the attachment properties of AIVs, four AIVs of different subtypes were investigated on human and pig tissues using virus histochemistry. Additionally, glycan array analysis was performed for further characterization of IAVs’ receptor structure tropism.

Generally, AIV attachment was more abundant to human tissues than to pig tissues. The attachment pattern was very strong to human conjunctiva and upper respiratory tract, but variable to the lower respiratory tract. AIVs mainly attached to α2,3-linked SA, but also to combinations of α2,3- and α2,6-linked SA.

The low attachment of these AIV isolates to pig tissues, but high attachment to human tissues, addresses the question whether AIVs in general require passage through pigs to obtain adaptions towards mammalian receptor structures.
       (SNIP)
Virus-host cell attachment (as determined by virus histochemistry) is a first important step to investigate the propensity of AIV infecting mammalian hosts. However, successful infection and replication is dependent on several additional cumulative factors apart from attachment alone. As exemplified by Kumari et al. the sole existence of α2,3 or α2,6-linked SA on the cell surface is not a warranty for a successful complete IAV replication cycle12. The existence of barriers preventing interspecies transmission of IAVs is well known3,8,9

However, in line with other studies, the reported results suggest that rather than the species barrier being determined by the receptor SA conformation alone, it comprises a combination of additional factors complementary to the receptor structure2,6,17,28,29. Such factors are e.g. the virus’ capacity of evading the host immune response and the ability to replicate efficiently in the infected host cell. Differences in e.g. host immune response and host cell biophysical properties might still require passage through pigs for an AIV to adapt to other mammalian hosts. Indeed, already Scholtissek et al. suggested that IAV host specificity is determined by several factors, and not a single factor6.

Still, as mentioned earlier, there are many reports of infection and replication of AIV in human and pig cells, both in vivo and in vitro21,30,31,32. More extensive histochemistry studies of IAV on human vs. pig sections would be needed in order to fully validate the rationale of the pig as a “mixing vessel” for IAV of avian and mammalian (human) type. 
Such studies should ideally be complemented by infection studies in cell culture, using multiple cell lines and ideally primary cells representing the tissue of interest, to investigate the virus’ ability to replicate30,31,32,33.
Finally, this study shows that AIV of various subtypes from diverse avian species have the capacity to both attach to α2,6-linked SA structures and have a broad capacity of attaching to human tissues.
The zoonotic potential of AIVs can thus not be neglected.
        (Continue . . . . )



While none of this negates that possibility that pigs could help serve up the next pandemic virus - even one of avian origin - it does suggest their participation is optional.

To paraphrase a much used Internet meme . . .  `Viruses, uh, find a way'.