Saturday, February 23, 2019

Saudi MOH Reports 4 New MERS Cases

Original Map Credit Wikipedia


Saudi Arabia's February surge in MERS cases continues with 4 new cases announced (1 late yesterday, 3 today). Of these two are secondary cases from hard hit Wadi Aldwasir, and two others are primary cases with camel contact; one in Mekkah, and the other in Jeddah.

Of note, two cases announced on Thursday from Wadi Aldwasir remain unclassified, and are still listed as `under investigation'.

So far in 2019, Saudi Arabia has announced 77 MERS cases and of those 49 have hailed from Wadi Aldwasir.  In addition to more than a dozen primary infections (some with camel contact, some without).
  • 7 cases have been listed as secondary, household contacts
  • 2 cases have been listed as secondary, community-acquired
  • 26 cases have been listed as secondary, healthcare-acquired.
Spillover of the MERS coronavirus from camels continues to reintroduce the virus into the local human population, but most human infections are still acquired from exposure to another infected human.  

Community transmission of the virus has thankfully been both sporadic and limited, and so the virus has fallen short of producing a sustained epidemic. Hopefully that will remain the case.
But a 2017 study found the virus's basic reproduction number (R0 : pronounced R-nought) was inching closer to the magic number of 1.0, which is what is required for an outbreak to have `legs' (see A Pandemic Risk Assessment Of MERS-CoV In Saudi Arabia).    
So we are monitoring this MERS surge closely, looking for any signs that the virus's patterns are changing.

CDC FluView Week 7 - Increased Activity & Rising H3N2 Clade 3C.3a In U.S.
Credit CDC - LINK


With influenza still increasing across the nation, and a noticeable shifting from H1N1 to H3N2 in several regions, this winter's flu season is likely to extend well into spring.  
As the graphic above indicates, while not as horrific as the 2017-18 H3N2 flu season - which is blamed for More Than 900,000 U.S. Hospitalizations & 80,000 Deaths - this year's epidemic has been far from mild.
And with a growing number of H3N2 infections being reported over the past few weeks - particularly in the Southeast and Midwest - the impact on older patients will likely increase.

First some excerpts from this week's FluView report from the CDC, then a quickly look at the rapidly shifting flu subtypes and clades across the country.

2018-2019 Influenza Season Week 7 ending February 16, 2019

All data are preliminary and may change as more reports are received.
An overview of the CDC influenza surveillance system, including methodology and detailed descriptions of each data component, is available at
Influenza activity continues to increase in the United States. Influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses continue to co-circulate. Below is a summary of the key influenza indicators for the week ending February 16, 2019:
  • Viral Surveillance:The percentage of respiratory specimens testing positive for influenza viruses in clinical laboratories increased. While influenza A(H1N1)pdm09 viruses predominated in most areas of the country, influenza A(H3) viruses have predominated in HHS Region 4 and accounted for 47% of subtyped influenza A viruses detected nationally during week 7. During the most recent three weeks, influenza A(H3) viruses were reported more frequently than influenza A(H1N1)pdm09 viruses in HHS Regions 6 and 7 and influenza A(H1N1)pdm09 and influenza A(H3) viruses were reported in approximately equal numbers in HHS Region 2.
    • Virus Characterization:The majority of influenza viruses characterized antigenically are similar to the cell-grown reference viruses representing the 2018–2019 Northern Hemisphere influenza vaccine viruses.
    • Antiviral Resistance:The vast majority of influenza viruses tested (>99%) show susceptibility to oseltamivir and peramivir. All influenza viruses tested showed susceptibility to zanamivir.
  • Influenza-like Illness Surveillance:The proportion of outpatient visits for influenza-like illness (ILI) increased to 5.1%, which is above the national baseline of 2.2%. All 10 regions reported ILI at or above their region-specific baseline level.
    • ILI State Activity Indictor Map: New York City and 30 states experienced high ILI activity; the District of Columbia and 11 states experienced moderate ILI activity; six states experienced low ILI activity; the U.S. Virgin Islands and three states experienced minimal ILI activity; and Puerto Rico had insufficient data.
  • Geographic Spread of Influenza: The geographic spread of influenza in Puerto Rico and 48 states was reported as widespread; one state reported regional activity; the District of Columbia reported local activity; the U.S. Virgin Islands and one state reported sporadic activity; and Guam did not report.
  • Influenza-associated Hospitalizations A cumulative rate of 27.4 laboratory-confirmed influenza-associated hospitalizations per 100,000 population was reported. The highest hospitalization rate is among adults 65 years and older (75.6 hospitalizations per 100,000 population).
  • Pneumonia and Influenza Mortality: The proportion of deaths attributed to pneumonia and influenza (P&I) was below the system-specific epidemic threshold in the National Center for Health Statistics (NCHS) Mortality Surveillance System.
  • Influenza-associated Pediatric Deaths: Seven influenza-associated pediatric deaths were reported to CDC during week 7.
(Continue . . . )

In a blog two days ago (see WHO: (Partial) Recommended Composition Of 2019-2020 Northern Hemisphere Flu Vaccine) we looked at the World Health Organization's unusual decision to delay selection of the H3N2 component of next fall's flu vaccine for 30 days due to the recent rise of a new, antigenically distinct strain (clade 3C.3a).

They wrote:
The majority of A(H3N2) viruses collected from September 2018 to January 2019 belonged to the phylogenetic subclade 3C.2a1b; however, the number of clade 3C.3a viruses has increased substantially since November 2018 in several geographic regions.
There has continued to be considerable genetic diversification of the HA and NA genes, but viruses in subclade 3C.2a2 were much less prevalent than in the previous reporting period.

In this week's FluView (week 7) Antigenic characterization of circulating H3N2 viruses, we can see a similar rise in the number of clade 3C.3a viruses detected this winter (bolding & underlining mine).
A (H3N2): Phylogenetic analysis of the HA genes from 381 A(H3N2) viruses revealed extensive genetic diversity with multiple clades/subclades co-circulating.
The HA genes of circulating viruses belonged to clade 3C.2a (n=62), subclade 3C.2a1 (n=122) or clade 3C.3a (n=197).
One hundred ninety-four A(H3N2) viruses were antigenically characterized by FRA with ferret antisera, and 128 (66%) A(H3N2) viruses tested were well-inhibited (reacting at titers that were within 4-fold of the homologous virus titer) by ferret antisera raised against A/Singapore/INFIMH-16-0019/2016 (3C.2a1), a cell-propagated reference virus representing the A(H3N2) component of 2018-19 Northern Hemisphere influenza vaccines.
Sixty-six (34%) viruses reacted poorly (at titers that were 8-fold or greater reduced compared with that of the homologous virus A/Singapore/INFIMH-16-0019/2016) and of those, 65 (98.5%) belonged to clade 3C.3a.
While more than half (51%) of all H3N2 viruses tested by the CDC this winter are now clade 3C.3a - just 7 weeks ago (week 1 FluView) just 18% belonged to clade 3C.3.
That increase is even more apparent when you look at the 254 H3N2 viruses examined by the CDC since the first week of January, 68% (174 of 254) now belong to this emerging clade.
As clade 3C.3a viruses are less well inhibited by this year's vaccine, its recent gains could make the remainder of this flu season more challenging, particularly for the elderly, who are often the most harshly affected by H3 flu viruses.
As always, it isn't too late to get the flu shot. But now is also the time to rigorously practice good flu hygiene. Stay home if you are sick, avoid crowds, wash your hands frequently, and cover your coughs and sneezes
If you think you have the flu, contact your doctor right away. Antivirals, when taken early by those at higher risk of complications, can be lifesaving. 

Friday, February 22, 2019

H5N6: Outbreak On Yunnan Farm & New WHO Candidate Vaccine


In the 18 months since China launched an aggressive nationwide H5+H7 poultry vaccination program, avian influenza reports (in poultry, and in humans) have been greatly suppressed across China.

Reported H7N9 activity has been almost nonexistent since last summer, but starting in August we did see a small uptick in H5N6 outbreaks in China's poultry, and 4 human infections in the last half of 2018.

Today China's MOA is reporting their first H5N6 outbreak since the end of November, once again in Yunnan Province, which reported two outbreaks three months ago.

A poultry H5N6 subtype of high-pathogenic avian influenza epidemic occurred in Huaping County, Yunnan Province

Date: 2019-02-22 16:58 Author: Source: Ministry of Agriculture and Rural Press Office 

The Information Office of the Ministry of Agriculture and Rural Affairs released on February 22nd, a high-pathogenic avian influenza epidemic of poultry H5N6 subtype occurred in Huaping County, Lijiang City, Yunnan Province.

On February 22, the Ministry of Agriculture and Rural Affairs received a report from the China Animal Disease Prevention and Control Center and was diagnosed by the National Avian Influenza Reference Laboratory. The H5N6 subtype highly pathogenic avian influenza epidemic occurred in poultry raised by a farmer in Huaping County.
The farmer stocked 2,861 poultry, 463 pigeons and 463 deaths. After the outbreak, the local authorities in accordance with the relevant plans and technical requirements for prevention and control, do a good job in the handling of the epidemic situation, have culled 559,17 poultry, all the sick and culled poultry have been harmless treatment.

While the number of H5N6 breakthrough events since China's massive poultry vaccination remain small, they appear to have increased over the past 6 months, possibly a sign of some antigenic drift in the H5N6 virus.

Adding weight to that idea, yesterday the World Health Organization released their updated semi-annual candidate vaccines For pandemic preparedness report, where they recommend development of a vaccine for a recently emerged, antigenically distinct H5N6 virus.

Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness
 February 2019

The development of influenza candidate vaccine viruses (CVVs), coordinated by WHO, remains an essential component of the overall global strategy for pandemic preparedness.
Selection and development of CVVs are the first steps towards timely vaccine production and do not imply a recommendation for initiating manufacture. National authorities may consider the use of one or more of these CVVs for pilot lot vaccine production, clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.
Zoonotic influenza viruses continue to be identified and evolve both genetically and antigenically, leading to the need for additional CVVs for pandemic preparedness purposes. Changes in the genetic and antigenic characteristics of these viruses relative to existing CVVs, and their potential risks to public health justify the need to select and develop new CVVs.
This document summarizes the genetic and antigenic characteristics of recent zoonotic influenza viruses and related viruses circulating in animals 1 that are relevant to CVV updates. Institutions interested in
receiving these CVVs should contact WHO at or the institutions listed in announcements published on the WHO website 2 .
Influenza A(H5)
Since their emergence in 1997, highly pathogenic avian influenza (HPAI) A(H5) viruses of the A/goose/Guangdong/1/96 haemagglutinin (HA) lineage have become enzootic in some countries, have infected wild birds and continue to cause outbreaks in poultry and sporadic human infections. These viruses have diversified genetically and antigenically, including the emergence of viruses with replacement of the N1 gene segment by N2, N3, N5, N6, N8 or N9 gene segments, leading to the need for multiple CVVs.
This summary provides updates on the characterization of A/goose/Guangdong/1/96-lineage A(H5) viruses and the current status of the development of influenza A(H5) CVVs.
Influenza A(H5) activity from 25 September 2018 to 17 February 2019
Three A(H5N6) human infections were detected in China during this period; no A(H5N1) human infections were reported. Since 2003 there have been 860 and 23 confirmed human infections with A(H5N1) and
A(H5N6) viruses, respectively. A/goose/Guangdong/1/96-lineage A(H5) viruses were detected in poultryand wild birds in multiple countries (Table 1).
Antigenic and genetic characteristics of influenza A(H5) viruses
The nomenclature for phylogenetic relationships among the HA genes of A/goose/Guangdong/1/96-lineage A(H5) viruses is defined in consultation with representatives of WHO, the Food and Agriculture
Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE) and academic institutions 3 .
A(H5) viruses circulating and characterized from 25 September 2018 to 17 February 2019 belong to the following clades:
Clade viruses were detected in birds in Bangladesh and India. The majority of viruses tested reacted poorly with post-infection ferret antiserum raised against the CVV derived from A/duck/Bangladesh/19097/2013 and were genetically more similar to A/duck/Bangladesh/17D1012/2018, from which a CVV is in development.
Clade viruses were detected in three humans, birds and environmental samples in China, as well as birds in at least nine other countries in Africa, Asia and Europe (Table 1). Two of the three human infections were fatal. The HAs of the clade viruses belonged to several genetic subgroups.
Viruses from humans, an increasing number of poultry and environmental samples from China, some poultry in Viet Nam and a wild bird (common gull) in the Russian Federation belonged to an HA subgroup not currently represented by an existing CVV (Fig. 1).
Correspondingly, viruses from this group reacted poorly to post-infection ferret antisera raised against available CVVs (Table 2). The detection in the Saratov region, Russian Federation, represents the first report of this HA subgroup outside of Asia.

Influenza A(H5) candidate vaccine viruses
Based on the current antigenic, genetic and epidemiologic data, a new A/Guangdong/18SF020/2018-like A(H5N6) CVV is proposed. The available and pending A(H5) CVVs are listed in Table 3
(Continue . . . )

The need for a new H5N6 human vaccine - and a recent uptick in H5N6 activity - may indicate that China's H5+H7 poultry vaccine may need updating as well.

Despite the dearth of H7N9 activity out of China since the vaccination campaign, a little over a year ago a single human H7N4 infection was reported (see Jiangsu China Reports 1st Novel H7N4 Human Infection) and yesterday's report also recommended the creation of a suitable candidate vaccine. 
Influenza A(H7) candidate vaccine viruses
Based on the current antigenic, genetic and epidemiologic data, a new A/chicken/Jiangsu/1/2018 (H7N4)-like CVV is proposed. The available and pending A(H7) CVVs are listed in Table 6.
A reminder that while avian flu activity has dropped globally over the past year - viruses have survived for millions of eons based on their ability to evolve and evade acquired herd immunity - and that modern vaccines and antivirals used to combat them generally have a limited lifespan.

We should enjoy this current lull for as long as it lasts, but we should not be surprised when the tide turns again.

Thursday, February 21, 2019

China MOA: African Swine Fever Outbreak In Yunnan Province


After going nearly a full month (January 20th - February 19) reporting just one ASF outbreak, over the past three days China's MOA has announced three new outbreaks, including in two newly impacted provinces (Guangxi & Shandong).
This lull in reporting began - perhaps coincidentally - about two weeks before, and lasted until about two weeks after, this year's Chinese New Year celebration (Feb 5th).
The third outbreak reported in as many days comes  from Yunnan Province, which last reported an outbreak on November 17th of 2018.

African swine fever epidemic in Lishui City, Yunnan Province
Date: 2019-02-21 16:42 Author: Source: Ministry of Agriculture and Rural Press Office  

The Information Office of the Ministry of Agriculture and Rural Affairs was released on February 21, and an African swine fever epidemic occurred in Lishui City, Nujiang Prefecture, Yunnan Province.

On February 21, the Ministry of Agriculture and Rural Affairs received a report from the China Animal Disease Prevention and Control Center, which was diagnosed by the Yunnan Provincial Animal Disease Prevention and Control Center, and an African swine fever epidemic occurred in a farm in Lishui City, Nujiang Prefecture. Up to now, the farm has 300 pigs, 6 diseases and 2 deaths.

Immediately after the outbreak, the Ministry of Agriculture and Rural Affairs sent a steering group to the local area. The local government has started the emergency response mechanism according to the requirements, and adopted measures such as blockade, culling, harmless treatment, disinfection, etc., to treat all the sick and culled pigs harmlessly. At the same time, all pigs and their products are prohibited from being transferred out of the blockade, and pigs are prohibited from being transported into the blockade. At present, the above measures have been implemented.

While the ASF virus doesn't infect humans, but it can be devastating for the pig industry, and the ramifications of its continued global spread could certainly impact the public's health and well-being. 

ASF has never been reported in North America, but the potential exists for its importation from China, Europe, or Africa. Late in 2018 the USDA released a new African Swine Fever Factsheet that discusses their preparations for a possible introduction of the virus into this country.


Keeping ASF Out

Because of the concern over ASF, USDA recently reviewed and further strengthened its longstanding stringent protections against the spread of the disease.These include:
  • Collaborating with states, industry and producers to ensure everyone follows on-farm biosecurity and best practices (including for garbage feeding in states where that is allowed);
  • Restricting imports of pork and pork products from affected countries; and
  • Working with CBP staff at ports of entry to increase passenger and baggage screening for prohibited products from affected countries.

Saudi MOH: 3 New MERS Cases (2 In Wadi Aldwasir)


Saudi Arabia's 2019 MERS surge continues with three new cases announced today, one from Buraidah (36, M, Primary - no camel contact), and two more cases (26, M  & 35, M) from hard hit Wadi Aldwasir; both currently unclassified as to how they were exposed, and listed as `under investigation'.

Since January 29th, Wadi Aldwasir has reported 47 MERS cases, involving both primary community acquired infections (with, and without camel contact), and at least 3 clusters (healthcare, household, and community).
  • 6 cases have been listed as secondary, household contacts
  • 2 cases have been listed as secondary, community-acquired
  • 25 cases have been listed as secondary, healthcare-acquired.
While providing few details, the MOH has released a new awareness video (in Arabic) that warns of the risks of camel contact, and according to a media transcript,  reminds people:
The Ministry of Health recommended that citizens very cautious when dealing with camels; so wear protective clothing and disinfect hands constantly, and other safety means.

She added that it must communicate with the nearest health center when you notice any of the following symptoms: high temperature, dry cough with pain in the throat, acute lung, muscle pain, difficulty breathing, diarrhea, and vomiting.
The command and control center of the Ministry of Health, revealed that the recent increase of secondary cases in Wadi propellants, is linked to the status of the patient developed symptoms, and found after the diagnosis of a number of positive samples in contact with members of his family and a number of those who visited him, and in contact with reviewers.
The full video can be viewed on YouTube at

WHO: (Partial) Recommended Composition Of 2019-2020 Northern Hemisphere Flu Vaccine


Twice each year influenza experts gather to make recommendations for the next flu vaccine; once in September for the following year's Southern Hemisphere vaccine, and again in February for the Northern Hemisphere's fall-winter vaccine.
Decisions must be make months in advance to give manufacturers time to produce, package, and distribute tens of millions of doses before the start of the next flu season. 
And while new vaccine manufacturing technology has shaved off some of the required lead time, the increasing complexity and diversity of seasonal flu viruses - which can spread and evolve much faster today due to our highly mobile society - make selecting vaccine viruses a far more difficult job with each passing year.

As the map above illustrates, at any given time, the flu season you see depends upon where you look. This year, H1N1 has been the predominate flu virus in the Northern Hemisphere - but with pockets of H3N2 in the Southern part of the United States, in some African countries, and in parts of Europe.
Further complicating matters, both of these Influenza A virus subtypes are constantly evolving, have divided (and continue to divide) into multiple subclades, which are constantly jockeying for dominance.
The challenge for the world's flu experts is to predict which of these battling subclades will be king of the viral mountain when the next flu season arrives six months from now.
As we saw in November of 2014 (see A `Drift’ In A Sea Of Influenza Viruses), the global fluscape can change abruptly, greatly reducing the effectiveness of the current vaccine.
This week the World Health Organization has brought together representatives from GISRS (Global Influenza Surveillance and Response System), along with members of OFFLU (the OIE/FAO Network on Animal Influenza), and other experts to recommend what flu strains to include in next fall's vaccine.
And this year, even more so than in recent memory, the world's seasonal flu viruses are in flux. So much so the WHO has taken the unusual move of delaying the selection of one of the major components - the H3N2 virus - until March 21st.
First, today's announcement - which includes a strain change for the H1N1 virus - then I'll return with more on why the WHO has taken the unusual step of delaying their H3N2 pick for another 30 days.

Recommended composition of influenza virus vaccines for use in the 2019-2020 northern hemisphere influenza season
21 February 2019

It is recommended that egg based quadrivalent vaccines for use in the 2019-2020 northern hemisphere influenza season contain the following:

  • an A/Brisbane/02/2018 (H1N1)pdm09-like virus;
  • an A(H3N2) virus to be announced on 21 March 2019*;
  • a B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage); and
  • a B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage).
It is recommended that the influenza B virus component of trivalent vaccines for use in the 2019-2020 northern hemisphere influenza season be a B/Colorado/06/2017-like virus of the B/Victoria/2/87-lineage.

* In light of recent changes in the proportions of genetically and antigenically diverse A(H3N2) viruses, the recommendation for the A(H3N2) component has been postponed. 

For more information

 From the accompanying WHO FAQ on this year's selection:
Why is there a delay in selecting the A(H3N2) virus component of 2019-20 influenza vaccines?
Influenza A(H3N2) viruses have presented an increasing challenge for vaccine virus selection due to frequent changes in the virus and difficulties in generating candidate vaccine viruses for use in egg-based manufacturing. Experts at the consultation reviewed various sources of data including virus surveillance, antigenic characterization, and virus fitness forecasts, and identified multiple co-circulating influenza A(H3N2) virus groups.
In recent months, the proportion of viruses in one antigenically distinct group has increased in many countries, prompting a delay in the selection of the A(H3N2) vaccine component. This delay will allow more time for monitoring virus circulation and characterisation of appropriate vaccine viruses.
The H3N2 virus emerged as a pandemic strain in 1968 (supplanting seasonal  H2N2), settling in the following year as a seasonal flu strain and remained the sole human influenza A strain until 1977, when H1N1 mysteriously reappeared after a 20 year absence.
Since then, H3N2 has co-circulated with (first) the old H1N1 strain (until 2009) and then the new H1N1pdm09 strain. Unlike in previous pandemics, the 2009 H1N1 virus did not supplant the existing (in this case, H3N2) influenza A virus. 
All of which makes H3N2 a bit long in the tooth, having been circulating now for more than a half century. Over that time it has had to reinvent itself innumerable times (via antigenic drift) to evade acquired immunity, resulting in an increasing number of subclades of the virus co-circulating around the globe.

For the past decade H3N2 viruses have all belonged to clade 3C, which have further divided into three subdivisions; 3C.1 , 3C.2, and 3C.3.  For the past few years, clade 3C.2 (and numerous subclades within it) have dominated.

In recent months, however, an upstart 3C.3 clade has begun picking up steam in some parts of the world, as explained in the following passage from a more detailed report released by the WHO today.
Influenza A(H3N2) viruses
The majority of A(H3N2) viruses collected from September 2018 to January 2019 belonged to the phylogenetic subclade 3C.2a1b; however, the number of clade 3C.3a viruses has increased substantially since November 2018 in several geographic regions. There has continued to be considerable genetic diversification of the HA and NA genes, but viruses in subclade 3C.2a2 were much less prevalent than in the previous reporting period.

Antigenic characterisation of clade 3C.2a viruses continued to be technically difficult because a large proportion of viruses did not agglutinate red blood cells, preventing HI analysis of such viruses. Virus neutralisation assays have become the preferred method for determining the antigenic characteristics of current A(H3N2) viruses
        (Continue . . . )

The bottom line, while H3N2 clade 3C.2a1b is still the most prevalent strain, a long-shot 3C.3a subclade is making some moves, and WHO's experts would like another 30 days to see if that subclade's momentum continues.
While there is no one `perfect' vaccine strain that will guarantee protection against all circulating H3N2 viruses, it's a numbers game, and you want to match the strain most likely to be dominant next fall.
No easy task, and given that thousands of lives, millions of dollars, and the reputation of the flu vaccine are all at stake, be very thankful this isn't your decision to make.