Tuesday, January 16, 2018

Reminder: CDC Grand Rounds Today - Public Health Response to Severe Influenza


Although I blogged on it in some detail on Saturday (see CDC Grand Rounds: Nuke Detonation Postponed, Severe Flu Response Instead), a quick reminder that the presentation will be held live today at 1pm EST. 

Public Health Response to Severe Influenza

January 16, 2018 at 1:00 p.m. (ET)

Note: January 16 CDC Public Health Grand Rounds topic change to: “Public Health Response to Severe Influenza”

Registration is not required to watch our free Grand Rounds presentations. The webcast link below is only active during the date and time of the session, but all sessions are archived for future viewing.

CDC Grand Rounds Live Web stream

The topic for CDC’s Public Health Grand Rounds on January 16 will now focus on influenza. With the spike in flu cases around the country, this Grand Rounds will provide key and timely information for public health professionals on how to reduce the spread of seasonal flu in communities and adjust to spot shortages in antiviral drugs because of high influenza activity in some areas.

To date, this influenza season is notable for the sheer volume of flu that most of the United States is seeing at the same time which can stress health systems. The vast majority of this activity has been caused by influenza A H3N2, associated with severe illness in young children and people 65 years and older.

Join us for this session of Grand Rounds to learn what steps can be taken to reduce the spread of flu in communities and adjust to spot shortages in antiviral drugs in some places experiencing high influenza activity.

Note: The previous public health topic will be rescheduled for a future Grand Rounds.

CDC’s Public Health Grand Rounds Presents:

“Public Health Response to a Sharp Increase in Severe Seasonal Influenza”
Tuesday, January 16, 2018
1:00 p.m. – 2:00 p.m. (ET)

Global Communications Center (Building 19)
Alexander D. Langmuir Auditorium
Roybal Campus
Presented By:

Anne Schuchat, MD (RADM, USPHS)
Principal Deputy Director
Centers for Disease Control and Prevention

Dan Jernigan, MD, MPH, Captain, USPHS
Director, Influenza Division
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
“Chasing Flu”

David Wentworth, PhD
Chief, Virology, Surveillance, and Diagnosis Branch, Influenza Division
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
“The Problem of H3N2”

Alicia Fry, MD, MPH, Captain, USPHS
Chief, Epidemiology and Prevention Branch, Influenza Division
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
“Mitigating Influenza with Vaccines and Antivirals”

WHO: Yellow Fever In Brazil - Vaccination Recommended For Visitors to São Paulo State


Last year's Yellow Fever epidemic in Brazil was the worst in years, with the virus turning up in urban areas that had not experienced outbreaks in decades (see Brazil: Yellow Fever Updates From The MOH, The CDC, and University of Wisconsin).  
Complicating matters, there is serious shortage of the Yellow Fever Vaccine (see CDC Announcement: Yellow Fever Vaccine Access) which is expected to continue well into 2018.
In November a WHO update noted 2 recent human infections in São Paulo, along with 580 epizootics in non-human primates reported since the previous July. 

Today, they are reporting increased levels of yellow fever activity across São Paulo, and have issued a recommendation that international travelers to that state get the yellow fever vaccine.

Updates on yellow fever vaccination recommendations for international travelers related to the current situation in Brazil

16 January 2018

This is an update to the WHO advice posted in the Disease Outbreak News of 27 January 2017, 6 March 2017, 20 March 2017, 4 April 2017, and 24 November 2017; and on the WHO International Travel and Health website on 31 January 2017, 14 February 2017, 6 March 2017, 17 March 2017, and 4 April 2017.

Since December 2016, Brazil is experiencing an upsurge of yellow fever virus activity. Between 1 December 2016 and 30 June 2017, 1,659 epizootics in non-human primates were registered in 21 states (Alagoas, Amazonas, Bahia, Goiás, Espírito Santo, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Pará, Paraíba, Paraná, Pernambuco, Rio Grande do Norte, Rio Grande do Sul, Rio de Janeiro, Rondônia, Roraima, Santa Catarina, São Paulo, Sergipe, and Tocantins), and in the Federal District; a total of 777 human cases were reported, including 261 fatal, in eight states (Espírito Santo, Goiás, Mato Grosso, Minas Gerais, Pará, Rio de Janeiro, São Paulo, and Tocantins), as well as in the Federal District. On 9 September 2017, the government of Brazil declared that seasonal yellow fever virus activity has subsided.

Following the 2017 winter season in the Southern hemisphere, an increased yellow fever virus activity was again observed. Between 1 July 2017 to 8 January 2018, yellow fever virus infection was confirmed in relation to 358 epizootics in non-human primates in the states of Mato Grosso do Sul (0.3% of cases), Minas Gerais (9%), Rio de Janeiro (0.7%), and São Paulo (90%). As of 8 January 2018, 687 epizootics were under investigation for yellow fever in 17 states (Alagoas, Bahia, Goiás, Espírito Santo, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Pará, Paraná, Pernambuco, Rio Grande do Norte, Rio Grande do Sul, Rio de Janeiro, Santa Catarina, São Paulo, Sergipe, and Tocantins), and in the Federal District.

Over the same period of time, yellow fever virus infection was laboratory confirmed in 11 human patients, including four who died, from the states of Minas Gerais (one fatal case), Rio de Janeiro (one case), São Paulo (8 cases, including two fatal), and the Federal District (one fatal case). As of 8 January 2018, 92 additional human cases were under investigation for yellow fever virus infection in 15 states (Bahia, Goiás, Espírito Santo, Mato Grosso do Sul, Minas Gerais, Pará, Paraíba, Paraná, Pernambuco, Piauì, Rio Grande do Norte, Rio Grande do Sul, Santa Catarina, São Paulo, and Tocantins), as well as in the Federal District.

Considering the increased level of yellow fever virus activity observed across the state of São Paulo, the WHO Secretariat has determined that, in addition to the areas listed in previous updates, the entire state of São Paulo should also be considered at risk for yellow fever transmission.

Consequently, vaccination against yellow fever is recommended for international travellers visiting any area in the state of São Paulo

The determination of new areas considered to be at risk for the yellow fever transmission is an ongoing process and updates will be provided regularly.

The current advice by the WHO Secretariat for international travellers going to areas in Brazil deemed to be at risk is the following:
  • Vaccination against yellow fever at least 10 days prior to the travel. Note that, as per Annex 7 of the International Health Regulations (2005), a single dose of a yellow fever vaccine approved by WHO is sufficient to confer sustained immunity and life-long protection against yellow fever disease. Travellers with contraindications for yellow fever vaccine (children below 9 months, pregnant or breastfeeding women, people with severe hypersensitivity to egg antigens, and severe immunodeficiency) or, over 60 years of age should consult their health professional for advice;
  • adoption of measures to avoid mosquito bites;
  • awareness of symptoms and signs of yellow fever;
  • seeking care in case of symptoms and signs of yellow fever, while travelling and upon return from areas at risk for yellow fever transmission.

For 2017, updates on country requirements for the International Certificate of Vaccination or Prophylaxis, with proof of vaccination against yellow fever, and WHO vaccination recommendations for international travellers, are available on the WHO International Travel and Health website: Annex 1 and country list . More specific information about requirements for the International Certificate of Vaccination or Prophylaxis, with proof of vaccination against yellow fever, implemented by Member States related to the current situation in Brazil in the Region of the Americas is available on the PAHO yellow fever website.

mBio: Pandemic Paradox - Early Life H2N2 Infection Enhanced Mortality From H1N1pdm09

18 known HA subtypes divided into  2  groups


A little over a year ago, in Science: Protection Against Novel Flu Subtypes Via Childhood HA Imprinting, we looked at a study that strongly suggested the first HA Group type influenza virus an individual is exposed to makes the biggest, and most lasting, impression on your immune system.
And that the resultant immune response may carry over to other - similar - subtypes within that HA group.
This has some pandemic planning implications since - if your first influenza exposure was to H1N1 or H2N2 (group1) - you may carry some degree of immunity to the H5 viruses (H5N1, H5N6, etc.). If, however, your first exposure was to H3N2 (group 2), you may carry some protection against H7N9 instead.

Today, however, we have a new study in the open-access journal mBio that suggests there is more to this first life exposure to influenza than previously thought.

During the 2009 H1N1 pandemic, and its subsequent return for the 2013-14 flu season, those born during the 1957 H2N2 pandemic saw the highest mortality (see mbio chart below).

This is doubly unexpected. 

H1N1 and H2N2 are both group 1 HA types, and some cross protection might be expected. Also, the mortality rate dropped for those born after 1957 - when H2N2 was still circulating - and didn't spike for those born during the 1968 pandemic when H3N2 (a group 2 HA type) was the only influenza A game in town.

There is some historical precedent for this, as during the 1918 pandemic those born prior to 1890 appear to have been at least partially protected by (an assumed) H1Nx virus that likely circulated prior to the H3Nx pandemic of that year.  


Those born in 1890, during the H3Nx pandemic, would have turned 28 in 1918, and as the famous W Curve Chart above illustrates, that is the precise age that saw the highest number of deaths.
While none of this invalidates the previously described HA Group type cross-protection theory, it does suggest there are exceptions to the rule.
Since I can't possibly do this highly technical and intriguing study justice in the space I have allotted, I heartily suggest you find a quiet corner, turn off your phone ringer for an hour, and immerse yourself in:
Pandemic Paradox: Early Life H2N2 Pandemic Influenza Infection Enhanced Susceptibility to Death during the 2009 H1N1 Pandemic

    Alain Gagnona,b, Enrique Acostaa, Stacey Hallmanc, Robert Bourbeaua, Lisa Y. Dillona, Nadine Ouellettea, David J. D. Earnd,e, D. Ann Herringf, Kris Inwoodg, Joaquin Madrenash, Matthew S. Millere,i

Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. 
For example, during the 2009 H1N1 “swine flu” pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population.
Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 “Spanish flu.” Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 “swine flu” pandemic and during the resurgent 2013–2014 H1N1 outbreak for those born at the time of the 1957 H2N2 “Asian flu” pandemic.
We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics.

IMPORTANCE The relatively low mortality experienced by older individuals during the 2009 H1N1 influenza virus pandemic has been well documented. However, reported situations in which previous influenza virus exposures have enhanced susceptibility are rare and poorly understood. One such instance occurred in 1918—when those born during the heterosubtypic 1890 H3Nx influenza virus pandemic experienced the highest levels of excess mortality.
Here, we demonstrate that this phenomenon was not unique to the 1918 H1N1 pandemic but that it also occurred during the contemporary 2009 H1N1 pandemic and 2013–2014 H1N1-dominated season for those born during the heterosubtypic 1957 H2N2 “Asian flu” pandemic.
These data highlight the heretofore underappreciated phenomenon that, in certain instances, prior exposure to pandemic influenza virus strains can enhance susceptibility during subsequent pandemics. These results have important implications for pandemic risk assessment and should inform laboratory studies aimed at uncovering the mechanism responsible for this effect.
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Although I'm coming up on my 12th anniversary of full-time flu blogging, I am humbled by how much less I know about influenza than I did when I started.

Equine H3N8: Looking At A long-shot In The Pandemic Sweepstakes

Viruses 2018, 10(1), 31; doi:10.3390/v10010031


When it comes to influenza, conventional wisdom can often to blind us to an ever-changing fluscape.  Many things we thought we knew five, or ten years ago, we now find have either changed . . . or were never true to begin with.
Consider that just 15 years ago bats, cattle, and dogs and cats were not generally considered susceptible to influenza viruses.
Since then we've learned that:
I could go on, with reports on other improbable flu hosts, including camels, donkeys, seals and sea lions, minks, and skunks . . . .  but the point is, when it comes to influenza . . . there are more places to look than just in humans, birds, and pigs.

While long-shots in the influenza pandemic derby, canine and equine flu are of particular interest because the H3N8 and H3N2 subtypes they carry are similar to pandemic strains of the past (see chart below).

There is a lot of debate over these pre-1900 influenza pandemics, with conflicting views over whether the 1890-93 `Russian flu’ was due to the H2N2, H3N2, or H3N8 virus, but with most attributing the 1900 outbreak to H3N8 (see Transmissibility and geographic spread of the 1889 influenza pandemic). 

In the past couple of years we've looked repeatedly at the evolution, and potential threat, of canine influenza (see J. Virology: Zoonotic Risk, Pathogenesis, and Transmission of Canine H3N2 and J. Infect. Dis.: Molecular, Antigenic & Pathological Features of Canine H3N2 Influenza) - particularly since the Asian H3N2 canine flu has arrived in North America.

Equine H3N8 influenza - because it has remained relatively stable for 50 years (aside from jumping to dogs in 2004) - gets less attention, although we have ventured there occasionally (see J.Virol.: Experimental Infectivity Of H3N8 In Swine).
While we don't know the source of any of the older pandemics (or regional epidemics) going back several centuries, historical accounts have occasionally linked them to concurrent outbreaks in domesticated animals.

In 2010 the NIH tag team flu experts David Morens and Jeffrey K. Taubenberger penned a fascinating account of the 1872 equine epizootic - an epidemic in horses that spread from Canada to Mexico in a matter of months - and brought transportation to a standstill in this country (see A New Look At The Panzootic Of 1872)

This report provides a tantalizing review of anecdotal reports of a concurrent epizootic affecting poultry, and even causing human illness across the nation.
They wrote:

An explosive fatal epizootic in poultry, prairie chickens, turkeys, ducks, and geese occurred over much of the populated United States between November 15 and December 15, 1872. The epizootic progressed in temporal-geographic association with a well-reported panzootic of equine influenza, which had begun in or around Markham, Ontario, during the last few days of September 1872,1–4 at a time when human influenza had not been recently prevalent.

The equine epizootic spread rapidly into the United States along railroad lines, with separate simultaneous introductions into Michigan and upper New York State. It quickly spread over the entire United States to the Caribbean and Central America (Figure 1). Horses, mules, and menagerie/circus zebras were involved, with “spill over” infections into dogs and cats.4

Numerous individual human cases and localized outbreaks throughout the United States, often associated with exposures to ill horses, were reported. The human disease, generally mild and uncomplicated, was popularly referred to as the “epizooty”, or “zooty”.4
Whether this was an avian flu that jumped to horses, or an equine flu that spilled over into poultry - or two separate events - may never be known.  But Taubenberger and Morens wrote in their conclusion:
Another microbial agent could have caused the avian outbreak; however, its strong temporal and geographic association with the equine panzootic, and its clinical and epidemiologic features, are most consistent with highly pathogenic avian influenza. The avian epizootic could thus have been an early instance of highly pathogenic avian influenza.
All of which serves as prelude to a new study, published in Viruses, which looks at an oddball - isolated -  case of equine H3N8 in a horse from Montana.  The virus, surprisingly, carried both North American and Malaysian Equine H3N2 gene segments, and showed the ability to infect and replicate in a variety of non-equine cell lines.

A link, and a few excerpts, from a much longer (and fascinating) report:

Phylogenetic Analysis and Characterization of a Sporadic Isolate of Equine Influenza A H3N8 from an Unvaccinated Horse in 2015

Chithra C. Sreenivasan 1, Sunayana S. Jandhyala 1, Sisi Luo 1, Ben M. Hause 2, Milton Thomas 3, David E. B. Knudsen 3, Pamela Leslie-Steen 3, Travis Clement 3, Stephanie E. Reedy 4, Thomas M. Chambers 4, Jane Christopher-Hennings 3, Eric Nelson 3, Dan Wang 1,5, Radhey S. Kaushik 1,3 and Feng Li 1,3,5,*
Received: 26 December 2017 / Accepted: 9 January 2018 / Published: 11 January 2018

Equine influenza, caused by the H3N8 subtype, is a highly contagious respiratory disease affecting equid populations worldwide and has led to serious epidemics and transboundary pandemics. This study describes the phylogenetic characterization and replication kinetics of recently-isolated H3N8 virus from a nasal swab obtained from a sporadic case of natural infection in an unvaccinated horse from Montana, USA.

The nasal swab tested positive for equine influenza by Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR). Further, the whole genome sequencing of the virus confirmed that it was the H3N8 subtype and was designated as A/equine/Montana/9564-1/2015 (H3N8). A BLASTn search revealed that the polymerase basic protein 1 (PB1), polymerase acidic (PA), hemagglutinin (HA), nucleoprotein (NP), and matrix (M) segments of this H3N8 isolate shared the highest percentage identity to A/equine/Tennessee/29A/2014 (H3N8) and the polymerase basic protein 2 (PB2), neuraminidase (NA), and non-structural protein (NS) segments to A/equine/Malaysia/M201/2015 (H3N8).

Phylogenetic characterization of individual gene segments, using currently available H3N8 viral genomes, of both equine and canine origin, further established that A/equine/Montana/9564-1/2015 belonged to the Florida Clade 1 viruses.
Interestingly, replication kinetics of this H3N8 virus, using airway derived primary cells from multiple species, such as equine, swine, bovine, and human lung epithelial cells, demonstrated appreciable titers, when compared to Madin–Darby canine kidney epithelial cells. These findings indicate the broad host spectrum of this virus isolate and suggest the potential for cross-species transmissibility.

Overall, this study provided us insights about the evolutionary relationship and in vitro cross-species infectivity of A/equine /Montana/9564-1/2015 (H3N8) virus. A comprehensive genome-scale analysis of new isolates is essential to understand the molecular evolution and phylodynamics of EIV, which in turn would help in the strategic selection of vaccine strains, effective surveillance, and control.
Antigenic and genetic variations caused by evolutionary processes play a critical role in determining the dynamics of host range and tropism of influenza viruses. Further in vivo studies are needed to evaluate the cross-species transmissibility of EIV H3N8 and its ability to cause infections and respiratory diseases in other mammalian hosts, including humans.
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If you are betting on the source of the next influenza pandemic - human, avian, or swine hosts (or a combination) - are by far the most likely springboards.  At least based on the past 100 years of observation.

But influenza is notoriously unpredictable, and we have to be prepared for the fact that every once in awhile, a long shot may come in.

Monday, January 15, 2018

Saudi MEWA: Fri-Mon Reports 6 New Cases Of H5N8


A small number of new H5N8 cases continue to be reported by the Saudi Ministry of Environment, Water & Agriculture (MEWA), with the following reports posted since Friday.

Registration (3) new infections Panevlonz birds (H5N8)

25/04/1439  (Friday)

The ministry continues in cooperation with the relevant authorities efforts to contain the outbreak of high pathogenic avian influenza (H5N8), and during the twenty-four hours last make sure there is (3) injuries in both Quwaiya province in Riyadh and Buraidah in Qassim region, and the city of Medina in the backyard traditional breeding, except one injured in the bird market in the city of Medina.
(Continue . . . )

Recording injury (one) new bird flu (H5N8)

26/04/1439 (Saturday)

The ministry continues in cooperation with the relevant authorities efforts to contain the outbreak of high pathogenic avian influenza (H5N8), and during the twenty-four hours past and make sure there is injury (one) in the traditional monsters breeding birds Quwaiya province in Riyadh

(Continue . . . .)

No new cases of avian influenza (H5N8) during the 24-hour last

27/04/1439  (Sunday)

The ministry continues to cooperate with the relevant authorities efforts to contain the outbreak of high pathogenic avian influenza (H5N8), where no new cases of the disease among birds did not appear during the four and twenty hours last

(Continue . . . )

Recording two goals new bird flu (H5N8)

28/04/1439 (Monday)

The ministry continues to cooperate with the relevant authorities efforts to contain the outbreak of high pathogenic avian influenza (H5N8), where the number of new infections confirmed in the laboratory of the disease among birds during the twenty-four hours last in the Kingdom (two cases) only in the city of Dammam and the province of Riyadh region Dhurma

(Continue . . .)

OIE Notification: H5N8 in Karnataka, India

Credit Wikipedia


For nearly two weeks there have been unconfirmed media reports of bird flu in Karnataka State, in southern India.  First described as H5N1, later reports (see FluTrackers' Thread India - Karnataka: chicken in Dasarahalli tested positive for bird flu H5N1 (media))
rolled back the identification to simply HPAI H5. 

Today the OIE has published a notification on this outbreak, which began on December 26th, and cites HPAI H5N8 as the culprit.