Friday, September 22, 2017

Virology: Five Distinct Reassortants of HPAI H5N6 In Japan - Winter 2016–2017


While it seems longer, it was just over ten months ago that HPAI H5N6 broke out from its original range of China/Laos/Vietnam and turned up - first in South Korea - followed days later in Japan (see Japan: H5N6 Virus Detected At Izumi, Kagoshima).
South Korea was hardest hit, but within three weeks Japan had reported 53 separate detections (of one or more) HPAI positive wild birds across 11 Prefectures, along with several poultry outbreaks.  Numbers that would steadily grow over the winter.
Like its more famous cousin H5N8, the evidence suggested that HPAI H5N6 was expanding its geographic horizons via enhanced carriage by wild and migratory birds (see map above).  While H5N1 spread around the globe in a similar fashion, both clade H5N8 and H5N6 have moved farther and faster than any HPAI virus previously seen.  
As these viruses have conquered new territories, they've encountered a variety of other Avian Influenza (AI) viruses along the way, and being both promiscuous and out on a spree, have generated a large number of reassortants. 
Influenza A viruses are broadly categorized by two proteins they carry on their surface; their HA (hemagglutinin) and NA (neuraminidase), producing subtypes like H5N1, H7N9, or H5N6.  There are currently 18 known HA subtypes and 11 known NA subtypes.

So, when we talk about a subtype, we're aren't necessarily just talking about a single viral threat, but often an expanding array of related viruses sharing the same (or similar) HA and NA genes.

Within each HA subtype there can be genetic groupings called clades, and often within each clade - subclades. Within each of these, many minor variants may exist. Add in the ability to mix-and-match internal genes, and you can come up with literally dozens of genotypes for each subtype.
Each can have different properties (virulence, transmissibility, host range, etc.), and each is on its own evolutionary path. 
Last December, in Cell Host Microbe: Genesis, Evolution and Prevalence of HPAI H5N6 In China, we saw a report that found that H5N6 had become the dominant HPAI H5 virus in Chinese ducks (replacing H5N1), with 34 distinct H5N6 genotypes, including 4 that have infected people.

When H5N6 invaded South Korea last winter, reports suggested continual evolution of the virus (see Korea H5N6: New Genetic Analysis & Investigating Its Rapid Spread), with researchers reporting no fewer than 5 new genotypes during the first month.

We've a new report this week in the journal Virology that finds similar rapid evolution took place with the H5N6 virus during its foray into Japan last winter.  The full report is available via PDF, and is well worth reading in its entirety.

Five distinct reassortants of H5N6 highly pathogenic avian influenza A viruses affected Japan during the winter of 2016–2017
Under a Creative Commons license
open access
Download PDF


•    H5N6 HPAIVs affected poultry and wild birds in Japan during the winter of 2016–2017.
•    HA genes of the Japanese H5N6 strains belonged to the clade
•    Existence of 3 distinct AIV-derived PA genes in the Japanese H5N6 HPAIVs was evident.
•    NS genes of the Japanese H5N6 HPAIVs originated from 2 distinct Chinese H5N6 HPAIVs.
•    Five distinct genotypes among the Japanese H5N6 HPAIVs were found.


To elucidate the evolutionary pathway, we sequenced the entire genomes of 89 H5N6 highly pathogenic avian influenza viruses (HPAIVs) isolated in Japan during winter 2016–2017 and 117 AIV/HPAIVs isolated in Japan and Russia. 

Phylogenetic analysis showed that at least 5 distinct genotypes of H5N6 HPAIVs affected poultry and wild birds during that period. 

Japanese H5N6 isolates shared a common genetic ancestor in 6 of 8 genomic segments, and the PA and NS genes demonstrated 4 and 2 genetic origins, respectively. Six gene segments originated from a putative ancestral clade H5N6 virus that was a possible genetic reassortant among Chinese clade H5N6 HPAIVs. In addition, 2 NS clusters and a PA cluster in Japanese H5N6 HPAIVs originated from Chinese HPAIVs, whereas 3 distinct AIV-derived PA clusters were evident.

These results suggest that migratory birds were important in the spread and genetic diversification of clade H5 HPAIVs.

 (Continue . . .  )

The H5N6 virus has caused at least 17 human infections in China, with a high fatality rate, but thus far we've seen no reports of human infection out of South Korea, Japan (or later Taiwan and the Philippines).  The following passage from the study's discussion addresses this:
From May 2014 through December 2016, 17 human cases of clade H5N6 HPAIV infection were reported in China (Jiang et al., 2017). Our analysis indicated that amino acid substitutions responsible for adaptation to mammalian hosts (Bussey et al., 2010; Hatta et al., 2001; Min et al., 2013; Steel et al., 2009; Yamada et al., 2010) were missing from the Japanese H5N6 isolates.
The T160A mutation in the HA protein is linked to the acquisition of binding specificity for α2,6- linked sialic acid receptors, which are predominant in the human upper respiratory tract (Gu et al., 2017; Wang et al., 2010); however, some clade H5Nx HPAIVs that carry the T160A mutation show limited binding specificity for α2,6-linked receptors (Guo et al., 2017; Kaplan et al., 2016). Additional studies are needed to definitively understand the effect of T160A on the receptor specificity of clade H5N6 HPAIVs.
In addition, to our knowledge, no human cases resulting from a G1.1.9 H5N6 HPAIV that is a potential progenitor of Japanese H5N6 HPAIVs have been reported. Thus, the zoonotic potential of Japanese H5N6 HPAIVs is considered to be low.

As we've discussed before, even small changes in a virus can either enhance, or reduce, its virulence, transmissibility, or host range  (see Differences In Virulence Between Closely Related H5N1 Strains).  
While it has been a stroke of good fortune that recent strains of H5N6 have - at least temporarily -  evolved away from mammalian adaptation, there are no guarantees how long that trend will continue.
The take away from all of this is that H5N6, like its H5N8 cousin, are rapidly spreading, multifaceted, and continually evolving avian flu threats. What we can say about their behavior and threat to public health today may not hold true tomorrow.

For more on the rapid evolution of clade  H5 viruses, you may wish to revisit:

J. Virulence : Altered Virulence Of (HPAI) H5N8 Reassortant Viruses In Mammalian Models
J Vet Sci: Evolution, Global Spread, And Pathogenicity Of HPAI H5Nx Clade
Study: Virulence Of HPAI H5N8 Enhanced By 2 Amino Acid Substitutions

J. Virology: Molecular Evolution and Emergence of Avian H5N6

Thursday, September 21, 2017

#NatlPrep : One For The Home, And One More For The Road


Note: This is day 21 of National Preparedness Month . Follow this year’s campaign on Twitter by searching for the #NatlPrep hash tag.
This month, as part of NPM17, I’ll be rerunning some edited and updated older preparedness essays, along with some new ones. 


A little over forty-five years ago - when I was a teenager in a sleepy central Florida town - I took a 3-night first aid class offered by the American Red Cross, and taught by our local fire chief.  Part of our homework was to put together a `cigar-box’  first aid kit, which we would pledge to carry in our cars, or keep in our home.
I made two.  One for the home, and one more for the trunk of my car.
While they weren’t exactly professional quality, and I’ve upgraded many times since, I’ve never lost the habit. The following year I went on to become an EMT, and two years after that, I was a paramedic. I confess to still feeling a bit naked these many years later without having a decent first aid kit within easy reach.
I’ll admit that owning two ambu-bags borders on the excessive, but I certainly feel better knowing they are there. 
In addition to my two main `jump bags', I've a couple of `minor' cuts & scrapes kits I keep stashed in my medicine cabinet and in an overnight bag I keep for traveling. 

Well equipped first aid kits are a necessity in every home, and ideally should also be found in the trunk of every car. While you can purchase a ready-made kit (the quality of which varies depending on price), I’ve always preferred to create my own. 
I undoubtedly have a more elaborate kit than most, but perhaps a look inside my auto first aid bag will inspire some of my readers to make one of their own.
The `bag’ is an old style Laptop computer case, with a handle and a shoulder strap.  I like these, because they have numerous compartments, are soft, and are reasonably waterproof.

On the `trauma’ side of the bag, I’ve got `Kling’ roll bandages, an ACE bandage, a couple of cravat `Triangle’ bandage (sling & swath), sterile 4x4 gauze pads, paper tape, Band-Aids, antibiotic cream and several absorbent feminine pads (they make excellent trauma dressings). 

On the opposite side, I’ve got an `ambu’ bag-mask resuscitator along with a selection of adult and child airways, a foam C-Collar, a B/P cuff, stethoscope, flashlight, and some ammonia caps – hidden away where you can’t see them are bandage shears, tweezers, and a magnifying glass, along with a spare pair of reading glasses.

There is also a penlight, a felt tipped pen, and a note pad.

Under the front `cover’ flap, I keep some basic OTC medicines, including aspirin, acetaminophen, some hand antiseptic, and a bulb syringe (can be used for minor suctioning).

Under the flap on the other side, I’ve got surgical & N95 masks, exam gloves, and a `space’ blanket.

And if that weren't enough, I've a non-medical emergency kit in my trunk as well. Some water, another space blanket, glow sticks (safer than road flares), gloves, a few tools, flashlight, etc.

Of course, having a kit isn’t enough.  You need to know how to use it. 
And for that, you need first aid training.  If you haven’t already taken a course, contact your local Red Cross chapter, and find out what is available in your area.   And don’t forget the CPR training (or recertification!) as well.
Whether you buy a ready-made kit, or make your own, now is a good time to make sure you are fully equipped to deal with a medical emergency.
For more information I would invite you to visit:

Maryland DOH: 7 Fairgoers Test Positive For Swine Variant H3N2v


We've had 3 pretty quiet weeks on the swine variant flu front since the September 1st announcement of the 20th case of 2017 (see FluView Week 34: 1 Novel H1N2v Flu Infection Reported In Ohio). This morning, however, we are learning of 7 additional swine variant (H3N2v) infections in Maryland linked to the Charles County Fair. 

This press release from the Maryland Department of Health, released late yesterday.

Testing points to a flu virus in 7 fair-goers who had close contact with swine 
None of those who attended Charles County event is seriously ill with H3N2v
Baltimore, MD (September 20, 2017) – The Maryland Department of Health has presumptively identified the influenza virus strain H3N2v (variant flu) in seven Maryland residents who had close contact with pigs at the Charles County Fair. None of the infected individuals has developed serious illness or been hospitalized. 

Influenza is an infection caused by the influenza virus which can affect people and other animals, including pigs and birds. Symptoms for the H3N2v strain are the same as seasonal flu and include fever and respiratory symptoms, such as sore throat and cough. Historically, there is limited human to human transmission from this strain of variant flu. The treatment recommendations for this strain of influenza are the same as for seasonal flu. 

Health officials recommend that people with influenza-like illness contact their healthcare provider and inform them if they have had pig contact within the past seven days. Providers are advised to contact their local health departments if they suspect variant flu in their patients to coordinate appropriate testing with their local health department. The Charles County Health Department can be reached at 301-609-6900 ext. 6025 and the St. Mary’s County Health Department can be reached at 301-475-4330. 

Twenty other cases of variant flu have been detected in other states this year. Of those, 18 were also the virus strain H3N2v. Illnesses associated with these variant flu infections have been mostly mild with symptoms similar to those of seasonal flu. In 2012, 13 individuals developed influenza after direct contact with sick pigs at the Queen Anne’s County fair in Maryland. 

Certain people are at higher risk for complications of influenza, including children under five, the elderly, pregnant women, and those with chronic heart, lung, liver, kidney and neurologic conditions or immunosuppression. The spread of influenza, including the possible spread of H3N2v, between humans can be prevented by: 

Avoiding close contact with sick people;

  • Limiting contact with others as much as possible if you are sick to keep from infecting them and staying home from work or school if you are sick until you are fever free for 24 hours without fever reducing medicines;
  • Covering your nose and mouth with a tissue when you cough or sneeze and dispose of the tissue immediately after use;
  • Washing your hands often with soap and water or alcohol-based hand rub if soap and water are not available;
  • Avoiding touching your eyes, nose and mouth;
  • Cleaning and disinfecting surfaces and objects that may be contaminated with germs like the flu; and
  • Getting the seasonal influenza vaccine when it becomes available. Although it is not effective against H3N2v, it is protective against other common strains of influenza.
The spread of influenza between pigs and humans can be prevented by:
  • Washing your hands frequently with soap and running water before and after exposure to pigs;
  • Never eating, drinking or putting things in your mouth in pig areas;
  • Considering avoiding exposure to pigs and swine barns this summer, especially if sick pigs have been identified and if you are high risk of complications from influenza;
  • Watching your pig for signs of illness and calling a veterinarian if you suspect they might be sick;
  • Avoiding close contact with pigs that look or act ill; and
  • Avoiding contact with pigs if you are experiencing flu-like symptoms.
Additional information from the Centers for Disease Control and Prevention regarding Swine Influenza/Variant Influenza Viruses is available here.

Due to concerns over additional possible transmission, Maryland's Secretary of Agriculture has issued an order closing the swine venues at two upcoming county fairs.

Last month, in EID Journal: Transmission Of Swine H3N2 To Humans At Agricultural Exhibits - Michigan & Ohio 2016, we looked at the risks of novel flu transmission in these types of venues, including from healthy-looking pigs.
Most years fewer than a dozen `swine variant' infections are reported in the United States, mostly involving farm or livestock workers. Most are mild, but it is likely that many others go undiagnosed.
A far cry from 2012, when 10 states reported more than 300 confirmed cases (see H3N2v Update: CDC Reports 52 New Cases, Limited H2H Transmission) assuming these 27 cases are confirmed by the CDC - would make 2017 the 2nd busiest swine variant year on record.
With state and county fair season continuing over the summer and into fall, it would not be unexpected to see additional, scattered reports of swine variant infection. 
While rarely as severe as avian flu in humans, swine influenza viruses nevertheless are considered to have some pandemic potential. The CDC's IRAT (Influenza Risk Assessment Tool) Rankings monitors and characterizes 14 different novel flu viruses, and has this assessment on H3N2v

H3N2 Variant:[A/Indiana/08/11]

Swine-origin flu viruses do not normally infect humans. However, sporadic human infections with swine-origin influenza viruses have occurred. When this happens, these viruses are called “variant viruses.” Influenza A H3N2 variant viruses (also known as “H3N2v” viruses) with the matrix (M) gene from the 2009 H1N1 pandemic virus were first detected in people in July 2011. The viruses were first identified in U.S. pigs in 2010. In 2011, 12 cases of H3N2v infection were detected in the United States. In 2012, 309 cases of H3N2v infection across 12 states were detected. The latest risk assessment for this virus was conducted in December 2012 and incorporated data regarding population immunity that was lacking a year earlier.
Summary: The summary average risk score for the virus to achieve sustained human-to-human transmission was in the moderate risk category (less than 6). The summary average risk score for the virus to significantly impact public health if it were to achieve sustained human-to-human transmission was in the low-moderate risk category (less than 5).

For some recent blogs on Swine variant influenza, and why the CDC closely monitors these infrequent human infections, you may wish to revisit:

Ohio: Henry County Fair Closes Pig Barn Over H1N2 Swine Flu

Second Ohio County Fair Closes Hog Barn Over Swine Flu

A Reminder About The `Other' Novel Flu Threat

MMWR: Investigation Into H3N2v Outbreak In Ohio & Michigan - Summer 2016

Wednesday, September 20, 2017

#NatlPrep: Because Sometimes It Is Darkest After The Storm

Note: This is day 20 of National Preparedness Month . Follow this year’s campaign on Twitter by searching for the #NatlPrep hash tag.
This month, as part of NPM17, I’ll be rerunning some edited and updated older preparedness essays, along with some new ones. 

Short term power outages affect most of us each year, usually lasting anywhere from a few minutes to a couple of hours.  Longer outages, while less common, are far from rare - as anyone who found themselves in the path of hurricanes Harvey, Irma, and Marie over the past month will attest.
While my power was restored late last week, there are still a few thousand without power in Florida, and with Marie's landfall a few hours ago, likely millions more are without electricity now in Puerto Rico. 
As so many have recently discovered (or rediscovered), after about 12 hours without electricity, the quality of life begins to sharply decline.  After 48 hours life just sucks.
While having no TV, or Internet, or electric lights might seem more of an inconvenience than anything else, sometimes not having power can be deadly (see Ninth person dead in Florida nursing home where Irma knocked out power).
During the summer of 2012, a powerful Derecho swept across the Mid-Atlantic states (see Picking Up The Pieces), killing 15 and leaving nearly 4 million people without power, some for more than 2 weeks. While 15 people died during the storm, at least 32 died of heat-related illnesses in the two weeks that followed.   This from a 2013 MMWR:
Heat-Related Deaths After an Extreme Heat Event — Four States, 2012, and United States, 1999–2009


June 7, 2013 / 62(22);433-436 On June 29, 2012, a rapidly moving line of intense thunderstorms with high winds swept across the midwestern and eastern United States, causing widespread damage and power outages.
Afterward, the area experienced extreme heat, with maximum temperatures exceeding 100°F (37.8°C) (1). This report describes 32 heat-related deaths in Maryland, Ohio, Virginia, and West Virginia that occurred during the 2 weeks following the storms and power outages. 

Most decedents (75%) were unmarried or living alone. Common underlying or contributing conditions included cardiovascular disease (14) and chronic respiratory disease (four). In at least seven (22%) of the deaths, loss of power from the storms was known to be a contributing factor. Overall, 22 (69%) decedents died at home, with lack of air conditioning reported in 20 (91%) of these deaths.
       (Continue . . . )

As I've written often (see #NatlPrep: Disaster Buddies) people who live alone - nearly 1 person in 10 in the United States - are particularly vulnerable during a disaster.
For some of them, having a place to go when staying put would endanger their safety, and a way to get there, can literally mean the difference between life and death.
Hurricanes, ice storms, Nor’easters, tornadoes, floods, tornadoes . . .  and even solar storms (see Solar Storms, CMEs & FEMA) are capable of crippling power production and delivery.
Add in our aging infrastructure, and the potential of cyber (or physical) attacks on the system, and the odds of seeing more major power outages only increases.
Without electrical power, water and gasoline doesn’t pump, elevators and air conditioners don’t run, ATM machines and banks close, grocery stores can’t take debit or credit cards, produce, meat and frozen foods spoil, and and everything from cooking, to flushing toilets, becomes a major challenge.
Particularly in urban settings. 
If a disaster struck your region today, and the power went out, stores closed their doors, and water stopped flowing from your kitchen tap for the next 7 to 10 days  . . .  do you have:
  • A battery operated NWS Emergency Radio to find out what was going on, and to get vital instructions from emergency officials?
  • A decent first-aid kit, so that you can treat injuries?
  • Enough non-perishable food and water on hand to feed and hydrate your family (including pets) for the duration?
  • A way to provide light (and in cold climates, heat) for your family without electricity?   And a way to cook?  And to do this safely?
  • A small supply of cash to use in case credit/debit machines are not working?
  • An emergency plan, including meeting places, emergency out-of-state contact numbers, a disaster buddy,  and in case you must evacuate, a bug-out bag?
  • Spare supply of essential prescription medicines that you or your family may need?
If your answer is `no’, you have some work to do.  A good place to get started is by visiting  
Unfortunately, a lot of people make the wrong choices when they do prepare.  They buy candles instead of battery operated lights, they use generators inside their house or garage, or resort to dangerous methods to cook or to heat their homes. 
As a result, when the power goes out, house fires and carbon monoxide poisonings go up. Each year hundreds of Americans are killed, and thousands affected, by CO poisoning (see In Carbon Monoxide: A Stealthy Killer).  
While preparedness may seem like a lot of work, it really isn’t.  You don’t need an underground bunker, an armory, or 2 years worth of dehydrated food.  But you do need the basics to carry on for a week or two, and a workable family (or business) emergency/disaster plan. 
But you need to make these preparations now, before the next threat appears on the horizon.  In central Florida, there wasn't a case of water, a flashlight, or a battery to be had a full 5 days before Irma struck.  Those who procrastinated were out of luck.

For more information on how to prepare, I would invite you  to visit:

A final note:  Living in Florida, and having endured some mighty uncomfortable power outages, I've come to really appreciate having a battery operated fan in my emergency kit.

The little fan above cost me about $12, runs for roughly 24 hours on 3 D cells, moves a pretty good amount of air, and makes a great little preparedness item. There are also USB fan options, which can run off of USB powerbanks (which in turn can be charged by solar panels).

CDC Update: Candida Auris - September 2017


Last summer (June 24th, 2016) the CDC issued a Clinical Alert to U.S. Health care facilities about the Global Emergence of Invasive Infections Caused by the Multidrug-Resistant Yeast Candida auris.
C. auris is an emerging fungal pathogen that was first isolated in Japan in 2009. It was initially found in the discharge from a patient's external ear (hence the name `auris').  Retrospective analysis has traced this fungal infection back over 20 years.
Since then the CDC and public health entities have been monitoring an increasing number of cases (and hospital clusters) in the United States and abroad, generally involving bloodstream infections, wound infections or otitis (see August Update).
Adding to the concern:
  1. C. auris infections have a high fatality rate
  2. The strain appears to be resistant to multiple classes of anti-fungals  
  3. This strain is unusually persistent on fomites in healthcare environments.
  4. And it can be difficult for labs to differentiate it from other Candida strains
Last month the CDC promoted the first ever Fungal Disease Awareness Week, and presented a COCA call webinar called Tackling an Invasive, Emerging, Multi-drug Resistant Yeast: Candida auris — What Healthcare Providers Need to Know, which is now archived and available online.

CIDRAP's Antimicrobial Stewardship Project (ASP) also held an hour long webinar (see below), which is now available on the CIDRAPASP Youtube channel.
 (Note: you'll find more than a dozen other on-topic videos available on this channel as well).
This week the CDC updated their C. Auris surveillance page, where they now show 126 confirmed cases and 27 probable cases, across 10 states (California was added this month). The number of colonized asymptomatic cases has risen to 143.

Tracking Candida auris

September 18, 2017: Case Count Updated as of August 31, 2017

Candida auris is an emerging fungus that presents a serious global health threat. C. auris causes severe illness in hospitalized patients in several countries, including the United States. Patients can remain colonized with C. auris for a long time and C. auris can persist on surfaces in healthcare environments. This can result in spread of C. auris between patients in healthcare facilities.

Most C. auris cases in the United States have been detected in the New York City area and New Jersey. Strains of C. auris in the United States have been linked to other parts of the world. U.S. C. auris cases are a result of inadvertent introduction into the United States from a patient who recently received healthcare in a country where C. auris has been reported or a result of local spread after such an introduction.

Please note that as of September 18, 2017, the total case counts reported include both probable and confirmed clinical cases; previously reported case counts included only confirmed cases. Case counts for some states are quite a bit higher than those listed before September 18, 2017 because of the change in reporting, and not because of a large increase in new cases. Read more below about how cases are defined.

WHO: The World Is Running Out Of Antibiotics


While pandemics and outbreaks of novel diseases like avian flu, MERS, and Zika make the immediate headlines, in terms of medium-to-long term threats, there is little that can match the potential harm from the rise of antibiotic resistant bacteria around the globe.
Despite decades of warnings, this threat is largely under appreciated by the public because its progression has been gradual, the loss of antibiotics incremental, and so far at least . . . there have always been replacement drugs available when an antibiotic has failed.
But the number of new antibiotics in the pipeline are desperately few, and the pace of newly emerging resistant bugs has increased greatly in recent years. While the numbers remain small, we are beginning to see the emergence of pan-resistant bacteria.

A few (of dozens) of unwelcome antimicrobial resistant milestones reported in the past couple of years include:

Eurosurveillance: Mcr-One, Two, Three And Counting
MMWR: Fatal Pan-Drug Resistant CRE - Nevada 2016
mBio: 1st Colistin & Carbapenem Resistant E. Coli Infection In A U.S. Patient
Eurosurveillance: Identification Of A Novel Colistin-Resistant MRC-2 Gene In E Coli - Belgium, 2016
CDC HAN: Alerting Healthcare Facilities Of 1st MCR-1 Gene Detection In US Patient

And just three weeks ago CIDRAP reported on a Hypervirulent, highly resistant Klebsiella identified in China, one which a week later was described as New Klebsiella strains 'worst-case scenario,' experts say. 
If we're in a war against resistant bacteria, the news from the front isn't good.
Today the World Health Organization released a grim assessment of the current state of antibiotic development, calling on pharmaceutical companies and researchers to `urgently focus on new antibiotics against certain types of extremely serious infections'.

News release 
A report, Antibacterial agents in clinical development – an analysis of the antibacterial clinical development pipeline, including tuberculosis, launched today by WHO shows a serious lack of new antibiotics under development to combat the growing threat of antimicrobial resistance.

Most of the drugs currently in the clinical pipeline are modifications of existing classes of antibiotics and are only short-term solutions. The report found very few potential treatment options for those antibiotic-resistant infections identified by WHO as posing the greatest threat to health, including drug-resistant tuberculosis which kills around 250 000 people each year.

"Antimicrobial resistance is a global health emergency that will seriously jeopardize progress in modern medicine," says Dr Tedros Adhanom Ghebreyesus, Director-General of WHO. "There is an urgent need for more investment in research and development for antibiotic-resistant infections including TB, otherwise we will be forced back to a time when people feared common infections and risked their lives from minor surgery."

In addition to multidrug-resistant tuberculosis, WHO has identified 12 classes of priority pathogens – some of them causing common infections such as pneumonia or urinary tract infections – that are increasingly resistant to existing antibiotics and urgently in need of new treatments.

The report identifies 51 new antibiotics and biologicals in clinical development to treat priority antibiotic-resistant pathogens, as well as tuberculosis and the sometimes deadly diarrhoeal infection Clostridium difficile.

Among all these candidate medicines, however, only 8 are classed by WHO as innovative treatments that will add value to the current antibiotic treatment arsenal.

There is a serious lack of treatment options for multidrug- and extensively drug-resistant M. tuberculosis and gram-negative pathogens, including Acinetobacter and Enterobacteriaceae (such as Klebsiella and E.coli) which can cause severe and often deadly infections that pose a particular threat in hospitals and nursing homes.

There are also very few oral antibiotics in the pipeline, yet these are essential formulations for treating infections outside hospitals or in resource-limited settings.

"Pharmaceutical companies and researchers must urgently focus on new antibiotics against certain types of extremely serious infections that can kill patients in a matter of days because we have no line of defence," says Dr Suzanne Hill, Director of the Department of Essential Medicines at WHO.

To counter this threat, WHO and the Drugs for Neglected Diseases Initiative (DNDi) set up the Global Antibiotic Research and Development Partnership (known as GARDP). On 4 September 2017, Germany, Luxembourg, the Netherlands, South Africa, Switzerland and the United Kingdom of Great Britain and Northern Ireland and the Wellcome Trust pledged more than €56 million for this work.

"Research for tuberculosis is seriously underfunded, with only two new antibiotics for treatment of drug-resistant tuberculosis having reached the market in over 70 years," says Dr Mario Raviglione, Director of the WHO Global Tuberculosis Programme. "If we are to end tuberculosis, more than US$ 800 million per year is urgently needed to fund research for new antituberculosis medicines".

New treatments alone, however, will not be sufficient to combat the threat of antimicrobial resistance. WHO works with countries and partners to improve infection prevention and control and to foster appropriate use of existing and future antibiotics. WHO is also developing guidance for the responsible use of antibiotics in the human, animal and agricultural sectors.

Note to editors

For more information, download the following reports:
The clinical pipeline analysis data can be explored in an interactive way through: