Monday, May 30, 2016

Detection Of Airborne H9 Nucleic Acid In Chinese Live Poultry Market


In China the link between live poultry markets (LPMs) and the spread (and reassortment of) avian flu strains is already well established, and it is easy to understand why.

Large quantities of birds of varying species (chickens, ducks, geese, quail, and others) are brought in from different farms, housed together in cramped quarters, and then slaughtered (and often de-feathered) in open air booths as thousands of people walk by. 

Not only does this expose humans to avian viruses, it facilitates the sharing of different avian flu subtypes (H5, H7, H9) among the birds, promoting continual reassortment and the creation of new clades, or subtypes.

In 2014, a year after the H7N9 virus emerged in China, in CDC: Risk Factors Involved With H7N9 Infection, we looked at a case-control study that pretty much nailed LPMs as the prime  risk factor for infection.

While even casual exposure to poultry in live bird markets was cited as the primary risk factor, people who owned, raised, or slaughtered birds at home, on farms, or in the wild were not found to be at any increased risk.

Last December, a Who's Who of avian flu experts, writing in The Lancet: Interventions To Reduce Zoonotic & Pandemic Risks From Avian Flu In Asia listed immediate actions that should be taken by LPMs to curb the evolution and spread of avian flu in Asia.

The detection of viral RNA (or sometimes live virus) in LPMs isn't new (see Macao Detects H7 In Poultry Market - Live Sales Halted 3 Days), and some studies (see H5N1: Hiding In Plain Sight) have shown these viruses may survive for days or even weeks under the right conditions.

But these detections have generally been on fomites (inanimate objects like knives, table tops, cages, etc.) or in environmental contamination from chicken manure, feathers, entrails, or dust.  

Less well defined is the airborne spread of avian viruses in these markets, although it may explain how a few people just walking past a live market have reportedly been infected.

Three years ago, in How to Aerosolize A Chicken, we looked at one plausible way this can happen, through the use of mechanical de-feathering machines used in some chicken stalls.
And there is some evidence that avian viruses can be spread from farm to farm - at least over short distances - by prevailing winds (see Bird Flu’s Airborne `Division).

Adding more weight to this idea, a year ago, in CIDRAP: H5N2 Roundup & Detection In Environmental Air Samples, we looked at air sampling conducted by the University of Minnesota around infected poultry farms that found evidence of airborne virus particles.

But until now, little has been published on the search for airborne avian flu viruses in and around live poultry markets in China.  

Which brings us to a study, published last week in the Chinese Medical Journal, which describes two years of environmental and air testing from one of the hundreds of LPMs in Nanning, China (Guangxi province).

They collected Aerosol samples from one (of 12) random stalls (including chickens, geese, and ducks) every week.  At the same time they collected floor sewage and feathers, and swabbed poultry cages and chopping blocks.

Samples were cataloged and tested for influenza A viral RNA and positive samples were then analyzed to determine their (H5/H7/H9) subtype.

RT-PCR testing is very sensitive, and the detection of viral RNA is a much lower bar than isolating live virus, and doesn't tell us about the viability of the viruses they detected.

The (open access) study found ample environmental evidence of viral contamination, and reports the first positive detection of Airborne H9 (presumably H9N2) in a Chinese LPM. 

Although not a huge threat to human health, H9N2 is increasingly on our radar because the number of human infections appear to be increasing, we've seen signs of increasing mammalian adaptations, and because it has contributed its internal genes to a number of reassorted avian flu viruses.

Guangxi Province has only reported 3 cases of H7N9, and so it isn't terribly surprising that H7 viruses were not detected, and while H5 viruses were found in roughly 20% of environmental samples, no airborne H5 was detected.

The full report can be read at the link below, I've included some excerpts from the discussion:

First Positive Detection of H9 Subtype of Avian Influenza Virus Nucleic Acid in Aerosol Samples from Live Poultry Markets in Guangxi, South of China.



Overall,  the present results suggest that AIV  nucleic  acid exist in aerosol and other environmental samples from LPMs of  Guangxi.  Aerosol  transmission  might  be  an  important  mode of human infected by AIV after visiting LPMs; thus, it is needed to monitor virus distribution in aerosol sample from LPMs.
Previous studies have shown that LPMs were closely linked to H9N2, H5N1, and H7N9 infection in human in 2003,[4]  2006, and 2013,[5] respectively.

LPMs promote the transmission of AIV from avian to human. It is still needed to confirm the transmitted mechanism through exposure  or  visiting  LPMs.  Chickens  were  successfully  infected  with  AIV  H5N1and  H9N2  by  aerosol  and  caused  higher titers of virus. [6,7]
Avian influenza H9 has been isolated animals  from  LPMs[8‑11]  and  from  air  in  chicken  houses  in  China. Our results first reported H9 subtype of AIV nucleic acid existing in aerosol sample from LPM of Guangxi, China, providing support for aerosol transmission of AIV in LPM.
H5 subtype of AIV nucleic acid was not detected positive in  aerosol  while  it  was  positive  in  other  four  styles  of  environmental samples. H9 subtype was positive in aerosol and other four styles of environmental samples in 2014.

It is still needed further study to investigate whether there are differences in viral viability between H5 and H9 subtypes in aerosol and other environmental samples. As  LPMs  play  an  important  role  in  the  dissemination  of  AIVs, active surveillance to monitor AIV in LPMs should be carried out as an early warning system for AIV outbreaks.

WHO Zika Virus Outbreak Global Response (Interim Report)


The World Health Organization has published a 14-page report outlining the WHO-led global response to the Zika Virus, and the emerging funding (or lack thereof) that they've received to date.

The report begins with brief sections on Zika's background and on last February's Strategic Response Framework and Operations Plan, which is summarized in the graphic below.

It then provides an agency by agency list of funding requests, the funding actually received, and the resultant gap.  At this point these funding gaps run (depending on which agency) from about 80% to 99%.

The full report is available HERE.

Sunday, May 29, 2016

Avoiding Naegleria


Each summer we see a handful of tragic deaths – mostly of children – due to a nearly always fatal condition called PAM (Primary amebic meningoencephalitis), caused by a brain infection from an amoebic parasite called Naegleria fowleri.

Dubbed the `brain eating amoeba' by the press, this parasite enters the brain through the nasal passages, usually due to the forceful aspiration of water (containing the amoeba) into the nose. 

Until a few years ago, nearly all of the Naegleria infections reported in the United States were linked to swimming in warm, stagnant freshwater ponds and lakes (see Naegleria: Rare, 99% Fatal & Preventable), making this pretty much a summer time threat.

In 2011, however,  we saw two cases reported in Neti pot users from Louisiana, prompting the Louisiana Health Department to recommend that people `use distilled, sterile or previously boiled water to make up the irrigation solution’ (see Neti Pots & Naegleria Fowleri).

While extraordinarily rare in the United States, every year Pakistan reports a dozen or more infections from this `killer amoeba’, as chlorination of their water supplies is often inadequate, and for many, nasal ablutions are part of their daily ritual. 

Unusually, in 2013 we saw a 4 year-old  infected through contact with a municipal water supply while visiting St. Bernard Parish, Louisiana.  Since then testing has revealed Naegleria in a number of municipal water supplies across the state of Louisiana (see Louisiana: 2nd Public Water System Reports Naegleria).

And just last month we looked at an MMWR: Epidemiological Investigation Into A Case Of Primary Amebic Meningoencephalitis  in California which suggested a poorly chlorinated spring-fed swimming pool was the likely source of infection and death of a 21 year old woman.  

This was also an unusual finding, and furthers the recent pattern of seeing PAM cases arise from atypical settings (Northern states, via neti pots and municipal water supplies, etc.) in the United States.

Up until a recently, infection with Naegleria fowleri was universally fatal, but in 2013 an investigational drug called miltefosine was used successfully for the first time to treat the infection.  Early diagnosis, and administration of this drug, are crucial however.

Even with this new drug, prevention is the key to saving lives, and leading the charge in educating the public is, a USF Philip T. Gompf Memorial Fund project, which was set up by a pair of Florida doctors who tragically lost their 10 year-old son to this parasite in 2009.  

Their twitter account -  @AmoebaSeason - is promoting Healthy and Safe Swimming Week 2016  all this week, which will culminate with with a twitter `Thunderclap' on May 31 at 4:00PM EDT urging the CDC to make brain amoeba infection reportable.

I'm hoping some of my readers will join in. 

In the meantime, their website offers a wealth of information on the amoeba, and some important safety advice to avoid this waterborne threat.

For some of my earlier blogs on Naegleria you may wish to revisit:

A Reminder About Naegleria
Reminder: COCA Call Today On Naegleria Fowleri & Cryptosporidium
MMWR: CDC Imports Investigational Drug For Amoebic Infections

Friday, May 27, 2016

NOAA: `Near Normal' Atlantic Hurricane Season Expected


With the caveat that it just takes one major land falling storm in a populated region to make for an epic hurricane season, today NOAA announced their prediction for this year’s Atlantic hurricane season.  

First their statement, after which I’ll have a bit more.

70 percent likelihood of 10 to 16 named storms

May 27, 2016 NOAA’s Climate Prediction Center says the 2016 Atlantic hurricane season, which runs from June 1 through November 30, will most likely be near-normal, but forecast uncertainty in the climate signals that influence the formation of Atlantic storms make predicting this season particularly difficult. 
NOAA predicts a 70 percent likelihood of 10 to 16 named storms (winds of 39 mph or higher), of which 4 to 8 could become hurricanes (winds of 74 mph or higher), including 1 to 4 major hurricanes (Category 3, 4 or 5; winds of 111 mph or higher). While a near-normal season is most likely with a 45 percent chance, there is also a 30 percent chance of an above-normal season and a 25 percent chance of a below-normal season. Included in today’s outlook is Hurricane Alex, a pre-season storm that formed over the far eastern Atlantic in January. 

“This is a more challenging hurricane season outlook than most because it’s difficult to determine whether there will be reinforcing or competing climate influences on tropical storm development,” said Gerry Bell, Ph.D., lead seasonal hurricane forecaster with NOAA’s Climate Prediction Center. "However, a near-normal prediction for this season suggests we could see more hurricane activity than we’ve seen in the last three years, which were below normal.”

Bell explained there is uncertainty about whether the high activity era of Atlantic hurricanes, which began in 1995, has ended. This high-activity era has been associated with an ocean temperature pattern called the warm phase of the Atlantic Multi-Decadal Oscillation or AMO, marked by warmer Atlantic Ocean temperatures and a stronger West African monsoon. 

However, during the last three years weaker hurricane seasons have been accompanied by a shift toward the cool AMO phase, marked by cooler Atlantic Ocean temperatures and a weaker West African monsoon. If this shift proves to be more than short-lived, it could usher in a low-activity era for Atlantic hurricanes, and this period may already have begun. High- and low-activity eras typically last 25 to 40 years.

In addition, El Niño is dissipating and NOAA’s Climate Prediction Center is forecasting a 70 percent chance that La Niña — which favors more hurricane activity — will be present during the peak months of hurricane season, August through October. However, current model predictions show uncertainty as to how strong La Niña and its impacts will be.

(Continue . . .)

While these outlooks can give us an idea of what kind of season to expect, long-range forecasting is still fairly crude, and the number of storms matters less than where the storms that do form end up going.

Below average hurricane years - such as we've seen for the past three seasons - are always welcome, but they don't necessarily turn out uneventful.

The outlook in 1992 was for a `below average' year, and with only 4 hurricanes and 3 tropical storms, it certainly met that mark. 

And were it not for the first hurricane of that year - a CAT 5 monster named Andrew that devastated a large swath of South Florida - there would be little reason to remember it.

Andrew was the last land falling CAT 5 storm to hit the US mainland. Before that, you'd have to go back to Camille, which struck the Gulf coast in 1969.

It's been more than 10 years since the last major (CAT 3+) storm has hit the United States (Wilma in 2005), and hopefully we'll avoid that again this year.

But the smart money is on preparing as if we won't get that lucky. 

Last Sunday, in Hurricane Preparedness 2016,we looked at many of the steps you and your family need to do to prepare for this year's hurricane season.

And lastly, when  it comes to getting the latest information on hurricanes, your first stop should always be the National Hurricane Center in Miami, Florida. Those on Twitter should also follow @FEMA, @ReadyGov. @CraigatFEMA, and @NHC_Atlantic  or  @NHC_Pacific.

Virulence Of A Novel Reassortant Canine H3N2 In Ferret, Dog and Mouse Models


For the past few years we've been following research into the emergence and evolution of an emerging avian-origin canine H3N2 virus, which first appeared in Korea nearly a decade ago, moved into China, and appeared in the United States in the spring of 2015.

Unlike the canine influenza virus (CIV) that emerged in North America in 2004 (H3N8) which jumped from equines, the HA and NA genes from A/canine/Korea/01/2007 (H3N2) are closely related to those identified in 2003 in chickens and doves in South Korea.

Over the next few years CIV H3N2 spread into China, and in 2011 a study that appeared in the Journal of General Virology, showed that it had begun to infect cats as well (see  Korea: Interspecies Transmission of Canine H3N2).

The plot thickened again when we saw evidence of reverse zoonosis, resulting in a  Canine H3N2 Reassortant With pH1N1 Matrix Gene, producing a novel hybrid between the 2009 H1N1 virus and CIV. 

When this H1N1 M gene turned up in reassorted swine variant viruses (H1N1v, H3N2v, H1N2v), The CDC speculated that `This M gene may confer increased transmissibility to and among humans, compared to other variant influenza viruses.’ – CDC HAN 2012
And just last April, in A Canine H3N2 Virus With PA Gene From Avian H9N2 - Korea, we saw yet another example of CIV reassortment, this time with an avian virus. 

The Canine H3N2 virus is very much a work in progress, as it continues to evolve, to expand both its geographic and host range, and to reassort with other viruses. 

All of which serves as prelude to a study, recently published in the Archives of Virology, which finds `significantly enhanced virulence' in mice infected with one of these H3N2/H1N1pdm reassortant viruses.

Kwang-Soo Lyoo, Woonsung Na , Minjoo Yeom, Dae-Gwin Jeong, Chang-Ung Kim, Jeong-Ki Kim, Daesub Song 

An outbreak of a canine influenza virus (CIV) H3N2 reassortant derived from pandemic (pdm) H1N1 and CIV H3N2 in companion animals has underscored the urgent need to monitor CIV infections for potential zoonotic transmission of influenza viruses to humans. 

In this study, we assessed the virulence of a novel CIV H3N2 reassortant, VC378, which was obtained from a dog that was coinfected with pdm H1N1 and CIV H3N2, in ferrets, dogs, and mice. 

Significantly enhanced virulence of VC378 was demonstrated in mice, although the transmissibility and pathogenicity of VC378 were similar to those of classical H3N2 in ferrets and dogs. This is notable because mice inoculated with an equivalent dose of classical CIV H3N2 showed no clinical signs and no lethality. 

We found that the PA and NS gene segments of VC378 were introduced from pdmH1N1, and these genes included the amino acid substitutions PA-P224S and NS-I123V, which were previously found to be associated with increased virulence in mice. 

Thus, we speculate that the natural reassortment between pdm H1N1 and CIV H3N2 can confer virulence and that continuous surveillance is needed to monitor the evolution of CIV in companion animals.

As companion animals, dogs and cats are continually exposed to human flu strains and are increasingly viewed as potential `mixing vessels’ for influenza reassortment (see Study: Dogs As Potential `Mixing Vessels’ For Influenza).

None of this is to suggest that canine influenza is on the verge of becoming a human health threat, but as the CDC notes in their Canine Flu FAQ, there are good reasons to watch viruses like these very closely. 

Can canine influenza viruses infect humans?

To date, there is no evidence of transmission of canine influenza viruses from dogs to people and there has not been a single reported case of human infection with a canine influenza virus.

However, influenza viruses are constantly changing and it is possible for a virus to change so that it could infect humans and spread easily between humans. Human infections with new influenza viruses (against which the human population has little immunity) are concerning when they occur. Such viruses could present pandemic influenza threats. For this reason, CDC and its partners are monitoring the canine influenza H3N8 and H3N2 viruses (as well as other animal influenza viruses) closely. In general, canine influenza viruses are considered to pose a low threat to humans.

Thursday, May 26, 2016

MHRP: 1st Detection Of Colistin Resistant E. coli in U.S. Resident

# 11,406

It has only been a little over six months since The Lancet published the first study on a newly discovered plasmid-mediated MCR-1 gene (see Return of the Plasmids) that conveys resistance to a 50-year-old (polymixin) antibiotic called colistin.

This is important since - despite its age and reputation for causing nephrotoxic side effects - colistin is the antibiotic of last resort for some types of resistant gram negative bacteria like E. coli and Klebsiella.  

And like the better known NDM-1 Carbepenum resistance gene - which came to prominence just over 5 years ago (see NDM-1: A New Acronym To Memorize) - this MCR-1 gene is carried by plasmids - which are snippets of DNA that can  transfer the gene to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species).

In short order other detections of MRC-1 started to come in from around the globe (see The Lancet: Dissemination Of The MCR-1 Colistin Resistance Gene) and EID Journal: Possible Transmission Of MCR-1 Harboring E. coli Between Companion Animals & Humans).

These findings have led to increased surveillance for this MCR-1 gene, particularly testing isolates that have shown signs of resistance to other antibiotics.

Which brings us to a press release this afternoon from the Military HIV Research Program: MHRP and a link to a study in Antimicrobial Agents and Chemotherapy, both announcing the first detection of an MCR-1 Resistant E. coli infection in a human on United States soil.

The U.S. Military HIV Research Program (MHRP)

SILVER SPRING, MD. - The Multidrug Resistant Organism Repository and Surveillance Network (MRSN) at the Walter Reed Army Institute of Research (WRAIR) characterized a transferrable gene for colistin resistance in the United States that may herald the emergence of truly pan-drug resistant bacteria.

Colistin is the last agent used to combat bacteria that are resistant to the strongest antibiotics. Colistin has remained the best tool available to treat multidrug resistant bacteria because bacteria were not exchanging genes for its resistance. This latest discovery shows that colistin may be losing its effectiveness in antimicrobial therapy. Now, bacteria may be exchanging resistance genes for colistin.

Alarms sounded in the microbiology community in late 2015 when the first transferrable gene for colistin-resistance was identified in China. Since the report, the global health community has monitored and searched for the occurrence of this gene in the food supply and in humans. This colistin-resistance gene has been reported in Europe and Canada and, as of now, is reported in the U.S.

A clinical sample from a urinary tract infection was collected from a patient in a military treatment facility in Pennsylvania. The sample was sent to the Walter Reed National Military Medical Center (WRNMMC) where colistin susceptibility was tested. The results showed that no safe dosage of colistin would be effective to treat such a bacterial infection. WRNMMC recognized colistin-resistance and sent a sample to WRAIR's MRSN for sequencing, which identified the colistin-resistant gene, mcr-1.

"Colistin is one of the last efficacious antibiotics for the treatment of highly resistant bacteria. The emergence of a transferable gene that confers resistance to this vital antibiotic is extremely disturbing. The discovery of this gene in the U.S. is equally concerning, and continued surveillance to identify reservoirs of this gene within the military healthcare community and beyond is critical to prevent its spread," reported Dr. Patrick McGann, MRSN, WRAIR.

Through intergovernmental communication, it was learned the CDC and USDA are also reporting a swine intestinal infection with a single mcr-1 positive E. coli strain. While there is no evidence that links these recent findings, the evidence of the strain in the U.S. is a public health concern. The gene is transferrable to other bacteria, which could worsen the current global crisis of antimicrobial resistance.

An urgent public health response is underway to contain and prevent potential spread of mcr-1. Active surveillance of multidrug resistant organisms (MDROs), such as mcr-1, allows for earlier and more accurate identification of originating sources. The collection and storage of isolates and samples in the MRSN's growing repository helps researchers identify trends in resistance and prevalence of MDROs and provide best practices for medical providers. The repository also enables them to compare isolates from previous occurrences to better respond to future findings. Recognized as a model program by the White House, the MRSN is a key component of the National Action Plan for Combating Antibiotic Resistant Bacteria (CARB).

With the MRSN's archive, this isolate will be archived for future studies to identify new countermeasures. "Through our surveillance system, we have the unique ability to coordinate source information with susceptibility and sequencing data, and if need be, go back to understand changes in infecting organisms to best treat infection and track emerging multidrug resistant organisms," COL Emil Lesho, Director of the MRSN, WRAIR.

This finding has been published by Antimicrobial Agents and Chemotherapy (AAC) of the American Society for Microbiology (ASM).

In early 2012 World Health Director-General Margaret Chan issued a dire warning about our dwindling antibiotic arsenal (see Chan: World Faces A `Post-Antibiotic Era) – a theme  echoed a year later by CDC Director Thomas Frieden during the release of a major US report on the threat (see McKenna On CDC Antibiotic Resistance Report).

A month scarcely goes by without our seeing more bad news the antibiotic resistance front, bringing the day when we may enter that post-antibiotic era ever closer.

If you haven’t already done so (or would like a refresher), I would highly recommend you watch  Maryn McKenna’s TED Talk - What do we do when antibiotics don’t work any more?.