Saturday, July 22, 2017

The Enigmatic, Problematic H3N2 Influenza Virus



















#12,630

For the past 10 weeks we've been watching a growing, often severe, out-of-season H3N2 flu epidemic in Southeast China (see Macao, Hong Kong & Guangdong Province All Reporting Heavy Flu Activity) which appears to be hitting Hong Kong the hardest. 
Yesterday, two Hong Kong University infectious disease experts suggested a recent mutation in the H3N2 virus may be one of the contributing factors to this summer flu epidemic (see Hong Kong: HKU Experts Call For Deploying Prophylactic Tamiflu To Avert Crisis).
With much of the reportage in Chinese, we've had to deal with syntax challenged machine translations, but overnight the South China Morning Post reported:
Mutation may be behind surge in flu cases this summer, Hong Kong experts say

Surge in number of cases could be due to variation in dominant strain, which may have rendered vaccines used in past two years ineffective
The operative words in this headline being `may' and `could'.

While several recent amino acid substitutions (including N121K) have turned up recently in H3N2 viruses in Hong Kong (and around the globe), it isn't at all clear how much of a factor they are in Hong Kong's current flu epidemic.

The H3N2 virus, which came to prominence as a pandemic strain in 1968 (supplanting 1957's pandemic H2N2), settled 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 in humans now for nearly 50 years. Over the past five decades 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.

Since 2009 seven distinct genetic groups have been defined for H3N2While all belong to clade 3C, they are divided into three subdivisions; 3C.1 , 3C.2, and 3C.3, with last November's ECDC Influenza Virus Characterization Report stating:
In 2014 three new subclades emerged, one in subdivision 3C.2, 3C.2a, and two in 3C.3, 3C.3a and 3C.3b , with subclade 3C.2a viruses dominating in recent months.
Since then we've seen this newly dominant  3C.2a subclade further split into 3C.2a1 and 3C.2a2 (see Eurosurveillance: Emergence Of A Novel Subclade Of Seasonal A/H3N2 - London). The following Eurosurveillance chart shows the recent evolution of H3N2 clade 3C.

As you can see, both 3C.2a1 and 3C.2a2 share the N121K substitution, which is the `mutation'  referenced in the SCMP article above. This amino acid substitution has increasingly been turning up in the literature over the past 6 months.

Last February, in a Eurosurveillance Rapid communication Interim estimates of 2016/17 vaccine effectiveness against influenza A(H3N2), Canada, January 2017 DM Skowronski  et al. found:
Sequence analysis revealed substantial heterogeneity in emerging 3C.2a1 variants by province and over time. Adjusted VE was 42% (95% confidence interval: 18–59%) overall, with variation by province. Interim virological and VE findings reported here warrant further investigation to inform potential vaccine reformulation. 
In other words, they found the H3N2 vaccine effectiveness was a lackluster 42%, and that the H3N2 virus was evolving at a substantial rate. They write:
In sequencing analysis, we identified considerable diversity among circulating influenza A(H3N2) strains, including a mix of genetic variants that differed geographically and with time.
The majority (80%) of A(H3N2) viruses included in our VE analysis belonged to the newly emerging clade 3C.2a1, but with continuing genetic evolution compared with the vaccine strain. Almost all (95%) 3C.2a1 viruses had both the N171K and N121K mutations in site D that distinguish this clade.
They end by saying:
Conclusion

Continued evolution in circulating 3C.2a variants and their derivatives, and the impact on vaccine protection, warrants ongoing monitoring to inform potential vaccine reformulation.

While a 40% VE is less than we'd like to see, it is far better than what we saw during the 2014-15 flu season when a late arriving `drifted' H3N2 virus practically negated that year's flu vaccine's effectiveness (see CDC HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus).

We've another study - referenced yesterday by the HKU experts - that found a far lower VE in Denmark for their H3N2 vaccine last winter, along with a very complex mixture of co-circulating H3N2 subclades.
J Clin Virol. 2017 Jun 29;94:1-7. doi: 10.1016/j.jcv.2017.06.007. [Epub ahead of print]
Changes in genetically drifted H3N2 influenza A viruses and vaccine effectiveness in adults 65 years and older during the 2016/17 season in Denmark.

Trebbien R1, Fischer TK2, Krause TG3, Nielsen L4, Nielsen XC5, Weinreich LS6, Lis-Tønder J7, Skov MN8, Christiansen CB9, Emborg HD3.


Abstract

RESULTS:

 
The genetic characterization revealed several genetically drifted viruses, which could be divided into four main clusters by the defining amino acid substitutions: 3C.2a/N121K/S144K, 3C.2a/T131K/R142K, 3C.2a1, and 3C.2a1/N121K.
Some of the drifted viruses appeared to be more prominent in vaccinated or non-vaccinated individuals, respectively. Overall the adjusted VE was 7.4% (95% confidence interval (CI): -6.0-19.2) among inpatients and 19.3% (95% CI: -5.7-38.4) among outpatients, respectively.

VE for the four main virus clusters was; cluster 3C.2a1: 38.8% (95% CI: -29.8-71.1), cluster 3C.2a/N121K/S144K: 9.2% (95% CI: -63.0-49.4), cluster 3C.2a/T131K/R142K: 19.0% (95% CI: -85.3-64.6), and cluster 3C.2a1/N121K: -12.2% (95%CI: -129.7-45.2).
CONCLUSIONS:

Several genetically drifted H3N2 viruses have been circulating in Denmark in the 2016-17 influenza season. An overall low VE was estimated and VE for the four main virus cluster indicate different VEs between the circulating drifted H3N2 viruses.

Copyright © 2017 Elsevier B.V. All rights reserved.

The VE against 3C.2a1 was nearly 40%, but for the remaining three drifted viruses was far lower, with the VE against the 3C.2a1/N121K virus almost nonexistent. These results all come from a cohort of over-65 aged patients, which tend to be the least protected by flu vaccines.
An equally dismal H3N2 VE was reported out of South Korea last winter (see PLoS One Interim estimates of the effectiveness of the influenza vaccine against A(H3N2) influenza in adults in South Korea, 2016–2017 season) although they did not provide any genetic breakdown of H3N2 subclades. 
Here in the United States, we saw a modest level of protection (34%) against H3N2, according to the CDC's MMWR report of June 30th.

2016–17 Influenza Vaccine Effectiveness

Data collected through the U.S. Influenza Vaccine Effectiveness Network during November 28, 2016–April 14, 2017, indicate that influenza vaccination this season reduced the overall risk for influenza-associated medical visits by 42% (95% CI = 35%–48%). Vaccine effectiveness against the predominant influenza A(H3N2) viruses was 34% (95% CI = 24%–42%) and vaccine effectiveness against influenza B viruses was 56% (95% CI = 47%–64%).
This fall's northern hemisphere flu vaccine will use the same (A/Hong Kong/4801/2014-like) H3N2 virus as last year's formulation, but will add a new H1N1 strain. Its effectiveness in preventing H3N2 infection this year may well depend upon which `flavor' of the H3N2 virus visits your region this winter.
The evolution of flu viruses - particularly H3N2 - is so rapid that it is impossible to know with any certainty what subtype - much less what subclade - will be dominant six months from now. 
And the strain that is king of the viral mountain in North America in January may not be on top in Europe, or Asia. Which means, by the time flu arrives in your area, this fall's H3N2 vaccine component could do better, worse, or about the same as last year. Guaranteed.

I'll certainly get the flu vaccine this year (as I do every year), but given the increasing genetic diversity of the H3N2 virus and the severity of Hong Kong's outbreak, the advice offered by DM Skowronski et al. in the conclusion of their Eurosurveillance report above is something we probably all ought to take to heart this fall.
Given that a substantial proportion of vaccinated people may remain unprotected against influenza A(H3N2) illness, other adjunct measures should be considered to minimise associated morbidity and mortality, particularly among high-risk individuals.
While it may not be as effective as we'd like, the flu vaccine – along with practicing good flu hygiene (washing hands, covering coughs, & staying home if sick) – remains your best strategy for avoiding the flu and staying healthy this winter.

And if you do get sick, early administration of antivirals - particularly for high-risk individuals - can make a real difference in severity, duration, and outcomes.


Friday, July 21, 2017

Italy Reports Two New Outbreaks Of H5N8

Credit Wikipedia




















#12,630


While greatly reduced over the past 3 months, we continue to see scattered outbreaks of HPAI H5N8 in Europe. In June we saw outbreaks reported in Belgium, Luxembourg, France, and the UK (see ESA Epidemiological Update: HPAI H5 Clade 2.3.4.4 Viruses In Europe).

Today Italy's Istituto Zooprofilattico Sperimentale delle Venezie has confirmed a pair of outbreaks in Mantua Province, in northern Italy.

Highly pathogenic avian influenza (HPAI) in Italy

2016/2017 - H5N5, H5N82016 - H7N72014/2015 - H5N8, H5N12013 - H7N7

2016/2017 – H5N5, H5N8

  • Outbreaks | PDF (last update: 21/07/2017)
  • Map | PDF (last update: 21/07/2017)
July 2017
21/07/2017  – On 20 July, the National Reference Laboratory (NRL) for Avian Influenza and Newcastle Disease confirmed as positive for Avian Influenza virus subtype H5N8 two farms located in Lombardy region: a rural holding and a fattening turkey industrial farm in Mantua province. Epidemiological investigations are ongoing in both outbreaks. An increase in mortality was reported in the previous days in one of the sheds of the industrial farm where about 18.900 fattening female turkeys (106 day-old) were present. Further information on virus characterization and on the cases will be provided as soon as available.

In the same date, Regional Authority of Lombardy notified a suspect of avian influenza in a laying hens farm (500.000 heads) in Mantua province.


Today, the NRL characterised both the viruses as Highly Pathogenic Avian Influenza.

The persistence of HPAI H5N8 in wild birds well into the summer - even at relatively low levels - is a decided change over what we've seen in previous years with this particular avian virus.
In 2015, after North America's biggest avian epizootic on record, the virus all but disappeared in the wild, and hasn't been reported in North American flocks in over two years (see PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl).
But the virus that returned to Europe last fall had acquired significant changes (via reassortment) during the summer of 2016. In addition to being far more virulent in wild and migratory birds (see Europe: Unusual Mortality Among WIld Birds From H5N8), it also displayed the ability to infect a much wider range of birds (see ESA list of 78 species).

All of which means that we can't rely on the old `rules' necessarily applying going forward.       

HK CHP Notified Of A Single H7N9 Case In Jiangsu Province

Jiangsu Province - Credit Wikipedia














#12,629


For the third week in a row China's NHFPC reports a single new H7N9 case over the past 7 days, this time in Jiangsu province.
     The Centre for Health Protection (CHP) of the Department of Health is today (July 21) monitoring a notification from the National Health and Family Planning Commission that one additional human case of avian influenza A(H7N9) was recorded from July 14 to 20 in Jiangsu, and strongly urged the public to maintain strict personal, food and environmental hygiene both locally and during travel.

     The 62-year-old female patient in Nanjing was known to have exposure to live poultry market and had onset on July 12.
         (Continue . . . )


 

Hong Kong: HKU Experts Call For Deploying Prophylactic Tamiflu To Avert Crisis

Flu Express - Severe Flu Week 28











#12,628


Hong Kong's out-of-season flu epidemic continues to worsen (see yesterday's Week 28: Hong Kong's Flu Activity Increases To `A Very High Level') with their Centre for Health Protection (CHP) announcing no fewer than 3 new institutional outbreaks, and another severe pediatric case, over night.

Also overnight, and causing quite a stir in the local media, two Hong Kong University infectious disease experts - Yuen Kwok-yung and David Christopher Lung - called upon the government to release 14-day prophylactic courses of  the antiviral drug Tamiflu (tm) - aka oseltamivir - to vulnerable elderly people to avert a crisis.

This from RTHK News:
Use Tamiflu urgently to control flu cases: experts
2017-07-21 HKT 12:00

Two infectious disease experts have called on the government to immediately administer the antiviral drug Tamiflu to vulnerable elderly people to control the current flu outbreak.

The microbiologists from the University of Hong Kong, Yuen Kwok-yung and David Christopher Lung, jointly issued a warning on Friday, saying that the public healthcare system is "on the verge of collapse" due to the summer flu cases.

In a jointly authored article, published in local newspaper Ming Pao, they said the season's peak will probably last at least two more weeks, and the government must act more aggressively to rein in the disease.
         (Continue . . . )

Similar reports appear in the Hong Kong Standard and other English language media outlets. Both of these experts are heavyweights in the world of influenza.
Title:
Chair of Infectious Diseases
Professor (Clinical)
Henry Fok Professor in Infectious Diseases


Clinical Assistant Professor
BSc (BioMedSc) (HK), MBBS (HK), MRCP (UK), FHKCP, FHKAM (Medicine), PhD (HK), FRCP(Edin & Glasgow), FCCP, FACP.

Oseltamivir can be used both for treatment and for prophylaxis, either post or pre-exposure. It is rare, however, to see such a `blanket' recommendation for prophylaxis for at risk individuals across an entire city.

The original article (in Chinese) is available at this link.  In it, these scientists discuss a mutation in the H3N2 virus that may be responsible for this summer's unusual epidemic (translation follows):
(1) viral factors: 2014/15-year-H3N2 influenza A winter peak was due to the emergence of antigenic drift (antigenic drift), but the epidemic of H3N2 influenza is not to drift. According to the recent Danish study showed that 2016/17 H3N2 influenza in a small antigenic variation (N121K), this variation has the potential to influenza vaccine used in the past two years failed.
Hong Kong H3N2 influenza A strains also appeared N121K variation, from July 2016 to March 2017, about 20% of the H3N2 strain appears N121K variation, while in May 2017, more than 35 percent of H3N2 strains N121K variation occurs. This variation may be the peak of the flu this summer one of the reasons.
This N121K variation has previously been linked to diminished vaccine effectiveness with the 3C.2a1 clade of the H3N2 virus, which we looked at in Eurosurveillance: Interim Estimates Of Flu Vaccine Effectiveness Against A(H3N2) - Canada, January 2017 and  Eurosurveillance: Emergence Of A Novel Subclade Of Seasonal A/H3N2 - London.



So far I've not seen any official response by the CHP or Hong Kong authorities.

Second Ohio County Fair Closes Hog Barn Over Swine Flu

Franklin County - Credit Wikipedia















#12,627


Last Friday we saw Clinton Co. Ohio Fair Close Hog Barn Over Swine H3N2, sending 200 market hogs to slaughter early.  Yesterday it was announced (h/t Shiloh on FluTrackers) that two hogs at the Franklin County Fair (Columbus, Ohio) had tested positive for swine H1N1, and that their exhibit had been closed as well. 
While swine influenza can sometimes jump to humans (where it is then dubbed a `swine variant' virus), so far, we've no reports of human infections from either of these two outbreaks.  
Two reports, then I'll return with a bit more on why we monitor outbreaks like these so closely.  First, from the Columbus Dispatch:

Influenza outbreak leads to slaughter of pigs at Franklin County Fair

By Marion Renault

After at least two hogs tested positive for swine influenza, almost 50 pigs on exhibit at the Franklin County Fair were removed Wednesday evening for slaughter.

Livestock areas have been disinfected and no swine flu is present on the fairgrounds, the Franklin County Agricultural Society said in a Facebook post Thursday afternoon. The fair will continue as planned through Saturday. 

“The Ohio Department of Agriculture was contacted immediately and every protocol was followed,” the post said. “Anyone coming to the fairgrounds can feel comfortable that the grounds are safe.”


(Continue . . . )

 And this statement from the Franklin County Agricultural Society:
 
STATEMENT FROM THE FRANKLIN COUNTY AGRICULTURAL SOCIETY:

The Ohio Department of Agriculture has confirmed two hogs tested positive for influenza at the Franklin County Fair.

Thanks to the proactive communication from of our Fair leadership and 4H advisors, our exhibitor was able to quickly identify an issue with his hogs and report it to the attending veterinarian. The Ohio Department of Agriculture was contacted immediately and every protocol was followed.

On Wednesday evening, out of an abundance of caution, all hogs were removed from the fairgrounds for harvest. All 48 were what we call market pigs, meaning they were already slated for market – to be processed.

The livestock areas were again disinfected, and the Fair will continue through Saturday, July 22. We do not presently have swine flu on the fairgrounds. Anyone coming to the fairgrounds can feel comfortable that the grounds are safe.

The 4H exhibitors showing the hogs will still participate in the livestock auction on Saturday, July 22, rewarding months of hard work and dedication.

“We followed, and continue to follow, every protocol per the Ohio Department of Agriculture to ensure the health of our animals, and most importantly, our exhibitors and fairgoers” says David Fleshman, president, Franklin County Agriculture Society. “We are grateful to everyone for exercising caution and acting in the best interest of our Fair and our community.”

Anyone who visited the Franklin County Fair and experiences flu-like symptoms, should contact a medical professional.

As a reminder to those visiting our livestock areas for the remainder of the Fair, we ask the following:
– Wash and/or sanitize hands thoroughly and often, particularly after handling animals and always before eating meals or touching your mouth (Hand washing/sanitizing stations can be found throughout the livestock barn, for convenience)
– No food or drink is allowed in the livestock barns
– No strollers, sippy cups or pacifiers are allowed in the livestock barns

Influenza viruses (primarily swine H1N1, H3N2, and H1N2) circulate commonly in swine herds, and while there is always a concern that one of these viruses could someday evolve  into a more `humanized' strain (as happened with H1N1 in 2009) - most of the time these infections are mild, and don't pose much of a threat to the pigs or the public.

But when infected pigs are brought into agricultural exhibits at county fairs, they can share flu viruses with other pigs (with a risk of reassortment) and are placed into a public venue where hundreds, even thousands, of visitors could be potentially exposed. 
Hence the closure, out of an abundance of caution, of these two exhibits.
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 many others probably go undiagnosed.

During the summer of 2012 we saw our largest outbreak to date, with 10 states reporting more than 300 confirmed cases, nearly all linked to county or state fair attendance (see H3N2v Update: CDC Reports 52 New Cases, Limited H2H Transmission).
Indiana reported the most cases (n=138), followed by Ohio (n=106).  While the H3N2v virus was the most commonly reported strain, H1N1v and H1N2v were also detected.
While most of these infections were mild, 16 people were hospitalized and 1 died (see MMWR: H3N2v Related Hospitalizations In Ohio – Summer 2012). Two years later, during a far less active swine flu year, FluView Week 17 reported A Fatal Swine Variant (H1N1v) Case In Ohio. 
And over this past winter, we looked at two severe swine variant flu infections in Europe (see here and here).  While rare, serious, even fatal infections can occur. 
Last August, over a period of several weeks, we followed reports of 18 people - all fair attendees - who were diagnosed with a swine variant (H3N2v) influenza virus in two states; Michigan and Ohio.  Among those blogs:
CDC FluView: 7 More H3N2v Cases (4 Michigan, 3 Ohio) In Week 33
Ohio: More Reports Of H3N2 In Exhibition Swine
CDC: Interim Guidance for Clinicians on Human Infections with Variant Influenza Viruses
Last October, from the MMWR: Investigation Into H3N2v Outbreak In Ohio & Michigan - Summer 2016, we learned that that 16 of the 18 cases analyzed belonged to a new genotype not previously detected in humans. From the report's summary:
What is already known about this topic?

Sporadic human infections and outbreaks with influenza viruses that normally circulate in swine have occurred in the past. The largest known outbreak of H3N2v virus infections occurred in 2012.

What is added by this report?

In August 2016, 18 laboratory-confirmed infections with H3N2v virus were reported among persons who had attended agricultural fairs in Michigan and Ohio. Sixteen of the 18 cases occurred in persons who were infected with a reassortant H3N2v virus that contained a hemagglutinin (HA) gene previously not detected in variant viruses.

The HA gene was likely introduced from humans into swine in 2010 or 2011, and viruses with this gene have circulated and evolved in swine to be genetically and antigenically different from both previous and currently circulating human seasonal influenza A(H3N2) viruses.

What are the implications for public health practice?


To minimize transmission of influenza viruses from swine to humans and from humans to swine, agricultural fair organizers should consider measures such as shortening the time swine are on the fairgrounds to ≤72 hours, immediately isolating ill swine, maintaining a veterinarian on call for the duration of the swine exhibition, providing prominent handwashing stations, and prohibiting food and beverages in animal barns. Persons at high risk for influenza-associated complications should be discouraged from entering swine barns.

The CDC maintains a comprehensive Swine/Variant Influenza page where you'll find the latest case counts, safety and prevention information, and guidance for health care providers.

Some information for exhibitors at county and state fairs include:
And for some earlier blogs on the evolution of swine viruses, you may wish to revisit:
PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza
Eurosurveillance: Seroprevalence Of Cross-Reactive Antibodies To Swine H3N2v – Germany
JID: Evolutionary Dynamics Of Influenza A Viruses In US Exhibition Swine
Live Markets & Novel Flu Risks In The United States

Thursday, July 20, 2017

MMWR: Cluster of Acute Flaccid Myelitis in Five Pediatric Patients - Arizona, 2016

Credit CDC AFM Surveillance Page

















#12,626


Acute flaccid myelitis (AFM) is a rare illness that affects a person’s nervous system, specifically the spinal cord. AFM is a subset of conditions that fall under a broader `umbrella' of syndromes called Acute Flaccid paralysis (AFP), which may include myelitis, peripheral neuropathy, myopathy, Guillain-Barré syndrome (GBS), toxic neuropathy, and other muscle disorders.
While the exact causes of Acute flaccid myelitis aren't fully understood, it has been linked to a number of viral infections, including West Nile Virus, Adenoviruses, and a number of (polio and non-polio) enteroviruses, including EV-71 and more recently, EV-D68.
In August of 2014 we saw a large increase in AFM cases tentatively linked to EV-D68, a relatively rare non-polio enterovirus that caused a nationwide outbreak of mild to moderate respiratory illness, mostly among children and teenagers (see Kansas City Outbreak Identified As HEV 68). 

While a circumstantial case has been made over the past couple of years (see EID Journal Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014), no definitive causal link to EV-D68 has been established. Some AFM cases have tested positive for EV-D68, while others have not.
AFM declined to low levels the U.S. in 2015 (see chart at top of this blog), but returned during the summer and fall of 2016. 
In response, last summer the CDC began publishing monthly updates on AFM as new cases began to surface. We also saw other reports from around the globe (see Taiwan CDC: 1st Case Of EV-D68 With Acute Flaccid Paralysis and EID Journal Upsurge In EV-D68 In The Netherlands, 2016), once again linking EV-D68 to at least some of these paralysis cases. 

The CDC is quick to point out what we know, and what we don't know about AFM.
What We Know

What we know about the AFM cases for which CDC has received information:

  • Most patients are children.
  • The patients’ symptoms have been most similar to complications of infection with certain viruses, including poliovirus, non-polio enteroviruses, adenoviruses, and West Nile virus. See a list of viruses associated with AFM.
  • Enteroviruses can cause neurologic illness, including meningitis. However, more severe disease, such as encephalitis and AFM, is not common. Rather, they most commonly cause mild illness.
  • CDC has tested many different specimens from the patients for a wide range of pathogens (germs) that can cause AFM. To date, we have not consistently detected a pathogen (germ) in the patients’ spinal fluid; a pathogen detected in the spinal fluid would be good evidence to indicate the cause of AFM since this illness affects the spinal cord.
  • The increase in AFM cases in 2014 coincided with a national outbreak of severe respiratory illness among people caused by enterovirus D68 (EV-D68). Among the people with AFM, CDC did not consistently detect EV-D68 in the specimens collected from them. In 2015 no cases of EV-D68 were detected. CDC did not receive information about large outbreaks of illness associated with EV-D68 detections in the United States in 2016. But information about sporadic cases of EV-D68 infections were sent during that time. Learn more about EV-D68.
What We Don’t Know

What we don’t know about the AFM cases for which CDC has received information:

  • Despite extensive testing, CDC does not yet know the cause of these AFM cases.
  • It is unclear what pathogen (germ) or immune response is causing the weakness and paralysis.
  • CDC has not yet determined who is at higher risk for developing AFM, or the reasons why they may be at higher risk.
  • See Prevention for information about how to protect your family from viral infections that may cause AFM.

All of which brings us to an MMWR report, published today, that describes a cluster of AFM pediatric cases in Maricopa County, Arizona in Aug- Sept of 2016. Once again, EV-D68 was detected in some, but not all, of the cases in this cluster.

Due to its length I've only included some excerpts.  Follow the link to read the full report.

Notes from the Field: Cluster of Acute Flaccid Myelitis in Five Pediatric Patients — Maricopa County, Arizona, 2016

Weekly / July 21, 2017 / 66(28);758–760
Sally A. Iverson, DVM1,2,3; Scott Ostdiek, MD4; Siru Prasai, MD2; David M. Engelthaler, PhD5; Melissa Kretschmer, MA2; Nicole Fowle2; Harlori K. Tokhie, MD4; Janell Routh, MD6; James Sejvar, MD7; Tracy Ayers, PhD6; Jolene Bowers, PhD5; Shane Brady, MPH3; Shannon Rogers, MS6; W. Allan Nix, PhD6; Ken Komatsu, MPH3; Rebecca Sunenshine, MD2,8; AFM Investigation Team

In 2016, CDC saw an increase in cases of acute flaccid myelitis (AFM); 144 persons in 37 states and the District of Columbia were confirmed to have AFM. After investigations in California (1) and Colorado (2) in 2014, CDC characterized AFM as an acute flaccid paralysis (AFP) distinguishable by magnetic resonance imaging (MRI) abnormalities of the gray matter of the anterior and posterior spinal cord segments, involving one or more spinal segments (3).

Although certain viruses (e.g., nonpoliovirus enteroviruses, adenoviruses, and West Nile virus) can cause rare cases of AFP, and findings from the 2014 outbreak investigations indicated that enterovirus D68 (EV-D68) was temporally associated with AFM, no viral etiology for AFM has been definitively established (3).
In September 2016, an acute care hospital in Arizona notified the Maricopa County Department of Public Health (MCDPH) of a suspected case of AFM and subsequent cluster of 11 children who were evaluated with similar neurologic deficits; differential diagnoses included transverse myelitis and AFM. The Maricopa County Department of Public Health, in cooperation with the Arizona Department of Health Services, CDC, the Translational Genomics Research Institute (TGen, Flagstaff, Arizona), and the acute care hospital, initiated an investigation to confirm AFM cases and identify an etiology. 
(SNIP)

This cluster of AFM at one children’s acute care hospital is the largest cluster identified to date in Arizona and is part of a nationally identified increase in AFM cases. Although no statewide surveillance system specific to AFM is available, this cluster was detected by physician reporting, highlighting the need for physicians to remain vigilant for this emerging disease and to report cases that fit the AFM case definition to their local health department.
Metagenomic analyses identified EV-D68 in NP swabs from the three patients for whom specimens were available, along with a specimen from a patient who did not meet the AFM case definition; therefore, no single etiology or risk factor was associated with only confirmed cases.

Patient and family history of asthma was the most common comorbidity reported among confirmed AFM cases and should be considered in future case investigations. Expanded analysis of infectious, postinfectious, and noninfectious etiologies might provide further insight into the mechanism of AFM.

(Continue . . . )
For additional information on EV-D68, and/or AFM, you may wish to revisit these blogs:
CIDRAP On The Lancet EV-D68 Analysis
Molecular evolution and the global reemergence of enterovirus D68 by genome-wide analysis
Along with these resources from the CDC:
COCA Clinical Reminder (August 27, 2015) – Notice to Clinicians: Continued Vigilance Urged for Cases of Acute Flaccid Myelitis.

The 2014 investigation summary is available here: Acute Flaccid Myelitis in the United States—August – December 2014: Results of Nation-Wide Surveillance.