Operational Biosurveillance

ADVISORY (Updated): Influenza in Previously Vaccinated Patients (Pacific NW and Colorado, USA)

Per our prior Advisory, we have report of another metropolitan hospital in the Pacific NW seeing influenza in previously vaccinated children. 

Here in western Colorado, we saw the death of an elderly woman who had a prior medical history of chronic pulmonary disease.  Both she and her husband were vaccinated for influenza, but the husband was the first to be infected, then the wife who later succumbed.

A notable phenomenon given we forecasted this outcome months ago for our hospital, prior to the advent of influenza season.

Several comments from readers indicate a healthy debate related to a chicken-egg problem: is what we are seeing true vaccine drift or simply a poor vaccine match in the first place?  A tricky question to answer...

ADVISORY: Influenza in Previously Vaccinated Children (Pacific NW, USA)

We have report of a significant bump in influenza-positive pediatric patients presenting to a major metropolitan hospital in the Pacific NW, USA over the last 2-3 weeks.  Of note, many of these patients were previously vaccinated for influenza at the start of the school year (~September). 

 

Differential diagnosis (in order of probability):

1. Waning immunity as the predominant type A influenza circulating is H3N2 in the Pacific NW.  Waning immunity over the course of a routine influenza season is an expected phenomenon.  Our team forecasted a moderate vaccine drift probability for A/H3N2 this season several months ago.

2.  Waning immunity as there are still significant levels of circulating A/H1N1 (2009) in the Pacific NW.  We believe this is highly unlikely and forecasted very low probabilities of vaccine drift for A/H1N1.

3.  Possible emergence of other type A influenza viruses such as A/H3N2-variant.  While we believe this is unlikely, we cannot exclude it.  One of the key indicators we have been monitoring is the appearance of influenza in patients who were previously vaccinated.

A Gap in Situational Awareness: A/H3N2v in the United States

The last public update from CDC regarding the status of A/H3N2v in the United States was January 6, referring to information end-dated (and originally posted) on December 23rd (exactly one month ago).  This update did not reflect test results for the Marin County suspect case.  The January 6th MMWR Editorial Note stated:

Human infections with the influenza viruses currently circulating among swine are rare. Since 2005, only 35 cases have been reported in the United States, but the frequency with which they have been detected increased in 2011. When different influenza viruses simultaneously infect a single host (e.g., a human or swine), exchange of genetic material can occur, resulting in a new influenza virus. Depending on the antigenic distance between the new virus and recently circulating seasonal viruses, little or no immunity might exist in the human population.

Despite this apparent concern, situational awareness has been scant, with substantial time deltas between detection and warning noted.  The latest Flu Weekly provides no information on A/H3N2v antigenic characterization.  There is no indication of "samples received for testing" versus "samples actually tested".  Therefore the lab processing backlog is in question.

Put another way:

 

"What is the status of A/H3N2v in the United States???"

 

 

 

 

Social Media, Public Health Accountability, and The Positive Outcome

If one examines every CDC Flu Weekly report since the 1997-1998 season, one notices stretches of editorial errors and careless data transcription in the early years.  It is almost as if those filling out the reports intuitively knew most people didn't bother to read the deeper complexity of the information- specifically that describing antigenic testing and compatibility with vaccine strains.

After SARS, H5N1 emergence in Asia, and the 2009 H1N1 influenza pandemic, many more are paying attention to the information.   Here in Operational Biosurveillance and elsewhere people noticed the emergence of A/H3N2v being reported and viewed it as an opportunity to tell CDC "here's your chance to make right".  Indeed that appears to be happening, with seed stock being moved to the vaccine manufacturers and very quickly thereafter movement to clinical trials.  These are good measures of progress for an agency we've grown quite frustrated with over the years. 

We are pleased to finally see guidance for clinicians trying to make the difficult decision in the context of an economic recession whether to test for influenza in their patients (i.e. children):

Currently, while there are  low levels of circulating seasonal influenza viruses, CDC recommends increasing collection of specimens from patients with influenza-like illness (ILI) , and having these specimens sent to the state or local laboratory for prioritization for rRT-PCR testing. States should specifically consider increasing collection of specimens from patients presenting with ILI in the following high priority areas:

1. ILI outbreaks, particularly among children in child-care and school settings, since these have been the settings associated with human-to-human influenza A(H3N2)v virus transmission.
2. Unusual or severe presentations of ILI, especially among children.
3. Medically attended ILI and ARI in children under 18 years of age

Our only nit-pick with the recommendations (albeit an important one) is to suggest that pediatricians should at least test medically attended ILI and ARI in children under 18 years of age who were vaccinated for this season's influenza.  This is a loose call at this point given the low number of cases identified so far, however it may overcome social reluctance to test.

We have pinged several physician and pediatric social networks to raise this issue to their attention- that testing children with influenza-like illness may enable quicker decision-making for response.  That we have an opportunity to shorten the time delta to having a vaccine if we need it for our patients.  However we still see "pandemic fatigue" and desensitization to anything related to the word "pandemic".  And yes, with all the talk of healthcare spending cuts physicians do appear to hesitate to test for fear of denial of coverage by insurance.  In our patient population, we hesitate to test because our patients are at poverty level already, without insurance, without Medicaid, and may be paying in cash.  Often these are our sickest patients and the very ones we should test. 

But this entire phenomenon of holding public health accountable for faster reporting of A/H3N2v, transparency in the decision process to move vaccine through trials just in case, and enhanced media visibility to, let's face it, a bare few cases that would have escaped notice just a few short years ago.  Technology does make us more vulnerable because we don't have as much ignorance to be blissful about.  But social media holds us nevertheless responsible for this information and the actions implied by that information.  One only needs to see the hashtag "H3N2" on Twitter to see the wave of social sensitization. 

Here we are hopeful that the convergence of better laboratory diagnostics, risk communication, transparency in response operations, and the accountability provided by social media brings positive change in public health.  And positive change improves our nation's resilience in the face of infectious disease crises.

Another Possible A/H3N2v Case in Marin County: Crucial Information Requirements

Marin County has identified a possble A/H3N2v pediatric case.  The clock is ticking now for CDC- how long will it take to announce this case in the MMWR?  How long did it take to identify this case in the first place?

Kudos to Dr. Jason Eberhart-Phillips for reporting this case.  The crucial information that needed to be provided in context with notification of this case was how many samples of type A influenza have been tested already in Marin County thus far and how many were found to be seasonal A/H3N2 versus A/H3N2v.  What is key at this point is to flesh out the percentiles and whether they are shifting or not.  This information is essential for proper situational awareness as the country evaluates additional cases. 

 

More Evidence of Human-Human Transmission of Swine-Origin Triple Reassortant Influenza A(H3N2) Virus In The United States

On December 23rd, CDC released another statement about the evolving situation with swine-origin triple reassortant influenza A(H3N2) virus in the United States.  Three more human infections, two of which associated with a daycare in West Virginia.  The latter is of greater concern than the former due to probable human-human transmission.  Time delays between submission of samples and public report by CDC remain high:

(Case A) Indiana, no evidence of human-human transmission- exposure from swine. 

• Day 0 (Oct 20th).  Patient symptomatic, hospitalized for 4 days.
• Day 2 (Oct 22nd).  Influenza-positive per in-house hospital laboratory testing.
• Day 8 (Oct 28th).  Indiana State Public Health Laboratory: "inconclusive influenza A virus".
• Day 11 (Oct 31st).  CDC confirms via genomic sequencing presence of "A(H3N2)v" (formerly known as S-OtrH3N2)
• Day 64 (Dec 23rd).  CDC publicly releases the above information.
• Summary:
  • Time delta: state public health recognition of unusual virus= 8 days
  • Time delta: clinical processing of patient to CDC awareness= 11 days
  • Time delta: CDC issuance of warning to the public= 64 and 56 days from initial clinical processing of the patient and state notification to CDC, respectively

(Cases B) West Virgina, evidence of human-human transmission.

• Day 0 (Nov 12th, approximate).  Pediatric patient recognized symptomatic by parents.
• Day 7 (Nov 19th).  Patient, who was already hospitalized for an unrelated issue, develops fever.
• Day 9 (Nov 21st).  Sample taken.  In-house hospital laboratory discovers sample is positive for influenza A.  Patient discharged home.
• ... No further information regarding when West Virginia's state laboratory or CDC processed the sample, which was A(H3N2)v-positive.
• Summary:
  • Time delta: state public health recognition of unusual virus= unknown
  • Time delta: clinical processing of patient to CDC awareness= unknown
  • Time delta: CDC issuance of warning to the public= 34 days from initial clinical processing of the patient (approx. Nov 19th) 

(Case C) West Virginia, same cluster / thread.

• Day 0 (Nov 29th).  2nd child at daycare center ill.
• Day 9 (Dec 7th).  West Virginia Office of Laboratory Services processes sample as "inconclusive"- forwards on to CDC.  This patient was part of a retrospective assessment, where clinical processing did not occur.
• .. No further information regarding when CDC processed the sample, which was A(H3N2)v-positive.
• Summary:
  • Time delta: CDC issuance of warning to the public= 34 days from state public health laboratory processing of the sample to CDC issuance of public warning

 

The key point is of course, we only know what we are able to know.  Our team leaned into the discussion in November to ensure CDC was aware we were 1) monitoring the situation and 2) are carefully documenting their performance in coupling warning to response.  And quietly behind the scenes we are engaging clinical practitioners in an effort to encourage more sampling among symptomatic patients who were vaccinated for this season.  We expect the predominance of this focus to be on pediatric patients, however we are not seeing social sensitization yet among pediatricians.  Messaging from CDC requires clarification and guidance regarding when to sample.

Currently, we are observing between large time deltas between clinical processing of these patients and CDC's issuance of public warning.  It is our opinion that if A(H3N2)v suddenly displaces current seasonal A/H3N2 or gains significant prevalence, the first point of recognition may be an abruptly overwhelmed pediatric medical infrastructure versus dramatically time-delayed reporting from CDC. 

The observations of public health performance during the 2009 influenza pandemic begin to repeat themselves...

 

Analysis of Warning Process: Swine-Origin Triple Reassortant Influenza A(H3N2) Virus In USA

We have been monitoring the situation with swine-origin triple reassortant influenza A(H3N2) virus (S-OtrH3N2) inside the United State for some time now.  Recent reports of likely human-human transmission sparked debate, discussed here in this post.

1.  First, the ECDC's risk assessment was an excellent discussion of the situation.  CDC's report may be found here.

2.  The time delays in issuing statements about the evolving situation reflect the forensic process and length of time it takes to recognize novel pathogens and execute public warning inside the United States.  In this case, a joint press releaseon Sept 2nd and 5th, respectively, from CDC and Pennsylvannia state officials announced recognition of S-OtrH3N2 pediatric cases in Indiana and Pennsylvania stemming from exposure to infected swine.  The breakdown of timelines as follows:

Case A (Indiana):

• Day 0 (July 23rd).  Parental recognition of a child with flu-like illness.  Child brought to local ED, clinical laboratory testing at the hospital positive for type A influenza.   Child found to have been vaccinated the prior fall, had chronic medical condition, discharged from the ED same day without anti-virals.
• Day 1 (July 24th).  Child returns to ED with a worsened clinical picture and admitted.
• Day 4 (July 27th).  Child does well and is discharged from the inpatient ward to home.  No further issues.
• Day 25 (Aug 17th).  Indiana State Department of Health Laboratories test the sample and discover suspect swine-origin influenza A (H3N2) virus.  CDC notified and sample forwarded to CDC for confirmation and further analysis.
• Day 27 (Aug 19th).  CDC confirms findings of the Indiana State DOH Lab. 
• Day 41 (Sep 2nd).  CDC reports publicly results of genomic sequencing: swine-origin triple reassortant influenza A(H3N2) virus that now includes segments of 2009 pandemic H1N1 virus.  Report indicates patient had contact with infected swine.
• Summary:
  
  • Time delta: state public health recognition of unusual influenza virus= 25 days
  • Time delta: clinical processing of patient to CDC awareness= 25 days
  • Time delta: CDC issuance of warning to the public= 41 and 14 days from initial clinical processing of the patient and state notification to CDC, respectively
    

Case B (Pennsylvania):

• Day 0 (Aug 20th).  Parental recognition of symptoms, take child to local ED.  Nasal swab positive for influenza A.  Child was vaccinated the prior fall.
• Day 3 (Aug 23rd).  Pennsylvania State Department of Health Laboratory idenifies suspected swine-origin influenza A (H3N2) virus.
• Day 4 (Aug 24th).  Pennsylvania state officials notify CDC of the findings.
• Day 6 (Aug 26th).  CDC confirms findings.
• Day 13 (Sep 2nd).  CDC reports publicly results of genomic sequencing: swine-origin triple reassortant influenza A(H3N2) virus that now includes segments of 2009 pandemic H1N1 virus.  Report indicates patient had contact with infected swine.
• Summary:
  • Time delta: state public health recognition of unusual influenza virus= 3 days
  • Time delta: clinical processing of patient to CDC awareness= 4 days
  • Time delta: CDC issuance of warning to the public= 13 and 7 days from initial clinical processing of the patient and state notification to CDC, respectively

Questions were asked openly of CDC, USDA, and Pennsylvania state officials on Sept 12th about how these cases were recognized.  More to the point, guidance for clinical sampling was requested publicly.  This request was never answered.  At this point, the situation had migrated to the top of biological threat monitoring list.  Lack of response was not reassuring.

On Nov 23rd, a probable human-human transmission cluster of S-OtrH3N2 cases was reported by CDC, with an evident 7-10 day lag between initial clinical processing, laboratory based recognition at the state level, and CDC issuance of a public statement.  This was a much better time delta and likely reflective of surveillance grid sensitization this particular issue. 

Overall, we see a drop from a time delta between clinical processing and CDC issuance of public warning of these events from 41 to 13 to 7 days as the situation evolved.  It was not until Nov 26th did media reports indicate a seed strain had been sent to vaccine manufacturers in case S-OtrH3N2 begins to overtake current circulating strains of influenza virus in the human population.

There are several summary observations to make at this point:

1. S-OtrH3N2 is our #1 pathogen of concern for the United States and the world at this time, from the perspective of potential social disruption.  Projected impact would be similar to that seen in a vaccine drift year of seasonal influenza (e.g. 2004 in the United States).  Thus far no fatalities have been observed, but the sample size is far too small at this time to make firm assertions of case fatality rate or morbidity profiles. 
2. CDC should be praised for proactively forwarding seed stock to vaccine manufacturers.  What will be interesting to observe at this point is the time delta between initial recognition of sustained human-human transmission and an order to ramp up and distribute S-OtrH3N2 vaccine to local healthcare providers.  In this instance CDC stands in much better position to execute more efficient warning to response operational coupling.
3. The above said, we note with great concern how long it took to recognize and effectively communicate to the public the initial situation in Indiana.  From the perspective of this author, a pediatrician practicing in a rural setting, there is no healthcare provider sensitization to this issue- i.e. there is no change at all in sampling procedures for children presenting with influenza-like illness.  It is as though this season is like any other.  Especially after the 2009 H1N1 pandemic experience and the current economic recession, we observe a general reluctance to test for influenza unless there is a compelling reason to do so.
4. Not all states have the surveillance capabilities of Pennsylvania and Iowa.  There is an incomplete understanding of how pervasive S-OtrH3N2 transmission is inside the United States at this time. 
5. Abrupt community inundation of pediatric flu-like illness, especially among children previously vaccinated for the 2010-2011 influenza season, should prompt an index of suspicion at least to obtain samples for testing by clinicians.  Submission of samples that are processed by state laboratories and moved up the chain to CDC is the only way to assess this evolving situation accurately.