A Journey Through The World of Pandemic Influenza

End of March

First a bit of personal business:

My "Day Job" is still in crisis mode as the newly hired Head Accountant decided six hours before he was due to show that he had changed his mind and would not be joining us after all. At this point in time we have no replacement candidate(s) so we are back to square one.

I am also facing yet another Month-end cycle where I will be performing the functions of three people so Journey will remain more dormant than not until such time as I either quit myself or we get that elusive replacement.

 

In a Reuters interview microbiologist Dr. Yi Guan of the University of Hong Kong, a highly respected and a leading expert in Avian Influenza, gave his long held assessment that diligent surveillance and rapid containment can prevent avian influenzas from gaining sustained human-to-human (H2H) transmission.

Proper Surveillance can stop flu pandemic

Reuters Tan Ee Lyn

[snip]

Guan, who studied the H5N1 bird flu virus after it showed up in people in Hong Kong in 1997 and has tracked its footprints all over the world ever since, is convinced that the world can stop the bug in its tracks if it has enough resolve.

"If proper surveillance is in place for animals and humans, yes, we can stop pandemic influenza forever. Not just for H5N1, it may also work for other subtypes of viruses," he said in an interview over the weekend.

"We have the ability to remove pandemics if we have a long-term strategy."

Guan, a professor at the University of Hong Kong, knows just how backbreaking and mundane surveillance work can be.

 

Reading the interview the phrase "In a perfect world" came to mind. Many things are "possible" but that doesn't make them necessarily something humanity can, in reality, accomplish.

Given that H5N1 is endemic in many countries, with many of them not known for their effective or efficient governance, surveillance and containment is something currently only theoretically possible.

But the theoretically possible has been accomplished before. Given dedication, audacity, and funding we have gone to the moon and eradicated Small Pox. Two things never previously accomplished and thought impossible by many. By reminding us that we have the potential to keep the lid on pandemics perhaps Dr. Guan will inspire greater effort and greater cooperation.

 

One can always hope.

 

SZ

 

US Pandemic Vaccine Supply

It has been awhile since I addressed anything specifically on influenza pandemic vaccines so I will restate my long held adamant belief and support of the development and stockpiling of pre-pandemic H5N1 vaccines. To be sure, pandemic vaccine, pre-pandemic or otherwise, is a complicated issue.

One need only review Maryn McKenna's seven part series for CIDRAP The Pandemic Vaccine Puzzle to glimpse the seemingly intractable complications (at least in the shorter term) and the difficult choices and decisions required.

Thursday US Health and Human Services (HHS) announced that their stockpile of H5N1 pre-pandemic vaccine supply currently stands at enough to immunize 13 million people. Unfortunately the US has a current population estimated at somewhere around 303 million people. That figures out to be roughly four percent of the population.

 

From CIDRAP:

US has enough H5N1 vaccine for 13 million people

Mar 20, 2008 (CIDRAP News) – A progress report released today says the US government has stockpiled enough prepandemic H5N1 influenza vaccine for 13 million people, more than double the number listed in the previous report, issued last July.

The United States is a large and prosperous country (when measured against the average). We are now in our eleventh year of facing the potential threat of a human pandemic from H5N1. Even if I choose to be generous and only count backward in time to when H5N1 began its forays into human infections with an ever forward and outward march around the globe to 2003 we are still five years on. After five years to only have four percent of our population covered by a pre-pandemic vaccine is not only sad, in my opinion, but pathetically so.

The report on pandemic preparations by the Department of Health and Human Services (HHS) also says the government plans to release a new version of its pandemic vaccine allocation plan in coming months, after considering comments at a series of recent meetings and forums.

The last (draft) version of the vaccine allocation guidance document can be found here.

As the allocation stands currently we are still 10 million shy of tier 1 qualified recipients. Those 10 million, according to these guidelines, would be the Infants/toddlers.

I anticipate changes to the above categories, a swapping of tiers for certain segments of the population. There are just far more who need to be protected than there is protection at this point, and to move a segment into Tier 1 priority means moving another segment out and farther down the priority line.

 

Tough choices. However tough it may be it is still something that has to be decided. And it has to be decided because we as a country, our leaders, and those who have been appointed by those leaders have failed to act with vision and boldness in the face of a potential severe influenza pandemic.

The 16-page report from HHS Secretary Mike Leavitt lists a wide range of HHS pandemic preparations. It emphasizes the agency's efforts to collaborate with other stakeholders in tackling problems like vaccine allocation and who should bear the burden of stockpiling supplies such as face masks, respirators, and antiviral drugs. The report is the fifth in a series that began in March 2006.

Concerning the H5N1 vaccine, the report says, "By the end of 2007, HHS had purchased and stockpiled 13 million courses of pre-pandemic vaccine." The previous report, issued in mid-July, said the agency had acquired 12 million doses of the vaccine, enough for 6 million people.

The vaccine, based on a clade 1 virus isolated from a Vietnamese patient in 2004, was approved by the Food and Drug Administration in April 2007. Although no one knows how well it would work against an emerging pandemic strain of H5N1, HHS officials hope it would provide some protection to those most at risk for exposure in the early months of a pandemic.

And there is the Cosmic Joke (or insult). Even though I am a staunch supporter of the pre-pandemic vaccine program, yes, even given the Swine Flu debacle of the '70s, the pre-pandemic vaccine may only provide the barest minimum of protection against H5N1. By "barest minimum" I mean that it is likely to keep most people from having a fatal infection, but they will still have a high probability of getting sick, some even severely so. Severe or no, recovery beats dead any day.

Additionally, if we encourage our critical front line personnel, Tier 1 folk, to also get the pneumonia vaccine (guards against bacterial pneumonia but not viral pneumonia), we will go a long way in avoiding the "severely ill" side of the potentials of being vaccinated with a far less than optimal pre-pandemic influenza vaccine – or so it is reasonably assumed given current understanding.

 

If it is safe to assume that the pre-pandemic vaccine for H5N1 that we do have will not protect most from getting ill from H5N1 while they perform their critical duties what about those workers bringing H5N1 into their homes, exposing their unprotected family members?

 

My son is a police officer, a "street cop", for a small city. As such he is in Tier 1 for vaccine priority as it stands currently. But honestly, knowing what I know about the vaccine, I shudder at the thought of him bringing infection home to his wife and (currently) one year old daughter, both of whom will be without even the minimal protection offered by the vaccine because there just aren't enough of them.

And what causes my shudders will be faced by all of those who receive this scarce vaccine. By not having enough we have reduced its benefit even further.

 

It is my belief that we have squandered valuable time and in so doing have potentially squandered human life. Fortunately, sometimes, we are afforded the opportunity to remedy our mistakes.

I take comfort in knowing that the vaccine issue is being attacked on any number of fronts, and perhaps, just perhaps, we will have all the time needed to overcome the difficulties and shortfalls.

 

One can only hope anyway.

 

SZ

News and Information during a Pandemic

My thanks to Lisa Schnirring of CIDRAP for bringing us a report from the recent US Department of Health and Human Services (HHS) tabletop exercise. This event brought together representatives from governmental agencies, health institutions, traditional news outlets, and internet forums and bloggers. The exercise was focused on then needs, dynamics, and interactions of information dissemination during a pandemic. Flublogia luminaries DemFromCT of FluWiki and Fla_Medic of Avian Flu Diary were in attendance as representatives of the Cyber Flu Community's "voice".

From Ms. Schnirring's CIDRAP report:

HHS includes online services in pandemic communication drill

[snip]

The exercise was the second time HHS has reached out to blogs. In May 2007, the department featured posts from bloggers such as Michael Coston of Avian Flu Diary and Greg Dworkin, MD, of FluWiki in a 5-week pandemic preparedness blog series. HHS Secretary Mike Leavitt hosts his own blog on the HHS Web site. He is the first cabinet secretary to use the online forum, according to HHS.

[snip]

"We recognize that during a pandemic information could be life-saving. As more and more people turn to the Internet for information and news, blogs have emerged as an important and influential communications tool," HHS said in its invitation to attend the tabletop exercise.

[snip]

At several points during the exercise, moderator Forrest Sawyer, a former news anchor with ABC and NBC who now runs his own media production and strategy company, Freefall Productions, asked the news media and online outlets to predict what their headlines would be and what information they would need from HHS, CDC, and other agencies.

During the exercise the communications officials from HHS floated the idea of "embedding" some of their staff in media organizations to ease access to official information during a pandemic. The agency also said its media access policies now treat reputable blogs and other reputable online services the same as traditional media organizations.

Stephanie Marshall, director of pandemic communications at HHS, told CIDRAP News that because growing numbers of people are going to online sources for news and information, "It's important for the government to understand how best to work with bloggers and other online journalists to distribute information. The exercise and the insights offered by the participating bloggers will help us improve and refine our existing pandemic communications plan."

 

Fla_Medic (Mike Coston) of Avian Flu Diary offers his own thoughts and observations of the off the record tabletop exercise:

HHS Pandemic Exercise

[snip]

The decision to include the flu forums and Internet bloggers in this exercise was a bold one.   I'm not sure that they know quite what to make of  us yet, but they obviously believe they can't ignore us. 

We are, in their words, `The New Media', and they are working out ways to work with us. 

 

 

As an Influenza Pandemic Blogger and Cyber Flu Community Addict I was nothing short of thrilled to see that the federal government recognizes the internet as something not easily ignored or dismissed and acknowledged the community as having a legitimate "place at the table".

 

Although we cyber "Flu Obsessed" are a small virtual community we can be vociferous, cantankerous, and downright self righteous at times. HHS's first experience with dealing with the Cyber Flu Community was during their Pandemic Flu Leaders Blog, on which DemFromCT and Fla_Medic were Flublogia's blogger representatives as well.

During that first intrepid online experiment there were times that members of Flublogia were so raucous and vitriolic that I found myself actually embarrassed, and for those that don't know me – that's pretty hard to accomplish. There are places within "the community" that I spare myself the aggravation of visiting (out of politeness I will refrain from mentioning them specifically). I find, alternately, their censorship or their "conspiracy theory" nature to be just too much for the Critical Thinking Libertarian region of my brain.

 

Flublogia, the Online Cyber Flu Community, is not without its faults. As such I am appreciative of the government's cautious trepidation in opening the door to us. I applaud their understanding that we are a "force" that isn't going anywhere any time soon so accommodation will, it is greatly hoped, benefit everyone.

During a pandemic, especially the early stages, information dissemination will be vital. At times of crisis and emergency the public's appetite for information is ravenous and insatiable and the traditional press has become sloppy. We in Flublogia, faults and all, do a remarkable and rapid job of "self-policing" in general when measured against the "traditional press". Additionally, we have been around long enough now to be a "known commodity", so while I understand the government's trepidation I am hopeful they are not paralyzed by it and the caution it inspires. Time will tell.

 

As it happens, while I have been composing this entry, I have been listening to CSPAN's program Tonight, Washington where the topic is Influence of foreign media on global issues. The juxtaposition of questions of purpose, credibility, sources, and dissemination between the "traditional" and the "new" media may be serendipitous and coincidental but at the same time informative of the terrible hurdles the government will have to surmount if and when the time comes to actually disseminate credible and timely pandemic information to the public.

I do not envy them their task.

 

SZ

Did She or Didn’t She

The influenza virus undergoes continual evolutionary change.  The swapping of whole genes between strains of influenza, reassortment, is known to be the mechanism that produced the 1957 and 1968 influenza pandemics, and therefore considered the main mechanism of producing our pandemic strains. 

Scientists, along with the “Flu Obsessed”, have been concerned that H5N1, currently a wholly avian influenza virus, would reassort with a human influenza virus. H1N1 and H3N2 being the two current human type A Influenza viruses in circulation.  In order to accomplish this sleight of hand on the genetic level a single virion (a single virus) from each different strain of virus, one from H5N1 and one from a currently circulating strain would have to infect the exact same human cell at the same time.

Now, without getting into a whole bunch of mind numbing scientific minutia there are tremendous hurdles that the second virus would have to overcome in order to infect a cell already co-opted by another virus.  For those curious, the mechanisms of those hurdles at work are cell apoptosis and cell superinfection; high points relevant to influenza can be found at the links. 

For those satisfied with the broad-brush strokes nature has it set up so that it is almost impossible for more than one influenza virion to gain entry into a cell, and apoptosis (the death of the invaded cell) occurs within hours of influenza entering a cell, variable, but 4 – 6 hours is probably the operative range.  Combined they form rather strong prima facie evidence that a single cell being infected by two different influenza strains is generally an extremely rare and difficult happenstance.

Yesterday CIDRAP’s Maryn McKenna reported on a bombshell that was dropped at the International Conference on Emerging Infectious Diseases by Indonesia’s Vivi Setiawaty of Biomedical and Pharmaceutical Research and Development about a 16 year old Indonesian girl who is reported to have been infected by H5N1 and H3N2 at the same time, known as a co-infection.

A snip from Ms. McKenna’s report offering an excellent glimpse into the confusing issues presented by this paper:

Throat and nasal-swab samples that were taken on the 6th day of her symptoms tested positive by reverse-transcriptase polymerase chain reaction (RT-PCR) for both avian influenza H5N1 and the seasonal flu strain H3N2 at the Indonesian National Institute of Health Research and Development. Serology test results were less clear. Antibody titers from serum samples taken the 6th day provided a weak indication of H5N1 infection (titer of 1:10) but were negative for H3N2; convalescent sera, on the other hand, gave a strong indication of H3N2 infection (titer of 1:640) but were negative for H5N1.

RT-PCR testing, the first test performed, and the one that came back positive for both H5N1 and H3N2, is the most prone to false results, and officially treated as presumptive pending further testing.  Blood was drawn the same day (6^th day of illness) and it came back showing a weak titer response for H5N1 but none at all for H3N2.  Blood tests that early in an infection are notorious for giving “false negatives” as the body generally hasn’t had enough time to produce antibodies that would be freely circulating in the blood.  This is true for human influenza infection, and as far as I am aware, at least generally true for an H5N1 infection.

The later blood test, referred to as “convalescent sera” (blood taken later or after recovery) was strongly positive for H3N2, and would be what one would expect to see after an infection since the body has had time to produce the freely circulating antibodies.  This same test came back negative for H5N1.  Blood tests several weeks after an infection are considered definitive when proving infection or non-infection, with the caveat that the tests were performed correctly of course.  Lastly, it is worth noting that H5N1 has historically produced a strong- to- excessively strong human immune response, so a lack of climbing antibody titers would seem unlikely in the extreme for an infection in a sixteen year old.

We have two choices when deciding what to believe.  We can believe the most prone to error test shows the correct results and believe that the most definitive test was done incorrectly producing a “false negative”.  Or we can believe that the test results as this report states are what they are but the interpretation of them may need further review.  Since no independent verification from a WHO reference laboratory was conducted we may never know for sure, but I choose to class this as a “maybe, but highly unlikely” case of a co-infection of H5N1 and H3N2 until I have more information.

I would be remiss if I didn’t say that being ill with two different strains of influenza at the same time is probably not impossible, and may not even be that terribly unusual when multi-strains are co-circulating in the population.  However, I am trying to say that those two strains would not likely infect the same human cell within such a short time span, something evolution has mechanisms in place to guard against. 

Added to the time and biological improbability is that now, to the best of our knowledge, avian influenza and human influenza do not infect the same types of human cells.

Since it is that, the two strains meeting up in the same cell(s) and exchanging genetic material, which makes this case such a potential bombshell I felt it important to list out all of the issues as I understand them that would argue against it, both in general and with this case specifically. 

Who knows, perhaps next week more information will be available and I will revise my opinion and assessments.  I would be the last person to say I have the answer to this puzzle, but I do have an insatiable appetite – an appetite not likely to be satisfied any time soon – to understand the myriad pieces spread out on the table before us.

SZ

Fifty Percent Staffing Level

Tomorrow we will be half way through the month of March, and tomorrow I hope to "put February to bed" at work.

For those that do not know, or may have forgotten, I work in the accounting department of a Vacation Rental Company that is wholly owned by a publicly traded Holding Company. The department started the year with a staffing level of four, a controller, his "second" (me), and two others.

At the beginning of January one of my coworkers announced his unexpected and immediate retirement and I absorbed his duties in their entirety. Then in February the controller left us. My department has been running with a staff of two. But since we are a subsidiary of a publicly traded company the reporting that we have to generate and submit to our corporate office is federally mandated (Sarbanes – Oxley, commonly known as SOX) and rigidly scheduled to meet those federal mandates.

 

It is widely suggested, as well as supported, that businesses and organizations will find themselves operating at somewhere around a fifty percent staffing level during a moderate to severe influenza pandemic, something I can relate to personally. Although I do not work in a business or industry that will find itself operating during a time of pandemic, and accounting is not exactly an "essential service", although, to be sure, money will still have to flow, I thought I would share with you a few of the things that I learned and equally enlightening, what had to happen to support my efforts and success.

 

I had an existing broad base of knowledge of all aspects of the department, database, and accounting software, however, since I am not the controller there were reporting functions, data collations, and spreadsheets that I only had a basic superficial knowledge of. I found myself hour-by-hour struggling to comprehend how "this or that" fed into "this or that", often getting it wrong any number of times until I finally managed the logic of the data flow and plopped the right number(s) in.

I had adequate basic knowledge of the myriad functions. I had a well established and proven matrix to follow. I had an entire company at my beck and call to support my stupid ill-informed questions. I had our software programmer made available to me at a moment's notice to assist with database malfunctions and miscellaneous support questions. I had a General Manager that "baby sat" me for two weeks, checking on me every other hour offering encouragement, cheerleading, offers of providing anything else that I might find myself requiring (within a business framework of course), at one point in the process the entire company was "booted off" the server for several hours so that I could have its resources all to myself, and lastly, I was determined to succeed.

And even with all of that, with every resource and advantage I could be given, I was only able to just manage. Perhaps a better way to state my point: The only way I could have been in a better position to succeed was to have my former boss standing over my shoulder walking me through the processes.

 

During a moderate to severe pandemic those who find themselves struggling to perform the duties of two or three missing colleagues will probably not [read surely not] have all of the wonderful support that I had. Many will not have a clear "play book" to refer to as they find themselves struggling with unfamiliar processes and procedures. And, unlike my situation where it was "just numbers" those struggling people may hold someone else's health, or even more frightening, life in their hands with their actions.

After my experiences these past three weeks I have a band new appreciation about how impossible those tasks will be – and my concern about our critical infrastructure has deepened considerably.

 

The good news from a personal perspective is that our new "third body" reports on March 24^th, a week from Monday. We will then be all the way up to a seventy-five percent staffing level, and after this that will feel wonderful indeed, as that will be manageable under the new organizational structure.

So all the "bad stuff" is behind me, with the caveat as long as our new accountant actually shows up on the 24^th.

I know I've said that I was back to posting before and then almost instantly made a liar, but I'm saying it yet again, this time I hope successfully with only life's normal interruptions and breaks for sanity.

 

SZ <Exhausted but pleased with accomplishing the impossible with a great deal of wonderful support>