Traveling With Ebola Is Not Traveling With Influenza

With everyone away at IDWeek, I've had time to think about Ebola and things like airport screening programs. I'm not supportive of outright travel bans. As many have eloquently said, bans will do more economic harm than good and hinder efforts in West Africa. However, I'm worried that we might be equating Ebola with Influenza. Many of the discussions concerning travel restrictions and Ebola spread have centered around models and estimates derived from respiratory viruses epidemics like the 2009 H1N1 influenza pandemic. Yes, influenza and Ebola are both viruses, but that's like equating a sparrow and an Allosaurus because they're both dinosaurs.

The first and perhaps most important difference between the current Ebola outbreak and the the 2009 H1N1 pandemic is that Ebola it is very slow moving. For example, the first case of Ebola is thought to have occurred 307 days ago on December 6th in a two-year old boy. Since that time there have been an estimated 8,032 cases (granted these could be underestimates). If you compare a similar 307-day period for 2009 H1N1, April 12, 2009 to February 12, 2010 CDC estimated that between 42 million and 86 million cases occurred in the US with a mid-level estimate of 59 million people infected. Think about that - 7300 times more cases of H1N1 using the mid-level estimate during the same 307 days.

Another difference between influenza and Ebola is the incubation period (time from exposure to symptoms). Generally, the incubation period for influenza is 1-4 days (2-day average). For Ebola symptoms appear 2 to 21 days after exposure with an average of 8 to 10 days.

A final difference between Ebola and 2009 H1N1, which seems to be overlooked in discussions of airport screenings and other control measures, is infectivity during the incubation period. Put another way, can you transmit the virus without knowing you are sick? With Ebola, humans are not infectious until they develop symptoms. In comparison, with 2009 H1N1 it's reported "that pre-symptomatic influenza transmission occurred via both contact and respiratory droplet exposure before the earliest clinical sign, fever, developed" in a ferret model. This finding has been confirmed in humans. Interestingly, SARS is not infectious prior to symptom development (see CDC and Zeng et al), which may explain why we were ultimately able to contain SARS (unlike influenza).

To summarize, Ebola is slower moving, has a much longer incubation period (especially compared to the duration of a transcontinental flight), and is not contagious before symptoms develop. What does this mean? It means that if Ebola was as infectious as influenza, millions would have already died - apocalypse. It also means that since Ebola is not transmissible during its long incubation period, it may be possible to quickly isolate patients when symptoms develop. Thus, airport screening on exit or entry could limit transmission and perhaps through early diagnosis allow Ebola infected patients to receive life saving treatment more quickly.

A more concrete example: Imagine a person infected yesterday with influenza but still asymptomatic during their two day-incubation period. This person would screen negative overseas and in the US. However, it's highly likely that they are already infectious or will become infectious during their flight. Thus, many other passengers in the airport and plane would take influenza home with them as a vacation souvenir. Screening doesn't work for influenza. This would not be the case with Ebola because they will detect their symptoms as they become infectious and only spread it though blood exposure - something unlikely so early in the infection even on a long transcontinental flight. And think about how many times another person has bled on you even when they were bleeding (i.e. the Ebola condition) versus how many times someone has coughed or sneezed on you when they were coughing and sneezing (the influenza condition). **cough**

Airport screening for Ebola symptoms may still be ineffective, but I would like to see a few more mathematical models analyzing the epidemiology of Ebola and the impact of specific screening programs. In the meantime, let's focus our attention and resources on the horrible plight in West Africa.

image source: xkcd

Flu: A ground-level view

This flu season seems to be having a huge impact, though the data from CDC don't seem to be giving a complete picture. It is clear that many states continue to be experiencing widespread activity, but the national data don't capture the severe morbidity and the mortality that is occurring in young adults due to H1N1. Just at my hospital we have had several young adults require ECMO. We have heard reports of hospitals having to borrow ventilators due to the number of patients with influenza associated ARDS, and we are aware of deaths due to hospitals exceeding their capacity to provide ECMO. There is the perception among many clinicians that the severity of disease seen this year exceeds that seen during the 2009 H1N1 pandemic. Part of the problem, at least in Virginia and many other states, is that influenza deaths in adults are not reportable, nor do we have accurate data on patients requiring mechanical ventilation or ECMO. Perhaps it's time to rethink influenza surveillance particularly since diagnostic testing has improved significantly over the past few years.

Critique of the WHO pandemic response is now out

We blogged early and often about the H1N1 pandemic, including posts about the controversy surrounding the WHO response and whether there was any industry influence at play. An independent expert panel has now released a draft report on the 2009 H1N1 response. Here are the media summaries from the NY Times, Science Magazine, and the Nature blog The Great Beyond.

Regarding the industry conflict-of-interest (COI) issue, the report takes WHO to task for poor handling of COI and lack of transparency, but concludes that there is "no evidence of attempted or actual influence by commercial interests on advice given to or decisions made by WHO." I’m not sure what such evidence would be required…direct cash payments to members of the WHO advisory committee? Anyway, given that the panel felt that WHO waited too long to call the pandemic, it is unlikely they’d conclude that this decision was driven by industry COI.

Read the report yourself—now that Iowa has thawed out and the sun has appeared, I have no time to detail all 15 of the recommendations the panel made.

H1N1 Flu Deaths in the UK on the rise

Per a government report in the BBC and other UK papers, there have been 39 deaths from the flu this winter with 36 confirmed as H1N1-related while the other three were caused by influenza B.  Unlike here in the US, the UK vaccination committee does not recommend a flu "jab" for healthy children less than 5 and other children ages 5 to 15.  All but one of the deaths occurred in people <65yo. Around 20% of all ICU beds in England are now filled with confirmed or suspected influenza patients.

Health Secretary Andrew Lansley said "the people we would wish to vaccinate are people in at-risk groups and over 65s who can be contacted via their GP." Which makes some sense since 23/38 deaths (one patients data wasn't available yet) were from high-risk groups. However, that still leaves 40% of patients without any risk factors. Since there is no vaccine shortage, I wonder why they aren't broadening their vaccine strategy to include younger children. As it is, only 23% of currently eligible children <5 get vaccinated.

The H1N1 virus continues to attack younger children and not older adults. In English children <4yo, the influenza incidence is 184 cases/100,000 while it is only 36 cases/100,000 in those >65yo. An epidemic is defined as an incidence >200 cases/100,000.  Seems like rapid vaccination of children might be a good idea, particularly when you look at the graph below showing 2010-2011 as an active year, similar to the spring of 2008-2009 season when H1N1 began.  If H1N1 vaccine was available in spring 2009, I bet they would have promoted it more than they are promoting the vaccine now.

Oh, Happy New Year!

BBC report (12/30/2010)
Guardian report (1/1/2011)

UK Health Protection Agency Epidemiological Report 30 December 2010

ILI Activity with 2010-11 in red  - taken from UK HPA report (link above)

2009 H1N1 Pandemic Response: Looking backward and forward

Recently in PLoS Medicine, Gabriel M. Leung from the Food and Health Bureau, Hong Kong and Angus Nicoll from the European Centre for Disease Prevention and Control reflected on the public health response to pandemic H1N1. They discuss what went right and what should be done now to augment our future responses.

I really liked that their primary points highlighted that "public health messages...should not confuse what could happen (and should be prepared for) with what is most likely to happen" and that "decisions regarding pandemic response during the exigencies of a public health emergency must be judged according to the best evidence available at the time."  I've pasted below the list of pandemic "Firsts" which included a special shout out to the challenging "blogosphere," of which this here ye olde blogge was a member.

Box 1. A Series of “Firsts” about Pandemic (H1N1) 2009

• The first pandemic to emerge in the twenty-first century. It has been more widespread and remains ongoing, compared to SARS.
  
• The first pandemic to occur after major global investments in pandemic preparedness had been initiated.
  
• The first pandemic for which effective vaccines and antivirals were widely available in many countries, thus requiring public health authorities to earn and retain the confidence of health care providers through whom such are usually distributed.
  
• The first influenza pandemic to coincide with the ongoing HIV/AIDS pandemic and for which preliminary data do not suggest a substantial, disproportionate impact on HIV-infected patients.
  
• The first pandemic that took place within the context of a set of International Health Regulations and global governance, which had not been widely tested until the present.
  
• The first pandemic with early diagnostic tests that led to rapid diagnosis but also an early obsession in the media and of policymakers with having reports of the numbers of those infected.
  
• The first pandemic with antivirals available in many countries that led to a hopeful expectation that the pandemic might be containable, leading to the preparation for and implementation of a “containment phase” in some places.
  
• The first pandemic in which intensive care was available in many countries to treat critically ill patients, fostering an expectation that everyone could be treated and cured.
  
• The first pandemic with instant communication so that early impressions (such as the experience and response in Mexico and the Ukraine) could be shared ahead of proper scientific analysis.
  
• The first pandemic in which web-based platforms of traditional journals expedited dissemination, complemented by other innovative online resources (e.g. PLoS Currents: Influenza, http://knol.google.com/k/plos-currents-i​nfluenza#, based on Google's knol technology).
• The first pandemic with a “blogosphere” and other rapid social media messaging tools that challenged conventional public health communication.

Source: G. Leung and A. Nicoll. Reflections on Pandemic (H1N1) 2009 and the International Response. PLoS Med 2010

Prior seasonal influenza infections protective against 2009 Pandemic flu (if you're a ferret)

Looking back at the 2009 flu season, I realize how calm it is now compared to then.  I hope it stays that way!  In that pandemic, the attack rate was 50% in young populations compared to perhaps 10% in adults.  Why would this be the case? Serologic analysis showed little cross-reactivity between recent seasonal influenza A(H1N1) viruses and pandemic A(H1N1). The authors of a recent JID paper postulated that the lower attack rate in adults could result from multiple past exposures to viruses with similar B epitopes or since there is conservation of T cell epitopes between pandemic H1N1 and seasonal influenza A, then cellular immunity may also reduce disease severity. There's also the fact that adults responded to a single dose of pandemic H1N1 vaccine, while children did not, suggesting that past exposure to seasonal strains is important.

To examine the role of prior immune reponses in seasonal influenza on exposure to pandemic H1N1, Laurie et al. in the Oct 1 JID, studied the impact of one or two prior infections in a ferret model.  The found that a single prior infection with a seasonal influenza A virus, A/Fukushima/141/2006 (H1N1) or A/Panama/2007/1999 (H3N2), reduced the duration of shedding following challenge with 2009 pandemic H1N1, but not reduce the infection rate nor did it reduce the transmission to other ferrets.

The authors then tested whether two prior infections with seasonal influenza was protective against pandemic H1N1.  They determined that infection with seasonal A(H1N1) followed by A(H3N2) reduced the infection rate along with the amount and duration of shedding in ferrets challenged with pandemic A(H1N1). Interestingly, no virus was transmitted to other ferrets, nor did the exposed naïve ferrets experience seroconversion to pandemic flu.

Good news, if you're a ferret.

Laurie KL, et al JID, October 1, 2010.

WHO exaggerated H1N1 Threat, Potential COI issues

Two separate European reports criticized the WHO for exaggerating the H1N1 threat and failing to disclose pharmaceutical conflicts of interest. The first report was from the Health and Family Affairs Committee of the Parliamentary Assembly of the Council of Europe (say that three times) and looked at the pandemic response and the second was from BMJ and the Bureau of Investigative Journalism and looked at the 2004 guidelines which were written by three experts with financial ties to Roche and GlaxoSmithKline. Washington Post article (here), BMJ+BIJ (here), Council of Europe article (here) and pdf of Council of Europe report (here). I wonder if N95 manufacturers are getting nervous?

Why your friends spread influenza and you don't

There was a really interesting study by Nicholas Christakis and James Fowler in the May 15th Economist (here) and posted online (full manuscript here). The general thought behind the study was that people in the center of social networks, the ones with more friends or connections, would be more likely to be infected with influenza sooner. Thus, if you could identify people in the center they could serve as an early warning system for flu. The problem is, this would take a significant amount of effort. The insight into this problem comes in the form of what is called the friendship paradox. This 'paradox' suggests that your friends have more friends than you do.

To test this theory, Christakis and Fowler identified 319 students and then 425 of their friends. If friendship paradox would work in identifying influenza then the 425 should get flu earlier. So they followed the 744 students from September to December 2009 during the H1N1 epidemic and found that the friends, the 425 more likely to be in the center of the network, developed influenza (self-diagnosed and confirmed) around 2 weeks earlier. In fact, self-reported symptoms peaked 83 days earlier and visits to healthcare facilities peaked 46 days earlier in the connected group. Maybe this is a new method that could be added to other monitoring systems. Either way, come influenza season, stay away from your friends, especially the ones who are really friendly.

Hurry up, CDC

It has been a while since we blogged about the ridiculously stupid mask fiasco, mainly because the 2009 H1N1 virus is off the radar in most parts of the country and world.

This hasn’t stopped California OSHA from citing UCSF for not requiring N95 masks for the care of patients with suspected or confirmed 2009 H1N1. A post from the EIN this morning details the citation, which includes a fine and a requirement to rectify the situation by June 6, 2010. Here is a short excerpt from that EIN post:

I am…concerned about the short time window which we have been given to rectify the situation. Given the availability of 2009 H1N1 vaccine and increasing evidence in the literature that N95 masks are not superior to surgical masks, we plan to appeal before making a change in our practice; however, it is unlikely that OSHA will be willing to consider such an appeal without a formal change in the CDC guidance. I have heard that the CDC will soon be providing updated guidance on infection control practices for 2009 H1N1 - does anyone know the status of these guidelines and when they will be available?

Given that the “2009 H1N1” is going to be with us as a seasonal strain now, the CDC has only two options that make any logical sense: either back off the mistaken N95 recommendation, or begin requiring N95 use for all suspected or confirmed seasonal flu.

It would be nice if CDC acted quickly, and if OSHA held its fire until new guidance is issued.

Addendum: Rather than spending its time and resources doing post-hoc punishment of hospitals that responded appropriately to 2009 H1N1, California OSHA should be doing more to reduce the real threat of HIV transmission in the porn industry. So far, Cal OSHA has taken the bold step of “setting up an advisory committee to study the issue”.

H1N1: One year later

This morning's New York Times has an OpEd piece by Dick Wenzel in which he reflects on the H1N1 influenza pandemic over the past year. Click here to read it.

H1N1 vaccine: they can't give it away

There's been a fair amount of media coverage on the latest Harvard poll on H1N1. I just went through the results of the poll, which can be viewed here, Slightly over 1,400 persons nationally were interviewed, and the poll has a margin of error of +/- 3.2% at a 95% confidence interval. The poll found that only 21% of adults have received the H1N1 vaccine, and of those who did not receive it, 58% cite they are concerned about the safety of the vaccine. Of those with children surveyed, only 36% reported that all of their children had been vaccinated with another 4% reporting that some of their children had been vaccinated. Of those whose children were unvaccinated, 75% cited safety concerns. Lastly, only 48% felt that healthcare workers should be required to receive the vaccine.

Given the amount of money and effort that has gone into this public health endeavor, I would rate the vaccination campaign as a failure. But I don't think that CDC should bear most of the blame for this. Unfortunately, the public couldn't be convinced that this vaccine is safe. Overcoming the constant stream of misinformation wasn't possible, and many people have difficulty sorting out the information that is credible. What I thought was particularly striking is that only half wanted healthcare workers to be required to get the vaccine. Given how tough consumers have become on healthcare workers with regards to transmission of infection in the hospital, I think that's a true measure of how badly this vaccine was viewed.

Unless there is an upsurge of H1N1 cases in the near future, I doubt that vaccine uptake will increase. The cake is baked.

Who is that masked...college student?

Researchers Allison Aiello and colleagues at the University of Michigan just published a study in the February issue of JID that assessed the benefit of (a) face masks or (b) face masks + hand hygiene vs. (c) control in preventing ILI in college residence halls (dorms) during the 2006-7 flu season. Each group (cluster) consisted of either one very large hall or a combination of 3 smaller halls (2 groups) for a total of 7 randomized halls. 1297 students were included in the study. Interestingly, spring break occurred during the study period which may have impacted the results. To bad the analysis couldn't tell us whether heading to the beach or skiing reduced the risk of influenza. In any case, they reported significant reductions in ILI in the mask+hand hygiene group during weeks 4-6 and in the mask only group during weeks 4-5 after influenza was first detected on campus.

An accompanying editorial by Titus Daniels and Tom Talbot, both at Vanderbilt, places the new findings in the context of the recent H1N1 'pandemic' and the N95 respirator debate. Importantly they suggest that the benefits seen in both face mask arms of the study may have been secondary to reduced viral shedding from infected mask wearers. They are correct to point out that the Michigan study supports the benefits of hand hygiene and it was also great to see them re-emphasize the importance of annual vaccination, particularly in health care workers, staying home when sick and compliance with proper respiratory etiquette.

Note: Both the article and editorial full-texts are available for free on the JID website; which is very nice for all who don't have a personal or university-based subscription.

Chart of the day

Today's New York Times has an interesting graphic of deaths due to influenza and pneumonia during the pandemic of 1957-58. CDC is using this to encourage vaccination against H1N1 in the event that a similar subsequent spring peak is seen.

New Year's Resolutions, Procrastination and Public Health

I suspect we've all made resolutions at some point, but studies show most of us fail to accomplish our goals. I mean, is Lindsay Lohan really going to stick to this? I give her until St. Patrick's Day, but I digress.

In a recent article, The Economist suggests that a major reason for our failure to accomplish our goals is that we have a tendency to procrastinate; no surprise there. We tend to put off unpleasant or costly things into the future. That would be OK if we would stick to a single delay, but it turns out that we are time-inconsistent or “present-biased” and will always put off tough or costly things to the next day. Tomorrow really is always a day away. They reference a paper by O’Donoghue and Rabin.

I suspect this tendency is at the heart of the public health problems we have in the US. When you build a road you have immediate gratification, but the gratification of a well-funded state health department is uncertain and certainly in the future. Perhaps a better example is one I suspect many of us in infection control will soon face: should we push our administration to restock our N95 mask cache that we used to meet the OSHA/CDC/IOM requirement to care for suspected H1N1 cases? Avian flu is still out there and is just as likely to become a pandemic as it was last year.

This issue really concerns me. Even in this mild pandemic, we all saw how quickly the supply chains dried up for critical supplies. However, I suspect that hospital administrators will assume that the next pandemic will be this mild or forget the supply chain difficulties we had. Even more of a concern for me is procrastination. Will they assume that they can delay purchasing N95s for a cache because we just had a pandemic so the next one won't happen soon? They can "wait 'til next year" just like our favorite Cubs fan. The problem is that next year they will wait until next year.

Fortunately, the Economist and authors Duflo, Kremer and Robinson offer a potential solution using an example of why so few African farmers use fertilizer and how this can be improved. The quick answer is that the tendency to procrastinate can be overcome by small upfront time-limited subsidies. This small investment ends up being far less costly than doing nothing or offering a larger subsidy later in the year. What this suggests is that public officials should offer a grant to hospitals who invest in their pandemic cache (mask, antivirals etc) in the next year, but remove the subsidy quickly. This could overcome the inertia to do nothing because of pandemic fatigue or procrastination. Of course, how can we overcome our public officials' tendency to procrastinate? They do have bridges to fix. Thoughts?

When flu is on your plane...

A study in BMC Medicine uses mathematical modelling to determine the number of infections that result from a single H1N1-infected passenger on a Boeing 747. As shown in the table below, it depends on the duration of the flight and the price of your ticket:

	Number who become infected
Flight duration	1st class	Economy
5 hours	0-1	2-5
11 hours	1-3	5-10
17 hours	2-5	7-17

Soon there'll be a new user fee from the airlines--$100 for lowest risk of H1N1 infection, $75 for moderate risk, and only $25 for highest risk! But wait, for only $150, your flight attendant will sell you a course of tamiflu. Of course, correct change is appreciated. Oh, I kid the airlines....

When flu comes home...

This week's New England Journal of Medicine has a study that looks at transmission of H1N1 flu in the household setting. The investigators studied 216 persons with flu (index cases) and their 600 household contacts over a 7-day follow up period. The attack rate for household contacts developing influenza-like illness (ILI) was 10%. The median age of the secondary cases was 14.5 years (median age of all household contacts was 26). Risk of acquiring ILI was age-dependent (compared to adults aged 18-50 years, children 0-4 years had a 3-fold risk, children 5-18 had a 2-fold risk, while the risk for those over 50 years was one-third that of adults under 50 years). The time from onset of symptoms in the index case to onset of symptoms in a secondary case was a median of 2.6 days.

Another H1N1 Vaccine Recall (FluMist)

Maryland-based MedImmune is recalling FluMist doses shipped in October and November after tests showed that it lost strength quickly after shipment. Per the CDC, this is a voluntary and non-safety related recall of 4.7 million doses similar to the one last week by Sanofi Pasteur. I know all indications are that this didn't impact the effectiveness of the vaccine, but I'm sure the anti-vaccine crowd will pounce on this and suggest that the vaccine was rushed and experimental. However, I won't glorify them by linking to them.

So how bad was the H1N1 pandemic?

According to a new paper in PLoS Medicine, Marc Lipsitch's modelling estimates that among persons with symptomatic H1N1:

• 1 in 70 required hospital admission
• 1 in 400 required ICU care
• 1 in 2,000 died

With data in hand, he argues in an NPR piece that this is a very mild pandemic. Not so, says Dr. Tom Frieden, Director of the CDC. An expert in risk communication speculates that CDC is avoiding describing the pandemic as mild out of fears that vaccine uptake will fall.

Influenza miscellany

Today's LA Times has an article on the effect that H1N1 influenza has had on the pork industry even though pigs haven't been part of the pandemic. On the other hand, here in Virginia, a flock of turkeys has been found to be infected with H1N1. Also in Virginia, 2 patients have been diagnosed with tamiflu-resistant H1N1, as have 2 patients at Johns Hopkins Hospital. And lastly, H1N1 has been diagnosed in a cheetah in a California zoo.

Quieting down on the H1N1 front

Iowa has now officially moved from “widespread” to “regional” to “local” activity. As the graphs below demonstrate, H1N1 has left our state for the time being. We haven’t had a positive influenza A in our hospital lab for over 2 weeks, the percent of visits due to ILI at Iowa ILINet sites is back to near baseline, and the number of patients hospitalized for influenza has plummeted.

Ironically, it is just this week that we got our first really big shipment of H1N1 vaccine (before, it was trickling in a few hundred doses at a time). So we’ll be doing most of the vaccinating after the virus has left town…yes, a “wave number next” could come along, but I doubt we’ll see another big bump in H1N1 cases in our state during the 09-10 season.

Decisions now begin to revolve around “walking back” the H1N1 response….when to lift visitor restrictions, how to approach vaccination going forward, and when we can begin treating H1N1 like……an influenza virus.