As of today, May 18th

Posted on May 18th, 2009 in Uncategorized | No Comments »

A map summarizing the current state of the H1N1 outbreak, courtesy of the WHO

The worldwide distribution of confirmed H1N1 cases

The worldwide distribution of confirmed H1N1 cases

Where are we?

Posted on May 11th, 2009 in Uncategorized | No Comments »

A summary of confirmed H1N1 cases to date

A summary of confirmed H1N1 cases to date

The data, as of this posting:

4694 cases of influenza A (H1N1) infection reported in 30 countries.

Confirmed deaths in Mexico attributed to H1N1 infection: 48.

Confirmed cases of H1N1 influenza in US: 2532.

Confirmed deaths in US attributed to H1N1 infection: 3.

Confirmed cases of H1N1 influenza in Canada:  284.

Confirmed deaths in Canada attributed to H1N1 infection: 1.

Confirmed cases of H1N1 influenza in Spain:  95.

The temptation at this point is to assume that the threat of H1N1 is over, and our limited attention span should now be focussed somewhere else.  From my vantage point, the following seems clear:

1) This H1N1 strain, at least in the currently circulating form, appears to produce symptoms comparable to seasonal influenza strains.  For now, the fears that we were dealing with a particularly virulent strain of influenza have not materialized.

2) The number of cases will continue to rise, as will the number of deaths.  But neither cases nor deaths appear to be rising as rapidly as initially feared.  The graphs below show the incidence rates (per 1000) associated with the 1918 pandemic and with the current H1N1 outbreak.  The  contrast between these graphs should be noted (note the dramatic difference in Y-axis values).

Incidence rates/1000, US, 1918 Influenza Pandemic
Incidence rates/1000, US, 1918 Influenza Pandemic

Incidence rates/1000, current H1N1 outbreak
Incidence rates/1000, current H1N1 outbreak

3)The apparent waning of this H1N1 outbreak is good news, but novel strains of this sort do not simply disappear into the ether.  At this stage, the fate of this strain in the Southern Hemisphere, where the influenza season is just beginning, bears keeping an eye on.  Similarly, many epidemic strains will resurface, often in a more distinctive and aggressive form, in a second wave of infection.  This ain’t over yet.

Remembrance of viruses past

Posted on May 6th, 2009 in Uncategorized | No Comments »

The data to date suggest that the current H1N1 strain is infecting individuals 17 and younger at a disproportionate rate.  While still unclear that this pattern will hold, we may be seeing a curious reflection of our collective immunological memory playing out.

To understand this pattern, we need to keep in mind the fact that all battles between our immune system and any invader — virus, bacteria, or foreign protein — play out in three dimensions.  Immune response is all about recognizing shapes that do not belong (“non-self”), and about mounting a concerted response to these alien shapes.  But that response takes time, and is usually most effective when the immune system re-encounters an alien shape it has seen at least once before (this, incidentally, is the logic behind immunizations).

HA and NA

A cartoon model of the influenza virus, showing the two important surface proteins: HA and NA

Influenza viruses, in turn, exploit aspects of our immune response to evade it.  First, they evolve in response to immune pressure by constantly changing the shape of their surface proteins, hemagglutinin (HA) and neuraminidase (NA), the only parts of the influenza virus our immune system “sees”. This enormously successful evolutionary strategy is made possible by the particularly sloppy copying of the viral genome that goes on every time the virus replicates. When you are a virus being hunted down by the immune system, sloppiness works.  Our immune system is thus always playing catch-up, reacting to the shifting shape of the invader.

But what the immune system appears to lack in foresight, it more than makes up for with memory.  In effect, our immune system remembers every shape it has ever encountered and responded to.  Like the grizzled sheriff in an old Western, our immune system can hold a grudge for a long time, and the second response will be swifter and deadlier than the first.  And now, a subtle wrinkle: the immune system can recognize and respond to shapes with great precision, but it is also capable of reacting, albeit less vigorously, to shapes similar to those it has seen before.

Hemagluttinin, one of the surface proteins of the influenza virus

Hemagglutinin, one of the surface proteins of the influenza virus

Our immune system’s ability to patrol for specific shapes, but also to keep an eye out for the shape neighborhood surrounding a specific shape, may help explain the pattern of infection we are seeing with the current H1N1 shape.  While this strain, is, as we mentioned in an earlier posting, entirely new, there have been other H1N1 outbreaks before.  The most recent noteworthy outbreak of H1N1 occurred in 1976, and prompted a massive vaccination program in the US, where more than 40 million individuals were vaccinated (and where the morbidity and mortality due to the side effects of vaccination — particularly a rise in Guillain-Barré syndrome– exceeded the effects of the influenza outbreak).  That H1N1 strain, and others related to it, likely remained in circulation for several years after the 1976 episode.  As a result, individuals that are 33 years old or older have likely been exposed to a version of H1N1, either through vaccination or through contact with the virus itself.  The collective immunological memory of middle-aged and older individuals may be conferring a protective effect on these demographic cohorts.  In contrast, younger individuals, whose immune systems have never seen the current H1N1 or any previous version of H1N1, may be more susceptible to infection, accounting at least in part for the strange demographic character of the current outbreak.

This argument, of course, is at this point only a hypothesis.  Among other things, it relies on the conjecture that individuals exposed to H1N1 in the 1970’s can in fact mount a more effective and swift immune response than that of immunologically naive younger individuals.  This, in turn, depends on the similarity in the surface proteins of the 1970’s H1N1 strains and those of the current strain.  We will know more about this in the days to come.

Some Pig

Posted on May 4th, 2009 in Uncategorized | No Comments »

Pigs at risk?

Pigs at risk?

A new, and potentially important wrinkle in the H1N1 story emerged over the weekend.  It concerns a pig farmer in Vancouver who returned from Mexico in the second week of April, resumed his normal work routine, and may have infected the swine herd he tends with H1N1.  Reports suggest that 200 or so pigs, out of a herd of 2200, exhibited “loss of appetite or fever”, and the source of the pig’s malaise has been traced to H1N1 infection — a strain identical to the one carried by the farm worker.

This story, if correct, has important implications.  First, it suggests that this influenza strain may have an impact on pig farming and pork production, with the attendant risks of economic and trade disruption.  More subtly, this story hints at the possibility that this H1N1 strain is capable of moving back and forth from pigs to humans and back again with relative ease.  As we discussed in a previous post, the transmission of influenza strains from non-human animal reservoirs to the human population is generally a rare, low probability event.  Similarly, the return trip should also be a unlikely occurrence.  Except, it appears, in this case.

The transfer of influenza strains from one species to another is usually difficult because viruses evolve in response (among other things) to the immune system of their host.  A flu strain shaped by the pig’s immune system is generally not ideally suited to evade the human immune system (although it will quickly begin to evolve in that direction once it gains a foothold in humans).  Conversely, a strain shaped by our immune system, as this H1N1 now is, should have a difficult time upon re-encountering the pig’s immune response.  The same applies to the ability of the virus to invade host cells: if you are good at gaining entry into the cells of a pig, you are probably quite poor at entering human cells.

Influenza strains, in short, usually live and die by the old adage “jack of all trades, master of none”.  But if the report about the Vancouver pig farmer is correct, we may be dealing with a rare exception. This H1N1 strain may have figured out how to remain camouflaged from both pig and human immune responses, and may be carrying the tools to gain entry in to both human and pig cells.  Such a strain deserves our attention, and, if it can indeed move back and forth between humans and pigs, will complicate our efforts to contain its spread.

Are we done yet?

Posted on May 4th, 2009 in Uncategorized | No Comments »

The data, as of this posting:

985 cases of influenza A (H1N1) infection reported in 20 countries.

Confirmed cases of H1N1 influenza in Mexico:   590

Confirmed deaths in Mexico attributed to H1N1 infection: 25.

Confirmed cases of H1N1 influenza in US:  226.

Confirmed deaths in US attributed to H1N1 infection: 1.

Confirmed cases of H1N1 influenza in Canada:  85

Confirmed cases of H1N1 influenza in Spain:  40

The weekend, once gain produced new information, as well as new speculation about the course and prospects of an H1N1 epidemic.

The public health authorities in Mexico announced that the first wave of H1N1 infections may have peaked in that country, and a consensus is beginning to emerge suggesting that this strain may not be as virulent as first feared.

Both of these statements are driven by still developing facts on the ground, and they may be largely correct.  Nevertheless, the conclusions that are been drawn from these and other developments– namely, that the concern about H1N1 was misguided, that the world has overreacted, and that influenza is old news– seem premature, if not downright foolish.

Public health authorities have to contend  both with our (and the media’s) short attention span and the difficulties we have handling ambiguity and uncertainty (see the “Guarantees and Predictions” post).  Coupled with our understandable desire to avert our attention away from unsettling events, many people are beginning to assume that this is all over. It is not. The reality is that the virus has now made its way around the world in a very short period of time, and the number of cases, both in the US and in the rest of the world, will likely continue to rise.  This outbreak is by no means over, although the consequences of the outbreak may turn out to be somewhat less dire than first reports might have suggested.

That said, the safe practices being promoted should still be observed.  An effective participatory democracy depends on an informed citizenry, and this outbreak is a perfect opportunity to educate ourselves about infectious disease in general, and influenza in particular. While this strain may fade for now, particularly in the Northern Hemisphere, where influenza season has come to a close, it may well reemerge in the next flu season, or gain a foothold in the Southern Hemisphere, where the flu season is only now beginning.

Flu seasonality ion the Northern Hemisphere (US)

Flu seasonality in the Northern Hemisphere (US)

Flu seasonality, Southern Hemisphere (NEw South Wales, Australia)

Flu seasonality, Southern Hemisphere (New South Wales, Australia)

Bird vs. Swine

Posted on May 2nd, 2009 in Uncategorized | No Comments »

Many people are feeling a sense of deja-vu about this newest influenza outbreak.  Two years ago, public health authorities were on the alert for a possible outbreak of bird flu, based on the deaths of 257 individuals around the world (out of a confirmed 421 cases in 15 countries).  The possible spread of that strain was a justifiable source of concern for governments around the world.  Fortunately, the pandemic of bird flu did not materialize, and the number of infected individuals remained low:  most of the infections had come about as a result of bird to human contact.

This H1N1 strain of swine flu is quite different. Its emergence provides an opportunity to contrast three important features of the influenza virus:  transmissibility, infectivity and severity.

Transmissibility refers to the ease with which the virus can be passed from one host to another.  H1N1 has our attention precisely because of its apparent  transmissibility– or more precisely, because of its capacity for transmission from one human host to another.   This stands in stark contrast with the bird flu, where it appeared that that influenza strain was seldom, if ever, capable of moving from an infected human to an uninfected human host.  As a result, virtually all of the confirmed bird flu cases occurred in individuals that had been in recent contact with infected poultry.  (As a general rule, the rate of viral transmission from an animal reservoir to a human host is exceedingly low, and requires repeated contact with infected animals or birds).

The H1N1 strain likely originated through pig-human contact, although this remains to be confirmed.  The location of this original transfer is still unknown, and may or may not be in the small town of La Gloria, in the state of Veracruz,  Mexico.  What is clear is that the majority of confirmed cases of H1N1 around the globe cannot be traced to pig-human contacts: people are not getting this flu from contact with pigs (or pork).

Infectivity: Infectivity measures the ease with which individuals exposed to a particular viral strain develop the infection.  Infectivity and transmissibility are clearly linked, but we do not as yet know much about the the infectivity of H1N1 strain.  The fact that the overwhelming majority of our immune systems have never seen anything resembling the H1N1 strain before increases this strain’s infectivity (making it, from the virus’ point of view, a particularly successful strain); we are still unclear about the extent of exposure required  to contract H1N1.  (Not surprisingly, given our previous discussion, the infectivity of the the bird flu strain was exceedingly low.)

Severity:  The severity of the H1N1 strain, as opposed to that of the bird flu, presents a  startling contrast.  While the lethality of the bird flu was close to 57%, H1N1 appears to be far less lethal, and results in far milder symptoms.   Some confusion on this score surfaced in earlier reports which suggested a high mortality rate from the H1N1 virus in Mexican cases.  It now appears that the number of deaths provisionally attributed to H1N1 may have been overestimated, and has been revised down from 176 to 101.  More subtly, the number of total cases of H1N1 in Mexico (the denominator when you are calculating the mortality rate for H1N1), may have been significantly underestimated.  This underestimate  arises for a variety of reasons: lag times in reporting, a weaker infrastructure in Mexico for the diagnosing and collating of cases,  the challenges associated with confirming a “probable case” as an unambiguous H1N1 infection, and the likelihood that in rural areas many individuals with the infection will not or cannot not enter the health care system.

The possibility that H1N1 first emerged in Mexico as a more virulent strain, and has since evolved into a milder strain cannot be ruled out, nor can the hypothesis that the health status of most of the Mexican population (including the presence of previous chronic infections) increases the severity of symptoms associated with H1N1 infection.  What is absolutely clear is that cases of H1N1 outside of Mexico are so far presenting with symptoms no more severe than those seen with ordinary seasonal flu strains.

Updating the facts

Posted on May 1st, 2009 in Uncategorized | No Comments »

As of this posting:

The number of confirmed cases of H1N1 influenza in Mexico: 156

The number of confirmed deaths in Mexico attributed of H1N1 influenza: 9

Incidence rate in Mexico: 1.42/1,000,000

Mortality rate in Mexico: 57/1000

The number of confirmed cases of H1N1 influenza in the US: 141

The number of confirmed deaths in the US attributed of H1N1 influenza:1

Incidence rate in US: 0.46/1,000,000

Mortality rate in the US: 7/1000

Number of countries reporting confirmed H1N1 cases: 13

Data source

And here is a link to a fascinating live map (shown above) of reported possible cases of H1N1.  The map is not entirely accurate, but it aggregates some fascinating sources of data, including news reports, official data releases, and Google searches. Approach with caution, but do check it out.

Guarantees and Predictions

Posted on May 1st, 2009 in Uncategorized | No Comments »

One of the difficult things to accept about this influenza episode is the uncertainty that surrounds many of the official pronouncements about the outbreak.  This uncertainty about “possible” pandemics or “probable” sources of contagion stems from two different sources.  First, there is still much we do not know about this particular virus and its hosts (more on this later).  But even if we knew everything there is to know– which we will not– we need to keep in mind that epidemiology is neither a deterministic, nor an inherently predictive discipline.  The statements that epidemiology is equipped to make are inherently probablistic.  We can predict that the chances of an outbreak are increasing (or decreasing) under certain circumstances, but we cannot guarantee that a particular strain will spread at a given location by a certain time.

The idea that all science deals in absolute truths and certainties is a profound misunderstanding of the nature of our work.  Many branches of science deal with problems where uncertainty is fundamental to the process or objects of study.  Epidemiology is a prime example: so many different processes determine the dynamics of an infection that we cannot be certain of any single outcome.

When the WHO decides to raise the pandemic alert to Phase 5, they are not predicting that a global influenza pandemic will occur.  Rather, in their judgement, the conditions on the ground make the possibility of a pandemic far more likely.  But prediction is not guarantee, and we cannot look to the science of complex phenomena for simple certainty.

Living with uncertainty

Posted on May 1st, 2009 in H1N1 | No Comments »

WHAT THIS BLOG IS ABOUT.

The prospect of a flu pandemic has certainly raised the level of anxiety for many people.  The purpose of this blog– which will continue as long as it makes sense to do so– is to provide some perspective on the information swirling around this new influenza strain.  In addition, I hope this blog will serve to dispel some of the more egregious myths about H1N1, and, wherever possible, to quell misinformation or rumors

TWO IMPORTANT DISCLAIMERS:

1) This blog represents the views and best judgement of one person, Dr. Rob Dorit, in the Dept. of Biological Sciences at Smith College.  It does not reflect the views, opinions or official policy of Smith College or of its officers, nor does it necessarily represent the views of my colleagues.

2) This blog is not intended as a source of medical advice.  Any reader in need of medical advice, or any reader who believes that s/he may be experiencing symptoms of H1N1 influenza, should immediately contact their heath practitioner.