AFD - Pathogenesis of H1N1

[sharon sanders]

CIDRAP: NEJM Articles On The Pathogenesis and Distribution Of H1N1 in Mexico


# 3410


Maryn McKenna, writing tonight for CIDRAP (Center For Infectious Disease Research And Policy) News, brings us an overview of two NEJM (New England Journal of Medicine) articles published today on the the H1N1 pandemic virus.

We?ve been waiting for clinical details to emerge, particularly regarding patients with bad outcomes or severe symptoms. What we learn today reinforces information we?ve only gotten in drips and drabs:

That while most people recover without incident, the H1N1 virus can cause serious respiratory illness and multi-organ failure in some patients ? even those without previously existing medical conditions.
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Here are the opening paragraphs to Maryn?s article. Follow the links to read it in it's entirety.

Novel H1N1 flu can cause severe respiratory illness

Maryn McKenna

Contributing Writer
Jun 29, 2009 (CIDRAP News) ? Novel H1N1 influenza can cause severe respiratory illness, profound lung damage, and death even in patients with no underlying conditions to make them vulnerable, a team of physicians from Mexico report in a rush article published online today by the New England Journal of Medicine (NEJM).

The analysis of 18 patients hospitalized with H1N1 (swine) flu at the National Institute of Respiratory Diseases (INER) in Mexico during the pandemic's earliest days reveals that fewer than half had underlying medical conditions, but more than half needed mechanical ventilation within a day of admission. Seven of the 18 died.

In a companion article, also published in advance online today, a multi-national team from Mexico and the United States document the age distribution of the first month of the H1N1 pandemic in Mexico, where the disease appears to have struck first, and confirm its unusual pattern of severe pneumonia among younger patients. Matching the pattern to those of earlier pandemics, the team speculates on the "biologic plausibility of partial protection" in older people exposed to mid-20^th century strains of seasonal flu.

(Continue . . .)
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Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med 2009 (published online Jun 29) [Full text]
Chowell D, Bertozzi S, Arantxa Colchero M et al. Severe respiratory disease concurrent with the circulation of H1N1 influenza. N Engl J Med 2009 (published online Jun 29) [Full text]


In a separate article, Lisa Schnirring of CIDRAP brings us a look at two more NEJM articles on the evolutionary path that the H1N1 virus has taken since it first appeared in 1918.

Experts look for clues in 1918 pandemic virus family tree

Lisa Schnirring

Staff Writer
Jun 29, 2009 (CIDRAP News) ? To outside observers, the novel H1N1 virus spreading quickly to every corner of the globe must seem like it came out of nowhere, but the organism is a fourth generation of the 1918 pandemic virus and comes from an H1N1 family tree that is colorful and complex, according to two historical reviews that appear today in the New England Journal of Medicine (NEJM).

Understanding the history of swine influenza viruses, particularly their contribution to the 1918 pandemic virus, underscores the need to better comprehend zoonotic viruses as well as the dynamics of human pandemic viruses that can arise from them, the authors report in an early online NEJM edition.

The world is still in a "pandemic era" that began in 1918, wrote three experts from the National Institute of Allergy and Infectious Diseases (NIAID), senior investigator David Morens, MD, medical epidemiologist Jeffery Taubenberger, MD, PhD, and NIAID director Anthony Fauci, MD.
(Continue . . .)
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Morens DM, Taubenberger JK, Fauci AS. The persistent legacy of the 1918 influenza virus. N Engl J Med 2009 Jul 16;361(3):225-29 [Full text]

Zimmer SM, Burke DS. Historical perspective?emergence of influenza A (H1N1) viruses. N Engl J Med 2009 Jul 16;361(3):279-85 [Full text]

 

[sharon sanders]

Re: AFD - Pathogenesis of H1N1

A Wide Spectrum Of Illness



# 3411



From almost the beginning of this novel H1N1 outbreak we?ve been warned by doctors to expect a wide spectrum of illness. Some people may become infected and show no symptoms at all (asymptomatic), while others may experience nothing worse than they?d normally see with seasonal flu.

Some people, we were warned, would see more severe illness. Particularly those with conditions that predisposed them to complications from influenza; asthma, diabetes, pregnancy, COPD, etc.

And for the most part, that?s the pattern we?ve been seeing. The vast majority of cases are either asymptomatic, mild, or no worse than `seasonal flu?.

Out of the millions of likely infections, most people are recovering.
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But for thousands of people, the course of this illness has been anything but `mild?. Here in the United States, more than 3,000 people ? mostly young adults and children ? have been hospitalized. Most had pre-existing medical conditions, but not all.

And regrettably, we?ve seen deaths too.

Not a lot by pandemic standards, perhaps. But that doesn?t diminish the tragedy of each loss.

Yesterday, we learned some of the details of the clinical courses (and some autopsies) from early severe cases out of Mexico. Maryn McKenna of CIDRAP reported:

The 18 patients were evenly divided by gender but ranged widely in age, from 9 months to 61 years, with a median age of 38. They were all at least moderately ill, with fever of at least 38?C (100.4?F), cough, and difficulty breathing; 4 of the 5 children had diarrhea.

Most had bloodwork findings that indicated acute viral infections, inflammation and cardiac distress. Half had low blood pressure that persisted after emergency treatment, and 10 of the 18 needed to be put on ventilators within 24 hours of arrival at the hospital.

<snip>

The patients had a difficult course, with renal failure in 1 survivor and 5 of the deceased and multi-organ failure in all 7 of the dead. Pathological examination of the lungs of one of the dead patients showed severe damage to lung tissue, but, with no bacterial infection evident, the researchers ascribed it to the primary viral pneumonia caused by the new flu. No evidence was found of co-infection with any other virus.
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While only a small subset of the total number of infections, the course of severe illness described above is a bit remarkable given that no evidence of secondary bacterial infection was found.

The presentation ? low blood pressure refractory to treatment and the rapid need for ventilator support ? is almost classic for sepsis (severe bacterial infection).

So the lack of any evidence of bacterial pneumonia in these cases is both surprising and puzzling.
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And via Crofsblog last night, in Canada: Severe H1N1 cases worry officials we get an excerpt from the Canadian Medicine blog: Recent severe cases of H1N1 flu worry health officials.

(Slightly reformatted for readability ? highlights mine)

Dr David Butler-Jones, the government's Chief Public Health Officer (above right), said that although the vast majority of the 7,775 cases detected in Canada so far (see the map below for a breakdown by province or visit the Public Health Agency's surveillance website) have been mild and have resulted in full recoveries, the anticipated "second wave" of infections this fall has been preceded already by the mysterious appearance in recent weeks of a small number of "severe" infections.



According to Dr Butler-Jones, the reason or reasons for the emergence of this new set of "severe" cases in Canada has not been determined, though epidemiologists with Health Canada and the Public Health Agency of Canada have been dispatched to study the matter.

Possible explanations, he explained, could include: genetic variations that result in either too little or too great an immune response in infected patients, a mutation in the H1N1 virus (which would augur potentially very serious consequences in the general population over the months to come, it would seem), or some combination of factors.

He warned that we should expect to see more cases in Canada over the coming months, including more severe cases, and more deaths.
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All of this pretty much matches the sparse reports we?ve been getting out of Argentina, where hospitals reportedly are being inundated with flu cases, and ICU?s are caring for scores of severe cases.


The take-away message here isn?t that the virus has mutated, or that the H1N1 virus is a stone cold killer.

It?s that even a `relatively mild? virus can have disastrous consequences for some small percentage of its victims. That while those with pre-existing conditions may be at greater risk, perfectly healthy people are not always guaranteed a good outcome.

That we shouldn?t trivialize this virus.
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Which means that we all need to continue to practice good flu hygiene; cover our coughs and sneezes, wash our hands frequently (or use alcohol sanitizer), and stay home when we are sick.

And the rapidly fulminating nature of this illness in some of its victims means we need to watch for serious complications in ourselves, and our loved ones, and to seek medical attention quickly if required.

The CDC recommends that people seek medical attention if someone:

• has difficulty breathing or chest pain
• has purple or blue discoloration of the lips
• is vomiting and unable to keep liquids down
• has signs of dehydration such as dizziness when standing, absence of urination, or in infants, a lack of tears when they cry
• has seizures (for example, uncontrolled convulsions)
• is less responsive than normal or becomes confused

Additionally, anyone with pre-existing conditions such as asthma, COPD, diabetes, pregnant women, or those with other serious underlying conditions who believe they are coming down with this flu ought to contact their doctor.

People who live alone could easily become overwhelmed by this illness and be unable to care for themselves, or even know when they needed to call for medical help.

All of this highlights the need for everyone to have, or become, a `flu buddy? to a friend, neighbor, or relative (see Pandemic Solutions: Flu Buddies).
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The eventual course of this pandemic remains uncertain, although there is little doubt about it presenting serious challenges.

It could remain `mild?; and by `mild?, we mean it may only kill a million people or so around the world ? or it could pick up virulence, and exact a much heavier toll.
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We?ll know how all of this turns out in three to five years.

Until then, the smart money is on getting our families, our businesses, and our communities prepared to deal with whatever hand this pandemic deals us.

For more information on preparedness, you can go to any of these reputable sites.

FEMA http://www.fema.gov/index.shtm
READY.GOV http://www.ready.gov/
AMERICAN RED CROSS http://www.redcross.org/
For Pandemic Preparedness Information: HHS Individual Planning Page
For more in-depth emergency preparedness information I can think of no better resource than GetPandemicReady.Org.
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You can also help by volunteering with the American Red Cross, The Medical Reserve Corps, CERT, or your Neighborhood watch.