Japan Considers Their Pre-Pandemic Vaccine Options

 

 

# 2268

 

 

 

Like a number of other countries, Japan has made a sizable investment in stockpiling a  pre-pandemic H5N1 vaccine, based on an earlier clade of the bird flu virus.    No one knows just how effective it will be against a pandemic strain, but the feeling it is, it may provide some protection.

 

 

The problem is, vaccines  have a limited shelf life. 

 

 

And millions of doses of Japan's stockpile will expire next year.   Authorities are faced with either using these vaccines, or losing them.

 

If they were to inoculate people with them, it is hoped these H5N1 antigens could remain protective for years inside the recipients.   

 

 

Of course, there is some risk involved.  

 

 

Only a few hundred people have received the H5N1 vaccines, and while no major adverse side-effects have been reported, the possibility exists that something could turn up if millions of people receive the shots.

 

 

This month Japan began inoculating about 6,000 medical personnel, the largest test of the vaccine to date, to see if any serious side effects showed up.   They are now trying to decide how many of the approximately 10 million remaining doses they want to distribute in their next major release of the vaccine.

 

 

According to today's article, in Japan Today, they are considering inoculating 1.5 million medical professionals, including doctors, nurses, and pharmacists.     Police, and other public safety workers, may receive the vaccine at a later date.

 

 

A hat tip to Mixin on Flutrackers for this link.

 

 

 

 

 

1.5 mil medical professionals eyed for expanded flu vaccinations

Monday 01st September, 05:56 AM JST

TOKYO —

The health ministry is considering inoculating about 1.5 million doctors and other medical professionals with pre-pandemic flu vaccines in a planned expansion of advance vaccinations to better prepare for a possible outbreak of new types of influenza, ministry sources said Sunday. Using the state’s stockpile of pre-pandemic vaccines, the Ministry of Health, Labor and Welfare started clinical trials in August targeted at around 6,400 people, including quarantine inspectors and workers at medical institutions for infectious diseases.

 

The ministry initially planned to expand the vaccinations to an additional 10 million people, including police officers and others engaged in ‘‘lifeline’’ services, if the safety and effectiveness of pre-pandemic vaccines were confirmed through the clinical tests. But the ministry has decided for now to limit the number of people targeted by the expanded vaccination program to 1.5 million, including doctors, nurses and pharmacists, after advice that expansion of the vaccination program should be implemented gradually, the sources said.

Watching Egypt Again

 

 

# 2267

 

 

 

Egypt hasn't reported a human case of H5N1 infection since April of this year, when a 2 year-old male child from Al-Honsaynya, Sharkea Governorate was diagnosed with the disease.   He was the 50th confirmed human case in Egypt ( where there have been 22 fatalities).

 

 

From time to time the Arabic press carries stories of suspected human infections, which thankfully, most of the time turn out to be false alarms.   Over the past couple of years, literally thousands of people have been tested for the virus, with only 50 positive results.

 

 

Today, after a long quiet spell, at least one Egyptian newspaper is reporting on a group of suspected cases.  

 

These are, of course, unconfirmed cases, and testing is pending.   Most of these cases, even those that are reported in the local press, have tested negative in the past.

 

We'll have to wait and see about these.

 

 

 

 

A hat tip to Pugmom on the Flu Wiki for picking up this article from elbadeel.net.

 

 

نقل 6 أشخاص إلي مستشفي حميات الزقازيق للاشتباه في إصابتهم بمرض أنفلونزا الطيور

 

31/08/2008

الشرقية: عادل الشاعر
استقبل مستشفي حميات الزقازيق ستة أشخاص يشتبه بإصابتهم بمرض أنفلونزا الطيور وهم «آية محمد جمعة 12 سنة ومني زكريا جودة 12 سنة وعماد زكريا جودة 55 سنة ومهدية مصطفي إبراهيم 45 سنة ومحمد جودة محمد 54 عاما، وولاء صبحي محمد محمد 8 سنوات وجميعهم من قرية نشوة التابعة لقرية بردين محافظة الشرقية، وتم حجز المصابين بالمستشفي للعلاج ولاستكمال التحاليل الطبية التي ستحدد إصابتهم بالمرض من عدمه.
شعرت مهدية مصطفي بإعياء تام مع ارتفاع شديد في درجة الحرارة مع التهاب في الحلق، وسعال مما دفع طبيب القرية إلي إبلاغ مستشفي الحميات باشتباه إصابة سيدة بمرض أنفلونزا الطيور، وبالكشف علي الأسرة والجيران تم اكتشاف أعراض مشابهة لأعراض المريضة الأولي وتم نقل طفلتين وأربعة أشخاص إلي المستشفي لإجراء التحاليل والفحوصات الطبية علي الجميع

 

 

 

6 Persons transferred to a hospital Dietetic Zagazig on suspicion of avian influenza illness

 
 

31/08/2008

 

Dietetic Zagazig hospital received six people suspected bird flu infection are any Mohammed Jumaa 12 years, Mona Zakaria quality of 12 years and Emad Zakaria quality aged 55 and Mahdi Ibrahim Mustafa 45 years and the quality of Muhammad Muhammad 54 years, and the loyalty Mohamed Mohamed Sobhi 8 years old, all from the village of euphoria To the village to two Eastern Province, was infected with booking hospital for treatment and completing medical tests that will determine whether or not sickened.
  

Mahdia Mustafa fatigue felt fully with very high temperature with sore throat, cough, which prompted doctors to inform the village hospital dietary suspicion injury Lady Bird flu disease, and to disclose to family and neighbors were discovered symptoms similar to the symptoms of the patient first has been the transfer of a child and four people to hospital To conduct tests and medical examinations for all

In Praise Of The Bug Out Bag

In Praise Of The Bug Out Bag

# 2266

In the vernacular, a `bug-out bag' (BOB) is a bag of emergency supplies, ideally kept at the ready, that one can grab on the way out the door during an emergency.

It isn't supposed to be a survival kit, but rather, to provide the essentials one might need during the first 72 hours of a forced, and sometimes unexpected, evacuation.

It should contain food, water, any essential prescription medicines, copies of important papers (ID's, insurance, important Phone #s), a first aid kit, portable radio, flashlight, extra batteries, and ideally blankets and extra clothes.

Sometimes emergencies occur with some warning, such as with a Hurricane, granting one a few days or hours to prepare. Other times they happen with such suddenness that there is no time to think, no time to prepare. Such as in an earthquake, a tornado, a chemical leak, or even a terrorist attack.

Every year, thousands, sometimes tens of thousands of Americans are forced to leave their homes in emergency evacuations. Most won't be ready.

Which is why everyone should have a BOB outfitted and ready to go.

This weekend, with the approach of Hurricane Gustav (that's Hanna on the right, still not quite ready for primetime), many thousands of residents along the Northern Gulf coast will either have their BOB's, or sorely wish they did.

In New Orleans residents are being told to evacuate, and that there will be no `shelter-of-last-resort', such as the Superdome, this time around.

New Orleans plans to get tough on residents who refuse to flee ahead of Hurricane Gustav.

08-29-2008 11:17 PM By BECKY BOHRER, Associated Press Writer

NEW ORLEANS (Associated Press) -- Police with bullhorns plan to go street to street this weekend with a tough message about getting out ahead of Hurricane Gustav: This time there will be no shelter of last resort. The doors to the Superdome will be locked. Those who stay will be on their own.

New forecasts Friday made it increasingly clear that New Orleans will get some kind of hit _ direct or indirect _ by early next week. That raised the likelihood people would have to flee, and the city suggested a full-scale evacuation call could come as soon as Sunday.

Those among New Orleans' estimated 310,000 to 340,000 residents who ignore orders to leave accept "all responsibility for themselves and their loved ones," the city's emergency preparedness director, Jerry Sneed, has warned.

As Katrina approached in 2005, as many as 30,000 people who either could not or would not evacuate jammed the Louisiana Superdome and the riverfront convention center. They spent days waiting for rescue in squalid conditions. Some died.

Stung by the images that flashed across the world, including the photo of an elderly woman dead in her wheelchair, her bodied covered with a blanket, officials promised to find a better way.

This time, the city has taken steps to ensure no one has an excuse not to leave. The state has a $7 million contract to provide 700 buses to evacuate the elderly, the sick and anyone around the region without transportation.

(Continue)

If you think having an emergency bug out bag sounds like something that only a camouflage wearing, gun toting survivalist would have on hand . . .think again.

Here is the advice from Ready.gov. They call is an Emergency Supply Kit, but the idea is the same.

Step 1: Get A Kit

• Get an Emergency Supply Kit,which includes items like non-perishable food, water, a battery-powered or hand-crank radio, extra flashlights and batteries. You may want to prepare a portable kit and keep it in your car. This kit should include:
  • Copies of prescription medications and medical supplies;
  • Bedding and clothing, including sleeping bags and pillows;
  • Bottled water, a battery-operated radio and extra batteries, a first aid kit, a flashlight;
  • Copies of important documents: driver’s license, Social Security card, proof of residence, insurance policies, wills, deeds, birth and marriage certificates, tax records, etc.

Step 2: Make a Plan

Prepare your family

• Make a Family Emergency Plan. Your family may not be together when disaster strikes, so it is important to know how you will contact one another, how you will get back together and what you will do in case of an emergency
• Plan places where your family will meet, both within and outside of your immediate neighborhood.
• It may be easier to make a long-distance phone call than to call across town, so an out-of-town contact may be in a better position to communicate among separated family members.
• You may also want to inquire about emergency plans at places where your family spends time: work, daycare and school. If no plans exist, consider volunteering to help create one.
• Plan to Evacuate
  • Identify ahead of time where your family will meet, both within and outside of your immediate neighborhood.
  • Identify several places you could go in an emergency, a friend's home in another town, a motel or public shelter.
  • If you do not have a car, plan alternate means of evacuating.
  • If you have a car, keep a half tank of gas in it at all times in case you need to evacuate.
  • Take your Emergency Supply Kit.
  • Take your pets with you, but understand that only service animals may be permitted in public shelters. Plan how you will care for your pets in an emergency.
• Take a Community Emergency Response Team (CERT) class from your local Citizen Corps chapter. Keep your training current.

A search of the Internet will find loads of information on BOBs, including some kits so chock full that it would require a pack mule to carry. Some restraint may be required when making a suitable BOB, particularly if you may be forced to carry it.

A bug-out-bag should be a smaller version of a much larger emergency supply that every household should maintain. While a BOB should provide for 72 hours of your family's needs, you should be prepared to stay at home, without outside assistance, for at least 2-weeks.

Many organizations, including some government agencies (US and others) have recommended that up to 3 months of preparations would be prudent, particularly in view of the current pandemic threat.

For more information on how to prepare your household, and your family, to withstand a 2-week or longer crisis visit www.pandemicflu.gov (family checklists) or www.getpandemicready.org.

Wellcome Trust To Fund Research Into `Pandemic' Mutations

 

 

# 2265

 

 

 

Wellcome Trust bills themselves as `an independent charity funding research to improve human and animal health. Established in 1936 and with an endowment of around £15 billion, it is the UK's largest non-governmental source of funds for biomedical research.'

 

 

Today they've released a lengthy, but interesting,  press release outlining their plan to fund research into why the H5N1 virus has not reached it's assumed pandemic potential.  To find out why it has not become efficiently transmitted from human-to-human.

 

This research will delve primarily into how the virus attaches itself to receptor cells.  It currently favors the a2,3 cells found in avian hosts and deep in the lungs of humans, eschewing the a2,6 cells found in the upper airways of humans. 

 

The type that seasonal influenza binds to.

 

A couple of past essays on receptor binding you may find of interest are RBD: Looking For The Sweet Spot  and  Study: Human Adaptation Of The H5N1 Virus.

 

This from the Wellcome Trust website.

 

 

 

 

Scientists examine bird flu infections to monitor for 'pandemic' mutations

1 September 2008

 

Scientists funded by the Wellcome Trust are to examine what is preventing the H5N1 avian influenza virus from causing a human pandemic and what mutations are required to realise its deadly potential. The research could hold the key to early identification of a potential influenza pandemic, and to developing drugs and a vaccine.

 

Since its reappearance in 1997, the H5N1 influenza virus has caused disease and death in millions of birds around the globe. The number of infections in humans is still relatively small, however: from 2003 to the end of June 2008 there had been 385 known cases in humans, 243 of them fatal (see note 1 below). So far, there appear to have been very few cases of human-to-human transmission.

 

Professor Ten Feizi at Imperial College London believes one reason why H5N1 has not yet evolved into an effective pathogen capable of widespread transmission between humans lies in how the virus attaches itself to the respiratory tract. She is leading an international research project, which has received over £720 000 from the Wellcome Trust, to identify the receptor molecules in the human respiratory tract to which viruses attach and to look at how changes in the binding protein on the surface of the virus might increase its ability to attach to the tract and cause infection.

 

Professor Feizi will work with Professors Menno de Jong and Jeremy Farrar from the Wellcome Trust's South-east Asia Programme in Vietnam, Dr Alan Hay and Dr Steve Gamblin at the Medical Research Council National Institute for Medical Research, London, and Dr Mikhail Matrosovich at the Philipps University of Marburg, Germany.

 

"Over the last few years, particularly in Asia, we have seen just how deadly the H5N1 virus can be," says Professor Farrar from the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam, where a number of people have been treated for infection by the virus. "So far, we have been relatively fortunate and there has been only limited evidence of the virus transmitting from human to human. The more we understand about the virus, how it interacts with the body, the better we will be prepared for any serious mutations that may arise."

 

In humans, influenza infection occurs via the respiratory tract, or airway. In order to cause disease, the virus must enter the body's cells where it can replicate and spread, but it must first find a site to which it can attach, known as a receptor. The virus can only attach to and enter the cells if the receptor fits into the binding proteins, or haemagglutinins (the "H" in H5N1), on the surface of the virus.

 

Previous research has shown that the haemagglutinin on H5N1 favours a particular form of receptor known as a "2,3 receptor". These are abundant on cells of birds, but in humans are found mostly on cells of the lower respiratory tract (the lungs). Professor Feizi and colleagues have shown that mucus in the upper airway in humans also contains 2,3 receptors, but here the mucus acts as a defence mechanism to which the virus binds, blocking its progress and enabling the body to "sweep out" the virus. Both factors suggest that huge doses of the virus are required in order to infect humans, a theory supported by evidence that those who have become infected have spent large amounts of time in close proximity to infected fowl.

 

As with all viruses, H5N1 is continually mutating, and it is changes that allow the virus to attach to “2,6 receptors” in the human upper airway that may enable the virus to become more infectious to humans.

 

"If the bird flu virus evolves to favour the receptors in our nose and throat like normal flu, the results could be devastating," says Professor Feizi from the Division of Medicine at Imperial College London. "We could have a virus which is not only highly infectious but is easily transmissible by coughing and sneezing."

 

Dr Hay and Dr Gamblin will isolate haemagglutinin from samples of the virus taken from the patients in Vietnam, and Dr Matrosovich will grow cultures of human airway cells and isolate cell-membrane receptors and secreted mucus. Then, using a technique known as neoglycolipid (NGL) microarray analysis developed by Professor Feizi and her colleagues, the team at Imperial College will identify which of the various receptor structures the haemagglutinins bind most strongly to. Dr Gamblin’s team will then use X-ray crystallography to probe, at the molecular level, how mutations might cause the bird virus to change into a human virus.

 

"If we can find out which mutations of haemagglutinin prefer which receptors, we may be able to identify quickly or even predict which mutations give the virus pandemic potential," says Professor Feizi.

 

Current antiviral treatments for influenza, such as Tamiflu, target neuraminidase (the "N" in H5N1), which is responsible for allowing the virus to jump off receptors on one cell and bind to those on another cell, and to replicate and spread once inside the body.

 

"Targeting the virus's ability to bind to the receptors - which until now has proved far more difficult - may provide an alternative, more effective way of preventing infection," says Professor Feizi. "We hope that our work will make this process simpler and faster."

Contact

Craig Brierley
Media Officer
Wellcome Trust
T +44 (0)20 7611 7329
E c.brierley@wellcome.ac.uk

 

Vietnam: Battle To Raise Bird Flu Awareness

 

 

# 2264

 

 

 

 

While Vietnam  has certainly made immense progress in its battle against the H5N1 virus, there can be little doubt that bird flu remains endemic in that country. 

 

This year, 26 of Vietnam's 64 districts have reported outbreaks in poultry.   And while the number of human infections has fallen dramatically over the past couple of years, a resurgence is feared.

 

 

Raising awareness, particularly among villagers and people who raise poultry, remains a high priority.   Joint projects between USAID and UNICEF are working to raise public awareness on the bird flu issue, along with UN agencies like the WHO and the FAO.

 

 

This report from IRIN (Integrated Regional Information Networks) which is an independent part of the UN Office for the Coordination of Humanitarian Affairs.

 

 

 

 

VIETNAM: Uphill battle to raise awareness of bird flu

 

 

Photo: Biotec

 

Veterinary officials check for avian influenza.

HAI NAM , 29 August 2008 (IRIN) - The key message that needs to be heard is that Avian Influenza (AI) is endemic in Vietnam and needs to be controlled, say UN officials involved in the battle to identify and contain avian influenza outbreaks.

 

According to the Vietnam Partnership for Avian and Human Influenza (PAHI), three provinces have reported new outbreaks in recent weeks.

 

Since the start of 2008, 44 districts in 26 of Vietnam's 64 provinces have reported outbreaks, highlighting the challenge the country faces in controlling the disease.

 

Overall since 2003, Vietnam has had 106 cases of human avian flu and 52 deaths.

 

Yet compared to 2004 and 2005, when 90 cases of human infection occurred with 39 deaths, [] Vietnam has made huge strides, according to David Payne, the UN Development Programme avian influenza specialist in Hanoi, "with only five infections since March 2008, all of whom died".

 

Payne gives the Vietnamese government high marks for recognising early on the severity of the AI problem and turning to the UN and the humanitarian community for advice and support.

 

"The office of the UN resident representative for Vietnam - with the World Health Organization (WHO), the Food and Agriculture Organization (FAO) and the UN Children’s Fund (UNICEF) taking the lead - has worked closely with the Ministry of Agriculture and Rural Development and other relevant ministries," said Payne, adding that UN agencies have taken a united approach to assisting the government.

 

(Continue)

Another Study: Flu Vaccines Do Not Reduce Mortality Rates In The Elderly

 

 

 

# 2263

 

 

 

It seems, we've heard this song before.

 

 

What follows is a press release announcing the publication of a study by researchers at the School of Public Health at the University of Alberta that will appear in the September issue of the American Journal of Respiratory and Critical Care Medicine, a publication of the American Thoracic Society.

 

 

 

As a press release, this announcement is designed to publicize this study, and the journal it appears in. That doesn't make it bad, or invalid.  But we need to recognize press releases for what they are: advertisements.  

 

As always, Caveat Lector.

 

 

 

In it we are presented with additional evidence that yearly seasonal influenza shots may not be as effective in the elderly at reducing overall mortality as previously believed.    Over the past year, we've seen several such studies that have reached similar conclusions.

 

 

You can read about a couple of these other studies  here and here.

 

 

While evidence may be mounting about a reduced effectiveness of the seasonal flu vaccine in the elderly, this hasn't translated (yet) into a consensus opinion or change in policy among medical professionals.  

 

 

More studies, such as this one, are needed.

 

 

A hat tip to Shiloh on Flutrackers for posting this link.

 

 

 

 

 

 

 

Public release date: 29-Aug-2008

Contact: Keely Savoie

ksavoie@thoracic.org
American Thoracic Society

 

Flu shot does not reduce risk of death

 

The widely-held perception that the influenza vaccination reduces overall mortality risk in the elderly does not withstand careful scrutiny, according to researchers in Alberta. The vaccine does confer protection against specific strains of influenza, but its overall benefit appears to have been exaggerated by a number of observational studies that found a very large reduction in all-cause mortality among elderly patients who had been vaccinated.

 

The results will appear in the first issue for September of the American Journal of Respiratory and Critical Care Medicine, a publication of the American Thoracic Society.

 

The study included more than 700 matched elderly subjects, half of whom had taken the vaccine and half of whom had not. After controlling for a wealth of variables that were largely not considered or simply not available in previous studies that reported the mortality benefit, the researchers concluded that any such benefit "if present at all, was very small and statistically non-significant and may simply be a healthy-user artifact that they were unable to identify."

 

"While such a reduction in all-cause mortality would have been impressive, these mortality benefits are likely implausible. Previous studies were likely measuring a benefit not directly attributable to the vaccine itself, but something specific to the individuals who were vaccinated—a healthy-user benefit or frailty bias," said Dean T. Eurich,Ph.D. clinical epidemiologist and assistant professor at the School of Public Health at the University of Alberta. "Over the last two decades in the United Sates, even while vaccination rates among the elderly have increased from 15 to 65 percent, there has been no commensurate decrease in hospital admissions or all-cause mortality. Further, only about 10 percent of winter-time deaths in the United States are attributable to influenza, thus to suggest that the vaccine can reduce 50 percent of deaths from all causes is implausible in our opinion."

 

Dr. Eurich and colleagues hypothesized that if the healthy-user effect was responsible for the mortality benefit associated with influenza vaccination seen in observational studies, there should also be a significant mortality benefit present during the "off-season".

 

To determine whether the observed mortality benefits were actually an effect of the flu vaccine, therefore, they analyzed clinical data from records of all six hospitals in the Capital Health region in Alberta. In total, they analyzed data from 704 patients 65 years of age and older who were admitted to the hospital for community-acquired pneumonia during non-flu season, half of whom had been vaccinated, and half of whom had not. Each vaccinated patient was matched to a non-vaccinated patient with similar demographics, medical conditions, functional status, smoking status and current prescription medications.

 

In examining in-hospital mortality, they found that 12 percent of the patients died overall, with a median length of stay of approximately eight days. While analysis with a model similar to that employed by past observational studies indeed showed that patients who were vaccinated were about half as likely to die as unvaccinated patients, a finding consistent with other studies, they found a striking difference after adjusting for detailed clinical information, such as the need for an advanced directive, pneumococcal immunizations, socioeconomic status, as well as sex, smoking, functional status and severity of disease. Controlling for those variables reduced the relative risk of death to a statistically non-significant 19 percent.

 

Further analyses that included more than 3,400 patients from the same cohort did not significantly alter the relative risk. The researchers concluded that there was a difficult to capture healthy-user effect among vaccinated patients.

 

"The healthy-user effect is seen in what doctors often refer to as their 'good' patients— patients who are well-informed about their health, who exercise regularly, do not smoke or have quit, drink only in moderation, watch what they eat, come in regularly for health maintenance visits and disease screenings, take their medications exactly as prescribed— and quite religiously get vaccinated each year so as to stay healthy. Such attributes are almost impossible to capture in large scale studies using administrative databases," said principal investigator Sumit Majumdar, M.D., M.P.H., associate professor in the Faculty of Medicine & Dentistry at the University of Alberta.

 

The finding has broad implications:

 

• For patients: People with chronic diseases such as chronic respiratory diseases such as chronic obstructive pulmonary disease, immuno-compromised patients, healthcare workers, family members or friends who take care of elderly patients and others with greater exposure or susceptibility to the influenza virus should still be vaccinated. "But you also need to take care of yourself. Everyone can reduce their risk by taking simple precautions," says Dr. Majumdar. "Wash your hands, avoid sick kids and hospitals during flu season, consider antiviral agents for prophylaxis and tell your doctor as soon as you feel unwell because there is still a chance to decrease symptoms and prevent hospitalization if you get sick— because flu vaccine is not as effective as people have been thinking it is."

 

• For vaccine developers: Previously reported mortality reductions are clearly inflated and erroneous–this may have stifled efforts at developing newer and better vaccines especially for use in the elderly.

 

• For policy makers: Efforts directed at "improving quality of care" are better directed at where the evidence is, such as hand-washing, vaccinating children and vaccinating healthcare workers.

 

Finally, Dr. Majumder said, the findings are a reminder to researchers that "the healthy-user effect is everywhere you don't want it to be."

Model Prisoners

# 2262

During the months of August, September, and sometimes into October my attentions are divided between pandemic issues and storms forming in the Caribbean and tropical Atlantic.

These three months are the peak of the six-month Atlantic Hurricane season, and this year, like many years in the recent past, looks to be an active one.

It wasn't always so. The decades of the 1970's and 1980's, and the first half of the 1990's, were relatively quiescent as far as 'canes went. Sure, we had them, but more infrequently than we've seen over the past 10 years.

When I was a kid, growing up in the 1950's and 1960's, Hurricanes were plentiful. Much like we see today.

These cyclical patterns aren't well understood, but they are well documented. We are in the midst of an upswing in tropical activity, and that is forecast to last for another decade . . . maybe longer.

On the eve of the third anniversary of Hurricane Katrina's landfall along the Louisiana/Mississippi coast we have a new threat lurking south of Cuba, with the potential to visit upon the Northern Gulf Coast a tremendous blow sometime in the next 120 hours or so.

I say `potential', because we do not know yet where Gustav is going, or even when it will arrive. We also don't know how strong it will be when it hits . . . someplace.

What we have are models, complex mathematical expressions of how this tropical system may interact with the atmosphere around it, giving us some ideas where Gustav may be going.

You may have seen these models, often called `spaghetti models' for obvious reasons, before. As you can see from this latest run, the models put Gustav approaching landfall somewhere between Texas and the Florida Panhandle on Monday or Tuesday.

Believe it or not, these models are showing a rare degree of unanimity. We don't often see all of the models pointing in the same general direction. Even so, that's a lot of territory to warn, particularly if your job is to decide whether or when to order an evacuation.

The NHC's (National Hurricane Centers) `consensus' plot takes all of these models and tries to formulate a `best guess' of where this storm is going.

Here is this afternoon's latest track. Don't just look at the center-line track . . . five days out the average margin for error is 300 miles either side of the track.

You have to look at the `cone'.

And in this case, it is a very large cone. And this `cone' may very well shift left or right several times over the next 72 hours, as new data gets input into these computer models.

Now, how do you decide who to evacuate . . . and when?

Adding to the confusion, we really don't have a very good handle on intensity forecasts. Right now, the smart money is on Gustav becoming a CAT 3 storm by Sunday . . . but nobody really knows.

And what will he be by Monday or Tuesday . . .?

The bottom line, right now, is we probably won't have a good idea where Gustav is going to land until Saturday morning, or perhaps Saturday night. And even then, the 48 hour forecast could be a couple of hundred miles off base.

Evacuating a city like New Orleans isn't something you do on a whim. It is a horrendously expensive undertaking, and it puts lives at risk as well. If you `pull the trigger' early enough to give people time to get out . . .you risk ordering an unnecessary evacuation.

If you wait . . . well, we saw what happened in 2005.

And it's not as if New Orleans is the only populous area that may need to evacuate. Depending on the strength of storm, many low lying areas would be highly vulnerable to a storm surge or hurricane force winds.

What should authorities be doing about people in Pensacola, or Mobile, or Beaumont, Texas?

They are all in the cone.

These are not easy times for emergency planners, and many tough decisions will have to be made in the coming hours.

Millions of gulf coast residents right now are watching, and waiting, essentially prisoners of these model runs. These are our best tools for forecasting the movement of a storm, even though they are subject to increasing margins for error the further out in time they project.

These `model prisoners' will have to decide, probably on Saturday, whether or not to evacuate. And where they will go. No easy task when hundreds of thousands of other people are all trying to do the same thing.

Yesterday, I was in the `cone'. Today I am not. Tomorrow, well . . . we'll know tomorrow.

That's life in Hurricane Alley.

Hopefully Gustav won't come my way. There's always Hanna . . . and her sisters, for me to worry about later next week - but that's next week.

If you've ever wondered why I am such a proponent of being prepared, the little graphic above should give you a pretty good idea.

Singapore To Begin 2-Week Financial Sector Pandemic Drill

 

 

# 2261

 

 

Roughly a year ago the United State's financial sector conducted a massive multi-week pandemic drill, sponsored by the Department of the Treasury, which tested the resiliency of our banking and financial centers during a crisis.   

 

Overviews of that drill can be viewed here and here.

 

Today, Singapore kicks off their own 2-week long drill, as detailed in this story from Channel NewsAsia.

 

 

 

 

Financial sector kicks off two-week drill to handle flu pandemic

By Nicholas Fang, Channel NewsAsia | Posted: 28 August 2008 2144 hrs

 

Singapore's Central Business District

 

SINGAPORE: Banks in Singapore are gearing up to handle a potential flu outbreak which could see up to 40 per cent of their staff being absent from work.

 

To test the financial sector's preparedness to handle a flu pandemic scenario, the industry started a two-week exercise on Thursday.

 

The drill is organised by the Monetary Authority of Singapore (MAS) and the Association of Banks in Singapore, along with government agencies.

 

Codenamed Exercise Raffles II, it builds on the first industry-wide drill conducted two years ago.

 

At that time, the key threat was a terrorist attack. Banks and other financial institutions in Singapore were then able to practise their contingency plans to handle such a crisis over the course of one day.

 

Exercise Raffles II started with a simulated outbreak of flu that is supposedly being spread efficiently between humans. This was then upgraded to a widespread pandemic.

 

Upon receiving the scenarios, banks began planning their appropriate responses. These include closing some branches due to a shortage of manpower and also to cut down transmission risks.

 

Some off-site cash machines will also have to be turned off as there are not enough staff to top them up. Groups of staff will also be split up to work in separate locations to minimise the spread of disease.

The planning will carry on for another week. Next Friday morning, practice drills will be carried out at branches of financial institutions in the Central Business District.

 

Temperature screening will be carried out at participating outlets and counter staff will be wearing face masks until 11am when the drill ends.

 

The Association of Banks in Singapore urges the public to cooperate during the drills on September 5.
- CNA/ir

Australian Editorial: A Battle To Secure Their Borders

 

# 2260

 

 

 

Nearly  40 years ago it was widely believed in medical circles that we were on the verge of eliminating infectious diseases as an ongoing threat to mankind.

 

 

In 1969, the Surgeon General of the United States, William H. Stewart, declared, "The war against diseases has been won." 

 

In the 3rd edition of the textbook Natural History of Infectious Disease, published in 1962, the forward declared that the late 20th century would be witness to "the virtual elimination of infectious disease as a significant factor in social life."

 

 

 

 

 

They were wrong, of course.   

 

 

Each year it seems we are confronted with new, mostly zoonotic diseases that have the potential (and even the likelihood) of infecting mankind.

 

Diseases that were unheard of in 1969 - such as AIDS, Hendra, Nipah, Lyme, Avian Flu - have emerged as major contenders.

 

 

And of course, old favorites - once thought on the way to elimination- are back at work as well.  Polio, mumps, measles, dengue and tuberculosis to name a few.

 

 

Today we get an editorial opinion from the Sydney Morning Herald by Peter Curson, professor of population and security, and Jonathan Herington, projects officer (biosecurity) for the Centre for International Security Studies at the University of Sydney.

 

 

They warn that the threats to our national security can often be microscopic in size.

 

 

 

 

 

The battle to secure our borders against a tiny, but lethal, enemy force

 

•  PETER CURSON, JONATHAN HERINGTON
  August 29, 2008

 

We once thought the battle against infectious disease was won.

 

Security experts now tell us this is not so. In a globalised, interconnected world - where people, trade and goods move around like never before - people, their pets, livestock, wildlife and crops are still vulnerable.

 

Animal and human diseases and insects respect no national borders. They move easily across time and space. Infections and insect pests once thought limited to certain parts of the world are now able to spread easily and quickly to Australia. And we still do not fully appreciate that human health is intimately connected to animal health and that wildlife and domestic animals and insects continue play a huge part in whether our livestock and crops prosper and whether we remain healthy.

 

SARS, Avian influenza and equine flu demonstrated quite clearly how poorly prepared we are for such events and the vulnerability of our trade, tourism, agricultural industry, biodiversity and human health to introduced diseases.

 

There are many potential threats to Australia's biosecurity. Some, such as invasive alien species, invertebrate and vertebrate pests, as well as animal infections, threaten the viability of our wildlife and rural industries, on occasions reaching out to affect us as well. The equine flu disaster and the Hendra virus outbreak in Queensland demonstrate this only too clearly. Others, such as avian influenza or a new pandemic of human flu, threaten the health of millions of citizens.

 

Most Australians believe that only developing nations have to worry about insect-borne diseases. Yet over the last 200 years, mosquitoes and fleas have been responsible for thousands of deaths and sickened millions of people in Australia.

 

(Continue reading)

CAP: Back To Basics

 

 

# 2259

 

 

 

 

With the recent discussions (see here, here, and here) over the need for more antibiotics to combat secondary bacterial pneumonias during a future pandemic, concerns over what antibiotics should be stockpiled and dispensed have been raised.

 

 

After all, we constantly hear of new, exotic, and difficult to treat bacterias that are rapidly developing resistance to our front-line antibiotics.  

 

 

What then?  

 

 

How do we deal with these superbugs during a pandemic?

 

 

The good news, at least according to this study by the University of Melbourne, is that 95% of community acquired pneumonias (CAPs) respond well to traditional antibiotics.    

 

 

 

That is, penicillins along with `atypical' antibiotics like Doxycycline or Erythromycin.

 

 

Whether this trend would hold up during some future pandemic is unknown, but for now,  I should think this has to be seen as relatively good news.  

 

 

Here is the media release from the University of Melbourne.

 

 

 

Stick with simple antibiotics for pneumonia to avoid the spread of hospital super bugs, says University of Melbourne researcher

 

Media Release, Wednesday 27 August 2008

 

Australian hospitals should avoid prescribing expensive broad-spectrum antibiotics for pneumonia to avoid the development of more drug-resistant super bugs, according to a University of Melbourne study.

 

The study, by PhD researcher and Austin Health Infectious Diseases consultant, Dr Patrick Charles, shows that only 5 per cent of people admitted to hospital with community-acquired pneumonia had infections caused by organisms that could not be successfully treated with penicillin combined with an “atypical” antibiotic such as doxycycline or erythromycin.

 

In the world’s largest study of its kind, Dr Charles studied almost 900 people admitted to six Australian hospitals over 28 months from 2004 to 2006.

 

Dr Charles’ research analysed samples of blood, urine, sputum and viral swabs of the nose and throat taken from 885 patients at the Austin, Alfred, Monash and West Gippsland hospitals in Victoria, the Royal Perth Hospital and Princess Alexandra Hospital, Brisbane.

 

He found that most cases of pneumonia were caused by easy to treat bacteria such as the pneumococcus or Mycoplasma, or alternatively by respiratory viruses that do not require antibiotic therapy.

 

Only five per cent of cases were caused by organisms that would require more expensive and broad-spectrum antibiotics, and these cases were nearly all in patients who’d had frequent hospital admissions or were residents of nursing homes.

 

“The study results show that current Australian guidelines for prescribing antibiotics for pneumonia are appropriate,’’ Dr Charles said.

 

“It shows that Australian doctors should resist the push which is occurring in some parts of the world – particularly the US - to prescribe broad spectrum antibiotics to treat essentially all possible causes.”

 

Dr Charles said the trend towards broad-spectrum antibiotics was being driven by laboratory-based studies of resistance rates in bacteria sent to the labs, rather than clinical studies of patients with pneumonia.

 

In the laboratory-based studies, the bacterial isolates often come from highly selected patients with more difficult to treat disease.

 

In addition, the fear of litigation made some doctors unnecessarily opt for more aggressive treatments.

 

However, the more frequently these broad-spectrum antibiotics were used, the more likely it was that bacteria would be become resistant to them.

 

“The emergence of antibiotic-resistant bacterial pathogens is one of the biggest threats to Australian health care standards and is closely linked to the inappropriate use of antibiotics,’’ Dr Charles said.

 

“By continuing to use more traditional antibiotics to treat most cases of pneumonia, Australian doctors can limit or delay the emergence of more resistant strains of bacteria.

 

“By using the broad-spectrum antibiotics less often, we can also prolong the effective lifespan of these drugs.

 

“Furthermore, in the US, Canada and some parts of Europe, they are seeing some serious complications which appear to be related to the overuse of some classes of broad-spectrum antibiotics that are frequently used there to treat respiratory infections.”

 

Dr Charles is a physician in Infectious Disease and General Medicine at the Austin Hospital in Melbourne. He is also an Honorary Lecturer in the University of Melbourne’s Department of Medicine at the Hospital.

 

His study was recently published in the journal Clinical Infectious Diseases and he will be conferred with a PhD for his research today at the University of Melbourne.

 

He received funding from the independent 201CC Research Fund to complete the study.

More information about this article:

Janine Sim-Jones
Media Officer
janinesj@unimelb.edu.au
Tel: +61 3 8344 7220
Mob: 0400 893 378

Vietnam Detects `New Strain' Of H5N1

 

 

 

# 2258

 

 

 

 

According to the Vietnam News Service, a new (for Vietnam) strain of the H5N1 virus has been detected within their borders, one they have named `Seven'.    

 

 

They surmise that this `new' strain was brought in via smuggled poultry from China. 

 

 

Given the level of testing being done, it would be difficult to pinpoint how long this `new' strain has been circulating in Vietnam. Additionally, from the description provided, it isn't clear exactly what strain of the H5N1 virus this article is talking about.    

 

 

Hopefully we'll get more details soon.

 

 

A hat tip to Dutchy on Flutrackers for posting this link.

 

 

 

 

 

 

Deadly H5N1 strain detected

 

(27-08-2008)

 

HA NOI — A strain of the H5N1 virus that poses a high risk of infecting humans and caused an avian flu epidemic in China, has appeared in smuggled poultry in Viet Nam according to Bui Quang Anh, the head of the Ministry of Agricultural and Rural Development’s Animal Health Department yesterday.

 

 

The infection mechanism of this  highly infectious strain of the H5N1 virus, named seven, had not been found so far, Anh said.

 

 

"We are studying more about this strain in our poultry and will soon know the results," said Nguyen Van Cam, the director of the Central Animal Diagnosis Centre.

 

 

The avian flu strain that has typically appeared in the Cuu Long (Mekong) Delta has been strain one, while the Song Hong (Red River) Delta has seen strain two, three and four with unknown infection mechanisms.

 

 

To prevent the strain from being spread, 242 million doses of H5N1 vaccines and 15 million of doses of H5N2 vaccines have been distributed to the localities, according to the department.

 

 

At this volume, just 76.5 per cent of poultry will be vaccinated.

 

 

Localities have typically neglected taking samples of poultry after being vaccinated. Only three out of 27 provinces that have undergone bird flu epidemics collected samples to test.

 

 

Some Cuu Long (Mekong) Delta provinces with a high volume of poultry infected with the H5N1 virus include Vinh Long at 9.25 per cent, Tra Vinh with 8.97 per cent, Soc Trang with 5.32 per cent and Long An with 5 per cent.

 

 

Anh said that more vaccines were being prepared. — VNS

Japan: Plan To Add 3,600 Ventilators

 

 

# 2258

 

 

Late last week the Japan Health Ministry announced their intention to ask for nearly 60 billion yen ($534 million US dollars) for pandemic funding in next year's budget.   

 

 

Today we learn that at least part of that funding (2 Billion yen) would go towards increasing the number of ventilators (or `respirators', as this article calls them) in medical districts around that nation. 

 

Two billion yen would translate to  roughly $5,000 per machine.

 

Of course, it isn't enough to have the ventilators. Patients on assisted ventilation required highly trained respiratory therapists to monitor and adjust their life support systems.   

 

 

How they plan to deal with those needs isn't addressed in this article.

 

 

 

 

 

 

Health ministry to introduce 3,600 respirators for new flu pandemic

 

Wednesday 27th August, 07:31 AM JST

TOKYO —

 

The health ministry has decided to introduce about 3,600 respirators at medical institutions across Japan to prepare for the possibility of a new influenza pandemic, ministry officials said Wednesday.

 

The Ministry of Health, Labor and Welfare plans to make budgetary request of about 2 billion yen in fiscal 2009 for the respirators, the officials said. Each of the nearly 360 medical districts in Japan would be given 10 respirators.

 

The ministry is studying how many existing respirators owned by Japanese hospitals can be used in the event that a new flu pandemic breaks out. Many people who have contracted the H5N1 strain of avian influenza, which has been spreading in Asia and is feared to mutate into a new flu, have had respiratory problems, making respirators essential in treating them.

 

CIDRAP News: Growing Tamiflu Resistance

 

# 2257

 

 

 

Robert Roos at CIDRAP (Center For Infectious Disease Research & Policy) news has a good overview of the recent reports of growing oseltamivir (Tamiflu) resistance in H1N1 seasonal influenza samples worldwide.

 

This is an ongoing story that I've covered here, here, and here.

 

 

As usual, CIDRAP provides more background information than most news reports.  I've just included a snippet, follow the link to read the entire article. 

 

 

 

 

H1N1 flu viruses growing more resistant to Tamiflu

 

Robert Roos  News Editor

 

Aug 25, 2008 (CIDRAP News) – With influenza season well under way in the southern hemisphere, one of the three kinds of seasonal influenza virus is becoming increasingly resistant to the antiviral drug oseltamivir (Tamiflu), the World Health Organization (WHO) reported last week.

 

Thirty-one percent (242 of 788) of influenza A/H1N1 isolates from 16 countries that were tested in recent months carried a mutation associated with oseltamivir resistance, the WHO said. In South Africa, all of the 107 isolates tested had this mutation, known as H274Y, the agency reported.

 

Other countries and areas that tested 10 or more isolates and found resistance included Australia, 100% (10 of 10 isolates); Ghana, 20% (2 of 10) Hong Kong, 17% (97 of 583); and Chile, 13% (4 of 32 isolates).

 

The findings strengthen a trend that that was first observed last January in Norway and subsequently in many other countries. Overall for the last quarter of 2007 and the first quarter of this year, 16% (1,182 of 7,528) of tested H1N1 isolates carried the resistance mutation, according to WHO figures. Resistance was found in 35 countries, mostly in the northern hemisphere, including in 12% of tested US isolates and 26% of tested Canadian isolates.

 

"What we're seeing is the evolution of the resistance gene and the distribution of it throughout the world," said Lance Jennings, a clinical virologist with the Canterbury District Health Board in Christchurch, New Zealand, and chair of the Asia-Pacific Advisory Committee on Influenza, as quoted in an Aug 22 Bloomberg News report.

 

(Continue Reading . . . )

A Reminder Of Why September Is National Preparedness Month

 

 

# 2256

 

 

 

September is the peak of the Atlantic Hurricane Season, and this year we are expecting an above average number of storms.    Today, as of 0800 hrs EDT, here are the areas the forecasters at the National Hurricane Center are watching. 

 

 

 

As you can see, we  have the remnants of Fay in Alabama, a full fledged Hurricane Gustav (probably headed for the Gulf of Mexico), and three (count'em, three) areas of suspicion in the Atlantic.

 

 

While the suspect areas in mid-ocean may never develop into any threat to land, Gustav shows every sign of being a very bad boy. 

 

He is forecast to strike Haiti later today, then skirt the southern coast of Cuba, and emerge into the Gulf of Mexico for the weekend.

 

 

 

After that, where he goes is anyone's guess.

 

 

Everyone along the gulf coast, from Florida to Mexico, needs to be watching this one carefully.

 

 

As I stated, September is National Preparedness month. 

 

And as this Ready.gov site tells us, we need to be prepared for emergencies.  We need to be ready for hurricanes, floods, earthquakes, tornadoes, and yes . . . even pandemics.

 

 

 

• Get A Kit
• Make A Plan
• Be Informed
• Get Involved

 

 

 

National Preparedness Month 2008

Sponsored by the U.S. Department of Homeland Security's (DHS) Ready Campaign

---

Join the Ready Campaign and our DHS partner Citizen Corps this September for the fifth annual National Preparedness Month (NPM). Register now to be a part of the 2008 NPM Coalition — visit http://ready.adcouncil.org.

 

This year the focus of NPM is to encourage citizens to take important preparedness steps:

• Get a Kit
• Make a Plan
• Be Informed
• Get Involved

 

In 2007, NPM had a record number of more than 1,800 NPM Coalition Members who worked to create a culture of emergency preparedness in the United States. We invite you to read the National Preparedness Month 2007 Journal to learn about some of the events and activities that took place across the country last year. In addition, President George W. Bush issued a proclamation declaring September as National Preparedness Month.

 

We hope your organization will join us in spreading the emergency preparedness message this year - and every year! If you have any questions, please don't hesitate to contact us at Ready@dhs.gov.

 

 

Uncovering Influenza's Achilles Heel

 

 

# 2255

 

 

 

One of the `upsides' to our heightened concerns over the H5N1 virus these past 3 years has been that influenza research has received a much needed shot in the arm.    

 

 

Many of these discoveries may someday result in better influenza fighting medicines and technologies, although tangible benefits such as those are likely still years away.  

 

 

Finding an `Achilles heel', a vulnerability across a wide spectrum of influenza viruses - one that can be exploited by a vaccine or an antiviral - has long been the holy grail of influenza researchers.

 

 

New research from the University of Texas at Austin, and Rutgers University, may be bringing us closer to that goal.

 

 

 

This from a press release from the University of Texas.

 

 

 

 

 

Discovery Opens Door for Drugs to Fight Bird Flu, Influenza Epidemics

 

August 25, 2008

 

AUSTIN, Texas — Researchers at The University of Texas at Austin and Rutgers University have reported a discovery that could help scientists develop drugs to fight avian flu and other virulent strains of influenza.

 

The researchers have determined the three-dimensional structure of a site on an influenza A virus protein that binds to one of the human protein targets, thereby suppressing a person's natural defenses to the infection and paving the way for the virus to replicate efficiently. This so-called NS1 virus protein is shared by all influenza A viruses isolated from humans, including avian influenza, or bird flu, and the 1918 pandemic influenza virus.

 

 

This image shows the binding pocket for the human CPSF30 protein on the influenza A virus NS1 protein (brown), with a fragment of the CPSF30 protein (blue) bound in the pocket. Work published this week in the Proceedings of the National Academy of Sciences reveals this interaction is a target for antiviral drug discovery. This image was generated using X-ray crystallography by K. Das, L. Ma, E. Arnold, R. Krug, G. Montelione and others, as part of a collaboration between Rutgers University and The University of Texas at Austin.

 

About 10 years ago, Professor Robert M. Krug at The University of Texas at Austin discovered that the NS1 protein binds a human protein known as CPSF30, which is important for protecting human cells from flu infection. Once bound to NS1, the human protein can no longer generate molecules needed to suppress flu virus replication.

 

Now, researchers led by Krug and Rutgers Professor Gaetano T. Montelione, have identified the specific NS1 binding pocket that grasps the human CPSF30 protein.

 

"Our work uncovers an Achilles heel of influenza A viruses that cause human epidemics and high mortality pandemics," said Montelione, professor of molecular biology and biochemistry at Rutgers. "We have identified the structure of a key target site for drugs that could be developed to effectively combat this disease."

 

A paper detailing the breakthrough discovery appears in the Proceedings of the National Academy of Sciences Early Edition and will be published in an upcoming print issue of the journal.

Krug is also a member of the Institute for Cellular and Molecular Biology at The University of Texas at Austin.

 

(Continue)

 

 

For more information, contact: Lee Clippard, College of Natural Sciences, 512-232-0675; Dr. Robert Krug, 512-232-5563; Dr. Guy Montelione, 732-986-8775.

Clinical Case Review Of 26 Chinese H5N1 Patients

 

 

#  2254

 

 

 

First, my thanks to SophiaZoe for posting this PLoS One study on her Blog, A Pandemic Chronicle.   

 

 

There is a good deal here to absorb, and many will want to read the entire study (always recommended), but I will try to hit the high spots of this overview of the clinical outcomes of 26 human H5N1 infections from China.

 

 

The study:

 

Clinical Characteristics of 26 Human Cases of Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in China

Hongjie Yu^1#, Zhancheng Gao^2#*, Zijian Feng^1#, Yuelong Shu^3#, Nijuan Xiang¹, Lei Zhou¹, Yang Huai¹, Luzhao Feng¹, Zhibin Peng¹, Zhongjie Li¹, Cuiling Xu³, Junhua Li⁴, Chengping Hu⁵, Qun Li⁶, Xiaoling Xu⁷, Xuecheng Liu⁸, Zigui Liu⁹, Longshan Xu¹⁰, Yusheng Chen¹¹, Huiming Luo¹², Liping Wei¹³, Xianfeng Zhang¹⁴, Jianbao Xin¹⁵, Junqiao Guo¹⁶, Qiuyue Wang¹⁷, Zhengan Yuan¹⁸, Longnv Zhou¹⁹, Kunzhao Zhang²⁰, Wei Zhang²¹, Jinye Yang²², Xiaoning Zhong²³, Shichang Xia²⁴, Lanjuan Li²⁵, Jinquan Cheng²⁶, Erdang Ma²⁷, Pingping He²⁸, Shui Shan Lee²⁹, Yu Wang¹, Timothy M. Uyeki³⁰, Weizhong Yang^1*

 

 

 

This study follows 26 (of 30)  reported human H5N1 cases treated in China between October, 2005 and April of 2008. 

 

 

The median age was 28, and 58% of these patients were female.

 

 

Out of 26 patients in this study, 17 (65%) died.

 

 

Interestingly, the average age of cases in this study was more than 10 years higher than we've seen from other countries, where the highest incidence of infection has been in the 10-19 year-old range.  

 

 

It is suggested in the study that  "The age profile of Chinese H5N1 cases may reflect exposure differences due to traditional social and cultural behaviours".

 

 

The good news (if it can be called that), at least for nations that have stockpiled antivirals, is the following:

 

 

Survival was significantly higher in cases that received any antiviral treatment than in untreated cases, and 5 of 8 adult cases that received standard oseltamivir treatment survived even though all were treated late in their illnesses.

 

 

 

 

Even cases that received the antiviral late, tended to survive, although it is noted that this is an anecdotal observation, and is not backed up with `virological data on antiviral susceptibilities or quantitative H5N1 viral shedding'.

 

 

 

Of the 14 patients who did not receive antivirals, only 1 (7%) survived.

 

 

 

And not only was oseltamivir (Tamiflu) effective, so apparently were the older (M2 Inhibitor) antivirals like Amantadine and Rimantadine.

 

 

. . .  the clade 2.3.4 and clade 2.2 H5N1 viruses isolated from cases in China were susceptible to both M2 inhibitors and neuraminidase inhibitors (unpublished data, China CDC). These findings suggest roles for either class of antiviral drugs as well as combination antiviral therapy for H5N1 cases in China.

 

 

 

Late hospital treatment was the norm among these Chinese patients, with some never receiving antivirals, even once hospitalized. 

 

 

Very few Chinese H5N1 cases received early antiviral treatment because only one patient was admitted within two days of illness onset, and no patients received outpatient antiviral treatment.

 

Antivirals were not administrated to most Chinese H5N1 cases until they were hospitalized with pneumonia. Oseltamivir was not available in some hospitals for treatment of some cases that died.

 

 

While antiviral therapy was the primary treatment, patients also routinely received broad spectrum antibiotics ceftriaxone (n = 6), moxifloxacin (n = 8) and azithromycin (n = 15).    

 

Most (88%) received high-dose corticosteroids (despite the WHO's admonition against their use).   

 

Out of 26 patients, 23 required ventilatory support (88%) and ARDS developed in 21 cases (81%) at a median of 8 days post-onset of the the illness.

 

Perhaps the most remarkable statistic of all is this:

 

 

Nine (35%) nonfatal cases were discharged at a median of 41 days (IQR 31.5–64.0) after illness onset.

 

 

In other words, the average hospital stay (among survivors) was just under 6 weeks.    

 

 

Two patients also received experimental blood plasma from previously infected survivors of the H5N1 virus.   It should be noted that these patients also received antivirals as well.

 

 

Experimental Treatment

 

Two critically ill adult H5N1 cases (31-year-old male, 44-year-old female) with ARDS were treated with convalescent plasma obtained from one of two fully recovered H5N1 adult donor cases.

 

Plasma was obtained 129 days after illness onset from an adult female case and 81 days after illness onset from an adult male case. Both donors' convalescent plasma tested negative for hepatitis B, hepatitis C, and HIV, and were separated and heat-inactivated at 56°C for 10 h before transfusion.

 

The male ARDS case received three units (200 mL/unit) of transfused convalescent plasma from the female donor for 2 days, beginning on illness day 13. His H5N1 viral titre in bronchial-alveolar lavage fluid declined substantially and was undetectable for the next 3 consecutive days after receipt of the third convalescent plasma dose.

 

The female ARDS case, who had a history of bronchiectasis, received one unit (200 mL) of transfused convalescent plasma from the male donor once daily for 3 days, starting on illness day 13. Further virological testing has not been done for this case. Both cases also received oseltamivir (75 mg po BID) on illness days 10–14 and days 8–12, respectively.

 

Both cases recovered fully and were discharged home.

 

 

Of the 17 fatalities (2 children, 1 adolescent, 14 adults), the average death occurred 10 days post-onset of the illness. 

 

 

The authors of the study describe the course of illness this way:

 

All H5N1 cases presented with pulmonary infiltrates, and all cases progressed rapidly to bilateral disease.

 

Many cases experienced respiratory failure, ARDS, and multi-organ failure, with hepatic dysfunction and cardiac failure. Leukopenia and lymphopenia were also common.

 

A recent molecular pathology study on two cases documented that in addition to the lungs, H5N1 virus infects the trachea and disseminates to other organs including the brain

 

 

 

Of interest is the different presentation of patients from various parts of the world (and presumably due to different clades of the virus).   Chinese patients not only tended to be older than average, they showed fewer upper respiratory symptoms.

 

 

Our findings suggest that H5N1 disease in Chinese patients generally begins with fever, cough, and sputum production, and progresses rapidly to lower respiratory disease.

 

Upper respiratory symptoms of rhinorrhea and sore throat were less common in China than observed in Hong Kong SAR, China [9], Thailand [13], Turkey [21], Azerbaijan [18], and Egypt [2]. Studies suggest that the lower respiratory tract is the major site for H5N1 viral replication, although initial infection may occur in either the upper or lower respiratory tract [30]–[33].

 

Diarrhea was present in only two H5N1 cases at admission, but developed in a quarter of cases during hospitalization. Diarrhea was a common presenting symptom among H5N1 cases in Vietnam [11], [12] and Thailand [13], but was reported infrequently among cases in Hong Kong SAR, China [9], [10], and Indonesia [4], [16].

 

H5N1 virus and viral RNA have been detected in feces and intestines of human H5N1 cases [12], [17], [30], [33]. Whether the gastrointestinal tract is a primary site for H5N1 virus infection is currently unknown.

 

 

 

The incidence of diarrhea reported post-hospitalization in these patients could be due to other factors than just the virus.  The administration of antibiotics, for example, can often cause this side effect.   

 

 

 

Twenty-six cases, with only 9 survivors, is a fairly small sample to draw firm conclusions from.   Late treatment (or no treatment with antivirals), also clouds the clinical picture considerably.

 

 

Since no autopsy results were included (likely not done due to cultural and religious objections), we don't have definitive answers as to the cause of deaths in these 17 fatalities.  

 

 

ARDS is often cited, but is this due to the virus?  Or due to a secondary bacterial pneumonia?  

 

 

The timing, 8 days into the illness, is suggestive of a secondary bacterial pneumonia, but tissue cultures would have been very useful in confirming that.  

 

 

While this study doesn't answer all of our questions, it does give us more insight into the clinical picture of H5N1 infection than we've had up till now.   

 

 

It also provides us with a pretty good indication that antivirals are at least partially effective in increasing survivability from the virus, even when administered late in the illness.