13th ICID Notes

[kent nickell]

From the 13th International Congress on Infectious Diseases in Kuala Lumpur, Malaysia

A few notes from Influenza in Animals and People which had four speakers...

J. Lubroth (Rome, Italy)

The combination of rice production and ducks in the same area appears important for long term maintenance of H5N1. Poultry vaccines have many logistical problems and are not well characterized for ducks and geese. Migration patterns of Anseridae may be most important (ducks, geese, swans). H7N7 and H9N2 also two important viruses to keep on the radar. Veterinary services for the huge agricultural industry need to be strengthened at all levels including policy and regulation. Sicker poultry bring lower prices but are bought when nothing else is available.

N. Shindo (Geneva, Switzerland)

There are 118 national influenza centers in 89 countries which are undergoing review for quality control in analyzing H5N1 and other influenza viruses by pcr. PCR results are being accepted by WHO from labs in Cambodia, China, Indonesia, Thailand, Turkey and Vietnam.

WHO may propose a new phase definition for comment. The goal would be to make it more workable for the current situation and for pandemic planners including businesses. We are still in phase 3 which is characterized by persistence in animals and small clusters primarily limited to extended family groups. Phase 4 would be evidence of sustained h2h which extends beyond the family group to involve a community. Designation of this phase could lead to actions such as development and deployment of a pandemic vaccine. Phases 5 and 6 would be the pandemic phase further characterized by the amount of geographic spread.

S. Giriputro (Jakarta, Indonesia)

A pulmonologist, hospital director and leader of the Indonesia H5 reponse team who has treated many H5N1 patients. As of April 2008 31 of 33 provinces have had poutrly outbreaks and 12 provinces have had human cases mainly in the island of Java. Fever, cough and breathlessness are common presenting symptoms and significant numbers also have GI symptoms. The age group has been 2-67 with a median of 20 and most cases 15-29. There is an equal male/female ratio. Half of the cases report direct contact with diseased poultry, another 40% have infected poultry in the area and 10% have no known source of infection. Average duration of illness from onset to death in 6-10 days. Survivors often spend at least 15 days in the hospital. Has not seen evidence of mild disease and seroprevalence studies have not supported mild disease. Only 2% of patients are seen within 2 days of onset of symptoms and 75% present and get started on tamiflu greater than 5 days after onset of symptoms. Usually evidence of multiorgan disease including liver and kidney. Double dose of tamiflu was not useful. No clear occupational risk factor. Most clusters involve family groups. Almost all patients have fever originally but less than 70% still have fever on admission to the hospital.

M. Tashiro (Tokyo, Japan)

Director of WHO collaborating lab in Japan. Clades 1, 2.1, 2.2, and 2.3 very distinct antigenically but all cause severe disease. Some live attenuated H5N1 vaccines have not shown good immunogenicity because of poor replication in the upper respiratory tract. Some cross reactivity has been seen in whole virus preparations grown in vero cells and used with adjuvant.

Makes the interesting point that H5N1 in humans is not 'influenza' as we know it but has many clinical and laboratory differences. It is a very severe disease affecting multiple organs and appears to have a strong cytokine storm. The vaccines developed so far have low immunogenicity compared to seasonal vaccines. There is no evidence of correlation of standard tests for antibody effectiveness. There are no standard methods, reagents or serum for this virus and no evidence for efficacy or antibody protection in humans. However, an antibody response may be more useful in H5N1 as the virus produces a viremia to infect multiple organs giving the antibodies more of a chance to work rather than being confined to the lungs. Very difficult decision to deploy vaccines in phase 3.

[ironorehopper]

Health experts: Global fight against bird flu remains weak, can worsen food crisis
The Associated Press , Kuala Lumpur | Fri, 06/20/2008 3:47 PM | National

The worst of the bird flu threat is over but the fight to eliminate the disease from poultry is weak - a situation that could worsen the global food crisis, health experts warned on Friday.

"The peak is over, but we still are dealing with any outbreaks, small outbreaks," Juan Lubroth, a senior official with the United Nations' Food and Agricultural Organization, said at an international medical conference.

"It's like a boiling pot, and we need to keep the lid on that before it gets worse," Lubroth said at the 13th International Congress on Infectious Diseases, held in Kuala Lumpur, Malaysia.

Bird flu is still active in 10 countries, down from 60 that have been affected since 2003.

Hot spots include China, Egypt, Indonesia, Nigeria, Pakistan and Vietnam.

Lubroth, the head of the FAO's Emergency Prevention System, said that "drawbacks and weaknesses" remain in the fight to eliminate the deadly H5N1 strain of the bird flu virus from the poultry sector.

He said death of poultry especially affects e poor, 80 percent of whom own livestock for their livelihood worldwide.

Lubroth said poultry is an important, inexpensive protein source for people who wonder every day, "What are we going to have for dinner tonight, or what will be available for tomorrow?"

He warned that failure to protect their food sources could worsen the global food crisis, caused by rising prices of rice, corn and other staples.

Lubroth said 240 million birds have died or been slaughtered, and millions of people's livelihoods shattered, because of bird flu.

Veterinary services around the world need to be strengthened and more experts trained, while reporting must be more transparent, he said, adding that countries have to use more surveillance and implement policies to deal with the disease.

"We fail to see that political commitment," he said.

Besides the threat to the food situation, bird flu could also endanger human lives more directly.

Sporadic suspected human-to-human transmission of H5N1 has been reported in Hong Kong, Vietnam and Indonesia, but none of the cases has been proven. Experts believe the virus remains difficult for humans to catch.

They fear, however, that it could mutate into a form that spreads easily among humans and trigger a pandemic that some say could quickly kill millions of people who would have no immunity to a new flu virus.

"If we want to avert a human pandemic, we must tackle the disease at the source - the source being poultry, the source being poor hygiene, the source being lack of regulatory infrastructures to improve the poultry production sector," Lubroth said.

Still, there was no evidence of sustained human-to-human transmission of H5N1, Nikki Shindo, an infection control specialist at the World Health Organization, told the conference.

Bird flu is "not posing a great public health risk" to humans clinically, he said.

Shindo said that 385 people have reportedly contracted the disease since 2003, and that 241 of them have died, about half of them in Indonesia.

Sardikin Giriputro, who has been at he forefront of Indonesia's campaign against bird flu, said that despite all preparations, "no country is prepared enough for the pandemic." (*)
-
http://www.thejakartapost.com/news/2...ood-crisis.htm
------

[Dutchy]

Bird flu mistaken as dengue, typhoid in Indonesia

By Tan Ee Lyn

KUALA LUMPUR, June 20 (Reuters) - Some cases of human bird flu in Indonesia have been variously misdiagnosed as dengue fever and typhoid, resulting in the late administration of drugs, a leading doctor in the country said on Friday.

Indonesia has had the highest number of human H5N1 cases in the world and while mortality rates are around 60 percent in other places, the figure is highest, or at 81 percent, in Indonesia.

Sardikin Giriputro, director of the Sulianti Saroso Infectious Disease Hospital in Indonesia, told an infectious disease conference in Kuala Lumpur that misdiagnoses and the late administration of drugs were partially responsible for the high mortality rates.

"It (H5N1) is misdiagnosed initially as dengue, bacterial pneumonia, typhoid and upper respiratory tract infection because of similar clinical features (symptoms)," Giriputro said.

Indonesia has had 135 confirmed human H5N1 cases from late 2003 to May 2008 and 110 resulted in deaths. The country reported two more confirmed cases this week, but these were not reflected in Giriputro's figures.

Oseltamivir, otherwise known by its brand Tamiflu, is considered the drug of choice against bird flu and Giriputro said fatalities mounted the later the drug was administered.

The survival rate was very high when Tamiflu was given less than 2 days after the onset of symptoms, but that plunged the later the drug was given.

"It's best if given less than 24 or 36 hours after the onset of symptoms," he told Reuters later.

While rapid test kits are now used to diagnose the disease in animals, Giriputro said these tools were much less reliable in people.

"It depends on the viral load (in samples taken from patients)," he said, adding that test results could turn out negative even if the person was infected with H5N1, simply because there was not enough virus in samples taken.

In a bid to reduce the death rate, the Indonesian government has begun distributing Tamiflu to health centres in areas where H5N1 cases have occurred.

"When doctors see influenza-like illnesses and where there is evidence of contact with sick poultry, then they give Tamiflu (without waiting for laboratory results)," Giriputro said.

While H5N1 remains essentially a disease among birds, experts have warned for years now that it could trigger a pandemic, killing millions of people, if it ever manages to become easily transmitted among humans.

http://wap.alertnet.org/thenews/newsdesk/KLR315115.htm

[kent nickell]

From Sir Roy Anderson, Imperial College, London Models of Tools for Optimizing Public Health Preparedness: The Case of Pandemic Influenza

Megacities defined as greater than 10 million people have special problems such as they tend to have large populations of lifestock right on the outskirts to feed the large population. Megacities also increase transmission events which amplify pathogen evolution likely leading to an increase in novel pathogens. Also huge increase in global travel with most small villages being at least close to a small airport which feeds into a large airport.

He's noticed that many infectious disease epidemics tend to have a few people that transmit many cases and many cases that don't transmit which can lead to a stuttering start before the exponential phase.

Although the serious SARS cases were thought to be the tip of the iceberg with many more less serious cases this was not borne out by seroprevalence studies which seems to also be the case for H5N1.

SARS had nine days after symptoms developed before peak viremia which allowed a better chance for isolation to work. This is not true for influenza where the peak viremia occurs about the same time as symptoms. (2-3 days after infection) The Indonesia experience shows the average time of people presenting as 5 days after symptoms. Most transmission will likely have already taken place before tamiflu is administered. Travel restrictions are also almost certain not to work. Studies have shown that they would have to be 99% effective to slow the pandemic for a few weeks.

It's important for planners to use modeling techniques to identify strategies before a pandemic. It is important to define objectives such as do you want to try and weather the storm with limited or no antivirals and vaccine? Do you want to try strategies that may stall the pandemic and give time to work on a vaccine? At what point in the pandemic is it most useful to use a certain strategy? It is useful to work this out ahead of time as time during a pandemic could be very limited and just using intuitive consensus building may not be as effective as good mathematical modeling. Such as is the 5-15 year old age group the best use of limited vaccine? Cost/benefit analysis is also useful to present to decision makers. Although vaccine programs can be very expensive they could still represent significant cost savings and decrease severe economic repercussions.

Due to the limited time for decision making during a pandemic it is probably best to have strong central planning/directives rather than let each state/province/district work it out on their own.

[sharon sanders]

Thank you Kent for these notes.

[kent nickell]

Emergence of EV71 in the Asia Pacific in the Last Decade presenters included A. Kiyu (Malaysia), M.H. Ooi (Malaysia), H. Shimizu (Japan) and H.S. Wu (Taiwan) (also director of the Taiwan national influenza lab)

EV71 first isolated in the USA 1969-1973. Has emerged in Asia over the last decade showing increased virulence. The disease appears at scattered intervals likely due to new cohorts of immunologically naive children. The disease is showing severe neurovirulence with infection of the brainstem and spinal cord which appears to lead to cardiac arrest possibly by involving the autonomous nervous system.

70% of symptomatic cases are children aged 1-5 and the most severe cases are often under 3 years. Death can be sudden with a day or two of symptoms and has happened at home and in the doctors office. This produces a very scary scenario for everyone concerned.

The virus is closely related to the HFMD Coxsackie A viruses especially CA16 and primers to diagnose the disease need to distinguish between the 2 as CA16 is much less severe and can also lead to HFMD epidemics.

This is emerging as the most important enterovirus after polio. Although there are different strains there appears to be cross-reactivity and a monovalent vaccine may be effective.

[Farmer]

Originally Posted by kent nickell

From the 13th Internatioanl Congress on Infectious Diseases in Kuala Lumpur, Malaysia

N. Shindo (Geneva, Switzerland)

There are 118 national influenza centers in 89 countries which are undergoing review for quality control in analyzing H5N1 and other influenza viruses by pcr. PCR results are being accepted by WHO from labs in Cambodia, China, Indonesia, Thailand, Turkey and Vietnam.

WHO may propose a new phase definition for comment. The goal would be to make it more workable for the current situation and for pandemic planners including businesses. We are still in phase 3 which is characterized by persistence in animals and small clusters primarily limited to extended family groups. Phase 4 would be evidence of sustained h2h which extends beyond the family group to involve a community. Designation of this phase could lead to actions such as development and deployment of a pandemic vaccine. Phases 5 and 6 would be the pandemic phase further characterized by the amount of geographic spread.

How ridiculous! Instead of declaring a Phase 4 based upon the current definition, they 'may propose' to redefine it to keep it at a 3!

I understand that there are concerns about potential economic consequences of raising the alert level, but there are also associated benefits. A move to Phase 4 will increase the sense of urgency for preparedness among citizens of all countries, motivate governments to redefine priorities and maybe, just maybe result in an overall improved public health outcome.

[ironorehopper]

Originally Posted by kent nickell

Emergence of EV71 in the Asia Pacific in the Last Decade presenters included A. Kiyu (Malaysia), M.H. Ooi (Malaysia), H. Shimizu (Japan) and H.S. Wu (Taiwan) (also director of the Taiwan national influenza lab)

EV71 first isolated in the USA 1969-1973. Has emerged in Asia over the last decade showing increased virulence. The disease appears at scattered intervals likely due to new cohorts of immunologically naive children. The disease is showing severe neurovirulence with infection of the brainstem and spinal cord which appears to lead to cardiac arrest possibly by involving the autonomous nervous system.

70% of symptomatic cases are children aged 1-5 and the most severe cases are often under 3 years. Death can be sudden with a day or two of symptoms and has happened at home and in the doctors office. This produces a very scary scenario for everyone concerned.

The virus is closely related to the HFMD Coxsackie A viruses especially CA16 and primers to diagnose the disease need to distinguish between the 2 as CA16 is much less severe and can also lead to HFMD epidemics.

This is emerging as the most important enterovirus after polio. Although there are different strains there appears to be cross-reactivity and a monovalent vaccine may be effective.

Asian doctors warn parents over HFM disease
20 Jun 2008 15:54:22 GMT
Source: Reuters
By Tan Ee Lyn

KUALA LUMPUR, June 20 (Reuters) -

Doctors warned parents in Asia on Friday not to take hand, foot and mouth disease (HFMD) lightly as it is increasingly associated with complications like encephalitis, which can be fatal.

HFMD affects mainly children under 10 years old. In the past, it was mostly caused by the coxsackievirus A16 and complications were rare.

But another little-known agent, enterovirus 71 (EV71), has crept onto the scene over the past 10 years in Asia, experts told an infectious disease conference in Kuala Lumpur.

"The ecology has changed and this has become a very important pathogen (infectious agent) in this part of the world, especially for HFMD, and people have to realize that," said M H Ooi, an expert on the disease at Universiti Malaysia Sarawak.

"Children may have a few days of skin rash, yet they can collapse suddenly of cardio-respiratory failure. The disease can progress very fast. We have seen patients die at home and in GP clinics. It's very traumatic for parents and doctors."

Ooi and his colleagues have been monitoring outbreaks of HFMD in Sarawak, Malaysia, since 2000.

Sarawak suffered three outbreaks of HFMD involving a total of about 1,400 patients in 2000, 2003 and 2006.

EV71 was the predominant cause in all three outbreaks, of which about 20 percent resulted in complications involving inflammation of the brain, Ooi said.

"Brain stem encephalitis with cardio-respiratory failure is the complication that causes most panic among parents," said Ooi.

HFMD swept through several provinces in China this year and has resulted in at least 42 deaths so far.

There are no vaccines or drugs for HFMD, which is believed to be passed among children through the faecal-oral and oral-oral routes.

Apart from encephalitis, EV71 can also cause paralysis and meningitis.

However, little is known of EV71.

"It is very important for us to find the reservoir of EV71. Is it in the water? We need to find out," said another speaker at the conference, Andrew Kiyu of the Sarawak Health Department.

Ooi said the only way to prevent complications was to be alert to certain signs, like high fever of long duration and lethargy in young victims.

"If the fever lasts more than 3 days, then the possibility of (complications) is very high. Coxsackievirus rarely causes fever. And even when it does, the fever is hardly ever more than 38.5 (Celsius)," Ooi said.

(Editing by Janet Lawrence)
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http://www.alertnet.org/thenews/newsdesk/T199332.htm
------

[Sally Furniss]

UN official: Bird biosecurity lapses could worsen food crisis

Lisa Schnirring Staff Writer

Jun 20, 2008 (CIDRAP News) – Lax biosecurity measures around poultry in some countries could lead to an increasing number of H5N1 avian influenza outbreaks that could exacerbate the global food crisis, an official from the United Nations Food and Agriculture Organization (FAO) said at an international infectious disease conference in Malaysia today.
Juan Lubroth, senior officer with the FAO's infectious diseases group, made the comments during symposia on influenza in animals and people at the International Congress on Infectious Diseases (ICID), which started yesterday in Kuala Lumpur and runs through Jun 22. ICID is the annual meeting of the International Society for Infectious Diseases.
Lubroth said though fewer countries have experienced recent avian flu outbreaks, numerous small outbreaks continue to occur, according to an Associated Press (AP) report today. "It's like a boiling pot, and we need to keep the lid on that before it gets worse," he said.
He said 80% of the world's poor depend on livestock for their livelihood, and poultry has been an inexpensive protein source, the AP reported. However, he added that about 240 million poultry have been slaughtered to control the spread of H5N1.
Failure to protect the food supply of the world's poor only makes worse the effect of rising prices of rice, corn, and other staples, Lubroth said.
Global veterinary service capacity needs to be expanded, and more countries need to be transparent regarding disease surveillance and develop surveillance systems and policies to manage the disease, he said. "We fail to see that political commitment."
In the abstract that accompanied the presentation, Lubroth wrote that veterinary experts worry that government officials, in a panic over the threat to human health, are focusing nearly all of their efforts on accumulating antiviral and vaccine stockpiles, "forgetting that the origin of the malady was—and remains—a poultry problem."
Lubroth wrote that a lag in funding for poultry safety initiatives has prevented national veterinary services from mounting the border and regulatory controls needed to contain the disease within Southeast Asia.
Biosecurity: stalled or improving?
Today's comments from the FAO seem to counter some of the recent comments from a UN official on the state of global pandemic preparedness. On Jun 18, David Nabarro, the UN's influenza coordinator, listed national improvements in poultry biosecurity as a reason behind the organization's assessment that the world is better prepared for an influenza pandemic, according to an earlier report. He also said more countries are focusing their efforts on the link between human and animal health.
Other pandemic experts, such as Michael T. Osterholm, PhD, director of the University of Minnesota Center for Infectious Disease Research and Policy, the publisher of CIDRAP News, disagree that the world is better prepared for a pandemic and say governments have not planned for supply, medicine, and utility disruptions that could severely damage the world's economy and worsen the impact of the disease on health.
Nabarro, however, expressed concern that the virus remains entrenched in several countries, particularly Indonesia, the country that has had the highest number of human cases and deaths.
Indonesia reports on diagnostic challenges in human cases
In another presentation during the same ICID symposia, Sardikin Giriputro, director of the Sulianti Saroso Infectious Disease Hospital in Jakarta, Indonesia, gave an update on that country's clinical cases and spoke of challenges in diagnosing H5N1 infections.
With 135 cases and 110 deaths from the disease, according the most recent World Health Organization (WHO) update, Indonesia has been hit harder than any other country by the H5N1 virus.
However, early this month Indonesia's health minister, Siti Fadilah Supari, said that the number of human cases has slowed this year, according to a Jun 5 AP report. She said only 18 people have been infected with the virus so far this year, compared with 27 for the same period in 2007 and 35 in 2006.
Giriputro said that some patients with H5N1 infections have been misdiagnosed with dengue fever and typhoid, which has delayed antiviral treatment, according to a report today from Reuters. Oseltamivir (Tamiflu) is the drug of choice for H5N1 illnesses and is best given within 24 to 36 hours of symptom onset.
He told the group that medical officials in Indonesia are finding that rapid test kits used to diagnose the H5N1 virus in animals are less reliable for testing human samples, according to the Reuters report.
"It depends on the viral load [from human samples],"Giriputro said, adding that false-negatives can occur when there isn’t enough virus in the human sample.
Indonesia's government has been distributing oseltamivir to health centers in areas that have had poultry outbreaks and human cases, he said. Physicians prescribe the virus without waiting for laboratory results if patients have influenza-like illnesses and may have had contact with sick poultry.
In an abstract that accompanied his talk, Giriputro said about 50% of Indonesia's H5N1 patients had a history of direct contact with sick birds, 30% had indirect contact, and 20% had no contact that could be determined.


http://www.cidrap.umn.edu/cidrap/con...eeting-jw.html

[kent nickell]

Advances in the Development of H5N1 Vaccines and Their Role in Pandemic Planning, Baxter Satellite Symposium


1st speaker Lance Jennings, Clinical Virologist, New Zealand

The statement of his I found most interesting was 'Pandemics behave as unpredictably as the influenza viruses that cause them'.

To me this implies that we should pay attention to the severity of H5N1 and not hope that it will get less virulent if it becomes more transmissible and indeed he stated that an H5N1 pandemic could be much worse than 1918. (To me this is a strong arguement for starting vaccine programs sooner rather than later)


2nd speaker Jonathan Van Tram, Epidemiologist specializing in influenza and pandemic preparedness, University of Nottingham, UK, recently chaired the ECDC Expert Advisory Group on H5N1 vaccines


Global spread of an influenza pandemic will most likely be rapid with the estimated time of a hypothetical start in Hong Kong to arriving in the UK of 2-4 wks if not sooner if an early infected businessman happens to get on the plane.

Both the 1918 and 1968 pandemics showed a wave as lasting 17 weeks with a peak at week 8.

Current estimates for start of vaccine production in the EU from time of identifying the pandemic virus is 22 weeks. This would likely still be of some use but may be better characterized as a 'post pandemic' vaccine or at least post 1st wave.

It would likely be at least 7 months before large amounts of virus is being produced globally to adequately immunize nations. Also the current recommendation is to give 2 doses spaced 3 weeks apart. Vaccine would come in at intervals requiring a prioritization schedule for who gets it. (Hard to do all this in a hurry and under pressure)

Some new strategies that are evolving are giving a dose or 2 of prepandemic vaccine (PPV) followed later by the true pandemic vaccine (TPV). One suggested risk stratification model puts giving 2 doses of TPV as the most risky as the logistics of accomplishing this are not favorable. Less risky is one dose of PPV and no TPV. Of about equal and lower risk are 1 dose of PPV with 1 dose of TPV and 2 doses of PPV. The least risk is 2 doses of PPV and one dose of TPV.

Recent vaccine studies are showing good safety, efficacy in animal models, and significant cross reactions between clades.

Prepandemic deployment of vaccine has complex scientific and political problems not the least of which is the public perception of the threat versus what they will tolerate as side effects of the vaccine. (Vaccinating millions of people will have real and perceived side effects) but could potentially have massive benefit.




3rd Speaker Noel Barrett, Biomedical Research Center, Baxter AG, Austria

Baxter has recently had good succes growing whole wild virus in Vero cell culture. Not using reverse genetics to attenuate the virus leads to rapid growth and high yields. This does all have to be done at BSL-3 of which they have a large production facility in the Czech Republic.

They used a clade 1 virus and the vaccine also showed significant cross reaction with other clades. Human trials of course can't be done but they did take serum from humans and injected it into mice and then challenged the mice with an LD50 dose of the appropriate virus and showed 80% protection.


4th Speaker Gregory Berezuk, Baxter BioScience, United States

He referenced the recent NEJM article http://content.nejm.org/cgi/content/full/358/24/2573

Volume 358:2573-2584 June 12, 2008 Number 24

A Clinical Trial of a Whole-Virus H5N1 Vaccine Derived from Cell Culture
Hartmut J. Ehrlich, M.D., Markus Müller, M.D., Helen M.L. Oh, M.D., Paul A. Tambyah, M.B., B.S., Christian Joukhadar, M.D., Emanuele Montomoli, Ph.D., Dale Fisher, F.R.A.C.P., Greg Berezuk, M.S., Sandor Fritsch, Ph.D., Alexandra Löw-Baselli, Ph.D., Nina Vartian, Ph.D., Roman Bobrovsky, Ph.D., Borislava G. Pavlova, Ph.D., Eva Maria Pöllabauer, M.D., Otfried Kistner, Ph.D., P. Noel Barrett, Ph.D., for the Baxter H5N1 Pandemic Influenza Vaccine Clinical Study Team


He also went on to add that they have extended this trial by re-immunizing some of the initial subjects. They took people from the first trial who had originally had 2 doses of the vaccine 21 days apart and gave them a booster 12-17 months later with a heterologous virus. This booster showed that the immune system had been well primed by the initial series and in 7 days gave good antibody titres to both the new and original virus. This data is supportive of using a prepandemic vaccine followed by a true pandemic vaccine.

[kent nickell]

21st Century Global Health Protection Julie Gerberding, United States

I think the US was very well represented by Dr. Julie Gerberding at this conference in Kuala Lumpur. She gave an hour plenary talk to hundreds of people from scores of countries and I would say came across as the type of knowledgeable and caring person that you would want in charge of one of the world's premiere infectious disease centers. She started off with a discussion of some of the recent food security issues including some recent Salmonella and E. coli cases and then went on to discuss ongoing world problems such as 1 million people dying annually from malaria. She then discussed climate change with flooding and other natural disasters occurring throughout the world and the problem of emerging infectious diseases such as increases in dengue and chikungunya.

She discussed the billions of people living in extreme poverty and some of her travels to distressed areas of the world. She had a combination of a humble yet strong presentation style which I think represented this US agency very well. She described something she has seen in numerous places that is heart wrenching and that is 'women and water'. The problem with not enough safe water and women especially spending an inordinate amount of time and energy walking for water and carrying water back to their residences and what a huge waste of human potential this is. I noticed that she seemed to relate extremely well with the women in the audience.

She went on to discuss avian flu and that she spends 90 minutes every Wednesday in the emergency operations center of the CDC being updated on pandemic preparedness. Nothing she has seen has given her any reason to be complacent about this threat. She went on to discuss the problem of complacency in some detail and how it is difficult to keep the public's and media's attention to this nature of threat.

One problem people have is 'who do you believe?'. CDC initiated a study to determine who people want to hear from in an emergency. Do they want to hear from her, from health ministers, infectious disease experts, or security experts? The study showed that most people trust their family doctor and would listen to them. So she stressed to the numerous doctors attending this conference from around the world to take a leadership role to avoid complacency.

[sharon sanders]

Thanks Kent. I also found Dr. Gerberding to be a very effective speaker. She is "down to earth".

On this thread are other reports of her remarks (not as good as yours!):



http://www.flutrackers.com/forum/showthread.php?t=72108

[gsgs]

> Current estimates for start of vaccine production in the EU from
> time of identifying the pandemic virus is 22 weeks

22 weeks is what they called "worst case".
More realistic seems the "best case", which gives 10 weeks here.

source: Paul Ehrlich Institut, www.pei.de
http://www.rki.de/nn_200126/DE/Conte...uenza/FAQ.html

(and that was before we had built approved cell-based production)


Why did the speaker say 22 weeks ? Are they deliberately giving
tricky numbers so to increase the efforts for other preparations ?

[kent nickell]

I think he was trying to be realistic with 22 weeks. Given that not everything moves smoothly under the best of circumstances and that things would be especially chaotic in the throes of a pandemic. In the question/answer period the Baxter people thought they could shave 10 weeks off that. Some planners and I think Sir Roy Anderson would be included here think that with all the novelty involved not to mention packageing, labeling, distribution, regulation and again the chaos across multiple levels during a pandemic that we would be lucky to have any substantial and reasonable doses within a year. There is also the 2 dose problem. Studies so far have spaced these at 3-4 wks and it is unsure if that can be shortened. To me it would be hard to imagine that we would have worldwide distribution of a pandemic vaccine 10 weeks after it is identified and even that runs into the 2 dose problem and the fact that the pandemic may be well on its way. There are still many unknowns. The best case would be that if a pandemic were to start it wouldn't explode but would show itself significantly enough for people to be motivated to spring into action. My thinking is that if we decided right now that we wanted to immunize several billion people that we would have our work cut out for us.

[gsgs]

slightly reformulated and simplified, you said:

> Some planners including probably Sir Roy Anderson think that
> we(USA?) won't have significant doses within a year

the disruption etc. is not important, IMO. In a severe pandemic we will concentrate
efforts. Compare with mobilization for war, it works even with (enemy-intended)
disruptions.


-------------------------------

10 weeks is the time for start of production, not for availability of all the doses.
For Germany PEI counts 6 further weeks for producing 80M doses
and another 6 weeks for the 2nd 80M doses. (figure from 2006)

So, you would start vaccination after 10 weeks.
After 16 weeks in total you could have 100% vaccinated with one dose
or 50% vaccinated with 2 doses 3 weeks apart.

As I understood, when you get 2 doses, the first dose could be badly-matching
prepandemic vaccine and only the 2nd dose strain-specific.
So, with a prepandemic stockpile for 50% of the population I calculate:

50% with one dose after 6 weeks
100% with one dose or 50% with 2 doses after 13 weeks
75% with 2 doses after 16 weeks (50% with full titers after 16 weeks, the other 25% with full titers
after at most 19 weeks)
87% with 2 doses and full titers after 22 weeks
100% with 2 doses and full titers after 25 weeks

you would vaccinate risk groups and spreader groups first, to increase the effect.

it's unclear how much 1 dose is, whether adjuvanted or not, whether the 80M doses
after < 10+6 weeks could be split into 160M smaller doses and why there is a
limit at all. If they can produce 80M doses in 6 weeks, then I assume they can produce
1000M doses in 6 weeks.

Also this "preparation time" of 10 weeks is presumably due to regulations
which may be weakened if a severe panflu starts.
I have read elsewhere, that it may be reduced.


I assume, the same would hold for the USA, should they file an APA with a vaccine
producer. But they hope to make it cheaper by scaling up their own production capacities.
Also, some vaccines may be less effective than others, so these countries
would discard their own supplies and have to buy the (more expensive) vaccine elsewhere.

[ironorehopper]

Rotavirus main cause of diarrhea in minors: conference

Rotavirus is the main cause of severe diarrhea in children under five years old, agreed doctors and professors at the 13th International Conference on Contagious Diseases in Kuala Lumpur in Malaysia.

Some 25-55 percent of the world’s children under five years old have contracted diarrhea, gastritis or enteritis from Rotavirus, said participants at the event.

Of the 661,000 children who die from gastritis and enteritis due to rotavirus annually, 90 percent of them are from Asia and Africa.

Diarrhea from rotavirus annually claims the lives of about 171,000 children under two years old in Asia alone, said experts.

More than 96 percent of 10,708 children aged from six months to two years old vaccinated against rotavirus have effectively fended off diarrhea, gastritis and enteritis from rotavirus, said researchers at the two-day event, which ended Sunday.

Reported by Thanh Tung

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http://www.thanhniennews.com/healthy...8&newsid=39559
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[HenryN]

Commentary

http://www.recombinomics.com/News/06..._Concerns.html

[HenryN]

Commentary at

http://www.recombinomics.com/News/06..._Concerns.html

[AlaskaDenise]

Originally Posted by niman

Commentary

http://www.recombinomics.com/News/06..._Concerns.html

Commentary

H5N1 Pre and Post-Pandemic Vaccine Concerns
Recombinomics Commentary 13:51
June 23, 2008

Both the 1918 and 1968 pandemics showed a wave as lasting 17 weeks with a peak at week 8.

Current estimates for start of vaccine production in the EU from time of identifying the pandemic virus is 22 weeks. This would likely still be of some use but may be better characterized as a 'post pandemic' vaccine or at least post 1st wave.

It would likely be at least 7 months before large amounts of virus is being produced globally to adequately immunize nations. Also the current recommendation is to give 2 doses spaced 3 weeks apart.

They took people from the first trial who had originally had 2 doses of the vaccine 21 days apart and gave them a booster 12-17 months later with a heterologous virus. This booster showed that the immune system had been well primed by the initial series and in 7 days gave good antibody titres to both the new and original virus. This data is supportive of using a prepandemic vaccine followed by a true pandemic vaccine.

The above comments from the International Conference on Infectious Diseases in Kuala Lumpur raise concerns that the current policy of waiting for the emergence of a pandemic followed by the creation of an appropriate vaccine may lead to a post pandemic vaccine, rather than a pandemic vaccine base on the time for manufacturing a vaccine compared to the time for the global expansion of the first wave. The current approach adopted by most countries is to stockpile vaccines for immunizing first responders at the start of a pandemic. This approach is based on concerns that early vaccinations may lead to unnecessary side effects if the targeted pandemic does not emerge.

However, a strong case can be made for the emergence of an H5N1 pandemic, and matches with the stockpiled vaccine will decline as the virus evolves. Although a pandemic H5N1 may be radically different that current circulating strains, H5N1 has been evolving through antigenic drift and changes in a small number of single nucleotide polymorphism can dramatically change transmissibility, in the absence of dramatic antigenic changes.

The evolution and expansion of H5N1 in recent years has been rapid and significant. The “Asian” version of H5N1 was first reported in 1996 in a Guangdong goose. The following year it was reported in humans in Hong Kong. Aggressive culling in Hong Kong created a lull in human cases, although there were repeated poultry outbreaks in the following years. In early 2003 there were human cases in a Hong Kong family that had visited Fujian province, as well as Beijing resident, who was initially diagnosed as SARS.

However, the explosion in H5N1 began at the end of 2003, beginning of 2004, when H5N1 was reported in countries to the east and southeast of China. These outbreaks produced human cases in Vietnam and Thailand. This H5N1 was designated clade 1. Related clade 2 isolates caused human cases in Indonesia (clade 2.1) and China (Fujian clade 2.3) in 2005, which is when Qinghai clade 2.2 was reported in long range migratory birds. The movement of clade 2.2 into long range migratory birds in the spring of 2005 led to the global expansion of clade 2.2 into 50 countries in Europe, the Middle East, and Africa and associated human cases in Turkey, Iraq, Azerbaijan, and Egypt in 2006, followed by Nigeria and Pakistan in 2007. It is likely that the human case in Bangladesh in 2008 was also the Qinghai strain. Most recently, Fujian clade 2.3 has been found in long range migratory birds in northern Japan, with related isolates in South Korea and eastern Russia.

Thus, the dramatic spread of clade 2 was been recent, and it accounts for virtually all reported human cases in the past few years. However, most approved pre-pandemic vaccines target clade 1, which was the H5N1 in humans when vaccine development programs began in early 2005.

Stockpiling these vaccines, or those targeting early clade 2 isolates, will not be optimal for the current clade 2 in circulation, as the various sub-clades evolve away from the 2005 isolates. Thus, these vaccines may be useful for priming patients now, but would have limited utility for a raging pandemic, and may in fact drive H5N1 evolution because of poor matches as seen in poultry vaccines.

However, use of these vaccine now, when H5N1 has not been established in human populations could delay adaptation to humans by reducing the number of human H5N1 infections.

Thus, the current policy of stockpiling older vaccine for use in first responders may have limited value if used after the pandemic begins, and use at that time may lead to a more rapid H5N1 evolution, which will decrease the utility of newer vaccines, which will still be chasing the evolving H5N1, even if the vaccine selection is limited to a pandemic H5N1 which has begun to emerge.


.

[AlaskaDenise]

Originally Posted by niman

Commentary at

http://www.recombinomics.com/News/06..._Concerns.html

Commentary

H5N1 Vaccine Stockpiling Concerns
Recombinomics Commentary 17:25
June 23, 2008

He also went on to add that they have extended this trial by re-immunizing some of the initial subjects. They took people from the first trial who had originally had 2 doses of the vaccine 21 days apart and gave them a booster 12-17 months later with a heterologous virus. This booster showed that the immune system had been well primed by the initial series and in 7 days gave good antibody titres to both the new and original virus. This data is supportive of using a prepandemic vaccine followed by a true pandemic vaccine.

The above comments are from a synopsis of a talk given at the 13th International Conference on Infectious Disease in Kuala Lampur, Malaysia by Gregory Berezuk of Baxter BioScience.

The original Baxter vaccine was grown in vero (African green monkey) cells and used a clade 1 isolate as the target. The published data indicated the initial response was weak and data was presented on patients with a titer of 20 or higher. However, the above comments suggest that a follow-up booster produced “good” antibody titers in 7 days against the original target as well as the heterologous (presumably clade 2) booster.

These data, coupled with reports on the time to produce a vaccine target, suggest that the current approved vaccines should be used to prime populations, rather than be stockpiled for use after the pandemic begins, which is the current plan for many countries.

Recently Japan, like other countries with active H5N1 infections and prior human infections, has announced plans to begin vaccinations of first responders, as well as a broader population, in the upcoming months, in advance of an H5N1 outbreak. This approach is supported by the above results, and provides a number of advantages over stockpiling.

Most of the current stockpiled vaccines are directed against clade 1 targets from 2004 patients in Vietnam. Although clade 1 is still in circulation in birds in southeast Asia, most of the human infections there are clade 2 (Fujian clade 2.3.4), which is also true for human infections in China. The recent reports of clade 2.3 in long range migratory birds in Japan, with related sequences in South Korea and southeastern Russia, may have contributed to Japan’s decision to accelerate its vaccination implementation plan, which is likely to target clade 2. Last year the H5N1 in Japan and South Korea was clade 2.2.2 (subclade of Qinghai strain).

Although the current set of targets may not be exact matches of circulating H5N1, the virus is not established in human populations, so the use of these vaccines is unlikely to accelerate H5N1 evolution. In contrast, stockpiling vaccine and subsequent use after a pandemic begins is likely to accelerate H5N1 evolution, which will impact subsequent vaccines, which will require approximately 6 month to create and distribute. Trailing a rapidly evolving H5N1 by six months would limit the effectiveness of the pandemic vaccine.

Thus, stockpiling vaccines for use by first responders may have significant downside for the general population, which could be overcome by starting vaccinations now, to prime a broad population for future booster shots.


.

[mixin]

There are many, many good abstracts from this conference. I've posted several on this forum and a number of the flu-related ones in the summaries forum here http://www.setbb.com/fluwiki2/.

The link to the Congress is here http://www.isid.org/13th_icid/index.shtml or you can search by session or title here http://www.x-cd.com/isid08/search.html