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**Mingus** · August 30, 2006, 12:00 PM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

There is many good reason to have so much question about that treatment option and you point it out somes.

For those who want, the original complete article that exposed that idea is available here at FT in that thread :
Convalescent Plasma Might Lessen H5N1 Mortality-empirical therapy against Spanish flu

I'll take time to read it completely before I do more comment but I'll say that this kind of "serotherapy" is used in veterinary medecine as a "lowtech" therapy when vaccine is not available and when the disease is already widespread.

We should understand that the principle is to directly inject the antibody from the survivor in the blood of the sick ones.

Many of the problems that is linked with blood transfusion will also be there.
Using it massively can lead to spreading "others blood-born diseases" like AIDS...

Here in Québec, we used the "serotherapy" method to reduce morbidity of the PMWS syndrome caused by the circovirus in the swine industry.
It showed some efficacity until the vaccine get ou this spring.

My job at the time was to check and double check by PCR the serum "lots" to be sure others swine blood-born diseases where not unclude in the serum intended to be use in the therapy.

I would like to hear comments from human medically skilled members on this...

Now I'll go read that article...

**wetDirt** · August 30, 2006, 01:48 PM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

Well, if you don't mind serum sickness, there is always this approach:

http://www.sciencedaily.com/releases/2006/03/060330084126.htm

A horse has lots more blood to give than a human, and can't give you those nasty diseases, although I'm sure they could have _something_ humans would not like much. How low-tech is this method? Do you just centrifuge the blood, separate serum, and go?

**kent nickell** · August 30, 2006, 02:17 PM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

In an associated editorial Dr. Treanor dealt with some of these issues and caveats...

Just a moment...

http://www.annals.org/cgi/content/full/0000605-200610170-00140v1

Avian Influenza: Exploring All the Avenues
John J. Treanor, MD

17 October 2006 | Volume 145 Issue 8

An excerpt:

Passive immunotherapy to treat infection with influenza viruses, including H5N1, has been effective in a mouse model. Other viral diseases offer ample precedent: Passive antibody prevents many human viral diseases, including varicella, rabies, hepatitis A and B, and respiratory syncytial virus (RSV). However, the distinction between prevention of disease and treatment of active disease is important. Few recent data support the use of passive antibody therapeutically after disease manifestations have already begun. For example, although passive antibody is highly effective at prevention of RSV infection in high-risk infants, systemic administration of antibody with high levels of RSV neutralizing activity is not useful therapeutically in infants with RSV disease ( 7).

Nevertheless, the concept is important and it should be explored further, especially given our lack of proven interventions to prevent or treat illness due to H5N1 influenza. The use of serum from recovered patients as the source of antibody for passive immunotherapy has the advantage of being technically simple, and ample numbers of convalescing patients should be available for plasmapheresis. The resulting antibody would be polyclonal, which would decrease the chance of an escape mutant developing in treated patients. The serum also might have antibody to other bacterial pathogens, which might decrease the severity of coexisting bacterial superinfections (a mechanism that may account for some of the efficacy of serotherapy in 1918). Balanced against these optimistic considerations are several major concerns. Formidable logistical hurdles would complicate the ability to obtain, characterize, and prepare these materials for use in the midst of an outbreak. As yet, we don't know if patients who recover from H5N1 influenza develop particularly high levels of antibody (8).

**Mingus** · August 30, 2006, 03:02 PM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

Originally posted by wetDirt

Well, if you don't mind serum sickness, there is always this approach:

http://www.sciencedaily.com/releases...0330084126.htm

From that link

Horse Antibodies Against The Bird Flu Virus H5N1 Are Effective As Treatment In Mice

Antibodies against the bird flu virus H5N1, derived from horses, prevent mice infected with H5N1 from dying from the virus. A study published in the open access journal Respiratory Research (http://respiratory-research.com) reveals that a dose of 100 µg of horse anti-serum effectively protects infected mice. These results suggest that anti-H5N1 antibodies developed in horses could potentially be used to prevent death from H5N1 influenza, or as early treatment for the disease, in humans.

I don't know if there is a higher risk of allergy associated with the use of Horse serum instead of human one...

**Mingus** · August 30, 2006, 03:44 PM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

Originally posted by wetDirt

How low-tech is this method? Do you just centrifuge the blood, separate serum, and go?

Something like that!

When I say low-tech I mean low tech...

The veterinary here haved heard of how It was done in some place in France and successfully reduce morbidity and mortality.

They where only harvested survivors blood in drums, let it decant in a garage for some night and then directly inject this to the youngs pigs before the critical age where they usually fall sick.
( You have to know that this circovirus disease has a long developping period a little bit like AIDS and almost every hoards are positives so the trick is to reduce the viral load to prolonge the healthy phase. )

The group that want to do this here haved the project of centrifugate the blood in olds washing machine...

So when they tell this to the lab administration here, they offer them a real professionnal service of centrifugating filtrating and quality control .( test for others diseases in the serum by PCR ) to ensure the best quality with all the modern scientific standards.

The project lasted for almost a year until the vaccine commercialisation.

So like vaccine, depending of how you like it safe you have the choice of get it very very low-teck.

**wetDirt** · August 30, 2006, 04:17 PM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

Originally posted by Mingus

Something like that!

When I say low-tech I mean low tech...

The veterinary here haved heard of how It was done in some place in France and successfully reduce morbidity and mortality.

They where only harvested survivors blood in drums, let it decant in a garage for some night and then directly inject this to the youngs pigs before the critical age where they usually fall sick.
...
The group that want to do this here haved the project of centrifugate the blood in olds washing machine...

...

So like vaccine, depending of how you like it safe you have the choice of get it very very low-teck.

*trembles* *runs* *hides*

**wetDirt** · August 30, 2006, 09:34 PM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

Originally posted by Mingus

I don't know if there is a higher risk of allergy associated with the use of Horse serum instead of human one...

Yes, very much. That's why they try not to use it anymore. I think there are still a few uses, tetanus antitoxin is one still. Something like 15% of the population will have a bad, but not life-threatening reaction, and an unlucky few who have had horse serum before will get anaphylactic shock. It appears to be a pretty desperate option, knowing that a large number of people will have severe side effects, and that this trick might only work once per person, because the side effects are likely to get worse the second time around. But in the face of a 75% CFR, the benefit to risk ratio could make sense for some.

**Mingus** · August 30, 2006, 10:04 PM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

Originally posted by wetDirt

But in the face of a 75% CFR, the benefit to risk ratio could make sense for some.

Denefinitively yes, the ethics questions are always around when talking of high CFR.

I had just took time to read the complete article.

Frankly, this is a great work that come right in time.
The most amazing thing is that is is a study realysed without many budget an made with old historical study from the 1918 era.

The "new" that is to conclude from that is that "seroterapy" can be apply to influenza even if the disease is a respiratory one.
They bring generals statisticals evidence from that historic documentation analysis.

The benefit from that kind of therapy seem statistically relevant, the side effects seem high from todays standard but the main goal to reduce mortality and morbidity is greatly helped.

The autors are couscious of the controversial matter of that "archa?c" medecine revisited.

They advocate the need to realise modern study to probe potency for the H5N1 treat.

Given the vast availability, and the low cost of the the "idea", his potency enven with his limits , it is a information we just can`t ignore.

This is a stong statistical study that must be followed by modern clinical data.

The idea of giving blood after recovered from the disease to help the later recover better is ... something like...

**gsgs** · August 31, 2006, 01:39 AM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

hmm...

So, in a pandemic will there be a (black-)market for blood from
recovered victims ?

Will there be lots of blood from recovered Chinese reaching USA
for low price before even panflu reaches America in full strength ?

Will recovered patients be at risk from illegal blood-hunters ?

**Mingus** · August 31, 2006, 07:11 AM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

Originally posted by gsgs

hmm...
So, in a pandemic will there be a (black-)market for blood from
recovered victims ?
Will there be lots of blood from recovered Chinese reaching USA
for low price before even panflu reaches America in full strength ?
Will recovered patients be at risk from illegal blood-hunters ?

There is no way to get the "blood-giving" outside of the current non-profit organisation like the Red-Cross or others NGO highly regulated.

Non ethical blood-giving will lead to non-ethical serum transfusion wich will spread blood-born diseases like AIDS all around.

Blood and serum should only be transit on a local scale to prevent all kind of disease spread

**Mingus** · August 31, 2006, 08:54 AM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

A collection of relevant quotes from the original statistical study...

(...) relevant studies involving 1703 patients were found. Treated patients, who were often selected because of more severe illness, were compared with untreated controls (...)
The overall crude case-fatality rate was 16% (54 of 336) among treated patients and 37% (452 of 1219) among controls.
(...)
The range of absolute risk differences in mortality between the treatment and control groups was 8% to 26% (pooled risk difference, 21% [95% CI, 15% to 27%]).
(...)
The overall crude case-fatality rate was 19% (28 of 148) among patients who received early treatment (after <4 days of pneumonia complications) and 59% (49 of 83) among patients who received late treatment (after 4 days of pneumonia complications). 
(...)
Only 2 trials (17, 19, 20) reported sufficient data to compare both early and late treatment groups with a control group. The mortality rates among patients treated within 4 days compared with controls were 32% (10 of 31) versus 53% (201 of 379) (17) and 14% (3 of 22) versus 43% (9 of 21) (19, 20).
(...)
The most commonly reported mild adverse event was a brief "chill" reaction with a transient elevation in body temperature by 1 to 2 °F 30 to 120 minutes after the transfusion. The rates of the chill reaction were reported as 16% (17), 75% (18), or 10% (25) of patients, or that the occurrence of this event was "frequent" (19, 20) or "infrequent" (23, 24), or seen in "some" patients (26).
(...)
One study reported a case of "anticipated anaphylaxis" after transfusion with non–ABO-matched blood, which was administered because no matched donor was available and the patient's condition was critical (the patient survived) (19, 20).
(...)
The overall rate of moderate to serious transfusion-related adverse events from studies (17, 19, 20, 23, 24) that provided quantifiable data was 4% (9 of 235 patients).
(...)
One study (19, 20) reported that 28 patients in the treatment group had more rapid resolution of fever (average duration, 9.5 days) and an increase in leukocyte count (average increase 3 days after transfusion, 7000 cells/mL) compared with 21 controls (average duration of fever, 15 days; no change in leukocyte count)
(...)
Data from Excluded Studies
Most excluded studies (Appendix Table) reported that use of influenza-convalescent blood products was beneficial (27–29, 32–43). One large study at a U.S. Army recruit training hospital investigated the use of influenza-convalescent serum in patients with Spanish influenza but not pneumonia (27). The treatment group consisted of 26 patients with influenza who were selected on the basis of highest fever and clinical severity of illness and were compared with a control group of 219 concurrent patients with uncomplicated influenza. Compared with controls, treated patients had faster resolution of fever (average, 3.6 days vs. 5.8 days), fewer cases of pneumonia (1 of 26 treated patients [4%] vs. 30 of 219 controls [13.7%]), and fewer deaths (0 of 26 patients vs. 6 of 219 patients [3%]).
(...)
Discussion
Our analysis suggests that patients with Spanish influenza pneumonia who received transfusion with influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death and improvements in clinical signs and symptoms. Adverse effects included chill reactions and possible exacerbations of symptoms in a few seriously ill patients.
(...)
Our subanalysis indicates that early treatment (after <4 days of pneumonia complications) was superior to late treatment (after 4 days of pneumonia complications). The mortality rate among controls and late-treated patients appeared similar and is consistent with the modern recognition that early definitive therapy for pneumonia and hypoxia is clinically important.
(...)
Our biological hypothesis for why mortality and morbidity may have been reduced is that the virus was neutralized by anti-influenza antibodies in the blood product. Rapid viral clearance would halt further replication and the stimulus for the cytokine cascade that is responsible for the acute respiratory distress syndrome
(...)
Reductions in the mortality rate may have also resulted from fewer secondary cases of bacterial pneumonia, empyema, and septicemia.
(...)

And then... on the cautiousness we must not forget

(...)
Our findings are provocative, but our review has important limitations. Studies were few, and the size of most was small. The medical and research practices of the 1920s are archaic by current standards. None of the studies was a blinded, randomized, or placebo-controlled trial.
(...)
Moreover, we could not acquire and analyze every study. World War I coincided with the most intense waves of the Spanish influenza pandemic, and wartime censorship, death, or illness of investigators and rapid demobilization of drafted physicians may have prevented the publication of negative (or positive) studies.
(...)
Current human H5N1 outbreaks are small, sporadic, and geographically distant. The comprehensive study of this treatment will probably require a global approach because a series of underpowered, nonstandardized, and nonrandomized case studies will not conclusively demonstrate or disprove efficacy. A central body of experts should be convened to consider H5N1 plasma therapy and to make recommendations regarding a research strategy and possibly treatment guidelines in the event that therapy is required before the research is completed. A standardized protocol could be created and then submitted by a consortium of international investigators to local or national investigational review boards.

And about technical details ...

In the event of a severe pandemic, antiviral agents, antibiotics, and intensive care medicine may be rationed or not available to most severely ill patients. Modern plasmatherapy may be an effective and practical health care delivery alternative. Large volumes of plasma are currently produced by existing hospital-based plasmapheresis and blood collection centers (60, 61), and U.S. Food and Drug Administration regulations (62) allow individuals to donate 1000 to 1200 mL of plasma per week. A single H5N1 convalescent donor could provide a weekly volume of plasma sufficient to treat multiple patients with H5N1 influenza. Donation is safe and entails few adverse events because the cellular components of the blood are returned to the donor under sterile conditions, and risks should not increase for convalescent donors. Locally produced plasma from convalescent donors or early vaccine recipients could be immediately effective in the event of a virulent influenza epidemic or other disease for which no good treatment exists.
(...)
As a point of discussion, existing transfusion practices could be used to administer acute convalescent plasma to patients with H5N1 infection, in quantities of at least 1 to 2 mL/kg of body weight (9, 62).

**Mingus** · August 31, 2006, 05:03 PM

Ethical dilema

Frankly, I am very surprised there is not much reaction,

This study may have point out the cheapest and mostly available treatment to effectively reduce morbidity and mortality in the course of a high CFR pandemic.

The method may be a archa?c medecice trick, it is not supposed to be harder to manage than blood transfusion and blood transfusion is used currently in modern medecine.

look...

relevant studies involving 1703 patients were found. (...) selected because of more severe illness (...)
The overall crude case-fatality rate was 16% among treated patients and 37% among controls.

Ok now,
imagine this hypothethical situation...

You haved been very sick but you recovered... some week later your childrens fell sick and the pneumonia turn bad very quick.

Would you, based on that study, feel the need to ask your doctor to collect some ml of you serum ( today, syringe filter exist that can collect only serum, it can be done in a ambulance almost costless) to inject it to your childs in the hope you help them to survive ???

I really would like to hear FT's member tought about that

**Snowy Owl** · August 31, 2006, 06:16 PM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

Thank you for the invitation Mingus,

As a parent of course I would do anything possible for my children. That being said, I will try to get as much information as possible concerning the virulence of the strain hanging around while I would try to get as much information on this process.

This is certainly a path worth consideration, but with actual datas.

**Shannon Bennett** · August 31, 2006, 07:51 PM

Re: Why blood of bird flu survivors is a lifesaver [Discussion]

I would like to preface my comments with the statement that I am not a health care professional.

Talk about being stuck on the horns of a dilemma. I think the possibility of lessening the dire outlook of the virus means we should investigate every avenue. In this case we need to address some specific concerns.

My sister is now suffering from Hep C, which the doctors believe she got many years ago from a blood transfusion. We all have either known someone or have read of people who got AIDS from transfusions. I know these were in the past but this method has me somewhat concerned. If we could not be assured of a safe product, the only way many of us would go ahead with a human based serum is using a source from previously healthy nuns or children. We need therefore to fix the problem now with possibly contaminated blood or, use an alternate source of serum. Otherwise, many of us will worry ourselves sick if we have only put off dying from bird flu for dying from AIDS?

As for horse serum, I wonder if a prick test would alert the future recipient of the inoculation of a possible adverse reaction? If so, then how long before you got the horse serum would you have to have been scratched? Are their alternative sources, chimps, cats, pigs? Have any of these been tested? Are horses susceptible to H5N1?

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