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  • China & Egypt Using AntiBody Plasma Treatment to Cure Bird Flu Cases

    Further evidence that Peng's mother likely to have died from bird flu. Also, treatment plan that saved Peng mentioned.


    2009-03-10

    <founder-content> </founder-content>Highly pathogenic avian influenza this person's word is a mouthful, for just in the area of separation birthday Spend three small PENG (a pseudonym) is obviously too high, so even though she almost died.


    For the domestic youngest person of highly pathogenic bird flu, Health Minister Chen Zhu told Shanxi specialized aspects "at all costs for medical treatment."

    From admission to the critically ill and then recovered, and hundreds of man-made travel PENG busy. 21 days, across both the old and the new Lunar New Year, but also across the life and death and beyond something.

    Observation period is still


    Since cold temperature, in Shanxi Province by the end of February is still cold.


    Shanxi Xiaoyi City Indus Village before the town is home PENG's Grandpa.



    Su Fang, director of the village health clinic every day to do door-to-door check for PENG, Xiaoyi City People's Hospital's experts also regularly follow-up to the village.


    Discharged February 3, the PENG good body no longer has a fever cold. A few days ago, Grandpa and Grandma go to the city with PENG two chest X-ray film, the situation is normal.


    PENG has at least six months observation period, every month, wanted to go to Taiyuan Fourth People's Hospital, a review by local doctors and nurses Xiaoyi special vehicles, the journey around 2 hours.


    Observation period was not strict requirements, and hospitalization ago, PENG life has been little change. PENG worried because playing much running will cough, originally strapped teeth Grandpa and grandma one, spent more than 800 yuan bought a electric toy car. PENG but only occasionally to play a while, more often and Sisters is still rough, happy when sisters hold each giggle. Only in the face of a stranger when, PENG will shrink to Grandpa behind, carefully looking at each other.


    Master of avian flu infection, PENG also under the age of three, is the person currently known avian flu patients, the youngest one. At the same time, she is also infected early eight patients, one of the earliest rehabilitation. The remaining seven patients, only 2 people eventually recovered.


    PENG does not know these, it would not care about. She was concerned that when the mother returned with her, when Hunan PLAYING again.


    Years ago, the pro tour in Hunan Province, to her and her family brought about by the disaster, are the three-year-old girl in any case can not be clearly known and understood.


    Suspected bird flu


    End of last year, PENG Yan-Mei He Weifang mother with two daughters went to Changsha, to visit his father at home job. except to accompany his mother went to market, and to do business aunt live rice, PENG how little out of the house, which was not quite satisfied with her.


    New Year's Day after his grandma and Grandpa suddenly came to Changsha, PENG put back to Shanxi.



    This is because HE Wei Mei (mother of Peng -Fla1) suddenly fell ill was admitted to hospital where he died a week after the announcement, the hospital's diagnosis was "severe pneumonia with acute respiratory distress syndrome."


    To make matters worse, PENG also begin fever. Back in Shanxi, the disease more and more serious, Grandpa He Hangen cloud that a child is just beginning on the road with tired, and can be PENG situation does not improve. Several urban areas in the village and hospital treatment is not effective after January 14, HE Han-yun and his wife to hurry with the granddaughter of the provincial capital Taiyuan.


    6:00 that evening, PENG was admitted to Children's Hospital of Shanxi Province. The chief physician on duty KANG Yu Zhang recalled that at the time the immediate girls pale gray hair, lips purple, and dull eyes, breathing shallow and promote, and even have no response to an acupuncture treatment.


    KANG Yu Zhang hastily asked 25-year executive director of the Medical Hao-ping. From the chest, the lung inflammation PENG extremely serious: white shadows of the lungs accounted for two-thirds of the total area, nearly half of the loss of respiratory function.


    Grandpa talk He Hangen cloud at the side of the family misfortune. When it comes to the child's mother a week ago of pneumonia at the time of the death of Hunan, vocational-sensitive so that the two doctors called to the elderly.


    "The child and her mother come into contact with live birds吗?"

    "Come into contact with, PENG's aunt on the sale of chickens and ducks in the live poultry market."

    People highly pathogenic avian influenza? KANG Yu Zhang said that when she and to look for a long time, chilling.


    Check-SARS wards


    Easy to discuss a bit, two doctors immediately reported to the Medical Service hospital immediately PENG quarantine measures taken, to the pediatric emergency center 100,000 to clean up the air pressure isolation wards, on the full range of emergency care equipment.


    Ex post facto analysis of the Ministry of Health experts believe that the reason why PENG can receive timely treatment and rehabilitation, first of all, thanks to early detection, from admission to isolation was found to less than two hours.


    Children's Hospital, director of leadership and the department have been recruited through the night to discuss the emergency hospital, diagnosed as pneumonia of unknown causes, that is people-specific SARS and bird flu, people are one of a high degree of suspicion of avian influenza. This conclusion promptly report to the Shanxi Provincial Health Department Emergency Response Office.


    Early the next morning, all the best medical experts in Taiyuan has been organized for a second consultation PENG. After a comprehensive analysis, the Group believes that children with symptoms of pneumonia of unknown causes in line with the standards, the network agreed to direct the Ministry of Health reported.


    January 15 afternoon, Shanxi Province Health Department of Health announced the launch emergency plan to respond to two. That night, PENG blood, it kind of secretion samples and related directly to Beijing.



    Ministry of Health dispatched two experts - Beijing Children's Hospital Professor Qian Suyun, First Hospital, Peking University Professor Wang Guangfa emergency "airborne" Taiyuan, meanwhile brought 100 milliliters Kexing Chinese companies and disease control of R & D-specific antibodies in plasma, In addition, the antiviral drug Tamiflu have effects. Later, the results proved that the plasma in the treatment process has played a good role.


    January 17, the Ministry of Health Office emergency response communications: Chinese Center for Disease Control and Prevention and the Chinese Academy of Medical Sciences of Shanxi censorship "unexplained pneumonia cases" Detect review samples, the results for the H5N1 avian influenza virus type, the cases of human infection confirmed cases of highly pathogenic avian influenza.


    According to the deployment of Health Department of Shanxi Province, Taiyuan PENG was emergency transferred to the Fourth People's Hospital emergency ward. This has more than 70 beds are in the building board room during the SARS emergency built, known as the "Shanxi Xiaotangshan." When the last SARS patient discharged from hospital cured, it no longer stationed in sick, in addition to regular disinfection, perennial locking gate.


    6 years after the SARS isolation wards have been re-enabled.


    Injection of "Wahaha"


    Children's Hospital of Shanxi Province, Liu Ke, deputy director of respiratory led war, and the Ministry of Health, Taiyuan four hospital peer together to form, including first aid, respiratory, radiology, paediatrics, nursing, etc. 15 person team of experts.


    However, including the Ministry of Health experts, no one met the exceptional cases of avian flu. Liu Ke-war was described as "feeling the stones across the river", "treading on thin ice", each time to fine-tune treatment program, must go through the Group of Experts argued repeatedly to take effect, then a lot of decisions are made at great risk of .
    Think because of being easy to use at the problem, broad-spectrum antibiotic was the first suspension. Soon, in the use of hormones on the Group of Experts had heated discussions. Diagnosis and treatment of atypical pneumonia in the previous on domestic hormone had been caused by improper use of sick "femoral head necrosis" and other sequelae. PENG, taking into account only 3 years old, hormone dosage was gradually have consciously stopped.


    Liu Ke-war said that the treatment of another key point, the patients are the implementation of the "moderate" respiratory support, that is, from top to bottom in the control of oxygen for the effort, it is necessary to meet the physical needs, but also to eliminate the use of breathing machine to the patients hazards.


    Treatment of early, PENG has refused to eat, the Group will move to the book read literacy PENG him, "What to eat? Ice cream? Milk? Wahaha?" When the reference to "Wahaha" when there is feebly PENG locations of the nod. The next two days, using injection needles collected PENG Wahaha calcium milk became the main diet, appetite stimulation, through a child's desire to survive.


    The Group believes that nutrition support can be provided for the treatment of much help to restore digestive function the first time, be able to quickly put nutrition to keep up with the years, in fact, any transfusion are the recovery of gastrointestinal function can not be replaced on the body to help.


    To pay
    At the same time, Taiyuan, Luliang city activated the human avian influenza contingency monitoring, reporting and implementation of epidemicd ay. 67 close contacts have also been isolated, beginning a sustained 15-day medical observation. HE Han-yun on one side of the isolation wards, totally do not know the world outside. In order to meet granddaughter, burning several attempts from jumping through the window of the elderly, health care workers were finally persuaded under.


    January 20, held at the Ministry of Health Human bird flu prevention and control work on television and telephone conference, Health Minister Chen Zhu, in particular regard to the Shanxi told: at all costs for medical treatment in children, children with treatment successful, will the National Human bird flu prevention and control work has great significance.


    Price quickly emerged - PENG admitted at the news, Children's Hospital of Shanxi Province and Taiyuan Fourth People's Hospital Outpatient Visits rapid decline, and even less than one-third of the same period last year.
    S
    hanxi Province Health Department director of high Guoshun commented that this is the price, are to pay.


    Eventually recovered and were discharged


    3 days later, after a group of experts carefully rescue, PENG start of the vital signs gradually stabilized.
    Experts in private joke, saying that it remanded back to betting yes.
    PENG state of getting better. A few days, she has been accustomed to watch the wearing think can only see the eyes of the people begin to see father mother exclaimed.


    Liu Ke Zhan and his colleagues take turns waiting, and the development of early psychological intervention plan, to accompany PENG play chat, and enhance her sense of identity. Later, PENG direct isolation wards where male doctors called the "father", female doctors and nurses called "Mother."


    However, the risk may occur at any time. LUO Hong-rounds in a Doctor inquiry, PENG suddenly cough up, droplets of the LUO Hong-splashed face. First time wards silence, all terrified, hastened to allow Tamiflu dose LUO Hong prevention.


    Then a few days, even if the cessation of oxygen PENG can and "mother" are playing, no longer coughing, lungs mutant images show obvious absorption, increasing the normal indicators of the signs.


    Ministry of Health experts early withdrawal.



    Chinese New Year's Eve evening, the night shifts round the head nurse does not remain in the hospital accompanied Lei PENG Chinese New Year.



    PENG three are the first two days the first month birthday, where all those involved in health care workers have to get together for PENG bought a variety of toys and gifts at ward installed colorful lanterns, the hospital also bought specially give PENG birthday cake.


    Zhang Lei, a smile recalled that PENG only eyes before looking at the "father", "mother" who playfully asked: "Why do not you mouth? how you?" Comparison of PENG Gang admitted to hospital at the time of appearance, Zhang Lei said that she felt very happy.


    February 3, at 21 days after admission, in accordance with the criteria established by the Ministry of Health, PENG was declared recovered and been discharged. Guoshun high up in the farewell ceremony, said the rehabilitation of PENG that people bird flu is preventable and governance.


    Has been hiding in the corridor of Zhang Lei is very sad, because after take off small PENG actually did not recognize her, not her mind. Until she gently shouted the name PENG, PENG only excitedly shouted "Zhang mother," quickly came running Zhang Lei's bosom.


    Zhang Lei no longer could, tears eyes. Call him a lover of the phone, loudly exclaimed: "I want children." Reporter Dong Tang
    更多精彩内容请登录京华网( www.jinghua.cn )
    More exciting content, please log in jinghua Net (www.jinghua.cn)


    http://epaper.jinghua.cn/html/2009-0...ent_399595.htm

  • Sally Furniss
    replied
    Re: China &amp; Egypt Using AntiBody Plasma Treatment to Cure Bird Flu Cases

    Call for blood donations for H1N1 in China
    Hebei called H1N1 influenza vaccine by patients and blood plasma
    ..Disease Control network, recently, Hebei Province, called influenza H1N1 influenza vaccine patients or those who contribute to caring, enthusiastic voluntary blood donation, for the treatment of patients with severe or critical.
    ... Medical Practice has proved that influenza A H1N1 influenza vaccine were recovered or the plasma containing the corresponding antibodies to the virus can be used for critically ill patients with severe or treatment.
    ..Hebei Province Health Department called on the age of 18-55 years old, recovered and was discharged home after 1 week or 2 weeks after the treatment of symptoms of influenza A H1N1 influenza patients, or the vaccination in January after the vaccination, please voluntary blood donation contribute to caring for critically ill patients relief.

    Leave a comment:


  • sharon sanders
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    hat tip Revere -
    Important flu paper on immune response

    Category: Bird flubiology
    Posted on: April 21, 2009 6:16 AM, by revere

    <!--proximic_content_on--> Every day, it seems, we find out that what we thought we knew about flu isn't the case. As one noted flu expert said to me once, "I knew much more about flu 20 years ago than I do now." So it's good to remember that we are also finding out a lot about flu that we never knew or even thought we knew. A case in point is an extremely important new paper in PLoS Medicine ( Khurana S, Suguitan AL Jr., Rivera Y, Simmons CP, Lanzavecchia A, et al.(2009) Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets. PLoS Med 6(4): e1000049; online as of last night). This work makes a major advance in the science of antibody response to avian influenza/H5N1 ("bird flu"). The advance has two aspects. One is the information the work generated. Even more important is the second part: opening up specific new questions for further research.

    Unlike much H5N1 work, this isn't based on experiments in mice, as important and fruitful as such work is and has been. Instead it examines the antibody response of victims of a 2004 bird flu outbreak in Vietnam. Of 18, 13 died. Blood samples were obtained from the survivors during their recoveries. These patients lived long enough to get a response from the part of their immune system that makes antibodies. What did that antibody response look like?

    The question is a difficult one to answer. In analogy with how we recognize other people, you might think of the features of the virus, as seen by the immune system, to be like what clothes it's wearing, what style and color they are and what tools the virus is using. Just as we only use some features of another person for recognition -- for example, we usually don't pay attention to their elbows as a way to recognize them but do notice their hair color -- our immune system also notes only certain features of the virus. But which ones? There are many practical and scientific reasons for wanting to know this. The presence of these specific antibodies might be useful for a marker of past infection, for example, or may signal a vulnerable part of the virus to attack with drugs or vaccines. We know that the antibody response is not confined to a single recognition feature but may involve many. Not surprisingly some of the most prominent signals for antibody response are the ones prominently displayed on the surface of the virus (where they are easily "seen"), particularly on the hemagglutinin (HA) protein. As a result, this protein has a tendency to change rapidly as it comes under selective pressure from the immune system. That's why we need different flu vaccines each year and why one form of flu doesn't protect us from others or even last year's. Is the HA protein the only recognition feature? Most of what we think we know about the human response to H5N1 comes from mouse experiments or analogies with human responses to seasonal influenza. As a result of this paper we now know much more about human response to H5N1 and, as importantly, we are pointed in directions to look for more answers.

    So what was done and how? The international team of researchers (US FDA/NIH, Oxford, Vietnam, Switzerland) took the antibody-response-containing serum of the H5N1 survivors and tested it against most of the proteins from the responsible viral isolate (A/Vietnam/1203/2004 (H5N1)), using whole-genome-fragment phage display libraries (GFPDL) to figure out the antibody targets. In addition they used a similar technique to explain why two pure (monoclonal) antibodies obtained from the blood of four of the same patients had different kinds of protection against other flu virus. Both protected against infection against closely related virus as the original infection (clade 1 on the family tree), but only one also protected against more distantly related bird flu virus from clade 2 (from Indonesia). Why?

    Here's a brief description of GFDPL. Genetic material from all eight segments of the H5N1/A/Vietnam virus (that's the whole-genome part) was inserted into the genetic program of a bacteriophage. A phage is a virus that infects bacteria. When it gets into the bacteria it does the same thing that viruses do when they infect our cells: it hijacks the bacterium's protein making machinery for the sole purpose of making copies of itself. Because fragments of the flu virus's genome have been included in the coat making gene of the bacteriophage, tremendous amounts of bacteriophage bearing viral protein fragments on their surface are produced. Each bacteriophage virus has only one such fragment, but in totality they display a whole library's worth of fragments, one per bacteriophage virus. I'm making this sound too simple, of course. Separating the different library volumes (each bearing a specific flu virus protein fragment) is an arduous process (called "panning," as in panning for gold). It involves repeated enrichment of the specific fractions. The science behind this marvelous, but it is always important to remember implementing it is usually hard work at the bench, much of it tedious, boring and often unsuccessful. A lot can go wrong along the way of an experiment with possibly dozens of sequential actions. We don't see this in the finished paper. After the climb to the level of reliable results, the difficult experience on the ladder becomes invisible. Anyway, using this technique and a closely related one (random peptide libraries) the NIH researchers and their colleagues were able to do two things. One was explain why the monoclonal antibodies acted differently on the two clades of H5N1. The other was to identify many new recognition targets ("epitopes") used by the immune systems of the Vietnamese patients to make antibodies.
    First the monoclonals. The antibody that only worked on clade 1 viruses targeted a portion of the HA (hemagglutinin) protein (L129) that differed in clade 1 and clade 2 viruses. That difference was enough to make the first monoclonal only work on clade 1. The second monoclonal, by contrast, targeted a portion of the HA that was identical in clade 1 and clade 2. In both cases the recognition sequences were on parts of the protein that were separated from each other in the protein sequence but which came close together when the HA was folded (think of a bunched up string that might have its two ends close together although they are on opposite ends). And while both of the recognition targets were in t receptor binding site, the second monoclonal bound to the viral protein target much more tightly than the first, suggesting that it is not only what an antibody recognizes that might be important but how tightly it binds to the recognition site. More research to do.

    What about the repertoire of targets seen in the patients? In other words, what other antibodies were in their sera and what were they directed against? Studies on mice mainly involve the HA protein, but this work revealed still more HA targets not known from mice and targets on neuriminidase (NA), M2e, M1 and NP. In addition, there were antibodies against the reading frame variant from PB1-F2. This is a protein that is not part of the viral structure but only appears when the virus is infecting someone. While we know something about it in experimental systems, there had never been solid evidence that it was being expressed in infected people. Not only is it being expressed, but this study suggests it is seen by the immune system and is a target.
    We still don't know if the antibodies in the survivors had anything to do with their survival. It may be that it is the other way around. The fact that they survived allowed enough time for their bodies to make antibodies. Do any of these targets involve viral clearance? Which ones? Which ones involve protection against the virus? Many of these antibody targets aren't seen in seasonal flu cases. Which ones are the result of the very severe pathology of bird flu rather than the virus itself? Can any of these antibodies be used to detect past infections that weren't apparent at the time?

    It's clear this paper is hardly the last word on the subject. On the contrary, it is more like the first word. There is much I left out of interest (PLoS Medicine is open access so you can read the paper and the accompanying editorial; the Editor's explanation at the end is quite understandable), but of greater importance is the door to further research it opens.

    This is very interesting research and tremendous fun to read. Fun or not, though, it is about a deadly serious problem. So any progress is welcome. And this is real progress.

    Leave a comment:


  • tropical
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    Originally posted by SuperNova1987A View Post
    From “Kansen Retto” (Pandemic Archipelago), a Japanese pandemic movie.

    After all attempts of treatment failed, a doctor tries convalescent blood
    transfusion into a teenage girl infected with a mysterious disease…

    (QUOTE)

    “At the time of a fight against Ebola in Africa, mortality rate was too high and
    doctors were totally overwhelmed. As a last resort, someone proposed to
    transfuse into suffering patients the blood of a person who had recovered
    from Ebola in the hope the antibody in the blood would work on Evora. It was
    a treatment that had any medical justification.

    European doctors opposed but Zairean doctors forced through. There was
    nothing else they could do and they were desparate to save their peers. Five
    out of eight patients survived.”

    (UNQUOTE)

    …and the girl survives.


    ____________________
    SN1987A
    In one of the H. Bransw. book, it is described such an treatment.

    In those days described in the above book, the Ebola reservoir was stil unknown (now discovered to be the fruit bat probably).

    Leave a comment:


  • SuperNova1987A
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    From “Kansen Retto” (Pandemic Archipelago), a Japanese pandemic movie.

    After all attempts of treatment failed, a doctor tries convalescent blood
    transfusion into a teenage girl infected with a mysterious disease…

    (QUOTE)

    “At the time of a fight against Ebola in Africa, mortality rate was too high and
    doctors were totally overwhelmed. As a last resort, someone proposed to
    transfuse into suffering patients the blood of a person who had recovered
    from Ebola in the hope the antibody in the blood would work on Evora. It was
    a treatment that had any medical justification.

    European doctors opposed but Zairean doctors forced through. There was
    nothing else they could do and they were desparate to save their peers. Five
    out of eight patients survived.”

    (UNQUOTE)

    …and the girl survives.


    ____________________
    SN1987A

    Leave a comment:


  • Giuseppe
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    Dextran is used in patients with volemic shock and for its supposed anti-infective properties:

    From PubMed:

    1: Hayashi T.
    [Studies on evaluation of natural products for antiviral effects and their
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    2: Maa YF, Ameri M, Shu C, Payne LG, Chen D.
    Influenza vaccine powder formulation development: spray-freeze-drying and
    stability evaluation.
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    4: Bergstrom DE, Lin X, Wood TD, Witvrouw M, Ikeda S, Andrei G, Snoeck R, Schols
    D, De Clercq E.
    Polysulfonates derived from metal thiolate complexes as inhibitors of HIV-1 and
    various other enveloped viruses in vitro.
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    5: Matiushichev VB, Potapenko LB, Dement'ev AA, Sokolov IN.
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    Klin Lab Diagn. 2002 Feb;(2):19-21. Russian. No abstract available.
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    Fusion and infection of influenza and Sendai viruses as modulated by dextran
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    9: Lüscher-Mattli M, Glück R, Kempf C, Zanoni-Grassi M.
    A comparative study of the effect of dextran sulfate on the fusion and the in
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    PMID: 8517791 [PubMed - indexed for MEDLINE]

    10: Krumbiegel M, Dimitrov DS, Puri A, Blumenthal R.
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    PMID: 1463322 [PubMed - indexed for MEDLINE]

    12: Balzarini J, Neyts J, Schols D, Hosoya M, Van Damme E, Peumans W, De Clercq
    E.
    The mannose-specific plant lectins from Cymbidium hybrid and Epipactis
    helleborine and the (N-acetylglucosamine)n-specific plant lectin from Urtica
    dioica are potent and selective inhibitors of human immunodeficiency virus and
    cytomegalovirus replication in vitro.
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    PMID: 1329650 [PubMed - indexed for MEDLINE]

    13: Hosoya M, Balzarini J, Shigeta S, De Clercq E.
    Differential inhibitory effects of sulfated polysaccharides and polymers on the
    replication of various myxoviruses and retroviruses, depending on the composition
    of the target amino acid sequences of the viral envelope glycoproteins.
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    PMID: 1725692 [PubMed - indexed for MEDLINE]

    14: Lüscher-Mattli M, Glück R.
    Dextran sulfate inhibits the fusion of influenza virus with model membranes, and
    suppresses influenza virus replication in vivo.
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    PMID: 2080868 [PubMed - indexed for MEDLINE]

    15: De Clercq E.
    Selective virus inhibitors.
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    Leave a comment:


  • Giuseppe
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    I think we should also search for Dextran Sulfate and derivatives, as these compounds were already widely studied in relation to other infectious diseases, notably in early stage of HIV/AIDS pandemic.

    Leave a comment:


  • Sally Furniss
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    Blood Shelf Life

    The blood stock has to be replaced regularly to keep a current supply of fresh blood and blood products. Blood products are refrigerated and all have a different shelf-life.

    * Red blood cells have a shelf life of forty-two days.
    * Plateles have a shelf life of five days
    * Fresh Frozen Plasma have a shelf life one year.
    * Cryoprecipitate have shelf life of one year.
    * And Frozen Plasma have a shelf life of four years.

    http://www.health.gov.mt/nbts/bldshelf.htm

    Leave a comment:


  • Sally Furniss
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    Meta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment?

    Thomas C. Luke, MD, MTMH; Edward M. Kilbane, MD, MPH; Jeffrey L. Jackson, MD, MPH; and Stephen L. Hoffman, MD, DTMH

    17 October 2006 | Volume 145 Issue 8

    Background: Studies from the Spanish influenza era reported that transfusion of influenza-convalescent human blood products reduced mortality in patients with influenza complicated by pneumonia. Treatments for H5N1 influenza are unsatisfactory, and convalescent human plasma containing H5N1 antibodies could be an effective therapy during outbreaks and pandemics.

    Purpose: To see whether transfusion with influenza-convalescent human blood products reduced the risk for death in patients with Spanish influenza pneumonia.

    Data Sources: Manual search of English-language journals from 1918 to 1925. Citations from retrieved studies were also searched.

    Study Selection: Published English-language studies that had at least 10 patients in the treatment group, used convalescent blood products to treat Spanish influenza pneumonia in a hospital setting, and reported on a control or comparison group.

    Data Extraction: Two investigators independently extracted data on study characteristics, outcomes, adverse events, and quality.

    Data Synthesis: Eight relevant studies involving 1703 patients were found. Treated patients, who were often selected because of more severe illness, were compared with untreated controls with influenza pneumonia in the same hospital or ward. 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). The range of absolute risk differences in mortality between the early treatment group and the late treatment group was 26% to 50% (pooled risk difference, 41% [CI, 29% to 54%]). Adverse effects included chill reactions and possible exacerbations of symptoms in a few patients.

    Limitations: Studies were few and had many methodologic limitations. No study was a blinded, randomized, or placebo-controlled trial. Some pertinent studies may have been missed.

    Conclusions: Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 plasma could be an effective, timely, and widely available treatment that should be studied in clinical trials.

    http://www.annals.org/cgi/content/fu...610170-00139v1

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  • Gert van der Hoek
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    http://www.hkam.org.hk/publications/...m0612p489a.pdf

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  • Gert van der Hoek
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    Could blood from H5N1 flu survivors help others?

    Robert Roos News Editor

    Sep 8, 2006 (CIDRAP News) – A recent report about the use of blood products to treat patients in the Spanish influenza pandemic of 1918 has sparked interest among those concerned about the threat of the next pandemic, but experts say it's far from clear whether the approach would be practicable in a pandemic today.

    In a report published last week, US military researchers said blood products obtained from recovering influenza patients apparently helped save the lives of some patients in the 1918 pandemic, and the same approach should be considered today in the face of another pandemic threat.

    Combing the medical literature from the Spanish flu era, the researchers found six controlled studies in which the use of blood plasma, serum, or whole blood from recovering flu patients reduced mortality in seriously ill patients. The authors hypothesize that antibodies in the blood products blunted the effects of the flu virus.

    "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," say Thomas C. Luke, of the Navy Bureau of Medicine and Surgery, and colleagues. Their report was published online by Annals of Internal Medicine.

    Luke and colleagues write that borrowed antibodies in blood products have been used to prevent and treat a number of infectious diseases, including rabies, measles, hepatitis B, cytomegalovirus, and respiratory syncytial virus.

    Six studies showed benefit
    The authors searched eight major medical journals for controlled trials of the use of blood products from recovering flu patients to treat a minimum of 10 severely ill patients. They found eight studies that met their criteria, ranging in size from 43 to 551 patients, with a total of 1,703. None of the trials was blinded or randomized, and the methods were rated as poor by today's standards. Most of the patients were men between the ages of 17 and 45.

    Six of the eight studies showed that the treatment improved survival. The overall case-fatality rate for treated patients was 16% (54 of 336), versus 37% among the controls (452 of 1,219). In addition, all eight reports said that patients showed clinical improvement after treatment. Moderate to serious transfusion-related adverse events occurred in 4% (9 of 235) of patients in studies that included such data.

    The timing of treatment made a difference. On the basis of data from four studies, patients treated within 4 days of the onset of pneumonia had an overall case-fatality rate of 19% (28 of 148), whereas those treated later had a fatality rate of 59% (49 of 83).

    Acknowledged limitations of the analysis include the small size of the studies, the lack of blinding, and the lack of placebo treatment. The authors also say they can't exclude the possibility that other studies yielded negative findings but went unpublished. Therefore they couldn't reach a firm conclusion about the effectiveness of the treatment.

    Nonetheless, they recommend that a committee of experts be set up to consider using plasma treatment for H5N1 patients and to recommend a research strategy.

    In an editorial accompanying the report, John J. Treanor, MD, an infectious disease expert at the University of Rochester, says the strategy deserves consideration, but he also raises some caveats.

    Passive immunotherapy for flu viruses, including H5N1, has worked in lab mice, Treanor writes. Such treatment prevents many viral diseases in humans, but little recent evidence supports using this approach to treat sick patients, he says. Also, obtaining and using blood products for treatment in the midst of an outbreak would involve "formidable logistical hurdles."

    Proving the concept of "serotherapy" for H5N1 would require running controlled trials in regions where human H5N1 cases are occurring, Treanor asserts. He believes the effort would be worthwhile: "We can, should, and must explore these issues about serotherapy now, in advance of the pandemic."

    Serotherapy called impractical
    Other experts who were asked about using this approach in the next pandemic expressed views ranging from guarded interest to dismissive skepticism.

    Michael T. Osterholm, PhD, MPH, didn't question the scientific plausibility of the idea, but argued that it wouldn't be practical in a pandemic. Osterholm is director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of the CIDRAP Web site.

    "We won't have the capacity to do much plasmapheresis [harvesting of plasma] of recovered patients because the system—healthcare workers and equipment—will collapse," Osterholm told CIDRAP News. "And with today's safety regulation, you couldn't do it like you did in 1918."

    He said supplies and equipment needed for blood transfusions and processing are likely to run out. "The entire healthcare system is a just-in-time delivery system for virtually everything. . . . You couldn't do it if you wanted to, because you just won't have the equipment. Blood banks don't have months and months of inventory on hand. The bags, tubing, needles, and reagents are made offshore."

    "Transfusion medicine is going to be severely challenged during a pandemic," Osterholm said. "Just transfusing the blood we need [will be difficult], let alone doing this kind of thing."

    Blood-bank official sees logistical problems
    Louis Katz, MD, chair of an American Association of Blood Banks task force on pandemic flu and the blood supply, acknowledged that supplies are likely to be a problem but said that using plasma from recovered patients could be helpful in a pandemic.

    The idea "is something we're trying to think about, but it hasn't made it into the first edition of our pandemic flu planning guidelines," said Katz, who is executive vice president of the Mississippi Valley Regional Blood Center in Davenport, Iowa.

    He said blood banks are likely to run short of both personnel and supplies in a pandemic, but supplies are the bigger worry.

    "We take delivery twice a month on critical lab reagents and once or twice a month on pheresis kits, so the maximum [inventory on hand] is a month," Katz said.

    His center doesn't have space to store 8 to 12 weeks' worth of supplies, and even if it did, suppliers might not be able to ramp up deliveries to permit stockpiling, he said. "The just-in-time economy has its advantages in terms of efficiency, but in a crunch there are serious problems," he added.

    Further, few recovered flu patients would be available to donate plasma in the early stage of a pandemic, Katz said. "I think there are substantial barriers to providing a lot of it during the first wave." He predicted the task would be "substantially easier" in the second wave of a pandemic.

    Katz thinks blood banks could get recovered patients to donate plasma, but not until weeks into the pandemic. "I think they'd come in, but whether we could process enough [blood products] to treat meaningful number of patients, I don't know," he said.

    If the pandemic resembled those in 1957 and 1968, in which "business operations weren't horribly disrupted, we probably could ramp up and make immune plasma fairly quickly," Katz said. "It totally depends on what happens."

    Another question is whether the Food and Drug Administration (FDA) would approve the use of blood plasma to treat flu patients. "It's complicated, but it becomes an issue of labeling," Katz said. "As long as I didn't label it 'hyperimmune influenza plasma,' I think they'd be fairly permissive." Before allowing such a label, the FDA would require clinical trials and other steps to certify the safety, purity, and potency of the product, he said.

    Summing up his thoughts on the topic, Katz said, "While theoretically it's a great idea, the logistics are going to be difficult."

    Dr. Jed Gorlin, medical director of Memorial Blood Centers in St. Paul, said the concept of using plasma to treat flu patients has been under discussion in blood-bank circles for a while.

    Gorlin said blood banks are worried about shortages of blood donors and of staff to collect blood in a pandemic. But he was more optimistic than Katz on the question of supplies and equipment.

    The 1918 flu pandemic lasted about 2 months in most places, he said, adding, "For things like bags and so on we easily have a month and often 2 months, so that part we're not particularly concerned about." On the other hand, other supplies, such as N95 breathing masks, may well run out, he said.

    "Blood centers are ahead of most hospitals in that we already have lists of critical reagents and equipment," Gorlin said. "We're already sensitive to our supply chain and in some cases we have alternative suppliers."

    Transfusion specialist interested
    Robert J. Bowman, MD, a transfusion medicine specialist at the University of Minnesota Medical School in Minneapolis, called the proposal "very interesting," at least theoretically.

    "I am unsure of the relative success of immunoglobulin preparations in treating viral illness but given the paucity of treatment options the strategy ought to be tried," he commented by e-mail.

    Criteria for acceptance of plasma donors would have to be developed, he said. Plasma could be tested for antibodies and used directly, or many units could be pooled and used to make a standardized intravenous immunoglobulin preparation (IVIG), he suggested.

    "Not only do I think this is possible, I think the idea should be tried with standardized IVIG preparations," Bowman wrote. If the treatment worked, its applicability would depend on collection agencies having enough staff and enough money to pay for the IVIG, he added.

    Bowman predicted that safety and other regulatory issues would be "manageable," but he acknowledged that supply interruptions could be a problem.

    He also said he was uncertain how much IVIG would cost or how long it would take to prepare. "We're not talking about days, we're talking weeks or months," he said. "It takes some time to pool it, then you have to fractionate it, and then there's testing. So it's a big deal. But all the technology is there."

    Luke TC, Kilbane EM, Jackson JL, et al. Meta-analysis: convalescent blood products for Spanish influenza: a future H5N1 treatment? Ann Intern Med 2006 Oct 17;145(8) (early online publication) [Full text]

    Treanor JJ. Avian influenza: exploring all the avenues. (Editorial) Ann Intern Med 2006 Oct 17; 145(8) (early online publication) [Full text]

    http://www.cidrap.umn.edu/cidrap/con...0806blood.html

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  • Gert van der Hoek
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    March 3, 2007

    Originally posted by Dutchy

    Farmer cured of bird flu donates serum for treatment of new human infection

    The farmer from East China's Anhui Province, who contracted the deadly H5N1 strain of bird flu last December but was later cured of the avian disease, was called in to donate his serum for treatment of another rural Chinese woman who was confirmed last month to have been infected of the same virus.

    Xu Longshan, spokesman and chief of the Fujian Provincial Professional Panel for Prevention and Control of Human Infection of Bird Flu, told Xinhua Saturday health workers from Anhui Province Thursday escorted the farmer, identified by his surname as Li, to Fuzhou, capital of Fujian Province, where experts from the blood center affiliated to the Fujian Provincial Bureau of Health got serum from him the second day.

    Li has returned back home.

    "The serum was brought to Jian'ou on the same day, and so far, medical workers have carried out the first round of injection on the woman who was just confirmed of being infected of the lethal strain of the avian disease," said Xu.

    "The method is new but is for sure to be of some effect in improving the woman's capability of fighting against new rounds of infection," said Xu, who admitted it would take some time before the woman could develop immunity of her own against the avian disease.

    Li from Fujian, 44, is a native of Damiao Village, a marketplace in the mountainous township of Xiaosong. The woman, who kept five chickens at her home, developed symptoms including fever on Feb. 18. She had visited village clinics and township hospitals before being hospitalized on Feb. 24 in the Jian'ou City hospital.

    She was confirmed to be infected with the virus by the Chinese Center for Disease Control and Prevention on Feb. 27. She is known to have eaten two chickens she had raised, but her husband and son, who also ate the chicken, have not developed bird flu.

    According to Xu, the woman patient was found with inflammation on her left lung when she came to the hospital on Feb. 24, but her pneumonia symptoms developed quickly and she went into a coma the next day. A chest X-ray on Feb. 25 shows large shadows on her lungs.

    As of Thursday evening, Li's body temperature and pulse had returned to normal, and her lungs and breathing appeared to be functioning better but she was still breathing with the help of a respirator, Xu said.

    Doctors say Li is still in a critical condition and they are trying to boost her immunity to prevent further organic infection.

    Over ten doctors and medical experts from local hospitals, and Beijing-based Chaoyang Hospital and Ditan Hospital are trying to work out a detailed treatment plan to save Li, said Xu Yongxi, head of the hospital.

    Policemen and hospital staff have been seen guarding the ward where the patient is staying and doctors are wearing thick, disinfected suits.

    The patient's husband is with her in the hospital, and her 13-year-old son, who now stays in her four-storey house with his grand-mother, looked saddened, and said he hoped his mother could recover soon.

    Li from Fujian is the country's first human case of bird flu in seven weeks since China reported on Jan. 10 that the other Li from Anhui, 37, had contracted bird flu last December but had recovered.

    The deadly H5N1 strain of bird flu has killed 14 people in China since 2003.

    Source: Xinhua

    http://english.peopledaily.com.cn/20...03_354016.html

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  • Gert van der Hoek
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    google translated; probably posted before.

    Unique governance avian serum to save patients

    2007-12-11

    Jiangsu confirmed the second case of highly pathogenic avian influenza in patients with Human Lu Wei is currently in stable condition. It was revealed that Lu Wei's body temperature has been normal, the lung inflammation also has changed for the better, and can eat normally, the patient's mood is also very stable. Containing avian influenza antibodies in human serum, for the treatment play a key role. \ 【Newspaper reporter on the 10th Nanjing Min electric】

    According to informed sources revealed that Lu Wei in late December 3 fever symptoms, throat swelling at the same time, symptoms such as generalized weakness, that is "double pneumonia under" hospital treatment. Diagnosed as being infected with highly pathogenic avian influenza, the Mainland medical treatment for his attention. National Chinese Health Minister Chen Zhu himself as team leader, and lived in Nanjing for this purpose for several days, several cases take part in discussions, listened carefully to the disease analysis and expert advice, and medical experts to discuss the development of treatment programs.

    Minister of Health appointed expert, head of

    It was revealed that because of pulmonary inflammation, Lu Wei两肺the emergence of large shadow, the experts have focused on him to take the antiviral drug treatment, nutritional support and hormone therapy, infusion every day and constantly adjusted according to disease agents now has been at the gradual improvement of inflammation.

    According to the experts involved in treatment, the patient is currently in stable condition and no complications, but in the future will continue to observe the situation. The expert, easily said, "not a big problem."

    Vaccine volunteers donate blood to save people

    It was revealed that the disease was diagnosed when Lu Wei, his relatives as soon as the Internet has on the body english avian influenza antibodies and blood group matched with his people, they first found a 44-year-old farmer, the farmers are suffering from bird flu after a successful blood transfusion treatment of others, but to do the work anyway, the farmers are reluctant to lose their serum Lu Wei.

    Subsequently, there is a laboratory job at the hospital volunteers, he had injected the bird flu vaccines, blood containing anti-bird flu body, he also happened to the blood group B, and Wei Lu of the B blood type match. Therefore, Lu Wei give input in two of the 200 milliliters of serum, a total of 400 milliliters.

    Allegedly, this is 400 milliliters contain the avian flu antibodies in serum on the success of Lu Wei treatment has played a pivotal role.

    Insiders revealed that the death of the first cases of human highly pathogenic avian influenza陆侃patients, the cause of death is precisely because the absence of timely and correct treatment, because the incidence him, all people have had I thought of the bird flu are just at him only aware of the death fast, but the rescue is late again.

    But was seen off at the cremation of the deceased Grandfather

    According to relatives said that they go out with a family of four individuals playing the home in recent years are a very rare thing, usually because the U.S. is busy all the time together total less than together.

    This family misfortune very saddened by the insiders, it is known, when cremation陆侃all relatives are not allowed to look at the scene (both in medical observation in isolation), only that time had not come into contact with the grandson of a person wearing a Grandfather isolation clothing for him to see them off.

    It was also revealed that eating chicken at the same time the mother and girlfriend陆侃blood samples were sent to laboratories in Beijing, the result is negative. Medical experts have said that this may be the two do not belong to her are susceptible due.

    http://www.takungpao.com/news/07/12/11/ZM-835279.htm

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  • Françoise Ramona
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

    Infection pulmonaire par le virus H5N1

    Un patient gu&#233;ri d'une grippe aviaire gr&#226;ce au plasma d'un convalescent

    Des sujets dans une r&#233;gion o&#249; des volailles &#233;taient infect&#233;es avec le m&#234;me type de virus(AFP)

    LE 7 juin 2006, un camionneur de 31 ans sans ant&#233;c&#233;dents a &#233;t&#233; admis &#224; l'h&#244;pital de Shenzhen dans le sud de la Chine en raison d'un syndrome f&#233;brile &#224; 40 &#176;C depuis quatre jours, associ&#233; &#224; une toux et &#224; une expectoration claire. La radiographie pratiqu&#233;e quarante-huit heures apr&#232;s l'admission a r&#233;v&#233;l&#233; l'existence d'un foyer basal gauche et d'opacit&#233;s nodulaires de la plage droite. La PCR r&#233;alis&#233;e le jour m&#234;me &#224; partir d'un pr&#233;l&#232;vement trach&#233;al a mis en &#233;vidence la pr&#233;sence d'un virus H5N1. Un traitement par oseltamivir &#224; la dose de 150 mg deux fois par jour a &#233;t&#233; prescrit le 12 juin. En moins de quarante-huit heures, les l&#233;sions du poumon droit ont diminu&#233; de taille mais, &#224; gauche, l'image restait identique. L'analyse quantitative de la PCR a r&#233;v&#233;l&#233; une augmentation de la charge virale en 26 heures passant de 1,31 10 puissance 5 copies &#224; 1,68 10 puissance 5 copies. Bien que des r&#233;sistances au traitement par oseltamivir aient &#233;t&#233; d&#233;crites, aucun signe en faveur d'une telle mutation g&#233;n&#233;tique n'existait chez ce patient.

    Plasma contenant des anticorps neutralisants. L'&#233;quipe du Dr Boping Zhou a eu l'id&#233;e de demander du s&#233;rum d'un patient convalescent &#224; des coll&#232;gues qui avaient d&#233;j&#224; trait&#233; des sujets atteints de grippe aviaire dans la r&#233;gion d'Angui o&#249; les volailles &#233;taient infect&#233;es par le m&#234;me type de virus H5N1 que dans celle de Shenzhen. Ils ont ensuite inject&#233; 200 ml de plasma contenant des anticorps neutralisants &#224; leur malade &#224; trois reprises en moins de quarante-huit heures. D&#232;s la premi&#232;re administration, la charge virale du patient a &#233;t&#233; r&#233;duite d'un facteur 12 et elle est devenue ind&#233;tectable en trente-deux heures. La radiographie effectu&#233;e le 15 juin a montr&#233; une nette r&#233;duction de la densit&#233; des l&#233;sions du lobe gauche et une normalisation de l'image &#224; droite. Le 16 juin, le traitement par oseltamivir a &#233;t&#233; suspendu et le patient a pu regagner son domicile le 4 ao&#251;t. L'analyse s&#233;rologique a confirm&#233; l'augmentation du taux d'anticorps neutralisants (exog&#232;nes, puis endog&#232;nes) du patient. L'analyse virale a confirm&#233; la similarit&#233; &#224; 99 &#37; des souches de H5N1 entre le patient hospitalis&#233; et le donneur de plasma : il s'agissait de virus Fujian-like H5N1 de clade 2.3 qui avaient &#233;t&#233; &#224; l'origine d'infections dans le sud de la Chine depuis 2005.

    Pour les auteurs, &#171;ce travail confirme l'int&#233;r&#234;t d'une immunoth&#233;rapie passive chez les sujets atteints d'infection par le virus H5N1. Ce type d'approche pourrait &#234;tre obtenue par des anticorps monoclonaux humanis&#233;s ou des anticorps polyclonaux&#187;.

    > Dr I. C.

    &#171; New England Journal of Medicine &#187; du 4 octobre 2007, pp. 1550-1451.

    Le Quotidien du M&#233;decin du : 24/10/2007


    http://www.quotimed.com/journal/inde...N=viewarticle&



    Treatment with Convalescent Plasma for Influenza A (H5N1) Infection


    Volume 357:1450-1451 October 4, 2007 Number 14

    Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

    To the Editor: A previously healthy 31-year-old male van driver presented to a local clinic in Shenzhen, in southern China, on June 7, 2006, with a 4-day history of a high fever (temperature, 39.9&#176;C), chills, and a cough with clear sputum. A chest radiograph obtained on June 9 revealed large opacities in the lower lobe of the left lung. A reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay and an isolate from a tracheal aspirate were positive for influenza A (H5N1) virus. Treatment with 150 mg of oseltamivir twice daily was started at 2 a.m. on June 12 (Figure 1). After 2 days, . . . [Full Text of this Article]


    http://content.nejm.org/cgi/content/extract/357/14/1450

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  • Sally Furniss
    replied
    Re: China &amp; Egypt Using Anti-Body Plasma Treatment to Cure Bird Flu Cases

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

    Originally posted by Florida1 View Post
    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.
    Complications and outcomes

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