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  • #16
    Re: Indonesia H2H Cover-up?

    http://www.recombinomics.com/News/05...sia_Novel.html
    Commentary

    Novel Human H5N1in Indonesia Raises Pandemic Concerns
    Recombinomics Commentary
    May 17, 2006

    The recent large cluster in Indonesia has refocused attention on human-to-human transmission and the novel cleavage site in human HA H5N1. Although cleavage sites can change, there has been no evidence for a species specific change.
    The first H5N1 isolated in Asia in 1996 in the Guangdong goose had the highly pathogenic sequences of RERRRKKR. That sequence has found in the human cases in 1997 as well as most human and animal isolates in Asia. In 2005 milder cases in northern Vietnam had been noted and those cases had lost an R in the cleavage site, which was then RERRKKR. Recently, China released human sequence data and those sequences were closely related to a Fujian strain, which was missing a K, giving the sequence RERRRKR. However, that cleavage site had been found in a duck in Fujian province and had been in bird H5N1 sequences dating back to 2003. The Qinghai strain of H5N1 has a unique sequence of GERRRKKR, which is found in virtually all of the Qinghai isolates, including human isolates from Iraq and Egypt.
    Thus, although the cleavage can change, the change is typically found in both mammals and birds. The bird H5N1 sequences from Indonesia have the common sequence of RERRRKKR and the recent sequences from Indonesia span isolates from 2003 to 2005. However, the human isolate from 2005 has the novel sequence RESRRKKR. This sequence is not found in any of the avian H5N1 Indonesian sequences or any other H5N1 sequence at GenBank. However, the one sequence is not definitive because there are some novel sequences that have not become widespread and may lack significance.
    However, a report that a cat sequence from Indonesia has the same change is cause for concern, as is the comment that many additional human sequences from Indonesia also have the same change. A large number of human isolates with RESRRKKR, in the absence of any avian sequences with RESRRKKR, would indicate that birds were not a source of the human H5N1 infections.
    These data raise concerns that the human sequences are due to infection by H5N1 from other humans or other mammals. Since there have been over 30 confirmed cases of human H5N1 in Indonesia, the WHO private database would have the answer to the frequency of human H5N1 with the novel cleavage site.
    If that data validates the comment that several human and cats sequences have the novel site, then the claims that the human cases were due to poultry infections would be suspect and the limited testing, which requires association with dying poultry should be expanded to those who have bird flu symptoms, but lack a poultry connection.

    Comment


    • #17
      Re: Indonesia H2H Cover-up?

      Well we keep coming back to cats. Though as I understand it they are mainly feral. Did this family have a pet cat?

      Comment


      • #18
        Re: Indonesia H2H Cover-up?

        <!-- / icon and title --><!-- message -->
        Bird flu human-to-human infection feared

        18 May 2006 <TABLE cellSpacing=0 cellPadding=0 width=5 border=0><TBODY><TR><TD height=5></TD></TR></TBODY></TABLE>
        JAKARTA: The World Health Organisation confirmed six more human cases of bird flu infections in Indonesia, including five members of a family whose case has triggered fears of human-to-human transmission.

        "There are six confirmations. One from Surabaya and five from Medan. One from Medan is still alive," said Sari Setiogi, the WHO's Indonesia spokeswoman.
        An outbreak of H5N1 bird flu involving up to eight members of a family at Medan in North Sumatra province has worried health agencies around the world but a Health Ministry official said on Wednesday it was not a case of human-to-human transmission.
        "The spread was through risk factors from poultry or other animals. There is no proof of human to human," Nyoman Kandun, director-general of disease control, said.
        "The world is watching us. We are not being hasty," he added.
        Four of the five family members have died and samples from a further three people believed to be part of the family cluster of infections are still being tested.
        The WHO has sent a team to the area near Medan. The agency said it was on alert for signs the virus is mutating into one that can be easily transmitted between people, a development that could signal the start of a pandemic in which millions could die.


        Such a mutation could occur anywhere there is bird flu, the WHO says.
        Kandun said authorities were still trying to identify the source of the virus in the cluster case in Kubu Simbelang village in Karo regency, about 50km (30 miles) south of Medan.
        But an Indonesian agriculture official who declined to be named told Reuters tests had shed no light on the case.
        "There is a big question mark. Blood samples from all kinds of animals from chickens, ducks, geese, birds, pigs, cats and dogs turned out negative so far. Manure has also been checked. The result is negative," the Jakarta-based official said.
        Some reports have suggested chicken manure used as fertiliser might be the link. Infected birds can excrete large amounts of the H5N1 virus and this can be one way it can spread to birds, and people.
        The sixth of the cases confirmed on Wednesday was a 38-year-old catering businesswoman from Surabaya who had dealt with live pigs and pork meat before she died last week.
        The latest deaths bring the number of Indonesians who have died from bird flu to 30, by far the highest death rate in the world this year from the disease.
        Bird flu has killed 115 people worldwide, the majority in east Asia, since reappearing in 2003. Virtually all the victims caught the disease from poultry.
        The H5N1 virus is endemic in much of Indonesia. On Tuesday a senior Agriculture Ministry official said H5N1 had been detected for the first time in poultry in remote eastern Papua province.
        http://www.stuff.co.nz/stuff/0,2106,3671206a12,00.html

        <!-- / message --><!-- controls -->
        Last edited by sharon sanders; May 17, 2006, 04:59 PM.

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        • #19
          Re: Indonesia H2H Cover-up?

          <!--StartFragment --> You can?t tell the players without a scorecard and the comments and actions have been quite bizzare. Although Dr Jeremijenko suggested there was a problem because the Vet and Med groups don?t talk, he was being kind and creating some lines to read between.


          The HA cleavage site is the first thing sequenced in most animal labs, so the difference between the cleavage sites must be well known. However, Hong Kong has data for both, and certainly knows that RESRRKKR is novel.

          Indonesia sends its human samples to Hong Kong (YI Guan and Maelik Perez) for confirmation. They have a huge sequencing lab and have commented in the past that the human Indonesian sequences were like the Indonesian poultry sequences, so they definitely have the human sequences.


          However, it is Hong Kong that has published ALL of the Indonesian bird sequences (one small set in 2004 when the first H5N1 sequences came out, and again in 2006 in assocaition with their recent publication on H5N1 saying that there were regional diffeences, and then again more recntly in the absense of publication. The recent sequences were bird isolates from Indonesia and both bird and human isolates from Vietnam. Hong Kong has also released prior to publication, 2006 bird sequences from Malaysia and Laos (showing that they were like the Fujian strain infecting people in China).


          Thus, Hong Kong has started releasing sequences prior to publication, has released many Indonesian bird sequences, and has released ZERO human sequences from Indonesia (the lone human sequence was released by the CDC).


          Yi Guan knows there is H2H in Vietnam and Indonesia. When WHO put out the nonsense on duck blood pudding for the cluster in early 2005, Yi Guan said it was not possible to develop symptoms 17 days after exposure, but WHO not only held onto their fairy tale, they actually used the 17 days in their new guidlines, saying that symptoms could occur 17 days after exposure, which was and is utter nosnense, but that?s how they denied H2H in that cluster.


          Now Yi Guan is again saying that the spread between the disease onset date of the index case in Indonesia and the family members is also too long for a common source, again implying H2H.


          Thus, Yi Guan knowns how many human sequneces have the novel cleavage site, knows there is H2H, yet is holding the human sequences.

          Clearly WHO or Indonesia or both don?t want that info released. When asked about earlier relase a few months ago, Yi Guan said they would reconsider if WHO changed its policy, implying the hold was linked to WHO. Hong Kong has now released many animal sequences, but the human sequences remain locked up, so it sounds like it is WHO or Indonesia or both, and I suspect it is BOTH that hold the key.

          Comment


          • #20
            Re: Indonesia H2H Cover-up?

            Thank you Dr. Niman for providing some clarity on the situation.

            Comment


            • #21
              Re: Indonesia H2H Cover-up?

              Correct me if I am wrong but wasn't it Indonesia that wanted to have patent rights to any vaccine that was created from a strain that was found within their country?

              Is it possible that the reason that none of the sequencences from Indonesia have been released is due to the fact that they are holding out until so they can get patent rights on a vaccine from such a strain?

              Comment


              • #22
                Re: Indonesia H2H Cover-up?

                Originally posted by siam
                Well we keep coming back to cats. Though as I understand it they are mainly feral. Did this family have a pet cat?
                siam, a pet cat would not be neccessary. All cats, given the chance, will lick a bowl out, leaving saliva behind. Patting a cat after it has cleaned it's self allows the person to be in contact with cat saliva. There may also be cat feces about.
                Last edited by Sally Furniss; November 26, 2006, 02:37 AM.

                Comment


                • #23
                  Re: Indonesia H2H Cover-up?

                  Maybe the mammalian sequence is a human one and thats why they are afraid to release it.

                  Comment


                  • #24
                    Re: Indonesia H2H Cover-up?

                    My guess is the novel cleavage site is swine.

                    Comment


                    • #25
                      Re: Indonesia H2H Cover-up?

                      Bird Flu Deaths in Indonesia Worry Health Officials </NYT_HEADLINE><SCRIPT language=javascript> <!-- function submitCCCForm(){ PopUp = window.open('', '_Icon','location=no,toolbar=no,status=no,width=65 0,height=550,scrollbars=yes,resizable=yes'); this.document.cccform.submit(); } // --> </SCRIPT>


                      <NYT_BYLINE type=" " version="1.0">
                      By DONALD G. McNEIL Jr.
                      </NYT_BYLINE>
                      Published: May 17, 2006
                      <NYT_TEXT>
                      A cluster of avian flu deaths in an Indonesian extended family has raised the possibility that the virus had passed between people there, the World Health Organization said yesterday.
                      There have been several avian flu clusters in Indonesia, but this is the largest known, and the different beginning dates of symptoms in the family are worrying, officials said.
                      The flu is spreading rapidly in Indonesian backyard flocks, and before this week, the country had 25 known human deaths, the second-highest number in the world after Vietnam.
                      "We haven't seen any evidence of spread beyond this cluster," said Maria Cheng, a W.H.O. spokeswoman. "The investigation is still at an early stage."
                      Reports of limited transmission of the virus from human to human raise concerns but not alarms among health officials ? there have been previous suspected cases, each involving a family member who spent hours nursing a sick relative. Unlike seasonal flu viruses, which attach in the nose or throat, making them easy to spread, the A(H5N1) virus is known to attach to receptors found deep in human lungs.
                      Reports from the village of Kubu Sembilang on the island of Sumatra, repeated on wire services and infectious disease Web sites, were somewhat confusing. Five family members have been confirmed by a W.H.O.-certified laboratory in Hong Kong as having the A(H5N1) virus. Either 7 or 8 members of the family were said to have shown symptoms, and six were reported to have died.
                      According to experts familiar with the case who were cited on recombinomics.com, a Web site tracking genetic changes in infectious diseases, the first to die was a 37-year-old woman who fell ill on April 27, two days before a large family barbecue, and died May 4. The other family members ? two sons, a brother, sister, neice and nephew ? developed symptoms after the barbecue and five more died between May 9 and May 14.
                      No tissue from the 37-year-old woman was tested, so it is possible that she died of something else and that other members of the family were also infected by something else. Local reports said both pork and chicken were served at the barbecue. Because pigs can catch avian and human flus, it is also possible the woman was infected by a pig or chicken before the barbecue, and other family members were infected later. In Indonesian villages, pigs are often cooked in the ground and diseases from undercooked pork are common.
                      Tests on poultry and pigs in the village have not found the virus. Ms. Cheng of the W.H.O. said no large poultry outbreak had been reported in the area, but many such outbreaks that caused human cases have been missed before in several countries. Indonesia has started a chicken-vaccination program but it has not yet been effective.
                      H5N1 avian flu is known to have infected 208 other people, of whom 115 have died, according to the official W.H.O. Web site, which was last updated on May 12.
                      Two other A(H5N1) deaths in Indonesia have been reported in the last week ? a 38-year-old caterer in Surabaya who worked with pigs and a 12-year-old boy.
                      Vietnam, where the current outbreak began in 2003, had 93 cases by the end of 2005, but started an aggressive poultry-vaccination drive last summer and has not had a case in humans or poultry this year.
                      Indonesia, by contrast, has been criticized by global veterinary health officials for failing to contain its poultry outbreak. Lack of money for vaccines and a lack of cooperation between federal and local health authorities has been blamed.

                      http://www.nytimes.com/2006/05/17/he...in&oref=slogin
                      </NYT_TEXT>

                      Comment


                      • #26
                        Re: Indonesia H2H Cover-up?

                        I'd really like for ALL the sequences to be available so they can be compared. I believe the WHO is acting at Pandemic Phase 4 in spite of the fact that they haven't declared it yet.
                        ~~~~~~~~~~~~~~~

                        On another topic, I have wanted to reply to Alaska Denise's and Laidback Al's posts on Ro (R sub zero) or basic reproductive number. Alaska Denise asked some time back if anyone thought the Ro in Indonesia was greater than 1... and it got me thinking about Ro and Ro measured at what level???

                        For a while last year there was some discussion that it might be >1: Reasoning was that it might be higher than thought because maybe some human cases were not having symptoms/dying, but simply developing antibodies. (If true, that would have been just ducky, in that the case fatality rates would have been less too and we could sleep better at night. CFRs over 60% are a mind blower! Evidently for Webster too. ) Well, no such luck! An Indonesian study of many people in several areas where there had been family clusters showed others had not been infected.

                        The modeling stuff is fascinating... I like it because you can think about what factors might determine or influence the "tipping point" for pandemic. It also helps me think about what is being considered and what might be left out of a working model...

                        A bit more about Ro:
                        As mentioned earlier... it's is used in epidemiological modeling to represent the basic reproductive number, that is, "the average number of new (secondary) cases of infection for each (primary) infective case introduced into a susceptible population with random contact".

                        Ro is determined by a combination of the following:
                        1. characteristics of the H5N1,
                        2. nature of human interactions and
                        3. number of contacts in the community
                        1 is the contribution of the virus, 2 & 3 are characteristics of interpersonal relationships and networks.

                        If Ro is less than 1, the virus is not propagating in a sufficient number of new human hosts to go pandemic. The virus dies out. If it's greater than, 1 it is propagating sufficiently.

                        Theoretically when Ro=1, we've reached a pandemic threshold. But if we're talking about a cluster in a family, maybe not... Ro depends on the network it's measured in. (Transmissibility, according to the paper Laidback Al referenced does not: http://www.flutrackers.com/forum/sho...2878#post12878 )

                        Families clearly have unique close interpersonal relationships. Family members live in very close living spaces in Asia, also sharing close contact with their animals (fowl and mammals). Except in this last Indonesian cluster, not with fowl, perhaps with pigs or cats or some other vector...?

                        Random thoughts and a graphic...

                        Here's a thread AD began back on 4/18 and a link to the pdf article: http://www.flutrackers.com/forum/showthread.php?t=4465

                        Originally posted by AlaskaDenise
                        http://octavia.zoology.washington.edu/disease/eid.pdf

                        the article starts on the lower right corner of the first page.

                        It says that if the "R0" (average number of secondary infections arising from one infected individual) ,exceeds one, it is an epidemic waiting to happen.

                        There is an interesting chart on the second page, showing how infections caused by the evolved strain can go on to become an epidemic.

                        Is there enough information available to the public to determine if the "limited human transmission" cases have shown evolution?
                        This graphic she refers to made me think of what Henry has said so many times, that as the virus spreads into new geographical areas and new species, the chances of it going pandemic increase... simply because of the ever-growing number of times virus encounters new host... that may be coinfected...

                        Click image for larger version

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                        • #27
                          Re: Indonesia H2H Cover-up?

                          Originally posted by niman
                          My guess is the novel cleavage site is swine.
                          Does any one have a map showing the Muslim and Christian areas in Indonesia?
                          Can the map be over laid with the bf outbreaks?

                          Comment


                          • #28
                            Re: Indonesia H2H Cover-up?

                            I think DB might be on to something...money, money, money

                            Comment


                            • #29
                              Re: Indonesia H2H Cover-up?

                              Commentray at

                              Comment


                              • #30
                                Swine to Human H5N1Transmission in Indonesia?

                                Swine to Human H5N1Transmission in Indonesia?

                                Recombinomics Commentary

                                May 17, 2006

                                Among the confirmed deaths on Wednesday was a 38-year-old catering businesswoman from Surabaya who had dealt with live pigs and pork meat before she died last week.

                                The above comments on a confirmed death in Surabaya are cause for concern. Last year H5N1 infected swine were identified in Surabaya. Reports indicated that all eight genes had been sequenced in Japan, and the sequence included a polybasic cleavage site. Although the sequence was generated over a year ago, it has not been made public via deposition at the public database at GenBank or Los Alamos. Instead it is almost certainly being withheld in the WHO private database.

                                Only one human H5N1 sequence has been deposited from Indonesia. That sequences has a novel HA cleavage site of RESRRKKR, which is not found in any sequence at GenBank. However, a recent report suggested that the novel sequence was in human isolates from Indonesia as well as a cat isolate from Indonesia.

                                Novel sequences are common in swine H5N1, in part because there are a limited number of such sequences. All public swine H5N1 sequences have come from China, and most have novel HA cleavage site. The common H5N1 sequence is RERRRKKR. Two of the swine sequences, A/swine/Guangdong/1/2003(H5N1) and A/swine/Shandong/2/03(H5N1), but even in these cases the nucleotide sequence that encodes the cleavage site is relatively rare. It is unique for the Guangdong sequence and shared with a few wild bird isolates in the Shandong sequence.

                                Several of the swine isolates, A/swine/Fujian/F1/2001(H5N1), A/swine/Fujian/1/2003(H5N1), A/swine/Guangdong/2/2003(H5N1), A/swine/Guangdong/4/2003(H5N1, A/swine/Guangdong/5/2003(H5N1) have the REIRRKKR sequence which is shared with a small number of waterfowl including Guangxi ducks, and A/swine/Anhui/2004(H5N1), which has REGRRKKR which is also found in a small number of waterfowl.

                                These small number of isolates in these swine H5N1 sequences raise the possibility that the novel sequence in the human isolates in Indonesia also come from swine. In any event, the human and swine sequences from Indonesia should be released, and the source of the novel HA cleavage site should be determined.

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