Dr Niman Comments on Indonesia (Oct 2006)
Posted in: darrelrussell.com edit
08 Jan 2009
| H5N1 Suspect Cluster in Makassar South Sulawesi Grows Recombinomics Commentary October 4, 2006 As Many As eight citizens who lived in Street Perintis Breakingprep Kemerdekaan, Makassar, were taken the sample of his blood because of experiencing the sign that was similar to the bird flu sufferer. Two among them, the older brother was siblings, Dion (7) and Mustarisa (4), underwent the intensive maintenance in the Public Hospital (RSU) Wahidin Sudirohusodo, on Tuesday (3/10). The official also combed the patient's neighbour.Two citizens, Nurwan (30) and Hidayati (21), kedapatan experienced the similar sign.The neighbour Dion that lived in Street Perintis Breakingprep Kemerdekaan KM 8 No 8 this took part in being taken the sample of his blood and was recommended to RS Wahidin to undergo the intensive maintenance. Six patients suspect this was their respective, Dion R (7), Mustarisa (4), Nur Asiah (11), Apriliyani, Paturungi, and Salsabil. From six patients tesrebut, four among them, Dion, Mustarisa, Nurasiah, and Salsabil entered on the same day, on Monday (2/10). The above translation indicates the number of hospitalized suspect H5N1 bird flu victims continues to increase in Makassar in South Sulawesi. In June a confirmed H5N1 case died in Makassar (http://www.recombinomics.com/News/09080603/H5N1_Sulawesi_Cluster.html) and recently the number of additional hospitalized patiens began to increase dramatically. Some of the earlier cases are recovering, so the recent cases could be seasonal flu, or H5N1 responding to Tamiflu treatment. The clustering in the same neighborhood, however, remains a cause for concern. Media Sources (http://www.flutrackers.com/forum/showthread.php?t=9614&page=4) Phylogenetic Trees (http://www.recombinomics.com/phylo.html) http://www.recombinomics.com/News/10040601/H5N1_Makassar_Cluster.html | |||||||||
Recombinomics Commentary
October 16, 2006
The "PCR test first, second, fourth, and the five results of the negative."
Only that third that said false positive or positive border line
The above description of the most recent confirmed H5N1 positive case raises additional questions about testing in Indonesia. The patient developed encephalitis and died. Multiple organs, including her brain were involved, yet most of the testing yielded negative results.
Negative results have also been reported for other severely ill contacts of H5N1 cases, incl;uding the large Garut cluster (http://www.recombinomics.com/News/08230601/H5N1_Cikelet_Grows_20.html). These negatives, frequently in samples collected after Tamiflu treatment has started, continue to raise concerns on the true extent of H5N1 infection in Indonesia.
Sequencing data clearly show that the vast majority of cases are not linked to H5N1 positive poultry (http://www.recombinomics.com/News/10050602/H5N1_Indo_Match_Failures.html), yet a poultry link is usually required for H5N1 testing of patients with bird flu symptoms
Now H5N1 is being detected in patients with symptoms of encephalitis. The sole surving member of the Karo cluster also developed a brain infection (http://www.recombinomics.com/News/06150602/H5N1_Sumatra_Neuro.html), but that infection was said to be negative for H5N1.
The current H5N1 positive fatal encephalitis case increases concerns hat H5N1 in human is much greater than the number of WHO confirmed cases.
.
Media Sources (http://www.flutrackers.com/forum/showthread.php?t=11217&highlight=year)
Phylogenetic Trees (http://www.recombinomics.com/phylo.html)
http://www.recombinomics.com/News/10160603/H5N1_Encephalitis_Indonesia.html
| H5N1 Match Failure in Indonesia Raises Pandemic Concerns Recombinomics Commentary October 5, 2006 Tests on 49 samples taken from birds on the islands of Sumatra, Java and Bali showed the H5N1 avian influenza virus has undergone no major changes, the ministry said in a statement today. The analysis was undertaken by a World Organization for Animal Health reference laboratory in Geelong, Australia. Samples of the H5N1 virus taken from birds were collected between September in 2005 and March. The above comments provide additional detail on the H5N1 bird samples sent to Australia for sequencing in an attempt to match the human H5N1 sequences from Indonesia. Prior to the sequencing of the above isolates, the bird H5N1 sequences failed to match (http://www.recombinomics.com/News/08120601/H5N1_Match_Unlikely.html) the human sequences. However, most of the initial bird sequences were from 2003 through the first half of 2005, while the first human sequence was from July 2005. Therefore, the match failure may have been due to recent H5N1 that were not reflected in the earlier sequences. 91 samples were sent to Australia for sequencing. Since the human isolates had already been sequenced, the question of major changes was not at issue. The human sequences had no evidence of reassortment, but virtually all samples from Java had a novel cleavage site that was associated with a number of additional changes in all 8 gene segments that were in the human isolates, but absent in the poultry isolates. The HA sequences from over 50 samples from Australia were deposited at Los Alamos over the past few months, and those sequences failed to match the human sequences. Only three of the bird isolates had the novel cleavage site. Two were from chickens in central Sumatra (http://www.recombinomics.com/News/09140601/H5N1_Sumatra_Chickens.html), but all of the human sequences with the novel cleavage site were from a duck in Indramayo on Java (http://www.recombinomics.com/News/08310601/H5N1_Indo_Duck_Cleavage.html). The third bird isolate with the novel cleavage site was from Java, but it only matched a few of the human sequences (http://www.recombinomics.com/News/10050601/H5N1_Asymptomatic_Chickens_Java.html). The vast majority of the human sequences matched each other, but did not match any bird sequence from Java. The above comments confirm that the recent bird sequences overlap the human sequences in time and location, but still fail to match, indicating the vast majority of human H5N1 sequences are from a source other than most of the H5N1 infected poultry in Indonesia. The failure of the above comments to address the match failure is cause for concern. Media Sources (http://www.flutrackers.com/forum/showthread.php?t=11306) Phylogenetic Trees (http://www.recombinomics.com/phylo.html) http://www.recombinomics.com/News/10050602/H5N1_Indo_Match_Failures.html | |||||||||
Recombinomics Commentary
October 7, 2006
The recent announcements of H5N1 bird flu in cats in Indonesia (http://www.recombinomics.com/News/10070601/H5N1_Indonesia_Cats.html), coupled with results from expanded sequencing of poultry (http://www.recombinomics.com/News/10050602/H5N1_Indo_Match_Failures.html) strongly signal the existence of a separate mammalian H5N1 reservoir in Indonesia that is responsible for the vast majority of human cases.
This separate reservoir creates significant problems, because most of the attention has focused on infected poultry, and the mammalian reservoir has been significantly under investigated and under reported.
Therefore, a review of the evolution of this mammalian reservoir is useful. Although Indonesia did not acknowledge H5N1 infections until 2004, the first isolates were from birds in 2003. Sequence analysis of the 2003 and 2004 isolates indicated the H5N1 was Clade 2 and had a number of genetic markers that were specific for Indonesia.
The first human case was reported in July of 2005, and the sequence of the isolate, A/Indonesia/5 (http://flu.lanl.gov/search/view_record.html?accession=ISDN125873&database=fluA)/2005 had the Indonesia specific markers, but also had a number of unique polymorphisms, including one that created a novel HA cleavage site (http://www.recombinomics.com/News/03260601/H5N1_Vaccine_Indo_Sequence.html), RESRRKKR. However, the second human isolate, A/Indonesia/6/2005 had the more common HA cleavage site, RERRRKKR, and was similar to bird isolates. Subsequent human isolates in 2005 had the novel cleavage site, but several had an additional silent change, so although the cleavage site matched the first sequence at the protein level, there were a number of changes at the nucleotide level that divided the sequences with the novel cleavage site into two groups.
However, as the number of sequences increased in early 2006, it became increasingly clear that the human sequences were separating from the poultry sequences, all of which had the common bird cleavage site. The first match of the human sequences was from H5N1 from a throat swab of a cat (http://effectmeasure.blogspot.com/2006/02/indonesia-and-questions-about-its.html) in Indramayu near a residence were two siblings died from H5N1 infections. The sequence of the cat isolate not only matched the more recent human sequences, but was very close to the sequences of the isolates from the two siblings, A/Indonesia/283H/2006 and A/Indonesia/286H/2006, as well as other human isolates from Indramayu, A/Indonesia/292H/2006 and A/Indonesia/304H/2006. New isolates in 2006 collected from patients in East and West Java were sequenced and all were matches of more recent sequences such as the four human and one cat isolate from Indramayu.
In May of 2006 however, there was a new cluster in the Karo regency in north Sumatra. This outbreak was the largest to date and involve secondary and tertiary transmissions of H5N1. Consequently a meeting was call by WHO and consultants in Jakarta in June. Included in the presentation was a phylogenetic tree (http://www.recombinomics.com/phylo/Indo_Karo_HA1.html) that summarized the H5N1 Indonesian isolates as of June 12, 2006.
The tree, which had the human sequences in green and the Karo cluster shaded in pink, clearly showed the match problem. All of the sequences with the novel cleavage site were on the lower portion of the tree and there were no poultry sequences on these two lower branches. Moreover, all of the recent human sequences from Java were on the lowest branch, which was even further from the poultry isolates. Thus, the human isolates were evolving away from the poultry isolates, suggesting the existence of a separate mammalian reservoir.
However, all of the human isolates were from July, 2005 or later, while most of the bird isolates were from earlier dates. Therefore 91 samples (http://www.recombinomics.com/News/08120601/H5N1_Match_Unlikely.html) were schedule for shipment to Australia for virus isolation and sequencing. The samples were from infections between September, 2005 and March, 2006.
As sequences from these more recent and geographically dispersed isolates began to be published, it was becoming increasingly clear that the vast majority of the human infections on Java were not from domestic poultry (http://www.recombinomics.com/News/08120601/H5N1_Match_Unlikely.html). Each human sequence mapped to the lower portion of the tree and which was more distinct from the bird sequences.
The second set of new bird sequences included an isolate with the novel cleavage site. It was from a duck on Indramayu (http://www.recombinomics.com/News/08310601/H5N1_Indo_Duck_Cleavage.html) isolated in 2006. However, that isolate match the upper branch of the human sequences, which were composed of six isolates from three patients in 2005. Thus, although every human isolate in 2006 was matching the lower branch, the one duck sequence matched the upper branch.
The third set of poultry sequence had two matched with the lower branch. However, the two matches were from chickens in central Sumatra from 2005. Thus, none of the poultry isolates matched the lower human branch, while all human isolates, as well as the cat isolate, matched the lower human branch.
These data again supported a separate reservoir for the human sequences, and the only matches on Java were from the one cat, and all human isolates. The recent announcement indicates more H5N1 has been detected in cats, but the sequences of those isolates have not been released. Swine H5N1 sequences have been reported, but none match (http://www.recombinomics.com/phylo/Nidom_swine_HA.html) the human sequences.
The match failures pose a major problem because testing of humans is largely limited to patients how have been near dead or dying poultry. However, the poultry association has not been linked to the human infections, so an expanded testing of patients with symptoms is warranted. Similarly, more sequencing of H5N1 from other reservoirs is warranted by the match failures between mammalian and avian sequences.
Media Sources (http://www.flutrackers.com/forum/showthread.php?t=11352)
Phylogenetic Trees (http://www.recombinomics.com/phylo.html)
http://www.recombinomics.com/News/10070602/H5N1_Indonesia_Mammalian.html
| H5N1 in Cats in Indonesia Recombinomics Commentary October 7, 2006 A study conducted by the Indonesian Environment Information Center (PILI) in Yogyakarta found that stray cats had caught the H5N1 virus through contact with infected poultry at traditional markets. The above comments provide additional evidence implicating an alternative source of H5N1 human infections in Indonesia. Recently, Indonesia summarized the results of poultry tests by a WHO affiliated lab in Australia (http://www.recombinomics.com/News/10050602/H5N1_Indo_Match_Failures.html). Concerns had been voiced in an H5N1 meeting in Jakarta in June because the sequences from the vast majority of human cases on Java did not match the poultry H5N1 collected between 2003 and 2005. Consequently, 91 poultry samples (http://www.recombinomics.com/News/08120601/H5N1_Match_Unlikely.html) were sent to Australia for virus isolation and sequencing. The samples were from collections between September 2005 and March 2006 and failed to match (http://www.recombinomics.com/News/08110601/H5N1_Match_Failure.html) Java poultry isolates with most of the sequences from patients. All but one of the human isolates from patients on Java had a novel cleavage site, RESRRKKR, as well as a number of associated changes in all 8 gene segments that readily distinguished the human sequences from the poultry sequence (see green sequences in lower branch (http://www.recombinomics.com/phylo/Indo_Karo_HA1.html)). One duck from Indramayu (http://www.recombinomics.com/News/08310601/H5N1_Indo_Duck_Cleavage.html) had the novel cleavage site, but that duck isolates had additional changes, including a silent change in the cleavage site, which was found in only a small subset of human isolates. The vast majority of human isolates, including those from Indramayu, failed to match the duck sequences. Two matching sequences were found in chickens in central Sumatra (http://www.recombinomics.com/News/09140601/H5N1_Sumatra_Chickens.html), but the match failure on Java, coupled with the almost universal matching of human sequences, including the first sequence isolate in July 2005 as well as isolates from a wide range of geographical locations, including East Java, suggested human infections were largely due to H5N1 in a reservoir other than poultry. The only match on Java of the human sequences was from a throat swab of a cat. A/feline/Indonesia/CDC1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=113495213&dopt=genbank)/2006(H5N1), from Jakarta on January 22, 2006. H5N1 has also been detected in swine in Indonesia, but the swine sequences, including the HA cleavage site, did not match the human sequences. The discovery of more H5N1 in cats in Indonesia raises the possibility that the cats are also in contact with an alternate reservoir. Sequence data on H5N1 from cats, and “infected poultry in traditional markets”, including those in and around Jakarta, where most of the reported human cases have been located, would help resolve the role of cats in H5N1 transmission. Media Sources (http://www.flutrackers.com/forum/showthread.php?t=11352) Phylogenetic Trees (http://www.recombinomics.com/phylo.html) http://www.recombinomics.com/News/10070601/H5N1_Indonesia_Cats.html | ||||||||
| Asymptomatic H5N1 Infected Chickens in Indonesia Recombinomics Commentary October 5, 2006 Head of the West Java Animal Husbandry Office, Rachmat Setiadi, said the warning was made following the discovery of healthy chickens that tested positive with H5N1 virus from a serology test conducted on 20 chickens around the house of two dead flu victims -- 23-year-old IJ and his 20-year-old brother -- in Kebonwaru area, Batunggal The above comments indicate asymptomatic chickens can carry H5N1 bird flu. Although many H5N1 sequences from birds and people in Indonesia have been published, the link between H5N1 in dead poultry, and H5N1 in dead patients has not been established. All reported sequences from human cases in 2006 on the island of Java have has a novel HA cleavage site. The novel cleavage site has only been detected in one duck (http://www.recombinomics.com/News/08310601/H5N1_Indo_Duck_Cleavage.html) on Java in Indramayu, and that sequence was similar to a few human sequences from late 2005 / early 2006 (in upper twig of lower branch of HA tree (http://www.recombinomics.com/phylo/Indo_Karo_HA1.html)). The vast majority of human cases are on a separate twig of the lower branch, and these do not match (http://www.recombinomics.com/News/08120601/H5N1_Match_Unlikely.html) any reported poultry isolates on Java. Matching sequences have been found in two chickens in central Sumatra (http://www.recombinomics.com/News/09140601/H5N1_Sumatra_Chickens.html), isolated in 2005. The H5N1 asymptomatic chickens on Java are positive for antibodies. It is not clear if H5N1 sequences have been detected in the asymptomatic birds. These infections could represent a separate reservoir. There have also been repots on the recovery of suspect bird flu victims. However, these patients have been H5N1 negative, so it remains unclear if they are infected with H5N1, or if the H5N1 sequence from these recovered is different than the H5N1 fatal cases. Almost all H5N1 human sequences in Indonesia are from fatal cases. Asymptomatic chickens in Vietnam (http://www.recombinomics.com/News/04230502/H5N1_Asymptomatic_Chickens.html) have also been reported previously. Clearly more surveillance and sequences from H5N1 infected people, birds, and other mammals are indicated. Media Sources (http://www.flutrackers.com/forum/showthread.php?t=11288) Phylogenetic Trees (http://www.recombinomics.com/phylo.html) | ||||||||
http://www.recombinomics.com/News/10050601/H5N1_Asymptomatic_Chickens_Java.html
Recombinomics Commentary
October 16, 2006
startled by the death of the patient with the sign of bird flu in RSU Banyumas from the Sigedang Village, the Kaliurip Village, the Madukara Subdistrict, Mistinem (32), on Friday (13/10).
More again startled when knew had a citizen of the Krinjing Village, the Lightning Village, of the Purwonegoro Subdistrict that currently also is treated in RSU Banyumas with the same sign.
The Krinjing village that beforehand had not canned be heard his name, currently suddenly became attention of the community.
A party of the official from the Health Service of the Regency (ET AL) also checked the condition for the Parimun house (17), the new patient RSU Banyumas.
The above translation describes the confirmed H5N1 fatality in Banyumas in Central Java, as indicated in today’s WHO update (http://www.who.int/csr/don/2006_10_16/en/index.html). Local media describe a second hospitalized patient who also transferred to RSU Banyumas from RSUD Banjarnegara. The second patient was from a neighboring village, Krinjing.
The two cases in Central Java as well as the confirmed cases from South Jakarta (http://www.recombinomics.com/News/10160601/H5N1_S_Jakarta.html) and Bandung (http://www.recombinomics.com/News/10160603/H5N1_Encephalitis_Indonesia.html) died on consecutive days. These three confirmed H5N1 deaths in three regions on Java are cause for concern.
Although the vast majority of confirmed H5N1 cases in Indonesia are from Java, a source of infection has not been identified (http://www.recombinomics.com/News/10050602/H5N1_Indo_Match_Failures.html). All human cases, except one from an infection in August, 2005 have been infected with H5N1 with a novel cleavage site. These patients fall into two groups. One, consisting of three patients infected in 2005 map to the upper branch of the bottom of the phylogenetic tree (http://www.recombinomics.com/phylo/Indo_Karo_HA1.html) presented at a WHO meeting in Jakarta in June. The vast majority of Java cases however, map to the lower portion of the tree. All human sequences that have been made public since the meeting, also map to the lower portion. This lower portion has no avian isolates.
The match failure was noted at the meeting, and 91 recent samples (http://www.recombinomics.com/News/08120601/H5N1_Match_Unlikely.html) were sent to a WHO affiliated lab in Australia, Over 50 bird sequences have been made public from these recent samples and only one bird isolate from Java had the cleavage site. However, it match the small group of three patients from 2005. This duck (http://www.recombinomics.com/News/08310601/H5N1_Indo_Duck_Cleavage.html)isolate was from Indramayu, but the patients from Indramayu mapped with the majority of cases, which are on the lowest branch.
Two chicken isolates did map to the lower branch. By these isolates were from 2005 in Central Sumatra, far from the human cases on Java, which have stretched from East Java to West Java and isolated during a time from from the index case in July, 2005 through the most recent deposits, from the summer of 2006.
The origin of these infections is unknown. The only non-human Java match was from cat, also from Indramayu. That sequence was closely related to the human sequences, including those from Indramayu.
The failure to identify the source of the H5N1 infections in Indonesia remains a cause for concern.
Media Sources (http://www.flutrackers.com/forum/showthread.php?t=11572)
Phylogenetic Trees (http://www.recombinomics.com/phylo.html)
http://www.recombinomics.com/News/10160604/H5N1_Banyumas_Indonesia.html
Recombinomics Commentary
October 11, 2006
"A 67-year-old woman living in the Cisarua area of Bandung had contact with fowl," the official from the bird flu information centre said by telephone. The woman was admitted to the hospital on Oct. 7 and was still alive, the official added.
The woman tested positive to the H5N1 virus after a test at a health ministry laboratory and one conducted by NAMRU, the U.S. Naval Medical Research Unit based in Jakarta, the official added.
Hadi Yusuf, the director of the Hasan Sadikin hospital in Bandung, southeast of the capital Jakarta, said the woman was being treated with the anti-viral drug Tamiflu and antibiotics.
"Her condition is bad. For a second day, she has been on a respirator and her blood pressure is high."
Yusuf said the woman had come down with a fever two weeks after being in the vicinity of dead chickens.
The above description confirms H5N1 bird flu in an elderly patient (67F) from the Bandung area. There is also evidence for neurological involvement, which is unusual for cases in Indonesia. Similarly, the patient is markedly older than most cases in Indonesia. The sole survivor from the infection in Karo also had neurological complications (http://www.recombinomics.com/News/06150602/H5N1_Sumatra_Neuro.html), but those problems may have been due to a secondary bacterial infection.
It remains unclear if the infection in the older patient with neurological complications represents a new H5N1 strain in the Bandung area. A large number of patients in the area have been hospitalized with symptoms, but most tested negative for H5N1 and recovered after Tamiflu treatment.
Although poultry was dying in the vicinity, to date all reported patients from Bandung have been infected with H5N1 with a novel cleavage site and additional markers that did not match the H5N1 in poultry on Java. The only bird isolate on Java with the novel cleavage site was from a duck on Indramayu (http://www.recombinomics.com/News/08310601/H5N1_Indo_Duck_Cleavage.html) and matched a small subset (http://www.recombinomics.com/News/08110601/H5N1_Match_Failure.html) of patients from 2005. All of the more recent isolates were readily distinguished from the H5N1 from the duck in Indramayu.
Recent reports from Indonesia have described H5N1 in cats (http://www.recombinomics.com/News/10070601/H5N1_Indonesia_Cats.html). H5N1 from a kitten in the Indramayu is the only match for the vast majority of the human H5N1 isolates.
Media Sources (http://www.flutrackers.com/forum/showthread.php?t=11217&page=2)
Phylogenetic Trees (http://www.recombinomics.com/phylo.html)
http://www.recombinomics.com/News/10110601/H5N1_Bandung_Confirmed.html
Recombinomics Commentary
October 20, 2006
the Official of the Maros Health of the Service took the sample of blood against five citizens in the Bontopaddingin Village, the Bontotallasa Village, the Subdistrict Toss Up, on Wednesday October 18 yesterday.The taking of the sample of this blood, related the death a baby, Fajrin, 2 months that was expected suspect avian influenza (AI) or bird flu.
They who were taken the sample of his blood respectively the two parents Fajrin, the Dervish, 22 years with his wife, dahlias, 29 years.Three other citizens were still being the grandfather and the close Fajrin family respectively Kurdin, 60 years, Hj Indeed, 55 years, and Harbiah, 35 years.A Service staff the Maros Health, Muhammad Said, SKM M. Cash that led the taking of the sample of this blood in the location, mentioned, from the five citizens, two including being expected suspect bird flu.
The above translation describes a suspect fatal H5N1 bird flu case in South Sulawesi. In addition, at least two family members are hospitalized and several contacts are being tested. The H5N1 situation in South Sulawesi remains unclear.
Last month a fatal confirmed case from Mekassar was announced. However, the patient had died in June. The WHO update (http://www.who.int/csr/don/2006_09_08a/en/index.html) indicated the delay in reporting the confirmation was because it was collected during routine testing. However, the WHO update failed to mention the deaths of two family members who also had bird flu symptoms (http://www.recombinomics.com/News/09080603/H5N1_Sulawesi_Cluster.html). Thus, the failure to report, couple with the misleading characterization by WHO is cause for concern.
Between the earlier fatal cluster and the current suspected fatal cluster, a large number of suspect cases have been hospitalized in South Sulawesi (http://www.recombinomics.com/News/10040601/H5N1_Makassar_Cluster.html). Although these cases have tested negative, patients have been treated with Tamiflu which may lower the level of circulating H5N1 to a level that is below detection. False negatives are common in H5N1 cases and frequently multiple tests are required to detect H5N1. A recent confirmed H5N1 fatality in Thailand was tested nine times (http://www.recombinomics.com/News/09260604/H5N1_Thailand_False_9.html) over several weeks, yet H5N1 was only detected at autopsy.
The frequency of H5N1 infections in Indonesian remains unclear. The H5N1 in patients does not match the H5N1 in poultry. Since a link to dead or dying poultry is usually required fro H5N1 testing, the level of H5N1 infections in patients with bird flu symptoms, but without a bird link is largely unknown.
If these patients have been infected with H5N1, they will have antibodies that can be detected 3-4 weeks after disease onset. It remains unclear how many of any surviving patients with bird flu symptoms are tested for convalescent H5N1 antibodies.
Similarly, sequence data from H5N1 positive cats has not been released. The only cat H5N1 sequence released to date does match the human H5N1 sequences, which provides additional evidence for a mammalian reservoir. Similarly, analysis of recently released H5N1 sequences in China show that recombination is frequent, and regions of identity are found in Indonesian patients (http://www.recombinomics.com/News/10190601/H5N1_China_Swine_Evolution.html), providing evidence for the introduction of new polymorphisms in Indonesia via migratory birds. H5N1 sequences from wild birds in Indonesia are also lacking.
The latest suspect cluster in Indonesia again highlights the need for expanded surveillance and more timely reporting.
Recent media reports indicate that there will be testing of waterfowl in the Trisik area, Yogyakarta, and the Eretan Coast, Indramayu. Thus far the only reported bird H5N1 from Java with the novel cleave site was from Indramayu (http://www.recombinomics.com/News/08310601/H5N1_Indo_Duck_Cleavage.html). Although it did not match the majority of human cases, it was close to a small subset of patients infected at the end of 2005. The only other bird isolates with the novel cleavage site were from central Sumatra (http://www.recombinomics.com/News/09140601/H5N1_Sumatra_Chickens.html).
Although the novel cleavage site has not been detected outside of Indonesia, many polymorphism from patients in Indonesia have been detected in H5N1 in China, strongly implicating these isolates in the evolution of H5N1 worldwide, including several polymorphism that were widely detected in Indonesian patients. Moreover, the origins of these H5N1 sequences in China could be found in low path isolates in Hong Kong in the late 1970’s indicating low path flu sequences are also closely involved in the evolution of H5N1, which is largely driven by recombination, which was readily detected in the H5N1 from poultry (http://www.recombinomics.com/News/03060605/H5N1_Recombination_Henan_PB2.html), waterfowl (http://www.recombinomics.com/News/03020602/WHO_Sequence_Hoarding.html), and swine in China.
Media Sources (http://www.flutrackers.com/forum/showthread.php?t=11770&highlight=sulawesi)
Phylogenetic Trees (http://www.recombinomics.com/phylo.html)
http://www.recombinomics.com/News/10200602/H5N1_S_Sulawesi.html
Recombinomics Commentary
October 16, 2006
The boy, who wasn't named by officials, was admitted to the Sulianti Saroso Hospital for Infectious Diseases on Thursday and died Saturday night, said Director Dr. Santoso Suroso.
He was believed to have become infected by dead chickens near his home in south Jakarta, Suroso said.
Almost all of the fatal human cases have been linked to contact with chickens or their droppings.
The above comments describe a suspect H5N1 bird flu fatality from southern Jakarta. Although the above report, as well as WHO updates, suggests the human infection is from chickens in the area, the sequences from chickens on Java have failed to match (http://www.recombinomics.com/News/10050602/H5N1_Indo_Match_Failures.html) the human H5N1 sequences on Java.
The match failure was discussed (http://www.recombinomics.com/News/08110601/H5N1_Match_Failure.html) at length at a WHO in Jakarta in June, 2006. Sequences of human cases on Java had a novel cleavage site and mapped to the bottom branch of a phylogenetic tree of H5N1 isolates in Indonesia had no bird isolates that were on that branch. Since that vast majority of bird flu tests on suspect bird flu patients are limited to those with some sort of linkage to dead or dying birds, the presence of dead or dying birds in H5N1 patients does not provide evidence that the human infection was due to the bird infections. These sequences from the bird isolates clearly indicate that the human infections are not from the H5N1 positive birds.
Since most of the bird sequences tested by June, 2006 were from isolates collected prior to the end of 2005, 91 samples collected from October, 2005 to March 2006 were sent to a WHO affiliated lab in Australia. After the June meeting, sequences of human isolates were released. All of the human isolates on Java had the novel cleavage site and fell onto the lower branch of the HA tree. Sequences in the other 7 gene segments from these isolates also matched each other, and failed to match the bird sequences.
The tests on the 91 samples (http://www.recombinomics.com/News/08120601/H5N1_Match_Unlikely.html) yielded over 50 sequences but the only match from a bird on Java was from a duck in Indramayu (http://www.recombinomics.com/News/08310601/H5N1_Indo_Duck_Cleavage.html). However, this isolate match H5N1 from three patients from 2005. It did not match the vast majority of human isolates from Java.
The only non-human isolate that did match the human isolates was from a cat on Indramyu, which was also closely related to human H5N1 isolates from Indramayu.
There have been no additional sequences from Australia, indicating that attempts to find matching sequences on Java have failed. Recent media reports suggest additional cat H5N1 infections (http://www.recombinomics.com/News/10070601/H5N1_Indonesia_Cats.html) have been detected. A broader screening of mammals and wild birds would be useful.
It is clear that most of the human H5N1 infections on Java are not from H5N1 in poultry and limiting human H5N1 testing to those with links to dead or dying poultry is generating an underestimate of H5N1 human infections.
Media Sources (http://www.flutrackers.com/forum/showthread.php?t=11642)
Phylogenetic Trees (http://www.recombinomics.com/phylo.html)
http://www.recombinomics.com/News/10160601/H5N1_S_Jakarta.html
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