H1N1- Ultimate News on influenza A - bird flu, swine flu & avian flu alerts

Health chiefs fear worst over family killed by bird flu

World health chiefs said today that they were increasingly concerned about the bird flu deaths of six Indonesians from one family, raising fears of the first human-to-human transmission of the deadly H5N1 virus.

Seven members of an Indonesian family in the village of Kubu Sembelang, northern Sumatra, have been infected with bird flu, of whom six have died, despite not coming into contact with diseased birds.

Last night, the Word Health Organisation said human transmission was a possible cause of the cluster, but said there was no evidence of a wider spreading of the virus.

"This is the most significant development so far in terms of public health," Peter Cordingley, spokesman for the West Pacific region of the WHO, told Reuters Television in Manila today. Source : Times

Swine to Human H5N1Transmission in Indonesia?

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. Source : recombinomics

Three Additional Family Members in Karo With Bird Flu Symptoms

"It is certainly alarming,'' said Dick Thompson, a WHO spokesman in Geneva. ``This is the largest H5N1 cluster we have seen. There are obviously important questions that we need answered. But right now it is too early in the investigation to say anything definitive.''
      
      Yesterday, three members of the family said they were feeling sick, with symptoms including headache and cough.
      
H5N1 bird flu symptoms in three additional family members are cause for concern.  As of yesterday these symptoms were mild, but should these relatives deteriorate, their illness would be alarming.  Six family members have already died and the index case developed symptoms about a week prior to symptoms in family members.  The symptoms in the index case were April 27 and all infected family members were at an April 29 barbeque strongly implicating human-to-human transmission.  H5N1 infection in three more family members would implicate human-to-human-to- human transmission in multiple family members.
      
Human-to-human transmission in Indonesia is also suggested by the many clusters with 5-10 day gaps between the disease onset date of the index case in additional family members.  In addition, the only human sequence that has been made public has a novel cleavage site.  One report has suggested that this novel sequence is found in additional human sequences, as well as a cat, and the swine in the Karo area have H5 antibodies. Since the sequence has not been reported in any poultry isolates, a non-poultry source is implicated  However, testing of patients in Indonesia is predicated on exposure to dead or dying poultry, which would underestimate H5N1 from sources other than poultry.
      
Since there are over 30 confirmed H5N1 cases in Indonesia, it is likely that sequences from many or most of these cases is at a private WHO database. Those sequences should be released immediately. Source : Recombinomics

H7N3 Bird Flu Confirmed in UK Poultry Worker : the conjuctivitis

the worker, who does not want to be named, has the H7N3 strain of bird flu which is not highly infectious
      
The above comments acknowledge that H7N3 has caused at least one case of conjunctivitis in Great Britain.  This case is not a surprise.  H7 infections in poultry frequently result in conjunctivitis cases in human contacts.  The most recent example was in British Columbia in 2004 where several poultry workers developed conjunctivitis from H7N3.  However the H7N7 outbreak in the Netherlands in 2003 produced over 80 cases of conjunctivitis in poultry cullers.
      
However, a sensitive assay was developed to detect H7 antibodies and hundreds or thousands of culler contacts had H7 antibodies, indicating human-to-human transmission of H7 is efficient.  The cases had mild symptoms or were asymptomatic.  However, a veterinarian developed pneumonia and died.  This is the only reported fatality from bird flu linked to a serotype other than H5N1.  The H7N7 isolated from the fatal case had PB2 E627K.
      
E627K was first reported in H5N1 from birds in the 16 isolates from Qinghai Lake, almost 1 year ago.  All Qinghai H5N1 PB2 sequences to date have also had E627K.  This polymorphism is liked to enhanced polymerase activity at lower (33 C) temperatures.  It is also associated with increased virulence in mammals.
      
Although the has been only one report of H5N1 in the UK, the Qinghai strain has been detected throughout Europe, raising serious issues about the sensitivity of the assay in the UK.  The UK surveillance failed to detect significant infections by H5N1 or low pathogenic serotypes, even though over 7000 birds were tested. The surveillance failed to detect any H7 infections.
      
The co-circulation  of H7 and the Qinghai strain of H5N1 is cause for concerns.  E627K could be acquired by H7N3 via recombination or reassortment.  This acquisition would likely increase virulence in an H7 which is probably readily transmitted between humans. Source : Recombinomics

Poor control in the UK or is the reality ?

Chickens at a farm near Dereham in Norfolk are to be slaughtered after dead birds tested positive for a strain of bird flu.
Officials said preliminary test results indicated it was likely to be the H7 strain not the deadly H5N1 variation.
Last month a swan in Cellardyke, Fife, tested positive for the H5N1 strain
      
The above comments describe a bird flu outbreak in Great Britain. Although the infectious agent may be H7, co-circulation of H7 and the Qinghai strain of H5N1 is cause for concern.
      
Great Britain has reported one positive H5N1 case.  However, results from test on over 7000 samples raise serious questions about the sensitivity of the surveillance testing.  Bird flu is common in wild birds.  Canada tested young ducks in August of 2005 and found H5 low pathogenic infections in many birds.  24% of the birds tested in British Columbia were H5 positive.  The frequency of positives will vary by species, age and season, but over an extend time period 5-10% of birds tested should be positive for some form of bird flu.  Testing in England only identified a few positive samples although over 7000 samples were tested.  This low detection rate may be related to collection procedures which include storing collected swabs a 4 C, where they could dry out and reduce the detection or isolation of avian influenza.
      
The surveillance detected only one H5N1 positive bird and no birds positive for H7.  The H7 or H5 infection of domestic poultry further suggests that the surveillance in England in particular, and Europe in general is inadequate.  The only country to detect H5N1 in live wild birds has been Russia. H5N1 has been detected in dead birds in many European countries.
      
Co-circulation of H5 and H7 is cause for concern.  In 2003 the Netherlands had an H7N7 outbreak,  This strain was readily transmitted from birds to human and human to human.  Over 80 cullers tested positive for H7 antibodies.  However, a follow-up study found H7 antibodies in contacts of the cullers, indicating efficient human to human transmission.  Most cases were mild with either no symptoms or mild flu symptoms.  Most of the cullers also had conjunctivitis.
      
However a veterinarian developed pneumonia and died.  The case is the only reported bird flu fatality by a serotype other than H5N1.  The H7N7 isolated from the veterinarian had a number of unique polymorphisms, including PB2 E627K.  E627K is universally found in H1, H2, and H3 isolates from humans.  Prior to Qinghai Lake, all H5N1 isolates with E627K were from mammals.  Many were from humans infected in Hong Kong in 1997 or Vietnam or Thailand in 2004.  Most of these cases were fatal.  E627K was also linked to virulence in experimental mice and increased polymerase activity at lower temperatures.
      
All 16 H5N1 isolates at Qinghai Lake had E627K.  All reported PB2 sequences for Qinghai H5N1 isolates have also had E627K, including the buzzard isolate from Denmark this year.  Dual infections involving H7 and H5N1 could allow the acquisition of E627K by H7.  The acquisition could be driven by reassortment or recombination.  H7 with E627K could be more virulent in humans and be easily transmitted between humans.  The increased efficiency of human infections could also be acquired by H5N1 via recombination with the receptor binding domain on H7.
      
The H7 infection on a large poultry farm in England highlights the poor surveillance in England as well as the rest of Europe. 
      
Countries reporting large numbers of negatives have serious surveillance issues, which are hazardous to the world’s health. Source : Recombinomics

Bird flu spreads to two more farms

Chickens at two more poultry farms in eastern England have tested positive for bird flu, the environment ministry said on Saturday.

"We can confirm preliminary tests indicate H7N3 (bird flu), but further tests are being carried out," said a spokeswoman, adding two free-range flocks will be slaughtered.

The H7N3 strain of bird flu was found on another farm nearby in the eastern English county of Norfolk earlier this week where 35,000 birds are being culled. The strain is less dangerous to humans than the feared H5N1 bird flu virus. Source : Reuters