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Asymptomatic H5N1 Bird Flu in Novosibirsk Russia
Recombinomics Commentary
August 6, 2005
The disease has been reported in a total of 13 villages:
In 5 villages, birds have shown clinical signs of the disease and deaths have been reported; birds have tested positive to antibodies to H5 and the virus has been isolated.
In 4 villages, no deaths have been reported, but birds have tested positive for antibodies to H5 and the virus has been isolated.
In the remaining 4 villages, no deaths have been reported, nor has the virus been detected in any of the birds. However, birds have tested positive to antibodies to H5.
Diagnosis:
Laboratories where diagnosis was made Number of animals examined Diagnostic tests used Dates Results
Federal Centre for Animal Health (ARRIAH) 70 ELISA(1) for antigen detection 23 July - 5 Aug. 2005 positive
All-Russia State Research Institute for Control, Standardisation and Certification of Veterinary Preparations 5 PCR(2) (M-protein gene) 23 July - 5 Aug. 2005 positive
Association for Scientific Production 'NPO Vektor' 62 haemagglutination test 23 July - 5 Aug. 2005 positive
Novosibirsk inter-regional veterinary laboratory, Federal Governmental University 5,324 ELISA(1) for antibody detection 28 July 2005 positive
Source of outbreaks or origin of infection: the epidemiological analysis has shown that the disease started in poultry in contact with wild waterfowl at open water reservoirs. Waterfowl are considered the primary source of the virus. In addition, there are reports of the disease in wild birds. Infection of domestic birds in all the affected localities, some of which are up to 600 km apart, occurred simultaneously. In all cases, the source of infection was wild waterfowl in lakes frequented by domestic birds.
The above detail the August 5 Russian OIE report helps explain the rapid spread of H5N1 along the southern border of Russia, the northern border of Kazakhstan, and Mongolia. Since H5 has been detected in the Chany Lake area previously, birds with antibody in the absence of isolated virus may have antibody from prior infections. The dead birds with antibody and virus probably represent a situation similar to the Qinghai Lake isolates from 12 dead birds. The birds with no deaths but antibody and virus are analogous to the asymptomatic birds described in Vietnam and Thailand. As noted in the WHO warning in the fall of 2004, H5N1 from fatal human infections could grow to high titers in experimentally infected ducks in the absence of symptoms.
The asymptomatic birds can transport H5N1, explaining the link between migratory birds and outbreaks in domestic poultry in Xinjiang Province (Tacheng and Changji), as well as the spread in the three countries to the north and west of the outbreaks in China.
The simultaneous appearance of symptoms in geographically dispersed regions also suggests a migratory bird vector. At Qinghai Lake, initial reports described 5 species infected by H5N1. The sequence data from 12 bird representing 3 species were virtually identical to each other. However, these isolates were all from fatal infections during a short time frame. The Qinghai report provided no data on isolates from live birds or changes. Moreover, the data suggested that some birds were dually infected, indicating that a large sampling was required.
Initial reports from Vektor labs indicate 9 isolates have been sequenced and they are similar to isolates from Vietnam, but distinct. The description would match a description of the Qinghai sequences, suggesting the recent isolates linked to migratory birds may have evolved similarly.
The simultaneous appearance of H5N1 in geographically dispersed areas raises questions on the intervention models that used outbreaks that begin at a single location. The sequences of the Qinghai isolates contained mammalian polymorphisms commonly found in humans and swine. The acquisition of these polymorphisms in birds could also generate simultaneous outbreaks of H5N1 in humans, eliminating the possibility of control via anti-virals and quarantine.
The rapid spread of the Qinghai-related isolates also impacts the pandemic vaccine effort. The protein difference in HA and NA of the Qinghai isolates relative to isolates in Vietnam strongly suggests that the current vaccine under development will not be effective against the Qinghai isolates. The ability of these isolates to infect and kill humans remains controversial. Boxun reports described 10 different H5N1 strains in China, including RK7. The description of RK7 matches the Qinghai isolates and details have ben published on human fatalities in Qinghai province. There have also been reports of pneumonia clusters in Tacheng. In addition to the China cases, there have been three groups of suspect human cases in Kazakhstan.
The first case was a poultry worker who developed double pneumonia and was in critical condition. The cause of his double pneumonia has not been described. He was said to have developed symptoms prior to the reported outbreak in the Pavlodar region, but the outbreak in Tacheng was at the beginning of June, well in advance of the patients hospitalization in late July.
Similarly, a family of 4 in Irtysh developed symptoms after eating goose meat from the same region. Their status has not been update.
A third cluster was reported in Eastern Kazakhstan. 15 people developed symptoms after eating chicken cutlets at a dining hall.
Russia has not reported any human cases, but most of the initial bird cases are in sparsely populated regions. As the H5N1 migrates into Europe and more densely populated areas, human infections may be reported. The H5N1 from Qinghai has clearly acquired a number of human polymorphisms, including PB2 E627K, which is associated with a poor outcome in humans infected with H5N1 or H7N7 containing E627K..
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