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EINet Alert ~ Sep 22, 2006
*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and notifications for emerging infections affecting the APEC member economies. It was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:
- Global: Cumulative number of human cases of avian influenza A/(H5N1)
- Global: Sanofi tests H7N1 flu vaccine for pandemic readiness
- Iraq: WHO confirms Iraq's third avian flu case
- Indonesia: 2 additional cases of avian influenza confirmed retrospectively
- Indonesia: Report of 66th avian flu case
- Japan: OIE launches Japan-funded project to fight avian flu
- South Korea: 5 Koreans had H5N1 virus but no illness
- Viet Nam: Tests on deceased Vietnamese prove negative for Avian Influenza
- USA: Roche ready to make Tamiflu in US
- USA: Montana Wild Bird Samples Undergo Additional Avian Influenza Testing
- Avian/Pandemic influenza updates
- Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia.
- Influenza Activity--United States and Worldwide, May 21--Sep 9, 2006
- Immunogenicity and Reactogenicity of 1 versus 2 Doses of Trivalent Inactivated Influenza Vaccine in Vaccine-Naive 5–8-Year-Old Children
- Planning for Pandemic Influenza: Business Contingency Planning
- Reports from the global campaign
- Preparing for Highly Pathogenic Avian Influenza: A Manual for Countries at Risk
Global: Cumulative number of human cases of avian influenza A/(H5N1)
Economy / Cases (Deaths)
Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 247 (144).
Global: Sanofi tests H7N1 flu vaccine for pandemic readiness
The trial involves 60 healthy people between the ages of 20 and 40, who will receive 2 doses of either 12 or 24 mg of the vaccine, with or without an aluminum hydroxide adjuvant (immune response booster), said Dr. Lars R. Haaheim of the University of Bergen. H7 avian flu viruses that have infected humans include the H7N7 strain that swept through Dutch poultry farms in 2003, forcing the destruction of about 30 million birds. The virus infected 89 people and caused generally mild symptoms, but 1 veterinarian died. In addition, 2 people were infected and suffered mild flu-like illnesses during a poultry outbreak of highly pathogenic H7N3 virus in British Columbia, Canada, in 2004. Also, a few Italian poultry workers were found to have antibodies to H7N1 and H7N3 viruses when they were tested in connection with avian flu outbreaks that occurred in Italy in 2002 and 2003. The workers did not report any flu-like illness at the time, but 1 reported conjunctivitis.
H5N1 and H7N1 are not the only avian flu strains considered to have current pandemic potential. Chiron Corp. is developing an experimental H9N2 vaccine. That strain caused serious illness in 3 people in Hong Kong in 1999 and 2003. Sanofi Pasteur is producing an experimental H5N1 vaccine for the US government under a $150 million contract awarded Sep 2005.
Iraq: WHO confirms Iraq's third avian flu case
WHO has retrospectively recognized Iraq's third human case of H5N1 avian influenza, involving a 3-year-old boy who was hospitalized with a mild illness in March and recovered. WHO says the boy was hospitalized in Baghdad 15 Mar 2006 but doesn't list his home, the source of his infection, or other details. WHO said shipment of test samples was difficult during Iraq's H5N1 outbreak, which is now considered over. The boy's initial test results were inconclusive, possibly because of sample deterioration during shipment. Repeated testing with different methods confirmed his infection.
The other 2 human cases in Iraq were fatal ones that occurred in Jan, involving a 39-year-old man and his 15-year-old niece from the province of Sulaimaniyah. H5N1 outbreaks in poultry were confirmed in the area in early Feb, and WHO was sent to the scene to assess the situation and support the local response.
Indonesia: 2 additional cases of avian influenza confirmed retrospectively
As of 14 Sep 2006, the Ministry of Health in Indonesia has confirmed 2 additional cases of human infection with the H5N1 avian influenza virus. These cases occurred Mar and May 2006. The first case occurred in a 5-year-old male from East Bekasi, West Java Province. He developed symptoms 4 Mar 2006, was admitted to hospital 6 Mar, and died 19 Mar. Test results, using 2 different assays, showed high antibody titer for H5N1 on consecutive serum samples taken on days 11 and 15 of his illness. These test results are consistent with new WHO criteria for laboratory confirmation. A field investigation at the time found that the case was exposed to diseased poultry, where some birds tested positive for the H5 virus subtype.
The second case is a 27-year-old male from Solok, West Sumatra Province. This case was identified during the tracing of contacts of the man's sister, a 15-year-old female who developed symptoms 17 May 2006 and was subsequently confirmed to be H5N1 infected. Her brother spent 6 days caring for her during her hospital stay. The brother developed mild symptoms, with no fever, 28 May 2006; his symptoms remained mild and he recovered within a few days. Despite his mild and atypical symptoms, the brother was tested as part of the Ministry of Health's protocol for contact tracing and the management of any contacts with symptoms. He was given a 5-day course of oseltamivir beginning 1 Jun and was placed in voluntary isolation pending recovery. Initial tests of samples collected from the 27-year-old male were negative for H5N1 infection. In Aug, follow-up testing of paired-serum samples found a 4-fold rise in neutralization antibody titer for H5N1, which meets the WHO criteria for laboratory confirmation. The male reported no contact with diseased or dead poultry in the days prior to symptom onset as he spent most of his time at the hospital. The investigation determined that he had exposure to his sister during her hospital stay, and that human-to-human transmission could not be ruled out as the source of his infection.
Indonesia: Report of 66th avian flu case
Japan: OIE launches Japan-funded project to fight avian flu
The "OIE/Japan Special Trust Fund Project on Avian Influenza Control in Asia" includes plans to boost early warning and rapid response systems by developing national disease information sharing systems and to update national and regional contingency plans for controlling H5N1 avian influenza. Other activities include epidemiologic training for field veterinarians and outfitting up to 17 laboratories with new equipment in the 8 countries to bolster diagnostic capabilities.
Also, WHO released a "road map" to help governments in the Asia-Pacific region prepare for emerging infectious diseases. Called the Asian Pacific Strategy for Emerging Diseases, the road map advises countries on how to prevent, detect, and respond to these diseases. The document was released by WHO's Western Pacific regional office. "In the early stages of a potential pandemic, it may be possible to stop or delay the spread of the virus by swiftly implementing pandemic influenza rapid response and containment measures," said WHO Acting Regional Director Richard Nesbit. But rapid globalization, urbanization, and increased cross-border travel will make it more challenging to implement such measures, he said. A WHO study conducted in 2004-05 showed that most countries in the region did not have adequate systems to contain a pandemic based on. Nesbit also said the risk of an avian flu pandemic "continues unabated". For more information, see: http://www.wpro.who.int/.
Also a World Bank expert recently proposed a new estimate of the global financial impact of a flu pandemic: $2 trillion. Jim Adams, who heads the World Bank's avian flu task force, made the projection at the annual meeting of the bank and the International Monetary Fund. Adams said a severe pandemic could cut the world gross domestic product by more than 3%.
South Korea: 5 Koreans had H5N1 virus but no illness
No outbreaks of H5N1 avian flu have been reported in South Korea since Mar 2004. Researchers have suggested that the H5N1 strain that struck Korea in 2003 and 2004 was less pathogenic for humans than the strains that infected people in Vietnam and Thailand. In a report in the Mar 2005 Journal of Virology, US and South Korean scientists said they had found differences between the Korean and Vietnamese H5N1 isolates in all 8 viral genes. In addition, Korean and Thai strains of H5N1 differed in their surface protein genes, the scientists said. They also found that the Korean strain had a low level of pathogenicity in mice.
A few asymptomatic and mild human cases of H5N1 infection have been reported previously. When the virus first infected humans in Hong Kong in 1997, a small number of poultry cullers, household contacts of patients, and healthcare workers tested positive despite having no serious illness. In addition, 2 elderly relatives of H5N1 patients in Vietnam tested positive for the virus Mar 2005. And in Jan 2006, WHO reported that 2 young Turkish brothers tested positive but were not sick. WHO has also said 2 cases in Indonesia had been recognised retroactively, including one where human-to-human transmission could not be ruled out. However, recent serologic surveys of healthy people with a history of exposure to H5N1 have found almost no one with evidence of infection. Most recently, researchers reported that among 351 Cambodian villagers who had extensive contact with infected poultry, none had antibodies to the virus.
Viet Nam: Tests on deceased Vietnamese prove negative for Avian Influenza
Also, an apparently peaceful military coup occurred in Thailand, one of the countries hit hard by H5N1 avian flu in 2004 and 2005. In July, the disease resurfaced in poultry after an 8-month lull, followed by WHO confirmation of 2 new human cases, both fatal. The UN's senior coordinator for avian influenza, David Nabarro, said the ongoing political crisis in Thailand may have weakened the government's response to avian flu outbreaks.
USA: Roche ready to make Tamiflu in US
Roche announced that its US supply chain for oseltamivir (Tamiflu), used to treat avian influenza and seasonal flu patients, is fully operational, meaning all aspects of its production are based on US soil. The company said it now has the capability to produce 80 million treatment courses of the drug annually in the US, which is stockpiling oseltamivir as part of efforts to prepare for a flu pandemic. The US Department of Health and Human Services (HHS) had asked Roche to establish a system that involves US sources for all phases of osteltamivir production, from synthesizing shikimic acid, the starting material, to packaging the medication. The company said HHS has ordered 21.3 million treatment courses of oseltamivir for the Strategic National Stockpile, all of which will be delivered by the end of this year. The long-term goal for the stockpile is 81 million courses by the end of 2008. Of that total, HHS says it will buy 50 million courses and will provide a 25% subsidy for states to purchase another 31 million courses. Roche says that with its own manufacturing network and 16 external contractors, it has more than enough capacity to meet the osteltamivir orders from 75 countries that are stockpiling the drug. Global annual production capacity will reach 400 million treatment courses by the end of this year. Approved for prevention and treatment of influenza in adults and children 1 year and older, osteltamivir is intended to treat influenza viruses in all clinical settings. It has been shown to be active against the H5N1 virus in the laboratory and in animals that are infected with an H5N1 avian flu strain taken from humans, according to Roche.
(CIDRAP 9/20/06 http://www.cidrap.umn.edu/ )
USA: Montana Wild Bird Samples Undergo Additional Avian Influenza Testing
The Departments of Agriculture and Interior are working collaboratively with States to sample wild birds throughout the US as well as in Canada and Mexico for the presence of highly pathogenic avian influenza (HPAI). As a result of this expanded testing program, USDA and DOI expect to identify additional cases of common strains of avian influenza in birds. Low pathogenic avian influenza commonly occurs in wild birds and can be found in a number of duck populations including the Northern pintail. It typically causes only minor or no noticeable symptoms. These strains of the virus include LPAI H5N1, commonly referred to as North American H5N1, which is very different from the more severe highly pathogenic H5N1 circulating overseas. Duck populations, including Northern pintail ducks, are commonly hunted. There is no known health risk to hunters or hunting dogs from contact with low pathogenic forms of avian influenza virus. Nevertheless, hunters are always encouraged to use common sense sanitation practices, such as hand washing and thorough cooking, when handling or preparing wildlife of any kind.
Avian/Pandemic influenza updates
- WHO: http://www.who.int/csr/disease/avian_influenza/en/index.html.
- UN FAO: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html. Read the report, “United Against Bird Flu”.
- OIE: http://www.oie.int/eng/en_index.htm.
- US CDC: http://www.cdc.gov/flu/avian/index.htm.
- The US government’s website for pandemic/avian flu: http://www.pandemicflu.gov/. Read the latest statements from US government officials.
- CIDRAP: http://www.cidrap.umn.edu/. Frequently updated news and scholarly articles.
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm.
- American Veterinary Medical Association: http://www.avma.org/public_health/influenza/default.asp.
- US Geological Survey, National Wildlife Health Center Avian Influenza Information:
http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp. Very frequent news updates.
(WHO; FAO, OIE; CDC; CIDRAP; PAHO; AVMA; USGS)
Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia.
Published 10 Sep 2006 in Nature Medicine online. Authors are Menno D de Jong et al. at the Oxford University Clinical Research Unit, 190 Ben Ham Tu, Ho Chi Minh City, Viet Nam.
Abstract: "Avian influenza A (H5N1) viruses cause severe disease in humans, but the basis for their virulence remains unclear. In vitro and animal studies indicate that high and disseminated viral replication is important for disease pathogenesis. Laboratory experiments suggest that virus-induced cytokine dysregulation may contribute to disease severity. To assess the relevance of these findings for human disease, we performed virological and immunological studies in 18 individuals with H5N1 and 8 individuals infected with human influenza virus subtypes. Influenza H5N1 infection in humans is characterized by high pharyngeal virus loads and frequent detection of viral RNA in rectum and blood. Viral RNA in blood was present only in fatal H5N1 cases and was associated with higher pharyngeal viral loads. We observed low peripheral blood T-lymphocyte counts and high chemokine and cytokine levels in H5N1-infected individuals, particularly in those who died, and these correlated with pharyngeal viral loads. Genetic characterization of H5N1 viruses revealed mutations in the viral polymerase complex associated with mammalian adaptation and virulence. Our observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis. The focus of clinical management should be on preventing this intense cytokine response by early diagnosis and effective antiviral treatment."
The authors conclude that their observations point to a central role for high viral burden in the pathogenesis of human H5N1 disease and suggest that timely suppression of viral replication should remain the mainstay for treatment of H5N1 influenza. Detection of virus RNA in blood and gastrointestinal canal are other interesting features of their data. To what extent, however, their observations are specific for H5N1 influenza is debatable. Their 2 groups of patients were not precisely comparable, the seasonal influenza patients being hospitalized at an earlier stage in the disease process and possibly from urban rather than rural communities. Of greater relevance may be the genetic constitution of their patients, since most humans are vulnerable to seasonal influenza, whereas few contract avian influenza. Furthermore, detrimental chemokine and cytokine cascades can be an accompaniment of other respiratory virus infections, such as severe respiratory syncytial virus (RSV) infections in infancy.
Influenza Activity--United States and Worldwide, May 21--Sep 9, 2006
During May 21--Sep 9, WHO and NREVSS collaborating labs in the US tested 14,751 respiratory specimens; 318 (2%) were positive for influenza. Of the positive results, 208 (65%) were influenza B viruses, 58 (18%) were influenza A (H1) viruses, 5 (2%) were influenza A (H3) viruses, and 47 (15%) were influenza A viruses that were not subtyped. The majority (92%) of these isolates were tested from mid-May through late Jun, when 3.6% of specimens tested were positive for influenza. Since July 1, of specimens tested, 0.6% were positive for influenza.
During May 21--Sep 9, the weekly percentage of patient visits to sentinel providers for influenza-like illness (ILI) remained below the national baseline of 2.5% and ranged from 0.6% to 0.9%. The percentage of deaths attributable to pneumonia and influenza as reported by the 122 Cities Mortality Reporting System remained below the epidemic threshold. 1 influenza-related pediatric death was reported to CDC during this period.
During May 21--Sep 9, influenza A (H3), influenza A (H1), and influenza B viruses cocirculated worldwide. Influenza A (H1) viruses predominated overall in Asia; however, in early summer, influenza B viruses predominated in Japan. In North America, small numbers of influenza A and influenza B viruses were reported. In Oceania, influenza A viruses predominated, with both influenza A (H1) and influenza A (H3) viruses circulating; influenza B viruses circulated at lower levels. In South America, influenza A (H1) viruses were most commonly reported, but influenza A (H3) and influenza B viruses also were identified.
Of 23 influenza A (H1) viruses that were collected during May 21--Sep 9 (3 from Asia, 18 from Latin America, and 2 from the US) and analyzed at CDC, 17 (74%) were antigenically similar to A/New Caledonia/20/99, the H1N1 component of the 2006--07 influenza vaccine. 6 (26%) of the influenza A (H1) viruses had reduced titers to antisera produced against A/New Caledonia. Of the 19 influenza A (H3) viruses (1 from Europe, 12 from Latin America, 3 from Asia, 2 from Oceania, and 1 from the US) that were characterized, 18 (95%) were antigenically similar to A/Wisconsin/67/2005, the H3N2 component of the 2006--07 influenza vaccine, whereas 1 (5%) had reduced titers to A/Wisconsin/67/2005.
Influenza B viruses currently circulating worldwide can be divided into 2 antigenically distinct lineages represented by B/Yamagata/16/88 and B/Victoria/2/87. The B component of the 2006--07 influenza vaccine belongs to the B/Victoria lineage. Of the 26 influenza B isolates collected during May 21--Sep 9 and characterized at CDC, 23 belonged to the B/Victoria lineage (1 from Europe, 5 from Latin America, 6 from Asia, and 11 from the US). 10 (43%) of the B/Victoria-lineage viruses were similar to B/Ohio/01/2005, the B component of the 2006--07 influenza vaccine, whereas 13 (57%) had reduced titers to B/Ohio.
During Dec 1, 2003--Sep 8, 2006, a total of 244 human cases of avian influenza A (H5N1) infection were reported to WHO from 10 countries; 23 of these cases were reported since May 21, 2006. A total of 143 (59%) of the 244 cases were fatal. All human cases were reported from Asia (Azerbaijan, Cambodia, China, Indonesia, Iraq, Thailand, Turkey, and Vietnam) and Africa (Djibouti and Egypt), with the most recent cases reported from China, Indonesia, and Thailand. To date, no human case of avian influenza A (H5N1) virus infection has been identified in the US.
Immunogenicity and Reactogenicity of 1 versus 2 Doses of Trivalent Inactivated Influenza Vaccine in Vaccine-Naive 5–8-Year-Old Children
Planning for Pandemic Influenza: Business Contingency Planning
Register for your free copy of CIDRAP's 10-Point Framework for Pandemic Influenza Business Contingency Planning. This original document was produced by CIDRAP staff and reviewed by 19 business professionals representing a wide spectrum of industry sectors and relevant job functions. Go to: http://www.cidrap.umn.edu/10points/go.do
(CIDRAP http://www.cidrap.umn.edu/ )
Reports from the global campaign
Preparing for Highly Pathogenic Avian Influenza: A Manual for Countries at Risk