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EINet Alert ~ Jul 18, 2008
*****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:
1. Influenza News
- Global: Cumulative number of human cases of avian influenza A/(H5N1)
- Hong Kong: Experts fear H5N1 avian influenza poultry vaccine has lost its effectiveness
- Indonesia: Officials suspect 38-year-old cargo worker died from H5N1 avian influenza infection
- Indonesia: Reports examine country's high H5N1 avian influenza death rate
- Indonesia: Officials detail reasons for withholding H5N1 avian influenza viruses
- Japan: Study finds no behavioral effects from Tamiflu
- USA: "Dragon" protein could be key to H5N1 avian influenza vaccines and therapies
- USA: Supercomputers identify potential new drugs to combat avian influenza
- USA: Vical Inc. to present phase 1 Data For pandemic influenza DNA vaccines
- USA: GAO reports progress in state medical surge planning, still much work to be done
- Egypt: Officials declare H5N1 avian influenza endemic in country's poultry flocks
- AVIAN/PANDEMIC INFLUENZA
- Using Quality Improvement Methods To Improve Public Health Emergency Preparedness: PREPARE For Pandemic Influenza
- Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza Presenting to Sulianti Saroso Infectious Diseases Hospital, Indonesia, 2005-2007
- A Global Perspective on Avian Influenza
- Towards Mutual Trust, Transparency and Equity in Virus Sharing Mechanism: The Avian Influenza Case of Indonesia
- Antiviral Drugs for the Control of Pandemic Influenza Virus
- Risk Communications: In Search of a Pandemic
- PHI2008--Envisioning Options for Integrated Public Health Information Systems for Low Resource Settings: Components, Connections, Partners, Strategies
- Nipah Virus Colloquium 2008
- Community Pan-Flu Preparedness: A Checklist of Key Legal Issues for Healthcare Providers
1. Influenza News
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: 385 (243).
Avian influenza age distribution data from WHO/WPRO: http://www.wpro.who.int/sites/csr/data/data_Graphs.htm.
WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 6.19.08): http://gamapserver.who.int/mapLibrary/
WHO’s timeline of important H5N1-related events (last updated 7.14.08):
Hong Kong: Experts fear H5N1 avian influenza poultry vaccine has lost its effectiveness
A poultry vaccine designed to protect chickens in Hong Kong from H5 avian influenza has lost effectiveness over the past seven years of use, an expert told the Chinese media recently. Yuen Kwok-yung, who heads the microbiology department at the University of Hong Kong, said that the virus is shifting away from the Fujian strain that it was developed for. He told city officials that they must ban all live chickens from markets before the vaccine becomes completely ineffective. Tests on birds in 2005 suggested that the vaccine generated only a quarter of the antibody response it did in 2001. "It takes time for the manufacturers to produce new vaccines. Hong Kong is taking its own risk if it still has live chickens in the market," Yuen said.
In early June, animal health workers detected the virus in poultry feces at several market stalls. They did not say if the testing was done in response to sick or dead birds, and the source of the virus has not been determined. Since then, officials have banned poultry from overnight stays in the market and have proposed a total ban on live poultry in Hong Kong markets. They have offered traders and farmers compensation packages in return for surrendering their sales licenses, but the offer has angered the poultry merchants, who have said the government's offer was too low, according to previous reports.
Indonesia: Officials suspect 38-year-old cargo worker died from H5N1 avian influenza infection
Asnawi Sandri, a 38-year-old father of two, died in the hospital on 10 Jul 2008, days after he came down with symptoms of the disease, including high fever, coughing and breathing difficulties, said Abdul Kadir, his brother-in-law. "The doctor told us he died of bird flu," he said. "The tests came back positive from Jakarta." Sandri lived in Belendung, a village 40 kilometers west of Jakarta, where chickens and ducks freely roam the dusty streets. But it is not clear where he contracted the H5N1 virus, with residents saying none of the poultry had fallen ill or died. Though officials took blood samples from relatives and neighbors, they have not culled any of the birds, Kadir said.
Asked whether she could confirm Sandri's cause of death, Health Ministry spokeswoman Lily Sulistyowati said: "I can't say now whether the tests were positive or negative. . .but we'll let the public know when we release our report at the end of the month." A member of the national bird flu commission, however, reportedly confirmed that the cargo worker died of bird flu, a local health worker said.
Indonesia: Reports examine country's high H5N1 avian influenza death rate
Two reports in the Singapore journal discuss H5N1 cases in Indonesia. One, written by Indonesian Ministry of Health (MOH) officials, looks at the 116 cases, including 94 fatal ones, the country recorded from 2005 through 2007 (the article also defends Indonesia's refusal to share H5N1 virus isolates with the WHO). A second article, written by hospital physicians, profiles the 27 cases, including 21 fatal ones, treated at Sulianti Saroso Infectious Diseases Hospital in Jakarta during that period. (Both reports, including full-text links, can be found in the Articles section of this bulletin).
According to the second report, Indonesia, like most developing countries, has few primary or secondary care hospitals with the protocols, isolation rooms, or cardio-respiratory support equipment to treat patients critically ill with H5N1 influenza. "This is probably the largest single contributor to the high mortality recorded," says the report, written by Sardikin Giriputro, MD, and colleagues. The MOH report cites the infection's nonspecific early clinical features, medical providers' unfamiliarity with the disease, and the late clinical stage of patients when hospitalized as potential causes of the high mortality. But with the increasing CFR over time, it adds, "the probability of an increase in the virulence of H5N1 viruses should also be considered."
Without a fast, convenient test for H5N1 infection, the disease is difficult to diagnose, the hospital article says. The MOH report says that 71 percent of H5N1 patients in Indonesia were treated with the antiviral drug oseltamivir (Tamiflu), but only two patients received it within the recommended time frame of 48 hours after the first symptoms. Those two patients survived. The survival rate decreased as the time to start treatment increased, the report says. Because early recognition is critical, the hospital report says, "The only conceivable solution is the development of cheap, effective point-of-care tests for H5N1 influenza that are as easy to use as a pregnancy test for example. These could be used by a rural primary healthcare clinic or district hospital in any developing country. This is clearly a challenge for the global scientific community."
In other observations, the MOH report says the CFR was significantly higher among females than males—89 percent versus 73 percent; it offers no explanation for the difference. Adults had a higher CFR than children, 83 percent versus 76 percent, but the difference was not significant. The median age for all case-patients was 20 years.
The MOH report also says that 24 percent of the 116 cases "occurred in 10 clusters of blood-related family members." According to the MOH authors, less than half of all the Indonesian patients—46 percent—had an "unmistakable history of direct contact with sick or dead poultry." Another 36 percent had been near sick or dead poultry without direct contact, and the possible sources for the other 18 percent were unclear, the report says.
Indonesia: Officials detail reasons for withholding H5N1 avian influenza viruses
The report, authored by four Indonesian scientists and officials, including Health Minister Siti Fadilah Supari, was published in the June issue of Annals Academy of Medicine Singapore. The article gives the Indonesian version of the sequence of events leading to the government's decision in January 2007 to stop sending H5N1 viruses to the WHO's reference labs. The essential reason was, and remains, the concern that samples provided freely by developing countries are used by companies in wealthy countries to develop vaccines and other products that the developing countries can't afford. Indonesia wants a guarantee that it will share in the benefits derived from the isolates it provides. "If the world continues to operate in this way, the discrepancies will become wider and wider," the article says. "The poor will become poorer and the richer become richer. It is the responsibility of all nations to change this situation."
In January 2007 the government made the "drastic decision" to withhold the specimens. Incidents that offended Indonesia began in April 2006, the report says. Scientists at international meetings started reporting results of analyses of H5N1 viruses from Indonesia, without first getting permission from, or even notifying, Indonesia. In other cases, foreign scientists who studied Indonesian viruses sent to the WHO offered to include Indonesian experts and officials as coauthors, but only "at a very late stage of the manuscript writing," according to the journal article. Another episode that played a role was the emergence in May 2006 of Indonesia's largest H5N1 case cluster—one probable and seven confirmed cases, all in blood relatives, seven of them fatal. The cluster raised fears that a pandemic was beginning. One result was that Indonesia was criticized for releasing genetic data only to a small network of researchers linked to the WHO and the CDC, the Indonesian authors wrote. In response to this "unfair" criticism, Indonesia decided that all its H5N1 virus sequence data at the CDC and Hong Kong University should be deposited in GenBank, a public database.
The Indonesian authors maintain that their policy is not a violation of the International Health Regulations (IHR) as revised in 2005. The regulations do not "literally or specifically" require countries to share biological samples related to potential public health emergencies, they argue. In their view, the IHR can be interpreted as requiring only the sharing of public health information, not biological materials.
The report also traces the series of meetings convened by the WHO to try to resolve the virus-sharing issue. At a meeting in November 2007, participants failed to reach a solution. But according to the Indonesian authors, the meeting brought an acknowledgement of a "breakdown of trust" in the global flu surveillance system and thereby "laid the foundation for a fundamental and significant change to the existing system."
Japan: Study finds no behavioral effects from Tamiflu
Oseltamivir, a neuraminidase inhibitor, is used to prevent and treat seasonal influenza. Because it is considered the most promising drug to date for use during an influenza pandemic, the United States and many other countries are stockpiling it. However, reports of self-injury and delirium in some Japanese children and adolescents who took the drug have raised concerns among regulators in other countries, including the United States. Some of the reported adverse events included the deaths of adolescent patients who fell from windows or balconies or ran into traffic.
Japan has also reported abnormal behaviors in young people who took zanamivir (Relenza), an inhaled neuraminidase inhibitor. However, three rounds of review by the US Food and Drug Administration (FDA) have found no evidence that oseltamivir contributed to neuropsychiataric events. Despite the findings, the FDA this spring advised Roche, the maker of Tamiflu, and GlaxoSmithKline, the maker of Relenza, to add warnings about the reported neuropsychiatric effects to the drug labels. In February 2008, the FDA and Roche sent a letter to US healthcare professionals about the labeling change. The letter acknowledged the reports, noted that the role of Tamiflu in the events had not been established, and advised that flu patients should be monitored for signs of abnormal behavior. In March 2008, Glaxo sent a similar letter to doctors regarding labeling changes for Relenza.
USA: "Dragon" protein could be key to H5N1 avian influenza vaccines and therapies
Scientists and researchers have taken a big step closer to a cure for the most common strain of avian influenza, or "bird flu," the potential pandemic that has claimed more than 200 lives and infected nearly 400 people in 14 countries since it was identified in 2003. Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory, in conjunction with scientists from China and Singapore, have crystallized and characterized the structure of one of the most important protein complexes of the H5N1 virus, the most common strain of bird flu.
The Argonne study focused on H5N1's RNA polymerase protein, which contains three subunits: PA, PB1 and PB2. After performing X-ray crystallography on the protein crystals, the researchers saw a surprising resemblance in the protein structure's image. "When we mapped out the PA subunit, it looked very much like the head of a dragon," said Argonne biophysicist Andrzej Joachimiak. "One domain looked like the dragon's brains, and the other looked like its mouth."
During RNA replication the phase during which the virus "reproduces" all three of the subunits of the protein assemble themselves in a particular configuration. In order for this congregation to take place, the researchers determined the end of the PB1 subunit has to insert itself and bind to the "dragon's mouth" part of the PA subunit. This unexpected relationship between the two subunits could inspire a number of different therapies or vaccines for H5N1 that rely on muzzling the "dragon's" jaws with another molecule or chemical compound that would block the PB1 subunit's access to the PA site, according to Joachimiak. "If we can put a bit in the dragon's mouth, we can slow or even potentially someday stop the spread of avian flu," he said. "Since we are talking about a relatively small protein surface area, finding a way to inhibit RNA replication in H5N1 seems very feasible."
The results of the study will be reported in an upcoming issue of Nature and can be found online at http://dx.doi.org/10.1038/nature07120.
USA: Supercomputers identify potential new drugs to combat avian influenza
Using computers at the San Diego Supercomputing Center and the National Center for Supercomputing Applications in Urbana-Champaign, Ill., the group ran complex programs to mimic the movements of a particularly wiggly protein called neuraminidase 1 (or N1), which the avian flu virus uses to spread infection to new cells. As the proteins changed shape according to physical laws, the computers picked up a "hot pocket" that appeared to be quite dynamic and flexible and therefore a target for medicines aimed at stopping the infection process. According to the researchers, the computer simulations represent an advance over other types of 3-D studies, such as crystallography, because they are able to capture a protein's constant twitching and jiggling in a sort-of motion picture instead of snap shots of the receptor at rest.
The team conducted a "virtual screen" of 1,883 compounds selected from the National Cancer Institute Diversity Set, using a computational tool called AutoDock. About 27 compounds showed significant promise, all having potentially the same or stronger bonding affinity with N1 than currently available anti-flu drugs like Tamiflu and Relenza. "The general idea is that we will be able to make a better drug through the strategic targeting of multiple active site pockets," said Amaro. Binding to more than one site by way of a chemical "bridge" can increase a drug's potency. The research now moves into the lab, where the compounds will undergo testing against the actual virus.
USA: Vical Inc. to present phase 1 Data For pandemic influenza DNA vaccines
The double-blind, placebo-controlled, dose-escalation trial was conducted in approximately 100 healthy volunteers age 18 to 45 at three U.S. clinical sites. The trial was designed to assess safety and immunogenicity following intramuscular vaccination with needle and syringe or with the Biojector(R) 2000 needle-free injection system in different cohorts, and to evaluate monovalent and trivalent Vaxfectin(R)-formulated DNA vaccines at various doses.
Vical's monovalent vaccine contains a plasmid (a closed loop of DNA) encoding the hemagglutinin (HA) surface protein from the H5N1 influenza virus strain, A/Vietnam/1203/04. It is designed primarily to elicit antibody responses against the H5 protein, but could elicit T-cell responses against H5 as well. Vical's trivalent vaccine contains the H5 plasmid plus separate plasmids encoding consensus sequences of two highly-conserved influenza virus proteins: nucleoprotein (NP) and ion channel protein (M2). The trivalent vaccine is designed to elicit a combination of T-cell and antibody responses against all three proteins. Both vaccines are formulated with the company's Vaxfectin(R) adjuvant, which has demonstrated effectiveness with a variety of DNA vaccines in multiple animal models as well as dose-sparing and immune-enhancing ability in animals with a conventional seasonal influenza vaccine.
USA: GAO reports progress in state medical surge planning, still much work to be done
GAO auditors found that of 20 states that were surveyed, many have made progress on three of the key components of medical surge planning: increasing hospital capacity, determining alternative care sites, and recruiting volunteer staff. However, only seven of them had adopted or were developing altered standards of medical care in response to a mass-casualty event. [Full text: http://www.gao.gov/new.items/d08668.pdf ].
Egypt: Officials declare H5N1 avian influenza endemic in country's poultry flocks
Officials in Egypt on 7 Jul 2008 filed a report with the World Organization for Animal Health (OIE) on several H5N1 outbreaks that have occurred in the country since February 2008 and formally declared that the disease is endemic in Egyptian poultry flocks. The report said Egypt will now file updates on its H5N1 outbreaks only every six months. News about poultry outbreaks in Egypt has been sparse this year, though the country reported a handful of human cases in February, March, and April 2008.
According to the latest OIE report, covering the months February though mid June 2008, Egypt has had 19 new outbreaks since the last update. Seven of them occurred after 1 May 2008. The most recent one was a small outbreak in Luxor that affected backyard chickens, geese, and ducks. About half of the most recent outbreaks occurred in backyard flocks; five occurred at live bird markets and four struck commercial farms, three of which housed layer chickens. Most of the outbreaks were along the Nile River delta.
Using Quality Improvement Methods To Improve Public Health Emergency Preparedness: PREPARE For Pandemic Influenza
Lotstein D, et al. Health Affairs. 2008;27(5):w328-w339
Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza Presenting to Sulianti Saroso Infectious Diseases Hospital, Indonesia, 2005-2007
Materials and Methods
A Global Perspective on Avian Influenza
Towards Mutual Trust, Transparency and Equity in Virus Sharing Mechanism: The Avian Influenza Case of Indonesia
Antiviral Drugs for the Control of Pandemic Influenza Virus
Risk Communications: In Search of a Pandemic
PHI2008--Envisioning Options for Integrated Public Health Information Systems for Low Resource Settings: Components, Connections, Partners, Strategies
Dates: 18-19 September 2008
PHI2008 will be hosted by Global Partners in Public Health Informatics (GPPHI) at the Center for Public Health Informatics (CPHI) at the University of Washington, Seattle, WA, USA. The idea of creating a partnership of governmental and non-governmental organizations, academic institutions and companies to define and develop a vision for addressing health challenges in low-resource settings through information and communications technologies was first articulated at PHI2007: Building a Global Partnership in Public Health Informatics. PHI2007 brought together nearly 200 individuals from across the globe who created the impetus for the Global Partners in PHI.
The Rockefeller Foundation recently funded the UW Center for Public Health Informatics to begin the planning process for the Global Partners organization. That process will take place over the coming year through an invitational meeting on Public Health Informatics at the Rockefeller Foundation conference center in Bellagio, Italy as well as at the second annual GPPHI meeting -- PHI2008 -- to be held in September 18-19, 2008 at the Bell Harbor Conference Center, Seattle, Washington, USA. The theme for the PHI2008 meeting is "Envisioning Options for Integrated Public Health Information Systems for Low Resource Settings: Components, Connections, Partners, Strategies."
Dates: 20-21 Oct 2008
In conjunction with the 10th anniversary of the discovery of Nipah virus and in remembrance of the outbreak, a colloquium will be held at University Malaya in Kuala Lumpur, Malaysia on 20-21 Oct 2008. Renowned Nipah virus experts have been invited to describe their latest research, offer an historical perspective of the outbreak and share their personal experiences during the outbreaks. It is hoped that the meeting will help foster closer research collaboration between Nipah virus researchers and generate consensus views on areas concerning Nipah virus that need greater research efforts.
Community Pan-Flu Preparedness: A Checklist of Key Legal Issues for Healthcare Providers
You can obtain a free copy of the Checklist at: