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Vol. Vol. XI No. 9 ~EINet News Brief ~ 2 May 2008 ~ EINet News Briefs ~ May 02, 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)
- Denmark: Officials identify low pathogenic H7 avian influenza in poultry
- India (Tripura): Samples from more birds positive for H5N1 avian influenza
- Indonesia: Economy runs massive H5N1 avian influenza drill
- Japan (Akita): Officials confirm H5N1 avian influenza virus in swans
- USA: HHS adds H5N1 avian influenza clade 2.2 vaccine to US stockpile
- USA: IOM argues that United States needs larger stockpile of antivirals
- Viet Nam (Son La): H5N1 avian influenza detected in another province

2. Infectious Disease News
- China (Anhui): Officials concerned over rise in hand, foot and mouth, 1884 cases/20 deaths
- China: Chinese officials dispute culpability for heparin related death in the US
- Malaysia: Dengue statistics show a decline from 2007, but officials claim they can do better
- Malaysia (Johor): 16 people are diagnosed with chikungunya
- Malaysia (Labuan): Six Filipinos hospitalized due to cholera infection
- Russia (Ingushetia): Man dies from Crimean-Congo Hemorrhagic Fever infection
- Singapore: Outbreak of hand, foot and mouth disease, Brunei also affected
- Thailand: Officials concerned with rise in dengue cases
- Canada (Toronto): City officials approve antivirals for city workers
- Canada (Ontario): Measles outbreak continues, source of initial infection still unknown
- Peru (Callao): Two crew members of Chinese fishing boat die, adenovirus suspected
- USA (Arizona): Measles outbreak shows no signs of slowing

3. Updates
- AVIAN PANDEMIC INFLUENZA

4. Articles
- Pandemic influenza planning in the United States from a health disparities perspective
- Public Response to Community Mitigation Measures for Pandemic Influenza
- Emerging Infectious Diseases –Volume 14, Number 5 – May 2008
- Serologic and genetic characterization analyses of a highly pathogenic influenza virus
- Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System

5. Notifications
- APEC EINet Pandemic Influenza Preparedness Virtual Symposium: Partnerships and Continuity Planning for Critical Systems
- Pandemic Planning for Academic Institutions (Webcast)
- US Federal officials discuss concerns about school-closures during a pandemic


1. Influenza News

Global
Global: Cumulative number of human cases of avian influenza A/(H5N1)
Economy / Cases (Deaths)

2008China / 3 (3)
Egypt / 7 (3)
Indonesia / 16 (13)
Viet Nam / 5 (5)
Total / 31 (24)

2007
Cambodia / 1 (1)
China / 5 (3)
Egypt / 25 (9)
Indonesia / 42 (37)
Laos / 2 (2)
Myanmar / 1 (0)
Nigeria / 1 (1)
Pakistan / 3 (1)
Viet Nam 8 (5)
Total / 88 (59)

2006
Azerbaijan / 8 (5)
Cambodia / 2 (2)
China / 13 (8)
Djibouti / 1 (0)
Egypt / 18 (10)
Indonesia / 55(45)
Iraq / 3 (2)
Thailand / 3 (3)
Turkey / 12 (4)
Total / 115 (79)

2005
Cambodia / 4 (4)
China / 8 (5)
Indonesia / 20 (13)
Thailand / 5 (2)
Viet Nam / 61 (19)
Total / 98 (43)

2004
Thailand / 17 (12)
Viet Nam / 29 (20)
Total / 46 (32)

2003
China / 1 (1)
Viet Nam / 3 (3)
Total / 4 (4)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 382(241).
(WHO 4.30.08 http://www.who.int/csr/disease/avian_influenza/en/index.html )

Avian influenza age distribution data from WHO/WPRO: http://www.wpro.who.int/sites/csr/data/data_Graphs.htm.
(WHO/WPRO 4.17.08)

WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 4.17.08): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 4.24.08): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html

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Europe/Near East
Denmark: Officials identify low pathogenic H7 avian influenza in poultry
Some 2,000 chickens and ducks had to be slaughtered in Fyn in Denmark on 29 Apr 2008 after a routine test uncovered a strain of bird influenza (low pathogenic H7 avian influenza), putting Norwegians on high alert.

Norway is keeping close contact with the Danish animal health authorities and continues to have a ban on fowl being allowed freedom to go outdoors (except under a roof and surrounded by netting. This is the first time in two years that the bird flu has been found in Denmark and the agricultural authorities have put an export ban in place for the time being. Although it was dramatic for the farmers affected, the Danish veterinary authorities tried to keep things calm, pointing out that the bird flu strain found is not the most dangerous one � H5N1-influenza.
(ProMED 4.29.08)

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Asia
India (Tripura): Samples from more birds positive for H5N1 avian influenza
Veterinary officials in India said on 26 Apr 2008 that samples from more birds in Tripura state had tested positive for the H5N1 virus, pushing to three the number of areas hit in the state in the two weeks prior to 26 Apr 2008. Asim Roy Barman, state animal resources department director, said that the two earlier outbreak sites were within four km of the border with Bangladesh, which has had extensive H5N1 outbreaks over the past several months. However, he said the latest outbreak was a surprise to officials because it is 50 km from the Bangladesh border. In April 2008, Tripura became the second Indian state to report H5N1 outbreaks this year. Nearly all of Tripura state, located in the far northeastern section of India, borders Bangladesh.
(CIDRAP 4.28.08)

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Indonesia: Economy runs massive H5N1 avian influenza drill
Hundreds of Indonesian villagers and health workers took part in a massive drill 25 Apr 2008 to prepare for a potentially devastating outbreak of human-to-human bird flu. The largest bird flu drill ever held in Indonesia, the country worst hit by the virus, involved the simulated outbreak of a pandemic that experts say could rapidly spread across the globe killing millions of people.

"This is the biggest drill in Indonesia. The objective is to test the preparedness of bird flu officials to manage an outbreak in case it happens," health ministry disease control chief I Nyoman Kandun said.

The three-day drill began at Tukaddaya village outside Jembrana, 80 km west of Denpasar on the island of Bali, with a man presenting himself to a clinic with the symptoms of avian influenza. Health workers initially think he has been in contact with infected chickens — until now the main way the virus has been caught by humans — but the man explains that he has not been handling birds at all. The virus is traced to another man in the village and health workers have to confront their worst fear — the first outbreak of bird flu being transmitted from human to human. The village is sealed off, birds and ducks are slaughtered and officials scramble to find and isolate other victims as they present themselves.

Villager I Wayan Nerken, 51, whose role in the drill was to report the sudden "death" of one of his chickens, said the exercise was "very useful. So far the information that we've got about bird flu has been limited to what we've seen on television. We don't really understand (how to act) when an infection happens," he said. More than 50 foreigners including 14 diplomats are taking part in the exercise, which is being covered by more than 50 local and international journalists.
(Agence France Presse 4.25.08)

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Japan (Akita): Officials confirm H5N1 avian influenza virus in swans
Japan on 29 Apr 2008 confirmed four swans found last week were infected with the H5N1 strain of bird flu. It was the first case of bird flu in Japan since March 2007 when the highly virulent H5N1 strain was found in a wild bird in Kumamoto prefecture on Japan's southern Kyushu Island.

The swans, three of which had died, were found on the shores of Lake Towada in northern Akita prefecture on 21 Apr 2008, the prefectural government said. Inspectors had initially detected the H5 subtype of bird flu in the dead swans and conducted further tests, the local government said 28 Apr 2008. Japan has been stepping up checks of birds after a series of bird flu outbreaks in South Korea over the past month. There are no chicken farms within a 10 km radius of the area where the swans were found, and no unusual incidents were noted at other farms. Local authorities plan to conduct on-site inspections at 15 farms within a radius of 30 km of the site where the swans were found, the official said.

Earlier on 29 Apr 2008, South Korea reported a suspected bird flu outbreak at a chicken farm in Ulsan City which, if confirmed, would be the first in the southeast, as the country grapples with its worst outbreak of avian influenza. South Korea previously confirmed 20 cases of the H5N1 strain in poultry in less than a month, despite having killed more than five million chickens and ducks, as the virus spreads at its fastest rate since the country reported its first case in 2003. No human deaths from the disease have been reported in South Korea or Japan.
(ProMED 4.29.08)

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Americas
USA: HHS adds H5N1 avian influenza clade 2.2 vaccine to US stockpile
The US Department of Health and Human Services (HHS) has accepted the first batch of H5N1 avian influenza vaccine based on the H5N1 variant known as clade 2.2, which has spread most widely across Asia, Europe, and Africa. Sanofi Pasteur announced 28 Apr 2008 that HHS is paying $192.5 million for the vaccine, which is being shipped in bulk form. The number of doses it represents will depend on the final formulation of the vaccine, but the amount could be used to make from 6.4 million to 38.5 million doses or more, the company said.

"This acceptance represents the US government's latest effort to diversify the vaccine stockpile program to include new strains of the H5N1 virus," Sanofi said. The vaccine is based on H5N1 clade 2.2, the variant that caused the outbreak in bar-headed geese and other birds at China's Quinghai Lake in 2005.

Clade 2.2 viruses have sparked outbreaks in more than 60 countries in Africa, Asia, and Europe, with human cases in Azerbaijan, China, Djibouti, Egypt, Iraq, Nigeria, Pakistan, and Turkey, the World Health Organization reported in February. US officials hope that existing H5N1 vaccines will provide some protection for critical personnel in the early stages of a pandemic, should the H5N1 virus evolve into a pandemic strain. In a pandemic, it is expected to take several months to develop and start producing a vaccine closely matched to the new strain.

The stockpile was begun with a Sanofi vaccine based on a clade 1 virus from Vietnam, he said. In 2006 and 2007 HHS purchased vaccines based on clade 2.1, a strain identified in Indonesia, from Sanofi, GlaxoSmithKline (GSK), and Novartis, he reported. In addition, he said the agency has bought some vaccine from Novartis that's based on clade 2.3, a strain from Anhui province in China. Robinson said the stockpile currently contains enough H5N1 vaccine to cover about 12 million to 13 million people, assuming two 90-microgram (mcg) doses per person. The vaccines are stored in bulk form, and it may be possible to use smaller doses if various trials of the vaccines with adjuvants (immune-boosting chemicals) are successful, he said.

"This fall we should hit our goal [of having enough vaccine] for 20 million people," Robinson said. "If the adjuvants become a reality we'll be able to have more than that."

Sanofi said the clade 2.2 vaccine supplied to HHS would be good for 6.4 million 90-mcg doses. But if the amount could be reduced to 15 mcg per dose � the amount for each strain in seasonal flu vaccines � the supply would amount to 38.5 million doses. "If we had a really successful adjuvant, it could be even much higher than the numbers in the press release," Sanofi spokesman Len Lavenda said. He said the company is working on adjuvants.
(CIDRAP 4.29.08)

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USA: IOM argues that United States needs larger stockpile of antivirals
The US government will need to expand its stockpile of antiviral drugs if the goal is to have enough doses to treat all patients and provide preventive treatment for some others at risk in an influenza pandemic, the Institute of Medicine (IOM) says in a report issued 25 Apr 2008. An IOM committee of experts asserts that the government needs to clarify its goals concerning antiviral use in a pandemic, because current planning documents are fuzzy on prophylactic use of the drugs. The nation currently has about 71 million treatment courses of antivirals in federal and state stockpiles, with a goal of 81 million courses, the report says. But in a pandemic, it might take more than twice that amount to treat sick patients and offer preventive doses to people at risk for exposure on the job, it asserts. In other key recommendations, the IOM report says:

  • The Department of Health and Human Services (HHS) should launch a national effort to develop a prioritization plan for antiviral treatment and prophylaxis in a pandemic, similar to the existing program for pandemic flu vaccine allocation. The plan should be designed to be adjusted as needed during a pandemic.
  • Healthcare and emergency workers who are in short supply and face repeated exposure to flu should be first in line for preventive antiviral treatment in a pandemic, followed by other healthcare and emergency workers and then by household contacts of flu patients.
  • The government should set up a federal advisory panel, similar to the Advisory Committee on Immunization Practices, to provide advice on public health and medical responses to a pandemic, including antiviral use.
  • The Shelf-Life Extension Program (SLEP) for antivirals in the federal stockpile—which extends the official shelf life for oseltamivir (Tamiflu) by two years — should be expanded to include state and private-sector antiviral stockpiles.
  • The government should consider using recently expired drugs that are in supplies outside the SLEP if a pandemic causes a shortage.

The report, titled Antivirals for Pandemic Influenza: Guidance on Developing a Distribution and Dispensing Program, was prepared by an eight-member committee chaired by June M. Osborn, MD, president emerita of the Josiah Macy, Jr. Foundation. As noted in the document, health officials hope that antiviral drugs will help the nation cope during the first several months of a pandemic, when no vaccine closely matched to the emerging virus will be available. The IOM committee was assigned to recommend best practices and policies for implementing a program of treatment and prophylaxis. However, because of the limited size of the national antiviral stockpile and the unclear goals for its use, "the committee was unable to provide specific guidance in regard to best methods and sites for dispensing," the report summary states.

"Based on federal government documents, it is not yet clear whether the goal of antiviral use is treatment, or a combination of treatment and prophylaxis," the IOM says. The Homeland Security Council's pandemic flu strategy says plans call for using antivirals only for treatment once a pandemic is under way. But HHS's pandemic flu plan gives recommendations on the use of antivirals for treatment and prophylaxis throughout a pandemic. Accordingly, says the report, "The committee recommends that the federal government clarify the national goals for antiviral use in an influenza pandemic. If these goals include treatment of all anticipated cases and a level of prophylaxis, fiscal appropriations will be needed to expand the national stockpile to meet these goals."
(CIDRAP 4.25.08)

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Viet Nam (Son La): H5N1 avian influenza detected in another province
Animal health officials in Vietnam said the H5N1 virus has been detected in another province, Son La in the northern part of the country, a report said 28 Apr 2008. The report said Vietnam's Department of Animal Health said that the outbreak occurred among chickens and ducks in a backyard poultry flock. Provincial authorities have isolated the site and disinfected the farm to prevent the spread of the virus, according to the report. The animal health department said two other locations in Vietnam are also battling the H5N1 virus: Tien Giang province in the south and Can Tho, the largest city in the Mekong Delta.
(CIDRAP 4.28.08)

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2. Infectious Disease News

Asia
China (Anhui): Officials concerned over rise in hand, foot and mouth, 1884 cases/20 deaths
As of 29 Apr 2008, a total of 1884 cases including 20 deaths of hand, foot and mouth disease (HFMD) due to enterovirus 71 (EV-71) have been reported among infants and young children. The 20 deaths are in Fuyang city in Anhui Province, China. All fatal cases died of serious complications such as neurogenic pulmonary edema due to EV-71 infection. The overall case fatality rate has decreased from 11 percent during 10-31 Mar 2008 to 0.2 percent during 17-29 Apr 2008. The number of hospitalized cases has gradually increased since late Mar 2008 with a sharp increase in the number of cases since 19 Apr 2008.

Public health experts predict that the number of cases will continue to increase and will peak around June-July 2008. Retrospective case investigation has revealed that sporadic cases had occurred since the beginning of March 2008. Cases have been reported from all over Fuyang city. Testing for a variety of respiratory diseases of the initial cases did not reveal any conclusive results. Subsequently, additional testing and several expert consultations were conducted at the national level. On 23 Apr 2008, EV-71 was confirmed. Health authorities informed WHO and Hong Kong Department of Health and the Province of Taiwan's Department of Health immediately on these results. Chinese health authorities have put in place targeted prevention and control measures in Fuyang city and Anhui Province, including enhanced surveillance, training of health care workers at all levels in treatment, prevention and control, strengthening of environmental health management, and the supervision and monitoring of drinking water quality. A public awareness campaign is ongoing, stressing the need for good personal hygiene.

Non-polio enteroviruses are common and distributed worldwide. Although infection often has no symptoms and goes unnoticed, these viruses are also associated with occasional outbreaks in which a larger-than-usual number of patients develop clinical disease, sometimes with fatal consequences. No specific anti-viral therapy is available, and treatment focuses on prevention of complications. As there is no vaccine for this virus, control measures are focused on classical hygiene measures including frequent hand washing and disinfection of soiled clothing and surfaces. In certain situations, it may be advisable to close child-care facilities and schools to reduce the intensity of transmission. It is not necessary to restrict travel or trade.
(ProMED 5.1.08)

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China: Chinese officials dispute culpability for heparin related death in the US
A contaminated blood thinner from China has been found in drug supplies in 11 countries, and federal officials said 21 Apr 2008 they had discovered a clear link between the contaminant and severe reactions now associated with 81 deaths in the USA. But a Chinese official disputed the assertion that the contaminant found in the drug, heparin, caused any deaths and insisted that his country's inspectors be allowed to inspect the American plant where the finished heparin vials were made. He said any future agreement to allow American inspections of Chinese firms should be reciprocal. "We don't have strong evidence to show that it is heparin or its contaminant that caused the problem," said the official, Ning Chen, second secretary at the Chinese Embassy. Chen said that illnesses associated with contaminated heparin had occurred only in the USA, which he said suggested that the problem arose in this country.

Dr. Janet Woodcock, director of the US Food & Drug Administration’s (FDA's ) drug center, said that German regulators uncovered a cluster of illnesses among dialysis patients who took contaminated heparin. She said Chinese officials had conceded that heparin produced in their country contained a contaminant, though they say it was not connected to the illnesses. "Heparin should not be contaminated, regardless of whether or not that contamination caused acute adverse events," Dr Woodcock said. "We are fairly confident based on the biological information that we have had that this contaminant is capable of triggering these adverse reactions." The FDA sent a warning letter on 21 Apr 2008 to Changzhou SPL, the Chinese plant identified as the source of contaminated heparin made by Baxter International in the United States. It warned that the plant used unclean tanks to make heparin, that it accepted raw materials from an unacceptable vendor, and that it had no adequate way to remove impurities.

The FDA has identified 12 Chinese companies that have supplied contaminated heparin to 11 countries -- Australia, Canada, China, Denmark, France, Germany, Italy, Japan, the Netherlands, New Zealand, and the United States. Deborah Autor, director of compliance at the FDA's drug center, said the agency did not know the original source of all the contamination or the points in the suppl had been tested with the most sensitive assays and had been found to be uncontaminated.

Scientific Protein Laboratories and Changzhou SPL said the company regretted the agency's decision to send a warning letter that, it said, did not reflect the company's current safety practices. The company said it had no way of detecting a contaminant present in heparin supplies throughout China. Baxter International, which bought heparin ingredients from SPL and sold the finished drug in the US, said its tests confirmed that the contaminant could cause illness. It disputed the FDA's analysis that its product was linked with 81 deaths, saying it had identified only five in which its product "may have contributed to the adverse outcome, though there is not yet enough medical data available to draw a firm conclusion that the reaction caused the death."
(ProMED 4.22.08)

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Malaysia: Dengue statistics show a decline from 2007, but officials claim they can do better
In the first three months of 2008, five municipal councils have been singled out as hotspots for dengue fever. They are Shah Alam (719 cases), Klang (582), Johor Baru (536), Kajang (514), and Subang Jaya (457). Health minister Datuk Liow Tiong Lai said: "It looks quite serious in the Klang Valley." Liow also revealed that Selangor topped the list for dengue fever with 3742 cases. It was followed by Kuala Lumpur (1119 cases) and Perak (1084 cases).

"We can prevent this. But we need the cooperation and support of the public besides cooperation of agencies especially local councils to come forward and work with the ministry. Then, we should be able to reduce the number of dengue fever cases." There has been a 29 percent decline in 2008 compared to the same period [1 Jan and 31 Mar] in 2007, which saw 34 deaths. So far, 25 people have died. It had been reported that an immediate stop work order was carried out on 25 construction sites in the Klang Valley by the Selangor Health Department for failing to keep the areas free from the Aedes mosquito.
(ProMED 4.29.08)

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Malaysia (Johor): 16 people are diagnosed with chikungunya
A total of 16 people in Kampung Ulu Choh [Johor state] have been diagnosed with chikungunya, a seldom-lethal viral fever with symptoms similar to dengue. Women and Family Development, Welfare and Health state Committee chairman, Dr Robia Kosai, said although the symptoms were similar to dengue fever, it was not a life-threatening disease [some deaths attributed to chikungunya virus infection occurred in the massive chikungunya epidemic that occurred in Indian Ocean islands 2005-2006 and in India].

"It is under control and was not classified as an outbreak. Chikungunya is a self-limiting disease, which means the patients will recover from it in due course, while treatment is symptomatic." Dr Robia said patients would suffer viral fever, including joint pains and measles-like rashes. Since the virus is spread by the Aedes mosquito, the same mosquito that carries the dengue virus, preventive measures such as fogging and health checks are conducted by the state Health Department in targeted areas.
(ProMED 4.28.08)

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Malaysia (Labuan): Six Filipinos hospitalized due to cholera infection
After being confirmed of having cholera, six people were admitted to the general hospital in Labuan. The six, who are Filipinos aged between one and 21, were the latest victims detected on the island in 2008. All of them were reported to be in stable condition. Of the victims four were from Pulau Daat, while the other two were from Kg Muslim. Confirming this to Bernama on 23 April 2008, State Health Department Director Dr Zaini Hussin said that his health enforcement unit would continue to monitor the situation in the area.
(ProMED 4.25.08)

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Russia (Ingushetia): Man dies from Crimean-Congo Hemorrhagic Fever infection
The Regional Centre of the Ministry of Emergencies has announced that a patient with Crimean-Congo hemorrhagic fever (CCHF) died 27 Apr 2008. He was admitted to the hospital intensive care unit in a severe condition and died several days later. Three people who had close contact with the patient are in the hospital now for observation. Another 25 people who had some contact with the patient are now under surveillance. Healthcare workers are carrying out home visits to identify suspected cases. There are 6,000 people living in 600 households. Blood specimens have been taken from all contact persons and sent to the Stavrapol Research Anti-plague Institute. As of 28 Apr 2008, there are no new cases.
(ProMED 4.30.08)

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Singapore: Outbreak of hand, foot and mouth disease, Brunei also affected
Several parents have expressed their concern over the Hand, Foot and Mouth Disease (HFMD) outbreak which has been reported in Singapore, where 880 new cases were reported in four days. This is especially so for those who traveled to the neighboring country Malaysia. Some teachers, administrative staff and cleaners scrubbed Singapore preschools and childcare centers on 25 Apr 2008 to curb the HFMD outbreak. With the latest Health Ministry of Singapore data showing 2008's total infections at 8400, officials are now providing daily updates instead of weekly ones.

At least 16 schools have been closed because of the outbreak. Another nine have been urged to voluntarily shut down for 10 days. The disinfection is aimed at halting the transmission of the disease, which is spread through saliva, blister fluid, feces and droplets in the air. Professionals have been called to service air conditioners and fumigate.

Sources said such HFMD cases have also occurred in Brunei but have been on the decline lately. From early to the end of August 2007, about 90 HFMD cases were recorded in Brunei, the Ministry of Health said, while from early March to mid April 2006, some 580 cases were recorded.
(ProMED 4.27.08)

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Thailand: Officials concerned with rise in dengue cases
Thailand's Public Health Ministry warned the public to be alert regarding dengue fever prevention measures as 12 patients died and over 10,000 have suffered from the disease during the first quarter of 2008, according to Chaiya Sasomsub, minister of public health, on 28 Apr 2008. From 1 Jan 2008 to 19 Apr 2008, the cumulative number of dengue fever patients soared to 10,901 and 99 percent of the patients completely recovered, Chaiya said. However, 12 patients in the country have been killed by dengue fever in 2008, he said. "When compared with the same period last in 2007, the number of dengue fever patients has increased by 80 percent," the minister was quoted as saying. Chaiya said he had instructed local health officials nationwide to maintain the campaign to eradicate the mosquito breeding habitats.
(ProMED 4.29.08)

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Americas
Canada (Toronto): City officials approve antivirals for city workers
Toronto's city council on 28 Apr 2008 approved a $1.5 million plan to treat nearly half of the municipal employee workforce with antiviral medication in the event of a pandemic, making it the first major Canadian city to stockpile the drugs. In approving the proposal to stockpile antiviral medications for some city employees, the Toronto city council heeded the recommendations of its medical officer of health, David McKeown, who advised that the city should act now to avoid a delay in acquiring a supply of oseltamivir (Tamiflu). Oseltamivir, a neuraminidase inhibitor, is used to treat seasonal flu and is both the first-choice drug for treating people infected with H5N1 avian influenza and the best hope for treatment if H5N1 evolves into a pandemic strain. Many countries have made stockpiling osteltamivir and other antiviral medications a component of their pandemic planning. "I believe it is a prudent measure to take for an event that is highly likely to occur," McKeown said.

In addition to the initial $1.5 million purchase that would treat up to 13,000 employees, the council also appropriated $606,000 to store the drug in a warehouse. Toronto could spend up to $5 million to stockpile drugs to keep the city workforce in place during an influenza pandemic. Though most council members supported the plan, some questioned which of Toronto's 24,000 municipal employees would receive the drug and how city officials would dispense the antivirals. Other council members asked whether the city was rushing into the antiviral purchase and if the city was taking on an extra burden that provincial and federal officials should shoulder. Though federal and state governments are the groups that typically fund and manage antiviral stockpiles, some major cities are organizing their own stockpiles. Terence Hurley, a spokesman for Roche, the maker of Tamiflu, pointed out that a US federal plan to subsidize state antiviral purchases contains a mechanism for some localities — Chicago, Los Angeles County, and New York City — to purchase the drug with federal support.
(CIDRAP 4.29.08)

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Canada (Ontario): Measles outbreak continues, source of initial infection still unknown
As of 14 Apr 2008, six health regions in southern Ontario, Canada, have reported 10 cases of IgM-positive measles since 19 Mar 2008. Of those cases, eight are epidemiologically linked either directly to or through a generation of cases who attended a Toronto attraction and were exposed to the initial case in this cluster. The source of this initial infection is not known. The first reported case had rash onset on 12 Mar 2008. One of the cases is likely imported. This person traveled from a high incidence measles area in the middle of the incubation period. This case is confirmed to be a different genotype (D4). Five of the epidemiologically linked cases have been genotyped so far and were confirmed to have infection with D8 virus. Testing for genotype confirmation is pending for the rest of the cases. Several investigations for other reports of rash illness are still ongoing.

Contact tracing and follow-up is ongoing and includes the public potentially exposed at school settings, day nurseries, doctor offices, a hair salon, local hospitals, retail centers, restaurants, and a Toronto attraction.

People attending school had to provide proof of two doses of measles, mumps, and rubella (MMR) vaccine to return. Susceptible exposed persons are being asked to remain in self-enforced quarantine until past the maximal incubation period and to call ahead when seeking medical assessment so that arrangements can be made to avoid exposure of others.
(ProMED 4.18.08)

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Peru (Callao): Two crew members of Chinese fishing boat die, adenovirus suspected
The cook (aged 40) and a crewmember (aged 38) of a Chinese fishing vessel died 9 Apr 2008 after suffering high fevers. Medical examinations have determined that eight other Chinese sailors have the deadly virus, but have not developed any illness. No medication was able to stop the progression of the disease.

Experts of the Forensic Medicine Institute of Public Prosecutions [IML] have determined that the cause of death was an adenovirus that has become extremely deadly. Adenoviruses are spread by physical contact or through the air and are one of the causes of the common flu, but were not considered fatal. The virus that causes severe acute respiratory [syndrome], an atypical pneumonia that first appeared in November 2002 in Guangdong Province, China, has been ruled out. The head of the IML, Luis Bromley Coloma, indicated that "we are facing an adenovirus that has mutated and become deadly, but it is still unknown what caused the mutation and how fast it can spread", which is why an Epidemiological Alert was declared.

The autopsy performed on the two victims found multiorgan edema in the brain, lungs, heart, liver, pancreas, and kidneys, and microhemorrhages in all organs. Toxicological, biological, and pathological tests performed revealed the presence of the mutated adenovirus. Now, health authorities are working to establish where and what generated the mutation to find a cure or a way to contain it.

Unfortunately, the Navy and International Maritime Health personnel boarded the Chinese ship to provide the care they needed, without taking the precautions needed to avoid contagion, hence it has been decided to quarantine them. The disease can manifest itself in 14 days to three months. Specialists from the IML, and epidemiologists from the Ministry of Defense, the Navy, and the Ministry of Health, met on 19 Apr 2008 to assess the results of the biological and pathological examinations in order to take the necessary preventive measures to avoid spread of the virus.

"The autopsies carried out indicate that the two Chinese crewmembers died from pneumonia resulting from an adenovirus, a cause of the flu that is not usually fatal. What happened in this case is that the virus has mutated and become deadly, and we are on an epidemiological alert,'' the head of the Institute of Forensic Medicine, Luis Bromley, said 19 Apr 2008. The specialist added that this outbreak has two characteristics: the victims are people with weakened immune systems, having been almost a year at sea, isolated and living in subhuman conditions. The other factor is still being studied — still unknown are the cause that led to the mutation and how to fight it.

(The identification of a 'mutated' adenovirus as the suspected cause of the deaths of members of the crew of a Chinese fishing vessel anchored off Callao is surprising. Adenoviruses are ubiquitous viruses that can be isolated from both sick and healthy individuals. Antibodies can be detected in virtually all humans, indicative of infection early in childhood and possible life-long persistence in adenoid and lung tissue. Morbidity and mortality associated with adenovirus infection are low, but adenovirus-associated respiratory and gastrointestinal disease can be serious especially in immunologically compromised patients.)
(ProMED 4.22.08)

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USA (Arizona): Measles outbreak shows no signs of slowing
Pima County's measles outbreak, the largest in the country, doesn't appear to be slowing, and some people who assume they are immune may not be, says the county's top public health doctor. "Basically, measles is the most infectious disease we know," said Dr. Michelle McDonald, chief medical officer for Pima County. She said the disease is spread by tiny droplets, blasted from the infected person's lungs through coughing. The virus can survive for two hours in the air. It can be inhaled, coming in contact with a mucous membrane, or be picked up by hand from a surface and inadvertently transmitted to a new victim's mouth, eyes, or nose. "Because of that, a single case is considered an outbreak," McDonald said.

So far 16 cases of measles have been confirmed in Pima County, but McDonald said there may be many more. It's likely that the cases popping up now are in the fourth or fifth generation, victims who are three or four sick people removed from the female Swiss tourist who is thought to have originally brought the disease here, said McDonald. The implication of that scenario is that with each successive generation the number of additional people who are exposed increases drastically. Not only are there massively larger numbers of possible exposures with each generation, but also it becomes increasingly difficult to track potential exposure situations.

"On the local level, we're looking at declaring a formal health emergency," McDonald said, although she said it might not be necessary, as Gov. Janet Napolitano last week appropriated $50,000 and the federal Centers for Disease Control and Prevention are supplying some MMR vaccine free of charge to the county. While many people think of it as a childhood ailment, measles can be far more dangerous — even fatal — for infants and adults, especially those with compromised immune systems, McDonald said. The disease can cause encephalitis and pneumonia. She said it usually is not life threatening in toddlers and school-age children.
(ProMED 5.1.08)

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3. Updates
AVIAN PANDEMIC INFLUENZA
(UN; WHO; FAO, OIE; CDC; Health Canada; CIDRAP; PAHO; USGS)

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4. Articles
Pandemic influenza planning in the United States from a health disparities perspective
Blumenshine P, et al. Emerg Infect Dis [serial on the Internet]. 2008 May http://www.cdc.gov/eid/content/14/5/709.htm#cit

Abstract
We explored how different socioeconomic and racial/ethnic groups in the United States might fare in an influenza pandemic on the basis of social factors that shape exposure, vulnerability to influenza virus, and timeliness and adequacy of treatment. We discuss policies that might differentially affect social groups' risk for illness or death. Our purpose is not to establish the precise magnitude of disparities likely to occur; rather, it is to call attention to avoidable disparities that can be expected in the absence of systematic attention to differential social risks in pandemic preparedness plans. Policy makers at the federal, state, and local levels should consider potential sources of socioeconomic and racial/ethnic disparities during a pandemic and formulate specific plans to minimize these disparities.

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Public Response to Community Mitigation Measures for Pandemic Influenza
Blendon RJ, et al. Emerg Infect Dis [serial on the Internet] 2008 May
http://www.cdc.gov/eid/content/14/5/778.htm

Abstract
We report the results of a national survey conducted to help public health officials understand the public's response to community mitigation interventions for a severe outbreak of pandemic influenza. Survey results suggest that if community mitigation measures are instituted, most respondents would comply with recommendations but would be challenged to do so if their income or job were severely compromised. The results also indicate that community mitigation measures could cause problems for persons with lower incomes and for racial and ethnic minorities. Twenty-four percent of respondents said that they would not have anyone available to take care of them if they became sick with pandemic influenza. Given these results, planning and public engagement will be needed to encourage the public to be prepared.

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Emerging Infectious Diseases –Volume 14, Number 5 – May 2008
This issue includes articles on the scale-up of multidrug-resistant tuberculosis laboratory services in Peru, leptospirosis in Taipei (2001-2006), transmission of avian influenza virus (H3N2) to dogs, and many other infectious disease topics. New issue online at:
http://www.cdc.gov/ncidod/eid/

Safety and reactogenicity profile of an adjuvanted H5N1 pandemic candidate vaccine in adults within a phase III safety trial Rumke HC, et al. Vaccine. 2008;26(19):2378-88

Abstract
A multicentre, randomized, phase III clinical trial in 5071 healthy adults was conducted to evaluate the safety and reactogenicity of a 15mug HA dose of a candidate oil-in-water emulsion-based adjuvant system (AS)-adjuvanted split-virion H5N1 (AS-H5N1) vaccine compared to a licensed seasonal influenza vaccine, Fluarixtrade mark.(1) Stringent criteria were used to evaluate adverse events and reactogenicity profile. Overall, 96.7% of the 5071 vaccinated subjects completed the study. Significantly more participants in the AS-H5N1 vaccine group reported general or local adverse events. Pain was the most common symptom in both treatment groups. Less than 1% of subjects withdrew from the study due to adverse events and no withdrawals were due to serious adverse events related to vaccination. The safety and reactogenicity profile of the AS-H5N1 candidate vaccine can be considered clinically acceptable in the context of its use against pandemic influenza.
(CIDRAP 4.29.08)

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Serologic and genetic characterization analyses of a highly pathogenic influenza virus
(H5N1) isolated from an infected man in Shenzhen
Chen X, et al. Journal of Medical Virology. 2008;80(6):1058-64

Abstract
Highly pathogenic avian influenza (HPAI) H5N1 virus caused a wave of outbreaks in China during 2005-2006, resulting in a total of 20 cases of human infection in 14 provinces of China. On June16, 2006, a case of H5N1 human infection was confirmed in Shenzhen. The virus isolated from the patient, A/Guangdong/2/06, was characterized genetically and the relationship between the tracheal virus load and the antibody titer of the infected man was analyzed. Serological analysis confirmed that the patient's neutralizating antibodies had been generated 2 weeks after the onset of symptoms. The patient's serum antibodies could efficiently neutralize A/Guandong/2/06 infectivity in vitro. Phylogenetic analysis showed that the H5N1 virus of Shenzhen belonged to subclade 2.3.4, which contained viruses that were mainly responsible for the outbreaks in domestic poultry and in the cases of human infection in southern China. Homology and molecular characterization analysis revealed that all the segments of Shenzhen H5N1 virus still belonged to avian segments. Several specific amino acid residue mutations were detected.
(CIDRAP 4.28.08)

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Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System
http://content.nejm.org/cgi/content/full/NEJMoa0803200 )
Kishimoto TK, et al. N Engl J Med 2008:358

Background
There is an urgent need to determine whether oversulfated chondroitin sulfate (OSCS), a compound contaminating heparin supplies worldwide, is the cause of the severe anaphylactoid reactions that have occurred after intravenous heparin administration in the USA and Germany.

Methods
Heparin procured from the FDA, consisting of suspect lots of heparin associated with the clinical events as well as control lots of heparin, were screened in a blinded fashion both for the presence of OSCS and for any biologic activity that could potentially link the contaminant to the observed clinical adverse events. In vitro assays for the activation of the contact system and the complement cascade were performed. In addition, the ability of OSCS to recapitulate key clinical manifestations in vivo was tested in swine.

Results
The OSCS found in contaminated lots of unfractionated heparin, as well as a synthetically generated OSCS reference standard, directly activated the kinin-kallikrein pathway in human plasma, which can lead to the generation of bradykinin, a potent vasoactive mediator. In addition, OSCS induced generation of C3a and C5a, potent anaphylatoxins derived from complement proteins. Activation of these 2 pathways was unexpectedly linked and dependent on fluid-phase activation of factor XII. Screening of plasma samples from various species indicated that swine and humans are sensitive to the effects of OSCS in a similar manner. OSCS-containing heparin and synthetically derived OSCS induced hypotension associated with kallikrein activation when administered by intravenous infusion in swine.

Conclusions
Our results provide a scientific rationale for a potential biologic link between the presence of OSCS in suspect lots of heparin and the observed clinical adverse events. An assay to assess the amidolytic activity of kallikrein can supplement analytic tests to protect the heparin supply chain by screening for OSCS and other highly sulfated polysaccharide contaminants of heparin that can activate the contact system.
(ProMED 4.28.08)

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5. Notifications
APEC EINet Pandemic Influenza Preparedness Virtual Symposium: Partnerships and Continuity Planning for Critical Systems
APEC EINet is pleased to host a special videoconference on pandemic influenza preparedness. This videoconference is a follow-up to our first “virtual symposium”, which was conducted in January 2006 with great success (participating economies were Australia, Canada, China, Korea, Philippines, Singapore, Chinese Taipei, Thailand, USA, and Viet Nam). You can view a five-minute videoclip of our previous virtual symposium at: http://depts.washington.edu/einet/symposium.html. Our upcoming videoconference will be held in late May 2008. It will take place during the evening hours of 29 May in the Americas and in the morning hours of 30 May in Asia, for approximately 5 hours. Our objective is to describe how private and public sectors in the APEC region can cooperate and work effectively to prepare for and respond to an influenza pandemic.

Through this videoconference, we hope to promote regional information sharing and collaboration to enhance pandemic preparedness. In order to improve preparedness regionally, it is vital to understand how each economy in the region is undertaking this task. In this process, EINet will:

  1. Bring together economies in a dynamic, real-time discussion on preparedness through the collaboration of the health and the business/trade sectors, with a focus on critical systems continuity.
  2. Share specific examples of current practices—e.g. scenario exercises, communication drills and policy evaluation.
  3. Use innovative technologies (e.g. Access Grid) for real-time, virtual interchange, enhancing their utility for future collaboration and response in the event of a pandemic.

Videoconferencing offers an alternative to in-person conferencing. It cuts down on the time and cost of traditional conferences requiring long-distance travel. Simultaneous communication with multiple sites is possible, with numerous visualization options. Real-time web-based information exchange is also possible, and, during an actual pandemic, the virtual medium would be a safe way to communicate when international travel is limited or prohibited.

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Pandemic Planning for Academic Institutions (Webcast)
http://ualbanycphp.org/GRS/eventpast.cfm?id=101

This program is co-sponsored by the Upper Midwest Center for Public Health Preparedness, and features Ms. Hosmanek who currently serves as facilitator for the University of Iowa Pandemic Influenza Task Force and also played an instrumental role in the ASPH/CDC Pandemic Influenza Collaborative Group, which developed the "Pandemic Influenza Preparedness Resource Kit for Academic Institutions." She will share information and resources available to academic institutions to support their pandemic influenza preparedness efforts, and lessons learned during the development and execution of the April 2007 tabletop exercise designed to prompt rapid decision-making and test the current Pandemic Plan at the University of Iowa.
(RGPHP 4.18.08)

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US Federal officials discuss concerns about school-closures during a pandemic
The US Department of Health and Human Services (HHS) on 30 Apr 2008 held a live Web seminar (webinar) to provide guidance on and field questions about school closures as a social distancing tool that could be used in an influenza pandemic. Many public health experts believe school closures could mitigate the effects of a pandemic. However, the benefits of school closures are difficult to measure, and many state and local health officials are unclear on what the trigger would be for closing schools.

The webinar was the third in a series to help state officials with pandemic planning activities. The department launched the webinars in March 2008, when it released comprehensive guidance for state officials. Dr Francisco Averhoff, of the Center for Disease Control and Prevention's (CDC's) Global Migration and Quarantine Division, said school closures are a common-sense approach to blunting the impact of a pandemic. "Schools are one of the most tightly packed environments where we have children," he said.

Dana Carr, a program specialist with the US Department of Education, advised school officials to become actively involved in their community pandemic planning efforts. She said communities vary on which level of government has the legal authority to close schools. "You don't want to be caught during a pandemic not knowing who's going to pull the trigger," she said. As with natural disasters, the Department of Education will likely provide waivers for "No Child Left Behind" requirements in regions that are hit hard by pandemic influenza, Carr said. Some school districts will be able to continue to provide educational content, using tools such as the Internet, conference calls, or television, she said, adding that the department is gathering more information on schools' distance learning plans and will provide more technical guidance to districts in a May 19 videoconference.

Barbara Bingham, director of the US Department of Labor's Compliance Assistance Office, acknowledged that student dismissal in a pandemic setting would have consequences for employers, who will face absenteeism when parents need to stay home and care for their school-age children. Though some employers are already considering telework arrangements, alternate work schedules, and paid leave for workers, many families still won't have access to flexible working arrangements and uninterrupted paychecks, she said.

"Alternate ways to give care include older children, small [group] child-care arrangements, and extended family members," Bingham said.

During the online question-and-answer portion of the webinar, federal officials were asked what would happen if schools were used for healthcare centers or even morgues. Carr said federal and state officials should start talking now about how they'd help the schools if buildings were contaminated with the virus and how they'd handle the psychological impact on communities that used schools as morgues. Another questioner asked if federal officials had considered the extra burden that both telecommuting and online learning would put on broadband Internet systems. Bingham responded that federal officials have been working closely with private industry to anticipate the demand. She said that in general, officials foresee enough broadband capacity, but some people and organizations could encounter access problems.

HHS's next pandemic planning webinar is slated for Jun 4, when officials will discuss workforce preparedness.
(CIDRAP 5.1.08)

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 apecein@u.washington.edu