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EINet Alert ~ Nov 06, 2009


*****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
- 2009 Cumulative number of human cases of avian influenza A/H5N1
- WHO situation update on pandemic influenza H1N1
- Global: Infection of farmed animals with the pandemic H1N1 virus
- Global: Reanalysis changes findings in respiratory protection study
- Norway: OTC antiviral sales approved
- Ukraine: WHO team arrives to assist with influenza probe
- Saudi Arabia: Hajj related vaccine campaign
- Afghanistan: Schools closed in wake of H1N1 death
- Thailand: Government steps up influenza screening measures
- Viet Nam: H5N1 avian influenza recurs in northern province
- Viet Nam: One more pregnant woman dies from A (H1N1) flu
- China: Nearly four million citizens vaccinated
- Hong Kong: Woman ill with H9 avian influenza
- Canada: Exportation of excess pandemic H1N1 vaccine antigen
- Canada: Advisors push seasonal vaccine
- USA: CDC urges states to focus vaccine on risk groups
- USA: CDC says vaccine shortage likely to outlast current H1N1 wave
- USA: FDA Publishes Guidance on Diagnostic Tests for 2009 H1N1 Influenza Virus
- USA: Interim Studies reaffirm two H1N1 vaccine doses in children, show safety in pregnant women
- Venezuela: Pandemic H1N1 reaches Yanomami Indians in the Amazon
- South Africa: Panel favors novel H1N1 in seasonal vaccine

2. Updates
- INFLUENZA A/H1N1
- AVIAN INFLUENZA

3. Articles
- Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China.
- Factors Associated With Death or Hospitalization Due to Pandemic 2009 Influenza A(H1N1) Infection in California
- Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines
- Quantifying the Impact of Immune Escape on Transmission Dynamics of Influenza
- The Transmissibility and Control of Pandemic Influenza A (H1N1) Virus
- Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift
- Oseltamivir-resistant pandemic (H1N1) 2009 influenza virus, October 2009
- Survey Study of the Knowledge, Attitudes, and Expected Behaviors of Critical Care Clinicians Regarding an Influenza Pandemic

4. Notifications
- APEC EINet "Hot Topics" Video Conference: Lessons Learned from the First Wave
- Resources from Canada for APEC Partners
- World Response Conference on Global Outbreak 2009: H1N1 Flu + H5N1 Flu
- EPIDEMICS²: Second International Conference on Infectious Diseases Dynamics
- 14th International Congress on Infectious Diseases (ICID)
- ISHEID Symposium on HIV and Emerging Infectious Diseases
- Avian Influenza: The Basics--an online training module
- Updated influenza guidance and information from the US CDC


1. Influenza News

Global
2009 Cumulative number of human cases of avian influenza A/H5N1

Economy / Cases (Deaths)
China/ 7 (4)
Egypt/ 36 (4)
Viet Nam/ 4 (4)
Total/ 47 (12)

***For data on human cases of avian influenza prior to 2009, go to: http://depts.washington.edu/einet/humanh5n1.html

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 442 (262) (WHO 9/24/09 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 (last updated 9/10/09)

WHO's map showing world's areas affected by H5N1 avian influenza (last updated 5/10/09): http://gamapserver.who.int/mapLibrary/

WHO's timeline of important H5N1-related events (last updated 7/27/09): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html

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WHO situation update on pandemic influenza H1N1

As of 25 October 2009, worldwide there have been more than 440,000 laboratory confirmed cases of pandemic influenza H1N1 2009 and over 5,700 deaths reported to WHO. As many countries have stopped counting individual cases, particularly of milder illness, the case count is likely to be significantly lower than the actual number of cases that have occurred. WHO is actively monitoring the progress of the pandemic through frequent consultations with the WHO Regional Offices and member states and through monitoring of multiple sources of data.

In the temperate zone of the northern hemisphere, influenza transmission continues to intensify marking an unusually early start to winter influenza season in some countries. In North America, the US, and parts of Western Canada continue to report high rates of influenza-like-illness (ILI) and numbers of pandemic H1N1 2009 virus detections; Mexico has reported more confirmed cases since September than during the springtime epidemic. In Western Europe, high rates of ILI and proportions of respiratory specimens testing positive for pandemic H1N1 2009 have been observed in at least five countries: Iceland, Ireland, the UK (N. Ireland), Belgium, and the Netherlands. Many other countries in Europe and Western and Central Asia are showing evidence of early influenza transmission, including in Spain, Austria, parts of Northern Europe, Russia, and Turkey. In Japan, influenza activity has also increased sharply, especially on the northern island, approximately 10 weeks ahead the usual start of the winter influenza season.

Pandemic influenza transmission remains active in many parts of the tropical zone of the Americas, most notably in several Caribbean countries. Overall transmission continues to decline in most but not all parts of the tropical zone of South and Southeast Asia. Little influenza activity has been reported in temperate region of the southern hemisphere since the last update.
(WHO 10/30/2009)

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Global: Infection of farmed animals with the pandemic H1N1 virus

Vigilance for changes in the H1N1 virus includes monitoring to detect possible influenza infections in susceptible animals, both mammals and birds, as well as humans. While most influenza A viruses circulating in mammals preferentially infect a single species, cross-species transmission is known to occur.

Since the new H1N1 pandemic virus emerged, a small number of infections in swine herds have been reported. Limited evidence suggests that these infections occurred following direct transmission of the virus from infected humans to swine. These isolated events have had no impact on the dynamics of the pandemic, which is spreading readily via human-to-human transmission. As human infections become increasingly widespread, transmission of the virus from humans to swine is likely to occur with greater frequency. In addition, pandemic H1N1 infections have been reported in turkeys in Chile and Canada and in a few pet animals in the USA. Again, these infections were isolated events and pose no special risks to human health.

Another concern is the continuing presence of the highly pathogenic H5N1 avian influenza virus in poultry in several countries, where the virus is endemic. While no one can predict how the H5N1 virus might behave under the pressures of a pandemic, all data to date have been reassuring.

Most recently, authorities in Denmark reported a novel H3N2 influenza virus in mink on several mink farms. Sequencing of the virus demonstrated a combination of human and swine genes that has not been identified previously in circulating influenza viruses. Testing of farm workers detected no spread of the virus to humans. However, the incident demonstrates the constantly evolving ecology of influenza viruses, the potential for surprising changes, and the need for constant vigilance, also in animals.

These recent findings further suggest that influenza A viruses in animals and humans increasingly behave like a pool of genes circulating among multiple hosts, and that the potential exists for novel influenza viruses to be generated in animals other than swine. This situation reinforces the need for close monitoring and close collaboration between public health and veterinary authorities.

When influenza infections are detected in farmed animals, WHO recommends monitoring of farm workers for signs of respiratory illness, and testing for H1N1 infection should such signs appear. FAO and OIE recommend that animals that are showing signs of illness be examined and properly managed, and allowed to fully recover before being transported or marketed. In addition, samples from infected animals and humans should be taken for full genome sequencing of the influenza viruses to determine if mutations have occurred that could lead to changes in virulence, host range or antiviral resistance. Such sequencing is also important to assess the possible origin of the case or outbreak.
(WHO 11/05/2009)

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Global: Reanalysis changes findings in respiratory protection study

A reanalysis prompted by reviewers has changed the conclusions of a study comparing N-95 respirators with surgical masks, raising questions about earlier findings that the N-95 devices were clearly more effective in protecting healthcare workers from respiratory illness. Raina MacIntyre and colleagues first presented their findings at a medical conference in mid-September, reporting that N-95s, compared with no respiratory protection, reduced the risk of confirmed influenza in hospital workers by 75%, whereas surgical masks had no protective effect. But at the Infectious Diseases Society of America (IDSA) annual meeting last week, MacIntyre's team presented a new analysis of their data, made at the request of peer reviewers. The reanalysis excluded the control group of unprotected workers. The result was that workers who wore N-95s still appeared to be better off than those with surgical masks, but the differences were no longer statistically significant.

According to MacIntyre, before presenting their findings at the recent IDSA meeting, the research team ran a new analysis to satisfy the concerns of reviewers. One change was to drop the control group of unprotected hospital workers, because of the reviewers' objection that those workers were not randomly assigned to not wear protection. (MacIntyre explained that her team had to use a convenience sample of workers from hospitals where mask-wearing was not the norm, because the Chinese workers would not accept being randomly assigned to doing without respiratory protection.) The other change was to make statistical adjustments to allow for the possibility of different risks of infection among the various hospitals in the study, MacIntyre said.

After those changes, the differences between the N-95s and surgical masks lost their statistical significance. "When the P value [test of significance] was adjusted for clustering and multiple testing, [there was] no significant difference between N-95 respirators and medical masks for the four primary outcomes," states the team's slide presentation, supplied by the IDSA.
(CIDRAP 11/05/2009)

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Europe/Near East
Norway: OTC antiviral sales approved

To ease response to the H1N1 pandemic, Norway is allowing over-the-counter sales of oseltamivir (Tamiflu) and zanamivir (Relenza). The new policy will be in effect until the middle of 2010. Norway has ordered 9.4 million doses of vaccine, but the manufacturer has reportedly not produced enough to meet demand.
(CIDRAP 11/04/2009)

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Ukraine: WHO team arrives to assist with influenza probe

86 people have died in Ukraine from flu and respiratory infections, the health ministry said on 4 Nov 2009, in an epidemic the World Health Organization said could be largely due to the pandemic (H1N1) 2009 influenza virus. The ministry said that almost half a million cases of flu and acute respiratory infections had been recorded since mid-October 2009 in this country of 46 million, while 24,000 people have been hospitalized. The WHO has sent a team of nine experts to Ukraine to help the authorities with the situation. Prime minister Yulia Tymoshenko has personally overseen a delivery of anti-flu medicines in the middle of the night, and pro-Western President Viktor Yushchenko even called on NATO for help.
(ProMED 11/05/2009)

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Saudi Arabia: Hajj related vaccine campaign

Saudi Arabian health officials said the country will immunize healthcare workers, hajj workers, and domestic pilgrims who will attend the hajj against the pandemic H1N1 virus. Vaccination won't be mandatory. About one million residents typically attend the hajj, which peaks near the end of November this year. The country recently received the first 11 million doses of its pandemic vaccine order.
(CIDRAP 11/02/2009)

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Asia
Afghanistan: Schools closed in wake of H1N1 death

The Afghan government on 01 Nov 2009 ordered the closure of all schools for 3 weeks in the wake of the country's first death from H1N1 flu. Education Minister Farouq Wardak said the closure was ordered "to safeguard the health of all Afghans." An engineer from Kabul was the flu's first victim in Afghanistan.
(CIDRAP 11/02/2009)

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Thailand: Government steps up influenza screening measures

Stringent disease controls are being put in place after a pregnant woman was confirmed to have died from type A (H1N1) influenza. On 28 Oct 2009, Public Health Minister Witthaya Kaewparadai ordered chief health officers in 11 provinces in the upper central region and lower North to strengthen flu-screening measures, particularly of pregnant women. The minister said every pregnant woman visiting a state hospital should be screened for the influenza virus. All would be asked if they have flu symptoms.

The ministry has also ordered health officials to look out for any signs of an outbreak of the avian flu, which struck the country 3 years ago. 11 areas in Lampang, Chiang Rai, Si Sa Ket, Phitsanulok, and Tak have reported unusual deaths of poultry, which has sparked a bird flu alert. About 800 isolation rooms have been prepared at state hospitals to keep patients suspected to have type A (H1N1) flu and those that might have bird flu away from each other and away from other patients, he said.

The flu infection rate is expected to rise dramatically in the coming months of the cold season. The number of deaths from type A (H1N1) influenza in Thailand was recorded at 182 as of last 24 Oct 2009, Mr Witthaya said.
(ProMED 10/30/2009)

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Viet Nam: H5N1 avian influenza recurs in northern province

Avian Influenza has re-emerged in the northern province of Dien Bien in Viet Nam, according to a report from the Animal Health Department under Viet Nam's Ministry of Agriculture and Rural Development on 2 Nov 2009. The virus broke out in nine local farms from 21 to 23 Oct 2009, killing hundreds of poultry. Poultry samples tested by the provincial animal health agency were positive for the H5N1 virus, according to the report.

Local animal health authorities have been implementing measures to curb the spread of the virus to nearby areas, including the culling of over 2,200 remaining poultry, said the department. Dien Bien currently is the only province of Viet Nam being re-hit by the virus after it was confirmed free of the H5N1 virus for several months in 2009.

Viet Nam has reported five human cases of bird flu infection thus far in 2009, four of which were fatal.
(ProMED 11/03/2009)

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Viet Nam: One more pregnant woman dies from A (H1N1) flu

The Department for Preventive Medicine and Environment under the Ministry of Health on 29 Oct 2009 confirmed one more death from the A (H1N1) influenza, raising the total death toll from the disease in the country to 36. Viet Nam also confirmed 10,568 A (H1N1) cases of infection in 59 provinces and cities nationwide. Of these, 10,286 have been discharged from hospital.
(ProMED 10/30/2009)

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China: Nearly four million citizens vaccinated

As the first country that issued a production license for 2009 pandemic H1N1 virus vaccines, China had inoculated more than 3.78 million people as of 31 Oct 2009, with no reports of serious adverse reactions, according to the Chinese Ministry of Health. About 33.4 million doses of vaccine have been approved for use as of 31 Oct 2009, 26 million of which have been dispatched to local medical institutions.

Calculating the current production abilities of the eight domestic vaccine manufacturers, a total of 100 million doses of pandemic (H1N1) 2009 influenza vaccine will be produced by the first quarter of 2010, according to the ministry. In the meantime, about 390 million people on the Chinese mainland are in need of influenza vaccines including service personnel of the People's Liberation Army and armed police forces, police, medical staff, teachers, students, people working at key public service posts, and patients with chronic or cardiovascular diseases, experts said.

As of 2 Nov 2009, more than 48,000 confirmed cases of pandemic (H1N1) 2009 influenza had been reported on the Chinese mainland, 74 percent of whom had recovered. Among the 118 serious cases, 84 were still in hospital, the ministry said. The Chinese mainland has reported seven deaths from influenza since 2 Oct 2009.
(ProMED 11/03/2009)

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Hong Kong: Woman ill with H9 avian influenza

The Hong Kong Centre for Health Protection is investigating an imported case of H9 influenza A infection involving a 47 year old Guangdong woman. The woman went to Hong Kong for medical treatment and was admitted to Queen Mary Hospital on 28 Oct 2009. She is stable and remains in isolation. Her family members have been put under medical surveillance. As she was in Guangdong during the incubation period, the centre has informed health authorities there along with the World Health Organization, the Ministry of Health, and Macau's health authorities of the development.

H9 influenza A is a mild form of avian influenza. Infection in humans is rare. This is the sixth time H9 viruses have been found in humans in Hong Kong. A total of four girls and one boy were confirmed to have suffered from H9 infection in 1999, 2003, 2007 and 2008.
(ProMED 11/03/2009)

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Americas
Canada: Exportation of excess pandemic H1N1 vaccine antigen

Canada's chief public health officer, Dr David Butler-Jones, said that the country's Glaxo plant has exported excess bulk pandemic H1N1 vaccine antigen. Sources did not say how much antigen had been produced. Butler-Jones said domestic fill-and-finish operations have not yet been able to package all the already-produced antigen for the Canadian market. He said the export would not slow vaccine delivery to Canadians.
(CIDRAP 11/04/2009)

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Canada: Advisors push seasonal vaccine

Canada's vaccine advisory group has recommended against delaying seasonal flu shots, a move that many provinces made after an unpublished study suggested the vaccine might raise the risk of contracting pandemic flu. The panel concluded that even if the finding is valid, the risk of skipping the seasonal shot outweighs the risk seen in the studies. The group also endorsed giving both seasonal and H1N1 shots at the same time.
(CIDRAP 11/02/2009)

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USA: CDC urges states to focus vaccine on risk groups

CDC Director Tom Frieden, MD, sent a letter 05 Nov 2009 to states commending them for their efforts to distribute pandemic vaccine when demand exceeds supply but emphasizing that the scarce supplies should first go to priority groups. He warned that giving early doses to those outside high-risk groups could undermine public health credibility. A spokesman said the CDC doesn't see confusion over allocation as widespread, but it wanted to underscore the importance of vaccinating vulnerable groups.
(CIDRAP 11/05/2009)

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USA: CDC says vaccine shortage likely to outlast current H1N1 wave

The head of the Centers for Disease Control and Prevention (CDC) predicted that the current wave of H1N1 influenza is likely to begin to wane before the shortage of vaccine for it eases. "It's likely that the current wave of infection will peak, crest, and begin to decline before there are ample supplies," Dr. Thomas Frieden told the House Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies.

In other comments, federal health officials described the slow growth of the vaccine virus as the fundamental reason for the current vaccine shortage and suggested that vaccine production difficulties are likely to continue as long as the process relies on growing actual flu viruses, as opposed to producing specific viral proteins.
(CIDRAP 11/04/2009)

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USA: FDA Publishes Guidance on Diagnostic Tests for 2009 H1N1 Influenza Virus

The U.S. Food and Drug Administration has published a guidance document that should help manufacturers develop diagnostic tests for the 2009 H1N1 influenza virus. Although there are not any FDA-approved or cleared tests that diagnose this specific infection, during this pandemic, manufacturers can submit a request to the FDA for an Emergency Use Authorization (EUA). If granted, the EUA will allow the test to be used during the national public health emergency declared by Department of Health and Human Services Secretary Kathleen Sebelius in April. The EUA authority is part of Project BioShield, which became law in July 2004.

This guidance document outlines what information the FDA recommends that manufacturers include in these EUA requests. It is available at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM188679.pdf, and will remain in effect throughout the public health emergency.
(FDA News Release 11/02/2009)

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USA: Interim Studies reaffirm two H1N1 vaccine doses in children, show safety in pregnant women

Interim clinical trial findings announced 02 Nov 2009 affirm that children younger than 10 need two pandemic H1N1 vaccine doses, and initial findings in pregnant women reveal no safety concerns and a need for only one dose.

Vaccine data for children
Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said interim results on vaccine in healthy children ages 6 months to 17 years confirm early results reported on Sep 21. The new findings show that children younger than 10 who receive a second 15-microgram (mcg) dose of pandemic H1N1 vaccine have significant immune response improvement. In the youngest children (6 to 35 months), 100% had a robust immune response after the second dose compared with only 25% after the first dose. In those ages 3 through 9, 94% had a robust immune response after the second dose, compared with 55% after the first dose. Immune responses were comparable in those receiving two 15-mcg doses and in those who got two 30-mcg doses, suggesting that the smaller dose is enough to elicit a strong immune response.

Efficacy in pregnant women
In the initial results on the vaccine in pregnant women, immune response to the pandemic H1N1 shot was similar to that seen in healthy adults. In a subgroup of 50 pregnant women participating in an NIH clinical trial, a preliminary analysis of blood drawn 21 days after vaccination showed the vaccine was likely protective in 23 of 25 women (92%) who received a single 15-mcg dose and that it was likely protective in 24 of 25 (96%) who received a single 30-mcg dose. Participants were between ages 18 and 39 and were in their second or third trimester when they began the study. The ongoing study will also assess the effects of a second dose. Investigators are using Sanofi's pandemic H1N1 vaccine, which does not contain the preservative thimerosal or an immune-response-boosting adjuvant.
(CIDRAP 11/02/2009)

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Venezuela: Pandemic H1N1 reaches Yanomami Indians in the Amazon

Influenza pandemic (H1N1) 2009 virus infection has appeared among Venezuela's Yanomami Indians, one of the largest isolated indigenous groups in the Amazon. According to a doctor's statement on 4 Nov 2009, the virus is suspected in seven deaths, including six infants. The deaths happened in forest villages near Venezuela's border with Brazil over the past 2 1/2 weeks, said Raidan Bernade, a Venezuelan doctor in a team sent to contain the outbreak and treat the ill. Doctors confirmed one of those who died had swine flu -- a 35 year old Yanomami woman who doctors believe was pregnant.
(New York Times 11/04/2009)

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Africa
South Africa: Panel favors novel H1N1 in seasonal vaccine

South Africa's National Institute of Communicable Diseases has recommended that South Africa include the pandemic H1N1 virus in its seasonal flu vaccine for next year. Barry Schoub, director of the institute, said it would be up to the nation's health department whether to follow the advice. Reports did not clarify whether the pandemic virus would replace the seasonal H1N1 strain in the vaccine or be added to it.
(CIDRAP 11/03/2009)

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2. Updates
INFLUENZA A/H1N1

The following websites provide the most current information, surveillance, and guidance.

- WHO
Influenza A/H1N1: http://www.who.int/csr/disease/swineflu/en/index.html
Influenza A/H1N1 frequently asked questions: http://www.who.int/csr/disease/swineflu/frequently_asked_questions/en/index.html
Pandemic Influenza Preparedness and Response - A WHO Guidance Document
http://www.who.int/csr/disease/influenza/pipguidance2009/en/index.html
International Health Regulations (IHR) at http://www.who.int/ihr/en/index.html.

- WHO regional offices
Africa: http://www.afro.who.int/
Americas: http://new.paho.org/hq/index.php?option=com_content&task=blogcategory&id=805&Itemid=569
Eastern Mediterranean: http://www.emro.who.int/csr/h1n1/
Europe: http://www.euro.who.int/influenza/ah1n1
South-East: http://www.searo.who.int/EN/Section10/Section2562.htm
Western Pacific: http://www.wpro.who.int/health_topics/h1n1/

- North America
US CDC: http://www.cdc.gov/flu/swine/investigation.htm
US pandemic emergency plan: http://www.flu.gov
MOH Mexico: http://portal.salud.gob.mx/index_eng.html
PHA of Canada: http://fightflu.ca

- Other useful sources
CIDRAP: Influenza A/H1N1 page: http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/biofacts/swinefluoverview.html
ProMED: http://www.promedmail.org/

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AVIAN INFLUENZA

- UN: http://www.undp.org/mdtf/influenza/overview.shtml UNDP's web site for information on fund management and administrative services and includes the website of the Central Fund for Influenza Action. This site also includes a list of useful links.
- WHO: http://www.who.int/csr/disease/avian_influenza/en/.
- UN FAO: http://www.fao.org/avianflu/en/index.html. View the latest avian influenza outbreak maps, upcoming events, and key documents on avian influenza.
- OIE: http://www.oie.int/eng/info_ev/en_AI_avianinfluenza.htm. Link to the Communication Portal gives latest facts, updates, timeline, and more.
- US CDC: Visit "Pandemic Influenza Preparedness Tools for Professionals" at: http://www.cdc.gov/flu/pandemic/preparednesstools.htm. This site contains resources to help hospital administrators and state and local health officials prepare for the next influenza pandemic.
- The US government's website for pandemic/avian flu: http://www.flu.gov/. View archived Webcasts on influenza pandemic planning.
- CIDRAP: http://www.cidrap.umn.edu/
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm Link to the Avian Influenza Portal at: http://influenza.bvsalud.org/php/index.php?lang=en. The Virtual Health Library's Portal is a developing project for the operation of product networks and information services related to avian influenza.
- US National Wildlife Health Center: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp Read about the latest news on H5N1 in wild birds and poultry.

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3. Articles
Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China.

Chen H, Cheung CL, Tai H, et al. Emerg Infect Dis. December 2009; doi: 10.3201/eid1512.091057. Available at http://www.cdc.gov/eid/content/15/12/pdfs/09-1057.pdf.

Summary. Resistance to oseltamivir was observed in influenza A pandemic (H1N1) 2009 virus isolated from an untreated person in Hong Kong, China. Investigations showed a resistant virus with the neuraminidase (NA) 274Y genotype in quasi-species from a nasopharyngeal aspirate. Monitoring for the naturally occurring NA 274Y mutation in this virus is necessary.

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Factors Associated With Death or Hospitalization Due to Pandemic 2009 Influenza A(H1N1) Infection in California

Louie JK, Acosta M, Winter K, et al. for the California Pandemic (H1N1) Working Group. JAMA. 04 November 2009; 302(17):1896-1902. Available at http://jama.ama-assn.org/cgi/content/full/302/17/1896.

Context. Pandemic influenza A(H1N1) emerged rapidly in California in April 2009. Preliminary comparisons with seasonal influenza suggest that pandemic 2009 influenza A(H1N1) disproportionately affects younger ages and causes generally mild disease.

Objective. To describe the clinical and epidemiologic features of pandemic 2009 influenza A(H1N1) cases that led to hospitalization or death.

Design, Setting, and Participants. Statewide enhanced public health surveillance of California residents who were hospitalized or died with laboratory evidence of pandemic 2009 influenza A(H1N1) infection reported to the California Department of Public Health between April 23 and August 11, 2009.

Main Outcome Measure. Characteristics of hospitalized and fatal cases.

Results. During the study period there were 1088 cases of hospitalization or death due to pandemic 2009 influenza A(H1N1) infection reported in California. The median age was 27 years (range, <1-92 years) and 68% (741/1088) had risk factors for seasonal influenza complications. Sixty-six percent (547/833) of those with chest radiographs performed had infiltrates and 31% (340/1088) required intensive care. Rapid antigen tests were falsely negative in 34% (208/618) of cases evaluated. Secondary bacterial infection was identified in 4% (46/1088). Twenty-one percent (183/884) received no antiviral treatment. Overall fatality was 11% (118/1088) and was highest (18%-20%) in persons aged 50 years or older. The most common causes of death were viral pneumonia and acute respiratory distress syndrome.

Conclusions. In the first 16 weeks of the current pandemic, the median age of hospitalized infected cases was younger than is common with seasonal influenza. Infants had the highest hospitalization rates and persons aged 50 years or older had the highest mortality rates once hospitalized. Most cases had established risk factors for complications of seasonal influenza.

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Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines

Black S, Eskola J, Siegrist C-A, et al. The Lancet. 31 October 2009; doi:10.1016/S0140-6736(08)61345-8. Available at http://www.lancet.com/journals/lancet/article/PIIS0140-6736%2809%2961877-8/abstract.

Summary. Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barré syndrome and 5.75 cases of sudden death would be expected to occur within six weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within six weeks of vaccination. 397 per one million vaccinated pregnant women would be predicted to have a spontaneous abortion within one day of vaccination.

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Quantifying the Impact of Immune Escape on Transmission Dynamics of Influenza

Park AW, Daly JM, Lewis NS, et al. Science. 30 October 2009; 326(5953):726-728; doi: 10.1126/science.1175980. Available at http://www.sciencemag.org/cgi/content/abstract/326/5953/726.

Abstract. Influenza virus evades prevailing natural and vaccine-induced immunity by accumulating antigenic change in the haemagglutinin surface protein. Linking amino acid substitutions in haemagglutinin epitopes to epidemiology has been problematic because of the scarcity of data connecting these scales. We use experiments on equine influenza virus to address this issue, quantifying how key parameters of viral establishment and shedding increase the probability of transmission with genetic distance between previously immunizing virus and challenge virus. Qualitatively similar patterns emerge from analyses based on antigenic distance and from a published human influenza study. Combination of the equine data and epidemiological models allows us to calculate the effective reproductive number of transmission as a function of relevant genetic change in the virus, illuminating the probability of influenza epidemics as a function of immunity.

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The Transmissibility and Control of Pandemic Influenza A (H1N1) Virus

Yang Y, Sugimoto JD, Halloran ME, et al. Science. 30 October 2009; 326(5953):729-733; doi: 10.1126/science.1177373. Available at http://www.sciencemag.org/cgi/content/abstract/326/5953/729.

Abstract. Pandemic influenza A (H1N1) 2009 (pandemic H1N1) is spreading throughout the planet. It has become the dominant strain in the Southern Hemisphere, where the influenza season has now ended. Here, on the basis of reported case clusters in the United States, we estimated the household secondary attack rate for pandemic H1N1 to be 27.3% [95% confidence interval (CI) from 12.2% to 50.5%]. From a school outbreak, we estimated that a typical schoolchild infects 2.4 (95% CI from 1.8 to 3.2) other children within the school. We estimated the basic reproductive number, R0, to range from 1.3 to 1.7 and the generation interval to range from 2.6 to 3.2 days. We used a simulation model to evaluate the effectiveness of vaccination strategies in the United States for fall 2009. If a vaccine were available soon enough, vaccination of children, followed by adults, reaching 70% overall coverage, in addition to high-risk and essential workforce groups, could mitigate a severe epidemic.

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Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift

Hensley SE, Das SR, Bailey AL, et al. Science. 30 October 2009; 326(5953):734-736; doi: 10.1126/science.1178258. Available at http://www.sciencemag.org/cgi/content/abstract/326/5953/734.

Abstract. Rapid antigenic evolution in the influenza A virus hemagglutinin precludes effective vaccination with existing vaccines. To understand this phenomenon, we passaged virus in mice immunized with influenza vaccine. Neutralizing antibodies selected mutants with single-amino acid hemagglutinin substitutions that increased virus binding to cell surface glycan receptors. Passaging these high-avidity binding mutants in naïve mice, but not immune mice, selected for additional hemagglutinin substitutions that decreased cellular receptor binding avidity. Analyzing a panel of monoclonal antibody hemagglutinin escape mutants revealed a positive correlation between receptor binding avidity and escape from polyclonal antibodies. We propose that in response to variation in neutralizing antibody pressure between individuals, influenza A virus evolves by adjusting receptor binding avidity via amino acid substitutions throughout the hemagglutinin globular domain, many of which simultaneously alter antigenicity.

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Oseltamivir-resistant pandemic (H1N1) 2009 influenza virus, October 2009

Weekly Epidemiological Record. 30 October 2009; 84(44). Available at http://www.who.int/wer/2009/wer8444.pdf.

Introduction. The earliest isolates of pandemic (H1N1) 2009 influenza virus were shown to be sensitive to the influenza virus neuraminidase inhibitors oseltamivir and zanamivir but resistant to the M2 inhibitors amantadine and rimantadine. WHO and other organizations have developed guidelines for the use of antiviral drugs in the clinical management of pandemic (H1N1) 2009 influenza virus infections on the basis of these data.

Since the initial characterization of pandemic (H1N1) 2009 influenza virus in March 2009, laboratories worldwide have been monitoring its susceptibility to neuraminidase inhibitors. The purpose of this article is to summarize current knowledge on oseltamivir-resistant pandemic (H1N1) 2009 influenza viruses and to highlight actions and recommendations that can minimize the emergence and transmission of resistant viruses. The information contained in this report is derived from published case reports, notifications to WHO under the International Health Regulations (2005), and analyses by WHO's collaborating centres and other laboratories. This information is subject to change as case investigations and epidemiological investigations are completed.

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Survey Study of the Knowledge, Attitudes, and Expected Behaviors of Critical Care Clinicians Regarding an Influenza Pandemic

Daugherty EL, Perl TM, Rubinson L, et al. Infect Control Hosp Epidemiol. December 2009; 30:1143-1149; doi: 10.1086/648085. Available at http://www.journals.uchicago.edu/doi/pdf/10.1086/648085.

Objective. Intensive care units (ICUs) are potential high-risk areas for the transmission of respiratory viruses such as influenza. An influenza pandemic is expected to result in a dramatic surge of critically ill patients, and ICU healthcare workers (HCW) are likely to be at high risk of infection.

Objective. To characterize the knowledge, attitudes, and expected behaviors of ICU HCWs concerning the risk of and response to an influenza pandemic.

Design, participants, and setting. A survey was distributed to 292 HCWs (ie, internal medicine house staff, pulmonary and critical care fellows and faculty members, nurses, and respiratory care professionals) at two hospitals in Baltimore, Maryland.

Results. Of the 292 HCWs, 256 (88%) completed the survey. Just over one-half of the respondents believed there is at least a 45% chance of an influenza pandemic within the next five years. However, only 41% reported knowing how to protect themselves during an outbreak. Despite this common belief that a pandemic is likely in the near future, 59% of those surveyed reported only minimal knowledge of the risks of and protective strategies for an influenza pandemic, and 20% reported being unlikely to report to work during a pandemic or being unsure about whether they would do so. The odds of reporting to work varied on the basis of race and responsibility for child care.

Conclusions. ICU HCWs reported having minimal knowledge concerning the risk of and response to an influenza pandemic, even though more that one-half of HCWs expect that a pandemic will occur in the near future. This finding in a high-risk setting is of concern, given that lack of knowledge among HCWs may result in increased nosocomial transmission to HCWs and patients. Interventions to improve knowledge of pandemics and understanding of risks among ICU HCWs are essential.

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4. Notifications
APEC EINet "Hot Topics" Video Conference: Lessons Learned from the First Wave

APEC EINet successfully hosted a videoconference on pandemic influenza: "Pandemic H1N1 preparedness: lessons learned & preparing for the second wave". The videoconference occurred 4 Nov 2009 Americas time and 5 Nov 2009 Asia time. Singapore, Australia, and the Philippines shared case studies regarding how preparedness plans affected the response to pandemic influenza, what worked, did not work, and what could be changed for a more effective response in the future. We wish to extend our thanks to participants from Australia, Mexico, Philippines, Singapore, Chinese Taipei, and the USA. Presentations will be made available on our website shortly.

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Resources from Canada for APEC Partners

"In the spirit of information sharing, APEC partners might be interested in some of our publicly available information on the H1N1 outbreak and response in Canada.

FluWatch is an excellent and regularly updated source of surveillance and epidemiological information on H1N1 - similar to some of the information being presented in the [Hot Topics] case studies. It can be found at: http://www.phac-aspc.gc.ca/fluwatch/09-10/index-eng.php.

Also, APEC partners might be interested in the guidance documents we've published in areas such as vaccinations, treatment, infection control and a range of other areas - again, addressing some of the questions with regards to public health measures being taken by member economies. Those can be found at: http://www.phac-aspc.gc.ca/alert-alerte/h1n1/guidance_lignesdirectrices-eng.php.">

Chris Boodram
Policy Analyst, Multilateral Relations, International Public Health Division
Strategic Policy Directorate

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World Response Conference on Global Outbreak 2009: H1N1 Flu + H5N1 Flu
Las Vegas, Nevada, 12-13 Nov 2009

The purpose is to create an Ad Hoc multi-sector Crisis Management Consortium during the event, to be studied as a model by communities worldwide. It is the first world event to invite leaders representing every sector of society to model a community process to help prepare, respond, and recover from a localized outbreak, as well as broader pandemic.
Additional information and registration available at http://wrcgo.eve-ex.com/.

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EPIDEMICS²: Second International Conference on Infectious Diseases Dynamics
Athens, Greece, 2-4 Dec 2009

Following the highly successful inaugural Epidemics Conference in Asilomar, USA in 2008, the organizers are pleased to announce a second conference in the series to be held in Athens, Greece in December 2009. H1N1 pdm abstract deadline: 13 November 2009.
Additional information and registration available at http://www.epidemics.elsevier.com/.

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14th International Congress on Infectious Diseases (ICID)
Miami, Florida, Mar 9-12, 2010

The deadline for abstract submissions to the 14th ICID has been extended to November 30th. Take advantage of reduced registration fees by registering on or before January 15, 2010.
Additional information and registration available at http://www.isid.org/14th_icid/.

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ISHEID Symposium on HIV and Emerging Infectious Diseases
Marseille, France, 24-26 Mar 2010

Tackling each topic from basic science to clinical applications, this meeting will deal with issues of HIV/AIDS, Viral Hepatitis, Emerging Infectious Diseases, and welcome many Key Opinion Leaders.

Submit an abstract before 9 Nov 2009: http://ems6.net/r/?F=t52gxqgrsuxuaj8rzw4tzbgnse3bjbkvlppph78fc3wvvx2943s5v72-1224022

Preliminary program: http://ems6.net/r/?F=t52gxqgrsuxuaj8rzw4tzbgnstb7z348677srxae9269mghaltvxj72-1224022

Registration and hotel booking are open on-line, we recommend you to secure your participation.

The ISHEID 2010 congress organizing office...
E-mail: isheid@clq-group.com; Ph. : +33 1 44 64 15 15 - Fax : +33 1 44 64 15 16

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Avian Influenza: The Basics--an online training module

This module, developed by the Minnesota Center of Excellence for Influenza Research and Surveillance (MCEIRS), contains a series of e-learning lessons. The objective of these lessons is to give the learner a basic understanding of avian influenza viruses and an overview of key facts on avian influenza in birds. Future e-learning modules will address advanced topics and explore emerging issues related to avian influenza.
Available at http://www.mceirs.umn.edu/training/.

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Updated influenza guidance and information from the US CDC

Letter from CDC to States
Released 05 November 2009
Available at http://www.cdc.gov/media/pdf/Final-H1N1-Letter-to-State-Officials--CDC-Director.pdf.

CDC Interim Guidance for Workers who are Employed at Commercial Swine Farms: Preventing the Spread of Influenza A Viruses, Including the 2009 H1N1 Virus
Released 04 November 2009
Available at http://www.cdc.gov/h1n1flu/guidelines_commerical_settings_with_pigs.htm.

Updated: Antiviral Safety Information Web Page
Released 03 November 2009
Available at http://www.cdc.gov/H1N1flu/antivirals/safety_info.htm.

2009 H1N1 Vaccine Dosage, Administration, and Storage
Released 03 November 2009
Available at http://www.cdc.gov/h1n1flu/vaccination/dosage.htm.

2009 H1N1 Influenza: Resources for Pharmacists
Released 03 November 2009
Available at http://www.cdc.gov/H1N1flu/pharmacist/.

Don't Get, Don't Spread Video
Released 30 October 2009
Available at http://www.cdc.gov/CDCTV/IR_DontGetDontSpread/index.html.

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 apecein@u.washington.edu