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EINet Alert ~ Feb 26, 2010


*****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
- 2010 Cumulative number of human cases of avian influenza A/H5N1
- Global: WHO situation update on pandemic influenza H1N1
- Global: WHO Director-General statement regarding the H1N1 pandemic status
- Global: WHO recommends developing new H9N2 vaccine virus
- Bulgaria: Pandemic H1N1 vaccination campaign to begin
- Czech Republic: Free pandemic H1N1 vaccine available to the general public
- Egypt: Three new H5N1 influenza cases confirmed
- Bhutan: First H5N1 outbreak reported in poultry
- Hong Kong: Probes into possible pandemic H1N1 vaccination reactions
- South Korea: Pandemic H1N1 vaccine made available to all
- Viet Nam: First human H5N1 avian influenza case of 2010
- Viet Nam (Nam Dinh & Soc Trang): Ducks found positive for H5N1 avian influenza
- Canada (British Columbia): No influenza reported at Olympics
- USA: Emergency departments see rise in flu-like illness
- USA (Texas): Tobacco-based influenza vaccine production
- USA: ACIP recommends annual flu shots for almost all
- USA: CDC will reduce H1N1 vaccine stockpiles

2. Updates
- INFLUENZA A/H1N1
- AVIAN INFLUENZA

3. Articles
- Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses
- Absolute Humidity and the Seasonal Onset of Influenza in the Continental United States
- Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence
- Triple Combination of Amantadine, Ribavirin, and Oseltamivir Is Highly Active and Synergistic against Drug Resistant Influenza Virus Strains In Vitro
- Seroprevalence Following the Second Wave of Pandemic 2009 H1N1 Influenza
- Assessment of the Efficacy of Commercially Available and Candidate Vaccines against a Pandemic H1N1 2009 Virus
- Novel Virus Influenza A (H1N1sw) in South-Eastern France, April-August 2009
- Effects of Early Oseltamivir Therapy on Viral Shedding in 2009 Pandemic Influenza A (H1N1) Virus Infection

4. Notifications
- Emerging Infectious Diseases in Response to Climate Change
- 14th International Congress on Infectious Diseases (ICID)
- International Swine Flu Conference (ISFC)
- ISHEID Symposium on HIV and Emerging Infectious Diseases
- CDC 7th International Conference on Emerging Infectious Diseases
- Options for the Control of Influenza VII
- Updated influenza guidance and information from the US CDC


1. Influenza News

Global
2010 Cumulative number of human cases of avian influenza A/H5N1
Economy / Cases (Deaths)
Egypt / 9 (3)
Indonesia / 1 (1)
Total / 10 (4)

***For data on human cases of avian influenza prior to 2010, go to: http://depts.washington.edu/einet/humanh5n1.html

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 478 (286)
(WHO 2/17/10 http://www.who.int/csr/disease/avian_influenza/country/cases_table_2010_02_17/en/)

Avian influenza age distribution data from WHO/WPRO (last updated 2/8/10): http://www.wpro.who.int/sites/csr/data/data_Graphs.htm

WHO's map showing world's areas affected by H5N1 avian influenza (status as of 2/12/10): http://gamapserver.who.int/mapLibrary/Files/Maps/Global_H5N1Human_2010_FIMS_20100212.png.

WHO's timeline of important H5N1-related events (last updated 1/4/10): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html

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Global: WHO situation update on pandemic influenza H1N1
As of 21 February 2010, worldwide more than 213 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 16,226 deaths.

Pandemic influenza H1N1 2009 virus continues to be the predominant influenza virus circulating worldwide. In addition to the increasing proportion of seasonal influenza type B viruses recently detected in China, low levels of seasonal H3N2 and type B viruses are circulating in parts of Africa, and Asia.
In the temperate zone of the northern hemisphere, pandemic influenza virus continues to be detected across many countries, however, overall influenza activity continues to wane in most places. The most active areas of transmission are currently in parts of south and southeast Asia and in limited areas of east and southeastern Europe.

In Southeast Asia, pandemic influenza virus continued to circulate in areas, however, the overall intensity of respiratory diseases activity remained low and unchanged, except in a few countries. In Brunei Darussalam, during February 2009, influenza activity was reported to be geographically widespread and was associated with an increasing trend and high intensity of respiratory diseases. Both Myanmar and Thailand have reported an increasing trend of respiratory diseases associated with geographically regional spread of influenza for the first half of February 2009, however, overall intensity currently remains low in both countries. In Thailand, approximately one third of provinces reported that >5% of medical visits were due to ILI during the most recent reporting week. In East Asia, virologic surveillance data suggest that pandemic influenza and seasonal influenza type B viruses continue to co-circulate. A recent increase in ILI activity in Mongolia may be due to an increase in the circulation of seasonal influenza type B viruses. Overall influenza activity continues to decline and return to baseline levels in both Japan and South Korea. In Hong Kong and in Chinese Taipei, pandemic influenza virus continues to circulate at low levels and overall ILI activity is substantially lower than what was observed during the fall months. In South Asia, overall influenza activity remained low, however, pandemic influenza virus transmission persists in the western part of India.

In Europe, pandemic influenza virus transmission persists across parts of central and southeastern Europe, but overall intensity remained low, except for Greece, Bulgaria, Turkey, Slovakia, the Republic of Moldova, and parts of the Russian Federation which continued to report a moderate intensity respiratory diseases activity. Although an increasing trend of respiratory diseases continued to be reported in Georgia, Slovakia, and parts of the Russian Federation, the increased activity may be due to other circulating respiratory viruses. Among countries testing at least 20 sentinel respiratory specimens during the past reporting week, none reported that more than 20% of specimens had tested positive for influenza.

In North Africa and West Asia, pandemic influenza virus continues to circulate at low levels as rates of illness in most countries in the region continued to decline or return to baseline. In Afghanistan, an increasing trend of respiratory diseases with moderate healthcare impact was reported, however, it is unknown if the recent increase is associated with circulation of influenza virus.

In Sub-Saharan Africa, limited data suggest that pandemic influenza virus transmission continued to be sporadic in most areas of the continent. Several countries in West Africa continue to report slight increases in the numbers of confirmed cases of pandemic influenza indicating that community transmission is likely beginning in the area; however, data are very limited.

In the Americas, both in the tropical and northern temperate zones, pandemic influenza virus continues to circulate at low levels but overall pandemic influenza activity continued to decline or remain low in most places. In Central America and Caribbean, pandemic influenza virus transmission persists but overall activity remains low or unchanged in most places.

In summary, pandemic influenza virus continues to circulate widely in the tropical regions and is persisting in some areas of Europe. Respiratory disease activity is increasing in many areas of the world due to increasing transmission of influenza type B and Respiratory Syncitial Virus. Seasonal influenza H3N2 continues to be detected in areas of Asia and east Africa.
(WHO 2/26/2010)

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Global: WHO Director-General statement regarding the H1N1 pandemic status
The Emergency Committee held its seventh meeting by teleconference on 23 February 2010. The Director-General sought the Committee's views on the determination of the pandemic status.

A detailed update was provided to the Committee on the global pandemic situation. After asking additional questions and reviewing the evidence and holding extensive discussion, the Committee was of the view that there was mixed evidence showing declining or low pandemic activity in many countries, but new community level transmission activity in West Africa. Moreover, they expressed concern that the winter months of the Southern Hemisphere had not yet started and there was uncertainty whether additional generalized waves of activity might occur and the need to not undermine preparations. The Committee advised that it was premature to conclude that all parts of the world have experienced peak transmission of the H1N1 pandemic influenza and that additional time and information was needed to provide expert advice on the status of the pandemic. The Committee accordingly suggested that the Committee be re-convened in a few weeks to review intervening developments and related epidemiological information.

Having considered these views, the current epidemiological evidence and other relevant information, the Director-General determined that there had been no change in the pandemic phase, and decided to continue to monitor the situation and developments closely and to convene the Committee again within the next several weeks.
Having considered the views of the Emergency Committee, and the ongoing pandemic situation, the Director-General determined to continue the three temporary recommendations, as modified, namely:
* countries should not close borders or restrict international traffic and trade;
* maintain surveillance of unusual flu-like illness & severe pneumonia;
* if ill, it is prudent to delay travel.
(WHO 2/24/2010)

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Global: WHO recommends developing new H9N2 vaccine virus
In a semiannual update on avian influenza activity, the WHO has recommended that health authorities begin developing a candidate vaccine virus for the most recently recovered isolates of avian flu strain H9N2. That subtype, which is endemic in poultry in parts of Asia and the Middle East, caused two unrelated human infections in Hong Kong in late 2009. Isolates from the patients were not completely reactive to ferret antiserum to the existing H9N2 candidate vaccine virus, which was isolated in 1999. That existing vaccine and one made from a 1997 isolate have been studied in eight clinical trials testing different formulations and dosages. The WHO also reported that strains of H5N1 avian flu belonging to at least five different viral clades have caused poultry outbreaks since September 2009, but the agency did not recommend that any additional H5N1 candidate vaccine viruses be developed.
(CIDRAP 2/19/2010)

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Europe/Near East
Bulgaria: Pandemic H1N1 vaccination campaign to begin
Bulgaria is set to launch its pandemic H1N1 vaccine campaign on 1 March 2010, targeting 80,000 doses to priority groups, including babies older than six months with certain medical conditions, pregnant women, and healthcare workers. The start of the program comes about three months after flu activity subsided in Bulgaria. The health ministry is asking doctors to recommend the vaccine to patients at high risk for flu complications.
(CIDRAP 2/25/2010)

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Czech Republic: Free pandemic H1N1 vaccine available to the general public
Czech Republic officials opened up the country's estimated 700,000 doses of novel H1N1 vaccine to the general public free of charge. Although vaccine uptake has been low in that country, officials hope the announcement will spur vaccination, especially in children. The vaccine will be available in vaccination centers, not in doctors' offices.
(CIDRAP 2/24/2010)

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Egypt: Three new H5N1 influenza cases confirmed
Three new avian influenza H5N1 virus infection cases have been reported in Egypt, bringing the total number to 102. The 100th case is a 10-year-old boy from Dakahlia governorate. The 101st case is a 13-year-old boy from Kafr El-Sheikh governorate. The 102nd case is a 30-year-old woman from Qellin city, Kafr El-Sheikh governorate.
(ProMED 2/25/2010 & 2/20/2010)

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Asia
Bhutan: First H5N1 outbreak reported in poultry
Agriculture officials in Bhutan reported the country's first H5N1 avian influenza outbreak, which struck free-range chickens in a village near the southwestern border with India, according to a report from the World Organization for Animal Health (OIE). The outbreak, located in Chhuka province, began 18 February 2010, killing eight birds and sickening 14 others. The remaining 28 birds on the premises were culled. The virus's presence in samples from the birds was confirmed by the High Security Animal Disease Laboratory in Bhopal, India, and at the National Institute of Animal Health in Bangkok, Thailand. Bhutan's report raises the number of countries that have been hit by H5N1 outbreaks to 63.
(CIDRAP 2/23/2010)

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Hong Kong: Probes into possible pandemic H1N1 vaccination reactions
Hong Kong's Centre for Health Protection is studying illnesses in several residents that arose after they received the H1N1 influenza vaccine. The cases include a 34-year-old man who experienced double vision, a 28-year-old pregnant woman whose fetus died, and paralysis in a 75-year-old woman and an 80-year-old man. The government was careful to say there are cases of paralysis and stillbirth in the territory every year.
(CIDRAP 2/23/2010)

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South Korea: Pandemic H1N1 vaccine made available to all
Pandemic H1N1 flu vaccine is now available to everyone in South Korea, including foreigners, not just to high-risk groups, the Ministry of Health, Welfare and Family Affairs announced 22 February 2010. The ministry urged vaccinations, saying that about 500 daily H1N1 cases are being reported, although the number has been on the decline.
(CIDRAP 2/22/2010)

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Viet Nam: First human H5N1 avian influenza case of 2010
A three year old girl in the central province of Khanh Hoa has tested positive for avian influenza H5N1 virus infection, becoming the country's first H5N1 patient of 2010, the Ministry of Health reported in Hanoi on 22 February 2010.

The girl, who lives in Ninh Hoa District's Ninh Than Commune, fell sick with fever, sore throat, cough, and a runny nose on 27 January 2010. She was admitted to Ninh Hoa Hospital the next day and was confirmed to be infected with the virus on 12 February 2010, according to the Ministry. The girl was recovering, the Ministry reported.

An inspection conducted in Ninh Than showed no sign of the avian flu in the commune, and the poultry raised by the girl's family showed no signs of sickness. However, the Ministry's inspectors found that about a month earlier, ostriches had died of an undiagnosed disease at a farm a kilometer from the patient's home.
(ProMED 2/24/2010)

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Viet Nam (Nam Dinh & Soc Trang): Ducks found positive for H5N1 avian influenza
Avian Influenza virus infection has recurred in Nam Dinh and Soc Trang provinces in Viet Nam with two flocks of ducks testing positive for the H5N1 virus.

The virus was detected in a flock of 630 ducks belonging to a farmer in Soc Trang's Thanh Thoi Thuan Commune after 500 of them died during the Lunar New Year holiday. The remaining ducklings in the flock were reportedly killed. None of the 45-day-old ducks had been vaccinated.

In the northern province of Nam Dinh's Nghi An Commune, the virus hit a seven-month-old flock. Provincial animal heath officials killed all 270 ducks in an effort to contain the disease.
(ProMED 2/19/2010)

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Americas
Canada (British Columbia): No influenza reported at Olympics
So far pandemic H1N1 influenza - as well as seasonal influenza - has been held not only off the podium but entirely away from the Vancouver Olympic Games. British Columbia provincial laboratory did not find a single influenza virus in samples it tested the week ending of 20 February 2010.
(CIDRAP 2/22/2010)

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USA: Emergency departments see rise in flu-like illness
Some of the nation's emergency departments are noting increases in flu-like illness cases that appear to be pandemic H1N1, and colleges are reporting the first increase in flu-like illness since the end of November, but it's not clear if these are early signs of a third pandemic flu wave.

On 24 February 2010, the American College of Emergency Physicians (ACEP) said in a Twitter post that some of its members were anecdotally reporting a new wave of pandemic H1N1 patients coming to emergency departments and asked if other physicians were seeing similar patterns.

Carl Schultz, MD, professor of emergency medicine at the University of California at Irvine, said that the increase in the number of influenza-like illnesses appears to be real, but he cautioned that many of the cases have not been confirmed as the pandemic H1N1 strain, because many departments stopped specifically testing for it because of low flu activity. Schultz chairs ACEP's disaster preparedness and response committee.

Tom Skinner, a spokesman for the US Centers for Disease Control and Prevention (CDC) said that the CDC has nothing to report on any increase in flu activity, but he said it is keeping watch of flu-like illness trends across the nation.

Meanwhile, the American College Health Association (ACHA) reported 24 February 2010 in its latest surveillance summary of influenza-like illnesses a 52% rise in cases, reflecting the first increase since the end of November. For the week ending 19 February 2010, the attack rate at schools was 4.1 cases per 10,000 students. Schultz said that the rise in college flu-like illnesses isn't particularly alarming, because activity had dropped to such a low level that a 52% increase is not sizeable.
(CIDRAP 2/24/2010)

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USA (Texas): Tobacco-based influenza vaccine production
Leaders of the Texas Plant-Expressed Vaccine Consortium announced a biotherapeutic manufacturing initiative designed to show proof of concept for a new technology that could increase the nation's capability to produce vaccines for infectious diseases, including influenza.

Project GreenVax, which utilizes tobacco plants rather than the current egg-based vaccine technology, holds the promise of shortening vaccine production to a fraction of the current time, allowing rapid response to newly emerging viruses not possible with current technology. The majority of funding for the project is provided by the Defense Advanced Research Projects Agency (DARPA).

The Consortium, comprised of G-Con, LLC and The Texas A&M University System, designed Project GreenVax for a projected final scale capacity of 100 million doses per month. The flexibility of the plant-based system, combined with its low cost and ability to massively scale, may provide vaccine protection not only to citizens of the United States, but to many parts of the world that cannot currently afford vaccines.
(Texas A&M Press Release 2/24/2010)

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USA: ACIP recommends annual flu shots for almost all
In the wake of the H1N1 influenza pandemic, the US Advisory Committee on Immunization Practices (ACIP) took the long-discussed step of recommending seasonal flu immunizations for nearly everyone, leaving out only small babies. The step extends the recommendation to all adults for the first time. Previous ACIP recommendations for seasonal flu immunization covered about 85% of the population but excepted healthy adults aged 19 to 49 who are not close contacts of people at risk for serious flu complications. Babies younger than six months are also excluded, as vaccination is considered too risky for them.

The new recommendation, which passed on a 12-0 vote with one abstention, was prompted in part by factors related to the H1N1 pandemic, including its impact on younger adults, the recognition of obesity as a possible risk factor for severe disease, and disproportionate effects on minority groups. The pandemic virus will be included in the 2010-11 seasonal vaccine.
(CIDRAP 2/24/2010)

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USA: CDC will reduce H1N1 vaccine stockpiles
Over the next two months, the Centers for Disease Control and Prevention (CDC) plans to reduce by half the amount of H1N1 vaccine it has pre-positioned in distribution depots around the country managed by McKesson Corp. The CDC has maintained 30 million doses at the sites. The agency said the main strategy will be not replacing three million doses that have been recalled, along with 15.3 million doses that are reaching their expiration dates between March and June.
(CIDRAP 2/23/2010)

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2. Updates
INFLUENZA A/H1N1
- 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 México: 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. 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 H5N1.
- 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 health officials prepare for an influenza pandemic.
- The US government's website for pandemic/avian flu: http://www.flu.gov/. "Flu Essentials" are available in multiple languages.
- CIDRAP: Avian Influenza page: http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/.
- 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 avian influenza H5N1 in wild birds and poultry.

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3. Articles
Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses
Kiso M, Kubo S, Ozawa M, et al. PLoS Pathog. 26 February 2010; 6(2): e1000786.
Available at http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000786.

Abstract. Currently, two neuraminidase (NA) inhibitors, oseltamivir and zanamivir, which must be administrated twice daily for 5 days for maximum therapeutic effect, are licensed for the treatment of influenza. However, oseltamivir-resistant mutants of seasonal H1N1 and highly pathogenic H5N1 avian influenza A viruses have emerged. Therefore, alternative antiviral agents are needed. Recently, a new neuraminidase inhibitor, R-125489, and its prodrug, CS-8958, have been developed. CS-8958 functions as a long-acting NA inhibitor in vivo (mice) and is efficacious against seasonal influenza strains following a single intranasal dose. Here, we tested the efficacy of this compound against H5N1 influenza viruses, which have spread across several continents and caused epidemics with high morbidity and mortality. We demonstrated that R-125489 interferes with the NA activity of H5N1 viruses, including oseltamivir-resistant and different clade strains. A single dose of CS-8958 (1,500 µg/kg) given to mice 2 h post-infection with H5N1 influenza viruses produced a higher survival rate than did continuous five-day administration of oseltamivir (50 mg/kg twice daily). Virus titers in lungs and brain were substantially lower in infected mice treated with a single dose of CS-8958 than in those treated with the five-day course of oseltamivir. CS-8958 was also highly efficacious against highly pathogenic H5N1 influenza virus and oseltamivir-resistant variants. A single dose of CS-8958 given seven days prior to virus infection also protected mice against H5N1 virus lethal infection. To evaluate the improved efficacy of CS-8958 over oseltamivir, the binding stability of R-125489 to various subtypes of influenza virus was assessed and compared with that of other NA inhibitors. We found that R-125489 bound to NA more tightly than did any other NA inhibitor tested. Our results indicate that CS-8958 is highly effective for the treatment and prophylaxis of infection with H5N1 influenza viruses, including oseltamivir-resistant mutants.

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Absolute Humidity and the Seasonal Onset of Influenza in the Continental United States
Shaman J, Pitzer VE, Viboud C, et al. PLoS Biol. 23 February 2010; 8(2): e1000316.
Available at http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1000316.

Abstract. Much of the observed wintertime increase of mortality in temperate regions is attributed to seasonal influenza. A recent reanalysis of laboratory experiments indicates that absolute humidity strongly modulates the airborne survival and transmission of the influenza virus. Here, we extend these findings to the human population level, showing that the onset of increased wintertime influenza-related mortality in the United States is associated with anomalously low absolute humidity levels during the prior weeks. We then use an epidemiological model, in which observed absolute humidity conditions temper influenza transmission rates, to successfully simulate the seasonal cycle of observed influenza-related mortality. The model results indicate that direct modulation of influenza transmissibility by absolute humidity alone is sufficient to produce this observed seasonality. These findings provide epidemiological support for the hypothesis that absolute humidity drives seasonal variations of influenza transmission in temperate regions.

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Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence
Li C, Hatta M, Nidom CA, et al. Proc Natl Acad Sci. 22 February 2010; doi: 10.1073/pnas.0912807107.
Available at http://www.pnas.org/content/early/2010/02/18/0912807107.

Abstract. The spread of avian H5N1 influenza viruses around the globe has become a worldwide public health concern. To evaluate the pathogenic potential of reassortant viruses between currently cocirculating avian H5N1 and human H3N2 influenza viruses, we generated all the 254 combinations of reassortant viruses between A/chicken/South Kalimantan/UT6028/06 (SK06, H5N1) and A/Tokyo/Ut-Sk-1/07 (Tok07, H3N2) influenza viruses by reverse genetics. We found that the presence of Tok07 PB2 protein in the ribonucleoprotein (RNP) complex allowed efficient viral RNA transcription in a minigenome assay and that RNP activity played an essential role in the viability and replicative ability of the reassortant viruses. When the pathogenicity of 75 reassortant H5 viruses was tested in mice, 22 were more pathogenic than the parental SK06 virus, and three were extremely virulent. Strikingly, all 22 of these viruses obtained their PB2 segment from Tok07 virus. Further analysis showed that Tok07 PB1 alone lacked the ability to enhance the pathogenicity of the reassortant viruses but could do so by cooperating with Tok07 PB2. Our data demonstrate that reassortment between an avian H5N1 virus with low pathogenicity in mice and a human virus could result in highly pathogenic viruses and that the human virus PB2 segment functions in the background of an avian H5N1 virus, enhancing its virulence. Our findings highlight the importance of surveillance programs to monitor the emergence of human H5 reassortant viruses, especially those containing a PB2 segment of human origin.

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Triple Combination of Amantadine, Ribavirin, and Oseltamivir Is Highly Active and Synergistic against Drug Resistant Influenza Virus Strains In Vitro
Nguyen JT, Hoopes JD, Le MH, et al. PLoS ONE. 22 February 2010; 5(2): e9332.
Available at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009332.

Abstract. The rapid emergence and subsequent spread of the novel 2009 Influenza A/H1N1 virus (2009 H1N1) has prompted the World Health Organization to declare the first pandemic of the 21st century, highlighting the threat of influenza to public health and healthcare systems. Widespread resistance to both classes of influenza antivirals (adamantanes and neuraminidase inhibitors) occurs in both pandemic and seasonal viruses, rendering these drugs to be of marginal utility in the treatment modality. Worldwide, virtually all 2009 H1N1 and seasonal H3N2 strains are resistant to the adamantanes (rimantadine and amantadine), and the majority of seasonal H1N1 strains are resistant to oseltamivir, the most widely prescribed neuraminidase inhibitor (NAI). To address the need for more effective therapy, we evaluated the in vitro activity of a triple combination antiviral drug (TCAD) regimen composed of drugs with different mechanisms of action against drug-resistant seasonal and 2009 H1N1 influenza viruses. Amantadine, ribavirin, and oseltamivir, alone and in combination, were tested against amantadine- and oseltamivir-resistant influenza A viruses using an in vitro infection model in MDCK cells. Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05), including the combination of two NAIs. Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadine- and oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable. Our data demonstrate that the TCAD regimen composed of amantadine, ribavirin, and oseltamivir is highly synergistic against resistant viruses, including 2009 H1N1. The TCAD regimen overcomes baseline drug resistance to both classes of approved influenza antivirals, and thus may represent a highly active antiviral therapy for seasonal and pandemic influenza.

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Seroprevalence Following the Second Wave of Pandemic 2009 H1N1 Influenza
Ross T, Zimmer S, Burke D, et al. PLoS Curr Influenza. 20 February 2010; PMC2820309.
Available at http://knol.google.com/k/seroprevalence-following-the-second-wave-of-pandemic-2009-h1n1-influenza#.

Background. In April 2009, a new pandemic strain of influenza infected thousands of persons in Mexico and the United States and spread rapidly worldwide. During the ensuing summer months, cases ebbed in the Northern Hemisphere while the Southern Hemisphere experienced a typical influenza season dominated by the novel strain. In the fall, a second wave of pandemic H1N1 swept through the United States, peaking in most parts of the country by mid October and returning to baseline levels by early December. The objective was to determine the seroprevalence of antibodies against the pandemic 2009 H1N1 influenza strain by decade of birth among Pittsburgh-area residents.

Methods & Findings. Anonymous blood samples were obtained from clinical laboratories and categorized by decade of birth from 1920-2009. Using hemagglutination-inhibition assays, approximately 100 samples per decade (n= 846) were tested from blood samples drawn on hospital and clinic patients in mid-November and early December 2009. Age specific seroprevalences against pandemic H1N1 (A/California/7/2009) were measured and compared to seroprevalences against H1N1 strains that had previously circulated in the population in 2007, 1957, and 1918. (A/Brisbane/59/2007, A/Denver/1/1957, and A/South Carolina/1/1918). Stored serum samples from healthy, young adults from 2008 were used as a control group (n=100). Seroprevalences against pandemic 2009 H1N1 influenza varied by age group, with children age 10-19 years having the highest seroprevalence (45%), and persons age 70-79 years having the lowest (5%). The baseline seroprevalence among control samples from 18-24 year-olds was 6%. Overall seroprevalence against pandemic H1N1 across all age groups was approximately 21%.

Conclusions. After the peak of the second wave of 2009 H1N1, HAI seroprevalence results suggest that 21% of persons in the Pittsburgh area had become infected and developed immunity. Extrapolating to the entire US population, we estimate that at least 63 million persons became infected in 2009. As was observed among clinical cases, this sero-epidemiological study revealed highest infection rates among school-age children.

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Assessment of the Efficacy of Commercially Available and Candidate Vaccines against a Pandemic H1N1 2009 Virus
Kobinger G, Meunier I, Patel A, et al. J Infect Dis. 19 February 2010; doi: 10.1086/651171.
Available at http://www.journals.uchicago.edu/doi/abs/10.1086/651171.

Background. The emergence and global spread of the pandemic H1N1 2009 influenza virus have raised questions regarding the protective effect of available seasonal vaccines and the efficacy of a newly produced matched vaccine.

Methods. Ferrets were immunized with the 2008-2009 formulations of commercially available live attenuated (FluMist; MedImmune) or split?inactivated (Fluviral; GlaxoSmithKline) vaccines, a commercial swine vaccine (FluSure; Pfizer), or a laboratory?produced matched inactivated whole?virus vaccine (A/Mexico/InDRE4487/2009). Adaptive immune responses were monitored, and the animals were challenged with A/Mexico/InDRE4487/2009 after 5 weeks.

Results. Only animals that received the swine or matched vaccines developed detectable hemagglutination?inhibiting antibodies against the challenge virus, whereas a T cell response was exclusively detected in animals vaccinated with FluMist. After challenge, all animals had high levels of virus replication in the upper respiratory tract. However, preexisting anti-pandemic H1N1 2009 antibodies resulted in reduced clinical signs and improved survival. Surprisingly, FluMist was associated with a slight increase in mortality and greater lung damage, which correlated with early up-regulation of interleukin-10.

Conclusions. The present study demonstrates that a single dose of matched inactivated vaccine confers partial protection against a pandemic H1N1 2009 virus, and it suggests that a higher dose or prime?boost regimen may be required. The consequences of mismatched immunity to influenza merit further investigation.

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Novel Virus Influenza A (H1N1sw) in South-Eastern France, April-August 2009
Nougairède A, Ninove L, Zandotti C, et al. PLoS ONE. 17 February 2010; 5(2): e9214.
Available at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009214.

Background. In April 2009, the first cases of pandemic (H1N1)-2009 influenza [H1N1sw] virus were detected in France. Virological surveillance was undertaken in reference laboratories of the seven French Defence Zones.

Methodology/Principal Findings. We report results of virological analyses performed in the Public Hospitals of Marseille during the first months of the outbreak. (i) Nasal swabs were tested using rapid influenza diagnostic test (RIDT) and two RT-PCR assays. Epidemiological characteristics of the 99 first suspected cases were analyzed, including detection of influenza virus and 18 other respiratory viruses. During three months, a total of 1,815 patients were tested (including 236 patients infected H1N1sw virus) and distribution in age groups and results of RIDT were analyzed. (ii) 600 sera received before April 2009 and randomly selected from in-patients were tested by a standard hemagglutination inhibition assay for antibody to the novel H1N1sw virus. (iii) One early (May 2009) and one late (July 2009) viral isolates were characterized by sequencing the complete hemagglutinine and neuraminidase genes. (iiii) Epidemiological characteristics of a cluster of cases that occurred in July 2009 in a summer camp were analyzed.

Conclusions/Significance. This study presents new virological and epidemiological data regarding infection by the pandemic A/H1N1 virus in Europe. Distribution in age groups was found to be similar to that previously reported for seasonal H1N1. The first seroprevalence data made available for a European population suggest a previous exposure of individuals over 40 years old to influenza viruses antigenically related to the pandemic (H1N1)-2009 virus. Genomic analysis indicates that strains harbouring a new amino-acid pattern in the neuraminidase gene appeared secondarily and tended to supplant the first strains. Finally, in contrast with previous reports, our data support the use of RIDT for the detection of infection in children, especially in the context of the investigation of grouped cases.

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Effects of Early Oseltamivir Therapy on Viral Shedding in 2009 Pandemic Influenza A (H1N1) Virus Infection
Ling L, Chow A, Lye D, et al. Clin Infect Dis. 5 February 2010; doi: 10.1086/651083.
Available at http://www.journals.uchicago.edu/doi/abs/10.1086/651083.

Background. Pandemic influenza (H1N1) 2009 is susceptible to oseltamivir. There are few reports on its clinical and virologic response to oseltamivir.

Methods. During the pandemic containment response in Singapore, all patients with positive polymerase chain reaction (PCR) results for pandemic influenza (H1N1) 2009 were hospitalized, given oseltamivir for 5 days, and discharged when daily PCR results for combined nasal and throat swab samples became negative. Six patients had concurrent positive viral culture and PCR results.

Results. The median age of the first 70 consecutive patients was 26 years (interquartile range, 21-38 years); 60% were men, and 29% had comorbidity. The mean time (±SD) from illness onset to hospital admission was 3±2 days. Influenza-like illness was noted in 63% of patients. Fever occurred in 91%, cough in 88%, sore throat in 66%, and rhinorrhea in 53% of patients. The mean duration (±SD) of viral shedding from illness onset was 6±2 days. Viral shedding persisted beyond 7 days in 37% of patients. Clinical features and viral shedding were similar between those with and without comorbidity, except the former had more cough and lower oxygen saturation. Patients receiving oseltamivir on days 1 to 3 of illness had significantly shorter viral shedding duration, compared with those treated from day 4 onwards (p<0.05). The mean durations (±SD) of positive PCR and viral culture results were 5±0.8 and 4±1.8 days, respectively, for 6 patients with concurrent positive viral culture and PCR results.

Conclusions. Prolonged viral shedding was noted in young immunocompetent adults with mild pandemic influenza (H1N1) 2009 despite receipt of oseltamivir. When prescribed during the first 3 days of illness, oseltamivir shortened the duration of viral shedding.

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4. Notifications
Emerging Infectious Diseases in Response to Climate Change
New York City, USA, 2 March 2010
This symposium examines the complex relationship between the climate, environment, and infectious diseases.
Additional information and registration available at http://www.nyas.org/Events/Detail.aspx?cid=aa4086a1-6917-4cd3-b14f-7317214ed96c.

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14th International Congress on Infectious Diseases (ICID)
Miami, Florida, USA, 9-12 Mar 2010
Additional information and registration available at http://www.isid.org/14th_icid/.

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International Swine Flu Conference (ISFC)
London, United Kingdom, 10-12 Mar 2010
Reflecting their strong agreement about the importance of the International Swine Flu Conference (ISFC), renowned medical experts have agreed to share end-to-end H1N1 prevention, preparedness, and response and recovery strategies at the event.
Additional information and registration available at http://www.new-fields.com/isfc_uk/.

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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.
Additional information and registration available at http://www.isheid.com/.

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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CDC 7th International Conference on Emerging Infectious Diseases
Atlanta, Georgia, USA 11-14 Jul 2010
The 2010 International Conference on Emerging Infectious Diseases (ICEID) is the principal meeting for emerging infectious diseases organized by CDC. This conference includes plenary and panel sessions, as well as oral and poster presentations, and covers a broad spectrum of infectious diseases of public health relevance. ICEID 2010 will also focus on the impact of various intervention and preventive strategies that have been implemented to address emerging infectious disease threats.
Additional information is available at http://www.iceid.org/.

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Options for the Control of Influenza VII
Hong Kong, 3-7 Sep 2010
Options for the Control of Influenza VII is the largest forum devoted to all aspects of the prevention, control, and treatment of influenza. As it has for over 20 years, Options VII will highlight the most recent advances in the science of influenza. The scientific program committee invites authors to submit original research in all areas related to influenza for abstract presentation. Accepted abstracts will be assigned for oral or poster presentation.
Additional information is available at http://www.controlinfluenza.com.

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Updated influenza guidance and information from the US CDC
2009 H1N1 Flu: Underlying Health Conditions among Hospitalized Adults and Children
Released 24 February 2010
Available at http://www.cdc.gov/H1N1flu/eip_underlying_conditions.htm

Questions and Answers: Behavioral Risk Factor Surveillance System (BRFSS) 2009 H1N1 Flu Modules for Influenza-like Illness (ILI) and Vaccination
Released 24 February 2010
Available at http://www.cdc.gov/h1n1flu/behavior_risk_factors_surv_sys.htm

Questions & Answers: Information on 2009 H1N1 impact by Race and Ethnicity
Released 24 February 2010
Available at http://www.cdc.gov/h1n1flu/race_ethnicity_qa.htm

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 apecein@u.washington.edu