Login   

EINet Alert ~ Mar 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
- WHO situation update on pandemic influenza H1N1
- Global: WHO declares H5N1 avian influenza still a threat
- Global: Task force sees waning attention to H5N1 avian influenza
- Egypt: 107th case of H5N1 avian influenza
- Australia: First H1N1 influenza case of the year>
- Cambodia: Nation Receives H1N1 influenza vaccine from WHO
- Nepal (Nawalparasi): Confirmation 500 birds have died of H5N1 avian influenza
- Thailand (Bangkok): One H1N1 death confirmed
- Viet Nam (Ho Chi Minh City): Illegal poultry trade continues among H5N1 deaths
- USA: Most H1N1 pandemic influenza indicators below baselines
- USA: H1N1 influenza on US campuses stays level
- USA: CDC reaffirms safety of H1N1 pandemic influenza vaccine
- USA: (Georgia) H1N1 pandemic influenza hospitalizations and deaths on the rise
- USA (Louisiana): H1N1 influenza clinics target rise in influenza activity

2. Updates
- INFLUENZA A/H1N1
- AVIAN INFLUENZA

3. Articles
- Age, influenza pandemics and disease dynamics
- High Probability of Avian Influenza Virus (H7N7) Transmission from Poultry to Humans Active in Disease Control on Infected Farms
- Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret
- Association of RIG-I with innate immunity of ducks to influenza
- Cross-neutralization of 1918 and 209 Influenza Viruses: Role of Glycans in Viral Evolution and Vaccine Design
- Preliminary Estimates of Mortality and Years of Life Lost Associated with the 2009 A/H1N1 Pandemic in the US and Comparison with Past Influenza Seasons
- Critical illness in children with influenza A/pH1N1 2009 infection in Canada

4. Notifications
- 28th Annual Infectious Disease Seminar for Physicians, Pharmacists and Other Healthcare Professionals
- Thailand Conference on Emerging Infectious and Neglected Diseases
- CDC 7th International Conference on Emerging Infectious Diseases
- Options for the Control of Influenza VII
- Influenza 2010: Zoonotic Influenza and Human Health


1. Influenza News

Global
2010 Cumulative number of human cases of avian influenza A/H5N1
Economy / Cases (Deaths)
Egypt / 16 (5)
Indonesia / 1 (1)
Viet Nam / 4 (1)
Total / 21 (7)

***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: 489 (289)
(WHO 3/16/10 http://www.who.int/csr/disease/avian_influenza/country/cases_table_2010_03_16/)

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

^top

WHO situation update on pandemic influenza H1N1
As of 21 March 2010, worldwide more than 213 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 16,931 deaths.

The most active areas of pandemic influenza virus transmission currently are in parts of Southeast Asia, West Africa, and in the tropical zone of the Americas. After a period of sustained pandemic influenza transmission in Thailand over the past two months, overall activity now appears to be decreasing. In West Africa, limited data suggests that active transmission of pandemic influenza virus persists without clear evidence of a peak in activity. In Central America and in the tropical zone of South America, an increasing trend of respiratory disease activity associated with circulation of pandemic influenza virus has been reported since early March 2010 in an increasing number of countries. Although pandemic influenza virus continues to be the predominant influenza virus circulating worldwide, seasonal influenza B viruses are predominate in East Asia, and have been increasingly detected at low levels across southeast and western Asia, eastern Africa, and in parts of Europe.

In Southeast Asia, pandemic influenza virus transmission has remained active and geographically widespread in Thailand since mid February 2010 and has been increasing since early March in Malaysia. In Thailand, the overall intensity of respiratory disease activity was reported to be low to moderate, and activity now appears to decreasing since mid March 2009; 10-22% of sentinel respiratory samples from patients with ILI tested positive for pandemic influenza during the most recent reporting week. In Malaysia, limited data suggests increasing detections of pandemic H1N1 cases over the past two weeks, although the extent and severity of illness is not currently known. Low numbers of seasonal influenza B viruses continue to be isolated in Thailand and in other parts of Southeast Asia.

In South Asia, pandemic influenza virus transmission remains variable across the subcontinent. In Bangladesh, an increasing trend in respiratory disease activity and increasing detections of H1N1 cases has been reported since late February 2010; however, overall intensity of disease activity remains low. In India, although overall pandemic influenza activity remains low, pandemic H1N1 cases continue be reported in Western India.

In East Asia, pandemic influenza virus transmission has declined substantially. Rates of ILI/ARI have returned to near baseline in Japan and Republic of Korea. In China, although overall ILI and pandemic influenza virus circulation has decreased substantially, circulation of seasonal influenza B viruses continues to be active (accounting for ~85% of all influenza viruses isolated during recent weeks). Similarly, in Mongolia, after experiencing a first peak of ILI activity due to circulation of pandemic influenza virus during November 2009, a second recent sharp peak of ILI activity occurred during late February and early March 2010 exclusively as a result circulating seasonal influenza B viruses. Overall influenza activity continues to remain low in Hong Kong SAR (China), Chinese Taipei, and DPR Korea.

In Sub-Saharan Africa, pandemic influenza activity remains variable. Limited data suggest that the most active areas of pandemic influenza virus transmission continue to be in West Africa and in limited areas of East Africa, particularly in Rwanda. Twenty-seven percent of respiratory specimens in Ghana, and 47% of specimens in Rwanda, tested positive for pandemic influenza virus during mid March 2010. In Senegal, a high intensity of respiratory diseases activity was reported in association with increased detections of pandemic influenza virus. Pandemic influenza virus continues to be the predominant influenza virus circulating in West and East Africa, however, small numbers of seasonal influenza H3N2 and seasonal influenza B viruses have also been identified.

In tropical zone of the Americas overall influenza activity remains low, however, active transmission of pandemic influenza virus may be increasing, particularly across Central America and parts of South America. An increasing trend of respiratory diseases activity associated with detections of pandemic influenza virus was reported in Guatemala, Nicaragua, El Salvador, and Panama. In Brazil, three consecutive weeks of increases in respiratory diseases activity have been associated with regional spread of pandemic influenza virus; three states in northern Brazil reported increases in detections of confirmed cases, however, the extent and severity of cases is not yet know. In Mexico, two weeks of increases (11-14% per week) in ILI and SARI were reported during late February and early March 2010, however, the extent to which respiratory disease activity has been due to pandemic influenza virus is not yet known.

In Europe, overall pandemic influenza virus transmission continued to decline or remain low in most countries. Of note, over 20% of sentinel specimens in Germany, Italy, and the Russian Federation tested positive for influenza, however, these increased sentinel detections of influenza virus were not associated with significant increases in overall rates of acute respiratory illness; in Italy and the Russian Federation, seasonal influenza B viruses were either dominant or co-dominant with pandemic H1N1, respectively. In Romania and in Poland, recent increases in rates of ILI or ARI have not been associated with increased detections of pandemic or other influenza viruses.

In North Africa and Western Asia, limited data suggests that pandemic influenza virus continues to circulate at low levels, as overall disease activity remained low across much of the region.

In the northern and the southern temperate zones of the Americas, overall pandemic influenza transmission remained low as influenza virus continues to circulate at low levels.

In the temperate zone of the southern hemisphere, overall influenza activity remained low, with sporadic detections of pandemic and seasonal influenza viruses.
(WHO 03/26/2010)

^top

Global: WHO declares H5N1 avian influenza still a threat
Newly confirmed human and poultry cases of avian influenza this year are a reminder that the virus poses a real and continuous threat to human health.

So far this year, 21 human cases of H5N1, including seven deaths, have been reported. Sixteen of those were in Egypt (including five deaths), four in Viet Nam (including one death), and one in Indonesia (who died). So far in 2010 Bangladesh, Bhutan, Cambodia, India, Israel, Myanmar, Nepal, and Viet Nam have all reported outbreaks of the disease in poultry or wild bird flocks, highlighting the fact that people often are falling sick and dying in the same areas that the virus is persistently present in the environment. H5N1 is considered endemic in Egypt and parts of South East Asia.

The presence of H5N1 in poultry poses a health risk in two ways. First, it places those in direct contact with birds - usually rural folk and farm workers - at risk of catching the often-fatal disease. Second, the virus could undergo a process of "reassortment" with another influenza virus and produce a completely new strain. This gene reassortment is also known as antigenic shift.

Experts say that the influenza virus is unpredictable, and that there is a constant risk that the H5N1 virus will combine with another strain of influenza. WHO and its partners are working to build surveillance systems to identify changes in the behavior of the virus.

Worldwide, human cases peaked at 115 (and 79 deaths) in 2006 and have generally declined since then, with 73 human cases (and 32 deaths) reported last year. The case fatality rate for reported human cases of H5N1 is around 59%.
(WHO 03/24/2010)

^top

Global: Task force sees waning attention to H5N1 avian influenza
An international team of experts, the Scientific Task Force on Avian Influenza and Wild Birds, expressed concern about the lagging interest and effort on the part of governments and the public over H5N1 avian influenza despite its persistence. The waning attention is resulting in reduced surveillance and research opportunities, along with declining coordination between environmental and agricultural authorities, even as the disease continues to spread, particularly in Egypt and parts of Asia. The task force, which issued its statement following a meeting at the United Nation's Food and Agriculture Organization (FAO) headquarters in Rome, said that poor farm biosecurity and the trading of infected poultry are the main causes of disease spread. Wild birds have received much blame for the spread of H5N1, but research has yet to show that they pose more than negligible risk to domestic poultry and humans.
(CIDRAP 03/23/2010)

^top


Europe/Near East
Egypt: 107th case of H5N1 avian influenza
The Egyptian Ministry of Health announced a new case of avian influenza in a child, aged four years, a resident in Beni Suef, bringing the number of those infected with the disease since it appeared in Egypt to 107.

The child had been admitted to Beni Suef General Hospital, suffering from high fever, cough, runny nose and pneumonia after exposure to infected birds. The child received Tamiflu treatment and was transferred to a hospital in the capital.
(ProMED 03/24/2010)

^top


Asia
Australia: First H1N1 influenza case of the year>
Australia's Influenza Complications Alert Network (FluCAN) picked up the nation's first pandemic H1N1 case this year requiring hospitalization, a woman of childbearing age with an underlying illness. The woman, described as of "child-bearing years but not pregnant," was the first case since 11 Dec 2009 reported by 13 major hospitals that are part of FluCAN.
(CIDRAP 03/23/2010)

^top

Cambodia: Nation Receives H1N1 influenza vaccine from WHO
Cambodia's health ministry has received 300,000 doses of H1N1 vaccine from the WHO, and a vaccination campaign may begin immediately. The doses received so far are intended for at-risk populations in four provinces, and more doses are on the way for other provinces. Cambodia has had 566 H1N1 cases with six deaths.
(CIDRAP 03/23/2010)

^top

Nepal (Nawalparasi): Confirmation 500 birds have died of H5N1 avian influenza
The World Organisation for Animal Health (OIE) has confirmed that around 500 backyard birds have died in Nawalparasi district in the past few weeks. Following the outbreak, a team of veterinarians was sent for a stamping out operation. Sources said the birds of a local resident tested positive for H5N1 virus in the central veterinary laboratory.
(OIE.int 03/23/2010)

^top

Thailand (Bangkok): One H1N1 death confirmed
The Ministry of Public Health reported one death from the influenza A (H1N1) in Thailand, raising the accumulated death toll to 219. The victim was identified as a 58-year-old man in Pattani. He was the only patient killed by the H1N1 infection at Saiburi Hospital. He had been suffering from congenital illnesses as well. The number of new patients was reported at 937 nationwide as of the week ending 19 March 2010. The accumulated number of H1N1 patients stood at 35,978.
(National News Bureau of Thailand Public Relations Department 03/22/2010)

^top

Viet Nam (Ho Chi Minh City): Illegal poultry trade continues among H5N1 deaths
Although Vietnam has reported two human deaths from H5N1 influenza already this year, the illegal sale and slaughter of chickens and other fowl that have not passed inspection continues in Ho Chi Minh City and surrounding areas. Authorities have offered little help in remedying the situation. Apparently poultry is brought to markets from the Mekong Delta by motorbike or car. The vehicles avoid highway inspection stations by speeding past or using back routes. In addition, traders whose poultry is seized warn other traders, who then disperse. Animal safety officials are calling on local police to crack down on the illegal trade. Vietnam has had 59 human deaths from H5N1 flu since the outbreak began in 2003 (the WHO has confirmed 58 of these to date, including one in 2010).
(CIDRAP 03/23/2010)

^top


Americas
USA: Most H1N1 pandemic influenza indicators below baselines
Pandemic flu activity remained at uncharacteristically low levels for week 10 of the season, the US Centers for Disease Control and Prevention (CDC) said in its most recent update, though the virus is still circulating amid anecdotal reports of increased activity in a few southern locations.

For the week ending 13 March 2010, most flu barometers stayed the same as the previous week. Deaths from pneumonia and flu dipped below the seasonal baseline for the first time in several weeks, while visits to doctors' offices for flu-like illnesses remained below the national baseline, according to the CDC's 19 March 2010 update. Lab-confirmed pandemic flu hospitalizations have leveled off, and the CDC said it received very few reports during week 10 of the current flu season.

As with the previous nine weeks, no states reported widespread activity. The number of states reporting regional activity dropped from five to three: Alabama, Georgia, and Mississippi. Flu-related doctors' visits were above regional baseline in only one CDC surveillance region, the southeast.

Local flu activity was reported by Puerto Rico and eight states: Arkansas, Hawaii, Louisiana, North Carolina, Oklahoma, South Carolina, Tennessee, and Texas.

Hospital officials in the Houston area have noted a small but steady increase in pandemic flu cases. Authorities at Texas Children's Hospital are reporting slight increases in the number of confirmed pandemic H1N1 cases over the past few weeks, along with a "small bump" in hospital admissions.

Meanwhile, public health officials in Florida's Volusia County recently upgraded the area's flu activity level from sporadic to localized. However, virus activity in neighboring Flagler County remained at sporadic levels, according to the state health department's latest update.

The CDC said it received two more reports of pediatric flu deaths, one from Oklahoma and the other from Texas. Both occurred earlier in the flu season. One involved the pandemic H1N1 virus, and the other was linked to an undetermined influenza A subtype that is thought to be the pandemic virus.

Of nearly 3,600 specimens that were tested during week 10, only 5.6% (200) were positive for influenza. Of all subtyped influenza A viruses, all were the pandemic H1N1 virus. Three influenza B viruses were reported.

No new cases of oseltamivir-resistant pandemic flu have been identified since the CDC's last report.
(CIDRAP 03/22/2010)

^top

USA: H1N1 influenza on US campuses stays level
Flu-like illness activity held at low levels on US college campuses last week, though regional activity continued in the Southeast, which was consistent with what federal officials observed. The attack rate was 1.5 cases/10,000 students, up just 0.2 cases/10,000 students from the previous week. There is no sign of a third wave and that it's unclear if flu activity will rise when students return from spring break.
(CIDRAP 03/23/2010)

^top

USA: CDC reaffirms safety of H1N1 pandemic influenza vaccine
As of mid February, about 86 million Americans had received the pandemic H1N1 vaccine, and so far no worrisome signals have emerged from extensive safety monitoring.

While no adverse event trends have emerged among those receiving vaccine, the CDC said it has seen some patterns with vaccine uptake. Most doses went to target groups, and coverage was higher in children than in adults. Of children under age 10 who received the vaccine, a group recommended to receive two doses, about 60% have gotten their second dose.

In adults, pandemic vaccine uptake was higher in whites than in blacks and Hispanics, though in children patterns did not vary by race or ethnicity.

In analyzing uptake patterns, the CDC is identifying opportunities to refine its messages to the public. For example, a recent survey of adults found that the top reason for not getting the vaccine was that many didn't think they needed to be immunized.

So far, the Vaccine Adverse Event Reporting System (VAERS), set up to detect possible signs of adverse events but not to verify a vaccine link, has shown that serious events related to the pandemic vaccine are no higher than with the seasonal flu vaccine, which has had an excellent safety profile.

The CDC's nongovernmental vaccine safety working group said it had enough data to detect adverse events and that it had so far found no connection to adverse event patterns and the pandemic H1N1 vaccine. The working group was set up to independently evaluate and synthesize H1N1 vaccine data.
(CIDRAP 03/23/2010)

^top

USA: (Georgia) H1N1 pandemic influenza hospitalizations and deaths on the rise
Now is not the time to decrease H1N1 vaccinations, said state officials from the Georgia Department of Community Health.

There have been a total of 1,012 H1N1 hospitalizations and 72 influenza associated deaths in Georgia since April 2009. Officials are concerned that high risk groups, particularly children, are not receiving the H1N1 vaccine.

While seasonal flu usually runs from October through May, H1N1 is still circulating and may continue for many months. Georgia experienced its first wave last spring and peaked with a second wave in September.
(Rome New-Tribune 03/24/2010)

^top

USA (Louisiana): H1N1 influenza clinics target rise in influenza activity
Reports from clinics and hospitals of rising flu-like illnesses over the past few weeks prompted Louisiana health officials to launch walk-in pandemic H1N1 flu vaccine clinics throughout the state this week. Louisiana's state health officer warned in a press release that another wave of infections could occur and urged residents to get vaccinated. The department also noted that other southern states, including the border states of Arkansas and Texas, were seeing rises in flu activity.
(CIDRAP 03/23/2010)

^top


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 CDC: http://www.cdc.gov/h1n1flu/update.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/index.html
ProMED: http://www.promedmail.org/

^top

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.

^top


3. Articles
Age, influenza pandemics and disease dynamics
Greer AL, Tuite A, Fisman DN. Epidemiology and Infection. 22 March 2010; doi:10.1017/S0950268810000579
Available at http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=7409060#

Abstract. The world is currently confronting the first influenza pandemic of the 21st century [caused by a novel pandemic influenza A (H1N1) virus]. Earlier pandemics have been characterized by age distributions that are distinct from those observed with seasonal influenza epidemics, with higher attack rates (and correspondingly increased proportionate or relative mortality) in younger individuals. While the genesis of protection against infection in older individuals during a pandemic is uncertain, differential vulnerability to infection by age has important implications for disease dynamics and control, and for choice of optimal vaccination strategies. Age-related vulnerability to infection may explain differences between school- and community-derived estimates of the reproductive number (R) for a newly emerged pandemic strain, and may also help explain the failure of a newly emerged influenza A (H1N1) virus strain to cause a pandemic in 1977. Age-related factors may also help explain variability in attack rates, and the size and impact of influenza epidemics across jurisdictions and between populations. In Canada, such effects have been observed in the apparently increased severity of outbreaks on Indigenous peoples' reserves. The implications of these patterns for vaccine allocation necessitate targeted research to understand age-related vulnerabilities early in an influenza pandemic.

^top

High Probability of Avian Influenza Virus (H7N7) Transmission from Poultry to Humans Active in Disease Control on Infected Farms
Bos MEH, te Beest DE, van Boven M, et al. The Journal of Infectious Diseases. 2010; 201: 000-00; doi: 10.1086/651663
Available at http://www.journals.uchicago.edu/doi/abs/10.1086/651663

Abstract. An epizootic of avian influenza (H7N7) caused a large number of human infections in The Netherlands in 2003. We used data from this epizootic to estimate infection probabilities for persons involved in disease control on infected farms. Analyses were based on databases containing information on the infected farms, personal visits to these farms, and exposure variables (number of birds present, housing type, poultry type, depopulation method, period during epizootic). Case definition was based on self reported conjunctivitis and positive response to hemagglutination inhibition assay. A high infection probability was associated with clinical inspection of poultry in the area surrounding infected flocks (7.6%; 95% confidence interval [CI], 1.4%-18.9%) and active culling during depopulation (6.2%; 95% CI, 3.7%-9.6%). Low probabilities were estimated for management of biosecurity (0.0%; 95% CI, 0.0%-1.0%) and cleaning assistance during depopulation (0.0%; 95% CI, 0.0%-9.2%). No significant association was observed between the probability of infection and the exposure variables.

^top

Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret
Rao SS, Kong WP, Wei CJ, et al. Plos One. 23 March 2010;5(3): e9812 doi:10.1371/journal.pone.0009812
Available at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009812

Abstract. Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge.

^top

Association of RIG-I with innate immunity of ducks to influenza
Barber MRW, Aldridge Jr. JR, Webster RG, et al. PNAS. 22 March 2010; doi: 10.1073/pnas.1001755107
Available at http://www.pnas.org/content/early/2010/03/03/1001755107

Abstract. Ducks and wild waterfowl perpetuate all strains of influenza viruses in nature. In their natural host, influenza viruses typically cause asymptomatic infection and little pathology. Ducks are often resistant to influenza viruses capable of killing chickens. Here, we show that the influenza virus sensor, RIG-I, is present in ducks and plays a role in clearing an influenza infection. We show evidence suggesting that RIG-I may be absent in chickens, providing a plausible explanation for their increased susceptibility to influenza viruses compared with ducks. RIG-I detects RNA ligands derived from uncapped viral transcripts and initiates the IFN response. In this study, we show that the chicken embryonic fibroblast cell line, DF-1, cannot respond to a RIG-I ligand. However, transfection of duck RIG-I into DF-1 cells rescues the detection of ligand and induces IFN-ß promoter activity. Additionally, DF-1 cells expressing duck RIG-I have an augmented IFN response resulting in decreased influenza replication after challenge with either low or highly pathogenic avian influenza virus. Implicating RIG-I in the antiviral response to an infection in vivo, we found that RIG-I expression is induced 200 fold, early in an innate immune response in ducks challenged with the H5N1 virus A/Vietnam/1203/04. Finding this natural disease resistance gene in ducks opens the possibility of increasing influenza resistance through creation of a transgenic chicken.

^top

Cross-neutralization of 1918 and 209 Influenza Viruses: Role of Glycans in Viral Evolution and Vaccine Design
Wei CJ, Boyington JC, Dai Kl, et al. Sci Transl Med. 24 March 2010;2(24); doi: 10.1126/scitranslmed.3000799
Available at http://stm.sciencemag.org/content/2/24/24ra21.abstract

Abstract. New strains of H1N1 influenza virus have emerged episodically over the last century to cause human pandemics, notably in 1918 and recently in 2009. Pandemic viruses typically evolve into seasonal forms that develop resistance to antibody neutralization, and cross-protection between strains separated by more than 3 years is uncommon. Here, we define the structural basis for cross-neutralization between two temporally distant pandemic influenza viruses-from 1918 and 2009. Vaccination of mice with the 1918 strain protected against subsequent lethal infection by 2009 virus. Both were resistant to antibodies directed against a seasonal influenza, A/New Caledonia/20/1999 (1999 NC), which was insensitive to antisera to the pandemic strains. Pandemic strain-neutralizing antibodies were directed against a subregion of the hemagglutinin (HA) receptor binding domain that is highly conserved between the 1918 and the 2009 viruses. In seasonal strains, this region undergoes amino acid diversification but is shielded from antibody neutralization by two highly conserved glycosylation sites absent in the pandemic strains. Pandemic HA trimers modified by glycosylation at these positions were resistant to neutralizing antibodies to wild-type HA. Yet, antisera generated against the glycosylated HA mutant neutralized it, suggesting that the focus of the immune response can be selectively changed with this modification. Collectively, these findings define critical determinants of H1N1 viral evolution and have implications for vaccine design. Immunization directed to conserved receptor binding domain subregions of pandemic viruses could potentially protect against similar future pandemic viruses, and vaccination with glycosylated 2009 pandemic virus may limit its further spread and transformation into a seasonal influenza.

^top

Preliminary Estimates of Mortality and Years of Life Lost Associated with the 2009 A/H1N1 Pandemic in the US and Comparison with Past Influenza Seasons
Viboud C, Miller M, Olson D, et al. PLoS Currents: Influenza. 20 March 2010; doi:PMC2843747.
Available at http://knol.google.com/k/cecile-viboud/preliminary-estimates-of-mortality-and/35hpbywfdwl4n/8?collectionId=28qm4w0q65e4w.1&position=1#

Abstract. The on-going debate about the health burden of the 2009 influenza pandemic and discussions about the usefulness of vaccine recommendations has been hampered by an absence of directly comparable measures of mortality impact. Here we set out to generate an "apples-to-apples" metric to compare pandemic and epidemic mortality. We estimated the mortality burden of the pandemic in the US using a methodology similar to that used to generate excess mortality burden for inter-pandemic influenza seasons. We also took into account the particularly young age distribution of deaths in the 2009 H1N1 pandemic, using the metric "Years of Life Lost" instead of numbers of deaths. Estimates are based on the timely pneumonia and influenza mortality surveillance data from 122 US cities, and the age distribution of laboratory-confirmed pandemic deaths, which has a mean of 37 years. We estimated that between 7,500 and 44,100 deaths are attributable to the A/H1N1 pandemic virus in the US during May-December 2009, and that between 334,000 and 1,973,000 years of life were lost. The range of years of life lost estimates includes in its lower part the impact of a typical influenza epidemic dominated by the more virulent A/H3N2 subtype, and the impact of the 1968 pandemic in its upper bound. We conclude that the 2009 A/H1N1 pandemic virus had a substantial health burden in the US over the first few months of circulation in terms of years of life lost, justifying the efforts to protect the population with vaccination programs. Analysis of historic records from three other pandemics over the last century suggests that the emerging pandemic virus will continue to circulate and cause excess mortality in unusually young populations for the next few years. Continuing surveillance for indicators of increased mortality is of key importance, as pandemics do not always cause the majority of associated deaths in the first season of circulation.

^top

Critical illness in children with influenza A/pH1N1 2009 infection in Canada
Jouvet P, Hutchison J, Pinto R, et al. Pediatric Critical Care Medicine. 19 March 2010; doi: 10.1097/PCC.0b013e3181d9c80b
Available at http://journals.lww.com/pccmjournal/Abstract/publishahead/Critical_illness_in_children_with_influenza.99601.aspx

Objective. To describe characteristics, treatment, and outcomes of critically ill children with influenza A/pH1N1 infection in Canada.

Design. An observational study of critically ill children with influenza A/pH1N1 infection in pediatric intensive care units (PICUs).

Setting. Nine Canadian PICUs.

Patients. A total of 57 patients admitted to PICUs between April 16, 2009 and August 15, 2009.

Interventions. --------.

Measurements and Main Results. Characteristics of critically ill children with influenza A/pH1N1 infection were recorded. Confirmed intensive care unit cases were compared with a national surveillance database containing all hospitalized pediatric patients with influenza A/pH1N1 infection. Risk factors were assessed with a Cox proportional hazard model. The PICU cohort and national surveillance data were compared, using chi-square tests. Fifty-seven children were admitted to the PICU for community-acquired influenza A/pH1N1 infection. One or more chronic comorbid illnesses were observed in 70.2% of patients, and 24.6% of patients were aboriginal. Mechanical ventilation was used in 68% of children, 20 children (35.1%) had acute lung injury on the first day of admission, and the median duration of ventilation was 6 days (range, 0-67 days). The PICU mortality rate was 7% (4 of 57 patients). When compared with nonintensive care unit hospitalized children, PICU children were more likely to have a chronic medical condition (relative risk, 1.73); aboriginal ethnicity was not a risk factor of intensive care unit admission.

Conclusions. During the first outbreak of influenza A/pH1N1 infection, when the population was naive to this novel virus, severe illness was common among children with underlying chronic conditions and aboriginal children. Influenza A/pH1N1-related critical illness in children was associated with severe hypoxemic respiratory failure and prolonged mechanical ventilation. However, this higher rate and severity of respiratory illness did not result in an increased mortality when compared with seasonal influenza.

^top


4. Notifications
28th Annual Infectious Disease Seminar for Physicians, Pharmacists and Other Healthcare Professionals
Hilton Head, SC, USA. 7-9 April 2010
This seminar is designed to provide practical, cutting-edge information to practicing physicians and other health care providers concerning evaluation and management of common infectious diseases as well as those making headlines.
Additional information available at: http://www.neoucom.edu/ce.

^top

Thailand Conference on Emerging Infectious and Neglected Diseases
Pattaya, Thailand, 3-4 June 2010
Outbreaks of various diseases, including SARS, avian influenza, influenza H1N1 pandemics, and the most recently chikungunya fever, continue to challenge our abilities to prepare for the emerging infectious disease threats. This conference, therefore, will facilitate national and international updating and sharing of knowledge, experiences, and scientific expertise which is crucial for handling these global threats.
Additional information and registration available at http://nstda.or.th/eid2010/.

^top

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/.

^top

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.

^top

Influenza 2010: Zoonotic Influenza and Human Health
Oxford, United Kingdom 22 Sep 2010
The Oxford influenza conference, Influenza 2010, will address most aspects of basic and applied research on zoonotic influenza viruses (including avian and swine) and their medical and socio-economic impact.
Additional information available at http://www.libpubmedia.co.uk/Conferences/Influenza2010/Home.htm.

^top

 apecein@u.washington.edu