EINet Alert ~ Oct 26, 2007

*****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:
- Global: Cumulative number of human cases of avian influenza A/(H5N1)
- Global: WHO expects pandemic vaccine capacity to soar
- Cambodia: FAO to focus on training in HPAI surveillance
- Indonesia (Banten): Young child is latest avian influenza H5N1 fatality
- Indonesia (Riau): 7 new suspected human cases of avian influenza H5N1 infection
- Myanmar (Bago): Official excerpts from OIE report on avian influenza H5N1 in poultry
- USA: Pandemic vaccine proposal favors health workers, children
- USA: Provides funding for FAO’s bird flu program
- Avian/Pandemic influenza updates

1. Articles
- CDC EID Journal, Volume 13, Number 10--Oct 2007
- Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses
- Study says H5N1 has varied effects in small land birds
- Bird flu virus in Europe – a hidden danger
- Study: Cold, dry air favors spread of flu in lab animals
- The Pandemic Vaccine Puzzle

2. Notifications
- WHO Interim Protocol: Rapid operations to contain the initial emergence of pandemic influenza
- ACIP endorses FluMist for 2-, 3-, and 4-year-olds
- White House aims to transform public health preparedness

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

Viet Nam / 3 (3)
Total / 3 (3)

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

Cambodia / 4 (4)
China / 8 (5)
Indonesia / 17 (11)
Thailand / 5 (2)
Viet Nam / 61 (19)
Total / 95 (41)

Azerbaijan / 8 (5)
Cambodia / 2 (2)
China / 13 (8)
Djibouti / 1 (0)
Egypt / 18 (10)
Indonesia / 56 (46)
Iraq / 3 (2)
Thailand / 3 (3)
Turkey / 12 (4)
Total / 116 (80)

Cambodia/ 1 (1)
China / 3 (2)
Egypt / 20 (5)
Indonesia / 35 (31)
Laos / 2 (2)
Nigeria / 1 (1)
Viet Nam 7 (4)
Total / 69 (46)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 332 (204).
(WHO 10/17/07 http://www.who.int/csr/disease/avian_influenza/en/index.html )

Avian influenza age distribution data from WHO/WPRO: http://www.wpro.who.int/sites/csr/data/data_Graphs.htm.
(WHO/WPRO 10/17/07)

WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 10/23/07): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 10/19/07): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html.


Global: WHO expects pandemic vaccine capacity to soar
WHO estimated that by 2010 the world may be equipped to make enough pandemic influenza vaccine to immunize 4.5 billion people—vastly more than in previous projections, though still well short of the world's population of 6.7 billion. Last spring WHO and manufacturers estimated that only about 100 million courses of flu vaccine based on the H5N1 avian flu strain could be produced immediately with standard technology. The new projection assumes that the demand for seasonal flu vaccines will continue to grow, stimulating vaccine producers to add capacity, and that adjuvants will make it possible to use less antigen (active ingredient) per dose of vaccine, stretching the supply. Adjuvants are chemicals included in some vaccines to provide a general stimulus to the immune system. Manufacturers this year have increased production capacity for trivalent (targeting three viral strains) seasonal flu vaccine to 565 million doses, compared with 350 million last year, WHO said. Experts in the field predict that the seasonal flu vaccine production capacity will rise to 1 billion doses in 2010, "provided corresponding demand exists," WHO says. Noting that production capacity depends on how much antigen is required for each dose, the agency added, "Scientists have recently discovered they can reduce the amount of antigen used to produce pandemic influenza vaccine by using water-in-oil substances that enhance the immune response." The statement apparently refers to adjuvants like that of vaccine producer GlaxoSmithKline (GSK). The new WHO projections were greeted with skepticism by some experts.
(CIDRAP 10/23/07)


Cambodia: FAO to focus on training in HPAI surveillance
FAO's activities in Cambodia to control and prevent the spread of the highly pathogenic avian influenza (HPAI) have just been boosted thanks to a US$ 1.9 million grant from the US Agency for International Development (USAID). The money is part of a new US$ 38 million package for the FAO’s HPAI programme worldwide. FAO will use the grant to support ongoing activities of the Ministry of Agriculture, Forestry and Fisheries to control avian influenza at its source in domestic poultry and waterfowl for the next 2 years. A major component of this project will be to continue the training of veterinary staff and village animal health workers (VAHWs) in the techniques of surveillance, and the recognition and systematic recording and reporting of suspected cases.

In Nov, FAO will commence a routine surveillance of wild birds together with the US-based Wildlife Conservation Society (WCS), focusing on sites and waterfowl species selected for their association with past outbreaks and/or the likelihood of mingling or sharing habitat with domestic fowl. The aim is to collect and test some 3,000 wild bird samples during a 6-month period. To complement the enhanced surveillance capacity, FAO has expanded the laboratory capacity of the National Animal Health and Production Investigation Centre to conduct serology and virus isolation on an increased number of samples. The FAO programme currently focuses on markets in Phnom Penh , Takeo and Kampong Cham but now that the laboratory's testing capacity has been enlarged, the surveillance is being expanded steadily to cover major live bird markets in all provinces in the country. Surveillance will focus on ducks, which the primary asymptomatic carriers of the H5N1 virus.

Other activities to be supported by the new funds include the setting up of a rapid response outbreak fund, and public awareness and education campaigns promoting biosecurity measures on farms, markets, households and elsewhere to reduce the risk of introduction and/or the spread of infection. FAO will also support the strengthening of the governance of the veterinary authority and the development of sound veterinary law in which the veterinary authority has clear responsibilities and adequate powers in all key areas of animal disease prevention.
(FAO 10/22/07 http://www.fao.org/avianflu/en/index.html )


Indonesia (Banten): Young child is latest avian influenza H5N1 fatality
A health ministry official in Indonesia said that a 4-year-old girl from Banten province died Oct 22, 2007 of H5N1 avian influenza. Lily Sulistyowati, a health ministry spokeswoman, said the girl was hospitalized 2 days before her death. Nyoman Kandun of the health ministry said investigators concluded that the girl had had contact with dead poultry in her neighborhood. If the girl's case is confirmed by WHO, it will be listed as Indonesia's 110th H5N1 case and 89th fatal one. The girl is from the same western suburb of Jakarta—Tangerang—as the country's most recent WHO-confirmed case-patient, a 12-year-old boy who died Oct 13. Officials were still investigating the case, but 4 chickens had previously died in the girl's neighborhood, another official at the Ministry's bird flu centre said. Contact with sick fowl is the most common way for humans to contract the deadly H5N1 strain of the virus. Bird flu is endemic in bird populations in most parts of Indonesia, where millions of backyard chickens live in close proximity to humans.
(CIDRAP 10/24/07; Promed 10/24/07)


Indonesia (Riau): 7 new suspected human cases of avian influenza H5N1 infection
7 children aged between 1 and 10 years old are suspected of having bird flu in Indonesia's Riau province [on the island of Sumatra], where 4 people have died of the virus in recent months, an official said 23 Oct 2007. "It is only suspicion, but we are [keen] to handle the case[s]," local head office head Hasanul Irbai was quoted as saying. The 7 children live in Siak regency, in the province on Sumatra island. "The Siak government will immediately send the children to the Arifin Achmad Hospital in Pekaanbaru (the provincial capital)," he said.
(Promed 10/24/07)


Myanmar (Bago): Official excerpts from OIE report on avian influenza H5N1 in poultry
Information received 24 Oct 2007, Ministry of Livestock & Fisheries, Rangoon, Myanmar.

Start date 19 Oct 2007; Date of previous occurrence 28 Jul 2007
Manifestation of disease: Clinical disease
Causal agent: Highly pathogenic avian influenza virus, Serotype H5N1 Nature of diagnosis: Suspicion, Clinical, Laboratory (basic), Laboratory (advanced), Necropsy
Outbreak Location: Bago (Oatsu Quarter)
Species: Birds: Susceptible 33 859; Cases 400; Deaths 400; Destroyed 33 459; Slaughtered 0
Affected population: 32 070 quail, 3118 quail eggs, 52 kg of feed, 1242 layer chickens, 147 ducklings and 30 500 hatching duck eggs were all destroyed.
Apparent morbidity rate: 1.18 percent; Apparent mortality rate: 1.18 percent; Apparent case fatality rate: 100.00 percent; Proportion susceptible removed; 100.00 percent
Source of infection: Unknown or inconclusive
Test: polymerase chain reaction (PCR), positive; rapid tests, positive.
(Promed 10/24/07)


USA: Pandemic vaccine proposal favors health workers, children
A federal interagency working group released a draft report detailing how the government would allocate limited vaccine supplies if a severe influenza pandemic grips the US, offering a tiered approach that flags key health and public safety personnel and children as top priorities. The report says the vaccine allocation plan is designed not only to save lives, but also to reduce the medical, social, and economic impacts of a pandemic. Vaccinations will be administered in tiers, which include 4 target groups: healthcare and community support services, critical infrastructure, homeland and national security, and the general population. For some of the target groups, the priority tier level would change depending on pandemic severity. Prioritizations were based on the most recent scientific research on pandemics and vaccines and on meetings with the public and stakeholders. The working group also sought the input of ethicists, including from the National Institutes of Health and a group from the Minnesota Center for Healthcare Ethics (MCHCE).

The highest-priority groups include deployed military and other critical national security personnel; emergency medical services, public safety workers, and key government officials; medical providers and public health workers; and pregnant women, infants, and toddlers. In adjusting priorities for different levels of pandemic severity, the rationing plan marks a shift from the federal pandemic plan released 2 years ago, which assumed a moderate pandemic. Compared with the older plan, the new proposal changes the priorities for a number of groups. For example, the proposal puts elderly people and other high-risk adults in the fourth tier, whereas high-risk adults ranked second, right after medical and public health workers, in the older plan. Also, essential utility and communications workers are in the second tier 2 under the new plan, but ranked near the end of the line under the old one.

Dorothy Vawter, associate director of MCHCE, said that the working group's recommendations represent a big step forward in pandemic planning. She expects that some disagreements with the prioritizations will arise out of the public comments and will probably prompt the group to fine-tune the report. Some people may be surprised to see the report's focus on social roles and responsibilities, and questions may be raised about the status of students and people who are unemployed, she said. Vawter said one prioritization issue in the report that surprised her was a category in a lower tier that lumps young adults with health problems comorbidities in a group with people as old as 105. "There's no distinction in that tier, and it seems like too big of a bucket," she said, adding that it's likely the group will make some adjustments in that category. The group said it will take public comments for 2 months and then revise the document, which will be considered a final interim report.
(CIDRAP 10/24/07)


USA: Provides funding for FAO’s bird flu program
The US will support FAO’s avian influenza control and prevention programme with an additional US$38 million, FAO announced today. The US is one of the biggest donors to the agency’s programme. With the new funding, US support to the FAO avian influenza programme has reached a total of about $63 million. FAO is currently assisting more than 100 countries in their efforts to prevent and control avian influenza. The US Agency for International Development (USAID) said in a letter to FAO that the contribution will be earmarked for core Highly Pathogenic Avian Influenza containment and control activities, including in-country surveillance and early warning, efforts to reduce disease transmission, and communication to increase public awareness and preparedness.

“Avian influenza will probably stay with us for several years to come. The support from the United States will enable FAO to continue and strengthen avian influenza prevention and control campaigns in affected countries,” said FAO’s Chief Veterinary Officer Joseph Domenech. "Our latest contribution reaffirms the confidence we place in FAO to contain and control Highly Pathogenic Avian Influenza at its animal source. Lending support to countries through FAO remains a key element in managing the global risk," said Ambassador Gaddi Vasquez of the US Mission to FAO. The new money will go into ongoing and new surveillance and response, planning, training, logistics, technical, laboratory, and communication projects and activities in western, eastern and southern Africa, Southeast Asia, the Indian sub-continent, Central Asia, central/eastern Europe, Indonesia and Egypt.

Cross-border surveillance and the more active involvement of local communities and village animal health workers in control and response activities will be some of the priority areas to be supported with US funding. Fresh money is also being directed at FAO’s current work on the socio-economic impact of HPAI, biosecurity and wild bird surveillance. USAID specified that as part of its support to FAO’s efforts to control HPAI globally, it was particularly interested in backing the UN agency’s aim to establish an avian influenza communications capacity. New US funds will also go to the Crisis Management Centre – Animal Health, an emergency response unit run by FAO, which in collaboration with the World Organisation for Animal Health (OIE) supports governments’ response to avian influenza and other transboundary animal diseases through the rapid provision of technical and operational expertise.

The main donors to FAO’s avian influenza programme, amounting to around $180 million, are: the US ($63 million); Australia ($14 million); Japan ($13 million); the United Kingdom ($10 million) and Sweden ($10 million); followed by UN Development Programme administered funds; Canada; Germany; the Asian Development Bank; France; Norway; Switzerland; Belgium; the European Commission and Spain. The avian influenza programme is also supported by financial resources from FAO’s Technical Cooperation Programme.
(FAO 10/17/07 http://www.fao.org/avianflu/en/index.html )


Avian/Pandemic influenza updates
- UN: http://www.un-influenza.org/ : progress report on avian influenza. Also, http://www.irinnews.org/Birdflu.asp provides information on avian influenza.
- WHO: http://www.who.int/csr/disease/avian_influenza/en/index.html.
- UN FAO: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html. Read about the FAO event that took place 7-12 Oct 2007: FAO building avian influenza response capacities: Hands-on training to give first responders a head start.
- OIE: http://www.oie.int/eng/info_ev/en_AI_avianinfluenza.htm
- US CDC: http://www.cdc.gov/flu/avian/index.htm.
- The US government’s web site for pandemic/avian flu: http://www.pandemicflu.gov/. Public Comments Sought on Draft of Flu Vaccine Allocation Plan.
- Health Canada: information on pandemic influenza: http://www.influenza.gc.ca/index_e.html. Update on Saskatchewan avian influenza outbreak
- CIDRAP: http://www.cidrap.umn.edu/.
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm.
- US Geological Survey, National Wildlife Health Center Avian Influenza Information: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp. Updated 19 Oct 2007 with information on H7N3 outbreak in Canada.


1. Articles
CDC EID Journal, Volume 13, Number 10--Oct 2007
CDC Emerging Infectious Diseases Journal Oct 2007 issue is now available at: http://www.cdc.gov/ncidod/EID/index.htm. Influenza-related articles: Preparedness for Highly Pathogenic Avian Influenza Pandemic in Africa by R.F. Breiman et al.; Influenza A and B Infection in Children in Urban Slum, Bangladesh by W.A. Brooks et al.; Confronting Potential Influenza A (H5N1) Pandemic with Better Vaccines by A. Haque et al.; Personal Protective Equipment and Antiviral Drug Use during Hospitalization for Suspected Avian or Pandemic Influenza by A. Swaminathan et al.; Chlorine Inactivation of Highly Pathogenic Avian Influenza Virus (H5N1) by E.W. Rice et al.; Multifocal Avian Influenza (H5N1) Outbreak by R.D. Balicer et al.; Super-Sentinel Chickens and Detection of Low-Pathogenicity Influenza Virus by P.I. Marcus et al.

Expedited articles can be viewed at: http://www.cdc.gov/ncidod/eid/upcoming.htm. Expedited influenza related articles are: Protection and Virus Shedding of Falcons Vaccinated against Highly Pathogenic Avian Influenza A Virus (H5N1); Role of Terrestrial Wild Birds in Ecology of Influenza A Virus (H5N1); Pandemic Influenza and Hospital Resources; Medical Students and Pandemic Influenza; Bird Flu: A Virus of Our Own Hatching.


Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses
John M Nicholls et al. Respiratory Research 2007, 8:73doi:10.1186/1465-9921-8-73
Abstract (provisional): Background Influenza virus binds to cell receptors via sialic acid (SA) linked glycoproteins. They recognize SA on host cells through their haemagglutinins (H). The distribution of SA on cell surfaces is one determinant of host tropism and understanding its expression on human cells and tissues is important for understanding influenza pathogenesis. The objective of this study therefore was to optimize the detection of alpha2,3 -linked and alpha2,6-linked SA by lectin histochemistry by investigating the binding of Sambucus nigra agglutinin (SNA) for SAalpha2,6Gal and Maackia amurensis agglutinin (MAA) for SAalpha2,3Gal in the respiratory tract of normal adults and children. Methods We used fluorescent and biotinylated SNA and MAA from different suppliers on archived and prospectively collected biopsy and autopsy specimens from the nasopharynx, trachea, bronchus and lungs of fetuses, infants and adults. We compared different methods of unmasking for tissue sections to determine if these would affect lectin binding. Using serial sections we then compared the lectin binding of MAA from different suppliers. Results We found that unmasking using microwave treatment in citrate buffer produced increased lectin binding to the ciliated and glandular epithelium of the respiratory tract. In addition we found that there were differences in tissue distribution of the alpha2,3 linked SA when 2 different isoforms of MAA (MAA1 and MAA2) lectin were used. MAA1 had widespread binding throughout the upper and lower respiratory tract and showed more binding to the respiratory epithelium of children than in adults. By comparison, MAA2 binding was mainly restricted to the alveolar epithelial cells of the lung with weak binding to goblet cells. SNA binding was detected in bronchial and alveolar epithelial cells and binding of this lectin was stronger to the paediatric epithelium compared to adult epithelium. Furthermore, the MAA lectins from 2 suppliers (Roche and EY Laboratories) tended to only bind in a pattern similar to MAA1 (Vector Labs) and produced a different binding pattern to MAA2 from Vector Labs. Conclusions The lectin binding pattern of MAA may vary depending on the supplier and the different isoforms of MAA show a different tissue distribution in the respiratory tract. This finding is important if conclusions about the potential binding sites of SAalpha2,3 binding viruses, such as influenza or human parainfluenza are to be made.


Study says H5N1 has varied effects in small land birds
A study on the effects of the H5N1 avian influenza virus on small land birds suggests it is often lethal in sparrows but has lesser effects on starlings and pigeons and does not readily spread to other birds of the same species. However, the researchers say their findings also suggest that sparrows and starlings could potentially spread the virus to poultry and mammals. The results of the study, conducted at St Jude Children's Research Hospital, were published online by Emerging Infectious Diseases.

Scientists have fleshed out some H5N1 patterns in waterfowl species, which have been shown to shed the virus for prolonged periods and are thought to play some role—along with poultry—in the geographic spread among the world's poultry populations. However, less is known about small terrestrial birds, which also intermingle with waterfowl and poultry. To gauge how the H5N1 virus behaves in small birds, the researchers inoculated sparrows, starlings, and pigeons with 4 different strains that were isolated from birds. 2 of the strains had previously been shown to infect waterfowl in Thailand, and 2 were recently isolated during wild-bird surveillance in Hong Kong. At the start of the study, the authors obtained cloacal swabs from the birds to rule out existing influenza A infections.

After the birds were inoculated with the H5N1 strains, researchers placed them with uninfected birds of the same species for 14 days to gauge virus transmission. The ratio of infected to uninfected birds was 1:1 for sparrows and starlings and 2:3 for pigeons. The birds were monitored each day for death and illness, and oropharyngeal and cloacal swabs were collected on days 2, 4, 6, 8, and 11 for sparrows and starlings and on days 3, 5, and 7 for pigeons. At the end of the 14-day period, the investigators collected serum samples from the inoculated and contact birds for hemagglutanin-inhibition testing.

Death rates were highest for the sparrows: 66% to 100% of them died, depending on the H5N1 strain they received. High viral loads were detected in dead sparrows' brain and lung tissues. However, none of the starlings or pigeons died. Regular testing after inoculation showed that all of the sparrows and starlings were infected, but infection in pigeons depended on the strain of the virus. 1 of the Hong Kong strains infected both sparrows and starlings, as well as all of the inoculated pigeons, though the authors found the viruses replicated relatively poorly in the pigeons. Virus titers showed sparrows and starlings shed similar amounts of the virus, but titers from cloacal swabs of sparrows were higher than those from the starlings. The researchers found no evidence of spread of the virus among the sparrows and pigeons. Only 1 starling showed evidence of transmission, involving 1 of the Hong Kong strains.

The authors concluded that that the birds varied in their susceptibility to the H5N1 viruses but that transmission to the contact birds was infrequent. Compared to earlier reports on the susceptibility of sparrows, starlings, and pigeons to a 1997 Hong Kong H5N1 virus, the current study suggests that the bird species are more susceptible to the more recent H5N1 isolates used in the study. A key question is whether smaller wild birds can be intermediate hosts or long-term reservoirs for the H5N1 virus. The results in sparrows suggest that they could potentially infect poultry and mammals, but, given the high death rate, wouldn't likely serve as a reservoir for prolonged viral shedding. Starlings, because they survived and shed the virus longer, could act as an intermediate host, but transmission evidence in the study was limited, the report says. The authors suggest that the role of pigeons in spreading the virus may be minor because they shed only small amounts of the virus and didn't transmit the disease to other pigeons. The researchers conclude that terrestrial wild bird species vary considerably in their susceptibility to H5N1 virus strains, and some species, such as sparrows, could suffer substantial losses during H5N1 outbreaks.

Boon ACM, et al. Role of terrestrial wild birds in ecology of influenza A virus (H5N1). Emerg Infect Dis 2007 Nov;
(CIDRAP 10/18/07)


Bird flu virus in Europe – a hidden danger
The avian influenza virus H5N1 could become entrenched in chickens and domestic ducks and geese in parts of Europe, FAO warned. The agency stressed that healthy domestic ducks and geese may transmit the virus to chickens and play a more important role in the persistence of the virus in the region than previously thought. H5N1 surveillance in countries with significant domestic duck and geese populations should be urgently increased. FAO’s Chief Veterinary Officer, Joseph Domenech, said “If it turns out to be true that the H5N1 virus can persist in apparently healthy domestic duck and geese populations, then countries need to urgently reinforce their monitoring and surveillance schemes in all regions with significant duck and geese production for the presence of H5N1.” The link between domestic ducks and geese and chickens is seen by many experts as one of the major underlying factors in outbreaks of HPAI in disease-entrenched countries. “We are particularly concerned about the Black Sea area which has a high concentration of chickens, ducks and geese,” said FAO senior animal health officer Jan Slingenbergh. Importantly, the Black Sea area serves as a main wintering area for migratory birds coming from Siberia and moving also to the Mediterranean and other regions. All countries bordering the Black Sea have experienced outbreaks of avian influenza in the past, favoured by traditional open poultry systems with poor separation between wild and domestic birds.

The link between the H5N1 virus and domestic ducks and geese has recently been confirmed in Germany. Scientists of the Friedrich-Loeffler-Institut have detected the H5N1 virus in diseased young ducks on a farm at the end of August. Further scrutiny at 2 other farms revealed that, despite the absence of clinical signs and mortality in these ducks, the animals had been in contact with the H5N1 virus, because their immune defense system showed antibodies, developed in response to the virus. Intensified monitoring finally confirmed pockets of H5N1 on one of the farms.

FAO considers that risk assessment, surveillance and virus search strategies should be reviewed, Domenech said. Countries with significant domestic duck and geese populations in Western and Central Europe as well as the Black Sea region should consider the incidence in Germany as a wake-up call and should not limit the virus search to chickens. Good surveillance is already in place in many European countries and the European Commission has issued in 2007 very comprehensive guidelines. But there are countries where more monitoring is urgently needed including more focus on ducks and geese which should be considered as particularly risky populations. After Asia and Africa, Europe could become the third continent where the H5N1 could become endemic in some areas, FAO said.
(FAO 10/25/07 http://www.fao.org/newsroom/en/news/2007/1000685/index.html )


Study: Cold, dry air favors spread of flu in lab animals
Scientists investigating why seasons drive annual influenza epidemics have charted how low humidity and cold temperatures contribute to the spread of the disease in laboratory animals. The research group, from Mt Sinai School of Medicine, published their findings in Public Library of Science Pathogens (PLoS Pathogens). In the 2-pronged study, the researchers first tested aerosol influenza A virus transmission at different relative humidities and temperatures among guinea pigs. Then they assessed whether cold temperatures influenced the immune response of infected animals by extracting RNA from their nasal tissues for polymerase chain reaction (PCR) testing.

The researchers used guinea pigs because they learned that guinea pigs kept for research purposes in 1919 at a New Mexico army base died during the 1918 flu pandemic, Peter Palese, senior author of the study, said. "We didn't know guinea pigs got the flu. They are no longer popular lab animals, and no one had tried them," he said. To tease out the effects of temperature and humidity on virus spread, the group performed 20 trials at different humidities and temperatures, each involving 8 animals For each trial, 4 guinea pigs were intranasally inoculated with influenza A virus. Then pairs of infected and uninfected animals were housed individually in adjoining cages. Nasal wash samples were collected from the animals about every other day, and serum samples were collected before infection and on day 17 after infection.

5 different humidity levels were tested at 20C: 20%, 35%, 50%, 65%, and 80%. The researchers found that transmission was most efficient at the 2 lowest humidity levels, at which 3 or 4 of the exposed guinea pigs became infected. At 50% relative humidity, only 1 of 4 animals contracted influenza. More were infected in 65% humidity, but no disease transmission was noted at 80% humidity. In the temperature experiments, animals were exposed to 5C, 20C, and 30C at different humidity levels. The investigators found that transmission was more efficient when guinea pigs were kept at 5C than at 20C, and at 30C they detected no disease spread. In addition, the duration of peak viral shedding at 5C was 40 hours longer than at 20C. In assessing the effect of low temperatures on innate immune response, the authors found that housing animals at 5C didn't greatly impair their immune response when compared with that of animals housed at 20C. This finding runs counter to the conventional wisdom, the authors asserted.
Lowen AC et al. Influenza virus transmission is dependent on relative humidity and temperature. PLoS Pathogens 2007 Oct ;3(10):e151.
(CIDRAP 10/19/07)


The Pandemic Vaccine Puzzle
Part 1: Flu research: a legacy of neglect
Editor's note: This is the first in a seven-part series investigating the prospects for development of vaccines to head off the threat of an influenza pandemic posed by the H5N1 avian influenza virus. The series puts advances in vaccine technology in perspective by illuminating the formidable barriers to producing an effective and widely usable vaccine in a short time frame.

The first article for the series, “Flu research: a legacy of neglect”, discusses the following:
A chronic low priority
Gaps in the knowledge base
Funding: A starvation diet
US leads other countries

Upcoming articles for this series:
Part 2: Vaccine production capacity falls far short
Part 3: H5N1 poses major immunologic challenges
Part 4: The promise and problems of adjuvants
Part 5: What role for prepandemic vaccination?
Part 6: Looking to novel vaccine technologies
Part 7: Reinforcing the research agenda
(CIDRAP 10/25/07)


2. Notifications
WHO Interim Protocol: Rapid operations to contain the initial emergence of pandemic influenza
Updated October 2007: This document replaces previous versions of the protocol. In brief, key changes include: More emphasis on rapid containment and less on rapid response which is covered in WHO guidelines for investigation of human cases of avian influenza A(H5N1) published in 2007; An expanded discussion of the decision-making process; Refinement of the containment strategy emphasizing the localized geographical approach and describing the key activities for Containment and Buffer Zones; A proposed approach for estimating the duration of a containment operation; New or updated annexes on ethical issues, non-pharmaceutical interventions, communications and laboratory preparedness. Annexes on antiviral stockpile planning and preparedness issues are under revision and and will be added in the near future. The protocol will be updated and revised as new information becomes available and more detailed guidance and tools are developed.
(WHO http://www.who.int/csr/disease/avian_influenza/guidelines/draftprotocol/en/index.html )


ACIP endorses FluMist for 2-, 3-, and 4-year-olds
A federal advisory committee endorsed FluMist, the nasal-spray form of seasonal influenza vaccine, as a good option for children aged 2 through 4 years. CDC's Advisory Committee on Immunization Practices (ACIP), in recommending FluMist for the age-group, said the needle-free vaccine should be given only to healthy children. The committee said children who have a history of asthma should receive a standard flu shot. The ACIP's vote came a little more than a month after the Food and Drug Administration (FDA) approved FluMist for children in the 2- to 4-year-old group. The vaccine's previous FDA indication and ACIP recommendation was only for healthy people between the ages of 5 and 49. FluMist contains a weakened form of live virus and is made by MedImmune, now part of AstraZeneca. The committee didn't recommend FluMist over regular flu shots, but simply designated it as an option for small children who fear injections. Flu shots in general are recommended for children aged 6 months to 5 years, among several other groups at risk for flu complications. The committee also recommended that a government program that funds vaccines for certain groups of children extend its coverage for FluMist to include the younger children, meaning more than 5 million children will be eligible to receive the nasal spray vaccine. The program covers children with Medicaid coverage, Native American and Alaska native groups, and some children whose medical insurance doesn't cover flu shots. MedImmune has produced about 4.5 million doses of FluMist for the 2007-08 flu season. Last year the company made about 3 million doses. With FluMist, 3 flu vaccines are now available in the US for children younger than 5 years. The others are Fluzone, made by Sanofi Pasteur Inc., approved for anyone older than 6 months, and Fluvirin, made by Novartis Vaccines and Diagnostics, licensed for ages 4 and up.
(CIDRAP 10/25/07)


White House aims to transform public health preparedness
The White House recently issued a lengthy homeland security directive aimed at bolstering the response of federal, state, and local public health systems to national emergencies such as bioterrorist attacks, influenza pandemics, and natural disasters. The directive, titled "Homeland Security Presidential Directive 21 (HSPD 21)," will "transform our national approach to protecting the health of the American people against all disasters," the document states. The directive says strategic improvements across government levels can better prepare the nation to "deliver appropriate care to the largest possible number of people, lessen the impact on limited healthcare resources, and support the continuity of society and government." The directive covers 4 main topics: biosurveillance, countermeasure stockpiling and distribution, mass-casualty care, and community resilience. Each area contains specific actions and timelines.

The directive calls on the secretary of the Department of Health and Human Services (HHS) to establish a national epidemiologic surveillance system that builds on existing networks and provides public health agencies with incentives to build new systems. HHS, with the assistance of other federal agencies, has been asked to establish a federal epidemiologic surveillance advisory committee task force. Among several measures to improve distribution plans and more closely manage stockpiles, the directive orders HHS and the Department of Homeland Security (DHS) to develop templates to help communities dispense medical countermeasures within 48 hours of an official order.

To better manage the nation's Strategic National Stockpile (SNS) of drugs and medical supplies, HHS will ensure transparency concerning stockpiling priorities and, with input from other federal agencies, will establish a system to annually review SNS inventories. HHS and other federal agencies will develop protocols for sharing countermeasures and medical goods between the SNS and other federal stockpiles and will explore developing reciprocal stockpile-sharing arrangements with other countries and international organizations.

The directive orders HHS, in coordination with the Defense, Veterans, and Homeland Security departments, to engage the help of state, local, academic, professional, and private groups in reviewing the nation's disaster medical system and surge capacity. HHS is to submit a report on gaps in those 2 areas and give a plan that addresses key deficits. HHS has also been asked to define how federal facilities can be factored more effectively into medical surge-capacity plans. To address potential legal, regulatory, or other barriers to public health preparedness, HHS, working with other agencies, must submit a report on possible regulatory or legislative solutions. Recognizing that addressing mental health consequences of a disaster can contribute to a more effective public health response, HHS and other agencies are to put together a federal advisory committee on disaster mental health.

HHS, along with the Defense, Commerce, Labor, Education, Veterans, and Homeland Security departments, is ordered to develop a plan to promote community preparedness and present it to the White House. DHS and HHS are assigned to develop a risk-awareness briefing for state and county officials and establish a mechanism to regularly update the public health risk briefings. HHS and DHS will develop and maintain a process for coordinating federal grant programs for public health and medical preparedness.

To further bolster preparedness, HHS and other agencies have been asked within the next year to develop core curricula and training exercises on disaster preparedness for federal executive departments and agencies. The directive calls for setting up, within the next year, the "National Center for Disaster Medicine and Public Health". The center is to lead federal efforts to develop core curricula, training, and research in various aspects of civilian and military medical preparedness. The White House has asked HHS to commission the Institute of Medicine to lead a forum to engage government officials, academic experts, professional societies, and private stakeholders in developing "a strategy for long-term enhancement of disaster pubic health and medical capacity" and the propagation of related training. HHS will submit to the White House a plan to use current funding programs to create incentives for private health facilities to enact preparedness measures that don't increase healthcare costs. The directive also establishes an Office for Emergency Medical Care within HHS to promote and fund emergency medicine research, promote regional emergency medicine partnerships, and promote local preparedness.
(CIDRAP 10/22/07)