EINet Alert ~ Sep 11, 2009

*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and notifications for emerging infections affecting the APEC member economies. It was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:

1. Influenza News
- Weekly APEC update of pandemic influenza H1N1
- Cumulative number of human cases of avian influenza A/H5N1
- Global: WHO situation update on pandemic influenza H1N1
- Global: Research indicates pandemic influenza H1N1 virus more potent than seasonal flu
- Regional: WHO urges Southeast Asian countries to prepare for surge in pandemic influenza H1N1
- Bangladesh: Avian influenza surveillance project uses short messaging service
- China: Research shows pork consumers’ reactions to influenza H1N1 pandemic
- Indonesia: Suspected human case of avian influenza H5N1 in Bali
- Iran: Death rate from seasonal flu higher than pandemic influenza H1N1
- Singapore: Pandemic H1N1 influenza detected in imported live pigs
- Ecuador: Presidential security chief dies of pandemic influenza H1N1 infection
- USA: Concerns of emergency room overload if fall brings increase of pandemic H1N1 cases
- USA: Providers struggle with obtaining seasonal influenza vaccine
- USA (Kansas): Human infection of swine influenza H3N2 reported

2. Updates

3. Articles
- Poor Clinical Sensitivity of Rapid Antigen Test for Influenza A Pandemic (H1N1) 2009 Virus
- Rewiring the RNAs of influenza virus to prevent reassortment
- Ducks as Sentinels for Avian Influenza in Wild Birds
- Receipt of Influenza Vaccine During Pregnancy Among Women With Live Births--Georgia and Rhode Island, 2004--2007
- Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Virus Infection in Two Summer Campers Receiving Prophylaxis--North Carolina, 2009
- Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus
- Trial of Influenza A (H1N1) 2009 Monovalent MF59-Adjuvanted Vaccine--Preliminary Report
- Response after One Dose of a Monovalent Influenza A (H1N1) 2009 Vaccine--Preliminary Report

4. Notifications
- Weekly Epidemiological Record Bulletin
- Policy Statement: Recommendations for the Prevention and Treatment of Influenza in Children, 2009 2010
- Updated guidance on pandemic influenza H1N1 from the US CDC
- The 2009 Influenza Pandemic: Selected Legal Issues

1. Influenza News

Weekly APEC update of pandemic influenza H1N1
China's health minister Chen Zhu on 8 Sep 2009, called the country's pandemic flu situation "grim," due to a surge in cases and clusters in the wake of schools resuming, Agence France-Presse (AFP) reported. Chen cited worries over a national holiday next month, which will prompt gatherings and travel, and the limited ability of China's flu vaccine company to supply enough pandemic H1N1 vaccine to meet demand. China has confirmed 5,592 cases, but has reported no deaths.
(CIDRAP 9/8/09)


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

China/ 7 (4)
Egypt/ 34 (4)
Viet Nam/ 4 (4)
Total/ 45 (12)

***For data on human cases of avian influenza prior to 2009, go to:

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 440 (262)
(WHO 8/31/09 http://www.who.int/csr/disease/avian_influenza/en/index.html )

Avian influenza age distribution data from WHO/WPRO:
http://www.wpro.who.int/sites/csr/data/data_Graphs.htm (WHO/WPRO 7/1/09)

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

WHO’s timeline of important H5N1-related events (last updated 7/29/09):


Global: WHO situation update on pandemic influenza H1N1
Tropical regions of South and Southeast Asia continue to experience geographically regional or widespread influenza activity (represented by countries such as India, Bangladesh, Myanmar, Thailand, Cambodia, Sri Lanka, and Indonesia). Many countries in the region are reporting increasing or sustained high levels of respiratory disease, and a few (Thailand and Brunei Darussalam) have begun to report a declining trend in the level of respiratory diseases.

In tropical regions of Central America and the Caribbean (represented by Costa Rica, El Salvador, Guatemala, Honduras, Panama, and Cuba), influenza activity continues to be geographically regional or widespread; however, most are now reporting a declining trend in the level of respiratory diseases.

Countries in the equatorial and tropical regions of South America (represented by Ecuador, Venezuela, Peru, and parts of Brazil) continue to experience geographically regional or widespread influenza activity, with many reporting an increasing trend in the level of respiratory diseases.

Although many countries in temperate regions of the southern hemisphere (Chile, Argentina, Australia, and New Zealand) have passed the peak of their winter influenza epidemic, sustained influenza activity continues to be reported in South Africa and in the Southern and Western parts of Australia.

In temperate regions of the northern hemisphere, there are wide geographical variations in the level of influenza activity being reported. In Japan, influenza activity continues to increase past the seasonal epidemic threshold, indicating an early beginning to the annual influenza season. In Canada and the United States, influenza activity remains low overall; however, regional increases are being detected in the southeastern United States. In Europe and Central and Western Asia, although little influenza activity is being reported, a few countries are reporting geographically widespread influenza activity (Austria and Israel) or an increasing trend in respiratory diseases (Netherlands and Romania).

Pandemic (H1N1) 2009 influenza virus continues to be the predominant circulating virus of influenza, both in the northern and southern hemisphere. All pandemic H1N1 2009 influenza viruses analyzed to date have been antigenically and genetically similar to A/California/7/2009-like pandemic H1N1 2009 virus.
(ProMED 9/6/09)


Global: Research indicates pandemic influenza H1N1 virus more potent than seasonal flu
Influenza pandemic (H1N1) 2009 virus can infect cells deeper in the lungs than seasonal flu, making people who catch it more likely to develop serious complications, research suggests.

The study published in the journal Nature Biotechnology provides the first laboratory corroboration of reports from front-line doctors. Seasonal strains of flu attach themselves almost exclusively to cells found in the nose, throat and upper airway, producing some of influenza's signature symptoms: a runny nose, scratchy throat and a dry cough. But the research shows that influenza pandemic (H1N1) 2009 virus -- by sticking to a greater range of receptors -- can also reach cells deep in the lungs.

In the latest research, Professor Ten Feizi and colleagues at Imperial College London carried out laboratory experiments in which 86 different receptors were exposed to seasonal and pandemic flu. The seasonal strains only locked onto the kind of receptors found in the upper respiratory track. But the influenza pandemic (H1N1) 2009 virus was also able to latch onto receptors found inside the lungs, although more weakly. The adhesion results in a more severe lung infection. Professor Feizi said: "If the flu virus mutates in the future, it may attach to receptors deep inside the lungs more strongly, and this could mean that more people would experience severe symptoms. We think scientists should be on the lookout for these kinds of changes in the virus so we can try to find ways to minimize the impact."

How severe the second wave outbreak is will depend largely on how many people have already had the illness, Professor Beddington added. And it is difficult to estimate the number of unreported cases, he said. Someone could just feel a bit sniffly and irritable but actually have the virus. If this applies to a large fraction of the population then the second wave will be small.

The research is published in the September 2009 issue of Nature Biotechnology available at http://www.nature.com/nbt/journal/v27/n9/full/nbt0909-797.html.
(ProMED 9/10/09)


Regional: WHO urges Southeast Asian countries to prepare for surge in pandemic influenza H1N1
A World Health Organization (WHO) official speaking to health ministers from 11 Southeast Asian nations on 9 Sep 2009 urged the region to prepare for another wave of pandemic flu cases as the northern hemisphere moves closer to its winter season, Agence France-Presse reported. The WHO told the group meeting in Kathmandu that although the virus has yet to take a big toll in Asia, hospitals should prepare for a surge of severe cases. "It is important to allocate appropriate resources and maintain the overall pandemic preparedness," the WHO Director for Southest Asia said.
(CIDRAP 9/9/09)


Bangladesh: Avian influenza surveillance project uses short messaging service
Bangladesh is conducting active highly pathogenic avian influenza (HPAI) surveillance in 150 out of 487 sub-districts as part of an USAID funded FAO project. A total of 450 community animal health workers (CAHW), 50 additional veterinary surgeons (AVS) and 150 Upazilla livestock officers (ULOs) are using short message service (SMS) gateway to collect data and report on disease and death in poultry. SMS gateway is a method of sending and receiving SMS messages between computers and mobile phones. Since October 2008, 21 HPAI outbreaks out of a total of 35 have been detected through this active surveillance program.

The SMS reporting structure is rather simple: at the end of the working day, each CAHW sends a SMS message with the total number of all investigated poultry (chickens, ducks and other birds) and their health status (the number of sick and dead birds) to the SMS gateway system. This data is used to monitor trends in disease and mortality in poultry. Additionally, CAHWs send flash reports by SMS on suspected outbreaks according to a case definition. The system then automatically contacts the ULO in the same area by SMS, who initiates an investigation by sending an AVS or visits the suspect outbreaks him/herself. After the investigation, the ULOs and AVS send a SMS message to the gateway server to declare the suspect outbreak as negative or report that it may require further diagnostic tests.
(ProMED 9/9/09)


China: Research shows pork consumers’ reactions to influenza H1N1 pandemic
Nearly two-thirds of China's consumers stopped eating pork in the early stages of the H1N1 influenza outbreak in 2009, and more than 1 in 5 consumers in the world's largest pork market still believe that eating pork can result in catching the flu virus, according to a survey of 1200 Chinese consumers commissioned in August 2009 by the US Meat Export Federation (USMEF).

Joel Haggard, senior vice president Asia-Pacific for USMEF, told the more than 600 global pork industry executives on 3 Sep 2009 that China -- both the world's largest pork producer and consumer -- may have been more affected by the H1N1 virus outbreak than previously suspected. "In the early stages of the outbreak, 64 percent of Chinese consumers refrained from pork consumption," said Haggard, citing research conducted 6-10 Aug 2009 by Sinotrace Marketing Research Company of 200 consumers in each of six Chinese cities: Beijing, Shanghai, Chongqing, Guangzhou, Nanjing, and Shenyang.

Even now, months after the initial outbreak, 21 percent of those surveyed still believe that eating pork can lead to catching the H1N1 virus. Despite efforts by the Chinese government to educate consumers regarding the safety of pork, nearly 55 percent of those who fear the connection between pork and the flu virus say that it is because the virus has been labeled "swine flu." "The research suggests that the initial Chinese consumer reaction to H1N1 was sharp, and that a significant number of consumers may still associate the virus with pork and hogs," said Haggard.
(ProMED 9/7/09)


Indonesia: Suspected human case of avian influenza H5N1 in Bali
Bali Husbandry Agency head I.B. Alit stated that avian flu was still present on the island of Bali, mostly among domesticated fowl. In addition, a pregnant woman from Gianyar Regency is being treated at Sanglah Hospital for avian influenza A(H5N1) virus infection. Her unborn baby was dead.

There has been no confirmed case of avian influenza (H5N1) virus infection in Indonesia since the beginning of 2009. There have been many tens of suspected cases reported in local Indonesia newspapers. In early August 2009, a human case was reported on the island of Bali, but this has not subsequently been confirmed. The present report must be regarded with some skepticism, pending confirmation from an official source.

It should be noted that in 2008 Indonesia said it would no longer routinely report cases of avian flu because of the negative reactions by other countries.

Meanwhile, bird flu H5N1 attacked hundreds of thousands of layer chickens in several farms in Kabupaten Banyumas, Central Java. Infected chickens had received avian influenza vaccination. A 50-year-old chicken farmer reported that thousands of infected chickens reared in Desa Limpakuwus, Kecamatan Sumbang had been vaccinated previously. "Vaccination does not assure immunity in chickens. Vaccination should be done repeatedly to avoid infection," he said on 8 Sep 2009. The avian influenza infection did not kill chickens that received vaccination, but it caused suppression of egg production.
(ProMED 9/5/09, 9/9/09)


Iran: Death rate from seasonal flu higher than pandemic influenza H1N1
The seasonal flu death rate is higher than the rate from pandemic influenza H1N1, the director of the Iranian Society of Internists said in Tehran on 5 Sep 2009. Compared with pandemic H1N1 flu, seasonal influenza kills more Iranians, but there are no official figures showing the exact death rate from seasonal flu across the country, Iraj Khosrow-Nia said. Khosrow-Nia said the old and those who have had chronic diseases are those most seriously affected by seasonal flu. Great numbers of people die of seasonal flu per annum in the country during the fall and winter, but the rate has not been registered so far, Khosrow-Nia explained.

As of 22 Jun 2009, a total of 285 cases of pandemic influenza H1N1 have been confirmed around the country. One person has also died from the pandemic H1N1 virus since then. But pandemic flu cases in Iran are mild, Khosrow-Nia said; we should be cautious but not panicky. The severity doesn't seem to be much different than what it is in the regular seasonal flu, Khosrow-Nia noted.

Mohammad-Mahi Guya, an official at the Infectious Diseases Department of the Health Ministry, also said that regular seasonal influenza is more dangerous than the pandemic (H1N1) 2009 virus. Guya recommended that high-risk groups (the old and those with chronic disease) should get vaccinated against the seasonal flu before the flu season sets in. Free seasonal flu shots are available for high-risk groups from the health ministry.
(ProMED 9/6/09)


Singapore: Pandemic H1N1 influenza detected in imported live pigs
The Agri-Food and Veterinary Authority (AVA) has detected the pandemic A (H1N1) virus in some pigs imported into Singapore from Indonesia's Pulau Bulan. But the AVA stressed that the pork available in Singapore is safe for consumption, as the H1N1 virus is not transmitted through the handling or consumption of pork or pork products.

AVA added it will step up its monitoring and inspection to ensure food safety, like increasing the number of daily pork samples taken for tests from 30 to 100. It will also take part in a comprehensive disease surveillance program on the Pulau Bulan farm, led by the Indonesian authorities. The aim is to identify and isolate affected pig houses. Restricted animal movement will also be imposed to ensure only healthy pigs are exported to Singapore. The AVA said this is in line with the World Organization for Animal Health's recommendation.

Meanwhile, steps have also been taken to make sure that everyone is safe. Dr Chew said: "The workers have already been putting on protective gear, masks, and have been practicing good hygiene procedures to avoid getting any potential infection." Suppliers have also been informed of the steps being taken so that they too can play their part by enhancing measures and ensuring everybody complies with the requirements.

AVA said that Singapore receives pork supplies from 25 countries. Singapore's import of 1000 pigs daily from Pulau Bulan constitutes some 20 per cent of the total pork consumed there.
(ProMED 9/4/09)


Ecuador: Presidential security chief dies of pandemic influenza H1N1 infection
Ecuador's presidential security chief, John Merino, died 6 Sep 2009 from pandemic H1N1 infection. He was first diagnosed with the novel flu strain on 10 Aug 2009. The virus has struck a host of other South American government officials over the past few weeks, including the presidents of Costa Rica and Colombia.
(CIDRAP 9/8/09)


USA: Concerns of emergency room overload if fall brings increase of pandemic H1N1 cases
As children return to school and promptly become infected with H1N1 influenza, emergency-room (ER) physicians nationwide are becoming increasingly anxious over their ERs' capacity to deal with an influx of flu patients. Many of the physicians work in emergency departments that experienced a spring onslaught of flu and fever cases when H1N1 first struck. In some cities, those cases were part of an early wave that receded; in others, the count of flu cases climbed and has kept climbing through summer months that usually are flu-free.

In either situation, the physicians say they are concerned that the expected fall increase in H1N1 flu—plus the annual arrival of seasonal flu—will significantly strain a system that has little capacity to handle excess demand. And if H1N1 flu undergoes enough mutation or reassortment to add significant virulence to its notable contagiousness, they add, chaos could result.

Potential for a perfect storm
"From what I have been reading, the flu season in the Southern Hemisphere has been very, very bad—they have been swamped with an increasing number of cases," said Dr. Stuart Bradin, an assistant professor of pediatrics and emergency medicine in the University of Michigan Health System. "So I think we are in quite a bit of danger of having a very bad flu season here. Having seasonal flu on top of that, and considering that the pandemic flu strain may become more virulent than its initial presentation, I think is the potential for a perfect storm."

Some physicians have been hearing early rumbles of that storm since H1N1 appeared in late April 2009. "The months of May, June, and July [2009] were three of our top six months ever, in terms of emergency department volume, going back at least 10 years," said Dr. Brian Zink, chair of emergency medicine at Warren Alpert Medical School at Brown University in Rhode Island.

Dr. David Munter, emergency department director at Sentara Obici Hospital in Suffolk, VA, said: "I have never before, in a 28-year career, seen flu in June, July, and August, but we had it, and it was all in teens and young adults. We had no summer dip [in cases] at all." He added: "I think when school starts, it will explode."

The physicians say that many of the flu patients they saw and expect to see are not gravely ill. Some, especially in the spring, were “worried well” seeking tests or reassurance. Most who came for care over the summer had fever and other flu-like symptoms, but did not need to be admitted to the hospital and were discharged to recover at home.

The spring wave of cases "increased our wait times and reduced efficiencies," Zink said. "Individuals who needed to be wearing masks, we had to stop and get masked in triage, so it slowed the triage process down. And we went into rooms masked and using contact precautions, which adds a little bit of time to each encounter. But we see 100,000 patients a year in our main hospital [ER], so if you add even a few minutes to each patient, it slows everything down."

Strategies for preventing overload
Around the country, emergency departments and the hospitals that house them are crafting solutions that they hope will head off an ER overload. Many are considering creating satellite triage stations located away from ERs—in hospital parking lots, repurposed clinics, or even drive-throughs—all of which rely on keeping flu patients out of the ER and bringing healthcare personnel out to meet them. Children's Healthcare of Atlanta, which operates three hospitals, recently placed on its website an interactive decision tool that allows parents to assess the severity of a child's symptoms so that only children who need emergency care will be brought to its ERs.

In Virginia, Munter envisions physically dividing his hospital's waiting room into two zones; one, a flu zone, would feed into a pre-designated isolation area within the ER. And the quality-focused Institute for Healthcare Improvement (IHI) will shortly publish a monograph proposing that flu patients be separated more radically, by being steered into what physicians call a "pathway"—a multi-step protocol triggered by a particular set of signs and symptoms—that would not only put them in certain rooms but process them at different speeds depending on results of tests given in a particular rapid order.

Several emergency physicians said that what they fear most for the fall and winter is not an onslaught of flu, but a slow crawl up the epidemic curve. An onslaught, they argued, would be recognized as a crisis and would trigger a coordinated response in the same way a plane crash does. But a steady increase, though it might eventually reach disastrous proportions, would be perceived at any moment as ER business as usual: vastly overcrowded but not deserving outside response.
(CIDRAP 9/9/09)


USA: Providers struggle with obtaining seasonal influenza vaccine
Just as this year's early seasonal influenza immunization drive is getting under way, some vaccination providers are having trouble getting vaccine doses, the Centers for Disease Control and Prevention (CDC) reported 9 Sep 2009. A CDC notice that was forwarded to members of the National Influenza Vaccine Summit (NIVS) said, "Providers seeking to order vaccine currently and during the past several weeks have experienced challenges in doing so."

The notice said the estimate of total seasonal vaccine production has been lowered slightly—from 118 million doses in late June 2009 to 114 million or 115 million now, or about 3%—but it did not describe this change as the sole or main factor in the difficulty. In late June 2009, the notice said, one vaccine manufacturer lowered its vaccine production estimate, causing some providers to switch their "prebooked" supply orders to other manufacturers. As a result, some doses that are normally available in summer or early fall are off the table.

In addition, the CDC said, more providers than usual may be trying to get vaccine, because of the H1N1 flu pandemic. Media coverage of H1N1 and the desire to complete seasonal flu immunizations before H1N1 vaccinations begin may have combined to boost demand for seasonal vaccine.

The first doses of H1N1 vaccine are expected to become available in mid October 2009. To make way for the H1N1 vaccination campaign, public health officials have been urging people to get their seasonal flu shots early, and vaccinations have begun in many areas. The CDC's Dr. Jeanne Santoli suggested that the seasonal vaccine supply is likely to improve as the season wears on.
(CIDRAP 9/9/09)


USA (Kansas): Human infection of swine influenza H3N2 reported
The US Centers for Disease Control and Prevention (CDC) reported a human infection with a swine influenza A/H3N2 virus in a patient from Kansas who had contact with pigs before getting sick on 28 Jul 2009. The patient is a child who was likely exposed to the virus through direct contact with pigs during a county fair, the Kansas Department of Health and Environment (KDHE) said. The illness was mild, the child has fully recovered, and no other family members reported symptoms.

H1N1 and H3N2 swine flu viruses are endemic in US pig populations; when the rare infections do occur in humans, they are typically in people with direct exposure to pigs. The number has risen slightly in past years, and so far in 2009 the CDC has received reports of 14 such cases. The KDHE said the increased number of cases this year is probably the result of increased influenza testing related to the H1N1 pandemic.

Jason Eberhart-Phillips, director of the KDHE, said it's critical for people to understand that the H3N2 virus is not related to the pandemic H1N1 virus. "This is not a mutation or a recombination of the pandemic strain, and it does not appear at this time to be a threat to human health," he said.

Though most cases of human infection with animal influenza viruses, such as swine H3N2, don't lead to human-to-human transmission, health officials always investigate the cases carefully to assess if they are spreading among humans, Eberhart-Phillips said.
(CIDRAP 9/4/09)


2. Updates
The following websites provide the most current information and advice.

Influenza A/H1N1: http://www.who.int/csr/disease/swineflu/en/index.html
Influenza A/H1N1 frequently asked questions: http://www.who.int/csr/swine_flu/swine_flu_faq_26april.pdf
Map of the spread of influenza A/H1N1: http://www.who.int/csr/don/GlobalSubnationalMaster_20090507_1800.png.

- North America
US CDC: http://www.cdc.gov/flu/swine/investigation.htm
US pandemic emergency plan: www.pandemicflu.gov
MOH Mexico: http://portal.salud.gob.mx/index_eng.html
PHAC Canada: http://www.phac-aspc.gc.ca/media/nr-rp/index-eng.php
PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm

- Other useful sources CIDRAP: Influenza A/H1N1 page: http://www.cidrap.umn.edu/cidrap/content
ProMED: http://www.promed.org


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


3. Articles
Poor Clinical Sensitivity of Rapid Antigen Test for Influenza A Pandemic (H1N1) 2009 Virus
Drexler JF et al. Emerg Infect Dis. October 2009. Available at http://www.cdc.gov/eid/content/15/10/pdfs/09-1186.pdf.

Influenza A pandemic (H1N1) 2009 virus RNA was detected by reverse transcription–PCR in 144 clinical samples from Bonn, Germany. A common rapid antigen–based test detected the virus in only 11.1% of these samples. The paramount feature of rapid test–positive samples was high virus concentration. Antigen-based rapid tests appear unsuitable for virologic diagnostics in the current pandemic.


Rewiring the RNAs of influenza virus to prevent reassortment
Gao Q and Palese P. Proc Natl Acad Sci. 8 September 2009. Available at http://www.pnas.org/content/early/2009/09/04/0908897106.short.

Influenza viruses contain segmented, negative-strand RNA genomes. Genome segmentation facilitates reassortment between different influenza virus strains infecting the same cell. This phenomenon results in the rapid exchange of RNA segments. In this study, we have developed a method to prevent the free reassortment of influenza A virus RNAs by rewiring their packaging signals. Specific packaging signals for individual influenza virus RNA segments are located in the 5′ and 3′ noncoding regions as well as in the terminal regions of the ORF of an RNA segment. By putting the nonstructural protein (NS)-specific packaging sequences onto the ORF of the hemagglutinin (HA) gene and mutating the packaging regions in the ORF of the HA, we created a chimeric HA segment with the packaging identity of an NS gene. By the same strategy, we made an NS gene with the packaging identity of an HA segment. This rewired virus had the packaging signals for all eight influenza virus RNAs, but it lost the ability to independently reassort its HA or NS gene. A similar approach can be applied to the other influenza A virus segments to diminish their ability to form reassortant viruses.


Ducks as Sentinels for Avian Influenza in Wild Birds
Globig A et al. Emerg Infect Dis. October 2009. Available at http://www.cdc.gov/eid/content/15/10/pdfs/09-0439.pdf.

To determine the effectiveness of mallards as sentinels for avian influenza virus (AIV) infection, we placed mallards in contact with wild birds at resting sites in Germany, Austria, and Switzerland. Infections of sentinel birds with different AIV subtypes confirmed the value of such surveillance for AIV monitoring.


Receipt of Influenza Vaccine During Pregnancy Among Women With Live Births--Georgia and Rhode Island, 2004--2007
US Centers for Disease Control and Prevention. MMWR. 11 September 2009; 58(35): 972-975. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5835a2.htm.

Pregnant women are at increased risk for complications from influenza. Since 2004, the Advisory Committee on Immunization Practices (ACIP) and American College of Obstetricians and Gynecologists (ACOG) Committee on Obstetric Practice have recommended that all pregnant women be vaccinated with the trivalent inactivated vaccine during any trimester of pregnancy. To assess the percentage of women who were vaccinated during pregnancy among women with recent live births, CDC analyzed data from the Pregnancy Risk Assessment and Monitoring System (PRAMS) from Georgia and Rhode Island, the two states that collected this information on the PRAMS survey. This report summarizes the results, which showed that in Georgia, the prevalence of influenza vaccination during the woman's most recent pregnancy increased from 10.4% in 2004 to 15.5% in 2006. In Rhode Island, vaccination prevalence increased from 21.9% in 2004 to 33.4% in 2007. During 2006 in Georgia, the most common reasons for not receiving vaccination were, "I don't normally get the flu vaccination" (69.4%), and "my physician did not mention anything about a flu vaccine during my pregnancy" (44.5%). Increased efforts are needed to assess vaccine coverage during pregnancy and to educate providers and pregnant women about ACIP and ACOG recommendations on providing intramuscular, inactivated influenza vaccine during any trimester of pregnancy. (Excerpt with references removed.)


Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Virus Infection in Two Summer Campers Receiving Prophylaxis--North Carolina, 2009
US Centers for Disease Control and Prevention. MMWR. 11 September 2009; 58(35): 969-972. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5835a1.htm.

Initial testing of the 2009 pandemic influenza A (H1N1) virus found it susceptible to neuraminidase inhibitors (oseltamivir and zanamivir) and resistant to adamantanes (amantadine and rimantadine). Neuraminidase inhibitors have been used widely for treatment and chemoprophylaxis of 2009 pandemic influenza A (H1N1); however, sporadic cases of oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infection have been reported worldwide, including nine U.S. cases identified as of September 4. On July 14, CDC was contacted by a physician at a summer camp in North Carolina regarding two cases of influenza-like illness (ILI) in adolescent girls receiving oseltamivir chemoprophylaxis during an ILI outbreak that had begun June 18. The two girls stayed in the same cabin, and both received oseltamivir during a mass chemoprophylaxis program in which approximately 600 campers and staff members received oseltamivir or zanamivir. On July 20 and July 22, the North Carolina State Laboratory of Public Health confirmed pandemic H1N1 virus infection in respiratory specimens from both girls. On August 14 and August 19, CDC detected the H275Y mutation (N1 numbering) in neuraminidase from both specimens by pyrosequencing. The H275Y mutation is associated with resistance to oseltamivir; zanamivir susceptibility is retained. A second mutation (I223V) in neuraminidase also was detected in both specimens. This is the first report of oseltamivir resistance in pandemic H1N1 cases with an epidemiologic link. Health-care providers should be aware that antiviral resistance can develop during chemoprophylaxis or treatment with subtherapeutic dosages and should follow published recommendations for antiviral medications. (Excerpt with references removed.)


Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus
Hancock K et al. NEJM. 10 September 2009. Available at http://content.nejm.org/cgi/content/full/NEJMoa0906453.

Background A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate seasonal vaccine strategies, we measured the antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups.

Methods Using a microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines.

Results A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults.

Conclusions Vaccination with recent seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had preexisting cross-reactive antibodies.


Trial of Influenza A (H1N1) 2009 Monovalent MF59-Adjuvanted Vaccine--Preliminary Report
Clark TW et al. NEJM. 10 September 2009. Available at http://content.nejm.org/cgi/content/full/NEJMoa0907650.

Background The 2009 pandemic influenza A (H1N1) virus has emerged to cause the first pandemic of the 21st century. Development of effective vaccines is a public health priority.

Methods We conducted a single-center study, involving 175 adults, 18 to 50 years of age, to test the monovalent influenza A/California/2009 (H1N1) surface-antigen vaccine, in both MF59-adjuvanted and nonadjuvanted forms. Subjects were randomly assigned to receive two intramuscular injections of vaccine containing 7.5 µg of hemagglutinin on day 0 in each arm or one injection on day 0 and the other on day 7, 14, or 21; or two 3.75-µg doses of MF59-adjuvanted vaccine, or 7.5 or 15 µg of nonadjuvanted vaccine, administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay and a microneutralization assay on days 0, 14, 21, and 42 after injection of the first dose.

Results Results of an interim analysis of the responses to the 7.5-µg dose of MF59-adjuvanted vaccine by days 14 and 21 are presented (data from four of the seven groups studied, for a total of 100 subjects). The most frequent local and systemic reactions were pain at the injection site and muscle aches, noted in 70% and 42% of subjects, respectively. Two subjects reported fever, with a temperature of 38°C or higher, after the first dosing. Antibody titers, expressed as geometric means, were generally higher at day 14 among subjects who had received two 7.5-µg doses of the MF59-adjuvanted vaccine than among those who had received only one by this time point (P=0.04 by the hemagglutination-inhibition assay and P<0.001 by the microneutralization assay). By 21 days after vaccination with the first dose of 7.5 µg of MF59-adjuvanted vaccine, the rates of seroconversion, as measured with the use of a hemagglutination-inhibition assay and a microneutralization assay, were 76% and 92% of subjects, respectively, who had received only one dose to date (with the second dose scheduled for day 21) and 88 to 92% and 92 to 96% of subjects, respectively, who had already received both doses (P=0.11 and P=0.64, respectively).

Conclusions In preliminary analyses, the monovalent influenza A (H1N1) 2009 MF59-adjuvanted vaccine generates antibody responses likely to be associated with protection within 14 days after a single dose is administered.


Response after One Dose of a Monovalent Influenza A (H1N1) 2009 Vaccine--Preliminary Report
Greenberg ME et al. NEJM. 10 September 2009. Available at http://content.nejm.org/cgi/content/full/NEJMoa0907413.

Background A novel influenza A (H1N1) 2009 virus is responsible for the first influenza pandemic in 41 years. A safe and effective vaccine is urgently needed. A randomized, observer-blind, parallel-group trial evaluating two doses of an inactivated, split-virus 2009 H1N1 vaccine in healthy adults between the ages of 18 and 64 years is ongoing at a single site in Australia.

Methods This preliminary report evaluates the immunogenicity and safety of the vaccine 21 days after the first of two scheduled doses. A total of 240 subjects, equally divided into two age groups (<50 years and 50 years), were enrolled and underwent randomization to receive either 15 µg or 30 µg of hemagglutinin antigen by intramuscular injection. We measured antibody titers using hemagglutination-inhibition and microneutralization assays at baseline and 21 days after vaccination. The coprimary immunogenicity end points were the proportion of subjects with antibody titers of 1:40 or more on hemagglutination-inhibition assay, the proportion of subjects with either seroconversion or a significant increase in antibody titer, and the factor increase in the geometric mean titer.

Results By day 21 after vaccination, antibody titers of 1:40 or more were observed in 116 of 120 subjects (96.7%) who received the 15-µg dose and in 112 of 120 subjects (93.3%) who received the 30-µg dose. No deaths, serious adverse events, or adverse events of special interest were reported. Local discomfort (e.g., injection-site tenderness or pain) was reported by 46.3% of subjects, and systemic symptoms (e.g., headache) by 45.0% of subjects. Nearly all events were mild to moderate in intensity.

Conclusions A single 15-µg dose of 2009 H1N1 vaccine was immunogenic in adults, with mild-to-moderate vaccine-associated reactions.


4. Notifications
Weekly Epidemiological Record Bulletin
WHO. 4 Sep 2009; 84(36): 361-372. Available at http://www.who.int/wer.

Contents of this issue:
Global influenza surveillance network: laboratory surveillance and response to pandemic H1N1 2009


Policy Statement: Recommendations for the Prevention and Treatment of Influenza in Children, 2009 2010
American Academy of Pediatrics Committee on Infectious Diseases.
Released 7 September 2009.
Available at http://pediatrics.aappublications.org/cgi/reprint/peds.2009-1806v1.


Updated guidance on pandemic influenza H1N1 from the US CDC
CDC Guidance on Helping Child Care and Early Childhood Programs Respond to Influenza during the 2009–2010 Influenza Season
Released 4 September 2009.
Available at http://www.cdc.gov/h1n1flu/childcare/guidance.htm.

Updated Interim Recommendations for the Use of Antiviral Medications in the Treatment and Prevention of Influenza for the 2009-2010 Season
Released 8 September 2009.
Available at http://www.cdc.gov/h1n1flu/recommendations.htm.

Interim Guidance for State and Local Health Departments for Reporting Influenza-Associated Hospitalizations and Deaths for the 2009-2010 Season
Released 8 September 2009.
Available at http://www.cdc.gov/H1N1flu/hospitalreporting.htm.


The 2009 Influenza Pandemic: Selected Legal Issues
Congressional Research Report for the People
Published 11 August 2009.
Available at http://opencrs.com/document/R40560/2009-08-11/.