EINet Alert ~ May 04, 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)
- Bangladesh: Avian influenza detected in poultry
- Indonesia: Request of written guarantee from WHO on sample sharing
- Malaysia: Warnings of smuggled chicken
- USA: CDC offers advice on citizen use of masks, respirators
- USA: GAO says financial markets not ready for a pandemic
- USA: New York group offers plan for rationing ventilators in pandemic
- Ghana: Reports of first avian influenza H5N1 outbreak
- Ghana: Excerpts from the OIE report on avian influenza in birds

1. Updates
- Avian/Pandemic influenza updates
- Seasonal Influenza

2. Articles
- Hospital Personnel Response during a Hypothetical Influenza Pandemic: Will they come to Work?
- A Simple Triage Scoring System Predicting Death and Need for Critical Resources for Use During Epidemics
- Recombinant Modified Vaccinia Virus Ankara–Based Vaccine Induces Protective Immunity in Mice against Infection with Influenza Virus H5N1
- Prevaccine Determination of the Expression of Costimulatory B7 Molecules in Activated Monocytes Predicts Influenza Vaccine Responses in Young and Older Adults
- Controlling Pandemic Flu: The Value of International Air Travel Restrictions
- Can Influenza Epidemics Be Prevented by Voluntary Vaccination?
- Detection of H5 Avian Influenza Viruses by Antigen-Capture Enzyme-Linked Immunosorbent Assay Using H5-Specific Monoclonal Antibody

3. Notifications
- Panel supports EU approval of cell-based influenza vaccine

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)

China / 2 (1)
Egypt / 16 (4)
Indonesia / 6 (5)
Laos / 2 (2)
Nigeria / 1 (1)
Total / 28 (14)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 291 (172).
(WHO 4/11/07 http://www.who.int/csr/disease/avianinfluenza/en/ )

Avian influenza age & sex distribution data from WHO/WPRO:
(WHO/WPRO 4/11/07)

WHO's maps showing world's areas reporting confirmed cases of H5N1 avian influenza in humans, poultry and wild birds (last updated 4/16/07):

WHO’s timeline of important H5N1-related events (last updated 4/20/07):

FAO map showing outbreaks among poultry (last updated 3/26/2007):


Bangladesh: Avian influenza detected in poultry
Some 8500 chickens have been culled in Bangladesh following the spread of bird flu in the country. "We have culled 8500 chickens in a one-sq-km area. It (the virus) was first identified at a government-run farm and then in 3 nearby farms," a government livestock official said 2 May 2007. Samples from other farms in the southwestern district of Jessore, where the outbreak occurred, had also been taken for analysis, he said. The cull took the total number of birds killed so far in Bangladesh to more than 70 000. Officials said Apr 2007 that around 66 000 birds at 22 farms had been destroyed after the disease spread in other parts of the country, including to the north. The disease was first identified in Bangladesh Mar 2007, after samples from a farm near the capital, Dhaka, tested positive for the H5N1 strain of bird flu. So far, there has been no report of any human infection in the impoverished nation. Bangladesh is home to hundreds of thousands of poultry farms employing more than a million people. It had already banned imports of live birds from more than 50 countries, including neighboring India and Myanmar, after outbreaks were detected there.
(Promed 5/3/07)


Indonesia: Request of written guarantee from WHO on sample sharing
Indonesia's health minister insisted that her country will not share any H5N1 virus samples with WHO until it has a written guarantee that the samples will not be shared with drug companies without Indonesia's permission. Indonesia stopped sending H5N1 samples to the WHO about 4 months ago out of concern that drug companies would use them to make vaccines that would be priced out of Indonesians' reach. Indonesia had agreed to resume sharing samples in return for a WHO promise not to turn samples over to drug companies without Indonesia's permission. But the country has not yet resumed sending samples. Health Minister Siti Fadilah Supari said WHO made oral promises, but Indonesia wants them in writing.
(CIDRAP 5/2/07 www.cidrap.umn.edu )


Malaysia: Warnings of smuggled chicken
Malaysia is stepping up vigilance over poultry smuggling amid fears that frozen chicken meat is being illegally shipped from China and other countries hit by bird flu. Customs officials have destroyed 28 tons of frozen chicken meat worth USD 29 500 that were seized 21 Apr 2007 from a truck that entered Malaysia's southern Johor state from neighboring Singapore. The report quoted that officials were concerned that the meat could have come from a country hit by bird flu. Several international syndicates are suspected to be involved in poultry smuggling, raking in profits because frozen chicken meat, particularly from China, is reportedly substantially cheaper than Malaysian poultry. The meat is believed to be repacked in Singapore before being smuggled through southern Malaysia and sold to food processing companies and restaurants. China has suffered dozens of bird flu cases in its vast poultry flocks. Malaysia was officially declared free of bird flu Jun 2006, 3 months after the last outbreak of the H5N1 strain was detected in chickens.
(Promed 4/27/07 http://promedmail.org )


USA: CDC offers advice on citizen use of masks, respirators
Though there is little scientific evidence to go on, wearing a surgical face mask may make sense for people who have to go into crowded public places during an influenza pandemic, federal health officials said. Furthermore, people who care for a pandemic flu patient at home or have other close contact with sick people in a pandemic should consider wearing an N-95 respirator, a more elaborate type of mask designed to stop virus-sized particles, CDC advised. CDC officials said avoiding crowded conditions and infected people are the most important precautions in a pandemic, but masks and respirators may provide additional protection. Standard precautions such as hand hygiene and social distancing should also be used.

"If people are not able to avoid crowded places, [or] large gatherings or are caring for people who are ill, using a facemask or a respirator correctly and consistently could help protect people and reduce the spread of pandemic influenza," CDC Director Dr. Julie Gerberding said. For example, people might choose to wear a face mask when going to a grocery store or a religious service, and they might want to use a respirator when visiting a sick neighbor to deliver food or medicine. Surgical face masks are simple masks designed to fit across the nose and mouth and catch large respiratory droplets produced by the wearer, but they also offer some protection from others' secretions. They are inexpensive and typically fit fairly loosely. N-95 respirators are thicker masks that are designed to fit tightly to the face and block at least 95% of small airborne particles. They must be specially fitted for the wearer.

CDC said people should consider wearing a face mask during a flu pandemic if: They have the flu and think they might come in close contact with others; They live with someone who has flu symptoms (resulting in possible exposure) and they need to be in a crowded public place; They are well and don't expect to have close contact with a sick person, but they need to be in a crowded place. People should consider wearing an N-95 respirator if they are well and expect to be in close contact with someone who is known or believed to have the flu, and particularly when caring for a sick person at home, the agency said.

Gerberding said the CDC is not recommending that people stockpile masks or respirators now. CDC is stockpiling masks and respirators for use by healthcare workers in a pandemic, mainly because the supply depends heavily on imports. "We have almost 52 million regular surgical masks, and of N-95 respirators we have almost 100 million in the stockpile, with several million more on order," Gerberding said. If N-95 respirators run short during a pandemic, face masks can be used instead—and should be used when close contact with sick people is expected, the CDC guidance says. Gerberding added that a respirator can lead to a "false sense of security," because if it fits poorly so that air can leak around it, it provides less protection. . . . "If you're going to choose a mask right now, it's probably best to think about a simple face mask that prevents your respiratory secretions from infecting someone else" and that also offers some protection from incoming droplets, she said.

May 3 CDC news release: http://www.cdc.gov/od/oc/media/pressrel/2007/r070503.htm
(CIDRAP 5/3/07 www.cidrap.umn.edu )


USA: GAO says financial markets not ready for a pandemic
A new report from Congress' Government Accountability Office (GAO) says key organizations that are the backbone of the US financial industry need to do more to prepare for an influenza pandemic and urges federal regulators to set deadlines for them to complete pandemic plans. The report notes that the pandemic threat is different from other disasters because it could affect large numbers of people simultaneously and strike in waves that last for weeks at a time over several months. The GAO focused its attention on 7 critical exchanges, markets, clearing organizations, and payment processors. The agency found that although all were planning for a pandemic, only one had completed a formal plan. Staff at 2 organizations told the GAO they had begun cross-training employees to handle critical duties, and staff at one organization had conducted a tabletop exercise. Another organization had a draft pandemic plan, but it didn't address how business functions would be maintained through varying levels of absenteeism.

Though the financial markets have made good strides since the Sep 11 terrorist attacks to spread their operations to dispersed back-up sites, the GAO warns that the industry shouldn't depend on the more dispersed operating centers to help them through a pandemic. "With global airline travel available, any disease outbreak could occur quickly and be widely spread within a short period of time," the report says. The GAO says that while federal regulators are discussing their pandemic planning expectations with the financial industry, they haven't told industry groups to include a severe pandemic scenario in their planning or to set dates for completing pandemic plans.

Both regulators and the financial markets have become concerned about how strong telecommunications systems will be during a pandemic, because most business continuity plans involve telecommuting, the report says. A modeling study from the National Communication System suggested there was enough bandwidth to handle the traffic, but problems could crop up in individual residential or commercial areas.
(CIDRAP 5/2/07 www.cidrap.umn.edu )


USA: New York group offers plan for rationing ventilators in pandemic
When the next flu pandemic comes, it's a good bet that ventilators will run short and clinicians will face wrenching decisions. Expecting that such choices will be excruciating for already stressed healthcare workers, a group of experts assembled by the New York State Department of Health (NYSDOH) is offering guidelines for rationing scarce ventilators. The group released a 52-page draft plan that provides detailed guidance for determining who will receive ventilator treatment in the face of a pandemic-related shortage. The plan calls for allocating ventilators in acute care hospitals solely on the basis of patients' medical need and chance of survival, without regard for age, occupation, ability to pay, etc. Tia Powell, MD, co-chair of the task force that wrote the guidelines, said, "People will certainly feel this proposal can be made better, but it's important to have some plan in place, and not simply defer to the overworked frontline provider in a crisis, to make a decision that you didn't grapple with when you had a good night's sleep and a meal."

The task force, called the New York State Workgroup on Ventilator Allocation in an Influenza Pandemic, has invited public comments on the proposed guidelines and plans to revise them in coming months. Once the guidelines are finished, the expectation is that New York hospitals could use them as an acceptable standard of care if ventilators ran short in a pandemic, said Guthrie S. Birkhead, MD, the other co-chair of the task force and director of the NYSDOH Center for Community Health. Given that status, the guidelines might offer hospitals some protection against legal liability for ventilator allocation, he said.

The plan is based on a set of ethical principles, including (1) healthcare workers' fundamental duty to care for patients, (2) the duty to steward scarce resources wisely, (3) the duty to plan in advance how to allocate ventilators, (4) statewide application of the allocation guidelines, so that the same rules apply in different hospitals and communities, and (5) transparency in proposing and refining the guidelines. The proposal depicts rationing as a last resort. Hospitals would need to limit the need for ventilators by canceling or postponing elective medical procedures and would be expected to acquire as many ventilators as possible from their own suppliers or networks and the state and federal stockpiles.

Unlike some other proposals for allocating ventilators, the New York group decided not to list either specific diseases, such as AIDS, or age as exclusion criteria. "We tried to focus more on functionality—we just want to know how sick you are and what your probability of survival is," said Powell. Patients who do get a ventilator will be reassessed after 48 hours and again after 120 hours to see if they still need and can benefit from the treatment, the proposal says. In an effort to protect primary treating physicians from the heavy burden of deciding whether their own patients will get or keep a ventilator, the guidelines assign the rationing decisions to the supervising clinician in charge of intensive care patients.

Some issues were more controversial than others. One was "whether there would be priority access for healthcare workers and other first responders," said Powell. "The group has proposed that there not be prioritized access for healthcare workers. Once you're a critically ill patient, it doesn't matter what you do for a living." Powell said another controversial issue was how to deal with patients in chronic care facilities, including those who are chronic ventilator users. "We proposed that people in chronic care facilities be offered a different standard," she said. "To be in a chronic care facility, by definition, you're stable, you're not acutely ill. . .We thought it was important to offer a haven for some of our most vulnerable chronically ill patients."

Acknowledging that ventilator rationing would be likely to trigger lawsuits, the proposal says that guidelines issued by the NYSDOH "would provide strong evidence for an acceptable standard of care during the dire circumstances of a pandemic." However, it adds, there is no guarantee that a court would accept this view. Only legislation would provide certain protection. To see the NYSDOH website on the plan: http://www.health.state.ny.us/diseases/communicable/influenza/pandemic/ventilators/

(CIDRAP 4/30/07 www.cidrap.umn.edu )


Ghana: Reports of first avian influenza H5N1 outbreak
News services reported the confirmation of H5N1 avian influenza on a chicken farm in Ghana, apparently making it the ninth African country to be hit by the virus. Agriculture Minister Ernest Debrah said the outbreak was discovered Apr 24 on a farm near the port city of Tema, east of the capital, Accra. Dr. Harry Opata, a WHO disease prevention officer, said the outbreak was confirmed by a veterinary lab in Accra and by the US Navy lab in Cairo, Egypt. He said about 100 chickens had died each day for the past 3 or 4 days. Debrah said about 1,700 birds have been destroyed to stop the outbreak. The farm was relatively isolated, and the surrounding area had been put under veterinary surveillance to prevent any spread. Ghana will join 8 other African countries that are facing or have faced H5N1 outbreaks in birds: Burkina Faso, Cameroon, Cote d'Ivoire, Djibouti, Egypt, Niger, Nigeria, and Sudan. Human cases have occurred in Egypt (34), Djibouti (1), and Nigeria (1). Nigeria reported sub-Saharan Africa's only confirmed human death from H5N1 early in 2007.
(CIDRAP 5/2/07 www.cidrap.umn.edu ; Promed 5/2/07 )


Ghana: Excerpts from the OIE report on avian influenza in birds
Information received 3 May 2007 from Veterinary Services Department, ACCRA, Ghana. Date of confirmation of event 28 Apr 2007. Manifestation of disease: Clinical disease. Causal agent: Highly pathogenic avian influenza virus type A Serotype H5N1. Outbreak Location: Greater Accra (Kakasunanka, Tema Municipal). Species Birds; Susceptible 2391; Cases 447; Deaths 447; Destroyed 1944; Slaughtered 0. Apparent morbidity rate 18.70 percent; Apparent mortality rate 18.70 percent; Apparent case fatality rate 100.00 percent; Proportion susceptible removed 100.00 percent. Epidemiology Source of infection - Unknown or inconclusive.

Samples have been sent to the OIE Reference Laboratory in Italy 2 May 2007. Results are pending.

Accra veterinary laboratory (National laboratory): Test hemagglutination (HA) test: Positive. Test hemagglutination inhibition test (HIT): Positive. Rapid tests: Positive.

Noguchi Memorial Institute for Medical Research (National laboratory): Test reverse transcription - polymerase chain reaction (RT-PCR): Positive. (Promed 5/3/07)


1. Updates
Avian/Pandemic influenza updates
- UN: http://influenza.un.org/. UN response to avian influenza and the pandemic threat; new news from Central Asia. Also, http://www.irinnews.org/Birdflu.asp provides information on avian influenza in order to help the humanitarian community; update on the Ghana situation.
- 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 .
- OIE: http://www.oie.int/eng/en_index.htm. Link to the avian influenza web portal: http://www.oie.int/eng/info_ev/en_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/. Information on the Community/Non-Occupational Mask Guidance plan.
- Health Canada: information on pandemic influenza: http://www.influenza.gc.ca/index_e.html.
- CIDRAP: http://www.cidrap.umn.edu/. Frequently updated news and journal articles.
- 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. Updates from Brazil and the US.


Seasonal Influenza
During week 17 (April 22 – 28, 2007), influenza activity continued to decrease in the US. Data from the U.S. WHO and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories indicated a decrease in the percentage of specimens testing positive for influenza. The percentage of visits for ILI to sentinel providers decreased during week 17 and was below the national baseline for the sixth consecutive week. 3 states reported regional influenza activity; 9 states reported local influenza activity; the District of Columbia, New York City, and 30 states reported sporadic influenza activity; and 8 states reported no influenza activity. The number of jurisdictions reporting widespread or regional influenza activity decreased from 5 for week 16 to 3 for week 17. The percent of deaths due to pneumonia and influenza remained below baseline levels for the entire influenza season to date.
(CDC http://www.cdc.gov/flu/weekly/ )


2. Articles
Hospital Personnel Response during a Hypothetical Influenza Pandemic: Will they come to Work?
Charlene Irvin et al. Acad Emerg Med Volume 14, 5 Supplement 1 13
Abstract: “A recent public health survey found half not likely to report to duty during an influenza pandemic. The CDC pandemic preparedness plans address ill workers, but there is no discussion of a potentially decreased workforce (from fears of contracting illness). Assessing the likelihood that hospital personnel would report to work, and issues that may affect this decision are important in the preparedness for any pandemic. Objectives To determine the willingness of hospital personnel to report to work in the hypothetical event of avian influenza pandemic (the avian influenza virus became person to person transmissible). Methods A voluntary, confidential, IRB approved survey was administered to 178 hospital personnel regarding their willingness to report to work, and what issues would be important in this decision, should an avian influenza pandemic occur. Results Of 178 surveys, 169 completed (95% response rate), with 34% doctors (Docs), 33% nurses, 33% clerical and other (OTHER) (average age = 38 years, Male 32%). When asked: In the event of an avian influenza pandemic, and patients were being treated at this hospital, would you report for work as usual: 50% yes, 42% maybe, and 8% no. Docs were more likely than Nurses or OTHER to respond Yes: Docs 73% (42/57), Nurses 44% (24/55), OTHER 33% (19/57); No: Docs 2% (1/57), Nurses 15% (8/55), OTHER 7% (4/57), p < 0.001. Males were more likely to respond Yes: 66% (34/51), Female 42% (45/108) p < 0.01. For the Maybe responders, the factor making the biggest difference (83%) was: How confident I am that the hospital can protect me. In 18% (30/169), financial incentives would not make a difference for them to report to work, even up to triple pay. Conclusions Personnel absenteeism during a pandemic due to fear of contracting an illness may result in significant personnel shortage and this issue should be addressed in pandemic disaster plans. Ensuring worker confidence in adequate personal protection may be more important than financial incentives.”


A Simple Triage Scoring System Predicting Death and Need for Critical Resources for Use During Epidemics
Daniel Talmor, et al. Acad Emerg Med Volume 14, 5 Supplement 1 157
Abstract: “Objectives In the event of pandemic influenza the number of critically ill victims will likely overwhelm capacity. To date, no standardized method for triaging pandemic victims exists. The objective of this study was to derive and validate a triage rule that would assess mortality risk. Methods Design: Retrospective analysis of prospectively collected data. Setting: The emergency departments (EDs) of two urban tertiary care hospitals. Patients: Three separate cohorts of ED patients with suspected infection comprising a total of 5,133 patients (n = 3206, 1118, 809). A triage decision rule was developed using only vital signs and patient age. The triage rule was derived from a cohort at center #1, and validated on a second cohort from center #1, and on a third cohort from center #2. The primary outcome for the analysis was in-hospital mortality. Secondary outcomes were intensive care admission and use of mechanical ventilation. Results Multiple logistic regression of the derivation cohort demonstrated the following as independent predictors of death: a) age > 65, b) altered mental status, c) respiratory rate > 30 breaths per minute, d) low oxygen saturation (pox < 90%); and, e) shock index > 1 (heart rate/blood pressure). A rule was created by assigning one point per covariate and validated using an internal and external validation cohort. The mortality rates in the external validation cohort were: 1 point (1.7%); 2 points (6%), 3 points (11%), and 4 points (32%). For predicting mortality, this model had an area under the ROC curve of 0.80 in the derivation set and 0.74 and 0.76 in the validation sets. The model was also effective at predicting need for ICU admission and mechanical ventilation. Conclusions If, as expected, patient demand far exceeds the capability to provide services in an epidemic, a fair and just system to allocate limited resources will be essential. The triage rule we have developed can serve as an initial guide for such a process.”


Recombinant Modified Vaccinia Virus Ankara–Based Vaccine Induces Protective Immunity in Mice against Infection with Influenza Virus H5N1
Joost H. C. M. Kreijtz, et al. The Journal of Infectious Diseases. 2007;195:1598-1606.
Abstract: “Since 2003, the number of human cases of infections with highly pathogenic avian influenza viruses of the H5N1 subtype is still increasing, and, therefore, the development of safe and effective vaccines is considered a priority. However, the global production capacity of conventional vaccines is limited and insufficient for a worldwide vaccination campaign. In the present study, an alternative H5N1 vaccine candidate based on the replication-deficient modified vaccinia virus Ankara (MVA) was evaluated. C57BL/6J mice were immunized twice with MVA expressing the hemagglutinin (HA) gene from influenza virus A/Hongkong/156/97 (MVA-HA-HK/97) or A/Vietnam/1194/04 (MVA-HA-VN/04). Subsequently, recombinant MVA–induced protective immunity was assessed after challenge infection with 3 antigenically distinct strains of H5N1 influenza viruses: A/Hongkong/156/97, A/Vietnam/1194/04, and A/Indonesia/5/05. Our data suggest that recombinant MVA expressing the HA of influenza virus A/Vietnam/1194/04 is a promising alternative vaccine candidate that could be used for the induction of protective immunity against various H5N1 influenza strains.”


Prevaccine Determination of the Expression of Costimulatory B7 Molecules in Activated Monocytes Predicts Influenza Vaccine Responses in Young and Older Adults
David van Duin et al. The Journal of Infectious Diseases. 2007;195:1590-1597. http://www.journals.uchicago.edu/JID/journal/issues/v195n11/37605/brief/37605.abstract.html
Abstract: “Background. Innate immunity, including Toll-like receptor (TLR)–mediated expression of the B7 costimulatory molecules CD80 and CD86, is critical for vaccine immunity. We examined whether CD80 and CD86 expression vary with aging and predict response to the trivalent inactivated influenza vaccine. Methods. One hundred sixty-two subjects between 21 and 30 years of age (the young group) or ⩾65 years of age (the older group) enrolled before vaccination. We determined TLR-induced monocyte CD80/CD86 expression by flow cytometry and vaccine antibody responses by hemagglutination inhibition. Results. The mean increase in TLR-induced CD80+ monocytes was reduced in older, compared with young, adults by 68% (P = .0002), and each decile increase of CD80+ cells was associated with an 8.5% increase in mean number of vaccine strains with a ⩾4-fold titer increase (P = .01) and a 3.8% increase in mean number of strains with a postvaccine titer ⩾1 : 64 (P = .037). Each decile decrease of CD86+ cells was associated with an 11% increase in the mean number of strains with a 4-fold increase (P = .002) and a 3.9% increase in the mean number of strains with a postvaccine titer ⩾1 : 64 (P = .07). Conclusions. CD80 and CD86 expression on activated monocytes is highly associated with influenza vaccine response. This approach prospectively identifies adults unlikely to respond to immunization who may benefit from alternative vaccines or antiviral prophylaxis during influenza outbreaks.”


Controlling Pandemic Flu: The Value of International Air Travel Restrictions
Joshua M. Epstein et al. PLoS ONE. 2007 May 2;2:e401. http://www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0000401
Abstract: “Background Planning for a possible influenza pandemic is an extremely high priority, as social and economic effects of an unmitigated pandemic would be devastating. Mathematical models can be used to explore different scenarios and provide insight into potential costs, benefits, and effectiveness of prevention and control strategies under consideration. Methods and Findings A stochastic, equation-based epidemic model is used to study global transmission of pandemic flu, including the effects of travel restrictions and vaccination. Economic costs of intervention are also considered. The distribution of First Passage Times (FPT) to the United States and the numbers of infected persons in metropolitan areas worldwide are studied assuming various times and locations of the initial outbreak. International air travel restrictions alone provide a small delay in FPT to the U.S. When other containment measures are applied at the source in conjunction with travel restrictions, delays could be much longer. If in addition, control measures are instituted worldwide, there is a significant reduction in cases worldwide and specifically in the U.S. However, if travel restrictions are not combined with other measures, local epidemic severity may increase, because restriction-induced delays can push local outbreaks into high epidemic season. The per annum cost to the U.S. economy of international and major domestic air passenger travel restrictions is minimal: on the order of 0.8% of Gross National Product. Conclusions International air travel restrictions may provide a small but important delay in the spread of a pandemic, especially if other disease control measures are implemented during the afforded time. However, if other measures are not instituted, delays may worsen regional epidemics by pushing the outbreak into high epidemic season. This important interaction between policy and seasonality is only evident with a global-scale model. Since the benefit of travel restrictions can be substantial while their costs are minimal, dismissal of travel restrictions as an aid in dealing with a global pandemic seems premature.”


Can Influenza Epidemics Be Prevented by Voluntary Vaccination?
Raffaele Vardavas, Romulus Breban, Sally Blower. PLoS Computational Biology Vol. 3, No. 5, e85 doi:10.1371/journal.pcbi.0030085.
Abstract: “Previous modeling studies have identified the vaccination coverage level necessary for preventing influenza epidemics, but have not shown whether this critical coverage can be reached. Here we use computational modeling to determine, for the first time, whether the critical coverage for influenza can be achieved by voluntary vaccination. We construct a novel individual-level model of human cognition and behavior; individuals are characterized by two biological attributes (memory and adaptability) that they use when making vaccination decisions. We couple this model with a population-level model of influenza that includes vaccination dynamics. The coupled models allow individual-level decisions to influence influenza epidemiology and, conversely, influenza epidemiology to influence individual-level decisions. By including the effects of adaptive decision-making within an epidemic model, we can reproduce two essential characteristics of influenza epidemiology: annual variation in epidemic severity and sporadic occurrence of severe epidemics. We suggest that individual-level adaptive decision-making may be an important (previously overlooked) causal factor in driving influenza epidemiology. We find that severe epidemics cannot be prevented unless vaccination programs offer incentives. Frequency of severe epidemics could be reduced if programs provide, as an incentive to be vaccinated, several years of free vaccines to individuals who pay for one year of vaccination. Magnitude of epidemic amelioration will be determined by the number of years of free vaccination, an individuals' adaptability in decision-making, and their memory. This type of incentive program could control epidemics if individuals are very adaptable and have long-term memories. However, incentive-based programs that provide free vaccination for families could increase the frequency of severe epidemics. We conclude that incentive-based vaccination programs are necessary to control influenza, but some may be detrimental. Surprisingly, we find that individuals' memories and flexibility in adaptive decision-making can be extremely important factors in determining the success of influenza vaccination programs. Finally, we discuss the implication of our results for controlling pandemics.”


Detection of H5 Avian Influenza Viruses by Antigen-Capture Enzyme-Linked Immunosorbent Assay Using H5-Specific Monoclonal Antibody
Qigai He et al. Clinical and Vaccine Immunology, May 2007, p. 617-623, Vol. 14, No. 5.
Abstract: “The unprecedented spread of highly pathogenic avian influenza virus subtype H5N1 in Asia and Europe is threatening animals and public health systems. Effective diagnosis and control management are needed to control the disease. To this end, we developed a panel of monoclonal antibodies (MAbs) against the H5N1 avian influenza virus (AIV) and implemented an antigen-capture enzyme-linked immunosorbent assay (AC-ELISA) to detect the H5 viral antigen. Mice immunized with denatured hemagglutinin (HA) from A/goose/Guangdong/97 (H5N1) expressed in bacteria or immunized with concentrated H5N2 virus yielded a panel of hybridomas secreting MAbs specific for influenza virus HA. The reactivity of each MAb with several subtypes of influenza virus revealed that hybridomas 3D4 and 8B6 specifically recognized H5 HA. Therefore, purified antibodies from hybridomas 3D4 and 8B6, which secrete immunoglobulin G (IgG) and IgM, respectively, were used as the capture antibodies and pooled hyperimmune guinea pig serum IgG served as the detector antibody. The specificity of the optimized AC-ELISA was evaluated by using AIV subtypes H5 H3, H4, H7, H9, and H10. Specimens containing AIV subtype H5 subtype yielded a specific and strong signal above the background, whereas specimens containing all other subtypes yielded background signals. The detection limits of the AC-ELISA were 62.5 ng of bacterium-expressed H5N1 HA1 protein and 124, 62, and 31 50% tissue culture infective doses of influenza virus subtypes H5N1/PR8, H5N2, and H5N3, respectively. Reconstituted clinical samples consisting of H5 AIVs mixed with pharyngeal-tracheal mucus from healthy chickens also yielded positive signals in the AC-ELISA, and the results were confirmed by reverse transcription-PCR. The tracheal swab samples from H9N2-infected chickens did not give positive signals. Taken together, the newly developed MAb-based AC-ELISA offers an attractive alternative to other diagnostic approaches for the specific detection of H5 AIV.”


3. Notifications
Panel supports EU approval of cell-based influenza vaccine
A committee that reviews medical product applications for the European Union (EU) recommended approval of a cell-based seasonal influenza vaccine made by Novartis, improving the company's chance of becoming the first to market a flu vaccine grown in cell culture instead of in eggs. The Committee for Medicinal Products for Human Use (CHMP), which reviews applications for 27 EU countries, found that Novartis's Optaflu vaccine, given to more than 3,400 people during clinical studies, met the CHMP's immunogenicity criteria. The CHMP said it concluded there is "a favourable benefit to risk ratio" for Optaflu and therefore recommended its authorization. The vaccine is intended for adults.

If the European Commission approves Optaflu, it may become the first seasonal flu vaccine made with cell-culture production techniques to go on the market. The Optaflu vaccine is grown in canine kidney cells. Cell-culture production is seen as slightly faster and considerably more flexible than traditional egg-based methods. Novartis said products made with cell-culture methods are safe for people who are allergic to eggs because they are not created with egg proteins. The new technology also offers the possibility of developing vaccine seed strains that more closely match the original "wild" virus. Cell-culture methods eliminate passage of the virus through eggs, where it may need to adapt before it can replicate. Novartis has said that Optaflu is a subunit vaccine, meaning it contains individual viral proteins rather than whole virus particles.

Novartis said it anticipates applying for US licensing of its cell-based flu vaccine in 2008. The company has conducted phase 1 and 2 clinical trials of the vaccine in the US and in Jul 2006 announced it would build a $600 million plant to make cell-culture flu vaccines. In May 2006 the US Department of Health and Human Services awarded Novartis a $220 million contract to develop cell-based flu vaccines, and Novartis has said the money would go toward the cost of the new facility. Depending on when its vaccine is approved by the Food and Drug Administration, the plant could begin production as early as 2011 and be ready for full production as early as 2012, with an annual output of 50 million doses of a trivalent vaccine. In the event of a flu pandemic, the facility is designed to have the capacity to make up to 150 million monovalent (single strain) doses each year within 6 months of a pandemic declaration, Novartis said.
(CIDRAP 4/27/07 www.cidrap.umn.edu )