EINet Alert ~ Jun 29, 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: H5N1, other influenza viruses show signs of drug resistance
- Global: FAO says avian influenza entrenched as new outbreaks appear
- Czech Republic: Avian influenza H5N1 detected in swan and poultry
- Germany: Avian influenza H5N1 found in wild birds
- Bangladesh: Avian influenza reported in poultry
- Indonesia (Riau): 101st human case, WHO confirmation
- Viet Nam: Avian influenza H5N1 infections in human and poultry
- Egypt (Qena) : 37th human case of avian influenza H5N1
- Togo: Avian influenza H5N1 confirmed in poultry

1. Updates
- Avian/Pandemic influenza updates

2. Articles
- Influenza articles from CDC EID Journal
- Mass Distribution of Free, Intranasally Administered Influenza Vaccine in a Public School System
- Optimizing the Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate
- Avian influenza: USDA Has Taken Important Steps to Prepare for Outbreaks, but Better Planning Could Improve Response

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 / 19 (5)
Indonesia / 26 (22)
Laos / 2 (2)
Nigeria / 1 (1)
Viet Nam 2 (0)
Total / 54 (33)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 317 (191).
(WHO 6/29/07 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 6/25/07)

WHO's maps showing world's areas reporting confirmed cases of H5N1 avian influenza in humans, poultry and wild birds (last updated 6/28/07): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 6/21/07): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html.


Global: H5N1, other influenza viruses show signs of drug resistance
Scientists are uncovering naturally occurring resistance in influenza to the antiviral drugs that can prevent or treat it, potentially complicating plans by authorities to build large drug stockpiles against a pandemic. At the International Conference on Options for the Control of Influenza, researchers outlined the discovery of mutations that appear to reduce the susceptibility of H5N1 avian flu to the leading antiviral drug, oseltamivir (Tamiflu). Other findings uncovered mutations in a seasonal flu strain, H1N1, that could reduce the effectiveness of another antiviral, zanamivir (Relenza), and a not-yet-released antiviral, peramivir. The mutations appear to be spontaneous and not the result of inappropriate use of the drugs.

Dr. Jennifer McKimm-Breschkin of Australia's CSIRO Molecular Health Technologies revealed that isolates from 2 of the H5N1 virus's 3 main groupings, or clades, have developed partial resistance to oseltamivir. Viruses recovered from domestic birds in Cambodia, a clade 1 country, became 6 to 7 times less sensitive to oseltamivir between 2004 and 2005. And 2005 isolates from Indonesia, the country where the clade 2 grouping arose, were 25 to 30 times less sensitive to oseltamivir than any of the clade 1 viruses collected in 2004. McKimm-Breschkin said, the virus remained virulent despite the mutation—which might explain why Indonesia has the world's highest case-fatality rate for H5N1 (80%). Influenza's ability to resist the action of antiviral drugs is a particular concern because only 4 licensed drugs in 2 classes work against it: oseltamivir and zanamivir (the neuraminidase inhibitors), and the older drugs amantadine and rimantadine (the adamantanes).

In Dec 2005, Dr. Menno de Jong and colleagues reported that 2 out of 8 patients treated at the Hospital for Tropical Diseases in Vietnam died of oseltamivir-resistant H5N1 flu. In Jan 2006, CDC urged physicians treating seasonal flu not to use the 2 older drugs, after routine tests revealed that 91% of isolates were resistant to them. And in Apr 2007, Dr. Shuji Hatakeyama reported in the Journal of the American Medical Association of 8 children who had been stricken with seasonal influenza B, were treated with oseltamivir, and subsequently showed mutations conferring resistance against the drug.

Dr. Elena Govorkova of St. Jude Children's Research Hospital kept a clade 2 virus from Turkey from replicating in ferrets by administering the equivalent of 2.5 times the standard human dose of oseltamivir, signaling that the drug may be able to overcome the mutation if administered early enough and in high enough doses. WHO currently is revising treatment recommendations for both dosing and timing of oseltamivir, based on the shared experience of clinicians who have treated H5N1 patients--earlier and longer treatment and higher doses may make a difference to patients' survival. McKimm-Breschkin said, if patients infected with less-susceptible strains of virus receive drug doses that are too low to overcome the mutation, the strains will survive and could develop greater resistance. She said the discovery should signal the need to include other drugs such as zamamivir in pandemic planning. But other researchers found mutations in H1N1 seasonal flu that could affect the usefulness of other drugs. 4 isolates from the Philippines showed changes that could interfere with the action of zanamivir and peramivir. Because zanamivir is little-used in the Philippines and peramivir is still in phase 1 trials, the researchers assume the mutations are spontaneous and not due to inadequate drug treatment.

But if the findings are bad news for the remaining influenza drugs, researchers demonstrated that there are other drugs entering the pipeline. An experimental drug called Fludase bypasses the flu virus altogether and instead temporarily blocks the lung-tissue receptors where the flu virus binds to replicate, Dr. Jessica Belser of Emory University said. In a small mouse study, the compound worked prophylactically to protect against H5N1 infection and as a treatment after exposure to the virus. The compound will enter phase 1 clinical trials this summer, Belser said.
(CIDRAP 6/22/07; Promed 6/22/07)


Global: FAO says avian influenza entrenched as new outbreaks appear
Joseph Domenech, the UN Food and Agriculture Organization (FAO) chief veterinary officer, said the response to the virus has improved significantly over the past 3 years, but it remains entrenched in several countries and will continue to spread. Domenech said at the Technical Meeting on Highly Pathogenic Avian Influenza and Human H5N1 Infection that except in Egypt and Indonesia, human H5N1 cases have been very sporadic. In the approximately 15 countries in Asia, Eastern Europe, and the Middle East where the virus has cropped up in the past 6 months, it was rapidly detected and eliminated or controlled, Domenech said. "Most countries have been very open about new outbreaks," he said. But Domenech cited the recent H5N1 outbreaks in birds in Bangladesh, Ghana, Togo, the Czech Republic, and Germany as illustrations of the need to shun complacency. He said containment and eradication of the virus will demand a long-term financial and political commitment, especially in the face of the "high risk poultry production and marketing practices that still continue in many countries." Domenech also called for increased monitoring of the virus, especially in countries that vaccinate poultry. "The H5N1 virus is not stable and keeps constantly changing. On one occasion in China last year a new virus strain appeared with different immunologic characteristics which made it necessary to modify vaccines used in the region concerned," he said. "This emergence of a new strain may have happened again more recently in Indonesia."
(CIDRAP 6/27/07)


Europe/Near East
Czech Republic: Avian influenza H5N1 detected in swan and poultry
Czech veterinaries reportedly revealed 27 Jun 2007 another case of bird flu, as tests confirmed the virus in a swan that died in Lednice, south Moravia. Further tests have yet to confirm whether the virus is the H5N1 strain, said Jaroslav Salava, who heads the veterinary administration in south Moravia. The Lednice water reservoirs are one of the most risky areas through which many wild birds move, but there are no big bird [poultry] farms around, Salava said. Also, turkeys at a farm in Tisova, east Bohemia, tested positive for H5N1 during the week of 18-24 Jun 2007 and those who did not die of bird flu had to be culled. On 28 Jun 2007, the virus was confirmed at another farm near Tisova. 60 broiler chickens in a flock of 27,800 on a commercial farm in the village of Norin tested positive for H5N1. Both farms are owned by the same company. Reportedly, the whole flock on the Norin farm was to be destroyed, along with other birds owned by Norin residents.
(Promed 6/28/07; CIDRAP 6/27/07)


Germany: Avian influenza H5N1 found in wild birds
After the confirmation 22 Jun 2007 of the presence of HPAIV (highly pathogenic avian influenza virus) H5N1 in 5 dead mute swans (Cygnus olor) and 1 Canada goose (Branta canadensis) at 2 lakes in Nuremberg, 3 further mute swans were found dead 26 Jun 2007 at a small lake about 180 km north of Nuremberg in Frohburg/Saxony. The cases were found in the course of a national testing program for dead birds. The Friedrich-Loeffler-Institut performed real-time RT-PCR (reverse transcription polymerase chain reaction) specific for HPAIV of Qinghai-like strains and proved that the viruses present in the Saxonian swans are highly pathogenic H5N1. This virus lineage had caused the epidemic among wild birds in Europe in 2006 and had also been responsible for the outbreaks in Hungary and the UK in 2007.

The examination of more than 16 000 wild birds comprising a total of 186 species since autumn 2006 had not yielded any H5N1 HPAI positive results. In 2007, a total of 1347 mute swans, 335 of which were found dead, had tested negative for H5N1. Nevertheless, it cannot be excluded that the virus has been continuously present at low prevalence and/or in clustered pockets of the wild bird population. Ongoing regional monitoring activities among the wild bird population will be intensified to check whether further pockets of H5N1 HPAIV infection are present in this region. In addition, enhanced biosecurity measures are to be implemented in poultry holdings. Authorities ordered farmers in the Nuremberg region to confine their poultry and banned the transport of poultry into and out of the area. The restrictions apply to an area within a 2.5-mile radius of where the infected birds were found. Officials also warned people not to let cats and dogs roam freely in the area.

Excerpts from OIE report:
Start date: 24 Jun 2007; Causal agent: highly pathogenic avian influenza virus, serotype H5N1. Nuremberg, Bavaria. Summary of outbreaks: Total outbreaks: 6; Species: wild species: Cases: 6; Deaths: 6; Destroyed: 0; Slaughtered: 0. Apparent case fatality rate: 100 per cent Source of infection: unknown or inconclusive. Affected birds: swans and ducks. Movement control is applied in the restriction zones as well as disinfection and sensitization of staff in poultry holdings in the restricted zones and reinforcement of wild birds monitoring.

Laboratory name and type: Friedrich-Loeffler-Institut. Polymerase chain reaction (PCR): positive.
(CIDRAP 6/25/07; Promed 6/27/07, Promed 6/28/07)


Bangladesh: Avian influenza reported in poultry
Avian flu was reported in another district, forcing the culling of 5,000 chickens. Abdul Motalib of the fisheries and livestock ministry said the outbreak was in a village in Thakurgaon district, 500 km northwest of the capital, Dhaka. The virus was first found near Dhaka, in central Bangladesh, in Mar 2007 and has since spread to northern regions. 16 of 64 districts have been affected. About 4 million Bangladeshis are directly or indirectly associated with poultry farming.
(CIDRAP 6/27/07; Promed 6/28/07)


Indonesia (Riau): 101st human case, WHO confirmation
As of 25 Jun 2007, the Ministry of Health of Indonesia has announced a new case of human infection of H5N1 avian influenza. A 3 year old girl from Riau Province developed symptoms 18 Jun 2007 and has since recovered. Investigations into the source of her infection indicate exposure to sick and dead poultry. Azizman Daad, the avian flu team leader at a hospital in the Riau capital of Pekanbaru, said the girl was treated with oseltamivir (Tamiflu) as soon as she was admitted. Of the 101 cases confirmed to date in Indonesia, 80 have been fatal.
(Promed 6/26/07; CIDRAP 6/25/07)


Viet Nam: Avian influenza H5N1 infections in human and poultry
A man from Bac Lieu province has been hospitalized with symptoms of bird flu after cooking and eating a duck which had died allegedly of bird flu. The 40 year old man, who is now in the Tropical Disease Hospital in Ho Chi Minh City, has been suffering from severe respiratory problems in the last few days. He works for a farmer who raises 350 ducklings, some of which died recently. The province's animal health authorities said 3 flocks of ducks in Bac Lieu's Hong Dan district had died recently with bird flu symptoms. They had been raised in the neighboring Soc Trang province. The man and the dead ducks are being tested for the H5N1. The latest deaths raised Viet Nam's death toll since 2003 to 44 people out of 98 reported cases. Since May 2007, 18 provinces and cities have been affected, in which 5 humans contracted the H5N1 strain of the disease and 2 died, taking the total death toll since 2003 to 44. 2 others, from Thanh Hoa and Vinh Phuc provinces, recovered and were discharged. The fifth, who is from Thai Nguyen province, is under treatment. All 5 either had direct contact with or had eaten dead fowl, deputy minister of health Trinh Quan Huan said 25 Jun 2007. He said the drug Tamiflu (oseltamivir) was still effective in treating the disease.

On 26 Jun 2007, 2 more Vietnamese provinces officially became bird flu-free, with Son La and Nam Dinh in the north reporting no new outbreaks in the last 21 days. There are 12 provinces and cities, mostly in the north, which remain on the list. Meanwhile, 2 new infected sites were discovered in Quang Nam province. Deputy minister of agriculture, Bui Ba Bong, warned 26 Jun 2007 that the epidemic could hit the south since the region is set for its autumn-summer rice harvest before which farmers tend to leave their fowls roam freely to find food. Of the 65 provinces and cities, 44 have completed this year's [2007] first round of vaccination for 83.86 million chickens, 59.39 million ducks, and 3.47 million white-winged ducks.
(Promed 6/27/07)


Egypt (Qena) : 37th human case of avian influenza H5N1
As of 25 Jun 2007, the Egyptian Ministry of Health and Population has confirmed a new human case of avian influenza A(H5N1) virus infection. The case has been confirmed by the Egyptian Central Public Health Laboratory and by the WHO H5 Reference Laboratory, US Naval Medical Research Unit No.3 (NAMRU-3). The case is a 4 year old boy from Qena Governorate. He developed symptoms 20 Jun 2007 and was admitted to hospital 21 Jun 2007. He is receiving treatment and is in stable condition. Initial investigations into the source of his infection indicate exposure to dead poultry. This patient is the third human bird flu case from Qena over the past month after a lull of nearly 2 months. Of the 37 cases confirmed to date in Egypt, 15 have been fatal.

Bird flu did extensive damage to the country's poultry industry and the economy as a whole after its arrival in Egypt, which has more confirmed bird flu cases among humans than any other country outside of Asia. Most of those who have fallen ill in Egypt were reported to have had contact with sick or dead household birds, primarily in northern Egypt where the weather is cooler than in the south. Around 5 million households in Egypt depend on poultry as a main source of food and income and the government has said this makes it unlikely the disease can be eradicated. The government still finds it hard to enforce restrictions on the movement and sale of live poultry.
(Promed 6/23/07, 6/26/07)


Togo: Avian influenza H5N1 confirmed in poultry
Independent tests have confirmed the presence for the first time of the H5N1 strain of bird flu in poultry from the West African nation of Togo. "The results of the tests from the world reference laboratory in Padua have come in: it is clearly H5N1," said agriculture minister, Yves Nagou Mado. It is the first time the virus has been detected in Togo. In neighbouring Nigeria, more than 1 million birds have been destroyed since the first outbreak there Feb 2006. Several thousand poultry birds have been found dead in Togo recently, most of them in the past week on the one farm in Sigbehoue, 45 km east of the capital Lome. The affected farm had received a shipment of chicks in Feb 2007 from neighbouring Ghana. The virus is often passed from one region to another when infected birds are transported for sale, Katinka Debalogh, UN Food and Agriculture Organisation's (FAO) Avian Flu response coordinator. "Industrial farms like this one [in Sigbehoue] typically see a lot of movement of live animals, so producers need to be careful about where the birds are coming from," Debalogh said.

The agriculture ministry said that measures had been taken to try and contain the possible spread of the virus, notably the slaughtering and disposal of infected poultry. Togo's minister of agriculture, Mr Nagou, indicated that localities and villages around the outbreak are under active monitoring. He added, "Culling of the animals in the infected premises will begin Thursday [28 Jun 2007]", and announced the installation of a committee of "crisis" charged to follow the evolution of the situation.

Excerpts from OIE report:
Date submitted to OIE 25 Jun 2007. Causal agent: highly pathogenic avian influenza virus; Serotype: H5N1
Outbreak 1 Sigbehoue, Lacs, Region Maritime.
Date of start of outbreak: 6 Jun 2007. Outbreak status: continuing (or date resolved not submitted)
Epidemiological unit: farm. Species: birds: Susceptible 5574; Cases 2505; Deaths 2505; Destroyed 3069; Slaughtered 0. Affected population: hens in an intensive system of farming. Source of infection unknown or inconclusive. Laboratory name and type: Padova (Italy) (OIE's Reference Laboratory): Test: RT-PCR: Result: positive. Rapid tests: positive
(Promed 6/23/07, 6/26/07, 6/28/07)


1. Updates
Avian/Pandemic influenza updates
- UN: http://influenza.un.org/. UN response to avian influenza and the pandemic threat. Also, http://www.irinnews.org/Birdflu.asp provides information on avian influenza in order to help the humanitarian community.
- 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 International Technical Meeting on Highly Pathogenic Avian Influenza and Human H5N1 Infection.
- OIE: http://www.oie.int/eng/en_index.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/. Read about the Pandemic Flu Leadership Forum and Blog.
- Health Canada: information on pandemic influenza: http://www.influenza.gc.ca/index_e.html. Link to: “Canada's Third Annual Wild Bird Survey For Avian Influenza is Underway”.
- CIDRAP: http://www.cidrap.umn.edu/. Pandemic preparedness Webinar recordings available for purchase.
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm. The website has been updated, with link to National Influenza Centers in PAHO Member States.
- US Geological Survey, National Wildlife Health Center Avian Influenza Information: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp. Updates for Hong Kong, Russia, Bangladesh, and Czech Republic, 22 Jun 2007.


2. Articles
Influenza articles from CDC EID Journal
CDC Emerging Infectious Diseases Journal, Volume 13, Number 7, 2007 issue is now available at: http://www.cdc.gov/ncidod/eid/. The following influenza articles are available in this issue: Effects of Internal Border Control on Spread of Pandemic Influenza by J.G. Wood et al.; Influenza Pandemics in Singapore by V.J. Lee et al.; Live Poultry Exposures, Hong Kong and Hanoi, 2006 by R. Fielding et al.; Little Evidence for Genetic Susceptibility to Influenza (H5N1) by Family Clustering by V.E. Pitzer et al.; Blood Screening for Influenza by M.K. Hourfar et al.; Human Influenza A (H5N1) Cases, Urban Areas, China by H. Yu et al.; Possible Avian Influenza (H5N1) from Migratory Bird, Egypt by M.D. Saad et al.; Avian Influenza Risk Perceptions, Laos by H.M. Barennes et al..


Mass Distribution of Free, Intranasally Administered Influenza Vaccine in a Public School System
L. Rand Carpenter et al. PEDIATRICS (doi:10.1542/peds.2006-2603). http://pediatrics.aappublications.org/cgi/content/abstract/peds.2006-2603v1
Abstract: “OBJECTIVE. School-based influenza vaccination programs are a potentially important method of protecting the community against influenza. We evaluated the feasibility and success of a large, school-based influenza vaccination campaign. METHODS. On-site administration of intranasally administered, live attenuated influenza vaccine was offered to all students and staff members in a large, metropolitan public school system in October to December 2005. We evaluated vaccine coverage levels, resources expended, and physician and parent attitudes and knowledge. RESULTS. Of 53420 public school students, 24198 were vaccinated with live attenuated influenza vaccine. Of 5841 school staff members, 3626 were vaccinated with live attenuated influenza vaccine or inactivated influenza vaccine. The proportions of students vaccinated were 56% among elementary schools, 45% among middle schools, and 30% among high schools. Schools with larger proportions of black or low-income families had lower vaccine coverage levels. The health department and school system expended 6900 person-hours during the campaign, and various health department clinics were closed for a total of 84 half-days. Community physicians were supportive of the campaign and frequently advised participation for eligible patients. Some physicians had misunderstandings about live attenuated influenza vaccine contraindications. Concern about adverse effects, having asthma, negative physician advice, and nonparticipation in any vaccination program were common reasons for students not participating. CONCLUSIONS. This influenza vaccination campaign in a large public school system achieved relatively high vaccine coverage levels but required a substantial resource commitment from the local health department. This evaluation has critical implications for the ongoing debate regarding immunization policies for school-aged children and preparedness plans for pandemic influenza.”


Optimizing the Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate
Riley S, Wu JT, Leung GM. PLoS Medicine 2007 June;4(6):1032-40. http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040218
Abstract: “Background: The recent spread of avian influenza in wild birds and poultry may be a precursor to the emergence of a 1918-like human pandemic. Therefore, stockpiles of human pre-pandemic vaccine (targeted at avian strains) are being considered. For many countries, the principal constraint for these vaccine stockpiles will be the total mass of antigen maintained. We tested the hypothesis that lower individual doses (i.e., less than the recommended dose for maximum protection) may provide substantial extra community-level benefits because they would permit wider vaccine coverage for a given total size of antigen stockpile. Methods and Findings: We used a mathematical model to predict infection attack rates under different policies. The model incorporated both an individual's response to vaccination at different doses and the process of person-to-person transmission of pandemic influenza. We found that substantial reductions in the attack rate are likely if vaccines are given to more people at lower doses. These results are applicable to all three vaccine candidates for which data are available. As a guide to the magnitude of the effect, we simulated epidemics based on historical studies of immunogenicity. For example, for one of the vaccines for which data are available, the attack rate would drop from 67.6% to 58.7% if 160 out of the total US population of 300 million were given an optimal dose rather than 20 out of 300 million given the maximally protective dose (as promulgated in the US National Pandemic Preparedness Plan). Our results are conservative with respect to a number of alternative assumptions about the precise nature of vaccine protection. We also considered a model variant that includes a single high-risk subgroup representing children. For smaller stockpile sizes that allow vaccine to be offered only to the high-risk group at the optimal dose, the predicted benefits of using the homogenous model formed a lower bound in the presence of a risk group, even when the high-risk group was twice as infective and twice as susceptible. Conclusions: In addition to individual-level protection (i.e., vaccine efficacy), the population-level implications of pre-pandemic vaccine programs should be considered when deciding on stockpile size and dose. Our results suggest that a lower vaccine dose may be justified in order to increase population coverage, thereby reducing the infection attack rate overall.”


Avian influenza: USDA Has Taken Important Steps to Prepare for Outbreaks, but Better Planning Could Improve Response
What GAO Found: “USDA is taking important steps to prepare for highly pathogenic AI. For example, the department has established mechanisms to prevent infected poultry (see photo) and products from being imported and has developed several surveillance programs to detect AI. In addition, USDA is developing response plans specific to highly pathogenic AI and has begun conducting exercises to test these plans. Moreover, USDA is building a National Veterinary Stockpile to maintain critical supplies, including equipment to protect responders. Finally, USDA has launched various AI research projects, including one to explore why the virus causes disease and death in some domestic poultry and wild birds but not in others. While USDA has made important strides, incomplete planning at the federal and state levels, as well as several unresolved issues, could slow response. First, USDA is not planning for the lead coordinating role that DHS would assume if an outbreak among poultry occurred that is sufficient in scope to warrant various federal disaster declarations. GAO’s prior work has shown that roles and responsibilities must be clearly defined and understood to facilitate rapid and effective decision making. Moreover, USDA response plans do not identify the capabilities needed to carry out the critical tasks associated with an outbreak scenario—that is, the entities responsible for carrying them out, the resources needed, and the provider of those resources. Furthermore, some state plans lack important components that could facilitate rapid AI containment, which is problematic because states typically lead initial response efforts. Finally, there are several unresolved issues that, absent advance consideration, could hinder response. For example, controlling an outbreak among birds raised in backyards, such as for hobby, remains particularly difficult because federal and state officials generally do not know the numbers and locations of these birds. In addition, USDA has not estimated the amount of antiviral medication that it would need during an outbreak or resolved how to provide such supplies in a timely manner. According to federal guidance, poultry workers responding to an outbreak of highly pathogenic AI should take antiviral medication to protect them from infection.”