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  • CDC - Avian Influenza Key H7N9 Points - May 3, 2013


    Situation Summary


    · Cases of human infection with a new avian influenza A (H7N9) virus continue to be detected in China since the first cases were internationally reported by the World Health Organization on April 1, 2013.
    · No cases of H7N9 have been detected in the United States or anywhere outside of China at this time.
    · As of May 1, 2013, 12:00PM EDT, 128 human cases of H7N9 infection had been reported, with 26 deaths.
      • On April 24, 2013 the Chinese National Health and Family Planning Commission announced that it would report H7N9 cases on a weekly rather than a daily basis. It’s possible that provinces or municipalities in China may report cases more frequently. However, for external communication purposes CDC will use the most recent official weekly numbers from China.

    • Most of the reported cases of human infection with H7N9 have had very serious illness. There also are reports of some milder illness and asymptomatic illness.
    • The evolving situation in China is of international public health concern because of the potential for this virus to change to trigger a pandemic, which could be severe based on the epidemiological information currently available.
    • An ongoing investigation suggests that most people have been infected with the virus after having contact with infected poultry or contaminated environments. (See “Avian Influenza Background” for information on how this type of transmission might occur.)
    • Follow-up investigations among close contacts of people infected with H7N9 by Chinese health officials indicate that there is no sustained (ongoing) spread of this virus from person to person at this time; however a few small clusters of human infection have occurred where the possibility of limited human-to-human spread cannot be excluded.
    • Based on previous experience with other avian influenza viruses, it would not be surprising to see some limited human-to-human spread of this H7N9 virus.
    • Most important, however, is the fact that there is no evidence of efficient and sustained (ongoing) spread in the community, which is what is needed to trigger a pandemic.

    What May Happen

    • It would NOT be surprising to see limited human-to-human transmission during the current H7N9 situation in China.
    • It’s also possible that H7N9 cases may at some point be detected in the United States (for example, in a traveler returning from China).
    • This would not signal an increase in the potential risk to the public’s health unless the transmission pattern of the virus was to change.
    • If a person in the United States has H7N9 flu, they will be isolated (separated from other people who are well) and cared for.
    • In addition, a contact investigation will be done with people who may have been exposed to the sick person.

    · Contact investigations are one of the ways CDC works with partners in the United States and other countries to protect the health of people exposed to an illness. This process involves finding, interviewing, and in some cases, testing or treating the people who came into contact with the sick person.
    • The purpose of a contact investigation for a traveler with H7N9 flu returning from China is to:
      • provide information to exposed passengers and crew so they can get preventive antiviral treatment if needed, recognize any symptoms of disease, isolate themselves if needed, and receive care.
      • refer passengers or crew with influenza-like illness for medical evaluation, testing, and antiviral treatment if needed.
      • determine whether spread of H7N9 flu may have occurred on the flight and which passengers were at greatest risk.

    • All of this can reassure us that the virus is not spreading further in the United States.

    Public Health Concern

    • The concern right now is that this H7N9 virus might either mutate or adapt to allow efficient transmission during the infection of mammals or reassort its gene segments with human influenza viruses during the co-infection of a single host, resulting in a new virus that might be transmissible from person to person.
    • Such events are believed to have preceded the influenza pandemics of 1918, 1957, 1968 and 2009.

    · Because H7N9 viruses do not commonly infect humans, there is probably little or no immune protection against them in the human population. (CDC is conducting serologic studies to confirm this.)
    • If sustained, ongoing human-to-human transmission of H7N9 viruses begins, many more people will become ill, some severely, and unfortunately more deaths will occur.
    • CDC is preparing for various scenarios – including sustained human-to-human transmission – to ensure that the agency will be in the best position to help protect the public from this virus.
    • It is important to note, however, that efficient and sustained human-to-human transmission would be needed to trigger a pandemic. There is no indication that such transmission is happening in China.

    · The investigation is ongoing and CDC will provide more information as it becomes available at http://www.cdc.gov/flu/avianflu/h7n9-virus.htm.
    What CDC Is Doing

    • CDC is following this situation closely and coordinating with domestic and international partners, including China CDC and the World Health Organization.
    • CDC is taking routine preparedness measures, including:
      • Developing a candidate vaccine virus that could be used to make vaccine if it becomes necessary. (See section “H7N9 Vaccine Development” for more information.)
      • Shipping a CDC-developed test kit to detect this virus that can be used by other public health laboratories. Information about these test kits is available at http://www.cdc.gov/flu/avianflu/h7n9...iagnostics.htm.
      • Establishing serologic methods to detect antibodies to H7N9 viruses.
      • Conducting studies to understand biological properties of the virus.
      • Conducting ongoing testing to determine H7N9 susceptibility to the licensed influenza antiviral drugs, oseltamivir (commercially known as Tamiflu&#174 and zanamivir (Relenza&#174 as well as investigational antiviral drugs.
      • Providing recommendations for travelers as needed.
      • CDC also is gathering more information to make a more thorough public health risk assessment.


    · Recent activities include:
    o An MMWR “Emergence of Avian Influenza A(H7N9) Virus Causing Severe Human Illness — China, February–April 2013” was published on May 1, 2013 and is available at http://www.cdc.gov/mmwr/preview/mmwr...=mm62e0501a1_w.
    o Shipping of the CDC-developed H7N9 diagnostic test kits began on April 25, 2013. To date, 81 test kits have been shipped domestically (75) and internationally (6). Test kits had been distributed to 43 states as of May 1, 2013.
    o On Monday, April 29, 2013, CDC received another H7N9 virus from China. This virus is known as “Shanghai/1” and came from one of the first human cases of H7N9 virus infection detected in China. (This is the second H7N9 virus isolate that CDC has received from China.)
    o CDC inoculated the virus into eggs. Like the first isolate received on April 11, this virus has grown well in eggs. CDC will share samples of this second virus as it did with the first.
    o On May 1, 2013, CDC communicated with the WHO Global Influenza Surveillance and Response System (GISRS) and vaccine manufacturers about the availability of a CDC H7N9 potential candidate vaccine virus.
      • The potential vaccine virus candidate has been designated “A/Shanghai/2/2013(H7N9)-PR8-IDCDC-RG32A.”
      • CDC used plasmid-based reverse genetics to recover a reassortant virus with the hemagglutinin (HA) and neuraminidase (NA) genes of A/Shanghai/2/2013(H7N9) and the remaining genes from A/Puerto Rico/8/1934(H1N1) in accordance with WHO guidelines for pandemic candidate vaccine virus development.


    o Results from testing this candidate vaccine virus suggest that it is “cross-reactive” to the wild type antiserum and thus “well-matched” with the H7N9 virus causing illness in China.
      • There are still some in vitro and in vivo studies that have to be completed to meet regulatory and biosafety requirements for a candidate vaccine virus. These studies are ongoing and should be completed by mid-May. The ferret safety testing is expected to be completed by May 14. (Dates of completion for ongoing studies are subject to change.) Under normal circumstances, release of reassortant viruses to vaccine manufacturers would not proceed until all such study results are available.
      • However, in the interests of expediting H7N9 research and vaccine developments efforts, CDC is making this potential H7N9 candidate vaccine virus available for order for qualified laboratories and manufacturers with the caveat that they must work on it in biosafety level 3 conditions and the understanding that the pending studies may not meet the criteria needed for this to be a successful candidate vaccine virus.
      • Once CDC finalizes testing on the candidate vaccine virus, qualified laboratories should be able to work with the vaccine virus in biosafety level 2 conditions with enhancements.


    o At this time, no decision has been made to mass-produce H7N9 vaccine in the United States (See section “H7N9 Vaccine Development for more information.),
    o In addition, neither the World Health Organization or the U.S. Food and Drug Administration have made any recommendation about which H7N9 potential candidate vaccine virus to use for vaccine manufacturing.
    o However, sometimes vaccine manufacturers begin production of influenza vaccines at their discretion before such decisions are made.
    o Making the potential candidate vaccine virus available slightly earlier than usual would give manufacturers the possibility of initiating early stages of vaccine production if they wish to do so.
    o CDC is also reviewing and analyzing new H7N9 virus sequences posted to public virus databases by the Chinese Public Health Authorities. Some of these sequences have come from animals and this allows CDC to compare the properties of the viruses infecting animals with those infecting humans.
    • Additional results from the CDC laboratories emerged this week as well:

    o CDC was able collect H7N9 antisera from the animal studies begun on April 15.
    o Additionally, human sera collected from past clinical studies evaluating earlier H7 subtype candidate vaccine virus were used to test for antibody “cross-reactivity” with the H7N9 virus. *Cross reactivity refers to the ability of antibodies developed against a vaccine virus to recognize and neutralize the H7N9 virus.

    o CDC also has issued guidance to inform key partners at ports of entry (Customs and Border Protection, airline flight crews, and Emergency Medical Services at international airports) about the current situation, ask them to be especially vigilant about recognizing illness in travelers from affected areas, and remind them of standard protocols for response to an infectious disease.
    o Together with partners at ports of entry, CDC staff is assessing ill travelers returning from affected areas to determine whether any additional public health action is needed.

    What Clinicians and Public Health Professionals Should Do


    • Patients with illness compatible with influenza (1) who have recently traveled to countries where human cases of novel influenza A (H7N9) virus infection have recently been detected or (2) who have had recent contact with confirmed human cases of infection with novel influenza A (H7N9) virus should be candidates for RT-PCR testing for influenza.

    · Clinicians should consider the possibility of H7N9 influenza infection in patients with illness compatible with influenza and an appropriate recent travel or exposure history.
    · Because of the potential severity of illness associated with H7N9 virus infection, it is recommended that all confirmed cases, probable cases, and H7N9 cases under investigation receive antiviral treatment with oseltamivir or zanamivir as early as possible. See Interim Guidance on the Use of Antiviral Agents for Treatment of Human Infections with Avian Influenza A (H7N9) in the United States on the CDC website.
    • Clinicians also should be aware of appropriate infection control guidelines for patients with suspected novel influenza A viruses.

    o Because it has been shown to cause severe respiratory illness in cases identified so far, health care personnel (HCP) caring for patients with suspected H7N9 virus infection should adhere to Standard Precautions plus Contact and Airborne Precautions, including eye protection, until more is known about the transmission characteristics of the A (H7N9) virus.
    o All clusters of respiratory illness in HCP caring for patients with severe acute respiratory illness should be investigated.
    · See Interim Guidance for Infection Control Within Healthcare Settings When Caring for Patients with Confirmed, Probable or Cases Under Investigation of Avian Influenza A(H7N9) Virus.
    What the Public Should Do

    · At this time, no cases of human infection with avian influenza A (H7N9) viruses have been detected in the United States and the virus does not seem to be spreading from person to person.
    · Other than advice for travelers or ill persons below, CDC is not making any additional or special recommendations for public action specific to H7N9.
    Travelers

    Travelers should continue to visit www.cdc.gov/travel or follow <s>@</s>CDCtravel on Twitter for up-to-date information about CDC’s travel recommendations.
    CDC does not recommend restricting travel to China at this time.
    Travelers to China should practice hand hygiene, follow food safety practices, and avoid contact with animals.
    o Travelers should wash their hands often or use hand sanitizer. They should try not to touch their eyes, nose, or mouth, except with very clean hands.
    o Travelers should eat meats and poultry products, including eggs, only if they have been cooked thoroughly.
    o Travelers should avoid touching animals, alive or dead, and should stay away from farms, poultry markets, or other markets where there are live or dead animals.
    Symptoms of H7N9 flu include fever, cough, and shortness of breath. If travelers get sick after returning from China, they should tell their doctors about their recent travel.
    H7N9 Vaccine Development

    While there is no evidence of sustained (ongoing) person-to-person spread of the H7N9 virus, the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), National Institutes of Health (NIH) and the Department of Health and Human Services (HHS) are taking standard pandemic preparedness precautions.
    As of today, a decision to produce H7N9 vaccine for a U.S. national vaccination response has not been made.
    However, given the number and severity of human illnesses from H7N9 in China, HHS and its partners are taking routine steps to develop a H7N9 candidate vaccine virus and are planning for H7N9 vaccine clinical trials.
    Influenza vaccine production is complex and can be unpredictable. It has many critical and time-sensitive steps; delay at any point during these steps can result in delays in the availability of influenza vaccine.
    It usually takes about six months to produce large quantities of influenza vaccine.
    The development of a high-yield candidate vaccine virus is the first step in developing a vaccine.
    o A candidate vaccine virus is a flu virus that CDC (or one of the other WHO Collaborating Centers) selects and prepares for use by vaccine manufacturers to make a flu vaccine. Candidate vaccine viruses are typically chosen based on their similarity to flu viruses spreading and causing illness in people as well as their ability to grow easily in chicken eggs, which is the method of manufacturing influenza vaccine traditionally used.
    o Without a high-yield candidate vaccine virus, it can be very difficult to manufacture vaccine to protect against a new influenza virus.
    o CDC, FDA, BARDA (Biomedical Advanced Research and Development Authority in the Office of the Assistant Secretary for Preparedness and Response) and vaccine manufacturers are collaborating to develop a high-yield candidate vaccine virus that could be used to begin production of an H7N9 vaccine.
    BARDA has existing contracts in place with manufacturers of U.S.-licensed influenza vaccines that use egg-, cell-, and recombinant-based technologies. These contracts can support the development, manufacturing, and clinical evaluation of H7N9 vaccines and adjuvants. These contracts also ensure that the candidate vaccine viruses developed would be shared freely and would support commercial scale manufacturing, if needed.
    Once the candidate vaccine virus has been developed, manufacturers can use it to develop a vaccine against the avian influenza A (H7N9) virus.
    Once a vaccine manufacturer receives a candidate vaccine virus, the manufacturer then creates what is known as a "seed strain." The seed strain is adapted to make the virus grow better using the manufacturer’s technology and production systems. Once the seed strain is prepared, the vaccine manufacturer uses it to grow large quantities of virus for producing flu vaccine.
    Influenza vaccine manufacturers need 8 to 11 weeks to make small lots of vaccine and test whether the candidate vaccine virus works well in the manufacturing process.
    o FDA and other WHO Essential Regulatory Laboratories will make reagents to test the potency of both cell- and egg-based vaccine lots.
    • NIH and vaccine manufacturers will sponsor clinical studies of investigational H7N9 vaccines to evaluate the safety and determine the optimal dosing and whether an adjuvant is needed for an adequate immune response. FDA is working closely with NIH and other stakeholders in the design of these clinical trials.
    o The clinical trials will be conducted among people who volunteer to participate in vaccine studies. Information about safety and how people’s immune systems respond to the vaccine will be important for planning vaccine production and a vaccine program, if such a program is needed.
    If it is decided that an H7N9 vaccination program is needed, even if production goes as planned, it would be several months before the first doses of H7N9 influenza vaccines are available.
    Although no decision has been made to initiate a H7N9 vaccination program in the United States, CDC recommends that local authorities and preparedness programs take time to review and update their pandemic influenza vaccine preparedness plans since it could take several months to ready a vaccination program, if one were necessary.
    Keep in mind that CDC and HHS continue to gather information to make a more thorough public health risk assessment. This is an evolving situation and there is still much to learn.
    Information will be shared as available at http://www.cdc.gov/flu/avianflu/h7n9-virus.htm.
    Avian Influenza Background

    &#183; Subtypes of H7 viruses are that have been identified in birds include the following: H7N1, H7N2, H7N3, H7N4, H7N5, H7N6, H7N7, H7N8, and H7N9.
    &#183; Most H7 viruses identified worldwide in wild birds and domestic poultry are low pathogenic avian influenza A (LPAI) viruses. LPAI viruses generally cause mild illness in birds, and some birds may not have symptoms.
    &#183; H7 virus infection in humans is uncommon, but has been documented in persons who have direct contact with infected birds, especially during outbreaks of H7 virus among poultry. Illness in humans may include conjunctivitis and/or upper respiratory tract symptoms.
    &#183; In humans, LPAI (H7N2, H7N3, H7N7) virus infections have caused mild to moderate illness.
    &#183; HPAI (H7N3, H7N7) virus infections have caused mild to severe and fatal illness in humans.
    • The H7N9 viruses recently reported in China are the first known human cases of H7N9 influenza infection.
    • To date, there have been no human infections with H7N9 in the United States or any countries other than China.
    • Different avian influenza A (H7N9) viruses have been identified in birds in North America. Wild waterfowl and shore birds may carry the virus during migrations and may introduce it to domestic poultry. The North American lineage of H7N9 is different from the Eurasian lineage of H7N9 viruses that are currently circulating in China.
    • The threat to humans from the North American lineage of H7N9 influenza viruses is low.
    • Avian flu viruses do not normally infect humans. However, sporadic human infections with avian flu do occasionally occur.
    • Most commonly, human cases of avian influenza happen in people with direct exposure to infected poultry.
    • Infected birds can shed a lot of flu virus, for example, in their droppings or their mucus. If someone touches an infected bird or an environment contaminated with virus and then touches their eyes, nose or mouth, they may be infected with bird flu virus.
    • There is some evidence that infection may also occur if the flu virus becomes airborne, such as when an infected bird flaps it wings. If someone were to breathe in airborne virus, it’s possible they could get infected.
    • While most instances of human infection with animal influenza viruses do not result in human-to-human transmission, each case should be fully investigated to be sure that such viruses are not spreading among humans and to limit further exposure of humans to infected animals, if infected animals are identified.

    &#183; Poultry, poultry products (eggs) and pork can be safely consumed provided they are properly cooked and properly handled during food preparation.
    &#183; Surveillance for avian influenza viruses in North American birds is under the purview of the USDA and the Department of the Interior (DOI). Questions regarding avian influenza infections in U.S. birds should be referred to these agencies.
    &#183; International cases of novel influenza A are reportable to the World Health Organization under the International Health Regulations (IHR 2005).
    &#183; In 2007, human infection with a novel influenza A virus became a nationally notifiable condition in the United States. Novel influenza A virus infections include all human infections with influenza A viruses that are different from currently circulating human influenza H1 and H3 viruses. Novel viruses include those that are subtyped as non-human in origin and those that are unsubtypable with standard methods and reagents.
    &#183; For more information about avian influenza, visit the CDC website at http://www.cdc.gov/flu/avianflu/index.htm.
    What is Known about Spread of Other Avian Influenza Viruses, Summary

    • Person-to-person spread of other avian influenza viruses is thought to have occurred in the past, most notably with H5N1 viruses.
    • In the majority of these instances, spread occurred after prolonged and close contact between the sick person and someone caring for them (most often a family member).

    &#183; See http://www.cdc.gov/flu/avianflu/h5n1...infections.htm for more information.
    Human-to-Human Spread, Background

    • It’s important to remember that human-to-human transmission ranges along a continuum; from occasional, “dead-end” human-to-human transmission, to efficient and sustained human-to-human transmission.
    • “Dead end” transmission usually refers to when a virus from an animal host infects a person and then there is some subsequent transmission that eventually burns out.
    • For example, when a host infects one person who then subsequently infects someone else that is called “first generation spread.” If that second person then infects someone else that is called “second generation spread,” and so forth.
    • Previously, third generation transmission of H5N1 viruses has been documented in one instance at least (Pakistan). (WHO, Weekly Epidemiological Record. “Human cases of avian influenza A(H5N1) in North-West Frontier Province, Pakistan, October–November 2007.”)
    • However, efficient and sustained (ongoing) transmission in the community is needed for an influenza pandemic to begin.

    CDC and China, Background

    • U.S. CDC Influenza Division began working with the China National Influenza Center (CNIC), part of the China CDC, in the late 1980s.
    • CDC helped China to establish the Chinese National Influenza Surveillance Network and laboratory capability in order to capture more of the influenza viruses circulating in China.
    • Since 2004, CDC and China CDC have participated in a series of cooperative agreements that have further improved and sustained China’s surveillance network and supported genetic, antigenic and drug resistance surveillance (in part to inform vaccine recommendations), and also strengthened influenza response capacity at all levels.
    • In October 2010, CNIC was designated as a World Health Organization Collaborating Center for Reference and Research on Influenza.
    • CNIC is one of a handful of WHO Collaborating Centers for Reference and Research on Influenza in the world (U.S. CDC in Atlanta, Georgia also is a WHO Collaborating Center).
    • Among other things, as a Collaborating Center CNIC regularly provides information from China’s recently enhanced surveillance system to help inform decisions about the composition of the seasonal flu vaccine.
    • Collaborating Centers also train researchers in specialized techniques, collect epidemiological information on influenza disease prevalence in China and surrounding countries, and assist in developing pandemic preparedness plans. They also receive, characterize, and preserve representative vaccine viruses sent from laboratories around the world, then share that information with other researchers.

    Links to Additional Information

    CDC Resources
    &#183; CDC will provide updated information as it becomes available at http://www.cdc.gov/flu/avianflu/h7n9-virus.htm.
    &#183; An MMWR “Emergence of Avian Influenza A(H7N9) Virus Causing Severe Human Illness — China, February–April 2013” was published on May 1, 2013 and is available at http://www.cdc.gov/mmwr/preview/mmwr...=mm62e0501a1_w.

    &#183; The World Health Organization Representative Office in China has published the statement and transcript from a press briefing held after the international H7N9 assessment team completed its mission to China. These materials who are available at http://www.wpro.who.int/china/en/.
    WHO Resources

    Other Organizations

    &#183; The European Centre for Disease Prevention and Control is publishing their latest updates and risk assessments on influenza A(H7N9) at “Avian influenza in humans.” This page is available at http://ecdc.europa.eu/en/healthtopics/avian_influenza/Pages/index.aspx.
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UnhideWhenUsed="true" Name="List Continue 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="List Continue 4"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="List Continue 5"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Message Header"/> <w:LsdException Locked="false" Priority="11" QFormat="true" Name="Subtitle"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Salutation"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Date"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Body Text First Indent"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Body Text First Indent 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Note Heading"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Body Text 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Body Text 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Body Text Indent 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Body Text Indent 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Block Text"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" QFormat="true" Name="Hyperlink"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="FollowedHyperlink"/> <w:LsdException Locked="false" Priority="22" QFormat="true" Name="Strong"/> <w:LsdException Locked="false" Priority="20" QFormat="true" Name="Emphasis"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Document Map"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Plain Text"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="E-mail 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SemiHidden="true" UnhideWhenUsed="true" Name="HTML Sample"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Typewriter"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Variable"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Normal Table"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="annotation subject"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="No List"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Outline List 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Outline List 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Outline List 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Simple 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Simple 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SemiHidden="true" UnhideWhenUsed="true" Name="Table Columns 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Columns 4"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Columns 5"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 4"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 5"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 6"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 7"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 8"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table List 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table List 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table List 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table List 4"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table List 5"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table List 6"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table List 7"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table List 8"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table 3D effects 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table 3D effects 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table 3D effects 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Contemporary"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Elegant"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Professional"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Subtle 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Subtle 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Web 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Web 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Web 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Balloon Text"/> <w:LsdException Locked="false" Priority="39" Name="Table Grid"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Theme"/> <w:LsdException Locked="false" SemiHidden="true" Name="Placeholder Text"/> <w:LsdException Locked="false" Priority="1" QFormat="true" Name="No Spacing"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading"/> <w:LsdException Locked="false" Priority="61" Name="Light List"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3"/> <w:LsdException Locked="false" Priority="70" Name="Dark List"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 1"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 1"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 1"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 1"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 1"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 1"/> <w:LsdException Locked="false" SemiHidden="true" Name="Revision"/> <w:LsdException Locked="false" Priority="34" QFormat="true" Name="List Paragraph"/> <w:LsdException Locked="false" Priority="29" QFormat="true" Name="Quote"/> <w:LsdException Locked="false" Priority="30" QFormat="true" Name="Intense Quote"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 1"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 1"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 1"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 1"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 1"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 1"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 1"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 1"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 2"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 2"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 2"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 2"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 2"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 2"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 2"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 2"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 2"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 2"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 2"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 2"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 2"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 2"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 3"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 3"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 3"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 3"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 3"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 3"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 3"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 3"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 3"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 3"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 3"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 3"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 3"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 3"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 4"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 4"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 4"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 4"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 4"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 4"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 4"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 4"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 4"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 4"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 4"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 4"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 4"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 4"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 5"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 5"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 5"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 5"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 5"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 5"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 5"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 5"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 5"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 5"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 5"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 5"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 5"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 5"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 6"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 6"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 6"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 6"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 6"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 6"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 6"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 6"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 6"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 6"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 6"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 6"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 6"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 6"/> <w:LsdException Locked="false" Priority="19" QFormat="true" Name="Subtle Emphasis"/> <w:LsdException Locked="false" Priority="21" QFormat="true" Name="Intense Emphasis"/> <w:LsdException Locked="false" Priority="31" QFormat="true" Name="Subtle Reference"/> <w:LsdException Locked="false" Priority="32" QFormat="true" Name="Intense Reference"/> <w:LsdException Locked="false" Priority="33" QFormat="true" Name="Book Title"/> <w:LsdException Locked="false" Priority="37" SemiHidden="true" UnhideWhenUsed="true" Name="Bibliography"/> <w:LsdException Locked="false" Priority="39" SemiHidden="true" UnhideWhenUsed="true" QFormat="true" Name="TOC Heading"/> <w:LsdException Locked="false" Priority="41" Name="Plain Table 1"/> <w:LsdException Locked="false" Priority="42" Name="Plain Table 2"/> <w:LsdException Locked="false" Priority="43" Name="Plain Table 3"/> <w:LsdException Locked="false" Priority="44" Name="Plain Table 4"/> <w:LsdException Locked="false" Priority="45" Name="Plain Table 5"/> <w:LsdException Locked="false" Priority="40" Name="Grid Table Light"/> <w:LsdException Locked="false" Priority="46" Name="Grid Table 1 Light"/> <w:LsdException Locked="false" Priority="47" Name="Grid Table 2"/> <w:LsdException Locked="false" Priority="48" Name="Grid Table 3"/> <w:LsdException Locked="false" Priority="49" Name="Grid Table 4"/> <w:LsdException Locked="false" Priority="50" Name="Grid Table 5 Dark"/> <w:LsdException Locked="false" Priority="51" Name="Grid Table 6 Colorful"/> <w:LsdException Locked="false" Priority="52" Name="Grid Table 7 Colorful"/> <w:LsdException Locked="false" Priority="46" Name="Grid Table 1 Light Accent 1"/> <w:LsdException Locked="false" Priority="47" Name="Grid Table 2 Accent 1"/> <w:LsdException Locked="false" Priority="48" Name="Grid Table 3 Accent 1"/> <w:LsdException Locked="false" Priority="49" Name="Grid Table 4 Accent 1"/> <w:LsdException Locked="false" Priority="50" Name="Grid Table 5 Dark Accent 1"/> <w:LsdException Locked="false" Priority="51" Name="Grid 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Locked="false" Priority="50" Name="Grid Table 5 Dark Accent 3"/> <w:LsdException Locked="false" Priority="51" Name="Grid Table 6 Colorful Accent 3"/> <w:LsdException Locked="false" Priority="52" Name="Grid Table 7 Colorful Accent 3"/> <w:LsdException Locked="false" Priority="46" Name="Grid Table 1 Light Accent 4"/> <w:LsdException Locked="false" Priority="47" Name="Grid Table 2 Accent 4"/> <w:LsdException Locked="false" Priority="48" Name="Grid Table 3 Accent 4"/> <w:LsdException Locked="false" Priority="49" Name="Grid Table 4 Accent 4"/> <w:LsdException Locked="false" Priority="50" Name="Grid Table 5 Dark Accent 4"/> <w:LsdException Locked="false" Priority="51" Name="Grid Table 6 Colorful Accent 4"/> <w:LsdException Locked="false" Priority="52" Name="Grid Table 7 Colorful Accent 4"/> <w:LsdException Locked="false" Priority="46" Name="Grid Table 1 Light Accent 5"/> <w:LsdException Locked="false" Priority="47" Name="Grid Table 2 Accent 5"/> <w:LsdException Locked="false" Priority="48" Name="Grid Table 3 Accent 5"/> <w:LsdException Locked="false" Priority="49" Name="Grid Table 4 Accent 5"/> <w:LsdException Locked="false" Priority="50" Name="Grid Table 5 Dark Accent 5"/> <w:LsdException Locked="false" Priority="51" Name="Grid Table 6 Colorful Accent 5"/> <w:LsdException Locked="false" Priority="52" Name="Grid Table 7 Colorful Accent 5"/> <w:LsdException Locked="false" Priority="46" Name="Grid Table 1 Light Accent 6"/> <w:LsdException Locked="false" Priority="47" Name="Grid Table 2 Accent 6"/> <w:LsdException Locked="false" Priority="48" Name="Grid Table 3 Accent 6"/> <w:LsdException Locked="false" Priority="49" Name="Grid Table 4 Accent 6"/> <w:LsdException Locked="false" Priority="50" Name="Grid Table 5 Dark Accent 6"/> <w:LsdException Locked="false" Priority="51" Name="Grid Table 6 Colorful Accent 6"/> <w:LsdException Locked="false" Priority="52" Name="Grid Table 7 Colorful Accent 6"/> <w:LsdException Locked="false" Priority="46" Name="List Table 1 Light"/> 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