CDC Internal Key Points: Avian Influenza A (H7N9) - Immunization ...

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CDC Internal Key Points: Avian Influenza A (H7N9) - Immunization ...

CDC Key Points - Avian Influenza A H7N9 VirusApril 19, 2013On Thursday, April 18, 2013, CDC conducted a Clinical Outreach and CommunicationActivity (COCA) conference call to provide a CDC Update for Clinicians on AvianInfluenza A (H7N9) Virus. Call information is available athttp://emergency.cdc.gov/coca/calls/2013/callinfo_041813.asp.CDC, together with Customs and Border Protection, has posted a message onmonitors in international arrival areas at airports that directs international travelersto the Travelers’ Health website for more information about H7N9 flu.CDC has developed guidance to inform key partners at ports of entry (Customs andBorder Protection and airline flight crews) about the current situation and to remindthem of standard protocols for response to an infectious disease.CDC is continuing to analyze the number of flights and passengers who arrive fromChina to U.S. ports of entry to assist in preparation for future communications andpublic health response efforts.CDC is working closely with Canadian and Mexican governments under the NorthAmerican Plan for Animal and Pandemic Influenza to coordinate our response.On Friday, April 19, 2013, CDC posted a Questions & Answers document called“H7N9 Flu and You” for the public. This Q&A is available athttp://www.cdc.gov/flu/avianflu/h7n9-basics.htm.CDC has also posted images of the H7N9 virus in CDC’s Public Health Image Library(PHIL). These images also are available on the CDC Flu website athttp://www.cdc.gov/flu/images.htm.CDC Team to ChinaIn response to a bi-lateral request from China for assistance with the H7N9response, 3 CDC experts (one laboratorian and two epidemiologists) are traveling toChina to support the Chinese Center for Disease Control and Prevention (ChinaCDC)’s response to the H7N9 outbreak. Included on the team are one laboratorianand two epidemiologists, who will travel to China in the next week.The laboratorian will represent the U.S. CDC Influenza Division laboratory andprovide expertise in reverse genetics, a central part of the process of developing anH7N9 vaccine.The epidemiologists will represent the U.S. CDC Influenza Division Epidemiology andPrevention Branch and assist with epidemiologic assessment.BackgroundU.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 Networkand laboratory capability in order to capture more of the influenza viruses circulatingin China.Since 2004, CDC and China CDC have participated in a series of cooperativeagreements that have further improved and sustained China’s surveillance network5


CDC Key Points - Avian Influenza A H7N9 VirusApril 19, 2013and supported genetic, antigenic and drug resistance surveillance (in part to informvaccine recommendations), and also strengthened influenza response capacity at alllevels.In October 2010, CNIC was designated as a World Health Organization CollaboratingCenter for Reference and Research on Influenza.CNIC is one of a handful of WHO Collaborating Centers for Reference and Researchon Influenza in the world (U.S. CDC in Atlanta, Georgia also is a WHO CollaboratingCenter).Among other things, as a Collaborating Center CNIC regularly provides informationfrom China’s recently enhanced surveillance system to help inform decisions aboutthe composition of the seasonal flu vaccine.Collaborating Centers also train researchers in specialized techniques, collectepidemiological information on influenza disease prevalence in China andsurrounding countries, and assist in developing pandemic preparedness plans. Theyalso receive, characterize, and preserve representative vaccine viruses sent fromlaboratories around the world, then share that information with other researchers.WHO Delegation: Joint Assessment TeamChina has invited a team of international influenza experts to carry out a one-weekjoint assessment of the H7N9 situation in the country.Dr. Nancy Cox, Director of the Influenza Division in the National Center forImmunization and Respiratory Diseases (NCIRD) at CDC, is among the influenzaexperts that have been invited to China for this collaboration. Dr. Cox departed for China on April 17, 2013.The team will assess the H7N9 outbreak and the response to guide furtherprevention and control measures.Members include Chinese experts on epidemiology, laboratory tests and clinicaltreatment, as well as experts and officials from the United States, Australia, theEuropean Union, and WHO. Results of the mission will be released to the public.ooIt is not unusual in this type of situation for such a team to be invited. It doesnot represent a sign of growing concern, but a sign of our sustained concern.This collaboration provides a good opportunity for experts to learn about theongoing investigation and for China to learn from other influenza experts.Use of Antiviral Drugs for Treatment of Human Infections with H7N9Questions & Answers:What does CDC recommend in terms of treatment against H7N9?CDC recommends that all H7N9 patients should be treated immediately with eitheroseltamivir (Tamiflu) or zanamivir (Relenza). "All H7N9 patients" means all confirmedcases, probable cases, and cases under investigation. The case definition includes febrile6


CDC Key Points - Avian Influenza A H7N9 VirusApril 19, 2013respiratory illness and an appropriate recent travel or exposure history (see CaseDefinitions to be Used for H7N9). Oseltamivir should be used for hospitalized patients.How is the CDC antiviral treatment guidance for H7N9 different from theantiviral treatment guidance for seasonal flu?For seasonal influenza, CDC recommends empiric treatment for suspect influenza in allhospitalized patients and high risk outpatients. The decision about whether or not totreat patients who are not at high risk is left to clinical discretion in the CDC seasonalantiviral guidance. The guidance for the use of influenza antiviral drugs against H7N9 ismore aggressive than it is for seasonal influenza. Because of the risk for severe diseaseassociated with H7N9 to date and the pandemic potential associated with this virus, CDCrecommends that ALL patients who have confirmed or probable H7N9, or even thosewho are under investigation for H7N9, be treated, regardless of their age or thepresence of underlying pre-existing medical conditions.SummaryBecause of the potential severity of illness associated with influenza A (H7N9) virusinfection, CDC recommends that all H7N9 patients (confirmed cases, probable cases,and cases under investigation of H7N9) receive antiviral treatment with either oraloseltamivir (Tamiflu®) or inhaled zanamivir (Relenza®) as early as possible.Treatment should be initiated even if it is more than 48 hours after onset of illness.Laboratory testing and antiviral treatment should occur simultaneously; antiviraltreatment should not be delayed while waiting for laboratory confirmation ofinfluenza or H7N9 infection. (For information regarding case investigation, specimencollection and laboratory testing, please see the CDC Health Alert Network Advisoryissued on April 5, 2013.It is important to remember that H7N9 investigations are ongoing andrecommendations on the use of antiviral medications to treat H7N9 infection inhumans may change as we learn more information. The current guidance has beendeveloped based on the current disease situation and available data about thetreatment of seasonal influenza A or B, and avian influenza A (H5N1) virusinfections.This interim guidance will be updated as additional information on H7N9 virustransmissibility, epidemiology, and antiviral susceptibility patterns becomesavailable.Key MessagesCDC has issued Interim Guidance on the Use of Antiviral Agents for Treatment ofHuman Infections with Avian Influenza A (H7N9) in the United States. The guidanceis available at: http://www.cdc.gov/flu/avianflu/h7n9-antiviral-treatment.htm.The interim guidance on the use of influenza antiviral medications to treat H7N9infections in humans was developed by subject matter experts at CDC, inconsultation with external influenza antiviral experts.7


CDC Key Points - Avian Influenza A H7N9 VirusApril 19, 2013The interim guidance for treatment of human infections with H7N9 influenza isnecessary in light of three important considerations:1. There is currently no vaccine available to help protect against human infectionwith H7N9 influenza.2. There has been high disease severity and substantial death among patients withconfirmed H7N9 influenza infection.3. There is currently limited human-to-human H7N9 virus transmission, but there ispotential for increased transmission in the future.This interim guidance recommends antiviral treatment for all confirmed cases,probable cases, and cases under investigation of human infection with avianinfluenza A (H7N9) virus infection.ooA confirmed case is a patient with laboratory-confirmed influenza A (H7N9).Laboratory confirmation is confirmed by CDC’s influenza laboratory or a CDCcertifiedpublic health laboratory using methods agreed upon by CDC and theCouncil of State and Territorial Epidemiologists (CSTE).A probable case is a patient with influenza-like illness (ILI*) for whomlaboratory diagnostic reverse transcriptase polymerase chain reaction (RT-PCR) testing is unsubtypeable. An unsubtypeable result would yield thefollowing results: positive for influenza A, negative for H1, negative for 2009H1N1 and negative for H3.* ILI is defined as fever (temperature of 100°F [37.8°C] or greater)and cough and/or sore throat.oA case under investigation is a patient with influenza-like illness for whomlaboratory diagnostic results are unknown, pending, or do not provide enoughdetail to confirm H7N9 influenza infection AND meets one of the followingexposure criterion:• Patients who have recently traveled to countries where human casesof H7N9 influenza virus infection have recently been detected,especially if there was recent direct or close contact with animals (suchas wild birds, poultry, or pigs) or where H7N9 viruses are known to becirculating in animals. Currently, China is the only country that hasrecently reported human cases of H7N9.• Patients who have had recent contact with confirmed human cases ofinfection with H7N9 virus.Clinicians should consider the possibility of H7N9 influenza infection in patients withillness compatible with influenza and an appropriate recent travel or exposurehistory. (See Case Definitions to be Used for Novel Influenza A (H7N9) CaseInvestigations in the United States on the CDC website.)Clinical benefit is greatest when antiviral treatment is administered early, ideallywithin 48 hours of symptom onset. However, antiviral treatment should still beinitiated in these patients even if it is more than 48 hours after the onset of illness.8


CDC Key Points - Avian Influenza A H7N9 VirusApril 19, 2013When given early in the course of treatment, antiviral drugs reduce the duration ofsymptoms and likelihood of complications in patients with uncomplicated illness (i.e.patients presenting with acute ILI in the absence of other influenza-relatedcomplications, like pneumonia), and reduce disease severity and mortality inhospitalized patients.Currently, no data are available regarding using neuraminidase inhibitors to treatpatients with H7N9 virus. However, laboratory testing indicates that H7N9 virusesare susceptible to the neuraminidase inhibitors — oseltamivir (Tamiflu®) andzanamivir (Relenza®) — but resistant to adamantanes (amantadine andrimantadine). Amantadine and rimantadine should not be used for treatment ofH7N9 virus infection.Uncomplicated Illness in OutpatientsAntiviral treatment with oseltamivir or zanamivir is recommended for all people withuncomplicated illness, even if the patient presents more than 48 hours after illnessonset.ooFor uncomplicated illness due to seasonal influenza, antiviral benefit has beendemonstrated when treatment is initiated within 48 hours of illness onset.However, treatment in uncomplicated patients who are confirmed, probable,or under investigation H7N9 cases is still recommended given the anticipatedlack of preexisting immunity to H7N9 viruses in humans, the rapidprogression and severity of H7N9 infection, the fatal outcomes associatedwith H7N9, and the low adverse event profile of oseltamivir and inhaledzanamivir.Initiating antiviral treatment as soon as possible after illness onset isespecially important for people at high risk of developing complications frominfluenza, including children younger than 2 years, adults aged 65 years andolder, pregnant women, and people with certain underlying health conditions.The complete list of people at high risk for influenza complications is availableat http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm.Decisions about initiating antiviral treatment for patients with mild disease whosesymptoms are nearly resolved should be based on clinical judgment. Those patientswho are not treated with antiviral medications should be monitored for progressionof illness.Inhaled zanamivir is not recommended for people with certain respiratory diseases,like asthma or chronic obstructive pulmonary disease. The recommended duration of treatment for patients with uncomplicated illness is 5days.Hospitalized PatientsAntiviral treatment should start as early as possible for hospitalized patients, even ifit is more than 48 hours from illness onset.For hospitalized patients with severe or complicated illness, treatment with oraloseltamivir is recommended. Inhaled zanamivir is not recommended for hospitalized9


CDC Key Points - Avian Influenza A H7N9 VirusApril 19, 2013patients because of the lack of data for inhaled zanamivir in patients with severeinfluenza illness.The optimal duration and dosage for influenza antiviral drugs are uncertain in severeor complicated influenza. Pending further data, longer courses of treatment (e.g., 10days of treatment) should be considered for severely ill, hospitalized H7N9 patients.oooClinical judgment and RT-PCR testing of lower respiratory tract specimensshould guide decisions to consider treatment regimens longer than 5 days forpatients with severe and prolonged illness.Patients with weakened immune systems, and severely ill hospitalizedpatients who may shed virus longer, may require longer treatment regimens.A higher dose of oseltamivir (e.g., 150 mg twice daily) has beenrecommended by some experts in immunocompromised and severely illhospitalized patients.Although oseltamivir is well-absorbed in critically ill patients, intravenous (IV)zanamivir should be considered for critically ill patients who cannot tolerate orabsorb oral oseltamivir because of suspected or known gastric stasis, malabsorption,or gastrointestinal bleeding.IV zanamivir is an investigational drug available by enrollment in a clinical trial orthrough a compassionate use request for emergency investigational new drugapproval (EIND) through the manufacturer with FDA approval. IV zanamivircompassionate use request may be made by contacting the GSK Clinical SupportHelp Desk via email (gskclinicalsupportHD@gsk.com) or by calling 1-877-626-8019or 1-866-341-9160.Influenza Antivirals BackgroundTwo FDA-approved influenza antiviral medications are currently recommended foruse in the United States to treat influenza: oral oseltamivir (Tamiflu®) and inhaledzanamivir (Relenza®).Oseltamivir and zanamivir are known as neuraminidase inhibitors and have activityagainst both influenza A and B viruses. (H7N9 is an influenza A virus.)When clinically indicated, influenza antiviral medications should be used to treatinfluenza patients as soon as possible, ideally (but not limited to) within 48 hours ofsymptom onset. For all confirmed, probable and cases under investigation ofinfection with H7N9 influenza, antiviral treatment is still recommended even ifstarted more than 48 hours after illness onset.Treatment of persons with suspected H7N9 influenza should not wait for laboratoryconfirmation of influenza.Antiviral treatment can also be considered for any previously healthy, non-high risk,symptomatic outpatient with confirmed or suspected influenza based upon clinicaljudgment, if treatment can be initiated within 48 hours of illness onset.For more information about antiviral medications, visithttp://www.cdc.gov/flu/antivirals/index.htm.10


CDC Key Points - Avian Influenza A H7N9 VirusApril 19, 2013DiagnosticsThe CDC H7N9 assay, which is comprised of primers and probes,* is intended for usewith RT-PCR (reverse-transcriptase polymerase chain reaction), which is a highlyaccurate and sensitive laboratory test for detecting and identifying flu virus inrespiratory specimens collected from patients presenting with flu symptoms. RT-PCRcan identify flu viruses by type and subtype.CDC was able to create its diagnostic test kit for detecting H7N9 without having theactual avian influenza A (H7N9) virus. CDC influenza experts within CDC’s Influenzalaboratories in Atlanta were able to analyze the genome of the H7N9 virus, whichwas made publicly available by Chinese public health authorities in a viral genesequence database called GISAID.* RT-PCR assays are testing procedures intended to detect the presence ofvirus genetic material. Primers and probes represent a section of DNA thatadheres to specific regions of virus genetic material. CDC’s primers andprobes for detecting the avian influenza A (H7N9) virus are intended for usewith CDC’s currently used RT-PCR assay (the CDC Flu rRT-PCR Dx Panel) fordetection of human influenza virus.What Clinicians and Public Health Professionals Should DoPatients with illness compatible with influenza (1) who have recently traveled tocountries where human cases of novel influenza A (H7N9) virus infection haverecently been detected or (2) who have had recent contact with confirmed humancases 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 withillness compatible with influenza and an appropriate recent travel or exposurehistory. See Interim Guidance on the Use of Antiviral Agents for Treatment of HumanInfections with Avian Influenza A (H7N9) in the United States on the CDC website.Clinicians also should be aware of appropriate infection control guidelines for patientswith suspected novel influenza A viruses.ooBecause it has been shown to cause severe respiratory illness in casesidentified so far, health care personnel (HCP) caring for patients withsuspected H7N9 virus infection should adhere to Standard Precautions plusContact, and Airborne Precautions, including eye protection, until more isknown about the transmission characteristics of the A (H7N9) virus.All clusters of respiratory illness in HCP caring for patients with severe acuterespiratory illness should be investigated.What the Public Should DoAt this time, no cases of human infection with avian influenza A (H7N9) viruses havebeen detected in the United States and the virus does not seem to be spreading fromperson-to-person.11


CDC Key Points - Avian Influenza A H7N9 VirusApril 19, 2013Other than advice for travelers or ill persons below, CDC is not making any additionalor special recommendations for public action specific to H7N9.Travelers• CDC does not recommend restricting travel to China at this time.• Although we do not know the source of the H7N9 virus, travelers to China shouldpractice hand hygiene, follow food safety practices, and avoid contact with animals.oooTravelers should wash their hands often or use hand sanitizer. They shouldtry not to touch their eyes, nose, or mouth, except with very clean hands.Travelers should eat meats and poultry products, including eggs, only if theyhave been cooked thoroughly.Travelers should avoid touching animals, alive or dead, and should stay awayfrom farms, poultry markets, or other markets where there are live or deadanimals.• Symptoms of H7N9 flu include fever, cough, and shortness of breath. If travelers getsick after returning from China, they should tell their doctors about their recenttravel.• Travelers should continue to visit www.cdc.gov/travel or follow @CDCtravel onTwitter for up-to-date information about CDC’s travel recommendations.• CDC will provide updated information as it becomes available. This information isavailable on the CDC website at http://www.cdc.gov/flu/avianflu/h7n9-virus.htm.Avian Influenza BackgroundSubtypes of H7 viruses are that have been identified in birds include the following:H7N1, H7N2, H7N3, H7N4, H7N5, H7N6, H7N7, H7N8, and H7N9.Most H7 viruses identified worldwide in wild birds and domestic poultry are lowpathogenic avian influenza A (LPAI) viruses. LPAI viruses generally cause mild illnessin birds, and some birds may not have symptoms.H7 virus infection in humans is uncommon, but has been documented in personswho have direct contact with infected birds, especially during outbreaks of H7 virusamong poultry. Illness in humans may include conjunctivitis and/or upper respiratorytract symptoms.In humans, LPAI (H7N2, H7N3, H7N7) virus infections have caused mild to moderateillness.HPAI (H7N3, H7N7) virus infections have caused mild to severe and fatal illness inhumans.The H7N9 viruses recently reported in China are the first known human cases ofH7N9 influenza infection.To date, there have been no human infections with H7N9 in the United States or anycountries other than China.12


CDC Key Points - Avian Influenza A H7N9 VirusApril 19, 2013Different avian influenza A (H7N9) viruses have been identified in birds in NorthAmerica. Wild waterfowl and shore birds may carry the virus during migrations andmay introduce it to domestic poultry. The North American lineage of H7N9 isdifferent from the Eurasian lineage of H7N9 viruses that are currently circulating inChina.The threat to humans from the North American lineage of H7N9 influenza viruses islow.Avian flu viruses do not normally infect humans. However, sporadic human infectionswith avian flu do occasionally occur.Most commonly, human cases of avian influenza happen in people with directexposure to infected poultry.While most instances of human infection with animal influenza viruses do not resultin human-to-human transmission, each case should be fully investigated to be surethat such viruses are not spreading among humans and to limit further exposure ofhumans to infected animals, if infected animals are identified.Poultry, poultry products (eggs) and pork can be safely consumed provided they areproperly cooked and properly handled during food preparation.Surveillance for avian influenza viruses in North American birds is under the purviewof the USDA and the Department of the Interior (DOI). Questions regarding avianinfluenza infections in U.S. birds should be referred to these agencies.International cases of novel influenza A are reportable to the World HealthOrganization under the International Health Regulations (IHR 2005).In 2007, human infection with a novel influenza A virus became a nationallynotifiable condition in the United States. Novel influenza A virus infections include allhuman infections with influenza A viruses that are different from currently circulatinghuman influenza H1 and H3 viruses. Novel viruses include those that are subtyped asnon-human in origin and those that are unsubtypeable with standard methods andreagents.For more information about avian influenza, visit the CDC website athttp://www.cdc.gov/flu/avianflu/index.htm.What is Known About Spread of Other Avian Influenza Viruses - SummaryPerson-to-person spread of other avian influenza viruses is thought to have occurredin the past, most notably with H5N1 viruses.For example, in 1997, in Hong Kong, there was evidence of limited transmission ofH5N1 virus to health care workers and household contacts of H5N1 patients. Thevirus did not spread further.In 2004, in Thailand, there was evidence of probable human-to-human spread in afamily cluster. Transmission was associated with prolonged very close contactbetween an ill child and her mother and her aunt. Transmission did not spread13


CDC Key Points - Avian Influenza A H7N9 VirusApril 19, 2013beyond one person. (Ungchusak et al, 2005. “Probable Person-to-PersonTransmission of Avian Influenza A (H5N1).”)In 2005, in Indonesia, limited person-to-person H5N1 transmission could not beexcluded in two clusters among patients who had no known contact with poultry orother animals. (Kandun et al, 2006. “Three Indonesian Clusters of H5N1 VirusInfection in 2005.”)In December 2007, limited, unsustained spread is thought to have occurred betweena sick son and his father. (Wang et al, 2008. “Probable limited person-to-persontransmission of highly pathogenic avian influenza A (H5N1) virus in China.”)Also in 2007, evidence gathered during an outbreak investigation in Pakistansupports the theory of initial transmission from poultry to humans followed byhuman-to-human transmission involving a third generation. (WHO, WeeklyEpidemiological Record, 2008. “Human cases of avian influenza A(H5N1) in North-West Frontier Province, Pakistan, October–November 2007.”)In the majority of these instances, spread occurred after prolonged and close contactbetween the sick person and someone caring for them (most often a familymember).Like seasonal influenza viruses, spread of avian flu viruses between people is thoughtto occur mainly through inhalation of droplets expelled by the sick person throughcoughing. There also has been some evidence to suggest that spread of theseviruses can occur after contact with mucus or stool and subsequent inoculation ofmucous membranes or the respiratory tract.This is why appropriate infection control and the use of personal protectiveequipment (including masks) is so important.There is no test to verify human-to-human spread. That determination is generallymade after a thorough epidemiological investigation.It is probable that other cases of human-to-human spread of avian influenza viruseshave occurred but transmission has not been sustained.Links to Additional InformationCDC will provide updated information as it becomes available athttp://www.cdc.gov/flu/avianflu/h7n9-virus.htm.CDC has posted a Questions & Answers document called “H7N9 Flu and You” for thegeneral public. This Q&A is available at http://www.cdc.gov/flu/avianflu/h7n9-basics.htm.CDC posted a Flu Spotlight: “Additional H7N9 Cases Reported in China; CDCReceives H7N9 Virus Isolate.” The spotlight is available athttp://www.cdc.gov/flu/spotlights/h7n9-cases-china.htm.CDC has posted Interim Guidance on the Use of Antiviral Agents for Treatment ofHuman Infections with Avian Influenza A (H7N9). The guidance is available athttp://www.cdc.gov/flu/avianflu/h7n9-antiviral-treatment.htm.14


CDC Key Points - Avian Influenza A H7N9 VirusApril 19, 2013CDC has posted Interim Guidance for Infection Control Within Healthcare SettingsWhen Caring for Patients with Confirmed, Probable, or Cases Under Investigation ofAvian Influenza A(H7N9) Virus Infection. The guidance is available athttp://www.cdc.gov/flu/avianflu/h7n9-infection-control.htm.CDC has posted Interim Guidance on Case Definitions to be Used for Novel InfluenzaA (H7N9) Case Investigations in the United States. This guidance is available athttp://www.cdc.gov/flu/avianflu/h7n9-case-definitions.htm.WHO updates information related to human cases of H7N9 avian influenza athttp://www.who.int/csr/don/en/.WHO has posted a Q&A for human infections with H7N9 avian influenza viruses. It isavailable athttp://www.who.int/influenza/human_animal_interface/faq_H7N9/en/index.html.The Chinese Center for Disease Control and Prevention has posted a Q&A documentrelated to this situation. It is available athttp://www.chinacdc.cn/en/ne/201303/t20130331_79282.html.The European Centre for Disease Prevention and Control is publishing their latestupdates and risk assessments on influenza A(H7N9) at “Avian influenza in humans.”This page is available athttp://ecdc.europa.eu/en/healthtopics/avian_influenza/Pages/index.aspx.15

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