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    Avian Influenza: H5N1

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    Oct.18.2022

    Avian Influenza: H5N1

    Synopsis

    Key Points

    • Avian influenza of H5N1 type is a zoonotic infection with highly pathogenic avian influenza type A virus, subtype H5N1 r1
    • Infection frequently presents with influenzalike symptoms, but it can be asymptomatic, mild, or have an aggressive clinical course with rapid deterioration
    • Real-time reverse transcription polymerase chain reaction testing on a pulmonary aspirate is the only test to definitely confirm diagnosis r2
      • H5N1 will test positive for influenza A by rapid antigen testing
      • Notify the state or local public health laboratory that an upper respiratory specimen or a bronchoalveolar or endotracheal aspirate is being sent for testing
      • If results are positive, the specimen is sent to CDC for confirmation
    • Hospitalization is recommended for patients diagnosed with probable or confirmed infection until clinical stability has been achieved r3
    • Oseltamivir is the recommended therapy, plus supportive care (eg, oxygen, if needed)
    • Complications include pneumonia, acute respiratory distress syndrome, septic shock, multiple organ dysfunction, and death
    • Prognosis is poor; H5N1 infection has more than 50% mortality r4

    Urgent Action

    • Administer supplemental oxygen to all patients in respiratory distress; ventilator support is recommended if condition does not improve with oxygen
    • Monitor blood pressure frequently and institute therapy for septic shock if patient is hypotensive despite adequate fluid resuscitation r5

    Pitfalls

    • Do not wait for confirmatory test results before administering oseltamivir to patients suspected of having H5N1 r6

    Terminology

    Clinical Clarification

    • Avian influenza of H5N1 type is a zoonotic infection caused by highly pathogenic avian influenza type A virus, subtype hemagglutinin 5, neuraminidase 1 r1
    • Highly infectious in birds; sporadic cases in humans have occurred in Africa, Asia, and the Middle East after prolonged and close contact with infected birds r1
    • Human-to-human spread is very rare; however, there is concern that mutation or recombination could result in a novel strain capable of sustained human-to-human transmission with pandemic potential r7
    • Presentation in humans ranges from mild conjunctivitis to severe respiratory illness with multiorgan involvement r8

    Classification

    • CDC case definitions r9
      • Confirmed case
        • Infection confirmed in CDC laboratory or CDC-certified public health laboratory using CDC-approved protocols or an FDA-authorized test that specifically detects H5N1
      • Probable case
        • Influenzalike illness in a patient who meets epidemiologic criteria, and
        • Laboratory test results do not provide a sufficient level of detail to confirm highly pathogenic avian influenza type A H5 virus infection
      • Case under investigation
        • Influenzalike illness in a patient who meets epidemiologic criteria, and
        • Confirmatory test results are unknown or pending
      • CDC epidemiologic criteria r9
        • Persons with recent exposure (within 10 days) to avian influenza A viruses through 1 of the following:
          • Close exposure (within 2 meters) to birds with confirmed avian influenza A virus infection by A(H5), A(H7), or A(H9) viruses
            • Bird exposures can include handling, slaughtering, defeathering, butchering, culling, or preparation of birds for consumption; direct contact with surfaces contaminated with feces or parts from infected birds, or visiting a live poultry market with confirmed bird infections or human infections with avian influenza A virus
          • Close (within 2 meters), unprotected (without use of respiratory and eye protection) exposure to a person who is a confirmed, probable, or symptomatic suspected case of human infection with avian influenza A virus
            • May occur in household or health care facility, for example
          • Unprotected (without use of respiratory and eye protection) exposure to avian influenza A virus in a laboratory
    • CDC clinical criteria r9
      • Signs and symptoms consistent with acute or lower respiratory tract infection or conjunctivitis, or complications of acute respiratory illness without an identified cause
      • Clinical spectrum of infection ranges from mild to severe
        • Mild flulike illness: cough, sore throat, fever or feeling feverish, rhinorrhea, fatigue, myalgia, arthralgia, headache
        • Conjunctivitis: red eye, discharge from eye
        • Moderate to severe illness: shortness of breath or difficulty breathing, altered mental status, seizures
      • Complications can include pneumonia, respiratory failure, acute respiratory distress syndrome, multiorgan failure, meningoencephalitis
    • CDC public health criteria r9
      • Public health authorities, in consultation with CDC, may determine that testing is needed in certain asymptomatic individuals as part of public health investigations

    Diagnosis

    Clinical Presentation

    History

    • Presents with flulike symptoms initially, but may present with more severe lower respiratory illness along with alteration of consciousness and seizures c1c2c3c4
      • Typical symptoms on presentation (occur in most cases) include: r10
        • Fever (typically higher than 38 °C) c5
        • Cough, with or without sputum (may be bloody) c6c7c8c9
        • Dyspnea c10
      • Gastrointestinal symptoms are common early in the course of disease and include: c11
      • Upper respiratory tract symptoms are less common: r10c15
        • Rhinorrhea and sore throat c16c17
      • Myalgia c18
      • Other less common symptoms include:
    • Will have history of recent exposure (within 10 days) to avian influenza A viruses via either contact with infected birds, an infected person, or laboratory exposure
      • Incubation period is typically 7 days or fewer, but frequently is only 2 to 5 days r11

    Physical examination

    • Respiratory signs r12c24
      • Tachypnea c25
      • Bilateral inspiratory crackles r12c26
    • Tachycardia c27
    • Fever
    • Bleeding gums r10c28
    • Conjunctival injection c29
    • Altered mental status c30
    • Active seizures c31

    Causes and Risk Factors

    Causes

    • Infection with avian H5N1 influenza virus c32
      • Virus is endemic among wild bird and poultry populations in Asian countries
      • Human infection occurs via contact with infected birds or poultry r13
      • Rarely, prolonged intimate contact with a severely ill patient has produced human-to-human transmission

    Risk factors and/or associations

    Age
    • 89% of all cases have occurred in those younger than 40 years r14c33
    • 52% of all cases have occurred in those younger than 20 years r14c34
    Sex
    • Increased severity and mortality in females have been attributed to increased female occupational exposure in recent outbreaks r15c35
    Other risk factors/associations
    • Travel to or residing in endemic areas, listed in decreasing order of risk: r14c36
    • Most common risk factor is handling sick or dead poultry during the week before onset of symptoms r11c46c47
      • Most patients acquire the infection from poultry they raise r11c48
    • Less common risk factors r11
      • Slaughtering birds c49
      • Plucking birds' feathers c50
      • Preparing poultry to eat c51
      • Eating raw or undercooked poultry c52

    Diagnostic Procedures

    Primary diagnostic tools

    • Suspect diagnosis in patients with signs and symptoms of an acute or lower respiratory tract infection or conjunctivitis without an identified cause who have recent exposure (within 10 days) to avian influenza A viruses via either contact with infected birds, an infected person, or laboratory exposure r9
    • Confirmation of diagnosis requires testing an appropriately obtained upper or lower respiratory tract specimen for avian influenza A virus
      • CDC recommends testing in persons who meet epidemiologic criteria and either clinical or public health response criteria r9c53
      • Preferred specimen is either a nasopharyngeal swab, a nasal aspirate or wash, or 2 swabs (a nasal or nasopharyngeal swab plus an oropharyngeal swab) combined into 1 viral transport media vial r2
        • In patients with severe lower respiratory tract involvement, also obtain endotracheal aspirate or bronchoalveolar lavage fluid as these specimens have a higher yield for detecting H5N1 r2
      • Collect respiratory specimens as soon as possible after illness onset and follow recommended infection control precautions
    • Notify state or regional health department as soon as possible and send respiratory specimens to state or regional health department for immediate testing r2c54
      • Real-time reverse transcription polymerase chain reaction testing of the aspirate for H5N1 is the only test to definitively confirm diagnosis c55
      • Commercially available influenza tests do not differentiate between seasonal influenza A viruses (circulating among humans) and avian influenza A viruses
      • If results are positive, state health department will undertake public health investigation with animal health partners and notify CDC
    • Obtain chest radiograph for all cases suspected to be caused by H5N1 r16c56
    • Evaluate patients with pneumonia, considering other sources of community-acquired pneumonia as a secondary infection, including: c57c58c59c60
      • Blood cultures
      • Sputum Gram stain and culture c61
      • Pleural fluid testing (if pleural effusion is present) c62
      • Urinary antigen testing

    Laboratory

    • Influenza real-time reverse transcription polymerase chain reaction diagnostic panel r2c63
      • Obtain specimens as soon as possible after illness onset, ideally within 7 days
        • Multiple respiratory specimens from different sites are obtained from the same patient on at least 2 consecutive days, if possible, to increase potential for H5N1 detection
      • Early after illness onset, provide a nasopharyngeal swab, a nasal aspirate or wash, or 2 swabs combined into 1 viral transport media vial (eg, nasopharyngeal and oropharyngeal swabs)
      • If severe lower respiratory involvement is present, obtain test results on bronchoalveolar or endotracheal aspirates
      • Place specimens into sterile viral transport media; immediately refrigerate with gel packs or in refrigerator at 4 °C
        • If specimen is to be examined within 72 hours, keep the specimen at 4 °C (2-8 °C) and ship on refrigerant gel packs
        • If specimen will not be examined for over 72 hours, store frozen at −70 °C or colder and ship on dry ice
      • Identify the H5N1 subtype of influenza, which is diagnostic

    Imaging

    • Chest radiography r16c64
      • Pneumonic infiltrates begin with an interstitial pattern and progress to an interstitial/alveolar pattern in the late stages in most patients
      • Further progression to diffuse bilateral confluent air space opacification can occur rapidly
      • Lower lung fields are involved in most patients
      • Not associated with pleural effusion

    Procedures

    Bronchoalveolar lavage c65
    General explanation
    • Bronchofiberscope is passed through the nose or mouth, down the trachea, and into the lung
    • Lung tissue is visually examined
    • Sterile saline is injected into the lung, then aspirated and collected for analysis
    Indication
    • Patients with significant lower respiratory tract disease and who need for sampling of deep secretions for analysis and identification of the causative microorganism, not adequately provided by an endotracheal aspirate
    • Visual examination of tracheal and alveolar tissue
    Contraindications
    • Patient unable to support ventilation during procedure
    • Hemodynamic instability
    Interpretation of results
    • Real-time reverse transcription polymerase chain reaction detection of H5N1 on bronchial aspirate confirms the diagnosis r2
    Endotracheal aspiration c66
    General explanation
    • A small amount of saline is instilled through an endotracheal tube; fluid is aspirated and examined r17
    • Patients infected with H5N1 are usually already intubated and ventilated for therapeutic purposes
    Indication
    • Patients with lower respiratory tract infection who are intubated r2
    Contraindications
    • Patients who are unstable (eg, recent myocardial infarction, unstable angina) r18
    Interpretation of results
    • Real-time reverse transcription polymerase chain reaction detection of H5N1 in aspirate is confirmatory r2

    Differential Diagnosis

    Most common

    • Bacterial pneumonia c67d1
      • Similar respiratory symptoms and fever that are not as severe as those of H5N1
      • Associated with high WBC cell count on CBC (more than 11,000 WBC/mL); compares with reported tendency toward leukopenia, lymphocytopenia, and thrombocytopenia in patients with H5N1
      • Chest radiography frequently shows lobar consolidation and pleural effusion in bacterial pneumonia
      • Sputum Gram stain and culture are usually diagnostic for bacterial pneumonia
    • Seasonal influenza c68d2
      • Similar symptoms as with H5N1 (eg, fever, myalgia, headache, sore throat, cough, rhinorrhea), although typically milder and occurring in annual outbreaks
      • Patients usually have had no close exposure to poultry or other birds
      • Gastrointestinal symptoms are usually not present
      • Typically positive results on rapid influenza diagnostic tests; differentiate from H5N1 by real-time reverse transcription polymerase chain reaction testing if needed
    • Respiratory syncytial virus c69d3
      • Respiratory symptoms similar to those of influenza, often with wheezing
      • More common in children, but can occur at any age, especially in immunocompromised patients
      • Rapid respiratory syncytial virus antigen testing can differentiate
    • COVID-19 infection r19c70d4
      • Symptoms are similar to those of H5N1 (eg, fever, myalgia, headache, sore throat, cough, dyspnea) and can be difficult to differentiate based on clinical manifestations alone r20
      • May progress to severe illness with respiratory distress and shock; complications such as renal failure and death are more common r20r21
      • Loss of taste or smell is highly suggestive
      • Suggestive laboratory findings include lymphopenia, elevated levels of lactate dehydrogenase, and transaminases
      • Chest imaging result is almost always abnormal, typically demonstrating bilateral infiltrates
      • Real-time reverse transcription polymerase chain reaction testing or antigen testing for SARS-CoV-2 will differentiate
        • A positive test result for COVID-19 does not rule out coinfection when both viruses are circulating

    Least common

    • Avian influenza: H7N9 c71
      • Symptoms and risk factors identical, but no cases reported outside of China
      • Real-time reverse transcription polymerase chain reaction testing for H7N9 will differentiate

    Treatment

    Goals

    • Prevent severe complications and mortality associated with H5N1
    • Prevent the spread of H5N1 to asymptomatic household or family contacts of patients with confirmed or probable cases r22

    Disposition

    Admission criteria

    In many patients, avian influenza has a rapid, aggressive clinical course, and the infection fatality rate is higher than that of seasonal influenza. Hospitalization may be considered even in patients in the initial stages of the disease until clinically stable r3

    Criteria for ICU admission
    • Worsening respiratory symptoms despite oxygen supplementation, especially when endotracheal intubation and ventilatory support are required
    • Hemodynamic instability
    • Evidence of single-organ or multiorgan failure

    Recommendations for specialist referral

    • Consult a critical care specialist if respiratory status is deteriorating despite oxygen supplementation, to prepare for more invasive respiratory support
    • Consult an infectious disease specialist for any patient with suspected, probable, or diagnosed H5N1 infection

    Treatment Options

    Hospitalized patients r3

    • Assess respiratory and hemodynamic status
      • Initiate supplemental oxygen to maintain SaO₂ over 90%
        • Early intervention with invasive positive pressure ventilation is recommended using lung-protective low-pressure and low tidal volume ventilation (to prevent barotrauma)
        • Oxygen for mild hypoxia can be delivered via nasal cannula; oxygen for severe hypoxia requires a face mask to accommodate high flow (eg, 10 L/minute) r3
        • Monitor using pulse oximetry
        • Administer supplemental oxygen to all patients in respiratory distress; ventilator support is recommended if condition does not improve with oxygen
      • Maintain conservative fluid management
    • Provide adequate infection control because of risk of infectious aerosols r23
      • Use particulate respirator (ie, N95, FFP2, or comparable), eye protection, gowns, gloves, airborne precautions, or negative pressure room
    • Initiate antiviral therapy with orally or enterically administered oseltamivir as soon as possible r6
      • Do not wait for confirmatory test results before administering oseltamivir to patients suspected of having H5N1
      • Inhaled zanamivir is not recommended for severely ill patients owing to a lack of substantiating data
      • There are insufficient data regarding efficacy of IV peramivir for hospitalized seasonal influenza patients
      • There is insufficient evidence describing use of baloxavir in H5N1; however, baloxavir does have activity against influenza A viruses and is approved for use in patients with seasonal influenza r24r25
        • The addition of baloxavir to neuraminidase inhibitor treatment did not result in improved clinical outcomes compared with a neuraminidase inhibitor alone in patients with severe seasonal influenza, but the combination reduced duration of infectious viral shedding compared with neuraminidase inhibitor treatment alone r26
      • For patients who cannot tolerate or absorb oral or enterically administered oseltamivir because of suspected or known gastric stasis, malabsorption, or gastrointestinal bleeding, use IV peramivir
      • In patients who develop progressive lower respiratory disease despite treatment with oseltamivir and/or peramivir, consider and investigate for possible viral resistance; in such cases, virus may remain susceptible to zanamivir r6
    • In a patient with suspected or probable H5N1 who presents with pneumonia, guidelines recommend empiric treatment of community-acquired pneumonia for the first few days until sputum and culture results are known r3
      • Typical empiric antibiotics would include a respiratory fluoroquinolone or a combination of a β-lactam plus a macrolide r27
      • Chemoprophylaxis with an antibacterial agent is not indicated in cases where no pneumonia is seen on the chest radiograph and there are no clinical indications of pneumonia r3

    Outpatients

    • For outpatients with severe, progressive, or complicated illness, oseltamivir is recommended r6
    • For outpatients with uncomplicated oseltamivir illness presenting within 2 days of illness onset, oral oseltamivir, inhaled zanamivir, IV peramivir, or oral baloxavir may be used r6

    Drug therapy

    • Antiviral r3c72
      • Neuraminidase inhibitors r3c73
        • Oseltamivir c74
          • Oseltamivir Phosphate Oral suspension; Premature Neonates younger than 38 weeks postmenstrual age: 1 mg/kg/dose PO twice daily for 5 days; consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Oseltamivir Phosphate Oral suspension; Premature Neonates 38 to 40 weeks postmenstrual age: 1.5 mg/kg/dose PO twice daily for 5 days; consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Oseltamivir Phosphate Oral suspension; Premature Neonates older than 40 weeks postmenstrual age and Term Neonates: 3 mg/kg/dose PO twice daily for 5 days; consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Oseltamivir Phosphate Oral suspension; Infants 1 to 8 months: 3 mg/kg/dose PO twice daily for 5 days; consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Oseltamivir Phosphate Oral suspension; Infants 9 to 11 months: 3.5 mg/kg/dose PO twice daily for 5 days; consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Oseltamivir Phosphate Oral suspension; Children weighing 15 kg or less: 30 mg PO twice daily for 5 days; consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Oseltamivir Phosphate Oral suspension; Children weighing 16 to 23 kg: 45 mg PO twice daily for 5 days; consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Oseltamivir Phosphate Oral suspension; Children weighing 24 to 40 kg: 60 mg PO twice daily for 5 days; consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Oseltamivir Phosphate Oral suspension; Children weighing more than 40 kg and Adolescents: 75 mg PO twice daily for 5 days; consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Oseltamivir Phosphate Oral capsule; Adults: 75 mg PO twice daily for 5 days; consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Administer oseltamivir even if more than 48 hours have passed since onset of illness r6
          • Oseltamivir can be administered via orogastric or nasogastric tube in critically ill patients r6
        • Peramivir r6c75
          • Peramivir Solution for injection; Hospitalized children 2 to 12 years who are unable to tolerate or absorb oseltamivir: 12 mg/kg/dose (Max: 600 mg/dose) IV once daily for 5 days as an alternative. Consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Peramivir Solution for injection; Children 2 to 12 years who are outpatients with uncomplicated, mild-to-moderate illness: 12 mg/kg (Max: 600 mg) IV as a single dose within 48 hours of symptom onset.
          • Peramivir Solution for injection; Hospitalized adolescents who are unable to tolerate or absorb oseltamivir: 600 mg IV once daily for 5 days as an alternative. Consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Peramivir Solution for injection; Adolescent outpatients with uncomplicated, mild-to-moderate illness: 600 mg IV as a single dose within 48 hours of symptom onset.
          • Peramivir Solution for injection; Hospitalized adults who are unable to tolerate or absorb oseltamivir: 600 mg IV once daily for 5 days as an alternative. Consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.
          • Peramivir Solution for injection; Adult outpatients with uncomplicated, mild-to-moderate illness: 600 mg IV as a single dose within 48 hours of symptom onset.
        • Zanamivir c76
          • Zanamivir Inhalation powder; Children and Adolescents 7 to 17 years: 10 mg by oral inhalation every 12 hours for 5 days starting within 48 hours of symptom onset.
          • Zanamivir Inhalation powder; Adults: 10 mg by oral inhalation every 12 hours for 5 days starting within 48 hours of symptom onset.
          • Not recommended for patients with underlying airway disease r6
        • Baloxavir
          • Baloxavir Marboxil Oral suspension; Children and Adolescents 12 to 17 years weighing less than 80 kg: 40 mg PO as a single dose given within 48 hours of symptom onset.
          • Baloxavir Marboxil Oral suspension; Children and Adolescents 12 to 17 years weighing 80 kg or more: 80 mg PO as a single dose given within 48 hours of symptom onset.
          • Baloxavir Marboxil Oral tablet; Adults weighing less than 80 kg: 40 mg PO as a single dose given within 48 hours of symptom onset.
          • Baloxavir Marboxil Oral tablet; Adults weighing 80 kg or more: 80 mg PO as a single dose given within 48 hours of symptom onset.

    Nondrug and supportive care

    • Most hospitalized patients require supplemental oxygen owing to compromised respiratory effort and hypoxia r3c77
      • Oxygen for mild hypoxia can be delivered via nasal cannula; oxygen for severe hypoxia requires a face mask to accommodate high flow (eg, 10 L/minute)
      • Monitor using pulse oximetry c78
      • Maintain oxygen saturation over 90%

    Comorbidities c79

    Special populations

    • Pregnant patients are treated with oseltamivir using the same antiviral dosage as nonpregnant patients r28

    Complications and Prognosis

    Complications

    • Complications are generally worse with late presentation of the patient for care
    • Pneumonia c80
      • Most patients with H5N1 infection have radiographic evidence of pneumonia at presentation r3
      • Often leads to acute respiratory distress syndrome and death r3
      • Empiric treatment with antibiotics is indicated using treatment guidelines for community-acquired pneumonia until definitive cause of pneumonia is known; antibiotic chemoprophylaxis is not otherwise recommended in patients without evidence of pneumonia r3
    • Acute respiratory distress syndrome c81
      • Life-threatening inflammatory process in the lungs as a result of pulmonary injury or infection r29
      • Often the precursor to death, acute respiratory distress syndrome has a high mortality rate in this disease r3
      • Do not administer high-dose corticosteroids for prophylaxis of acute respiratory distress syndrome, because they are not effective and increase risk of patients with H5N1 acquiring opportunistic infections r3
    • Septic shock r5c82
      • A subset of sepsis with circulatory and cellular/metabolic dysfunction associated with a higher risk of mortality
      • Monitor blood pressure frequently and institute therapy for septic shock if patient is hypotensive despite adequate fluid resuscitation
    • Multiorgan dysfunction r3c83
      • Frequently the result of septic shock and mainly affecting the lungs, kidneys, and liver
      • Often the precursor to death in patients with H5N1
    • Secondary infection (bacterial and fungal) c84
      • Less common complication; can be cause of significant morbidity and mortality
    • Encephalitis r11c85
      • Rare, but can be precursor to death
      • Unclear if caused by infection with the H5N1 virus, inflammatory response to H5N1, or another infection (eg, secondary bacterial pneumonia)
    • Death c86

    Prognosis

    • Mortality rate over 50% out of confirmed human cases of H5N1 reported to WHO between 2003 and 2021 r4
      • Highest case fatality rate is 76% for people aged 10 to 19 years r14c87
      • Lowest case fatality rate is 40% for people aged older than 50 years r14c88

    Screening and Prevention

    Screening c89

    Prevention

    • For the general population, avoid the following: r30
      • Contact with ill or dead poultry, especially in countries where H5N1 is pandemic c90c91
      • Contact with feces from wild or domestic birds c92
      • Unprotected contact with soil, water, cages, tools, and other fomites that have touched feces and other secretions from wild or domestic birds in countries where H5N1 is pandemic
      • Poultry farms and bird markets in countries where avian influenza has caused disease in birds or people c93
      • Ingestion of or contact with contaminated water (fresh water that may contain feces from infected birds) in countries where H5N1 is endemic c94
    • Individuals exposed to avian influenza A virus
      • Exposed individuals are monitored for 10 days for temperature of 38 °C or higher or any new respiratory symptoms c95
        • Evaluate patients who develop fever or symptoms and test for H5N1
      • Chemoprophylaxis r22c96
        • Initiate oral oseltamivir or inhaled zanamivir chemoprophylaxis, preferably within 48 hours of exposure, if indicated based on risk for infection
          • Asymptomatic contacts of confirmed or probable cases r22
            • Highest-risk exposure: household or close family member contacts with unprotected, prolonged close contact to a confirmed or probable case
              • Recognized risk of transmission
              • Antiviral chemoprophylaxis should be administered
            • Moderate-risk exposure: health care personnel with unprotected close contact with a confirmed or probable case or nonhousehold members with prolonged unprotected close contact with a confirmed or probable case outside of a health care facility
              • Unknown risk of transmission
              • Antiviral chemoprophylaxis could be considered depending on type of exposure and whether the close contact is at higher risk for complications from seasonal influenza
            • Low-risk exposure: people who have had social contact of a short duration with a confirmed or probable case in a nonhospital setting (eg, in a community or workplace environment)
              • Transmission unlikely
              • Chemoprophylaxis is not routinely recommended
          • Persons with unprotected exposure in a laboratory r22
            • Persons with an unprotected exposure in a laboratory setting may have high-risk or moderate-risk exposure; chemoprophylaxis should be evaluated on a case-by-case basis
          • Persons with exposure to birds infected with avian influenza
            • Chemoprophylaxis with influenza antiviral medications can be considered, allowing for the following:
              • Type and duration of exposure
              • Time since exposure
              • Known infection status of the birds to which the person was exposed
              • Whether the exposed person is at higher risk for complications from seasonal influenza
        • Treatment dosage of oral oseltamivir or inhaled zanamivir (twice daily) is recommended instead of typical antiviral chemoprophylaxis regimen r22c97c98
        • Treatment duration is 5 days if there is no ongoing exposure; treat for 10 days if exposure ongoing (eg, in the household)
        • If the close contact patient becomes symptomatic after being treated with oseltamivir chemoprophylaxis for 3 or more days, oseltamivir should be stopped as soon as treatment with inhaled zanamivir (twice daily) or oral baloxavir can be initiated r22
          • Some novel influenza A viruses may rapidly become resistant to oseltamivir but remain zanamivir-susceptible and baloxavir-susceptible
    • H5N1 vaccine r31c99
      • National Pre-pandemic Influenza Vaccine Stockpile contains 4 vaccines against different strains of H5N1
      • Vaccine is not available for commercial use
      • United States maintains this vaccine for use in the event that the virus mutates and becomes pandemic
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