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H5N1 Avian Influenza Information for Providers

Clinical Guidelines: Caring for Patients with Suspected or Confirmed Avian H5N1 Influenza

All patients who meet clinical and epidemiologic criteria for avian H5N1 influenza should be reported immediately to the New York City Health Department. The following clinical guidance should be followed:

Admitting Suspect Avian H5N1 Influenza Patients
  • Providers are encouraged to admit patients with suspected avian H5N1 influenza to ensure that infection control precautions are enforced and to enhance the ability to monitor the patient’s condition. Especially in those cases where avian H5N1 influenza is strongly suspected (e.g., known exposure to confirmed human case or infected poultry overseas), the patient should be admitted to the hospital until laboratory test results are available to confirm or rule out H5N1 infection. For highly suspect cases who refuse hospital admission, the New York City Health Department has the authority to detain patients in the hospital suspected of having a communicable disease that may pose an imminent and significant threat to the public health for evaluation, if indicated, while awaiting laboratory test results (Section 11.55 in the NYC Health Code).

  • The decision to hospitalize a suspected avian H5N1 influenza case will be based on the physician’s clinical evaluation and assessment of epidemiologic risk factors, on whether adequate precautions can be taken at home to prevent the potential spread of infection, and on whether the patient will be readily available for follow up. (NOTE: Suspect cases occurring among tourists staying at a hotel or in persons living in congregate settings may need to be hospitalized while awaiting laboratory test results.)

  • Despite the current low risk of person-to-person transmission, patients not admitted should be separated from other household members as much as possible. All household members should carefully follow recommendations for hand hygiene, and tissues used by the ill patient should be placed in a plastic bag and disposed with other household waste. Although no studies have assessed the use of masks at home to decrease the spread of infection, use of surgical or procedure masks by the patient and/or caregiver during interactions may be of benefit. Separation of eating and drinking utensils for use by a patient with influenza is not necessary, as long as they are washed with warm water and soap.

Infection Control Measures

Diagnostic Testing
  •  Obtain clinical specimens for avian H5N1 influenza diagnostic testing. Complete the specimen submission form and INCLUDE the form with the specimens. The New York City Health Department courier will pick up the specimens and transport them to appropriate public health reference laboratories for testing. Do not send specimens for viral culture to a hospital or commercial laboratory; for safety reasons, avian H5N1 influenza may only be cultured in Basic Safety Level 3+ laboratory facilities. DOHMH personnel will maintain contact with the patient’s providers to ensure timely relaying of testing results.

  • Evaluate alternative diagnoses. An alternative diagnosis should be based on laboratory tests with high positive-predictive value (e.g., blood culture, PCR, Legionella urinary antigen, pleural fluid culture, transthoracic aspirate culture, etc.). If an alternate etiology is identified, the possibility of co-infection with an avian H5N1 influenza virus may still need to be considered if there is a strong epidemiologic link with possible exposure to an infected human or birds overseas.

Treatment
  • Initiate antiviral treatment with oseltamivir (Tamiflu) or zanamivir (Relenza) – the neuraminidase inhibitors - as soon as possible, even if laboratory results are not yet available (see Table below for dosing regimens.) Oseltamivir is available both in pill and suspension form, and zanamivir is available as an inhaled powder. The neuraminidase inhibitors are preferred because the majority of avian H5N1 influenza A viruses currently affecting humans are resistant to amantadine and rimantadine, and resistance to adamantanes typically develops rapidly when they are used for treatment of influenza. Clinical trials have shown that neuraminidase inhibitors can decrease the illness duration due to seasonal influenza by several days when they are initiated within 48 hours of illness onset. The clinical effectiveness of antiviral drugs for treatment of avian H5N1 influenza is unknown, but it is likely that the earlier treatment is initiated, the greater the likelihood of benefit. Viral isolates from any case of avian H5N1 influenza will be tested by CDC for resistance to the currently licensed antiviral medications. Oseltamivir is available as an oral suspension for use in children. However, none of the available influenza antivirals is currently FDA-approved for use among children aged <1 year. In particular, the safety and efficacy of oseltamivir have not been studied in children aged <1 year for either treatment or prophylaxis of influenza. The decision by an individual physician to treat children aged <1 year in an emergency setting with an antiviral medication on an off-label basis must be made on a case-by-case basis, with full consideration of the potential risks and benefits.

Contact Tracing
  • Though human-to-human transmission of avian H5N1 influenza has occurred only very rarely, DOHMH personnel will assist providers in identifying and monitoring close contacts of suspected or confirmed avian H5N1 influenza patients. Such contacts might include household and social contacts, family members, workplace or school contacts, and/or healthcare providers who had unprotected close contact (i.e., did not use droplet or standard precautions) starting 24 hours prior to the patient’s symptom onset.

  •  Asymptomatic contacts should be asked to take their temperature at least twice daily. In conjunction with the New York Cith Health Department, asymptomatic contacts should be monitored by telephone or home visit daily for 10 days after their last contact with the suspected case-patient to assess for development of symptoms consistent with avian H5N1 influenza. Asymptomatic contacts should not be given antiviral chemoprophylaxis. Quarantine of asymptomatic contacts at home or in another facility is not considered necessary at the present time based on the epidemiologic characteristics of the current avian H5N1 influenza outbreak in Asia and Europe.

  •  Symptomatic contacts of suspected avian H5N1 influenza patients should seek medical attention immediately when symptoms develop and should notify their healthcare provider of recent contact with a suspected avian H5N1 influenza case. The DOHMH should be immediately notified of any contact who develops fever and respiratory symptoms suggestive of avian H5N1 influenza infection; recommendations on whether empiric antiviral treatment is indicated for symptomatic contacts will be made on a case-by-case basis.

Patients Testing Positive for Avian H5N1 Influenza:
  • Patients with laboratory-confirmed avian H5N1 influenza should be isolated and treated with a neuraminidase inhibitor.

  • Healthcare personnel should use standard and droplet infection control precautions; airborne precautions should be used during procedures that may generate aerosols (e.g., bronchoscopy or intubation).

  • Avian H5N1 influenza patients should be isolated from patients with seasonal influenza, since such measures may decrease the risk of co-infection and viral genetic reassortment.

  • For patients suspected to have secondary bacterial infections (e.g., pneumonia due to pneumococci or staphylococci, including methicillin-resistant strains), appropriate antibacterial therapy should be employed. Supportive measures such as intravenous fluids, parenteral feeding, and intubation with mechanical ventilation should be employed as medically indicated.

  • There are currently no data to suggest that corticosteroids or other disease modifying agents (e.g., anti-tumor necrosis factor agents) are effective in the treatment of avian H5N1 influenza.

Table. Recommended Daily Dosage of Antivirals for Treatment and Prophylaxis

(Adapted from Prevention and Control of Influenza Recommendations of the Advisory Committee on Immunization Practices [ACIP], July 2005.)

 Age Groups (years)
Antiviral Agent1-67-910-1213-64>65
Amantadinea
Treatment, influenza A (duration 5 days)5mg/kg body weight/day up to 150 mg in two divided dosesb5mg/kg body weight/day up to 150 mg in two divided dosesb100 mg twice dailyc100 mg twice dailyc<100 mg/day
Prophylaxis, influenza A5mg/kg body weight /day up to 150 mg in two divided doses b5mg/kg body weight /day up to 150 mg in two divided doses b100 mg twice dailyc100 mg twice dailyc<100 mg/day
Rimantadined
Treatment,e influenza A (duration 5 days)NAfNANA100 mg twice dailyc, g100 mg/day
Prophylaxis, influenza A5m/kg body weight /day up to 150 mg in two divided dosesb5m/kg body weight /day up to 150 mg in two divided dosesb100 mg twice dailyc100 mg twice dailyh100 mg/day
Zanamiviri, j
Treatment, influenza A and B (duration 5 days)NA10 mg twice daily10 mg twice daily10 mg twice daily10 mg twice daily
Oseltamivir
Treatment,k influenza A and B (duration 5 days)dose varies by child's weightldose varies by child's weightldose varies by child's weightl75 mg twice daily75 mg twice daily
Prophylaxis, influenza A and BNANANA75 mg/day75 mg/day

Notes

NOTE: Amantadine manufacturers include Endo Pharmaceuticals (Symmetrel (R)-tablet and syrup) and Geneva Pharms Tech (Amantadine HCL-capsule); USL Pharma (Amantadine HCL-capsule and tablet); and Alpharma, Carolina Medical, Copley Pharmaceutical, HiTech Pharma, Mikart, Morton Grove, and Pharmaceutical Associates (Amantadine HCL-syrup), and Sandoz. Rimantadine is manufactured by Forest Laboratories (Flumadine (R)-tablet and syrup); Corepharma , Impax Labs (Rimantadine HCL-tablet), and Amide Pharmaceuticals (Rimantadine HCL-tablet). Zanamivir is manufactured by GlaxoSmithKline (Relenza (R)-inhaled powder). Oseltamivir is manufactured by Roche Pharmaceuticals (Tamiflu (R)-tablet). Information based on data published by the U.S. Food and Drug Administration at www.fda.gov, accessed 3/30/2005.

  • a The drug package insert should be consulted for dosage recommendations for administering amantadine to persons with creatinine clearance <50 ml/min/1.73m2.

  • b 5 mg/kg body weight of amantadine or rimantadine syrup = 1 tsp/2.2 lbs.

  • c Children aged >10 years who weigh <40 kg should be administered amantadine or rimantadine at a dosage of 5 mg/kg body weight /day.

  • d A reduction in dosage to 100 mg/day of rimantadine is recommended for persons who have severe hepatic dysfunction or those with creatinine clearance <10 ml/min. Other persons with less severe hepatic or renal dysfunction taking 100 mg/day of rimantadine should be observed closely, and the dosage should be reduced or the drug discontinued, if necessary.

  • e Approved by FDA only for treatment among adults.

  • f Not applicable.

  • g Rimantadine is approved by FDA for treatment among adults. However, certain experts in the management of influenza consider it appropriate for treatment among children. (See American Academy of Pediatrics, 2003 Red Book.)

  • h Older nursing home residents should be administered only 100 mg/day of rimantadine. A reduction in dosage to 100 mg/day should be considered for all persons aged >65 years if they experience possible side effects when taking 200 mg/day.

  • i Zanamivir administered via inhalation using a plastic device included in the medication package. Patients will benefit from instruction and demonstration of the correct use of the device.

  • j Zanamivir is not approved for prophylaxis.

  • k A reduction in the dose of oseltamivir is recommended for persons with creatinine clearance <30 ml/min.

  • l The dose recommendation for children who weigh <15 kg is 30 mg twice a day. For children who weigh >15 to 23 kg, the dose is 45 mg twice a day. For children who weigh >23 to 40 kg, the dose is 60 mg twice a day. And for children who weigh >40 kg, the dose is 75 mg twice a day.