Influenza

WHO Rapid Advice Guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus

May 2006


Summary

Human cases of avian influenza A(H5N1) infection have remained rare and sporadic, but the disease is very severe and the case fatality is high. With the H5N1 virus now confirmed in birds in more than 50 countries, additional sporadic human cases should be anticipated. Using innovative guideline development methods based on the best available evidence, the WHO assembled an international panel of experts in March 2006 to develop rapid advice for the pharmacological management of patients with H5N1 infection. The recommendations are classified as strong or weak and cover several specific patient and exposure groups for the treatment and chemoprophylaxis of H5N1 virus infection. All recommendations are specific to the current pre-pandemic situation and are based on careful consideration of the current evidence about benefits, harms, burdens and cost of interventions. As there are currently no clinical trials in patients with avian influenza H5N1 disease, the overall quality of evidence on which to base judgments is very low.

Recommendations for treatment of patients with confirmed or strongly suspected human infection with the H5N1 virus

Where neuraminidase inhibitors are available :

  • Clinicians should administer oseltamivir treatment (strong recommendation); zanamivir might be used as an alternative (weak recommendation). The quality of evidence if considered on a continuum is lower for the use of zanamivir compared to oseltamivir.
  • Clinicians should not administer amantadine or rimantadine alone as a first-line treatment (strong recommendation).
  • Clinicians might administer a combination of a neuraminidase inhibitor and an M2 inhibitor if local surveillance data show that the H5N1 virus is known or likely to be susceptible (weak recommendation), but this should only be done in the context of prospective data collection.

Where neuraminidase inhibitors are not available:

  • Clinicians might administer amantadine or rimantadine as a first-line treatment if local surveillance data show that the H5N1 virus is known or likely to be susceptible to these drugs (weak recommendation).

Recommendations for chemoprophylaxis
To assist countries in prioritizing the use of antiviral drugs for chemoprophylaxis, particularly where their availability is limited, a three-tier-risk categorization for exposure was developed (see Risk categories).

Where neuraminidase inhibitors are available:

  • In high risk exposure groups , including pregnant women, oseltamivir should be administered as chemoprophylaxis, continuing for 7–10 days after the last exposure (strong recommendation); zanamivir could be used in the same way (strong recommendation) as an alternative.
  • In moderate risk exposure groups, including pregnant women, oseltamivir might be administered as chemoprophylaxis, continuing for 7-10 days after the last exposure (weak recommendation); zanamivir might be used in the same way (weak recommendation).
  • In low risk exposure groups oseltamivir or zanamivir should probably not be administered for chemoprophylaxis (weak recommendation). Pregnant women in the low risk group should not receive oseltamivir or zanamivir for chemoprophylaxis (strong recommendation).
  • Amantadine or rimantadine should not be administered as chemoprophylaxis (strong recommendation).

Where neuraminidase inhibitors are not available:

  • In high or moderate risk exposure groups, amantadine or rimantadine might be administered for chemoprophylaxis if local surveillance data show that the virus is known or likely to be susceptible to these drugs (weak recommendation).
  • In low risk exposure groups, amantadine and rimantadine should not be administered for chemoprophylaxis (weak recommendation) .
  • In pregnant women, amantadine and rimantadine should not be administered for chemoprophylaxis (strong recommendation).
  • In the elderly, people with impaired renal function and individuals receiving neuropsychiatric medication or with neuropsychiatric or seizure disorders, amantadine should not be administered for chemoprophylaxis (strong recommendation).

Recommendations for other treatments:
Routine use of corticosteroids, use of immunoglobulin and interferon, and ribavirin. should not be used outside the context of a randomised trial, but ribavirin particularly should not be used in pregnant women (strong recommendation).

Recommendations for use of antibiotics
It is not possible to make specific recommendations about individual antibiotics because resistance patterns vary widely from country to country. However, the general recommendations that were made are:

  • In patients with severe community-acquired pneumonia regardless of the geographical location, clinicians should follow appropriate clinical practice guidelines (strong recommendation).
  • In patients with confirmed or strongly suspected H5N1 infection who do not need mechanical ventilation and have no other indication for antibiotics, clinicians should not administer prophylactic antibiotics (strong recommendation).
  • In patients with confirmed or strongly suspected H5N1 infection who need mechanical ventilation, clinicians should follow clinical practice guidelines for the prevention or treatment of ventilator-associated or hospital-acquired pneumonia (strong recommendation).

The panel encourages feedback on all aspects of these guidelines, including their applicability in individual countries. Emergence of new influenza A viral subtypes or a change in the pathogenicity or transmissibility of the H5N1 virus, the development of new pharmacological agents or the availability of important clinical research data will lead to an update of these guidelines.

 Risk categories


High risk exposure groups are currently defined as:

  • Household or close family contacts of a strongly suspected or confirmed H5N1 patient, because of potential exposure to a common environmental or poultry source as well as exposure to the index case.

Moderate risk exposure groups are currently defined as:

  • Personnel involved in handling sick animals or decontaminating affected environments (including animal disposal) if personal protective equipment may not have been used properly.
  • Individuals with unprotected and very close direct exposure to sick or dead animals infected with the H5N1 virus or to particular birds that have been directly implicated in human cases.
  • Health care personnel in close contact with strongly suspected or confirmed H5N1 patients, for example during intubation or performing tracheal suctioning, or delivering nebulised drugs, or handling inadequately screened/sealed body fluids without any or with insufficient personal protective equipment. This group also includes laboratory personnel who might have an unprotected exposure to virus-containing samples.

Low risk exposure groups are currently defined as:

  • Health care workers not in close contact (distance greater than 1 meter) with a strongly suspected or confirmed H5N1 patient and having no direct contact with infectious material from that patient.
  • Health care workers who used appropriate personal protective equipment during exposure to H5N1 patients.
  • Personnel involved in culling non-infected or likely non-infected animal populations as a control measure.
  • Personnel involved in handling sick animals or decontaminating affected environments (including animal disposal), who used proper personal protective equipment
Share