TREATMENT AND VACCINATION FOR H5N1 VIRUS IN HUMANS

Recommendations from management aspects

The H5N1 virus that was found to be major cause of human illness and death in Asia is resistant to amantadine and rimantadine, two antiviral medications commonly used for influenza. Two other antiviral medications, oseltamavir and zanamavir, would probably work to treat influenza caused by H5N1 virus, but additional studies still need to be done to demonstrate their safety and effectiveness.Treatment modalities recommended for the clinical management of human H5N1 virus infection is shown in table.

When there is evidence for sustained human-to-human transmission of H5N1 or another novel avian influenza virus emerges, strict recommendations need to be developed. Whenever feasible, sequential clinical data collection and virological sampling (for analysis at WHO-designated laboratories) should be performed during treatment or should apparent failures of chemoprophylaxis occur. Self-medication in the absence of appropriate clinical or public health advice is discouraged. When considering chemoprophylaxis for H5N1 infection, priority should be given to standard infection control practices. This includes protection of health care workers and individuals involved in eradication of animals infected with H5N1 virus as well as household contacts of H5N1 patients.

For treatment of patients with confirmed or strongly suspected human infection with the H5N1 virus, where neuraminidase inhibitors are available for therapy:

Clinicians should administer oseltamivir treatment (strong recommendation); zanamivir might be used as an alternative (weak recommendation).
In these patients, 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.

For treatment of patients with confirmed or strongly suspected H5N1 infection, where neuraminidase inhibitors are not available for therapy:

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).
In general, decisions to initiate antiviral chemoprophylaxis should be guided by the risk stratification described below. Stratification is based on observational data for reported cases of human H5N1 infection and on high quality data from studies of seasonal influenza.

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 metre) 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.

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).

We recommend that countries develop their own guidelines for the assessment of human patients in whom there is a suspicion of influenza A (H5N1) infection. These should include the criteria required to initiate treatment pending confirmatory laboratory testing. Such guidelines will reflect geographical location with respect to recent outbreaks of avian influenza H5N1 in birds and the locally available resources.