Apr 20, 2007 (CIDRAP News) – In the wake of a clinical conference, the World Health Organization (WHO) has modified its recommendations on treatment for patients with H5N1 avian influenza by strengthening a warning against corticosteroids and suggesting the option of using higher doses of osteltamivir in some cases, among other advice.

The meeting, held in Antalya, Turkey, Mar 19 to 21, brought together clinicians, virologists, epidemiologists, and others to share their observations and unpublished data on treatment of H5N1 patients, the WHO said in a statement yesterday.

Since the last clinical conference of its kind was held in Hanoi in May 2005, eight more countries have reported human H5N1 infections, the WHO said. The current WHO global avian flu count is 291 cases with 172 deaths in 12 countries, from Indonesia to Egypt and Nigeria. The disease is fatal in humans about 60% of the time.

In previous treatment advice in May 2006, the WHO warned against routine use of corticosteroids except in the context of randomized trials. In its new statement, the agency said corticosteroids have not been effective, "and prolonged or high-dose corticosteroids can result in serious adverse effects in H5N1 patients, including opportunistic infections. Corticosteroids should not be used routinely, except for persistent septic shock with suspected adrenal insufficiency."

In line with the meeting discussions, the WHO offered these additional conclusions about treating H5N1 patients:

• Early treatment with oseltamivir (Tamiflu), recommended as the first-line medication for H5N1 infections, is useful for reducing mortality, and treatment is warranted even when the drug is started late, because evidence suggests prolonged virus replication.
• Modified regimens of oseltamivir treatment, including two-fold higher dosage, longer duration, and possibly combination therapy with amantadine (in countries where the H5N1 virus is susceptible to the drug), "may be considered on a case-by-case basis," especially in patients who have pneumonia or worsening disease.
• Antibiotic prophylaxis should not be used. However, antibiotics are appropriate for the initial treatment of patients who have pneumonia, using evidence-based guidelines for treating community-acquired pneumonia. When possible, microbiologic studies should guide antibiotic use in H5N1 patients.
• Therapy for H5N1-associated acute respiratory distress syndrome (ARDS) should follow evidence-based guidelines for treating sepsis-associated ARDS and should involve mechanical ventilation with low tidal volume.

The advance release of WHO´s updated clinical guidance comes as researchers from Southeast Asia and the United States are launching a study to determine if doubling the standard dose of oseltamivir will improve its effectiveness against H5N1 influenza or severe seasonal flu. As reported previously, the researchers, part of the Southeast Asia Influenza Clinical Research Network, hope to enroll 400 patients in the study over the next 2 years.

The WHO first mentioned combining oseltamivir with amantadine therapy in its last treatment guideline update in May 2006. It said clinicians should use oseltamivir as first-line treatment but should consider adding one of the older antiviral drugs, amantadine or rimantadine, to the regimen if surveillance suggests local H5N1 strains are susceptible to them.

That recommendation was based on data showing that some strains of H5N1, mostly those from China and Indonesia, were susceptible to the older drugs.

In its statement yesterday, the WHO urged clinicians who modify current antiviral drug regimens to keep detailed records on the treatment and response.

A more detailed report from the meeting will be published later in a scientific journal as updated WHO recommendations on H5N1 clinical management, the WHO said.

See also:

Apr 19 WHO summary

May 2006 WHO guidelines for treatment of H5N1 patients

Mar 29 CIDRAP News article "International network to study high-dose Tamiflu"

May 22, 2006, CIDRAP News article "WHO sees role for older antivirals in some H5N1 cases"