World Health Organization Updates Guidelines for Avian Influenza Virus Management

August 28, 2007 — Oseltamivir remains the primary recommended antiviral treatment for management of avian Influenza A(H5N1) virus infection, according to guidelines updated by the World Health Organization (WHO) on August 15. The guidelines are available on the WHO Web site at: http://www.who.int/csr/disease/avian_influenza/guidelines/clinicalmanage07/en/index.html.
"Experiences clearly show that to reduce mortality, patients should receive treatment with oseltamivir as early as possible, but treatment remains effective even when patients present late," John Oxford, from St. Bartholomew's and the Royal London Hospital, United Kingdom, says in a news release. "H5N1 has proven to be an extremely virulent virus in humans, and in some countries, we have seen the need to use higher and longer doses of oseltamivir to gain maximum benefit."
Beginning in late 2003, widespread infection among poultry and birds with H5N1 in several continents has increased the risk for human exposure to the virus. As of August 16, 2007, the H5N1 strain has infected 321 humans and caused 194 deaths worldwide, with a cumulative case-fatality rate of about 60%. Respiratory failure with acute respiratory distress syndrome (ARDS) is the major complication in hospitalized patients, often with rapid progression to multiorgan failure. To date, there has been no standardized approach for clinical management.
The current guidelines, which replace the 2004 WHO interim guidelines on clinical management of H5N1 infection and update recommendations on pharmacologic management published by WHO in June 2006, review pharmacologic and supportive therapies that are frequently used and offer advice on case management in humans.
The evidence base for the updated guidelines includes review of the literature and reports on cases of H5N1 presented at the first WHO Consultation on Human H5N1 Infections held in Hanoi, Vietnam, in May 2005, and at the Second WHO Consultation on Clinical Aspects of Human Infection with Avian Influenza (H5N1) Virus held in Antalya, Turkey, in March 2007.
At the second WHO consultation, a working group of experts in critical care medicine, pulmonary medicine, infectious diseases, pediatrics, and public health, as well as clinicians directly involved in treating patients infected with A(H5N1), met to develop recommendations and establish standards for clinical management of A(H5N1) infections in humans.
Because of limited data available from human infections with A(H5N1), other evidence was considered from human seasonal influenza, pertinent animal models, severe acute respiratory syndrome (SARS) and other respiratory virus infections, and ARDS from other causes.
Specific clinical recommendations for management of A(H5N1) virus infection are as follows:
To improve understanding of the disease and identify appropriate treatment, care for H5N1 infections in humans should be standardized, and clinical and treatment information should be shared promptly.
Oseltamivir is still the first-line recommendation for antiviral therapy. In early stages of H5N1 virus infection, oseltamivir reduces mortality. Oseltamivir is also indicated when the patient presents for clinical care at later stages of the disease because the A(H5N1) virus continues to replicate for a prolonged period. Oseltamivir is the only neuraminidase inhibitor previously used in clinical management of A(H5N1), and it is the only antiviral agent strongly recommended by the WHO for treatment of patients infected with the A(H5N1) virus.
Especially in patients with pneumonia or progressive disease, modified regimens incorporating treatment with oseltamivir may be considered on a case-by-case basis. These may include a 2-fold higher dosage; longer duration of treatment; and, in countries where A(H5N1) viruses are likely to be susceptible to adamantanes, possibly combination therapy with amantadine or rimantadine. Prospective data collection should continue during use of these modified regimens.
Although corticosteroids should not be used routinely, they may be considered in cases of septic shock associated with suspected adrenal insufficiency mandating use of vasopressors. However, prolonged or high-dose corticosteroids can lead to opportunistic infection or other serious adverse events in patients infected with the A(H5N1) virus.
Antibiotic chemoprophylaxis should not be given routinely except when pneumonia is present. In these cases, published evidence-based guidelines should initially be followed for antibiotic therapy of community-acquired pneumonia. Microbiologic testing, when available, should determine the best choice of antibiotics for suspected bacterial coinfection.
Whenever possible, oxygen saturation should be monitored routinely with pulse oximetry and arterial blood gases at presentation and during subsequent care. Hypoxemia should be corrected with supplemental oxygen.
Treatment of A(H5N1) virus-associated ARDS should follow published evidence-based guidelines for sepsis-associated ARDS, and it should include strategies of mechanical ventilation for lung protection.
Inhaled zanamivir has not been studied in H5N1 infection in humans. However, serious lower respiratory tract or extrapulmonary disease may impede adequate delivery of inhaled zanamivir.
"Standardization of clinical care and antiviral management is fundamental to improve understanding of the disease course and to identify the appropriate therapy," the authors of the guidelines conclude. "Developing recommendations based solely on clinical reports from humans infected with influenza A(H5N1) virus is problematic due to insufficient data currently in the public domain, and the inconsistency of data collection from A(H5N1) virus-infected individuals. Collaborative sharing of clinical and treatment data from affected patients in different regions and countries is essential to improve understanding of this disease and to refine optimal case management."
World Health Organization. Published online August 23, 2007.
http://www.who.int/csr/disease/avian_influenza/guidelines/clinicalmanage07/en/index.html.