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WHO Urges Rapid Use of Antivirals in H1N1

New Guidelines on H1N1 Influenza Urge Quicker Use of Antivirals

Robert Lowes

November 12, 2009 — Updated treatment guidelines for H1N1 influenza from the World Health Organization (WHO) urge clinicians to administer antiviral medications as soon as possible to patients in at-risk groups with flu symptoms, patients with pneumonia, and those with uncomplicated influenza-like illness that worsens or fails to improve within 72 hours.

The reason for immediate antiviral therapy is that a mild case of H1N1 influenza can morph into a deadly disease such as pneumonia within 24 hours, according to the revised guidelines released Tuesday.

“The virus can take a life within a week,” Nikki Shindo, MD, a medical officer in WHO’s Global Influenza Programme, said during a press conference today. “The week of opportunity is very narrow in regard to the progression of the disease. The medicine needs to be administered before the virus destroys the lungs.”

Patients in at-risk groups who should receive antivirals once they experience flu symptoms include pregnant women, children younger than 2 years, and individuals with chronic illnesses such as respiratory problems, according to Dr. Shindo.

Dr. Shindo said that earlier WHO guidelines focused on treating severe disease stemming from the H1N1 virus. The updated guidelines, she explained, have more to say about preventing severe disease, especially with the use of antiviral medications. Initial guidance about antivirals had been more conservative because WHO “had almost no experience” in regard to their effectiveness and because supplies were limited, said Dr. Shindo. Now, WHO has more data about the safety and usefulness of the medicine, and supplies are more ample.

The updated guidelines state that clinicians should not delay antiviral treatment for patients with suspected H1N1 influenza for the sake of conducting tests to confirm the diagnosis. In addition, a negative result from some rapid influenza diagnostic tests should not justify withholding antiviral therapy because these tests “miss many infections with pandemic H1N1 virus.”

The first-line antiviral for treating the H1N1 virus is oseltamivir (Tamiflu), according to WHO. If oseltamivir is not available, it is not possible to administer it to a particular patient, or if the virus is resistant to oseltamivir, the guidelines recommend that clinicians use zanamivir (Relenza), which is inhaled.

To ensure easier access to treatment, public health authorities should distribute antivirals through general practitioners and not primarily through hospitals, said Dr. Shindo. “Patients should not have to visit the hospital to get antivirals prescribed,” she said. “This should help ensure that individuals get the care they need faster. This will leave hospitals freer to treat the more severe cases.”

Although Dr. Shindo emphasized the need for the earlier use of antivirals, she said that people not in the at-risk groups who are experiencing only mild flu symptoms do not need to take antiviral therapy. Nor should healthy individuals take it as a preventive measure.

WHO Guidelines Do Not Conflict With CDC Directives

The updated WHO guidelines specify watchful waiting for 72 hours for patients who have uncomplicated influenza-like illness and who do not have an underlying medical condition that puts them at risk. Hallmarks of progressive illness that warrant antiviral therapy include:

* Shortness of breath, hypoxia, and fast or labored breathing in children, which would suggest oxygen impairment or cardiopulmonary insufficiency.
* Altered mental status, unconsciousness, drowsiness, and seizures, which suggest central nervous system complications.
* Evidence of sustained virus replication or invasive secondary bacterial infection.
* Severe dehydration, expressed as decreased activity, dizziness, decreased urine output, and lethargy.

By necessity, this recommendation for follow-up requires patient education, Dr. Shindo said. Clinicians should instruct patients who initially present with uncomplicated influenza-like illness to return for another visit if they develop these or other symptoms of progressive illness — or do not get better — within 72 hours from the onset of symptoms, according to WHO.

The Centers for Disease Control and Prevention (CDC) have not issued any guidance on follow-up care for influenza patients that stipulates a 72-hour time frame, but the agency does advise patients who do not improve within a few days that they might have a complication like a secondary infection, said Anthony Fiore, MD, a medical epidemiologist with the CDC’s National Center for Immunization and Respiratory Diseases.

“I do not see the WHO recommendations as being in conflict [with the CDC directives],” Dr. Fiore told Medscape Infectious Diseases. CDC recommendations on administering antiviral medications are revised on average every 4 to 6 weeks, said Dr. Fiore. “We will look at the WHO guidance and the evidence base used to develop the guidance as part of [our] revision.”

The updated treatment guidelines are available on the WHO Web site.

CDC Update

At a CDC press briefing today, Anne Schuchat, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, provided an updated estimate of H1N1 cases using data extrapolated from the CDC’s Emerging Infections Program .

The CDC estimates that during the first 6 months of the pandemic (April through October 17, 2009), a total of 22 million people (range, 14 – 34 million) in the United States became infected with H1N1 influenza. Of these, 98,000 people (range, 63,000 to 153,000) were hospitalized; and 3900 (range, 2500 – 6100) died.

The data are also broken down by age group and highlight that fact that numbers of cases, hospitalizations, and deaths are disproportionately higher in people aged 64 years and younger than in older individuals.

These numbers will be updated every 3 to 4 weeks, she said.

Dr. Schuchat also discussed the effect of H1N1 influenza in patients with diabetes, which afflicts about 19% of adults hospitalized for H1N1. According to Dr. Schuchat, people with diabetes should be vaccinated (with the injectable vaccine not the nasal spray) against H1N1. People with diabetes who also have respiratory illness should receive antiviral therapy, which should be initiated prior to availability of test results. Patients with diabetes should also ensure that they have been vaccinated against pneumococcal infections.

To date, 41.6 million doses of H1N1 vaccine have become available. “This is more than we had before but not as much as we had hoped to have by today,” Dr. Schuchat said. Currently, 94 million doses of seasonal influenza vaccine have been distributed, with 114 million doses total expected by the end of the year.

Emma Hitt, PhD, contributed to this report.