While we’ve not seen any new cases of H7N9 in China since August, concerns remain that this virus is still circulating in the wild, and that it could reappear this fall or winter in humans. Given the lab studies over the summer which suggest this virus – more than any other avian flu virus we’ve seen – shows signs of adaptation to mammals (see Science: H7N9 Transmissibility Study In Ferrets), worries over its potential spread beyond China has prompted the CDC to issue repeated guidance documents.
Late yesterday (Sept. 30th), two new guidance documents were posted, both dealing with antiviral medications and infection with, or exposure to, the H7N9 virus.
We’ll take them one at a time. First, in this blog, we’ll look at antiviral treatment. I’ll post a second blog on chemoprophylaxis later this afternoon.
Due to their length I’ll only post excerpts. You’ll want to follow the links to read them in their entirety.
Interim Guidance on the Use of Antiviral Agents for Treatment of Human Infections with Avian Influenza A (H7N9) Virus - Monday, September 30, 2013 8:46:00 PM
This document replaces “Interim Guidance on the Use of Antiviral Agents for Treatment of Human Infections with Avian Influenza A (H7N9) Virus” posted on April 18, 2013. Since that date, a Health Advisory with updated recommendations for testing and updated case definitions for H7N9 virus infection were released to reflect current epidemiology of H7N9 cases and risk assessment for infection. This guidance on antiviral treatment has been updated to be consistent with current CDC and World Health Organization recommendations, and provides updated recommendations for antiviral treatment of confirmed cases and probable cases of human infection with avian influenza A (H7N9), as well as cases under investigation for human infection with avian influenza A (H7N9) virus in the United States.
The previous guidance recommended antiviral treatment for all confirmed cases, probable cases, and cases of H7N9 under investigation.The new guidance continues to recommend treatment for all hospitalized H7N9 cases, and for confirmed and probable outpatient H7N9 cases. The primary change in the new guidance is that outpatient cases under investigation who have had recent close contact with a confirmed H7N9 case should receive antiviral treatment, whereas outpatients meeting only the travel exposure criteria for a case under investigation are not recommended to receive antiviral treatment (see Interim Guidance on Case Definitions to be Used for Novel Influenza A (H7N9) Case Investigations in the United States). For guidance on investigation of close contacts of confirmed or probable cases, see new Interim Guidance on the Use of Antiviral Medications for Chemoprophylaxis of Close Contacts of Persons with Avian Influenza A (H7N9) Virus Infection).
- Initiation of antiviral treatment with a neuraminidase inhibitor is recommended as early as possible for hospitalized patients who are confirmed cases, probable cases, or H7N9 cases under investigation, even if more than 48 hours has elapsed since illness onset.
- For hospitalized patients and patients with severe or complicated illness, treatment with oral or enterically administered oseltamivir is recommended. Inhaled zanamivir is not recommended because of the lack of data for use in patients with severe influenza disease.
- Laboratory testing and initiation of antiviral treatment should occur simultaneously; treatment should not be delayed while waiting for laboratory testing results. (For information regarding collection and laboratory testing, please see Interim Guidance for Specimen Collection, Processing, and Testing for Patients Who May Be Infected with Avian Influenza A (H7N9) Virus.)
- The recommended treatment course for uncomplicated influenza is two doses per day of a neuraminidase inhibitor medication for 5 days; however, the optimal duration and dose are uncertain for severe or complicated influenza. Pending further data, longer courses of treatment (e.g., 10 days of treatment) should be considered for severely ill hospitalized H7N9 patients.
- Clinical judgment and virologic testing of lower respiratory tract specimens by rRT-PCR should guide decisions to consider treatment regimens longer than 5 days for patients with severe and prolonged illness, until clearance of viral shedding. For patients with lower respiratory tract disease, lower respiratory tract specimens, such as bronchoalveolar lavage or endotracheal aspirate, are preferred; an oropharyngeal (throat) swab may be collected if lower respiratory specimens are not available.
- Longer treatment regimens might be necessary in immunosuppressed persons who may have prolonged viral replication and also are at risk of developing antiviral-resistant virus.
- A higher dose of oseltamivir has been recommended by some experts (e.g., 150 mg twice daily in adults with normal renal function) for treatment of influenza in immunocompromised patients and in severely ill hospitalized patients, although it is unknown if this provides clinical benefit [38-40].
- Although oral or enterically delivered oseltamivir is well absorbed in critically ill influenza patients [41-45], for patients who cannot tolerate or absorb oral oseltamivir because of suspected or known gastric stasis, malabsorption, or gastrointestinal bleeding, the use of investigational intravenous (IV) zanamivir should be considered. IV zanamivir is an investigational parenterally administered neuraminidase inhibitor product available by enrollment in a clinical trial or compassionate use under an emergency investigational new drug (EIND) request to the manufacturer. An IV zanamivir compassionate use request may be made by contacting the GSK Clinical Support Help Desk via email (gskclinicalsupportHD@gsk.com) or by calling 1-877-626-8019 or 1-866-341-9160. The GSK Clinical Support Help Desk will provide information and instructions on obtaining IV zanamivir, assess eligibility for clinical trials, and provide the EIND form that needs to be completed to obtain FDA approval of release of the drug.
- It is possible that some H7N9 viruses may rapidly become oseltamivir-resistant and remain zanamivir-susceptible . If a hospitalized patient treated with oseltamivir manifests progressive lower respiratory symptoms, resistant virus should be considered, and, after consultation with the CDC Influenza Division, investigation for antiviral resistance should be performed and oseltamivir should be stopped when IV zanamivir can be initiated.
Uncomplicated Illness in Outpatients
- Initiation of antiviral treatment with a neuraminidase inhibitor is recommended as early as possible for outpatients who are confirmed cases, probable cases, or cases under investigation based on exposure criteria consisting of contact with a confirmed human H7N9 case. Treatment is not currently recommended for outpatients whose exposure criteria consists only of travel to an area with H7N9 cases (see Interim Guidance on Case Definitions to be Used for Novel Influenza A (H7N9) Case Investigations in the United States).
- When warranted, antiviral treatment should be initiated as early as possible, even if more than 48 hours has elapsed since illness onset. For H7N9, treatment is recommended even for otherwise healthy persons, but is especially important for those at higher risk of influenza complications: this includes children <5 years, with highest risk for those aged <2 years old, adults aged >65 years, pregnant women, and persons with certain underlying medical conditions. Please see link for complete list of people considered to be at higher risk for influenza complications at Influenza Antiviral Medications: Summary for Clinicians.
- For outpatients with uncomplicated disease in whom fever is absent and symptoms are nearly resolved, decisions to initiate antiviral treatment should be based on clinical judgment. Persons who are not treated with antiviral medications should be monitored for progression of illness.
- Recommended duration of treatment for uncomplicated illness is 5 days.
- Inhaled zanamivir is not recommended for persons with underlying airway disease (e.g., asthma or chronic obstructive pulmonary disease).
Of note, investigational intravenous (IV) zanamivir is mentioned as a potential IV treatment option - but not peramivir - which received a temporary EUA (Emergency Use Authorization) during the 2009 H1N1 pandemic. Approved for use in Japan and Korea, Peramivir’s U.S. Phase III trial was halted in November of 2012 for `futility’, and its future remains uncertain in the United States.