In June 2006, a 31-year-old male patient with highly pathogenic avian influenza (HPAI) H5N1 virus infection was treated with convalescent plasma that was obtained from a patient who had recovered from HPAI H5N1 illness earlier that year. HPAI H5N1 viral load from respiratory specimens decreased after 3 doses of convalescent plasma, with undetectable levels within 32 hours. Two other HPAI H5N1 patients who received convalescent plasma from an HPAI H5N1 case or an H5N1 vaccine recipient have been reported. One systematic review on the effectiveness of convalescent plasma and hyperimmune immunoglobulin in the treatment of severe acute respiratory infections of viral aetiology suggested that such treatment is safe and may reduce mortality. Convalescent plasma therapy is experimental and not yet approved for clinical use.
Intravenous neuraminidase inhibitors
Parenteral formulations of neuraminidase inhibitors have been developed and include intravenous peramivir and intravenous forms of oseltamivir and zanamivir, but they are not licensed or available in most countries. Intravenous peramivir is currently approved in the US and Europe for the treatment of acute uncomplicated influenza in patients 2 years and older who have been symptomatic for no more than two days. Intravenous zanamivir is currently available on a compassionate use basis through investigational new drug (IND) application. The WHO recommends that treatment with intravenous neuraminidase inhibitors should be used in accordance with relevant emergency-use provisions. Intravenous neuraminidase inhibitors are not recommended for use outside of the context of clinical trials.
A new inhaled long-acting neuraminidase inhibitor that was approved in Japan for use against human influenza. It is chemically similar to zanamivir and is converted into its active form in the lungs where higher concentrations of drug persist, permitting treatment of seasonal influenza with a single drug dose. Little is known about the clinical efficacy of laninamivir against HPAI H5N1, and it is not currently recommended for this purpose.
Although not licensed for the treatment of influenza in most countries, it has been demonstrated to increase efficacy with oseltamivir against some HPAI H5N1 viruses in mouse models. However, studies of SARS patients treated with ribavirin have found strong associations between high-dose therapy and progressive haemolytic anaemia. A World Health Organization (WHO) panel concluded that there is insufficient data on either its efficacy or safety to recommend its use for the treatment of influenza.
The WHO recommends against the use of corticosteroids in the management of HPAI H5N1 disease in humans. In seasonal influenza virus infection, studies have demonstrated that corticosteroid use is associated with persistent viral replication 7 days after symptom onset. One study reported that early use of glucocorticoids is a risk factor for critical illness and death with 2009 H1N1 virus infection. Corticosteroids should be used, though, when indicated for other reasons (e.g., asthma exacerbation, adrenal insufficiency, preterm labour).
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