March 19, 2014
H1N1 Death Risk Dramatically Lowered If Antivirals Are Administered Within Two Days Of Symptoms
Lawrence LeBlond for redOrbit.com - Your Universe Online
Tamiflu treatments have been somewhat controversial over the past few years, with some evidence showing the H7N9 bird flu gaining resistance to the drug and others questioning the effectiveness of the antiviral medication.
However, according to a large meta-analytical study, it has been found that adults hospitalized with H1N1 during the 2009-2010 influenza pandemic were 25 percent less likely to die from the disease if they were administered an antiviral dose of neuraminidase inhibitors (NAIs), which includes Tamiflu. The findings also indicate that treatment within two days of onset of flu symptoms halved the risk of death compared to later treatment or no treatment at all.
The study, published in The Lancet Respiratory Medicine journal, involved more than 29,000 patients from 38 countries.
"Many governments have stockpiles of Tamiflu that are close to expiry. But until now, they had no adequate data to assist them in deciding if lives were saved in 2009-2010 or not, and whether they should replenish or not," explains lead author Professor Jonathan Nguyen-Van-Tam, from the University of Nottingham in the UK.
"The situation is made more complex by the fact that when an influenza pandemic occurs, even with the best will in the world, vaccine arrives six months too late and its public health benefit is therefore moderate at best,” he said.
Nguyen-Van-Tam, working with colleagues from the Post-pandemic Review of anti-Influenza Drug Effectiveness (PRIDE) research consortium, assessed the effects of NAI treatments on death in patients hospitalized with confirmed infection between January 2, 2009 and March 14, 2011. The team utilized a statistical model to compensate for the effects of treatment propensity and other confounding factors such as treatment with corticosteroids and antibiotics.
An analysis of the data from 78 studies involving patients of all ages revealed to the team that NAI treatment reduced the risk of death by 19 percent when given at any time. However, to maximize the rate of survival, NAIs should be given within two days of symptoms developing. For each day that antiviral treatment was delayed after two days from date of onset, a 20-percent-per-day increase in the risk of death was observed when compared to treatment that started within two days.
The team found similar effects in the treatment of patients who were pregnant and adult patients who were in intensive care with more severe symptoms. However, there was no significant reduction in death risk in young children who were administered NAIs at any time.
"Since placebo-controlled trials of NAIs are not ethically feasible during a pandemic, the evidence we have assembled is likely to be the best that is available,” said Nyugen-Van-Tam in a statement.
“Our data suggest that in line with US Centers for Disease Control and Prevention recommendations, treatment guidance policies should emphasise that NAI treatment should be started as soon as possible for any hospitalised adult who presents with influenza that is suspected or confirmed. Since so many patients with severe influenza are not admitted to hospital within 48 hours of symptom onset, the same applies to adults in the community who are appreciably unwell with influenza like illness or who have underlying risk conditions. If clinical suspicion is high, one should not wait for laboratory confirmation before starting treatment,” he concluded.
Commenting on the paper, Alicia Fry from the CDC said, “As expected, early treatment seems to be optimal, and treatment shouldn't be delayed by even 1 day to wait for diagnostic test results; however, if the patient presents for care more than 2 days after illness onset, treatment might still have some benefit, especially if they are severely ill.”
“Although additional evidence for the benefits of NAI treatment in children admitted to hospital, and how to optimise treatment, are needed, in the absence of any other influenza-specific treatment, the potential benefit from NAI treatment for severely ill children is substantial and outweighs any potential risk associated with treatment," she added.
"Continuing efforts to identify other anti-influenza treatment options, especially those with different virus targets or mechanisms of action, might improve our ability to care for severely ill patients with influenza and reduce the risk of mortality further," noted Fry in the comment.