Research published this week in a leading medical journal says that based on current evidence, which is limited and not easily generalized to children in the current swine flu epidemic, the antivirals oseltamivir (Tamiflu) and zanamivir (Relenza) are unlikely to prevent complications in children infected with swine flu.
The study was led by Dr Matthew Thompson, senior clinical scientist at the University of Oxford, UK, and appears online in the 10 August issue of the BMJ.
Children are a high risk group during seasonal flu epidemics, which typically affect 40 per cent of pre-schoolers and 30 per cent of school age children, who are also the main route of transmission into households, said the researchers.
They went on to explain that the current control strategy for treating patients who get the flu and preventing its spread includes use of antivirals because vaccination coverage is often low and there is not enough time to make vaccine and get it to everyone who needs it because it's a continual race against emerging strains.
The last time this strategy was examined was in 2005 which is why they decided to do a new review and re-assess the benefits and harms of antivirals.
For this review Thompson and colleagues pooled and re-analyzed data from randomized controlled trials of the neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) in treatment of children with seasonal influenza who were treated at home (ie not hospitalized).
They found that the antivirals provided a small benefit by shortening the duration of illness by a day and a half, and they reduced transmission in households, but they had little effect on asthma flare ups, increased ear infections and the likelihood of children needing antibiotics. Tamiflu also carries an increased risk of vomiting.
The effects of these drugs on the incidence of serious complication and the current A/H1N1 swine flu strain remain undetermined, they wrote.
For their analysis they reviewed data from published and unpublished controlled trials. They searched well known registeries, consulted with manufacturers and authors to make a comprehensive list of the trials.
They then selected only those trials that were randomized and controlled, assessed neuraminidase inhibitors in children aged 12 and under who were treated in the community (that is, not in hospital), with confirmed or clinically suspected influenza and did a systematic meta-analysis where they re-analyzed the pooled data.
The main measures of effectiveness that they looked for were how long it took for the illness to resolve and how many children in the households involved caught the flu.
After applying the eligibility criteria, the researchers found a total of four trials testing the antivirals in children treated at home for the flu. Two used Tamiflu (oseltamivir ) and two used Relenza (zanamivir). Between them the four trials covered 1,766 children (1,243 with confirmed influenza, of whom 55 to 69 per cent had influenza A).
They also found another three randomized trials (one with Tamiflu and two with Relenza) that tested the antivirals for postexposure prophylaxis (ability to prevent flu). These covered a total of 863 children.
The researchers emphasized that none of these trials tested the effectiveness of the two drugs against the current pandemic strain of swine flu.
After reviewing the results of these trials, Thompson and colleagues found that:
* The treatment trials showed a reduction in median times to resolution of symptoms, or return to normal activities, or both, of between 0.5 and 1.5 days, but this was significant in only two trials.
* Treatment was not linked with a reduced use of antibiotics.
* In the three postexposure prophylaxis trials, a 10 day course of oseltamivir (Tamiflu) and zanamivir (Relenza) resulted in an 8 per cent decrease in the incidence of symptomatic influenza (the 95 per cent confidence interval ranged from 5 to 12 per cent).
* Based on only one trial, oseltamivir (Tamiflu) "did not reduce asthma exacerbations or improve peak flow in children with asthma".
* While zanamivir (Relenza) was well tolerated, oseltamivir (Tamiflu) was linked with an increased risk of vomiting.
The authors concluded that:
"Neuraminidase inhibitors provide a small benefit by shortening the duration of illness in children with seasonal influenza and reducing household transmission. They have little effect on asthma exacerbations or the use of antibiotics."
"Their effects on the incidence of serious complications, and on the current A/H1N1 influenza strain remain to be determined," they added.
In the meantime, several new antiviral drugs are undergoing trials which may change this result in the future. One such drug showed promise in final stage trials, where according to this week's announcement from its manufacturer, the Japanese global pharma company Daiichi Sankyo, it outperformed Tamiflu in tests on children.
The study was led by Dr Matthew Thompson, senior clinical scientist at the University of Oxford, UK, and appears online in the 10 August issue of the BMJ.
Children are a high risk group during seasonal flu epidemics, which typically affect 40 per cent of pre-schoolers and 30 per cent of school age children, who are also the main route of transmission into households, said the researchers.
They went on to explain that the current control strategy for treating patients who get the flu and preventing its spread includes use of antivirals because vaccination coverage is often low and there is not enough time to make vaccine and get it to everyone who needs it because it's a continual race against emerging strains.
The last time this strategy was examined was in 2005 which is why they decided to do a new review and re-assess the benefits and harms of antivirals.
For this review Thompson and colleagues pooled and re-analyzed data from randomized controlled trials of the neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) in treatment of children with seasonal influenza who were treated at home (ie not hospitalized).
They found that the antivirals provided a small benefit by shortening the duration of illness by a day and a half, and they reduced transmission in households, but they had little effect on asthma flare ups, increased ear infections and the likelihood of children needing antibiotics. Tamiflu also carries an increased risk of vomiting.
The effects of these drugs on the incidence of serious complication and the current A/H1N1 swine flu strain remain undetermined, they wrote.
For their analysis they reviewed data from published and unpublished controlled trials. They searched well known registeries, consulted with manufacturers and authors to make a comprehensive list of the trials.
They then selected only those trials that were randomized and controlled, assessed neuraminidase inhibitors in children aged 12 and under who were treated in the community (that is, not in hospital), with confirmed or clinically suspected influenza and did a systematic meta-analysis where they re-analyzed the pooled data.
The main measures of effectiveness that they looked for were how long it took for the illness to resolve and how many children in the households involved caught the flu.
After applying the eligibility criteria, the researchers found a total of four trials testing the antivirals in children treated at home for the flu. Two used Tamiflu (oseltamivir ) and two used Relenza (zanamivir). Between them the four trials covered 1,766 children (1,243 with confirmed influenza, of whom 55 to 69 per cent had influenza A).
They also found another three randomized trials (one with Tamiflu and two with Relenza) that tested the antivirals for postexposure prophylaxis (ability to prevent flu). These covered a total of 863 children.
The researchers emphasized that none of these trials tested the effectiveness of the two drugs against the current pandemic strain of swine flu.
After reviewing the results of these trials, Thompson and colleagues found that:
* The treatment trials showed a reduction in median times to resolution of symptoms, or return to normal activities, or both, of between 0.5 and 1.5 days, but this was significant in only two trials.
* Treatment was not linked with a reduced use of antibiotics.
* In the three postexposure prophylaxis trials, a 10 day course of oseltamivir (Tamiflu) and zanamivir (Relenza) resulted in an 8 per cent decrease in the incidence of symptomatic influenza (the 95 per cent confidence interval ranged from 5 to 12 per cent).
* Based on only one trial, oseltamivir (Tamiflu) "did not reduce asthma exacerbations or improve peak flow in children with asthma".
* While zanamivir (Relenza) was well tolerated, oseltamivir (Tamiflu) was linked with an increased risk of vomiting.
The authors concluded that:
"Neuraminidase inhibitors provide a small benefit by shortening the duration of illness in children with seasonal influenza and reducing household transmission. They have little effect on asthma exacerbations or the use of antibiotics."
"Their effects on the incidence of serious complications, and on the current A/H1N1 influenza strain remain to be determined," they added.
In the meantime, several new antiviral drugs are undergoing trials which may change this result in the future. One such drug showed promise in final stage trials, where according to this week's announcement from its manufacturer, the Japanese global pharma company Daiichi Sankyo, it outperformed Tamiflu in tests on children.
