Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials
BMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b3172 (Published 10 August 2009) Cite this as: BMJ 2009;339:b3172
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
A systematic review of the use of oseltamivir for treatment of
influenza in children garnered significant media coverage in the UK (1).
Whilst the review was limited to trials of seasonal influenza treatment,
in the accompanying podcast one author said that it is ‘highly likely
[seasonal and pandemic strains] behave exactly the same’ (2). On the basis
that across two trials of oseltamivir treatment, 20 extra children vomited
compared to placebo groups, and despite acknowledging their analysis was
not sufficiently powerful to detect differences in complications of
influenza infection, the same author told ITN news that ‘in mild
[influenza] the benefits of treatment do not outweigh any harms’ (3). We
wanted to see whether media coverage has affected parents’ views on the
drug.
Between the 15th and 25th September 2009 we approached the parents of
276 children presenting for any reason to a Paediatric Emergency
Department in central London, and invited them to complete a survey on
their attitudes to oseltamivir (Tamiflu). 29 refused and were excluded
from analysis, and some didn’t finish the survey, mainly because they were
seen by medical staff prior to completion. The parents were mostly mothers
(66%), accompanying children with a median age of 4 years.
Words associated with Tamiflu were ‘Swine flu’ (176; 71%), ‘Worried’
(105; 43%), and ‘Side-effects’ (100; 40%). 41 (17%) associated it with
‘Safe’, and 58 (23%) with ‘Dangerous’. Parents were asked to choose which
(up to three) of a list of sentences about Tamiflu they most agreed with.
The most popular choices were ‘I am worried that Tamiflu would give my
child unpleasant side-effects’ (112; 45%), ‘I am worried that not enough
is known about Tamiflu’ (97; 39%), and ‘I am confused by what I’ve heard
about giving Tamiflu to children with swine flu’ (84; 34%).
Parents were almost five times more likely to want their children
treated with Tamiflu than not if the diagnosis had been made by their GP
(42% versus 9%), but this was reversed if the diagnosis was not made by a
doctor (23% versus 33%). In both scenarios many parents didn’t know
whether they would want their child treated or not (Figure).
When asked about swine flu vaccines in development, 84 (34%)
associated them with ‘Side effects’. However, parents were more than 8
times more likely to want their children vaccinated than not.
This data demonstrates significant public anxiety about the use of
oseltamivir for the treatment of influenza in children. Parental
reluctance to treat undermines the public health response to pandemic
influenza and in the context of the emergence of severe disease (4,5),
could be harmful.
Figure: Parental responses to two statements: ‘If my child’s GP
thought they had swine flu, I would want my child to take Tamiflu’ (number
shown in blue), and ‘If I thought my child had swine flu I would want them
to have Tamiflu even if we couldn’t get to see a doctor’ (red).
References:
1. Shun-Shin M, Thompson M, Heneghan C, Perera R, Harnden A, Mant D.
Neuraminidase inhibitors for treatment and prophylaxis of influenza in
children: systematic review and meta-analysis of randomised controlled
trials. BMJ 2009; 339: b3172.
2. http://podcasts.bmj.com/bmj/2009/08/14/a-pandemic-of-pandemic-
news/ (accessed 25th Sept 2009).
3. http://www.youtube.com/watch?v=QwcEKBYbXWU&feature=player_embedded
(accessed 25th Sept 2009).
4. Hackett S, Hill L, Patel J, Ratnaraja N, Ifeyinwa A, Farooqi M,
Nusgen U, Debenham P, Gandhi D, Makwana N, Smit E, Welch S. Clinical
characteristics of paediatric H1N1 admissions in Birmingham, UK. Lancet
2009; 374: 605.
5. Lister P, Reynolds F, Parslow R, Chan A, Cooper M, Plunkett A,
Riphagen S, Peters M. Swine-origin influenza virus H1N1, seasonal
influenza virus, and critical illness in children. Lancet 2009; 374: 605-
7.
Acknowledgements: KDJJ is grateful for support from the UK NIHR, and
an NIHR Comprehensive Biomedical Research Centre.
Competing interests:
None declared
Competing interests: No competing interests
Sir, Shun-Shin and colleagues have reported that the effects of
neuraminidase inhibitors in children with confirmed seasonal flu are
similar to those observed in adults, symptoms are shortened by about one
day with no proven effect on complication rates but there is a 5%
additional risk of vomiting in children.(1,2)
The letter from Sherine Thomas and colleagues (above) reports that
less than 10% of those admitted to an Infectious Disease unit with
suspected pandemic flu actually had this illness and the letter by
Williams and McCarron in the same issue of the BMJ reported that only 2 of
28 patients admitted to an isolation ward with suspected pandemic flu
actually had this condition whilst vulnerable patients with conditions
such as asthma, bronchiectasis and pneumonia were placed at increased risk
by being admitted to a ward where two patients with pandemic flu were
being nursed.(3) The diagnostic rate in the community would presumably be
even lower.
If antiviral drugs have the same effect on pandemic flu as on
seasonal flu, the above evidence suggests that treating 100 patients with
suspected pandemic flu would result in fewer than 10 patients having their
length of symptoms shortened by about one day and up to five patients may
vomit (especially younger patients).
The UK Department of Health has stated that antiviral therapy will be
given to suspected cases of pandemic flu “as a safety measure”. As the
benefits of antiviral therapy in pandemic flu are unknown, it would surely
be better and more ethical to conduct a randomised controlled trial of the
effects of antiviral therapy on the present strain of pandemic flu. As the
numbers affected are large and the time course of illness is short, the
results of such a trial could be available in a matter of weeks.
1. Shun-Shin M, Thompson M, Heneghan C, Perera R, Hamden A, Mant D.
Neuraminidase inhibitors for treatment and prophylaxis of influenza in
children: systematic review and meta-analysis of randomised controlled
trials. BMJ 2009; 339: b3172
2. Burch J, Corbett M, Stock C, Nicholson K, Elliot AJ, Duffy S,
Westwood M, Palmer S, Stewart L. Prescription of anti-influenza drugs for
healthy adults: a systematic review and meta-analysis. The Lancet
Infectious Diseases 2009 DOI:10.1016/S1473-3099(09)70199-9
3. Williams J, McCarron B. A/H1N1 Pandemic, Case definition is too
loose. BMJ 2009; 339:415
Competing interests:
None declared
Competing interests: No competing interests
Sir
Reading previous rapid responses to Shu-Shin et al' paper (1) and a
selection of the world literature (2-10) a rural general practitioner as
me might conclude that a/ the severity of swine flu is generally very low,
indeed lower than seasonal flu (the flu of every year) and b/ prevention
and treatment of swine flu in healthy persons, children and adults is not
justifiable and have common side effects, in some cases important ones
(see in www.equipocesca.org a full version into English, French,
Portuguese and Spanish).
But WHO (World Health Organization) papers and policy transmit to me
and my patients different ideas: a/ swine flu is a terrible and dangerous
disease, and b/ prevention and treatment of flu swine is justifiable,
necessary and urgent.
It looks like WHO participating in a "disease mongering" campaign.
They will know why.
Juan Gérvas, GP
1- Shun-Shin M, Thompson M, Heneghan C et al. Neuraminidase
inhibitors for treatment and prophylasis of influenza in children:
systematic review and meta-analysis of randomized controlled trials. BMJ.
2009;339;b3172.
2- Burch J, Corbett M, Stock C et al. Prescription of anti-influenza drugs
for healthy adults: a systematic review and meta-analysis. Lancet Infec
Dis. 2009;doi:10.1016/S1473-3099(09)70199-9.
3- Ellis C, McEven R. Who should receive Tamiflu for swine flu? BMJ.
2009;339:b2698.
4- Evans D, Cauchemez S, Hayden FG. “Prepandemic” immunization for novel
influenza viruses, “swine flu” vaccine, Guillain-Barré syndrome and the
detection of rare severe adverse affects. J Infect Dis. 2009;200:321-8.
5- Kitching A, Roche A, Balasegaran S et al. Oseltamivir adherence and
side effects among children in three London schools affected by influenza
A (H1N1), May 2009. An Internet based cross sectional survey.
Eurosurvillance 2009;29:1-4.
6- Moreno DM, Taubenberger JK. Understanding influenza backward. JAMA.
2009;302:679-80.
7- Sheridan C. Flu vaccine makers upgrade technology and pray for it.
Nature Biotechnolgy. 2009;27:489-91.
8- Simonsen L, Taylor RJ, Vibourd C et al. Mortality benefits of influenza
vaccine in elderly people: an ongoing controversy. Lancet Infect Dis.
2007;7:658-66.
9- Smith S, Demicheli V, Di Pietrantonj C, Harden AR et al. Vaccines for
preventing influenza in healthy children. Cochrane Database Syst Rev.
2008;(2):CD004879.
10- White N, Webster R, Govorkovs E et al. What is the optimal therapy for
patients with H5N1 infection? PLoS Med. 2009;6:e1000091.
Competing interests:
None declared
Competing interests: No competing interests
Sir,
We share concerns about the syndromic prescription of oseltamivir in
the community for possible seasonal or pandemic influenza-like illness
(ILI), and highlight the importance of investigating such patients at the
community-hospital interface.
In late 2008, a surge of ILI in the local community was reflected in
a rise in admissions to our hospital. In December 2008 we tested 321
specimens from hospital patients, staff and relatives for respiratory
viruses by multiplex RT-PCR (1). Viral RNA was detected in 191 (60%)
samples, of which 124 (39%) were influenza A PCR positive. During the 6
week outbreak period, 85 inpatients had oseltamivir sensitive H3 seasonal
influenza A, and there was a concurrent nosocomial outbreak of oseltamivir
resistant H1 influenza A in immunocompromised patients (7 confirmed
isolates) and a further 24 cases of untyped influenza A (2). Rapid access
to RT-PCR tests was essential in order to prioritise who should be
isolated in hospital and those whose contacts might need antiviral
prophylaxis, and to identify those with oseltamivir-resistant influenza.
During the current pandemic, the North West was relatively spared but
GP consultations and hospitalisations for ILI peaked in week 30 of 2009.
Of the RCGP and NHS Direct random testing during weeks 18-31, the
positivity rates for a/H1N1v in the North West were 7.7% and 6.9%
respectively, compared to national rates of 21.8% (RCGP) and 8% (NHS
Direct) (3).
During July (weeks 27-30) 2009, 23 adults were admitted to our
infectious disease service following a diagnosis of possible pandemic
influenza in the community, 83% having already received oseltamivir. Only
2 (9%) were positive for influenza A on RT-PCR. Among the remainder, 9
(39%) had community acquired pneumonia, 4 had bacteraemias with different
organisms, 2 had other severe infections (malaria, TB pericarditis) and 3
had severe systemic illness (thyrotoxicosis, diabetes, rheumatoid
arthritis flare).
This suggests that more than 90% of patients with ILI could receive
unnecessary oseltamivir in the community, reflecting recent diagnostic
experience in Australia (4) and with suspected imported pandemic influenza
in Sweden (5).
As other potentially life-threatening illnesses are being missed, we
suggest that clinical assessment of patients is required and that
algorithm based prescribing of oseltamivir in the community requires
rethinking, especially as its therapeutic effectiveness is limited, even
in hospital patients (1).
References
1.McGeer AJ. Diagnostic testing or empirical therapy for patients
hospitalized with suspected influenza: what to do? Clin Infect Dis 2009;
48(Suppl 1): S14-9.
2.Health Protection Agency. Outbreak of influenza at an acute
hospital in the north-west of England. Health Protection Report 6 Feb
2009; 3(5) available from
http://www.hpa.org.uk.libaccess.lib.mcmaster.ca/hpr/archives/2009/hpr050...
3.Health Protection Agency North West. North West Influenza Bulletin
7 Aug 2009; 3. Available from
http://www.hpa.org.uk.libaccess.lib.mcmaster.ca/web/HPAwebFile/HPAweb_C/...
4.Eizenberg P. The general practice experience of the swine flu
epidemic in Victoria — lessons from the front line. Med J Aust 1 Jul
2009; 191: 1-3. Available from
http://www.mja.com.au.libaccess.lib.mcmaster.ca/public/issues/191_03_030...
5.Follin P, Lindqvist A, Nyström K, Lindh M. A variety of respiratory
viruses found in symptomatic travellers returning from countries with
ongoing spread of the new influenza A(H1N1)v virus strain.
Eurosurveillance 18 Jun 2009; 14(24) available from
http://www.eurosurveillance.org.libaccess.lib.mcmaster.ca/ViewArticle.as...
Competing interests:
None declared
Competing interests: No competing interests
Recent concern has been expressed about the routine use of
oseltamivir in the treatment of children with influenza. It is
inappropriate given the collective data to suggest that treatment with
antiviral medications is not of benefit to children with influenza. The
CDC advises that clinical judgment is an important factor in treatment
decisions. Physicians should continue to follow guidance from health
authorities, as appropriate to seasonal influenza or pandemic H1N1.
As we begin to learn more about novel H1N1, we have only identified a few
high risk patient groups (e.g. neurocognitive dysfunction, neuromuscular
disability, etc.) for whom therapy is imperative. However, we now have
normal children who have developed progressive life-threatening disease.
In the absence of biomarkers that predict disease progression,
withholding antiviral therapy could result in more serious illness, as is
already being reported with novel H1N1.
In our own study, we enrolled 695 children in a randomized, double-
blind, placebo-controlled analysis, and clearly demonstrated significant
treatment benefits:
• Reduction of new diagnoses of otits media infections (by 44%)
• Lower incidence of physician-prescribed antibiotics
• Reduction in median duration of illness by 36 hours
• Reduction of cough, coryza and duration of fever.
No evidence of drug toxicity was found. We did not detect an increased
rate of resistance. Further, with regard to safety, based on a review of
data and clinical reports, the U.S. FDA recently granted Emergency Use
Authorization for oseltamivir in treatment and prophylaxis of pandemic
H1N1 in pediatric patients 1 year and younger.
Children have been disproportionally impacted by novel H1N1. As they
return to school in the western hemisphere, there’s no doubt that American
and European clinics and hospitals will be caring for thousands of
influenza-infected children. Health professionals must continue to follow
public health guidance and apply clinical judgment with regard to
pharmacologic interventions.
While prudent physicians always worry about toxicity and are concerned
about the development of resistance, the body of evidence supports
oseltamivir as an effective treatment of novel H1N1 in children and
adults. Antiviral therapy will be especially important until an effective
vaccine can be developed and widely distributed.
Ref: Oral oseltamivir treatment of influenza in children; Journal of
Pediatric Infectious Diseases, April 2001
Competing interests:
I am on the Board of Directors of Gilead Sciences
Competing interests: No competing interests
Neuraminidase inhibitors have shown a reduction in time to resolution
of symptoms between 0.5 and 1.5 days; and reduction in time to resolution
of illness between 0.4 and 1.5 days. (1) All these figures have been
claimed to be statistically significant (P<0.05), but one question
remains unanswered- are these figures clinically significant too?
Moreover, with neuraminidase inhibitors, no reductions in asthma
exacerbations were seen. A very little (10%)/no change in antibiotic use
were observed. Even the incidence of acute otitis media in children aged 6
-12 years remained unchanged. Thus neuraminidase inhibitors were not
effective in reducing the complications of influenza.
Now the big question is-are neuraminidase inhibitors cost-effective?
Although no cost-effective analysis was done in the RCT included in the
meta-analysis, but attempt could have been made to make this review and
meta-analysis to deliver on this front also; that would have made this
meta-analysis, a cost-effective analysis also; a more fruitful study,
particularly in the wake of current pandemic of H1N1 influenza.
References
1. Shun-Shin M, Thompson M, Heneghan C, Perera R, Hamden A, Mant D.
Neuraminidase inhibitors for treatment and prophylaxis of influenza in
children: systematic review and meta-analysis of randomised controlled
trials. BMJ 2009; 339: b3172
Competing interests:
None declared
Competing interests: No competing interests
The relatively small reduction in symptom duration reported by Dr
Shun-Shin and colleagues[1] in response to treatment with neuraminidase
inhibitors was consistent with the results of a systemic review conducted
by the Centre for Reviews and Dissemination, that assessed the
effectiveness oseltamivir (tamiflu) and zanamivir (relenza) in healthy and
at-risk adults,[2,3] and children,[3] presenting with symptoms of
influenza. However, it is important to highlight the paucity of good
quality data, particularly for children. Most of the trials included in
both the review by Shun-Shin et al., and our review of symptom duration in
children, had methodological flaws, were clinically heterogeneous, and
were based on 1,766 children. The data for healthy and at-risk adults was
slightly more robust, based on just over 4,000 healthy adults and just
under 2,500 at-risk adults.
The reduction of 0.5 to 1.5 days in the duration of symptoms for
children, was similar to that seen in our review of healthy adults
(reduction of 0.55 days for tamiflu and 0.57 days for relenza), and at-
risk groups (reduction of 0.74 days for tamiflu and 0.98 days for
relenza). As with our review, the focus of the review by Shun-Shin et al.
was seasonal influenza. Given the seasonal context in which the drugs were
assessed, viral shedding was not investigated as an outcome in either
review, which would have been an appropriate outcome to assess their
effectiveness in the containment stage of a pandemic. In addition, the
numbers of children in the prophylactic trials included in the review by
Shun-Shin et al. was small, with only 1085 index cases and 863 child
contacts. The primary reason for making antiviral drugs available to those
at-risk during seasonal influenza outbreaks, is to prevent influenza-
related complications, not to reduce symptom duration. Care should be
taken when applying the results of these reviews to the pandemic
situation, as the context in which antiviral drugs are used may differ
between seasonal outbreaks and a pandemic, and between different phases of
a pandemic.
We agree with Shun-Shin et al. that there is a need to gather good
quality evidence on the effectiveness of neuraminidase inhibitors,
particularly with regard to complication rates and adverse events, for
adults considered at-risk and otherwise healthy adults, as well as
children. Until reliable evidence becomes available on whether or not
these drugs protect people from developing what could be life-threatening
complications, we consider that it is reasonable that antiviral drugs are
available to people at an increased risk of suffering influenza-related
complications as a precautionary measure.
References
1 Shun-Shin M, Thompson M, Heneghan C, Perera R, Harnden A, Mant D.
Neuraminidase inhibitors for treatment and prophylaxis of influenza in
children: systematic review and meta-analysis of randomised controlled
trials. BMJ 2009;339:b3172 doi:10.1136/bmj.b3172.
2Burch J, Corbett M, Stock C, Nicholson K, Elliot AJ, Duffy S,
Westwood M, Palmer S, Stewart L. Prescription of anti-influenza drugs for
healthy adults: a systematic review and meta-analysis. The Lancet
Infectious Diseases 2009 DOI:10.1016/S1473-3099(09)70199-9.
3Burch J, Paulden M, Conti S, Stock C, Corbett M, Welton N, Ades AE,
Sutton A, Cooper N, Elliot AJ, Nicholson K, Duffy S, McKenna C, Stewart L,
Westwood M, Palmer S. Antiviral drugs for the treatment of influenza: A
Systematic Review and Economic Evaluation. In Press. Health Technology
Assessment.
Competing interests:
None declared
Competing interests: No competing interests
Shun-Shin et al. provide a timely review of the effectiveness of antivirals for treatment and prophylaxis of influenza virus infections (1). They are cautious about the applicability of results to pandemic influenza A/H1N1, but while this virus appears to have remained susceptible in vitro to neuraminidase-inhibitors we might expect that effectiveness against the pandemic virus would be similar to seasonal influenza A strains. While new controlled trials could be established to confirm the effectiveness of antivirals against the pandemic strain, there should by now be sufficient observational data to show that this is the case. Further trials would need to be very large to have high statistical power to detect differences in effectiveness between pandemic and seasonal strains.
We would like to raise some important points which we worry may lead to unnecessary confusion about the usefulness of antivirals, based on the review (1). Firstly, it is important to distinguish the use of antivirals for treatment of illness versus their use as prophylaxis against infection or illness, and in future it may be helpful to conduct separate reviews. In the current pandemic antiviral treatment, primarily with oseltamivir, has been widely used in many countries including the UK, as part of ‘mitigation phase’ protocols. Antiviral post-exposure prophylaxis has rarely been used since the initial ‘containment phase’ protocols. The conclusion that “neuraminidase inhibitors … [shorten] the duration of illness … and [reduce] household transmission” could mislead because it does not clarify that the latter refers to antiviral prophylaxis among contacts (whereas the former refers to treatment).
The 8% reduction in household transmission at first seems rather small, until closer study of Figure 3 reveals that this is an estimate of the absolute risk reduction, from around 12% in the placebo arm to around 4% in the antiviral arm (1), corresponding to a relative risk reduction of almost 70%. The use of absolute risk reductions is appropriate in many situations, but in this scenario it is not. A household contact of an index case will face different risks of influenza virus infection depending on their characteristics (e.g. age, and vaccination history) and the characteristics of the index case (e.g. age), as well as the characteristics of the virus (2). Secondary attack rates are typically much higher for pandemic influenza viruses than seasonal influenza viruses because of the lack of population immunity. In our own household study in Hong Kong, secondary attack rates of confirmed seasonal influenza in 2008 were 8% (2), and naïve application of the review results suggests that antiviral prophylaxis would eliminate household transmission. An 8% reduction would be far less impressive on pandemic secondary attack rates of 22% to 33% (3).
The timing of antiviral adminstration is a crucial factor in effectiveness. A large trial demonstrated that oseltamivir was most effective if given within 12 hours of illness onset (1). Viral replication peaks around the time of illness onset (4), and infectiousness is thought to be correlated with viral shedding, indicating that later administration of antiviral treatment may not lead to substantial reductions in infectiousness or onwards transmission. Nevertheless it is important to understand the potential indirect benefits of antiviral treatment, and a detailed analysis of existing data has suggested that oseltamivir treatment alone may lead to approximately 16% reductions in household transmission (5). Further studies of the indirect benefit of antiviral treatment on household transmission are certainly warranted.References
- Aoki FY, Macleod MD, Paggiaro P, Carewicz O, El Sawy A, Wat C, et al. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother. 2003;51(1):123-9.
- Cowling BJ, Chan KH, Fang VJ, Cheng CK, Fung RO, Wai W, et al. Facemasks and Hand Hygiene to Prevent Influenza Transmission in Households: A Randomized Trial. Ann Intern Med. 2009.
- World Health Organization. Assessing the severity of an influenza pandemic. 2009 [cited 2009 August 10]; Available from: http://www.who.int/csr/disease/swineflu/assess/disease_swineflu_assess_2...
- Carrat F, Vergu E, Ferguson NM, Lemaitre M, Cauchemez S, Leach S, et al. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. Am J Epidemiol. 2008;167(7):775-85.
- Halloran ME, Hayden FG, Yang Y, Longini IM, Jr., Monto AS. Antiviral effects on influenza viral transmission and pathogenicity: observations from household-based trials. Am J Epidemiol. 2007;165(2):212-21.
Competing interests:
None declared
Competing interests: No competing interests
Do the authors believe that it right to respond to and speak through media on national television and radio?
-
Evidently, evidence based medicine should be the bedrock of modern medicine, and the CEBM in Oxford is in the forefront of same. But would it perhaps be more appropriate to be modest about a relatively small meta-analysis of research that relates to a different situation and a different variant of the disease.
-
Unless there was break-through evidence of direct harm, would it would have been more appropriate to give patients, health professionals and the DOH a chance to read the 'new' evidence, and make decisions together ?
-
I would have thought that our (GP) colleagues would have tried to avoid the huge unnecessary parental anxiety that this sort of media coverage can generate during a pandemic. Especially when they are introduced as 'medical experts' to the public by the BBC and other media.
Competing interests:
None declared
Competing interests: No competing interests
Oseltamivir for children with suspected influenza A H1N1
Due to the great relevance that pandemic influenza A (H1N1)
is having nowadays, specially about the controversy of using
neuraminidase inhibitors as empiric treatment in children,
we have consider as something important to study our
patients treated with oseltamivir and observe how many of
them had at the end a positive result of PCR (Polymerase
Chain Reaction) for influenza A H1N1. Our objective is to
think calmly about the use of antiviral drugs and to
describe the diagnosis in children that received initially
treatment at the time of admission without having truly
influenza A.
We took in clinical information from children that have been
admitted in our hospital with suspected influenza A, from
15th June to 15th October 2009. In total, we obtained data
of 133 children, 16 of them (12%) were patients from
Oncology Department. Rest of children were 107 (88%) no
oncological patients. The age range width of these last ones
patients was from 19 days to 16 years old, with a median age
of 2,9 years; being 54.2% of them males. Nasal swabs samples
were collected from all patients to analyse PCR for H1N1
and, before knowing the results, 57 (42,8%) of them received
empiric treatment with oseltamivir:
(here goes table 1 [added 1 November 2009])
It can be observed that 62,5% of the non oncological
children received empiric treatment without being infected
with influenza A H1N1. We believe a debate should be opened
about current criteria to prescribe antiviral treatment at
the time of admission, because these criteria are in general
quite a lot wide and includes very frequent symptoms in this
season, as fever, cough, mucus, difficult respiratory,
pneumonia,… On second thought, we have to mention that these
criteria have been restricted during the time of the study,
and at the current time, they are more strict, giving the
physicians the choice to treat or not, depending on the
individual characteristics of the patient.
Moreover, final diagnosis of non oncological
children who received empiric treatment with oseltamivir and
finally had PCR H1N1 negative (30 patients) were:
- 13 patients (43%) Acute asthmatic crisis
- 7 patients (23%) Pneumonia (2 of these 7 had also pleural
effusion)
- 4 patients (13%) Fever syndrome
- 3 patients (10%) Laryngitis
- 2 patients (6%) Viral infection
- 1 patient (3%) Acute otitis media
Therefore, we can deduce that overall difficult
respiratory and cough (very frequent in asthma and
pneumonia) make physicians think in influenza A, because
these symptoms are strongly associated with a high pre-test
possibility of having H1N1 infection (and so to received
antiviral treatment). We may note that having any kind of
pneumonia has been sometimes a criterion to give oseltamivir
treatment, just to prevent possible severe complications of
infection or coinfection of H1N1.
Official criteria to prescribe neuraminidase
inhibitors for treatment in children are constantly updated.
Knowing the uncertain data about its real effectiveness
preventing severe cases (1); secondary effects that have
been reported (2) (although we declare that in our patients
we had no unintended effects) and the special susceptibility
of children (3), it may be good to have a critical
reflection before prescribing oseltamivir.
1 Shun-Shin M, Thompson M. Neuraminidase inhibitors for
treatment and prophylaxis of influenza in children:
systematic review and meta-analysis of randomised controlled
trials. BMJ. 2009 Aug 10;339:b3172.
2. Strong M, Burrows J, Redgrave P. A/H1N1 pandemic.
Oseltamivir's adverse events. BMJ. 2009 Aug 11;339:b3249
3. Jefferson T, Jones M, Doshi P, Del Mar C Possible harms
of oseltamivir--a call for urgent action. Lancet. 2009 Oct
17;374(9698):1312-3
Competing interests:
None declared
Competing interests: Number of children treated with oseltamivir PCR H1N1 + PCR H1N1 - Non oncolgical 18 (37,5%) 30 (62,5%) 48 Oncological 8 (88,8%) 1 (11,1%) 9TOTAL 26 31 57