Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Media
- Bastiaan Kole (11 August 2009)
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Effectiveness of antivirals: Important to distinguish treatment from prophylaxis
- Benjamin J. Cowling, Sophia Ng, Ira M. Longini (11 August 2009)
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Antiviral drugs for treating influenza: Effectiveness in children similar to that for at-risk and otherwise healthy adults
- Jane Burch, Lesley Stewart (12 August 2009)
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Neuraminidase inhibitors: Are they cost-effective?
- Rajiv Mahajan, Kapil Gupta (Assistant Professor), Vinod Kapoor (Associate Professor) (14 August 2009)
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Children with novel H1N1 Warrant Treatment
- Richard Whitley (17 August 2009)
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Experiences of the flu
- Sherine Thomas, Alistair R. O. Miller, Saye H. Khoo, Helen Winslow, Roberto Vivancos, Mark Hopkins, Nick J. Beeching, Mike B. J. Beadsworth (18 August 2009)
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Disease mongering by WHO
- Juan Gérvas (22 August 2009)
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We need a randomised trial of antiviral therapy for pandemic flu
- B Ronan O'Driscoll, Peter M Turkington (26 August 2009)
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Parental anxiety over oseltamivir
- Kelsey DJ Jones, RWF Breakey, Jennifer N Clough, Harriet M Gunn, Seema Pattni, Ian K Maconochie, Rebecca Salter, and Gareth Tudor-Williams. (19 October 2009)
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Oseltamivir for children with suspected influenza A H1N1
- Marta Gómez Fernández-Vegue, Yolanda Tovar Vicente, Marciano Sánchez Bayle, and Julia Cano (29 October 2009)
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Bastiaan Kole, Freelance GP Oxfordshire
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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 |
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Benjamin J. Cowling, Assistant Professor School of Public Health, The University of Hong Kong, Hong Kong, Sophia Ng, Ira M. Longini
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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
Competing interests: None declared |
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Jane Burch, Research Fellow Centre for Reviews and Dissemination, Lesley Stewart
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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 |
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Rajiv Mahajan, Assistant Professor (Pharmacology) Adesh Institute of Medical Sciences & Research, Bathinda, Kapil Gupta (Assistant Professor), Vinod Kapoor (Associate Professor)
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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 |
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Richard Whitley, Professor of Pediatrics 35233
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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%)
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 |
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Sherine Thomas, SPR in Infectious Diseases and Tropical Medicine Royal Liverpool University Hospital, Prescot street, Liverpool, L7 8XP, Alistair R. O. Miller, Saye H. Khoo, Helen Winslow, Roberto Vivancos, Mark Hopkins, Nick J. Beeching, Mike B. J. Beadsworth
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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/hpr0509.pdf 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/12496e30120650 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_030809/eiz10737_fm.html 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.aspx?ArticleId=19242 Competing interests: None declared |
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Juan Gérvas, Rural General Practitioner Canencia de la Sierra (Madrid) Spain
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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 |
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B Ronan O'Driscoll, Consultant Respiratory Physician Salford Royal University Hospital, Salford, M6 8HD, Peter M Turkington
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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 |
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Kelsey DJ Jones, Clinical Research Fellow Centre for Respiratory Infection, Imperial College, London, RWF Breakey, Jennifer N Clough, Harriet M Gunn, Seema Pattni, Ian K Maconochie, Rebecca Salter, and Gareth Tudor-Williams.
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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 |
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Marta Gómez Fernández-Vegue, Medical Resident (Pediatrics) Hospital Infantil Universitario Niño Jesús (Avda. Menéndez Pelayo 65, 28009 MADRID (SPAIN), Yolanda Tovar Vicente, Marciano Sánchez Bayle, and Julia Cano
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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]) 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%) 9 TOTAL 26 31 57 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 |
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