EVIDENCE-BASED CHILD HEALTH: A COCHRANE REVIEW JOURNALEvid.-Based Child Health 7: 1791–1792 (2012)Published online in Wiley Online Library (http://www.evidence-basedchildhealth.com). DOI: 10.1002/ebch.1872

Commentary

Commentary on ‘Neuraminidase inhibitors for preventingand treating influenza in children (published trials only)’

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Wang K,Shun-Shin M, Gill P, Perera R, Harnden A. Neuraminidase inhibitors for preventing and treating influenza inchildren (published trials only). Cochrane Database of Systematic Reviews 2012, Issue 4. Art. No.: CD002744.DOI: 10.1002/14651858.CD002744.pub4.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summaryarticle.

Influenza virus is an important contributor to health-care utilization and morbidity during seasonal epi-demics and rare pandemics, such as the 2009 H1N1influenza pandemic. Although influenza is a self-limited illness, symptoms may last for one week ormore. Influenza-associated complications may occur,especially in children with comorbid conditions suchas neuromuscular weakness or congenital heart disease(1–3).

In a Cochrane Review updated to include datafrom the H1N1 influenza pandemic, Wang et al. (4)found that neuraminidase inhibitors (NAIs), such asoseltamivir and zanamivir, reduced influenza symp-toms by 1.5 days, while a new, long-acting NAI,lanamivir octanoate, reduced symptoms by 2.8 days.NAI prophylaxis provided a modest reduction ininfluenza transmission among household contacts; onecase was prevented for every 13 household contactstreated. The impact of these findings ought to be con-sidered in the context of total resource utilization,implications for special populations and availabilityof alternate prevention strategies.

Influenza results in substantial medical costs. Theannual medical costs for children <5 years of agewith influenza range from $62–$279 million forthose evaluated in the emergency department to$44–$163 million for those requiring hospitalizationin the US (5). Projections based on historical dataestimate that a virulent pandemic, which H1N1 bycomparison was not, would result in dangerous over-crowding and bed shortages at children’s hospitals (6).As the average length of stay for influenza hospitaliza-tion is 2.8 days (7), it is possible that 1.5 fewer days ofsymptoms could lessen the burden on hospital crowd-ing and resource utilization during pandemic periods.An economic analysis showed that empiric oseltamivirfor suspected or proven influenza in unvaccinated chil-dren 1–12 years of age in the US is potentially costeffective (8). If one includes indirect costs, such asthose resulting from caregiver absenteeism, the poten-tial savings are even greater.

By contrast, the benefit of NAI prophylaxis ofunvaccinated household contacts is vastly overshad-owed by the benefit of routine immunization of chil-dren against influenza. Vaccine effectiveness exceeds70% when the vaccine strains are well-matchedwith circulating influenza strains (9). School-agechildren are the primary sources of communitytransmission and vaccination of school-age childrenagainst influenza prevents influenza-attributable mor-tality among elderly adults more effectively than vac-cinating elderly adults (10). Unfortunately, fewer than25% of healthy, school-age children in the US receivean influenza vaccine (11). Therefore, we believe thatstrategies to prevent influenza should emphasize vac-cination rather than post-exposure prophylaxis withNAIs.

There are special populations of children, such asthose with asthma or chronic conditions, who are atparticularly high risk for complications from influenzarequiring hospitalization or leading to death (12, 13).In 2003, these children accounted for 12% of influenzaadmissions but 26% of hospital costs (7). Amongchildren with asthma, oseltamivir recipients had betterlung function and fewer asthma exacerbations duringthe first week of illness than did placebo recipients(14). Among children requiring intensive care unithospitalization, those treated with oseltamivir hada shorter length of stay compared with those nottreated (15). Although there is a paucity of evidencefor improved outcomes among children with othercomorbid conditions who receive oseltamivir, it islikely that the benefit will equal or exceed the benefitsconferred to otherwise healthy children.

This review confirms previously accepted knowl-edge that NAIs are effective for treatment and preven-tion of influenza. Framing the benefit in the contextof our overburdened healthcare system, and applyingit to special populations, early use of NAIs to treatchildren with influenza-like symptoms during a knownoutbreak, could meaningfully reduce patient morbid-ity and healthcare costs. During non-epidemic periods,

Copyright 2012 John Wiley & Sons, Ltd.

1792 Commentary

however, it may be prudent to reserve oseltamivirfor those children with laboratory-confirmed influenzainfection. As with all medications, we advocate forjudicious use to preserve their effectiveness, and eventhough NAIs are well tolerated, the most effective planis still prevention by vaccination.

Declarations of interest

No disclosures or declarations of interest.

Michelle Parker1,2 and Samir S. Shah1,2,3*1 Division of Hospital Medicine, Cincinnati Children’s Hospital

Medical Center, Cincinnati, OH, USA2 Department of Pediatrics, University of Cincinnati College of

Medicine, Cincinnati, OH, USA3 Division of Infectious Diseases, Cincinnati Children’s Hospital

Medical Center, Cincinnati, OH, USA

Correspondence to: Dr Samir S. Shah, Division of Hospital Medicine,Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue,ML 9016, Cincinnati, OH 45 229, USAE-mail: Samir.shah@cchmc.org

Keywords: influenza, neuraminidase inhibitors, treatment

References

1. Bhat N, Wright JG, Broder KR, Murray EL, Greenberg ME, GloverMJ, et al. Influenza-associated deaths among children in the UnitedStates, 2003–2004. The New England Journal of Medicine 2005;353: 2559–2567.

2. Harper SA, Fukuda K, Uyeki TM, Cox NJ, Bridges CB. Preventionand control of influenza. Recommendations of the AdvisoryCommittee on Immunization Practices (ACIP). Morbidity andMortality Weekly Report. Recommendations and Reports 2005; 54:1–40.

3. Keren R, Zaoutis TE, Bridges CB, Herrera G, Watson BM,Wheeler AB, et al. Neurological and neuromuscular disease asa risk factor for respiratory failure in children hospitalized with

influenza infection. Journal of the American Medical Association2005; 294: 2188–2194.

4. Wang K, Shun-Shin M, Gill P, Perera R, Harnden A.Neuraminidase inhibitors for preventing and treating influenzain children. Cochrane Database of Systematic Reviews 2012; 1:CD002744.

5. Fairbrother G, Cassedy A, Ortega-Sanchez IR, Szilagyi PG,Edwards KM, Molinari NA, et al. High costs of influenza: directmedical costs of influenza disease in young children. Vaccine 2010;28: 4913–4919.

6. Sills MR, Hall M, Fieldston ES, Hain PD, Simon HK, Brogan TV,et al. Inpatient capacity at children’s hospitals during pandemic(H1N1) 2009 outbreak, United States. Emerging InfectiousDiseases 2011; 17: 1685–1691.

7. Hassan F, Lewis TC, Davis MM, Gebremariam A, Dombkowski K.Hospital utilization and costs among children with influenza, 2003.American Journal of Preventive Medicine 2009; 36: 292–296.

8. Lavelle TA, Uyeki TM, Prosser LA. Cost-effectiveness ofoseltamivir treatment for children with uncomplicated seasonalinfluenza. Journal of Pediatrics 2012; 160: 67–73 e6.

9. Jefferson T, Rivetti A, Harnden A, Di Pietrantonj C, Demicheli V.Vaccines for preventing influenza in healthy children. CochraneDatabase of Systematic Reviews 2008; 2: CD004879.

10. Longini IM Jr. A theoretic framework to consider the effectof immunizing schoolchildren against influenza: implications forresearch. Pediatrics 2012; 129 (Suppl 2): S63–S67.

11. Fiore AE, Uyeki TM, Broder K, Finelli L, Euler GL, SingletonJA, et al. Prevention and control of influenza with vaccines:recommendations of the Advisory Committee on ImmunizationPractices (ACIP), 2010. Morbidity and Mortality Weekly Report.Recommendations and Reports 2010; 59: 1–62.

12. Miller EK, Griffin MR, Edwards KM, Weinberg GA, SzilagyiPG, Staat MA, et al. Influenza burden for children with asthma.Pediatrics 2008; 121: 1–8.

13. Centers for Disease Control and Prevention. Severe influenzaamong children and young adults with neurologic andneurodevelopmental conditions – Ohio, 2011. Morbidity andMortality Weekly Report 2012; 60: 1729–1733.

14. Johnston SL, Ferrero F, Garcia ML, Dutkowski R. Oral oseltamivirimproves pulmonary function and reduces exacerbation frequencyfor influenza-infected children with asthma. The PediatricInfectious Disease Journal 2005; 24: 225–232.

15. Coffin SE, Leckerman K, Keren R, Hall M, Localio R, ZaoutisTE. Oseltamivir shortens hospital stays of critically ill childrenhospitalized with seasonal influenza: a retrospective cohort study.The Pediatric Infectious Disease Journal 2011; 30: 962–966.

If you would like to make a comment on the above article, you are invited to submit a letter to the Editorby email (child@ualberta.ca). Selected letters may be edited and published in future issues of the journal.

Copyright 2012 John Wiley & Sons, Ltd. Evid.-Based Child Health 7: 1791–1792 (2012)DOI: 10.1002/ebch.1872