Correspondence

Influenza-Associated Deaths among Children

N Engl J Med 2006; 354:1317-1318March 23, 2006

Article

To the Editor:

Bhat et al. (Dec. 15 issue)1 report on influenza-related deaths among children during the 2003–2004 influenza season. Combining medical records, autopsy reports, and analyses of virus isolates, their timely study provides estimates of the deaths that may have been caused by influenza. However, we question the authors' recommendation that vaccine coverage should be improved among children, for several reasons. First, a considerable proportion of the reported deaths were among children under six months of age, for whom influenza vaccination is not approved. Second, about 12 percent of the children who died had been vaccinated. Furthermore, the efficacy of influenza vaccination is far from optimal and, in specific patient groups, even doubtful.2,3 In the season that was studied, efficacy was diminished because of a mismatch between wild virus and vaccine strains. If one combines these arguments with the fact that the number of cases in the 2003–2004 influenza epidemic was above average, millions of children would have to be vaccinated each year in order to prevent one influenza-related death. We conclude that universal vaccination of children is not justified.

Johannes C. van der Wouden, Ph.D.
Herman J. Bueving, M.D., Ph.D.
Siep Thomas, M.D., Ph.D.
Erasmus University Medical Center Rotterdam, 3000 DR Rotterdam, Netherlands
j.vanderwouden@erasmusmc.nl

3 References

1. 1

   Bhat N, Wright JG, Broder KR, et al. Influenza-associated deaths among children in the United States, 2003-2004. N Engl J Med 2005;353:2559-2567
   Full Text | Web of Science | Medline

2. 2

   van der Wouden JC, Bueving HJ, Poole P. Preventing influenza: an overview of systematic reviews. Respir Med 2005;99:1341-1349
   CrossRef | Web of Science | Medline

3. 3

   Cates CJ, Jefferson TO, Bara AI, Rowe BH. Vaccines for preventing influenza in people with asthma. Cochrane Database Syst Rev 2004;2:CD000364-CD000364
   Medline

To the Editor:

Bhat and colleagues describe 153 influenza-associated deaths among children in the United States during the 2003–2004 influenza season. However, data regarding the use of antiviral medications was omitted. Antiviral therapy has been shown to reduce symptoms and complications requiring antibiotics in children.1 In an analysis of data from two national surveys, my colleagues and I found that physicians prescribed antiviral medications to patients in whom they diagnosed influenza only 19 percent of the time.2 Adults received antiviral medications more frequently than children. We suggested that the lower rate of prescribing for children was due to the labeling of antiviral drugs and a reluctance to expose children to newer medicines.2

The series of influenza-related deaths reported by Bhat and colleagues cannot be used for a definitive assessment of efficacy. However, it would be interesting to know what proportion of the children received antiviral therapy, a fact that would shed light on the activity of these medications in this setting.

Jeffrey A. Linder, M.D., M.P.H.
Brigham and Women's Hospital, Boston, MA 02115
jlinder@partners.org

2 References

1. 1

   Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG. Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. BMJ 2003;326:1235-1235
   CrossRef | Web of Science | Medline

2. 2

   Linder JA, Bates DW, Platt R. Antivirals and antibiotics for influenza in the United States, 1995-2002. Pharmacoepidemiol Drug Saf 2005;14:531-536
   CrossRef | Web of Science | Medline

Author/Editor Response

With regard to the comments by Dr. Van der Wouden and colleagues: the U.S. Advisory Committee on Immunization Practices (ACIP) currently does not recommend influenza vaccination for all children but does recommend annual influenza vaccination for specific groups on the basis of their increased risk of influenza-related morbidity. In 2004, annual vaccination was recommended for all children 6 to 23 months of age. Data from our surveillance led the ACIP in 2005 to expand its recommendations to include persons with conditions that compromise respiratory function, such as neuromuscular disorders.1 In February 2006, the ACIP voted to expand annual vaccine recommendations to include all children 6 to 59 months of age.2 This last recommendation will be published in the 2006 recommendations of the ACIP on the prevention and control of influenza.2

Influenza-related death may be rare in relation to the number of children targeted for vaccination, but improvements in vaccine coverage among children may also reduce the substantial burden of morbidity due to influenza that leads to school absenteeism, hospitalization, and lost work due to child care.3-5 Further work to quantify the reductions that are possible in all of these outcomes is needed to frame the debate regarding universal pediatric vaccination. Because antiviral drugs and influenza vaccine are not approved for children under the age of six months, the ACIP recommends immunization of household contacts to reduce transmission to this vulnerable group.

We were unable to assess the effectiveness of influenza vaccine from our surveillance data, because all cases were defined by outcome, without a comparison group. Younger age and antigenic mismatch may affect the effectiveness of vaccination. However, some protection is expected.1 Therefore, influenza vaccination should be provided to high-risk populations, in whom protection is most needed.

With regard to the comments by Dr. Linder: our study found medical-record documentation of the presence or absence of antiviral therapy in 73 of the 153 children reported to have died (48 percent) (data not previously reported). Among these 73, 10 patients received adamantanes and 18 received oseltamivir, and treatment within 48 hours after the onset of illness was documented in 15 cases. Without a comparison control population, it is not possible to draw any conclusions from these data.

Niranjan Bhat, M.D.
David K. Shay, M.D., M.P.H.
Timothy M. Uyeki, M.D., M.P.H.
Centers for Disease Control and Prevention, Atlanta, GA 30333
nbhat@cdc.gov

5 References

1. 1

   Harper SA, Fukuda K, Uyeki TM, Cox NJ, Bridges CB. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2005;54:1-40[Erratum, MMWR Morb Mortal Wkly Rep 2005;54:750.]
   Medline

2. 2

   Meeting of the Advisory Committee on Immunization Practices, Atlanta, Georgia, February 21–22, 2006. Meeting minutes will be posted at http://www.cdc.gov/nip/ACIP. Official recommendations will be available at http://www.cdc.gov/mmwr/index.html.
   

3. 3

   Thompson WW, Shay DK, Weintraub E, et al. Influenzaassociated hospitalizations in the United States. JAMA 2004;292:1333-1340
   CrossRef | Web of Science | Medline

4. 4

   Neuzil KM, Hohlbein C, Zhu Y. Illness among schoolchildren during influenza season: effect on school absenteeism, parental absenteeism from work, and secondary illness in families. Arch Pediatr Adolesc Med 2002;156:986-991
   Web of Science | Medline

5. 5

   O'Brien MA, Uyeki TM, Shay DK, et al. Incidence of outpatient visits and hospitalizations related to influenza in infants and young children. Pediatrics 2004;113:585-593
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   M. E. Falagas, P. K. Koletsi, E. K. Vouloumanou, P. I. Rafailidis, A. M. Kapaskelis, J. Rello. (2010) Effectiveness and safety of neuraminidase inhibitors in reducing influenza complications: a meta-analysis of randomized controlled trials. Journal of Antimicrobial Chemotherapy 65:7, 1330-1346
   CrossRef

2. 2

   B. Ghebremedhin, I. Engelmann, W. Konig, B. Konig. (2009) Comparison of the performance of the rapid antigen detection actim Influenza A&B test and RT-PCR in different respiratory specimens. Journal of Medical Microbiology 58:3, 365-370
   CrossRef

3. 3

   Natasha B. Halasa, Michael A. Gerber, Qingxia Chen, Peter F. Wright, Kathryn M. Edwards. (2008) Safety and Immunogenicity of Trivalent Inactivated Influenza Vaccine in Infants. The Journal of Infectious Diseases 197:10, 1448-1454
   CrossRef