Correspondence

Pneumococcal Conjugate Vaccine in Children

N Engl J Med 2004; 350:84-85January 1, 2004

Article

To the Editor:

In their trial of a 9-valent pneumococcal conjugate vaccine in children with human immunodeficiency virus infection and those without infection, Klugman and colleagues (Oct. 2 issue)1 found an increased risk of asthma among vaccinees. We assessed this risk in a randomized, controlled trial of the 7-valent pneumococcal conjugate vaccine in northern California.2

From 1995 to 1998, a total of 37,868 children at Kaiser Permanente received pneumococcal conjugate vaccine or control meningococcal C conjugate vaccine. The risk of a first hospitalization or emergency department visit for asthma (International Classification of Diseases, code 493.xx) was assessed with the use of Cox regression analysis. We conducted an intention-to-treat analysis of follow-up data through 2002 (keeping in the control group the 23 percent of controls who received pneumococcal conjugate vaccine after the completion of the trial). A total of 359 children were hospitalized for asthma, and 1210 were seen in the emergency department for asthma. The risk of asthma that required hospitalization did not differ significantly between the two groups (relative risk in the pneumococcal-vaccine group, 1.03; 95 percent confidence interval, 0.84 to 1.27), nor did the risk of asthma that required a visit to the emergency department (relative risk, 1.09; 95 percent confidence interval, 0.97 to 1.22). Intention-to-treat and per-protocol analyses that ended at the completion of the trial (in April 1999) also showed no significant difference between the groups with respect to hospitalization or an emergency department visit for asthma. In contrast to the findings reported by Klugman et al., we found no association between conjugate pneumococcal vaccination and severe asthma.

Editor's note: Drs. Davis and Shinefield and Mr. Fireman report having received research grants from Wyeth–Ayerst, maker of the referenced pneumococcal conjugate vaccine.

Robert L. Davis, M.D., M.P.H.
Kaiser Permanente Vaccine Studies Center, Oakland, CA 94612
rdavis@u.washington.edu

Bruce Fireman, M.A.
Kaiser Permanente Division of Research, Oakland, CA 94612

Henry R. Shinefield, M.D.
Kaiser Permanente Vaccine Studies Center, Oakland, CA 94612

2 References

1. 1

   Klugman KP, Madhi SA, Huebner RE, Kohberger R, Mbelle N, Pierce N. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N Engl J Med 2003;349:1341-1348
   Full Text | Web of Science | Medline

2. 2

   Black S, Shinefield H, Fireman B, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J 2000;19:187-195
   CrossRef | Web of Science | Medline

Author/Editor Response

We are gratified to learn that there was only a small, statistically nonsignificant excess of asthma episodes among recipients of the 7-valent conjugate pneumococcal vaccine in the northern California study.1 Differences in study design, follow-up, and detection of cases make direct comparisons of rates difficult to interpret. The administration of meningococcal conjugate in controls and the continued inclusion in the control group of the 23 percent of controls who received pneumococcal vaccine after the completion of the trial may have reduced the strength of the association between vaccination and asthma in that study. On the assumption of a follow-up time per group of 107,000 person-years in the California study,1 the intention-to-treat rates of asthma episodes in that study were 760 per 100,000 person-years among vaccinees and 707 per 100,000 person-years among controls (an excess of 53 episodes per 100,000 person-years). In Soweto, South Africa, there were 128 episodes per 100,000 person-years in vaccinees and 71 per 100,000 in controls (an excess of 57 episodes per 100,000 person-years). The higher rates in California may be due to increased identification of outpatient diagnoses of asthma (the Soweto data include only patients in whom asthma was diagnosed at the hospital) and higher rates of asthma among older children included in the California follow-up study. Attack rates of asthma continue to be monitored in our trial, and these data suggest that they should continue to be monitored in post-marketing surveillance and in ongoing trials of pneumococcal conjugate vaccine in the Czech and Slovak Republics, the Gambia, and the Philippines.

Keith P. Klugman, M.B., B.Ch., Ph.D.
Emory University, Atlanta, GA 30322
kklugma@sph.emory.edu

Shabir A. Madhi, M.B., B.Ch.
Respiratory and Meningeal Pathogens Research Unit, Bertsham, Gauteng 2013, South Africa

Robert Kohberger, Ph.D.
Wyeth, Pearl River, NY 10965

1 References

1. 1

   Black S, Shinefield H, Fireman B, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J 2000;19:187-195
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Froukje Oosterhuis-Kafeja, Philippe Beutels, Pierre Van Damme. (2007) Immunogenicity, efficacy, safety and effectiveness of pneumococcal conjugate vaccines (1998–2006). Vaccine 25:12, 2194-2212
   CrossRef

2. 2

   Marilla G Lucero, Vernoni E Dulalia, Rhea Angela N Parreño, Dolores Lim-Quianzon, Hanna Nohynek, Helena Makela, Gail Williams, Marilla G Lucero. 2004. Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and pneumonia with consolidation on x-ray in children under two years of age. .
   CrossRef

3. 3

   Shaine A Morris, Henry H Bernstein. (2004) Immunizations, neonatal jaundice, and animal-induced injuries. Current Opinion in Pediatrics 16:4, 450-460
   CrossRef