Elsevier

The Lancet

Volume 368, Issue 9546, 28 October–3 November 2006, Pages 1495-1502
The Lancet

Articles
Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case-control study

https://doi.org/10.1016/S0140-6736(06)69637-2Get rights and content

Summary

Background

When seven-valent pneumococcal conjugate vaccine was introduced in the USA, many children were vaccinated on schedules that differed from those tested in clinical trials. Our aim was to assess the effectiveness of the vaccine against various pneumococcal serotypes, and to measure the effectiveness of the recommended dose schedule and of catch-up and incomplete schedules.

Methods

Invasive disease, defined as isolation of pneumococcus from a sterile site, was identified in children aged 3–59 months through the US Centers for Disease Control and Prevention's Active Bacterial Core surveillance. We tested isolates for serotype and antimicrobial susceptibility. Three controls, matched for age and zip code were selected for each case. We calculated the matched odds ratio for vaccination using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness was calculated as one minus the adjusted matched odds ratio times 100%.

Findings

We enrolled 782 cases and 2512 controls. Effectiveness of one or more doses against vaccine serotypes was 96% (95% CI 93–98) in healthy children and 81% (57–92) in those with coexisting disorders. It was 76% (63–85) against infections that were not susceptible to penicillin. Vaccination prevented disease caused by all seven vaccine serotypes, and by vaccine-related serotype 6A. Several schedules were more protective than no vaccination; three infant doses with a booster were more protective against vaccine-type disease than were three infant doses alone (p=0·0323).

Interpretation

The seven-valent pneumococcal conjugate vaccine prevents invasive disease in both healthy and chronically ill children. The vaccine is effective when used with various non-standard schedules.

Introduction

Seven-valent pneumococcal conjugate vaccine was designed to prevent pneumococcal disease in young children. In randomised, blinded, controlled clinical trials of this vaccine and a closely related nine-valent version, the vaccines were highly effective against invasive infections,1, 2, 3, 4 moderately so against pneumonia,3, 4, 5 and somewhat so against otitis media.6 On the basis of such evidence, the seven-valent vaccine was licensed to prevent pneumococcal disease in infants in the USA and was recommended for use in all children younger than 2 years and in children aged 2–4 years in a high-risk category.7, 8

After licensure, health-care providers began using the vaccine, with various schedules. Providers gave doses to infants at ages 2 months, 4 months, 6 months, and 12–15 months, according to the four-dose schedule developed in clinical trials of the seven-valent vaccine, and used several recommended but largely untested catch-up schedules7 in older infants and toddlers. Between August, 2001, and September, 2004, the seven-valent vaccine was often in short supply, and health-care providers were frequently unable to give the recommended number of doses.9 Nonetheless, surveillance data indicated that vaccine introduction substantially diminished the burden of invasive disease.10, 11, 12

To assess the effectiveness of the seven-valent pneumococcal conjugate vaccine we did a matched case-control study. Our primary objective was to measure effectiveness of pneumococcal conjugate vaccine against invasive disease caused by various pneumococcal strains, including the seven vaccine serotypes in children 3–59 months old, and to assess effectiveness of various schedules.

Section snippets

Study population

Cases of invasive pneumococcal disease were identified through the Active Bacterial Core Surveillance (ABCS). This population and laboratory based surveillance system is operated by the US Centers for Disease Control and Prevention (CDC) as part of its Emerging Infections Program Network.13 The surveillance area was defined to include cases from San Francisco, California; Denver, Colorado; Connecticut state; Atlanta, Georgia; Minnesota (Minneapolis and Saint Paul in 2001 and the entire state

Results

We identified 1267 children with invasive pneumococcal disease during the period under study. Of these children, 485 (38%) were not enrolled: 146 (12%) had no isolate available for serotyping; 113 (9%) could not be located; the parents of 161 (13%) refused to allow them to participate; matched controls could not be enrolled for 11 (1%); and 16 (1%) lacked a confirmed vaccination history. A further 38 (3%) were not enrolled for other reasons, such as identification more than 120 days after

Discussion

The seven-valent conjugate vaccine was protective in children 3–59 months old against disease caused by all seven serotypes contained in the vaccine, against disease caused by antibiotic-resistant strains, and against all invasive pneumococcal disease irrespective of serotype. Our results accord with findings of earlier clinical trials in which seven-valent or nine-valent conjugate vaccine formulations were given in highly controlled settings in which infants were vaccinated on three-dose or

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