Elsevier

The Lancet

Volume 362, Issue 9381, 2 August 2003, Pages 355-361
The Lancet

Articles
Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial

https://doi.org/10.1016/S0140-6736(03)14022-6Get rights and content

Summary

Background

Streptococcus pneumoniae is the main cause of invasive bacterial disease in children aged younger than 2 years. Navajo and White Mountain Apache children have some of the highest rates of invasive pneumococcal disease documented in the world. We aimed to assess the safety and efficacy of a seven-valent polysaccharide protein conjugate pneumococcal vaccine (PnCRM7) against such disease.

Methods

In a group-randomised study, we gave this vaccine to children younger than 2 years from the Navajo and White Mountain Apache Indian reservations; meningococcal type C conjugate vaccine (MnCC) served as the control vaccine. Vaccine schedules were determined by age at enrolment. We recorded episodes of invasive pneumococcal disease and serotyped isolates. Analyses were by intention to treat and per protocol.

Findings

8292 children enrolled in the trial. In the per protocol analysis of the primary efficacy group (children enrolled by 7 months of age) there were eight cases of vaccine serotype disease in the controls and two in the PnCRM7 group; in the intention-to-treat analysis we noted 11 cases of vaccine serotype disease in the MnCC control group and two in the PnCRM7 group. After group randomisation had been controlled for, the per protocol primary efficacy of PnCRM7 was 76·8% (95% CI −9·4% to 95·1%) and the intention-to-treat total primary efficacy was 82·6% (21·4% to 96·1%).

Interpretation

PnCRM7 vaccine prevents vaccine serotype invasive pneumococcal disease even in a high risk population. Other regions with similar disease burden should consider including this vaccine in the routine childhood vaccine schedule.

Introduction

Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality in people of all ages, but especially in those at the extremes of age, and in those who live in developing countries. Before the introduction of pneumococcal conjugate vaccine, the rate of invasive pneumococcal disease in children younger than 2 years was 166·9 per 100 000 child-years in the USA.1 The burden of invasive pneumococcal disease in young children in developing countries is substantially higher than that in developed countries. For example, the incidence of invasive pneumococcal disease in children younger than 12 months was reported to be 224 and 349 per 100 000 in The Gambia and South Africa, respectively.2, 3 Rates of non-bacteraemic pneumococcal pneumonia in young children are estimated to be two to ten times those of invasive disease. There are an estimated 1·9 million deaths worldwide from acute respiratory illness in children younger than 5 years each year, many of these deaths are caused by S pneumoniae.4

People of the Navajo and White Mountain Apache tribes in southwestern USA, and Alaska Native populations are at high risk of invasive pneumococcal disease.5, 6, 7, 8 Between 1983 and 1990, the rate of invasive pneumococcal disease in White Mountain Apache children younger than 2 years was 1820 per 100 000, and for Navajo children the rate was 537 per 100 000 between 1989 and 1996—frequencies that do not compare favourably with those in of the general US population. Reasons for the increased risk of disease are unknown.

For young children, pneumococcal polysaccharide vaccines provide little protection against pneumococcal disease because those younger than 2 years of age respond poorly to T-cell independent antigens such as pure polysaccharide antigens. However, infants and young children are very capable of mounting a brisk immune response to T-cell dependent antigens. As a result, serotype-specific pneumococcal polysaccharide-protein conjugate vaccines, which result in a T-cell dependent immune response have been developed. One such vaccine, a seven-valent pneumococcal vaccine conjugate to CRM197 (PnCRM7), has proved efficacious against invasive pneumococcal disease in children younger than 2 years of age in a Northern California population9 and against pneumococcal otitis media in young children in Finland.10

We aimed to determine the efficacy of this pneumococcal conjugate vaccine against invasive pneumococcal disease in American Indian children at high risk of invasive pneumococcal disease. Unlike the Northern California Kaiser Permanente (NCKP) study, we used a group-randomised design to assess the potential effect of the vaccine in a community, measuring indirect effects of the vaccine through reduction in carriage and secondary attack rates. Analyses of indirect effects of the vaccine will be reported separately.

Section snippets

Population sites

On the Navajo and White Mountain Apache Indian reservations, health care is provided through the Indian Health Service (IHS) agency of the federal Department of Health and Human Services. Each reservation is divided into geographic administrative areas called service units that vary in size and scope of healthcare facilities.

The Navajo Nation is one of the largest Indian tribes in the USA with about 200 000 members and the largest reservation in the country, which covers more than 25 000 square

Results

We assessed 10 864 infants for eligibilty—about 80% of children within the target age range (figure). After exclusion of children who were ineligible and those whose parents declined to participate, we enrolled 8292 (76·3%) infants in the study between April 30, 1997, and Dec 31, 1999. Therefore, about 60% of the age-eligible population participated in the trial. Of the 8292 enrolled infants, 8091 (97·5%) resided in one of the 38 units of randomisation. The remaining 201 infants resided in

References (16)

  • BG Williams et al.

    Estimates of world-wide distribution of child deaths from acute respiratory infections

    Lancet

    (2002)
  • LH Moulton et al.

    Design of a group-randomized Streptococcus pneumoniae vaccine trial

    Controlled Clin Trials

    (2001)
  • K Robinson et al.

    Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995–1998: opportunities for prevention in the conjugate vaccine era

    JAMA

    (2001)
  • S Usen et al.

    Epidemiology of invasive pneumococcal disease in the Western Region, The Gambia

    Pediatr Infect Dis J

    (1998)
  • A Karstaedt et al.

    Pneumococcal bacteremia during a decade in children in Soweto, South Africa

    Pediatr Infect Dis J

    (2000)
  • MM Cortese et al.

    High incidence rates of invasive pneumococcal disease in the White Mountain Apache population

    Arch Intern Med

    (1992)
  • O'Brien KL, Croll J, Parkinson AJ, Reid R, Santosham M. Active laboratory-based surveillance for invasive Streptococcus...
  • M Davidson et al.

    Invasive pneumococcal disease in an Alaska Native population, 1980 through 1986

    JAMA

    (1989)
There are more references available in the full text version of this article.

Cited by (327)

View all citing articles on Scopus
View full text