ArticlesEfficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial
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)
- et al.
Estimates of world-wide distribution of child deaths from acute respiratory infections
Lancet
(2002) - et al.
Design of a group-randomized Streptococcus pneumoniae vaccine trial
Controlled Clin Trials
(2001) - et al.
Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995–1998: opportunities for prevention in the conjugate vaccine era
JAMA
(2001) - et al.
Epidemiology of invasive pneumococcal disease in the Western Region, The Gambia
Pediatr Infect Dis J
(1998) - et al.
Pneumococcal bacteremia during a decade in children in Soweto, South Africa
Pediatr Infect Dis J
(2000) - 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...
- et al.
Invasive pneumococcal disease in an Alaska Native population, 1980 through 1986
JAMA
(1989)
Cited by (327)
Infectious diseases in Indigenous populations in North America: learning from the past to create a more equitable future
2023, The Lancet Infectious DiseasesChallenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group
2019, The Lancet Respiratory MedicineMaking sense of differences in pneumococcal serotype replacement
2019, The Lancet Infectious Diseases