Abstract

Streptococcus pneumoniae is a leading cause of pneumonia, the most common cause of childhood death. Papua New Guinean children experience high rates of nasopharyngeal pneumococcal colonization within weeks of birth, predisposing them to pneumococcal disease. In a trial to determine the safety and immunogenicity of early infant vaccination with 7-valent pneumococcal conjugate vaccine (7vPCV), we investigated the impact of early schedules on pneumococcal carriage.Infants were randomized at birth to receive 7vPCV in a 0–1–2-month (n=101) or a 1–2–3-month (n=105) schedule or no 7vPCV (n=106). All children received 23-valent pneumococcal polysaccharide vaccine at age 9months. We cultured nasopharyngeal swabs (NPS) collected at ages 1, 2, 3, 4weeks and 3, 9, 18months, and middle ear discharge if present. Pneumococcal serotypes were identified by the Quellung reaction.A total of 1761 NPS were cultured. The prevalence of pneumococcal carriage was 22% at 1week of age, rising to 80% by age 3months and remained >70% thereafter, with high-density carriage in 42% of pneumococcus-positive samples. We identified 63 different serotypes; 43% of isolates from controls were 13vPCV serotypes. There were no significant differences in 7vPCV serotype carriage between 7vPCV recipients and controls at any age (22% vs. 31% at 9months, p=0.2). At age 9months the prevalence of non-7vPCV carriage was 17% higher in 7vPCV recipients (48%) than in controls (25%, p=0.02). More non-7vPCV serotypes were isolated from ear discharge in 16 7vPCV recipients than from 4 controls (48% vs. 25%, p=0.13).The limited impact of neonatal or accelerated infant 7vPCV schedules on vaccine serotype carriage is probably due to the early onset of dense carriage of a broad range of pneumococcal serotypes. While serotype-independent pneumococcal vaccines are needed in high-risk populations, the underlying environmental factors and sources of infection must be investigated.http://clinicaltrials.gov/ct2/show/NCT00219401.

Highlights

  • Pneumonia is the most common cause of death in children worldwide [1]

  • In a trial to determine the safety and immunogenicity of early infant vaccination with 7-valent pneumococcal conjugate vaccine (7vPCV), we investigated the impact of early schedules on pneumococcal carriage

  • In the highlands of Papua New Guinea (PNG), colonization of the nasopharynx starts within weeks of birth, with all infants acquiring S. pneumoniae by 3 months of age and high carriage rates being maintained throughout childhood [4,5,6]

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Summary

Introduction

Pneumonia is the most common cause of death in children worldwide [1]. Streptococcus pneumoniae (the pneumococcus) is a major cause of pneumonia as well as other invasive diseases such as meningitis and bacteraemia. The introduction and widespread use of PCVs in first world countries has resulted in a significant decline in nasopharyngeal carriage and IPDs caused by vaccine serotypes in children under the age of 2 years. PCV given at ages 6, 10 and 14 weeks in third world countries and 2, 4 and 6 months with a booster in the second year of life in first world countries are immunogenic and reduce nasopharyngeal carriage of pneumococcal serotypes included in PCVs [10,15]. A pneumococcal polysaccharide vaccine has previously been shown to reduce pneumonia mortality in PNG children when given between the ages of 6 months and 5 years [16]. We aim to describe the effect of 7vPCV on nasopharyngeal carriage of pneumococci and pneumococcal serotypes when given either in a 0–1–2 or 1–2–3-month schedule. We look at the effect of 7vPCV on pneumococci isolated from ear discharge swabs of children with tympanic membrane perforation (TMP) due to OM

Methods
Study design
Nasopharyngeal swab collection
Culture of nasopharyngeal swabs and ear swabs
Serotyping
Statistical analysis
Ethical considerations
Study population characteristics
Age-specific prevalence of pneumococcal carriage by allocated group
Serotype-specific data
Pneumococcal isolation rates from middle ear discharge
Discussion
Conflicts of Interest

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