A Longitudinal Study of Streptococcus pneumoniae Carriage in a Cohort of Infants and Their Mothers on the Thailand-Myanmar Border

Background Pneumococcal disease is a major cause of childhood death. Almost a third of the world's children live in Southeast Asia, but there are few data from the region on pneumococcal colonization or disease. Our aim was to document the dynamics of pneumococcal carriage in a rural SE Asian birth cohort. Methods We studied 234 Karen mother-infant pairs in Northwestern Thailand. Infants were followed from birth and nasopharyngeal swabs were taken from mother and infant at monthly intervals until 24 months old. Results 8,386 swabs were cultured and 4,396 pneumococci characterized. Infants became colonized early (median 45.5 days; 95% confidence interval [CI] 44.5-46.0) and by 24 months had a median of seven (range 0–15) carriage episodes. Maternal smoking and young children in the house were associated with earlier colonization (hazard ratio [HR] 1.5 (95% CI 1.1–2.1) and 1.4 (95% CI 1.0–1.9)). For the four commonest serotypes and non-typeable pneumococci, previous exposure to homologous or heterologous serotypes resulted in an extended interval to reacquisition of the same serotype. Previous colonization by serotypes 14 and 19F was also associated with reduced carriage duration if subsequently reacquired (HR [first reacquisition] 4.1 (95% CI 1.4–12.6) and 2.6 (1.5–4.7)). Mothers acquired pneumococci less frequently, and carried them for shorter periods, than infants (acquisition rate 0.5 vs. 1.1 /100 person-days, p<0.001; median duration 31.0 vs. 60.5 days, p = 0.001). 55.8% of pneumococci from infants were vaccine serotypes (13-valent pneumococcal conjugate vaccine, PCV13), compared with 27.5% from mothers (p<0.001). Non-typeable pneumococcal carriage was common, being carried at least once by 55.1% of infants and 32.0% of mothers. Conclusions Pneumococcal carriage frequency and duration are influenced by previous exposure to both homologous and heterologous serotypes. These data will inform vaccination strategies in this population

Comparison of NPS culture and serotyping results by processing method.

<p>1,107 nasopharyngeal swabs evaluated by both methods.</p

Individual pneumococcal serotype acquisition rates, by NPS culture/serotyping method.

<p>100 infants were included in each group; each serotype considered independently.</p>a<p>Acquisition rate per day.</p>b<p>Non-typeable pneumococcal colonisation excluded.</p

Infant carriage pneumococcal serotype distribution, by latex sweep serotyping.

<p>Results of culture of 8,736 swabs from 364 infants. The bars indicate the number of isolates of each serotype and the dashed lines indicate the cumulative frequency (cumulative frequency of 67% is indicated by the vertical arrows). Dark grey bars highlight PCV13 serotypes.</p

Duration of first pneumococcal carriage episode, stratified by NPS culture/serotyping method.

<p>100 infants were included in each group.</p

Relationship between colonisation density and agreement between WHO culture and latex sweep result.

<p>Relationship between colonisation density and agreement between WHO culture and latex sweep result.</p

Study flow diagram.

<p>* Described in detail in reference <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067933#pone.0067933-Turner3" target="_blank">[8]</a>.</p

Pneumococcal serotypes most commonly carried in infants and their mothers (ranked by overall isolation frequency).

a<p>OR for the serotype being carried at any time point (adjusted for number of swabs collected per individual; all <i>P</i><.05).</p>b<p>Excluding non-typeable (NT) pneumococci.</p

Observed and modeled age at first pneumococcal acquisition in the cohort of infants.

<p>Observed and modeled age at first pneumococcal acquisition in the cohort of infants.</p

Effect of previous carriage on reacquisition and carriage duration of common pneumococcal serotypes, controlling for age and carriage of heterologous serotypes (comparing first episodes of serotype carriage, not necessarily the infant's first ever carriage episode, with subsequent episodes of carriage of the same serotype).

a<p>Cox proportional hazards model.</p>b<p>Time from clearance of a serotype to subsequent reacquisition.</p>c<p>Parametric survival model (Weibull distribution).</p