Kinetics of antibodies against pneumococcal proteins and their relationship to nasopharyngeal carriage in the first two months of life.

INTRODUCTION: The currently used Streptococcus pneumoniae vaccines have had a significant impact on the pneumococcal diseases caused by the serotypes they cover. Their limitations have stimulated a search for alternate vaccines that will cover all serotypes, be affordable and effective in young children. Pneumococcal protein antigens are potential vaccine candidates that may meet some of the shortfalls of the current vaccines. Thus, this study aimed to determine the relationship between antibodies against pneumococcal protein antigens and nasopharyngeal carriage in infants. METHODS: One hundred and twenty mother-infant pairs were enrolled into the study. They had nasopharyngeal swabs(NPS) taken at birth and every two weeks for the first eight weeks after delivery, and blood samples were obtained at birth and every four weeks for the first eight weeks after delivery. Nasopharyngeal carriage of S. pneumoniae was determined from the NPS and antibodies against the pneumococcal proteins CbpA, PspA and rPly were measured in the blood samples. RESULTS: The S. pneumoniae carriage rate in infants increased to that of mothers by eight weeks of age. The odds of carriage in infants was 6.2 times (95% CI: 2.0-18.9) higher when their mothers were also carriers. Bacterial density in infants was lower at birth compared to their mothers (p = 0.004), but increased with age and became higher than that of their mothers at weeks 4 (p = 0.009), 6 (p = 0.002) and 8 (p<0.0001). At birth, the infants' antibodies against CbpA, and rPly pneumococcal protein antigens were similar, but that of PspA was lower (p<0.0001), compared to their mothers. Higher antibody concentrations to CbpA [OR (95% CI): 0.49 (0.26-0.92, p = 0.03)], but not PspA and rPly, were associated with protection against carriage in the infants. CONCLUSION: Naturally induced antibodies against the three pneumococcal protein antigens were transferred from mother to child. The proportion of infants with nasopharyngeal carriage and the bacterial density of S. pneumoniae increased with age within the first eight weeks of life. Higher concentrations of antibodies against CbpA, but not PspA and rPly, were associated with reduced risk of nasopharyngeal carriage of S. pneumoniae in infants

Highly Accurate Diagnosis of Pleural Tuberculosis by Immunological Analysis of the Pleural Effusion

Pleural TB is notoriously difficult to diagnose due to its paucibacillary nature yet it is the most common cause of pleural effusions in TB endemic countries such as The Gambia. We identified both cellular and soluble biomarkers in the pleural fluid that allowed highly accurate diagnosis of pleural TB compared to peripheral blood markers. Multi-plex cytokine analysis on unstimulated pleural fluid showed that IP-10 resulted in a positive likelihood ratio (LR) of 9.6 versus 2.8 for IFN-γ; a combination of IP-10, IL-6 and IL-10 resulted in an AUC of 0.96 and positive LR of 10. A striking finding was the significantly higher proportion of PPD-specific IFN-γ+TNF-α+ cell population (PPD-IGTA) in the pleural fluid compared to peripheral blood of TB subjects. Presence of this pleural PPD-IGTA population resulted in 95% correct classification of pleural TB disease with a sensitivity of 95% and specificity of 100%. These data suggest that analysis of the site of infection provides superior diagnostic accuracy compared to peripheral blood for pleural TB, likely due to the sequestration of effector cells at this acute stage of disease

Effects of mother’s log-antibody concentrations against <i>CbpA</i>, <i>PspA</i> and <i>rPly</i> at delivery on infant’s log-antibody concentrations and difference in infant’s antibody concentrations between carriers and non-carriers at birth, 4 and 8 weeks.

<p>Effects of mother’s log-antibody concentrations against <i>CbpA</i>, <i>PspA</i> and <i>rPly</i> at delivery on infant’s log-antibody concentrations and difference in infant’s antibody concentrations between carriers and non-carriers at birth, 4 and 8 weeks.</p

Kinetics of antibodies against pneumococcal proteins and their relationship to nasopharyngeal carriage in the first two months of life

<div><p>Introduction</p><p>The currently used <i>Streptococcus pneumoniae</i> vaccines have had a significant impact on the pneumococcal diseases caused by the serotypes they cover. Their limitations have stimulated a search for alternate vaccines that will cover all serotypes, be affordable and effective in young children. Pneumococcal protein antigens are potential vaccine candidates that may meet some of the shortfalls of the current vaccines. Thus, this study aimed to determine the relationship between antibodies against pneumococcal protein antigens and nasopharyngeal carriage in infants.</p><p>Methods</p><p>One hundred and twenty mother-infant pairs were enrolled into the study. They had nasopharyngeal swabs(NPS) taken at birth and every two weeks for the first eight weeks after delivery, and blood samples were obtained at birth and every four weeks for the first eight weeks after delivery. Nasopharyngeal carriage of <i>S</i>. <i>pneumoniae</i> was determined from the NPS and antibodies against the pneumococcal proteins CbpA, PspA and rPly were measured in the blood samples.</p><p>Results</p><p>The <i>S</i>. <i>pneumoniae</i> carriage rate in infants increased to that of mothers by eight weeks of age. The odds of carriage in infants was 6.2 times (95% CI: 2.0–18.9) higher when their mothers were also carriers. Bacterial density in infants was lower at birth compared to their mothers (p = 0.004), but increased with age and became higher than that of their mothers at weeks 4 (p = 0.009), 6 (p = 0.002) and 8 (p<0.0001). At birth, the infants’ antibodies against <i>CbpA</i>, and <i>rPly</i> pneumococcal protein antigens were similar, but that of <i>PspA</i> was lower (p<0.0001), compared to their mothers. Higher antibody concentrations to <i>CbpA</i> [OR (95% CI): 0.49 (0.26–0.92, p = 0.03)], but not <i>PspA</i> and <i>rPly</i>, were associated with protection against carriage in the infants.</p><p>Conclusion</p><p>Naturally induced antibodies against the three pneumococcal protein antigens were transferred from mother to child. The proportion of infants with nasopharyngeal carriage and the bacterial density of <i>S</i>. <i>pneumoniae</i> increased with age within the first eight weeks of life. Higher concentrations of antibodies against <i>CbpA</i>, but not <i>PspA</i> and <i>rPly</i>, were associated with reduced risk of nasopharyngeal carriage of <i>S</i>. <i>pneumoniae</i> in infants.</p></div

Effects of mother’s log-antibody concentrations against <i>CbpA</i>, <i>PspA</i> and <i>rPly</i> at delivery on infant’s log-antibody concentrations and difference in infant’s antibody concentrations between carriers and non-carriers at birth, 4 and 8 weeks.

<p>Effects of mother’s log-antibody concentrations against <i>CbpA</i>, <i>PspA</i> and <i>rPly</i> at delivery on infant’s log-antibody concentrations and difference in infant’s antibody concentrations between carriers and non-carriers at birth, 4 and 8 weeks.</p

Dynamic relationship between concentration of antibodies against <i>CbpA</i>, <i>PspA</i> and <i>rPly</i> and nasopharyngeal carriage in infants.

<p>Dynamic relationship between concentration of antibodies against <i>CbpA</i>, <i>PspA</i> and <i>rPly</i> and nasopharyngeal carriage in infants.</p

Concentration of antibodies against <i>CbpA</i>, <i>PspA</i> and <i>rPly</i> in mothers’ (closed circles) and cord blood (open circles) at birth.

<p>The horizontal black lines represent the average log-plasma antibody concentrations. The p values indicate the difference between the average antibody concentration for the specific pneumococcal antigen between mothers’ venous blood and infants’ cord blood at birth.</p

The density of <i>S</i>.<i>pneumoniae</i> in the nasopharynx in the first eight weeks after birth in infants (A) and the first eight weeks after delivery in mothers (B).

<p>The horizontal black lines represent the average Real-time Ct value, which is inversely correlated with the density. The p value indicates the evidence of variation of the density over the eight week period.</p

Dynamic of nasopharyngeal carriage and influence of concentration of antibodies against <i>CbpA</i>, <i>PspA</i> and <i>rPly</i> in infants.

<p>Dynamic of nasopharyngeal carriage and influence of concentration of antibodies against <i>CbpA</i>, <i>PspA</i> and <i>rPly</i> in infants.</p