18 research outputs found

    A Retrospective Cohort Analysis of Pediatric Tuberculosis in North Carolina, 1994-2002

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    Background: The incidence of pediatric tuberculosis (TB) in North Carolina decreased from the mid 1990s to 200l. In 2002, the number of pediatric TB cases increased from 9 in 2001 to 32 in 2002, representing more than a 250% increase. Objective: To describe the epidemiology and clinical characteristics of pediatric TB in North Carolina and identify factors contributing to the rise in tuberculosis cases among children less than 15 years of age. Methods: Retrospective review of TB surveillance data and local health department records of all reported pediatric TB cases and their source case between the years 1994 and 2002. Results: 180 cases of pediatric TB were reported from 1994-2002. The incidence of pediatric TB increased from 0.53 to 1.85 per 100,000 from 2001 to 2002. TB case rates in 2002 were higher in children less than 5 years of age (3.05 per 100,000) compared to children 5-14 years of age (1.28 per 100,000). TB case rates were 10- to 44-fold higher among minority children compared to non-Hispanic white children. Although there was no significant increase in the incidence of TB in the Hispanic pediatric population, there was a significant increase in the proportion of Hispanic children with tuberculosis (p-value =.04). Children with a foreign association accounted for an increasing proportion of pediatric TB cases over time, however, the increase was not statistically significant (p-value = 0.09). Transmission of TB to children could have been prevented in 6.75% of cases had a source case identified the child as a contact, and in 11.7% of cases had the source case completed prophylaxis for latent TB infection. TB disease may have been prevented in 7.2% of cases had the contact investigation not been delayed, 2.2% of cases had children with latent TB infection completed prophylaxis, and in 4.4% of cases had child contacts <5 years of age with a negative PPD taken or received prophylaxis. Overall, 51/180 cases (28.3%) might have been prevented had appropriate measures been taken. Conclusion: The incidence of pediatric TB increased significantly from 2001 to 2002. TB in the minority population continues to be a problem. TB in children with a foreign-association is increasing. Improvements in contact investigations and completion of prophylaxis for LTBI may reduce the incidence of pediatric TB.Master of Public Healt

    PD-1 and CTLA-4 expression on PPD-specific CD4 T-cells in response to TB treatment.

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    <p><b>A.</b> Representative plot showing the gating scheme used to identify PD-1, CTLA-4, and 2B4 expression on PPD-specific CD4 T-cells. Single, live, CD3<sup>+</sup>, CD4<sup>+</sup> cells were gated for CD27 and CD45RO. The naïve CD4 T cell population was identified (CD27<sup>+</sup>CD45RO<sup>-</sup>) and selected to set gates for PD-1, CTLA-4 and 2B4 as this population typically does not express inhibitory molecules. These gates were then applied to PPD-specific and total CD4 T-cell populations. <b>B.</b> Expression of PD-1, CTLA-4, and 2B4 on PPD-specific CD4 T-cells in untreated and treated TB disease. <b>C.</b> Correlation between baseline CD4 T-cell count and frequency of PD-1 and CTLA-4 expression on PPD-specific CD4 T-cells in untreated and treated TB disease. Lines of best fit, along with Spearman’s rank correlation coefficient and corresponding p-values are shown <b>D.</b> Expression of PD-1, CTLA-4, and 2B4 on CMV-specific CD4 T-cells in untreated and treated TB disease in our HIV-TB and TB cohorts. <b>E</b>. Expression of PD-1, CTLA-4, and 2B4 on total CD4 T-cells in untreated and treated TB disease in our HIV-TB and TB cohorts. <b>F</b>. Bar graph depicts the co-expression patterns of PD-1, CTLA-4, and 2B4 on PPD-specific CD4 T-cells in untreated and treated TB disease in our HIV-TB and TB cohorts. To assess expression of inhibitory molecules on PPD and CMV-specific CD4 T-cells, only samples with at least 50 cytokine positive cells and 2-fold higher responses than negative control samples were included to allow for a statistically valid analysis. * denotes p<0.05, ** p<0.01, *** p<0.001 by Wilcoxon matched-pairs signed rank test. denotesp<0.05, denotes p<0.05,  p<0.01, p<0.01,     p<0.001 by Mann-Whitney test.</p

    TB therapy alters maturation phenotype of PPD-specific CD4 T-cells.

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    <p><b>A.</b> Representative example of differentiation marker expression on PPD-specific CD4 T-cells. PPD-specific CD4 T-cells (red dots) are overlaid onto density plots of CD27 and CD45RO and CD27 and CD57, gated on total CD4 T-cells. <b>B.</b> Frequency of PPD-specific CD4 T-cells expressing CD27<sup>+</sup>CD45RO<sup>+</sup> (CM), CD27<sup>-</sup>CD45RO<sup>+</sup> (EM), and CD57<sup>+</sup> (TD) phenotypes. <b>C.</b> Correlation between baseline CD4 T-cell count and frequency of PPD-specific CD4 T-cells expressing CM and TD phenotypes in untreated and treated TB disease. Lines of best fit, along with Spearman’s rank correlation coefficient and corresponding p-values are shown <b>D.</b> Frequency of CMV-specific CD4 T-cells expressing CM, EM, and TD phenotypes in our HIV-TB and TB cohorts. <b>E.</b> Frequency of naïve, CM, EM, and TD subsets on total CD4 T-cells in untreated and treated TB disease in our HIV-TB and TB cohorts. To assess maturation phenotype on PPD and CMV-specific CD4 T-cells, only samples with at least 50 cytokine positive cells and 2-fold higher responses than negative control samples were included to allow for a statistically valid analysis. The Wilcoxon matched-pairs signed rank test was used for paired comparisons (HIV-TB cohort) while the Mann-Whitney test was used to analyze unpaired data (TB cohort and comparisons between cohorts). * denotes p<0.05, ** p<0.01, *** p<0.001 by Wilcoxon matched-pairs signed rank test. denotesp<0.05, denotes p<0.05,  p<0.01, p<0.01,     p<0.001 by Mann-Whitney test.</p

    TB therapy alters the functional profile of PPD-specific CD4 T-cells.

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    <p><b>A.</b> Representative plot showing the gating scheme used to identify cytokine/chemokine positive cells. Single, live, CD3<sup>+</sup>, CD4<sup>+</sup> T cells were gated for CD27 and CD45RO to identify the total CD4 memory population. Cytokine/chemokine gates were then applied to the total CD4 memory population to identify cytokine/chemokine positive cells. <b>B.</b> Total frequency of IFN-Îł, TNF-α, IL-2, and MIP-1ÎČ produced by memory CD4 T-cells in untreated and treated TB disease within our HIV-TB and TB cohorts. Background cytokine/chemokine production from the negative control sample was subtracted. <b>C.</b> Pie graph displaying the proportion of cytokine/chemokine<sup>+</sup> CD4 T-cells producing all 4 cytokines/chemokines (light grey wedge) or any combination of 3 cytokines/chemokines (medium gray), 2 cytokines/chemokines (dark grey), or a single cytokine/chemokine (black wedge) in untreated and treated TB disease. The bar graph depicts the relative contribution of each cytokine/chemokine producing subset to the overall PPD-specific CD4 T-cell response. “G” denotes IFN-Îł, “2” denotes IL-2, “T” denotes TNF-α, and “M” denotes MIP-1ÎČ. For all bar graphs bars represent the interquartile range (IQR), horizontal lines denote the median, and whiskers the 10<sup>th</sup> and 90<sup>th</sup> percentiles. Solid bars represent our HIV-TB cohort, patterned bars represent our TB cohort. Light gray represents untreated TB disease while dark gray represents treated TB disease. Statistical analysis was performed using the Wilcoxon matched-pairs signed rank test for paired data (HIV-TB cohort) and the Mann-Whitney test for unpaired data (TB cohort or comparisons between cohorts).* denotes p<0.05, ** p<0.01, *** p<0.001 by Wilcoxon matched-pairs signed rank test. denotesp<0.05, denotes p<0.05,  p<0.01, p<0.01,     p<0.001 by Mann-Whitney test.</p

    Maternal transfer of IgA and IgG SARS-CoV-2 specific antibodies transplacentally and via breast milk feeding

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    Background Although there have been many studies on antibody responses to SARS-CoV-2 in breast milk, very few have looked at the fate of these in the infant, and whether they are delivered to immunologically relevant sites in infants. Methods Mother/infant pairs (mothers who breast milk fed and who were SARS-CoV-2 vaccinated before or after delivery) were recruited for this cross-sectional study. Mother blood, mother breast milk, infant blood, infant nasal specimen, and infant stool was tested for IgA and IgG antibodies against SARS-CoV-2 spike trimer. Results Thirty-one mother/infant pairs were recruited. Breast milk fed infants acquired systemic anti-spike IgG antibodies only if their mothers were vaccinated antepartum (100% Antepartum; 0% Postpartum; PConclusion Vaccination antepartum followed by breast milk feeding appears to be the best way to provide systemic and local anti-SARS-CoV-2 antibodies for infants. The presence of high titer SARS-CoV-2-specific IgA in the nose of infants points to the potential importance of breast milk feeding early in life for maternal transfer of mucosal IgA antibodies. Expectant mothers should consider becoming vaccinated antepartum and consider breast milk feeding for optimal transfer of systemic and mucosal antibodies to their infants

    Maternal transfer of IgA and IgG SARS-CoV-2 specific antibodies transplacentally and via breast milk feeding.

    No full text
    BackgroundAlthough there have been many studies on antibody responses to SARS-CoV-2 in breast milk, very few have looked at the fate of these in the infant, and whether they are delivered to immunologically relevant sites in infants.MethodsMother/infant pairs (mothers who breast milk fed and who were SARS-CoV-2 vaccinated before or after delivery) were recruited for this cross-sectional study. Mother blood, mother breast milk, infant blood, infant nasal specimen, and infant stool was tested for IgA and IgG antibodies against SARS-CoV-2 spike trimer.ResultsThirty-one mother/infant pairs were recruited. Breast milk fed infants acquired systemic anti-spike IgG antibodies only if their mothers were vaccinated antepartum (100% Antepartum; 0% Postpartum; PConclusionVaccination antepartum followed by breast milk feeding appears to be the best way to provide systemic and local anti-SARS-CoV-2 antibodies for infants. The presence of high titer SARS-CoV-2-specific IgA in the nose of infants points to the potential importance of breast milk feeding early in life for maternal transfer of mucosal IgA antibodies. Expectant mothers should consider becoming vaccinated antepartum and consider breast milk feeding for optimal transfer of systemic and mucosal antibodies to their infants
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