Economic evaluation of pneumococcal conjugate vaccination in The Gambia

<p>Abstract</p> <p>Background</p> <p>Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7), but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia.</p> <p>Methods</p> <p>We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars) per disability-adjusted life year (DALY) averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings.</p> <p>Results</p> <p>Assuming 90% coverage, a program using a 9-valent PCV (PCV9) would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine), compared to no intervention, a PCV9 vaccination program would cost$670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910,$670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia.</p> <p>Conclusions</p> <p>Based on the information available now, infant PCV vaccination would be expected to reduce pneumococcal diseases caused by <it>S. pneumoniae </it>in The Gambia. Assuming a cost-effectiveness threshold of three times GDP per capita, all PCVs examined would be cost-effective at the tentative Advance Market Commitment (AMC) price of$3.5 per dose. Because the cost-effectiveness of a PCV program could be affected by potential serotype replacement or herd immunity effects that may not be known until after a large scale introduction, type-specific surveillance and iterative evaluation will be critical.</p

Comparative analysis of the humoral immune response to Moraxella catarrhalis and Streptococcus pneumoniae surface antigens in children suffering from recurrent acute otitis media and chronic otitis media with effusion.

Item does not contain fulltextA prospective clinical cohort study was established to investigate the humoral immune response in middle ear fluids (MEF) and serum against bacterial surface proteins in children suffering from recurrent acute otitis media (rAOM) and chronic otitis media with effusion (COME), using Luminex xMAP technology. The association between the humoral immune response and the presence of Moraxella catarrhalis and Streptococcus pneumoniae in the nasopharynx and middle ear was also studied. The levels of antigen-specific IgG, IgA, and IgM showed extensive interindividual variation. No significant differences in anti-M. catarrhalis and anti-S. pneumoniae serum and MEF median fluorescence intensity (MFI) values (anti-M. catarrhalis and antipneumococcal IgG levels) were observed between the rAOM or COME groups for all antigens tested. No significant differences were observed for M. catarrhalis and S. pneumoniae colonization and serum IgG levels against the Moraxella and pneumococcal antigens. Similar to the antibody response in serum, no significant differences in IgG, IgA, and IgM levels in MEF were observed for all M. catarrhalis and S. pneumoniae antigens between OM M. catarrhalis- or S. pneumoniae-positive and OM M. catarrhalis- or S. pneumonia-negative children suffering from either rAOM or COME. Finally, results indicated a strong correlation between antigen-specific serum and MEF IgG levels. We observed no significant in vivo expressed anti-M. catarrhalis or anti-S. pneumoniae humoral immune responses using a range of putative vaccine candidate proteins. Other factors, such as Eustachian tube dysfunction, viral load, and genetic and environmental factors, may play a more important role in the pathogenesis of OM and in particular in the development of rAOM or COME.1 juni 201

Deletions flanked by breakpoints 3 and 4 on 15q13 may contribute to abnormal phenotypes

Non-allelic homologous recombination (NAHR) between segmental duplications in proximal chromosome 15q breakpoint (BP) regions can lead to microdeletions and microduplications. Several individuals with deletions flanked by BP3 and BP4 on 15q13, immediately distal to, and not including the Prader–Willi/Angelman syndrome (PW/AS) critical region and proximal to the BP4–BP5 15q13.3 microdeletion syndrome region, have been reported; however, because the deletion has also been found in normal relatives, the significance of these alterations is unclear. We have identified six individuals with deletions limited to the BP3–BP4 interval and an additional four individuals with deletions of the BP3–BP5 interval from 34 046 samples submitted for clinical testing by microarray-based comparative genomic hybridization (aCGH). Of four individuals with BP3–BP4 deletions for whom parental testing was conducted, two were apparently de novo and two were maternally inherited. A comparison of clinical features, available for five individuals in our study (four with deletions within BP3–BP4 and one with a BP3-BP5 deletion), with those in the literature show common features of short stature and/or failure to thrive, microcephaly, hypotonia, and premature breast development in some individuals. Although the BP3–BP4 deletion does not yet demonstrate statistically significant enrichment in abnormal populations compared with control populations, the presence of common clinical features among probands and the presence of genes with roles in development and nervous system function in the deletion region suggest that this deletion may have a role in abnormal phenotypes in some individuals