Biology subjects

Weinberger, D. M.

Publications and source records attributed to Weinberger, D. M..

4 recordsLinked to original sources

bioRxiv2018

Response of pneumococcus to changes in temperature and oxygen varies by serotype, lineage, and site of isolation

BackgroundPneumococcus, a bacterium that typically resides in the nasopharynx, is exposed to a variety of temperature and oxygen levels in the upper respiratory tract and as it invades the lung, tissues, and blood. The response to these variations likely varies by strain and could influence the fitness of a strain and its virulence. We sought to determine the effect of environmental variability on the growth characteristics of pneumococcus and to evaluate correlations between variability in growth characteristics between strains and biological and epidemiological characteristics. MethodsWe evaluated the effect of temperature and oxygen on the growth of 256 pneumococcal isolates representing 53 serotypes, recovered from healthy carriers and from disease patients. Strains were grown at a range of temperatures anaerobically or in ambient air with and without catalase and were monitored by reading the optical density. Regression models were used to evaluate bacterial and environmental factors associated with characteristics of the growth curves. ResultsMost isolates grew to the maximal density at the temperature of the nasopharynx (~33C) and under aerobic conditions (with catalase). Maximum density achieved was positively associated with the presence of N-acetylated sugars in the capsule and negatively associated with the presence of uronic acids. Reaching a greater density at an early time point was positively associated with the prevalence of serotypes among healthy carriers in the pre-vaccine period. DiscussionEnvironmental variability affects the growth of pneumococcus, with notable differences between isolates and by serotype. Such variability could be influenced by characteristics of the capsule and might affect virulence and transmissibility.

microbiology↗

bioRxiv2018

Challenges in estimating the impact of vaccination with sparse data

BackgroundThe synthetic control (SC) model is a powerful tool to quantify the population-level impact of vaccines, because it can adjust for trends unrelated to vaccination using a composite of control diseases. Because vaccine impact studies are often conducted using smaller subnational datasets, we evaluated the performance of SC models with sparse time series data. To obtain more robust estimates of vaccine effects from noisy time series, we proposed a possible alternative approach, \"STL+PCA\" method (seasonal-trend decomposition plus principal component analysis), which first extracts smoothed trends from the control time series and uses them to adjust the outcome.\n\nMethodsUsing both the SC and STL+PCA models, we estimated the impact of 10-valent pneumococcal conjugate vaccine (PCV10) on pneumonia hospitalizations among cases <12 months and 80+ years of age during 2004-2014 at the subnational level in Brazil. The performance of these models was also compared using simulation analyses.\n\nResultsThe SC model was able to adjust for trends unrelated to PCV10 in larger states but not in smaller states. The simulation analysis confirmed that the SC model failed to select an appropriate set of control diseases when the time series were sparse and noisy, thereby generating biased estimates of the impact of vaccination when secular trends were present. The STL+PCA approach decreased bias in the estimates for smaller populations.\n\nConclusionsEstimates from the SC model might be biased when data are sparse. The STL+PCA model provides more accurate evaluations of vaccine impact in smaller populations.

epidemiology↗

bioRxiv2018

Decline in pneumococcal disease in unimmunized adults is associated with vaccine-associated protection against colonization in toddlers and preschool-aged children

Vaccinating children with pneumococcal conjugate vaccines disrupts transmission, reducing disease rates in unvaccinated adults. When considering changes in vaccination strategies (e.g., removing doses), it is critical to understand which groups of children contribute most to transmission. We used data from Israel to evaluate how the build-up of vaccine-associated immunity in children was associated with declines in IPD due to vaccine-targeted serotypes in unimmunized adults. Data on vaccine uptake and prevalence of colonization with PCV-targeted serotypes were obtained from a unique study conducted among children visiting an emergency department in southern Israel and from surveys of colonization from central Israel. Data on invasive pneumococcal disease in adults were obtained from a nationwide surveillance study. We compared the trajectory of decline of IPD due to PCV-targeted serotypes in adults with the trajectory of decline of colonization prevalence and trajectory of increase in vaccine-derived protection against pneumococcal carriage among different age groupings of children. The declines in IPD in adults were most closely associated with the declines in colonization and increased vaccination coverage in children in the range of 36-59 months of age. This suggests that preschool-aged children, rather than infants, are responsible for maintaining the indirect benefits of PCVs.

epidemiology↗

bioRxiv2018

Do pneumococcal conjugate vaccines (PCVs) reduce childhood pneumonia mortality? An assessment across socioeconomic groups in Brazil

BackgroundUnderstanding the real-world impact of pneumococcal conjugate vaccines (PCVs) on pneumonia mortality is critical, given the expectation that PCVs can substantially reduce the burden of pneumonia deaths in children under five years. However, surprisingly few post-vaccine introduction studies have estimated the benefit of PCVs for childhood mortality, and results have been inconsistent.\n\nMethodsWe investigated the long-term trends in child pneumonia mortality in Brazil (1980-present) and assessed the impact of PCV10 on childhood pneumonia mortality, both nationally and in municipalities stratified by socioeconomic status (SES), after the vaccine was introduced in Brazil in 2010.\n\nFindingsBetween 1980 and 2010, a period when Brazils Human Development Index (HDI) rose from 0.55 to 0.71, national pneumonia mortality in children under five decreased 10-fold. Despite rapid uptake of PCV10 following its introduction in 2010, our primary analytical method found no significant decline in national childhood pneumonia mortality, although a secondary analysis found a 10 percent decline in some but not all strata. However, at the municipal level we found significant reductions in childhood pneumonia mortality of up to 24% in low SES strata.\n\nInterpretationContrary to expectations, we found that PCV use led to at best modest savings in childhood pneumonia mortality at the national level in a middle-income country. In contrast, we found evidence that PCV led to larger reductions in low-income settings; a similar benefit might occur when PCVs are introduced in other low-SES settings. The long-term findings underscore that improvements in nutrition, hygiene, education, and healthcare play a major role in reducing pneumonia mortality.\n\nFundingThis work was funded by a grant from the Bill & Melinda Gates Foundation (OPP1114733). DMW also acknowledges support from the Bill and Melinda Gates Foundation (OPP1176267) and the National Institute of Allergy and Infectious Diseases (R01AI123208)

epidemiology↗