Monitoring the Risk of Type-2 Circulating Vaccine-Derived Poliovirus Emergence During Roll-Out of Type-2 Novel Oral Polio Vaccine.

Although wild poliovirus type 2 has been eradicated, the prolonged transmission of the live- attenuated virus contained in the type-2 oral polio vaccine (OPV2) in under-immunized populations has led to the emergence of circulating vaccine-derived poliovirus type 2 (cVDPV2). The novel OPV2 (nOPV2) was designed to be more genetically stable and reduce the chance of cVDPV2 emergence while retaining comparable immunogenicity to the Sabin monovalent OPV2 (mOPV2). This study aimed to estimate the relative reduction in the emergence risk due to the use of nOPV2 instead of mOPV2.

Analysis of population immunity to poliovirus following cessation of trivalent oral polio vaccine.

Background: The global withdrawal of trivalent oral poliovirus vaccine (OPV) (tOPV, containing Sabin poliovirus strains serotypes 1, 2 and 3) from routine immunization, and the introduction of bivalent OPV (bOPV, containing Sabin poliovirus strains serotypes 1 and 3) and trivalent inactivated poliovirus vaccine (IPV) into routine immunization was expected to improve population serologic and mucosal immunity to types 1 and 3 poliovirus, while population mucosal immunity to type 2 poliovirus would decline. However, over the period since tOPV withdrawal, the implementation of preventive bOPV supplementary immunization activities (SIAs) has decreased, while outbreaks of type 2 circulating vaccine derived poliovirus (cVDPV2) have required targeted use of monovalent type 2 OPV (mOPV2).

Methods: We develop a dynamic model of OPV-induced immunity to estimate serotype-specific, district-level immunity for countries in priority regions and characterize changes in immunity since 2016.

Real-time prediction model of cVDPV2 outbreaks to aid outbreak response vaccination strategies.

Background: Circulating vaccine-derived poliovirus outbreaks are spreading more widely than anticipated, which has generated a crisis for the global polio eradication initiative. Effectively responding with vaccination activities requires a rapid risk assessment. This assessment is made difficult by the low case-to-infection ratio of type 2 poliovirus, variable transmissibility, changing population immunity, surveillance delays, and limited vaccine supply from the global stockpile.

The impact of disruptions caused by the COVID-19 pandemic on global polio eradication.

In early 2020, the COVID-19 pandemic led to substantial disruptions in global activities. The disruptions also included intentional and unintentional reductions in health services, including immunization campaigns against the transmission of wild poliovirus (WPV) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2). Building on a recently updated global poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model, we explored the implications of immunization disruption and restrictions of human interactions (i.

New analytic approaches for analyzing and presenting polio surveillance data to supplement standard performance indicators.

Background: Sensitive surveillance for acute flaccid paralysis (AFP) allows for rapid detection of polio outbreaks and provides essential evidence to support certification of the eradication of polio. However, accurately assessing the sensitivity of surveillance systems can be difficult due to limitations in the reliability of available performance indicators, including the rate of detection of non-polio AFP and the proportion of adequate stool sample collection. Recent field reviews have found evidence of surveillance gaps despite indicators meeting expected targets.

Violence, insecurity, and the risk of polio: A systematic analysis.

Background: Since the introduction of polio vaccines in the 1950's and 60's, eradication of poliovirus from the world has been technically feasible. Progress towards this goal, however, has been uneven and influenced by social and political factors that challenge the implementation of robust immunization programs. While violence and insecurity are often cited as barriers to eradication, current global risk models are largely based on virologic and immunologic indicators measured at national levels.

Polio immunity and the impact of mass immunization campaigns in the Democratic Republic of the Congo.

Background: In order to prevent outbreaks from wild and vaccine-derived poliovirus, maintenance of population immunity in non-endemic countries is critical.

Methods: We estimated population seroprevalence using dried blood spots collected from 4893 children 6-59months olds in the 2013-2014 Demographic and Health Survey in the Democratic Republic of the Congo (DRC).

Results: Population immunity was 81%, 90%, and 70% for poliovirus types 1, 2, and 3, respectively.

Mapping for Health in Cameroon: Polio Legacy and Beyond.

During the poliovirus outbreak in Cameroon from October 2013 to April 2015, the Ministry of Public Health's Expanded Program on Immunization requested technical support to improve mapping of health district boundaries and health facility locations for more effective planning and analysis of polio program data. In December 2015, teams collected data on settlements, health facilities, and other features using smartphones. These data, combined with high-resolution satellite imagery, were used to create new health area and health district boundaries, providing the most accurate health sector administrative boundaries to date for Cameroon.

Measuring polio immunity to plan immunization activities.

The Global Polio Eradication Initiative is closer than ever to achieving a polio-free world. Immunization activities must still be carried out in non-endemic countries to maintain population immunity at levels which will stop poliovirus from spreading if it is re-introduced from still-infected areas. In areas where there is no active transmission of poliovirus, programs must rely on surrogate indicators of population immunity to determine the appropriate immunization activities, typically caregiver-reported vaccination history obtained from non-polio acute flaccid paralysis patients identified through polio surveillance.

Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.

Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1.

Analysis of vaccination campaign effectiveness and population immunity to support and sustain polio elimination in Nigeria.

Background: The world is closer than ever to a polio-free Africa. In this end-stage, it is important to ensure high levels of population immunity to prevent polio outbreaks. Here, we introduce a new method of assessing vaccination campaign effectiveness and estimating immunity at the district-level.

Graph Estimation with Joint Additive Models.

In recent years, there has been considerable interest in estimating conditional independence graphs in high dimensions. Most previous work has assumed that the variables are multivariate Gaussian, or that the conditional means of the variables are linear; in fact, these two assumptions are nearly equivalent. Unfortunately, if these assumptions are violated, the resulting conditional independence estimates can be inaccurate.

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

Background: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.

Methods: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci.

Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.

Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides.

Whole-genome sequence-based analysis of high-density lipoprotein cholesterol.

We describe initial steps for interrogating whole-genome sequence data to characterize the genetic architecture of a complex trait, levels of high-density lipoprotein cholesterol (HDL-C). We report whole-genome sequencing and analysis of 962 individuals from the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) studies. From this analysis, we estimate that common variation contributes more to heritability of HDL-C levels than rare variation, and screening for mendelian variants for dyslipidemia identified individuals with extreme HDL-C levels.

Resequencing and clinical associations of the 9p21.3 region: a comprehensive investigation in the Framingham heart study.

Background: 9p21.3 is among the most strongly replicated regions for cardiovascular disease. There are few reports of sequencing the associated 9p21.

Fast computation for genome-wide association studies using boosted one-step statistics.

Motivation: Statistical analyses of genome-wide association studies (GWAS) require fitting large numbers of very similar regression models, each with low statistical power. Taking advantage of repeated observations or correlated phenotypes can increase this statistical power, but fitting the more complicated models required can make computation impractical.

Results: In this article, we present simple methods that capitalize on the structure inherent in GWAS studies to dramatically speed up computation for a wide variety of problems, with a special focus on methods for correlated phenotypes.

Behavior of QQ-plots and genomic control in studies of gene-environment interaction.

Genome-wide association studies of gene-environment interaction (GxE GWAS) are becoming popular. As with main effects GWAS, quantile-quantile plots (QQ-plots) and Genomic Control are being used to assess and correct for population substructure. However, in G x E work these approaches can be seriously misleading, as we illustrate; QQ-plots may give strong indications of substructure when absolutely none is present.