Identifying Host Genetic Risk Factors in the Context of Public Health Surveillance for Invasive Pneumococcal Disease

Host genetic factors that modify risk of pneumococcal disease may help target future public health interventions to individuals at highest risk of disease. We linked data from population-based surveillance for invasive pneumococcal disease (IPD) with state-based newborn dried bloodspot repositories to identify biological samples from individuals who developed invasive pneumococcal disease. Genomic DNA was extracted from 366 case and 732 anonymous control samples. TagSNPs were selected in 34 candidate genes thought to be associated with host response to invasive pneumococcal disease, and a total of 326 variants were successfully genotyped. Among 543 European Americans (EA) (182 cases and 361 controls), and 166 African Americans (AA) (53 cases and 113 controls), common variants in surfactant protein D (SFTPD) are consistently underrepresented in IPD. SFTPD variants with the strongest association for IPD are intronic rs17886286 (allelic OR 0.45, 95% confidence interval (CI) [0.25, 0.82], with p = 0.007) in EA and 5′ flanking rs12219080 (allelic OR 0.32, 95%CI [0.13, 0.78], with p = 0.009) in AA. Variants in CD46 and IL1R1 are also associated with IPD in both EA and AA, but with effects in different directions; FAS, IL1B, IL4, IL10, IL12B, SFTPA1, SFTPB, and PTAFR variants are associated (p≤0.05) with IPD in EA or AA. We conclude that variants in SFTPD may protect against IPD in EA and AA and genetic variation in other host response pathways may also contribute to risk of IPD. While our associations are not corrected for multiple comparisons and therefore must be replicated in additional cohorts, this pilot study underscores the feasibility of integrating public health surveillance with existing, prospectively collected, newborn dried blood spot repositories to identify host genetic factors associated with infectious diseases

Modeling the Cost-Effectiveness of the Integrated Disease Surveillance and Response (IDSR) System: Meningitis in Burkina Faso

Background: Effective surveillance for infectious diseases is an essential component of public health. There are few studies estimating the cost-effectiveness of starting or improving disease surveillance. We present a cost-effectiveness analysis the Integrated Disease Surveillance and Response (IDSR) strategy in Africa. Methodology/Principal Findings: To assess the impact of the IDSR in Africa, we used pre- and post- IDSR meningococcal meningitis surveillance data from Burkina Faso (1996–2002 and 2003–2007). IDSR implementation was correlated with a median reduction of 2 weeks to peak of outbreaks (25 th percentile 1 week; 75 th percentile 4 weeks). IDSR was also correlated with a reduction of 43 meningitis cases per 100,000 (25 th –40: 75 th-129). Assuming the correlations between reductions in time to peak of outbreaks and cases are related, the cost-effectiveness of IDSR was $23 per case averted (25 th-$30; 75 th- cost saving), and $98 per meningitis-related death averted (25 th-$140: 75 th – cost saving). Conclusions/Significance: We cannot absolutely claim that the measured differences were due to IDSR. We believe, however, that it is reasonable to claim that IDSR can improve the cost-effectiveness of public health surveillance

Cost analysis of an integrated disease surveillance and response system: case of Burkina Faso, Eritrea, and Mali

<p>Abstract</p> <p>Background</p> <p>Communicable diseases are the leading causes of illness, deaths, and disability in sub-Saharan Africa. To address these threats, countries within the World Health Organization (WHO) African region adopted a regional strategy called Integrated Disease Surveillance and Response (IDSR). This strategy calls for streamlining resources, tools, and approaches to better detect and respond to the region's priority communicable disease. The purpose of this study was to analyze the incremental costs of establishing and subsequently operating activities for detection and response to the priority diseases under the IDSR.</p> <p>Methods</p> <p>We collected cost data for IDSR activities at central, regional, district, and primary health care center levels from Burkina Faso, Eritrea, and Mali, countries where IDSR is being fully implemented. These cost data included personnel, transportation items, office consumable goods, media campaigns, laboratory and response materials and supplies, and annual depreciation of buildings, equipment, and vehicles.</p> <p>Results</p> <p>Over the period studied (2002–2005), the average cost to implement the IDSR program in Eritrea was $0.16 per capita,$0.04 in Burkina Faso and $0.02 in Mali. In each country, the mean annual cost of IDSR was dependent on the health structure level, ranging from$35,899 to $69,920 at the region level,$10,790 to $13,941 at the district level, and$1,181 to $1,240 at the primary health care center level. The proportions spent on each IDSR activity varied due to demand for special items (e.g., equipment, supplies, drugs and vaccines), service availability, distance, and the epidemiological profile of the country.</p> <p>Conclusion</p> <p>This study demonstrates that the IDSR strategy can be considered a low cost public health system although the benefits have yet to be quantified. These data can also be used in future studies of the cost-effectiveness of IDSR.</p

Persistence of serogroup C antibody responses following quadrivalent meningococcal conjugate vaccination in United States military personnel

AbstractSerogroup C meningococcal (MenC) disease accounts for one-third of all meningococcal cases and causes meningococcal outbreaks in the U.S. Quadrivalent meningococcal vaccine conjugated to diphtheria toxoid (MenACYWD) was recommended in 2005 for adolescents and high risk groups such as military recruits. We evaluated anti-MenC antibody persistence in U.S. military personnel vaccinated with either MenACYWD or meningococcal polysaccharide vaccine (MPSV4). Twelve hundred subjects vaccinated with MenACYWD from 2006 to 2008 or MPSV4 from 2002 to 2004 were randomly selected from the Defense Medical Surveillance System. Baseline serologic responses to MenC were assessed in all subjects; 100 subjects per vaccine group were tested during one of the following six post-vaccination time-points: 5–7, 11–13, 17–19, 23–25, 29–31, or 35–37 months. Anti-MenC geometric mean titers (GMT) were measured by rabbit complement serum bactericidal assay (rSBA) and geometric mean concentrations (GMC) by enzyme-linked immunosorbent assay (ELISA). Continuous variables were compared using the Wilcoxon rank sum test and the proportion of subjects with an rSBA titer ≥8 by chi-square. Pre-vaccination rSBA GMT was <8 for the MenACWYD group. rSBA GMT increased to 703 at 5–7 months post-vaccination and decreased by 94% to 43 at 3 years post-vaccination. GMT was significantly lower in the MenACWYD group at 5–7 months post-vaccination compared to the MPSV4 group. The percentage of MenACWYD recipients achieving an rSBA titer of ≥8 decreased from 87% at 5–7 months to 54% at 3 years. There were no significant differences between vaccine groups in the proportion of subjects with a titer of ≥8 at any time-point. GMC for the MenACWYD group was 0.14μg/mL at baseline, 1.07μg/mL at 5–7 months, and 0.66μg/mL at 3 years, and significantly lower than the MPSV4 group at all time-points. Anti-MenC responses wane following vaccination with MenACYWD; a booster dose is needed to maintain protective levels of circulating antibody

Public Health Impact After the Introduction of PsA-TT: The First 4 Years.

BACKGROUND: During the first introduction of a group A meningococcal vaccine (PsA-TT) in 2010-2011 and its rollout from 2011 to 2013, >150 million eligible people, representing 12 hyperendemic meningitis countries, have been vaccinated. METHODS: The new vaccine effectiveness evaluation framework was established by the World Health Organization and partners. Meningitis case-based surveillance was strengthened in PsA-TT first-introducer countries, and several evaluation studies were conducted to estimate the vaccination coverage and to measure the impact of vaccine introduction on meningococcal carriage and disease incidence. RESULTS: PsA-TT implementation achieved high vaccination coverage, and results from studies conducted showed significant decrease of disease incidence as well as significant reduction of oropharyngeal carriage of group A meningococci in vaccinated and unvaccinated individuals, demonstrating the vaccine's ability to generate herd protection and prevent group A epidemics. CONCLUSIONS: Lessons learned from this experience provide useful insights in how to guide and better prepare for future new vaccine introductions in resource-limited settings

Whole genome sequencing to investigate the emergence of clonal complex 23 Neisseria meningitidis serogroup Y disease in the United States

In the United States, serogroup Y, ST-23 clonal complex Neisseria meningitidis was responsible for an increase in meningococcal disease incidence during the 1990s. This increase was accompanied by antigenic shift of three outer membrane proteins, with a decrease in the population that predominated in the early 1990s as a different population emerged later in that decade. To understand factors that may have been responsible for the emergence of serogroup Y disease, we used whole genome pyrosequencing to investigate genetic differences between isolates from early and late N. meningitidis populations, obtained from meningococcal disease cases in Maryland in the 1990s. The genomes of isolates from the early and late populations were highly similar, with 1231 of 1776 shared genes exhibiting 100% amino acid identity and an average πN = 0.0033 and average πS = 0.0216. However, differences were found in predicted proteins that affect pilin structure and antigen profile and in predicted proteins involved in iron acquisition and uptake. The observed changes are consistent with acquisition of new alleles through horizontal gene transfer. Changes in antigen profile due to the genetic differences found in this study likely allowed the late population to emerge due to escape from population immunity. These findings may predict which antigenic factors are important in the cyclic epidemiology of meningococcal disease