Alpha C protein of group B Streptococcus as a potential vaccine candidate

Group B Streptococcus (GBS) is a leading cause of life-threatening infection in neonates and young infants, pregnant women, and non-pregnant adults with underlying medical conditions. Immunization has theoretical potential to prevent significant morbidity and mortality from GBS disease. Alpha C protein (α C), found in 70% of non-type III capsule polysaccharide group B Streptococcus, elicits antibodies protective against α C-expressing strains in experimental animals and is an appealing carrier for a GBS conjugate vaccine. We determined whether natural exposure to α C elicits antibodies in women and if high maternal α C-specific serum antibody at delivery is associated with protection against neonatal disease. An ELISA was designed to measure α C-specific IgM and IgG in human sera. A case-control design (1:3 ratio) was used to match α C-expressing GBS colonized and non-colonized women by age and compare quantified serum α C-specific IgM and IgG. Sera also were analyzed from bacteremic neonates and their mothers and from women with invasive GBS disease. Antibody concentrations were compared using t-tests on log-transformed data. Geometric mean concentrations of α C-specific IgM and IgG were similar in sera from 58 α C strain colonized and 174 age-matched non-colonized women (IgG 245 and 313 ng/ml; IgM 257 and 229 ng/ml, respectively). Delivery sera from mothers of 42 neonates with GBS α C sepsis had similar concentrations of α C-specific IgM (245 ng/ml) and IgG (371 ng/ml), but acute sera from 13 women with invasive α C-expressing GBS infection had significantly higher concentrations (IgM 383 and IgG 476 ng/ml [p=0.036 and 0.038, respectively]). Convalescent sera from 5 of these women 16-49 days later had high α C-specific IgM and IgG concentrations (1355 and 4173 ng/ml, respectively). In vitro killing of α C-expressing GBS correlated with total α C-specific antibody concentration. Invasive disease but not colonization elicits α C-specific IgM and IgG in adults. Whether α C-specific IgG induced by vaccine would protect against disease in neonates merits further investigation. ^

Survey of VFC provider knowledge of catch-up regimens and contraindications to vaccination in Houston, Texas

In 2004, Houston had one of the lowest childhood immunization levels among major metropolitan cities in the United States at 65% for the 4:3:1:3:3 vaccination series. Delays in the receipt of scheduled vaccinations may be related to missed opportunities due to health care provider lack of knowledge about catch-up regimens and contraindications for pediatric vaccination. The objectives of this study are to identify, measure, and report on VFC provider-practice characteristics, knowledge of catch-up regimens and contraindications, and use of Reminder recall (R/R) and moved or gone elsewhere (MOGE) practices among providers with high (>80%) and low (<70%) immunization coverage among 19-35 month old children. The sampling frame consists of 187 Vaccines for Children (VFC) providers with 2004 clinic assessment software application (CASA) scores. Data were collected by personal interview with each participating practice provider. Only ten VFC providers were successful at maximizing vaccinations for every vignette and no provider administered the maximum possible number of vaccinations at visit 2 for all six vignettes. Both coverage groups administered polio conjugate vaccine (PCV), haemophilus influenza type b (Hib), and diphtheria, tetanus and acellular pertussis (DTaP) most frequently and omitted most frequently varicella zoster vaccine (VZV) and measles, mumps, and rubella (MMR) vaccine. ^

Influenza vaccination and peoples' knowledge and attitudes towards it: Factors that influenced influenza vaccination during the 2004--2005 influenza vaccine shortage

Influenza and pneumonia together comprise the seventh leading cause of death among adults in the U.S and were responsible for 65,163 deaths in 2003 and an average of 36,000 deaths per year in the United States from 1990 to 1999. Vaccination is efficacious and cost-effective in terms of preventing the infection and reducing both health care costs and productivity losses associated with influenza illness. The vaccine shortage of 2004–2005 resulted in a 39% decrease in the influenza vaccine supplies. During the fall of 2004, we conducted a nationwide, random-digit dialing, telephonic-interview survey of 1,202 adults aged 18 years and older to ascertain influenza vaccine knowledge, attitude and behavior. Of the 1,202 total interviewed subjects, 44.7% had received or intended to receive vaccine at the time of the survey (2004–05) and 39.6% had received the influenza vaccine the previous year (2003–04). Receipt of vaccine increased with previous receipt of the influenza vaccine (OR 13.17, 95% CI 8.65–20.08), increased motivation status (OR 7.58, 95% CI 4.03–14.25), subjective risk status (OR 3.33, 95% CI 2.23–4.97), age (OR 1.83, 95% CI 1.22–2.75) and previous receipt of the pneumococcal vaccine (OR 1.75, 95% CI 1.02–3.0). The influenza vaccine shortage of 2004–05 did not have a negative impact on the vaccination rates of study population. In addition to the increased rates, a large majority of respondents were also aware of the shortage of influenza vaccine during the 2004–05 season, about the indications for receiving the influenza vaccine, about alternative methods to prevent contracting the influenza and increased motivation to receive the vaccine. ^

Use of pneumococcal vaccine in people with chronic disease in United States

Objective. The risk of complications and deaths related to pneumococcal infections is high among high risk population (i.e. those with chronic diseases such as diabetes or asthma), despite current immunization recommendations. The aim of this study is to evaluate the use of pneumonia vaccine in adults with and without diabetes or asthma by year of age and whether immunization practices conform to policy recommendations. ^ Methods. Data were drawn from 2005 Behavioral Risk Factor Surveillance Study. Age specific estimated counts and proportions of pneumonia vaccination status were computed. The association of socio-demographic factors with vaccination status was estimated from multiple logistic regression and results were presented for adults (18-64yrs) and elderly (65 or older). ^ Results. Overall 12.3% of the adults and 61.5% of elderly reported ever received pneumonia vaccine. 66.8% of diabetics and 72.6% of asthmatics received the vaccine among elderly. 33.4% of diabetics and 21.6% of asthmatics received the vaccine among adults. These numbers are far away from Healthy people 2010 objective coverage rates of 90% for elderly and 60% for high risk adults. Though diabetes was one of the recommendations for the pneumonia vaccine still the status was less than 70% even at older ages. Although asthma was not an indication for pneumonia vaccine, asthmatics still achieved 50% level by an early age of 60 and reached up to 80% at as early as 75 years. In those having both asthma and diabetes, although the curve reaches to 50% level at a very early age of 40yrs, it is not stable until the age of 55 and percentages reached to as high as 90% in older ages. Odds of receiving pneumonia vaccine were high in individuals with diabetes or asthma in both the age groups. But the odds were stronger for diabetics in adults compared to those in the elderly [2.24 CI (2.08-2.42) and 1.32 CI (1.18-1.47)]. The odds were slightly higher in adults than in elderly for asthmatics [1.92 CI (1.80-2.04) and 1.73 CI (1.50-2.00)].The likelihood of vaccination also differed by gender, ethnicity, marital status, income category, having a health insurance, current employment, physician visit in last year, reporting of good to excellent health and flu vaccine status. ^ Conclusion. There is a very high proportion of high risk adults and elderly that remain unvaccinated. Given the proven efficacy and safety of vaccine there is a need for interventions targeting the barriers for under-vaccination with more emphasis on physician knowledge and practice as well as the recipient attitudes.^

Burden of invasive pneumococcal disease in Harris County, Texas (2003--2010) and the implication for enhanced public health surveillance of isolates

Invasive pneumococcal disease (IPD) causes significant health burden in the US, is responsible for the majority of bacterial meningitis, and causes more deaths than any other vaccine preventable bacterial disease in the US. The estimated National IPD rate is 14.3 cases per 100,000 population with a case-fatality rate of 1.5 cases per 100,000 population. Although cases of IPD are routinely reported to the local health department in Harris County Texas, the incidence (IR) and case-fatality (CFR) rates have not been reported. Additionally, it is important to know which serotypes of S. pneumoniae are circulating in Harris County Texas and to determine if ‘replacement disease’ is occurring. ^ This study reported incidence and case-fatality rates from 2003 to 2009, and described the trends in IPD, including the IPD serotypes circulating in Harris County Texas during the study period, particularly in 2008 and 2010. Annual incidence rates were calculated and reported for 2003 to 2009, using complete surveillance-year data. ^ Geographic information system (GIS) software was used to create a series of maps of the data reported during the study period. Cluster and outlier analysis and hot spot analysis were conducted using both case counts by census tract and disease rate by census tract. ^ IPD age- and race-adjusted IR for Harris County Texas and their 95% confidence intervals (CIs) were 1.40 (95% CI 1.0, 1.8), 1.71 (95% CI 1.24, 2.17), 3.13 (95% CI 2.48, 3.78), 3.08 (95% CI 2.43, 3.74), 5.61 (95% CI 4.79, 6.43), 8.11 (95% CI 7.11, 9.1), and 7.65 (95% CI 6.69, 8.61) for the years 2003 to 2009, respectively (rates were age- and race-adjusted to each year's midyear US population estimates). A Poisson regression model demonstrated a statistically significant increasing trend of about 32 percent per year in the IPD rates over the course of the study period. IPD age- and race-adjusted case-fatality rates (CFR) for Harris County Texas were also calculated and reported. A Poisson regression model demonstrated a statistically significant increasing trend of about 26 percent per year in the IPD case-fatality rates from 2003 through 2009. A logistic regression model associated the risk of dying from IPD to alcohol abuse (OR 4.69, 95% CI 2.57, 8.56) and to meningitis (OR 2.42, 95% CI 1.46, 4.03). ^ The prevalence of non-vaccine serotypes (NVT) among IPD cases with serotyped isolates was 98.2 percent. In 2008, the year with the sample more geographically representative of all areas of Harris County Texas, the prevalence was 96 percent. Given these findings, it is reasonable to conclude that ‘replacement disease’ is occurring in Harris County Texas, meaning that, the majority of IPD is caused by serotypes not included in the PCV7 vaccine. Also in conclusion, IPD rates increased during the study period in Harris County Texas.^

A retrospective cohort study of the duration of hepatitis B vaccine immunity and associated factors in pediatric dialysis patients

Dialysis patients are at high risk for hepatitis B infection, which is a serious but preventable disease. Prevention strategies include the administration of the hepatitis B vaccine. Dialysis patients have been noted to have a poor immune response to the vaccine and lose immunity more rapidly. The long term immunogenicity of the hepatitis B vaccine has not been well defined in pediatric dialysis patients especially if administered during infancy as a routine childhood immunization.^ Purpose. The aim of this study was to determine the median duration of hepatitis B immunity and to study the effect of vaccination timing and other cofactors on the duration of hepatitis B immunity in pediatric dialysis patients.^ Methods. Duration of hepatitis B immunity was determined by Kaplan-Meier survival analysis. Comparison of stratified survival analysis was performed using log-rank analysis. Multivariate analysis by Cox regression was used to estimate hazard ratios for the effect of timing of vaccine administration and other covariates on the duration of hepatitis B immunity.^ Results. 193 patients (163 incident patients) had complete data available for analysis. Mean age was 11.2±5.8 years and mean ESRD duration was 59.3±97.8 months. Kaplan-Meier analysis showed that the total median overall duration of immunity (since the time of the primary vaccine series) was 112.7 months (95% CI: 96.6, 124.4), whereas the median overall duration of immunity for incident patients was 106.3 months (95% CI: 93.93, 124.44). Incident patients had a median dialysis duration of hepatitis B immunity equal to 37.1 months (95% CI: 24.16, 72.26). Multivariate adjusted analysis showed that there was a significant difference between patients based on the timing of hepatitis B vaccination administration (p<0.001). Patients immunized after the start of dialysis had a hazard ratio of 6.13 (2.87, 13.08) for loss of hepatitis B immunity compared to patients immunized as infants (p<0.001).^ Conclusion. This study confirms that patients immunized after dialysis onset have an overall shorter duration of hepatitis B immunity as measured by hepatitis B antibody titers and after the start of dialysis, protective antibody titer levels in pediatric dialysis patients wane rapidly compared to healthy children.^

HPV vaccine coverage in Texas counties: An application of multilevel, small area estimation

Health departments, research institutions, policy-makers, and healthcare providers are often interested in knowing the health status of their clients/constituents. Without the resources, financially or administratively, to go out into the community and conduct health assessments directly, these entities frequently rely on data from population-based surveys to supply the information they need. Unfortunately, these surveys are ill-equipped for the job due to sample size and privacy concerns. Small area estimation (SAE) techniques have excellent potential in such circumstances, but have been underutilized in public health due to lack of awareness and confidence in applying its methods. The goal of this research is to make model-based SAE accessible to a broad readership using clear, example-based learning. Specifically, we applied the principles of multilevel, unit-level SAE to describe the geographic distribution of HPV vaccine coverage among females aged 11-26 in Texas.^ Multilevel (3 level: individual, county, public health region) random-intercept logit models of HPV vaccination (receipt of ≥ 1 dose Gardasil® ) were fit to data from the 2008 Behavioral Risk Factor Surveillance System (outcome and level 1 covariates) and a number of secondary sources (group-level covariates). Sampling weights were scaled (level 1) or constructed (levels 2 & 3), and incorporated at every level. Using the regression coefficients (and standard errors) from the final models, I simulated 10,000 datasets for each regression coefficient from the normal distribution and applied them to the logit model to estimate HPV vaccine coverage in each county and respective demographic subgroup. For simplicity, I only provide coverage estimates (and 95% confidence intervals) for counties.^ County-level coverage among females aged 11-17 varied from 6.8-29.0%. For females aged 18-26, coverage varied from 1.9%-23.8%. Aggregated to the state level, these values translate to indirect state estimates of 15.5% and 11.4%, respectively; both of which fall within the confidence intervals for the direct estimates of HPV vaccine coverage in Texas (Females 11-17: 17.7%, 95% CI: 13.6, 21.9; Females 18-26: 12.0%, 95% CI: 6.2, 17.7).^ Small area estimation has great potential for informing policy, program development and evaluation, and the provision of health services. Harnessing the flexibility of multilevel, unit-level SAE to estimate HPV vaccine coverage among females aged 11-26 in Texas counties, I have provided (1) practical guidance on how to conceptualize and conduct modelbased SAE, (2) a robust framework that can be applied to other health outcomes or geographic levels of aggregation, and (3) HPV vaccine coverage data that may inform the development of health education programs, the provision of health services, the planning of additional research studies, and the creation of local health policies.^