Impact of the US Maternal Tetanus, Diphtheria, and Acellular Pertussis Vaccination Program on Preventing Pertussis in Infants <2 Months of Age: A Case-Control Evaluation.

BACKGROUND: Infants aged <1 year are at highest risk for pertussis-related morbidity and mortality. In 2012, Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccine was recommended for women during each pregnancy to protect infants in the first months of life; data on effectiveness of this strategy are currently limited. METHODS: We conducted a case-control evaluation among pertussis cases <2 months old with cough onset between 1 January 2011 and 31 December 2014 from 6 US Emerging Infection Program Network states. Controls were hospital-matched and selected by birth certificate. Mothers were interviewed to collect information on demographics, household characteristics, and healthcare providers. Provider-verified immunization history was obtained on mothers and infants. Mothers were considered vaccinated during pregnancy if Tdap was received ≥14 days before delivery; trimester was calculated using Tdap date, infant's date of birth, and gestational age. Odds ratios were calculated using multivariable conditional logistic regression; vaccine effectiveness (VE) was estimated as (1 - odds ratio) × 100%. RESULTS: A total of 240 cases and 535 controls were included; 17 (7.1%) case mothers and 90 (16.8%) control mothers received Tdap during the third trimester of pregnancy. The multivariable VE estimate for Tdap administered during the third trimester of pregnancy was 77.7% (95% confidence interval [CI], 48.3%-90.4%); VE increased to 90.5% (95% CI, 65.2%-97.4%) against hospitalized cases. CONCLUSIONS: Vaccination during pregnancy is an effective way to protect infants during the early months of life. With a continuing resurgence in pertussis, efforts should focus on maximizing Tdap uptake among pregnant women.

Generalisability of vaccine effectiveness estimates: an analysis of cases included in a postlicensure evaluation of 13-valent pneumococcal conjugate vaccine in the USA.

OBJECTIVES: External validity, or generalisability, is the measure of how well results from a study pertain to individuals in the target population. We assessed generalisability, with respect to socioeconomic status, of estimates from a matched case-control study of 13-valent pneumococcal conjugate vaccine effectiveness for the prevention of invasive pneumococcal disease in children in the USA. DESIGN: Matched case-control study. SETTING: Thirteen active surveillance sites for invasive pneumococcal disease in the USA. PARTICIPANTS: Cases were identified from active surveillance and controls were age and zip code matched. OUTCOME MEASURES: Socioeconomic status was assessed at the individual level via parent interview (for enrolled individuals only) and birth certificate data (for both enrolled and unenrolled individuals) and at the neighbourhood level by geocoding to the census tract (for both enrolled and unenrolled individuals). Prediction models were used to determine if socioeconomic status was associated with enrolment. RESULTS: We enrolled 54.6% of 1211 eligible cases and found a trend toward enrolled cases being more affluent than unenrolled cases. Enrolled cases were slightly more likely to have private insurance at birth (p=0.08) and have mothers with at least some college education (p<0.01). Enrolled cases also tended to come from more affluent census tracts. Despite these differences, our best predictive model for enrolment yielded a concordance statistic of only 0.703, indicating mediocre predictive value. Variables retained in the final model were assessed for effect measure modification, and none were found to be significant modifiers of vaccine effectiveness. CONCLUSIONS: We conclude that although enrolled cases are somewhat more affluent than unenrolled cases, our estimates are externally valid with respect to socioeconomic status. Our analysis provides evidence that this study design can yield valid estimates and the assessing generalisability of observational data is feasible, even when unenrolled individuals cannot be contacted.

Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study.

In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geo-coding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8-91.9%; adjusted estimate: 82.5%, 95% CI 65.6-91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.

Association between community socioeconomic factors, animal feeding operations, and campylobacteriosis incidence rates: Foodborne Diseases Active Surveillance Network (FoodNet), 2004-2010.

BACKGROUND: Campylobacter is a leading cause of foodborne illness in the United States. Campylobacter infections have been associated with individual risk factors, such as the consumption of poultry and raw milk. Recently, a Maryland-based study identified community socioeconomic and environmental factors that are also associated with campylobacteriosis rates. However, no previous studies have evaluated the association between community risk factors and campylobacteriosis rates across multiple U.S. states. METHODS: We obtained Campylobacter case data (2004-2010; n = 40,768) from the Foodborne Diseases Active Surveillance Network (FoodNet) and socioeconomic and environmental data from the 2010 Census of Population and Housing, the 2011 American Community Survey, and the 2007 U.S. Census of Agriculture. We linked data by zip code and derived incidence rate ratios using negative binomial regression models. RESULTS: Community socioeconomic and environmental factors were associated with both lower and higher campylobacteriosis rates. Zip codes with higher percentages of African Americans had lower rates of campylobacteriosis (incidence rate ratio [IRR]) = 0.972; 95 % confidence interval (CI) = 0.970,0.974). In Georgia, Maryland, and Tennessee, three leading broiler chicken producing states, zip codes with broiler operations had incidence rates that were 22 % (IRR = 1.22; 95 % CI = 1.03,1.43), 16 % (IRR = 1.16; 95 % CI = 0.99,1.37), and 35 % (IRR = 1.35; 95 % CI = 1.18,1.53) higher, respectively, than those of zip codes without broiler operations. In Minnesota and New York FoodNet counties, two top dairy producing areas, zip codes with dairy operations had significantly higher campylobacteriosis incidence rates (IRR = 1.37; 95 % CI = 1.22, 1.55; IRR = 1.19; 95 % CI = 1.04,1.36). CONCLUSIONS: Community socioeconomic and environmental factors are important to consider when evaluating the relationship between possible risk factors and Campylobacter infection.

Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: a matched case-control study.

BACKGROUND: In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was licensed and recommended in the USA for prevention of invasive pneumococcal disease in children. Licensure was based on immunogenicity data comparing PCV13 with the earlier seven-valent formulation. Because clinical endpoints were not assessed for the new antigens, we did a postlicensure matched case-control study to assess vaccine effectiveness. METHODS: Cases in children aged 2-59 months were identified through active surveillance in 13 sites. Controls were identified via birth registries and matched to cases by age and postal (zip) code. The primary objective was the vaccine effectiveness of at least one dose against the 13 serotypes included in PCV13. Secondary objectives included vaccine effectiveness against all-cause invasive pneumococcal disease, against antibiotic non-susceptible invasive pneumococcal disease, and among children with and without underlying conditions. Vaccine effectiveness was calculated as (1 - matched odds ratio) × 100%. FINDINGS: We enrolled 722 children with invasive pneumococcal disease and 2991 controls; PCV13 serotype cases (217 [30%]) included most commonly serotypes 19A (128 [18%]), 7F (32 [4%]), and 3 (43 [6%]). Vaccine effectiveness against PCV13 serotypes was 86·0% (95% CI 75·5 to 92·3), driven by serotypes 19A and 7F, for which vaccine effectiveness was 85·6% (95% CI 70·6 to 93·5) and 96·5% (82·7 to 100), respectively. We also identified statistically significant effectiveness against serotype 3 (79·5%, 95% CI 30·3 to 94·8) and against antibiotic non-susceptible invasive pneumococcal disease (65·6%, 44·9 to 78·7). Vaccine effectiveness against all-cause invasive pneumococcal disease was 60·2% (95% CI 46·8 to 70·3). Vaccine effectiveness was similar among children with (81·4%, 95% CI 45·4 to 93·6) and without (85·8%, 74·9 to 91·9) underlying conditions. INTERPRETATION: PCV13 appears highly effective against invasive pneumococcal disease among children in the USA in the context of routine and catch-up schedules, although some new vaccine antigens could not be assessed. PCV13 immunisation provides a robust strategy for combating pneumococcal antimicrobial resistance. FUNDING: Centers for Disease Control and Prevention.

Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance.

BACKGROUND: In 2000, seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the USA and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and moderate increases in non-PCV7 type IPD. In 2010, PCV13 replaced PCV7 in the US immunisation schedule. We aimed to assess the effect of use of PCV13 in children on IPD in children and adults in the USA. METHODS: We used laboratory-based and population-based data on incidence of IPD from the Active Bacterial Core surveillance (part of the Centers for Disease Control and Prevention's Emerging Infections Program) in a time-series model to compare rates of IPD before and after the introduction of PCV13. Cases of IPD between July 1, 2004, and June 30, 2013, were classified as being caused by the PCV13 serotypes against which PCV7 has no effect (PCV13 minus PCV7). In a time-series model, we used an expected outcomes approach to compare the reported incidence of IPD to that which would have been expected if PCV13 had not replaced PCV7. FINDINGS: Compared with incidence expected among children younger than 5 years if PCV7 alone had been continued, incidence of IPD overall declined by 64% (95% interval estimate [95% IE] 59-68) and IPD caused by PCV13 minus PCV7 serotypes declined by 93% (91-94), by July, 2012, to June, 2013. Among adults, incidence of IPD overall also declined by 12-32% and IPD caused by PCV13 minus PCV7 type IPD declined by 58-72%, depending on age. We estimated that over 30 000 cases of IPD and 3000 deaths were averted in the first 3 years after the introduction of PCV13. INTERPRETATION: PCV13 reduced IPD across all age groups when used routinely in children in the USA. These findings provide reassurance that, similar to PCV7, PCVs with additional serotypes can also prevent transmission to unvaccinated populations. FUNDING: Centers for Disease Control and Prevention.

Early-onset group B streptococcal disease in the United States: potential for further reduction.

OBJECTIVE: To describe lapses in adherence to group B streptococcus (GBS) prevention guidelines among cases of early-onset GBS disease in term and preterm neonates and to estimate the potential for further reduction in disease burden under current prevention strategies. METHODS: We reviewed labor and delivery and prenatal records of mothers of neonates with early-onset GBS disease (aged younger than 7 days with GBS isolated from a normally sterile site) identified at population-based surveillance sites in 2008-2009. We interviewed prenatal care providers about GBS screening practices and obtained relevant laboratory records. We evaluated the data for errors in prenatal screening, laboratory methods, communication of results, and intrapartum antibiotic prophylaxis. Using published data on screening sensitivity and intrapartum prophylaxis effectiveness, we estimated the potential reduction in cases under optimal prevention implementation. RESULTS: Among 309 cases, 179 (57.9%) had one or more implementation errors. The most common error type in term and preterm case-patients was prenatal screening (80 of 222 [36.0%]) and intrapartum prophylaxis (46 of 85 [54.1%]), respectively. We estimated that under optimal implementation, cases of early-onset GBS disease could be reduced by 26-59% with the largest benefit from a single intervention coming from improved use of intrapartum prophylaxis (16% decrease). CONCLUSION: Further reduction of early-onset GBS disease burden is possible under current prevention strategies, particularly with improved implementation of antibiotic prophylaxis. However, even with perfect adherence to recommended practices, the decline in cases may be modest. Therefore, novel prevention approaches such as improved intrapartum assays and vaccines are also needed.