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.

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.

The Changing Epidemiology of Coccidioidomycosis in Los Angeles (LA) County, California, 1973-2011.

Coccidioidomycosis, also known as Valley Fever, is often thought of as an endemic disease of central California exclusive of Los Angeles County. The fungus that causes Valley Fever, Coccidioides spp., grows in previously undisturbed soil of semi-arid and arid environments of certain areas of the Americas. LA County has a few large areas with such environments, particularly the Antelope Valley which has been having substantial land development. Coccidioidomycosis that is both clinically- and laboratory-confirmed is a mandated reportable disease in LA County. Population surveillance data for 1973-2011 reveals an annual rate increase from 0.87 to 3.2 cases per 100,000 population (n = 61 to 306 annual cases). In 2004, case frequency started substantially increasing with notable epidemiologic changes such as a rising 2.1 to 5.7 male-to-female case ratio stabilizing to 1.4-2.2. Additionally, new building construction in Antelope Valley greatly rose in 2003 and displayed a strong correlation (R = 0.92, Pearson p<0.0001) with overall LA County incidence rates for 1996-2007. Of the 24 LA County health districts, 19 had a 100%-1500% increase in cases when comparing 2000-2003 to 2008-2011. Case residents of endemic areas had stronger odds of local exposures, but cases from areas not known to be endemic had greater mortality (14% versus 9%) with notably more deaths during 2008-2011. Compared to the 57 other California counties during 2001-2011, LA County had the third highest average annual number of cases and Antelope Valley had a higher incidence rate than all but six counties. With the large number of reported coccidioidomycosis cases, multi-agency and community partnering is recommended to develop effective education and prevention strategies to protect residents and travelers.