Ruth Link-Gelles

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 Preventions 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.

Infection Control Assessment of Ambulatory Surgical Centers

CONTEXT More than 5000 ambulatory surgical centers (ASCs) in the United States participate in the Medicare program. Little is known about infection control practices in ASCs. The Centers for Medicare & Medicaid Services (CMS) piloted an infection control audit tool in a sample of ASC inspections to assess facility adherence to recommended practices. OBJECTIVE To describe infection control practices in a sample of ASCs. DESIGN, SETTING, AND PARTICIPANTS All State Survey Agencies were invited to participate. Seven states volunteered; 3 were selected based on geographic dispersion, number of ASCs each state committed to inspect, and relative cost per inspection. A stratified random sample of ASCs was selected from each state. Sample size was based on the number of inspections each state estimated it could complete between June and October 2008. Sixty-eight ASCs were assessed; 32 in Maryland, 16 in North Carolina, and 20 in Oklahoma. Surveyors from CMS, trained in use of the audit tool, assessed compliance with specific infection control practices. Assessments focused on 5 areas of infection control: hand hygiene, injection safety and medication handling, equipment reprocessing, environmental cleaning, and handling of blood glucose monitoring equipment. MAIN OUTCOME MEASURES Proportion of facilities with lapses in each infection control category. RESULTS Overall, 46 of 68 ASCs (67.6%; 95% confidence interval [CI], 55.9%-77.9%) had at least 1 lapse in infection control; 12 of 68 ASCs (17.6%; 95% CI, 9.9%-28.1%) had lapses identified in 3 or more of the 5 infection control categories. Common lapses included using single-dose medication vials for more than 1 patient (18/64; 28.1%; 95% CI, 18.2%-40.0%), failing to adhere to recommended practices regarding reprocessing of equipment (19/67; 28.4%; 95% CI, 18.6%-40.0%), and lapses in handling of blood glucose monitoring equipment (25/54; 46.3%; 95% CI, 33.4%-59.6%). CONCLUSION Among a sample of US ASCs in 3 states, lapses in infection control were common.

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.

Epidemiology of Invasive Pneumococcal Disease Among High-Risk Adults Since the Introduction of Pneumococcal Conjugate Vaccine for Children

BACKGROUND Certain chronic diseases increase risk for invasive pneumococcal disease (IPD) and are indications for receipt of 23-valent pneumococcal polysaccharide vaccine (PPV23). Since the pediatric introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, incidence of IPD among adults has declined. The relative magnitude of these indirect effects among persons with and without PPV23 indications is unknown. METHODS We evaluated IPD incidence among adults with and without PPV23 indications using population- and laboratory-based data collected during 1998-2009 and estimates of the denominator populations with PPV23 indications from the National Health Interview Survey. We compared rates before and after PCV7 use by age, race, PPV23 indication, and serotype. RESULTS The proportion of adult IPD cases with PPV23 indications increased from 51% before to 61% after PCV7 introduction (P < .0001). PCV7-serotype IPD declined among all race, age, and PPV23 indication strata, ranging from 82% to 97%. Overall IPD rates declined in most strata, by up to 65%. However, incidence remained highest among adults with PPV23 indications compared with those without (34.9 vs 8.8 cases per 100 000 population, respectively). Apart from age ≥65 years, diabetes is now the most common indication for PPV23 (20% of all cases vs 10% of cases in 1998-1999). CONCLUSIONS Although IPD rates have declined among adults, adults with underlying conditions remain at increased risk of IPD and comprise a larger proportion of adult IPD cases in 2009 compared with 2000. A continued increase in the prevalence of diabetes among US adults could lead to increased burden of pneumococcal disease.

Use of surveillance data to estimate the effectiveness of the 7-valent conjugate pneumococcal vaccine in children less than 5 years of age over a 9 year period.

BACKGROUND Case-control studies evaluating post-licensure effectiveness of conjugate vaccines can be laborious and costly. We applied an indirect cohort method to evaluate the effectiveness of seven-valent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) and compared the results to the effectiveness measured using a standard case-control study conducted during the same time period. METHODS IPD cases among children 2-59 months old were identified through the Active Bacterial Core surveillance system during 2001-2009. We used logistic regression to calculate the odds ratio of vaccination (versus no vaccination) among cases (PCV7-type IPD cases) and non-cases (non-PCV7-type IPD cases), controlling for the presence of underlying conditions. Vaccine effectiveness (VE) was calculated as one minus the adjusted odds ratio. RESULTS Among 4225 IPD cases reported during 2001-2009, 2680 (63%) had serotype information and vaccine history. Effectiveness of ≥ 1 dose of PCV7 against PCV7-types was 88% (95% confidence interval (CI) 78-94%) among children with comorbid conditions and 97% (95% CI 92-98%) among healthy children. Among healthy children, VE was higher in 2001-2003 (97%, 95% CI 95-98%) compared to 2004-2009 (81%, 95% CI 64-90%). The annual estimates of VE in 2004-2009 showed great variability and wide confidence intervals due to the small number of PCV7-type cases. CONCLUSIONS An indirect cohort design using IPD surveillance data confirms the findings of the case-control study and, therefore, appears suitable for estimating PCV7 effectiveness. This method would be most useful shortly after vaccine introduction, and less useful in a setting of very high vaccine coverage and fewer vaccine-type cases.

Geographic and Temporal Trends in Antimicrobial Nonsusceptibility in Streptococcus pneumoniae in the Post-vaccine era in the United States

BACKGROUND We examined whether observed increases in antibiotic nonsusceptible nonvaccine serotypes after introduction of pneumococcal conjugate vaccine in the United States in 2000 were driven primarily by vaccine or antibiotic use. METHODS  Using active surveillance data, we evaluated geographic and temporal differences in serotype distribution and within-serotype differences during 2000-2009. We compared nonsusceptibility to penicillin and erythromycin by geography after standardizing differences across time, place, and serotype by regressing standardized versus crude proportions. A regression slope (RS) approaching zero indicates greater importance of the standardizing factor. RESULTS  Through 2000-2006, geographic differences in nonsusceptibility were better explained by within-serotype prevalence of nonsusceptibility (RS 0.32, 95% confidence interval [CI], .08-.55 for penicillin) than by geographic differences in serotype distribution (RS 0.71, 95% CI, .44-.97). From 2007-2009, serotype distribution differences became more important for penicillin (within-serotype RS 0.52, 95% CI, .11-.93; serotype distribution RS 0.57, 95% CI, .14-1.0). CONCLUSIONS  Differential nonsusceptibility, within individual serotypes, accounts for most geographic variation in nonsusceptibility, suggesting selective pressure from antibiotic use, rather than differences in serotype distribution, mainly determines nonsusceptibility patterns. Recent trends suggest geographic differences in serotype distribution may be affecting the prevalence of nonsusceptibility, possibly due to decreases in the number of nonsusceptible serotypes.

Effect of the 2009 Influenza A(H1N1) Pandemic on Invasive Pneumococcal Pneumonia

BACKGROUND Because pneumococcal pneumonia was prevalent during previous influenza pandemics, we evaluated invasive pneumococcal pneumonia (IPP) rates during the 2009 influenza A(H1N1) pandemic. METHODS We identified laboratory-confirmed, influenza-associated hospitalizations and IPP cases (pneumococcus isolated from normally sterile sites with discharge diagnoses of pneumonia) using active, population-based surveillance in the United States. We compared IPP rates during peak pandemic months (April 2009-March 2010) to mean IPP rates in nonpandemic years (April 2004-March 2009) and, using Poisson models, to 2006-2008 influenza seasons. RESULTS Higher IPP rates occurred during the peak pandemic month compared to nonpandemic periods in 5-24 (IPP rate per 10 million: 48 vs 9 (95% confidence interval [CI], 5-13), 25-49 (74 vs 53 [CI, 41-65]), 50-64 (188 vs 114 [CI, 85-143]), and ≥65-year-olds (229 vs 187 [CI, 159-216]). In the models with seasonal influenza rates included, observed IPP rates during the pandemic peak were within the predicted 95% CIs, suggesting this increase was not greater than observed with seasonal influenza. CONCLUSIONS The recent influenza pandemic likely resulted in an out-of-season IPP peak among persons ≥5 years. The IPP peaks magnitude was similar to that seen during seasonal influenza epidemics.

Invasive pneumococcal disease among children with and without sickle cell disease in the United States, 1998 to 2009

Background: Children with sickle cell disease (SCD) are at increased risk of illness and death from invasive pneumococcal disease (IPD). The introduction in 2000 of the 7-valent pneumococcal conjugate vaccine and penicillin prophylaxis for children with SCD has greatly reduced the incidence of IPD in this population. However, a recent report suggested an increase in cases of IPD in children with SCD. Methods: Using data from Active Bacterial Core surveillance, we analyzed trends in hospitalizations, mortality and serotype among children with SCD compared with other children. We used neonatal screening data to estimate SCD population denominators for each Active Bacterial Core surveillance site. Results: From 1998 to 2009, 3069 cases of IPD occurred among African-American children less than 18 years of age in the Active Bacterial Core surveillance catchment area. Of these, 127 (4.1%) had SCD identified by medical chart review and 185 (6.0%) had 1 or more IPD risk factors, excluding SCD. Rates of IPD among children with SCD declined by 53% (1118 vs. 530 per 100,000) whereas the overall rates among African-American children declined by 74% (54 to 14 per 100,000). For all time periods, children with SCD and IPD were more likely to be hospitalized (84%–92% vs. 31%–56%) and more likely to die (6%–17% vs. 1%–2%) than children with no risk factors. Conclusions: Although the rate of IPD in children with SCD has dropped dramatically since 7-valent pneumococcal conjugate vaccine introduction, the rate of IPD in children with SCD remains higher than that of the general population of African-American children, pointing to the need for more effective prevention efforts to prevent IPD in children with SCD.

Cost-effectiveness of administering 13-valent pneumococcal conjugate vaccine in addition to 23-valent pneumococcal polysaccharide vaccine to adults with immunocompromising conditions.

BACKGROUND In June, 2012 a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) was added to the recommendation for immunocompromised adults who were previously recommended to receive only 23-valent pneumococcal polysaccharide vaccine (PPSV23). PCV13 may be more effective, though it covers fewer disease-causing strains. OBJECTIVE We examined the incremental cost-effectiveness of adding one dose of PCV13 to the pre-2012 recommendation of PPSV23 for adults with 4 immunocompromising conditions who are at increased risk of pneumococcal disease: HIV/AIDS, hematologic cancer, solid organ transplants, and end stage renal disease. METHODS We used a probabilistic model following a single cohort of 302,397 immunocompromised adults. We used vaccination coverage and disease incidence data specific to each immunocompromising condition. Assumptions about PPSV23 and PCV13 vaccine effectiveness were based on two randomized controlled trials and several observational studies conducted among HIV-infected adults. Because no such studies have been conducted among other immunocompromised populations, we made further assumptions about the relative vaccine effectiveness in those groups. Cost-effectiveness ratios were determined for each condition and for all 4 groups in total. RESULTS Our model indicated that adding one dose of PCV13 to adults in the United States with 4 immunocompromising conditions would cost

Cost-Effectiveness of Using 2 vs 3 Primary Doses of 13-Valent Pneumococcal Conjugate Vaccine

16 million (in 2009