Sara Y. Tartof

Analysis of a Uropathogenic Escherichia coli Clonal Group by Multilocus Sequence Typing

ABSTRACT Although many strain typing methods exist for pathogenic Escherichia coli, most have drawbacks in terms of resolving power, interpretability, or scalability. For this reason, multilocus sequence typing (MLST) is an appealing alternative. However, its applicability to different pathogens in specific epidemiologic contexts is not well understood. Here, we applied a previously established MLST method based on housekeeping genes to a well-characterized collection of uropathogenic E. coli isolates to compare the discriminatory ability of this procedure with that of enterobacterial repeat intergenic consensus (ERIC2) PCR, serogrouping, and pulsed-field gel electrophoresis (PFGE). Among 45 E. coli isolates studied, 17 different multilocus sequence types (ST) were identified. One MLST group (designated ST69 complex) was comprised of 22 isolates, all belonging to uropathogenic and bacteremic E. coli strains previously defined as clonal group A (CgA) by ERIC2 PCR. The ST69 strains contained five different serogroups and 14 PFGE types. ERIC2 PCR CgA strains belonging to different MLST groups were also identified. Interestingly, one cow E. coli isolate, previously shown by PFGE to be closely related to a human uropathogenic CgA strain, was found to cluster with the ST69 strains. All of the other animal and environmental CgA isolates had different MLST profiles. The discriminatory power of this MLST method based on housekeeping genes appears to be higher than that of ERIC2 PCR but lower than that of PFGE for epidemiologic study of uropathogenic E. coli.

Waning Immunity to Pertussis Following 5 Doses of DTaP

OBJECTIVE: To assess the risk of pertussis by time since vaccination in children in Minnesota and Oregon who received 5 doses of acellular pertussis vaccines (DTaP). METHODS: These cohort analyses included Minnesota and Oregon children born between 1998 and 2003 who had 5 DTaP doses recorded in state Immunization Information Systems. Immunization records and statewide pertussis surveillance data were combined. Incidence rates and risk ratios for pertussis were calculated for the 6 years after receipt of the fifth DTaP dose. RESULTS: The cohorts included 224 378 Minnesota children and 179 011 from Oregon; 458 and 89 pertussis cases were identified in Minnesota and Oregon, respectively. Pertussis incidence rates rose each year of follow-up: 15.6/100 000 (95% confidence interval [CI]: 11.1–21.4) at year 1 to 138.4/100 000 (CI: 113.3–166.9) at year 6 (Minnesota); 6.2/100 000 (CI: 3.3–10.6) in year 1 to 24.4/100 000 (CI: 15.0–37.8) in year 6 (Oregon). Risk ratios increased from 1.9 (CI: 1.3–2.9) in year 2 to 8.9 (CI: 6.0–13.0) in year 6 (Minnesota) and from 1.3 (CI: 0.6–2.8) in year 2 to 4.0 (CI: 1.9–8.4) in year 6 (Oregon). CONCLUSIONS: This evaluation reports steady increase in risk of pertussis in the years after completion of the 5-dose DTaP series. This rise is likely attributable in part to waning immunity from DTaP vaccines. Continuing to monitor disease burden and vaccine effectiveness in fully vaccinated children in coming years will be important to assess ongoing risk as additional cohorts vaccinated solely with acellular pertussis vaccines are introduced.

Vaccines and the Risk of Multiple Sclerosis and Other Central Nervous System Demyelinating Diseases

IMPORTANCE Because vaccinations are common, even a small increased risk of multiple sclerosis (MS) or other acquired central nervous system demyelinating syndromes (CNS ADS) could have a significant effect on public health. OBJECTIVE To determine whether vaccines, particularly those for hepatitis B (HepB) and human papillomavirus (HPV), increase the risk of MS or other CNS ADS. DESIGN, SETTING, AND PARTICIPANTS A nested case-control study was conducted using data obtained from the complete electronic health records of Kaiser Permanente Southern California (KPSC) members. Cases were identified through the KPSC CNS ADS cohort between 2008 and 2011, which included extensive review of medical records by an MS specialist. Five controls per case were matched on age, sex, and zip code. EXPOSURES Vaccination of any type (particularly HepB and HPV) identified through the electronic vaccination records system. MAIN OUTCOMES AND MEASURES All forms of CNS ADS were analyzed using conditional logistic regression adjusted for race/ethnicity, health care utilization, comorbid diseases, and infectious illnesses before symptom onset. RESULTS We identified 780 incident cases of CNS ADS and 3885 controls; 92 cases and 459 controls were females aged 9 to 26 years, which is the indicated age range for HPV vaccination. There were no associations between HepB vaccination (odds ratio [OR], 1.12; 95% CI, 0.72-1.73), HPV vaccination (OR, 1.05; 95% CI, 0.62-1.78), or any vaccination (OR, 1.03; 95% CI, 0.86-1.22) and the risk of CNS ADS up to 3 years later. Vaccination of any type was associated with an increased risk of CNS ADS onset within the first 30 days after vaccination only in younger (<50 years) individuals (OR, 2.32; 95% CI, 1.18-4.57). CONCLUSIONS AND RELEVANCE We found no longer-term association of vaccines with MS or any other CNS ADS, which argues against a causal association. The short-term increase in risk suggests that vaccines may accelerate the transition from subclinical to overt autoimmunity in patients with existing disease. Our findings support clinical anecdotes of CNS ADS symptom onset shortly after vaccination but do not suggest a need for a change in vaccine policy.

A change in vaccine efficacy and duration of protection explains recent rises in pertussis incidence in the United States

Over the past ten years the incidence of pertussis in the United States (U.S.) has risen steadily, with 2012 seeing the highest case number since 1955. There has also been a shift over the same time period in the age group reporting the largest number of cases (aside from infants), from adolescents to 7–11 year olds. We use epidemiological modelling and a large case incidence dataset to explain the upsurge. We investigate several hypotheses for the upsurge in pertussis cases by fitting a suite of dynamic epidemiological models to incidence data from the National Notifiable Disease Surveillance System (NNDSS) between 1990–2009, as well as incidence data from a variety of sources from 1950–1989. We find that: the best-fitting model is one in which vaccine efficacy and duration of protection of the acellular pertussis (aP) vaccine is lower than that of the whole-cell (wP) vaccine, (efficacy of the first three doses 80% [95% CI: 78%, 82%] versus 90% [95% CI: 87%, 94%]), increasing the rate at which disease is reported to NNDSS is not sufficient to explain the upsurge and 3) 2010–2012 disease incidence is predicted well. In this study, we use all available U.S. surveillance data to: 1) fit a set of mathematical models and determine which best explains these data and 2) determine the epidemiological and vaccine-related parameter values of this model. We find evidence of a difference in efficacy and duration of protection between the two vaccine types, wP and aP (aP efficacy and duration lower than wP). Future refinement of the model presented here will allow for an exploration of alternative vaccination strategies such as different age-spacings, further booster doses, and cocooning.

Declining Effectiveness of Herpes Zoster Vaccine in Adults Aged ≥60 Years

Understanding long-term effectiveness of herpes zoster (HZ) vaccine is critical for determining vaccine policy. 176 078 members of Kaiser Permanente ≥60 years vaccinated with HZ vaccine and three matched unvaccinated members were included. Hazard ratios and 95% confidence intervals (CIs) associated with vaccination at each year following vaccination were estimated by Cox regression model. The effectiveness of HZ vaccine decreased from 68.7% (95% CI, 66.3%-70.9%) in the first year to 4.2% (95% CI, -24.0% to 25.9%) in the eighth year. This rapid decline in effectiveness of HZ vaccine suggests that a revaccination strategy may be needed, if feasible.

Vaccination Against Zoster Remains Effective in Older Adults Who Later Undergo Chemotherapy

BACKGROUND Approximately 40% of adults develop invasive cancer during their lifetimes, many of whom require chemotherapy. Herpes zoster (HZ) is common and often severe in patients undergoing chemotherapy, yet there are no data regarding whether these patients retain specific protection against HZ if they had previously received zoster vaccine. We conducted a study to determine whether zoster vaccine was effective in patients who subsequently underwent chemotherapy. METHODS The cohort study consisted of Kaiser Permanente Southern California members aged ≥60 years treated with chemotherapy. The exposure variable was receipt of zoster vaccine prior to initiation of chemotherapy. Incident HZ cases were identified using International Classification of Diseases, Ninth Revision diagnostic codes. HZ incidence rates were calculated; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. RESULTS There were 91 and 583 HZ cases in the vaccinated and unvaccinated cohorts, respectively, yielding an incidence rate of 12.87 (95% CI, 10.48-15.80) vs 22.05 (95% CI, 20.33-23.92) per 1000 person-years. Thirty-month cumulative incidence was 3.28% in the vaccinated group and 5.34% in the unvaccinated group (P < .05). The adjusted HR for HZ was 0.58 (95% CI, .46-.73) and showed no significant variation by age, sex, or race. HZ incidence rates remained increased in the small subgroup of persons receiving zoster vaccine within 60 days before chemotherapy, but this was the only group affected by indication bias. No vaccinated patients underwent hospitalization for HZ, compared with 6 unvaccinated patients. CONCLUSIONS Zoster vaccine continues to protect against HZ if recipients later undergo chemotherapy. Our findings provide an additional rationale for offering zoster vaccine to indicated adults while they are immunocompetent.

A Comprehensive Assessment Across the Healthcare Continuum: Risk of Hospital-Associated Clostridium difficile Infection Due to Outpatient and Inpatient Antibiotic Exposure.

BACKGROUND Limitations in sample size, overly inclusive antibiotic classes, lack of adjustment of key risk variables, and inadequate assessment of cases contribute to widely ranging estimates of risk factors for Clostridium difficile infection (CDI). OBJECTIVE To incorporate all key CDI risk factors in addition to 27 antibiotic classes into a single comprehensive model. DESIGN Retrospective cohort study. SETTING Kaiser Permanente Southern California. PATIENTS Members of Kaiser Permanente Southern California at least 18 years old admitted to any of its 14 hospitals from January 1, 2011, through December 31, 2012. METHODS Hospital-acquired CDI cases were identified by polymerase chain reaction assay. Exposure to major outpatient antibiotics (10 classes) and those administered during inpatient stays (27 classes) was assessed. Age, sex, self-identified race/ethnicity, Charlson Comorbidity Score, previous hospitalization, transfer from a skilled nursing facility, number of different antibiotic classes, statin use, and proton pump inhibitor use were also assessed. Poisson regression estimated adjusted risk of CDI. RESULTS A total of 401,234 patients with 2,638 cases of incident CDI (0.7%) were detected. The final model demonstrated highest CDI risk associated with increasing age, exposure to multiple antibiotic classes, and skilled nursing facility transfer. Factors conferring the most reduced CDI risk were inpatient exposure to tetracyclines and first-generation cephalosporins, and outpatient macrolides. CONCLUSIONS Although type and aggregate antibiotic exposure are important, the factors that increase the likelihood of environmental spore acquisition should not be underestimated. Operationally, our findings have implications for antibiotic stewardship efforts and can inform empirical and culture-driven treatment approaches.

Effectiveness of Herpes Zoster Vaccine in Patients 60 Years and Older With End-stage Renal Disease

BACKGROUND Unlike in a healthy population, the protection of herpes zoster (HZ) vaccine in end-stage renal disease (ESRD) patients might be insufficient, considering data demonstrating suboptimal response to other vaccines. The study evaluates the association between HZ vaccination and the subsequent HZ risk among ESRD patients. METHODS This cohort study included ESRD patients age ≥60 years who were enrolled in Kaiser Permanente Southern California. The vaccinated cohort included 582 patients who received HZ vaccine during 01/01/2007 through 12/31/2013. Each vaccinated patient was matched to five unvaccinated patients on age, sex, and dialysis duration. Subjects were passively followed through their electronic health records to identify HZ incidence. Cox regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) associated with vaccination. Kaplan-Meier estimates of the cumulative incidence were generated. RESULTS The number of HZ cases was 16 in 1373 person-years (11.7 per 1000 person-years; 95% CI, 7.1-19.0) among the vaccinated and 126 in 5644 person-years (22.3 per 1000 person-years; 95% CI, 18.7-26.6) among the unvaccinated. The 36-month cumulative risk of incident HZ was 4.1% and 6.6%, respectively. HZ vaccination was associated with a reduced risk of HZ (adjusted HR = 0.49; 95% CI, .29-.85). The reduced risk seems more prominent if the vaccine is given within two years of dialysis initiation. CONCLUSIONS Among ESRD patients age ≥60 years, receipt of HZ vaccine was associated with a lower incidence of HZ. In addition, HZ vaccination soon after the initiation of dialysis may provide greater protection.

Trends and disparity in zoster vaccine uptake in a managed care population

OBJECTIVES Zoster vaccine is recommended for prevention of herpes zoster among adults aged 60 years and older. We examined the zoster vaccination rates during 2007-2011 and assessed association with age, sex, race/ethnicity, neighborhood income and education attainment in eligible adults at Kaiser Permanente Southern California, a managed care organization in the US. METHODS We calculated annual zoster vaccination rate among members ≥60 years without documented contraindications. Multivariable logistic regression was performed to examine factors associated with zoster vaccine uptake in an open cohort of 819,466 adults. RESULTS The zoster vaccination rates increased annually in all groups and the overall rate reached 21.7% in 2011 (P-trend<0.001). Coverage was highest among individuals aged 65-74 years, who were female and non-Hispanic White. In the adjusted analysis, odds of vaccination decreased by age. Females (odds ratio [OR]=1.19, 95% confidence interval [CI]=1.17-1.20) and those who lived in neighborhoods with higher education attainment were more likely to be vaccinated (>75% vs. <50% adults with some college education: OR=1.76, 95% CI=1.73-1.80). Compared to Whites, non-Hispanic Blacks and Hispanics were less likely to receive the vaccine (non-Hispanic Blacks: OR=0.56, 95% CI=0.55-0.58; Hispanics: OR=0.59, 95% CI=0.58-0.60). CONCLUSION The zoster vaccine coverage is higher in this insured population than previously reported in the US general population, but it remains low. Significant racial/ethnic disparity was observed and worsened even among individuals with relatively equal access to zoster vaccination.

Zoster Vaccine and the Risk of Postherpetic Neuralgia in Patients Who Developed Herpes Zoster Despite Having Received the Zoster Vaccine

BACKGROUND Although it is evident that zoster vaccination reduces postherpetic neuralgia (PHN) risk by reducing herpes zoster (HZ) occurrence, it is less clear whether the vaccine protects against PHN among patients who develop HZ despite previous vaccination. METHODS This cohort study included immunocompetent patients with HZ. The vaccinated cohort included 1155 individuals who were vaccinated against HZ at age ≥60 years and had an HZ episode after vaccination. Vaccinated patients were matched 1:1 by sex and age with unvaccinated patients. Trained medical residents reviewed the full medical record to determine the presence of HZ-related pain at 1, 2, 3, and 6 months after HZ diagnosis. The incidence of PHN was compared between vaccinated and unvaccinated -patients. RESULTS Thirty vaccinated women (4.2%) experienced PHN, compared with 75 unvaccinated women (10.4%), with an adjusted relative risk of 0.41 (95% confidence interval, .26-.64). PHN occurred in 26 vaccinated men (6.0%) versus 25 unvaccinated men (5.8%), with an adjusted relative risk of 1.06 (.58-1.94). These associations did not differ significantly by age. CONCLUSIONS Among persons experiencing HZ, prior HZ vaccination is associated with a lower risk of PHN in women but not in men. This sex-related difference may reflect differences in healthcare-seeking patterns and deserve further investigation.