Tracy Pondo

Changes in Neisseria meningitidis Disease Epidemiology in the United States, 1998–2007: Implications for Prevention of Meningococcal Disease

BACKGROUND In January 2005, a quadrivalent (serogroups A, C , Y, and W-135) meningococcal conjugate vaccine was licensed for use in adolescents. This report describes the epidemiologic features of meningococcal disease in the United States from January 1998 through December 2007, before and during implementation of adolescent quadrivalent meningococcal conjugate vaccination. METHODS Data were collected from active surveillance for invasive Neisseria meningitidis conducted through the Active Bacterial Core surveillance (ABCs) sites during 1998-2007. Isolates from cases were serogrouped at the ABCs site and confirmed at the Centers for Disease Control and Prevention. Estimates of the incidence and number of cases in the 50 states were calculated, standardizing for race and age group. RESULTS In the period 1998-2007, a total of 2262 cases of meningococcal disease were reported from ABCs sites; 11.3% of these cases were fatal. The estimated United States average annual incidence of meningococcal disease was 0.53 cases per 100,000 population (95% confidence interval, 0.51-0.55), and an estimated 1525 (95% confidence interval, 1470-1598) cases occurred annually. The annual incidence decreased 64.1%, from 0.92 cases per 100,000 population in 1998 to 0.33 cases per 100,000 population in 2007. Infants aged <1 year have the highest incidence of meningococcal disease (5.38 cases per 100,000 population). After introduction of the quadrivalent meningococcal conjugate vaccine, no significant decrease in serogroup C or Y meningococcal disease was seen among those aged 11-19 years in 2006-2007, compared with 2004-2005. CONCLUSIONS Before the introduction of the quadrivalent meningococcal conjugate vaccine, the incidence of meningococcal disease in the United States decreased to a historic low. However, meningococcal disease still causes a substantial burden of disease among all age groups. Future vaccination strategies may include targeting infants and preventing serogroup B meningococcal disease.

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.

Epidemiology of Invasive Group A Streptococcal Infections in the United States, 2005–2012

BACKGROUND Invasive group A Streptococcus (GAS) infections are associated with significant morbidity and mortality rates. We report the epidemiology and trends of invasive GAS over 8 years of surveillance. METHODS From January 2005 through December 2012, we collected data from the Centers for Disease Control and Preventions Active Bacterial Core surveillance, a population-based network of 10 geographically diverse US sites (2012 population, 32.8 million). We defined invasive GAS as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis (NF) or streptococcal toxic shock syndrome (STSS). Available isolates were emm typed. We calculated rates and made age- and race-adjusted national projections using census data. RESULTS We identified 9557 cases (3.8 cases per 100 000 persons per year) with 1116 deaths (case-fatality rate, 11.7%). The case-fatality rates for septic shock, STSS, and NF were 45%, 38%, and 29%, respectively. The annual incidence was highest among persons aged ≥65 years (9.4/100 000) or <1 year (5.3) and among blacks (4.7/100 000). National rates remained steady over 8 years of surveillance. Factors independently associated with death included increasing age, residence in a nursing home, recent surgery, septic shock, NF, meningitis, isolated bacteremia, pneumonia, emm type 1 or 3, and underlying chronic illness or immunosuppression. An estimated 10 649-13 434 cases of invasive GAS infections occur in the United States annually, resulting in 1136-1607 deaths. In a 30-valent M-protein vaccine, emm types accounted for 91% of isolates. CONCLUSIONS The burden of invasive GAS infection in the United States remains substantial. Vaccines under development could have a considerable public health impact.

Epidemiology of Invasive Early-Onset Neonatal Sepsis, 2005 to 2014

BACKGROUND: Group B Streptococcus (GBS) and Escherichia coli have historically dominated as causes of early-onset neonatal sepsis. Widespread use of intrapartum prophylaxis for GBS disease led to concerns about the potential adverse impact on E coli incidence. METHODS: Active, laboratory, and population-based surveillance for culture-positive (blood or cerebrospinal fluid) bacterial infections among infants 0 to 2 days of age was conducted statewide in Minnesota and Connecticut and in selected counties of California and Georgia during 2005 to 2014. Demographic and clinical information were collected and hospital live birth denominators were used to calculate incidence rates (per 1000 live births). We used the Cochran–Amitage test to assess trends. RESULTS: Surveillance identified 1484 cases. GBS was most common (532) followed by E coli (368) and viridans streptococci (280). Eleven percent of cases died and 6.3% of survivors had sequelae at discharge. All-cause (2005: 0.79; 2014: 0.77; P = .05) and E coli (2005: 0.21; 2014: 0.18; P = .25) sepsis incidence were stable. GBS incidence decreased (2005: 0.27; 2014: 0.22; P = .02). Among infants <1500 g, incidence was an order of magnitude higher for both pathogens and stable. The odds of death among infants <1500 g were similar for both pathogens but among infants ≥1500 g, the odds of death were greater for E coli cases (odds ratio: 7.0; 95% confidence interval: 2.7–18.2). CONCLUSIONS: GBS prevention efforts have not led to an increasing burden of early-onset E coli infections. However, the stable burden of E coli sepsis and associated mortality underscore the need for interventions.

Epidemiology of Infant Meningococcal Disease in the United States, 2006-2012

BACKGROUND: The incidence of meningococcal disease is currently at historic lows in the United States; however, incidence remains highest among infants aged <1 year. With routine use of Haemophilus influenzae type b and pneumococcal vaccines in infants and children in the United States, Neisseria meningitidis remains an important cause of bacterial meningitis in young children. METHODS: Data were collected from active, population- and laboratory-based surveillance for N meningitidis conducted through Active Bacterial Core surveillance during 2006 through 2012. Expanded data collection forms were completed for infant cases identified in the surveillance area during 2006 through 2010. RESULTS: An estimated 113 cases of culture-confirmed meningococcal disease occurred annually among infants aged <1 year in the United States from 2006 through 2012, for an overall incidence of 2.74 per 100 000 infants. Among these cases, an estimated 6 deaths occurred. Serogroup B was responsible for 64%, serogroup C for 12%, and serogroup Y for 16% of infant cases. Based on the expanded data collection forms, a high proportion of infant cases (36/58, 62%) had a smoker in the household and the socioeconomic status of the census tracts where infant meningococcal cases resided was lower compared with the other Active Bacterial Core surveillance areas and the United States as a whole. CONCLUSIONS: The burden of meningococcal disease remains highest in young infants and serogroup B predominates. Vaccines that provide long-term protection early in life have the potential to reduce the burden of meningococcal disease, especially if they provide protection against serogroup B meningococcal disease.

Evaluation of sex, race, body mass index and pre-vaccination serum progesterone levels and post-vaccination serum anti-anthrax protective immunoglobulin G on injection site adverse events following anthrax vaccine adsorbed (AVA) in the CDC AVA human clinical trial

BACKGROUND Anthrax vaccine adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. METHODS We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trials vaccinated cohort (n=1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n=227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. RESULTS Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. CONCLUSIONS Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants.

Meningococcal Carriage Among Georgia and Maryland High School Students

BACKGROUND Meningococcal disease incidence in the United States is at an all-time low. In a previous study of Georgia high school students, meningococcal carriage prevalence was 7%. The purpose of this study was to measure the impact of a meningococcal conjugate vaccine on serogroup Y meningococcal carriage and to define the dynamics of carriage in high school students. METHODS This was a prospective cohort study at 8 high schools, 4 each in Maryland and Georgia, during a school year. Students at participating schools received quadrivalent meningococcal conjugate vaccine that uses diphtheria toxoid as the protein carrier (MCV4-DT). In each state, 2 high schools were randomly assigned for MCV4-DT receipt by students at the beginning of the study, and 2 were randomly assigned for MCV4-DT receipt at the end. Oropharyngeal swab cultures for meningococcal carriage were performed 3 times during the school year. RESULTS Among 3311 students, the prevalence of meningococcal carriage was 3.21%-4.01%. Phenotypically nongroupable strains accounted for 88% of carriage isolates. There were only 5 observed acquisitions of serogroup Y strains during the study; therefore, the impact of MCV4-DT on meningococcal carriage could not be determined. CONCLUSIONS Meningococcal carriage rates in US high school students were lower than expected, and the vast majority of strains did not express capsule. These findings may help explain the historically low incidence of meningococcal disease in the United States.

Racial Disparities in Invasive Streptococcus pneumoniae Infections, 1998–2009

BACKGROUND Before the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), invasive pneumococcal disease (IPD) rates among blacks were twice the rates in whites. We measured the effects of trends in PCV7-type and non-PCV7-type IPD rates on racial disparities in overall IPD and estimated the proportion of IPD caused by serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13). METHODS We analyzed data from the Active Bacterial Core surveillance system, which performs active, laboratory- and population-based surveillance for IPD for 29.2 million people in the United States, for the period 1998-2009. For patients with unknown race, we multiplied imputed race to calculate age-, race-, and serotype-specific IPD incidence rates. RESULTS During 1998-2009, 47 449 IPD cases were identified; race was unknown for 5419 (11%). After multiple imputation, 31 981 (67%) patients were considered white and 13 750 (29%) black. PCV7-type IPD rates in all ages in both races decreased to <1 case per 100 000, whereas there were no decreases in overall IPD rates after 2002. By 2009, PCV13 serotypes caused 71% of cases among whites aged <5 years compared with 58% among blacks (P < .01). PCV13 serotypes caused 50% of IPD cases in whites aged ≥5 years compared with 43% among blacks (P < .01). CONCLUSIONS Despite near elimination of PCV7-type IPD in both races, overall disparities in IPD rates persisted because non-PCV7-type IPD rates are higher among blacks. Whereas PCV13 introduction may reduce racial disparities in IPD, higher valency conjugate vaccines and strategies to directly address underlying causes are needed to eliminate IPD disparities.

Epidemiology and Trends of Pertussis among Infants — United States, 2000–2015

Abstract Background Pertussis, a cyclic respiratory disease, causes the greatest morbidity and mortality among infants, particularly those too young to be vaccinated. Following a resurgence of pertussis in the 1990s, a recommendation was made in 2012 to vaccinate during every pregnancy in order to prevent infant disease. We describe pertussis trends from 2000–2015 among U.S. infants aged <1 year. Methods We analyzed infant pertussis cases reported through the National Notifiable Diseases Surveillance System from 2000 to 2015. Incidence rates (cases per 100,000 population) among various age groups (<2, 2– <4, 4– <6, and 6–<12 months) were calculated using National Center for Health Statistics population estimates as denominators. Negative binomial regression was used to estimate the annual average percent change with a linear trend; P < 0.05 was significant. Results From 2000 to 2015, 48,909 infant pertussis cases and 255 deaths were reported; infants aged <2 months accounted for 38.7% of cases. The age distribution of infant cases was stable from 2000 to 2009 but changed from 2010 to 2015 (Fig. 1), as the proportion of cases aged 4–<12 months increased annually on average by 4.7% (P < 0.001). Annual incidence was highest among <2 month olds; however, rates increased among older infants (Fig. 2): 7% average annual increase among infants aged 4–<6 months and 11% among infants aged 6–<12 months (P < 0.001 for each). The proportion of infants hospitalized decreased over time in each age group (P < 0.001 for all) with the largest annual average declines among 4–<6 (−5.1%) and 6–<12 month (−5.9%) olds. For all age groups, hospitalization rates were relatively stable, but non-hospitalization rates increased (P < 0.05 for all). The case–fatality ratio (CFR) was highest among <2 month olds (1.6%); CFRs decreased over time among <2 and 2–< 4 month olds (P < 0.05 for each). Conclusion Pertussis incidence remains highest among infants aged <4 months, although the age distribution appears to be changing. Decreasing proportions of infants hospitalized may suggest a true decline in disease severity or an increase in reporting of less severe disease. Ongoing monitoring of infant pertussis is needed to better understand the impact of vaccinating pregnant women to prevent pertussis in young infants. Disclosures All authors: No reported disclosures.

737The Impact of Obesity and Diabetes on the Risk and Outcomes of Invasive Group A Streptococcus Infections in Adults, Active Bacterial Core Surveillance (2010-2012)

of Invasive Group A Streptococcus Infections in Adults, Active Bacterial Core Surveillance (2010-2012) Gayle E. Langley, MD, MPH; Tracy Pondo, MSPH; Lee Harrison, MD; Monica M. Farley, MD; Mary Lou Lindegren, MD, MPH; Megin Nichols, DVM, MPH, DACVPM; Ann Thomas, MD, MPH; Kathryn Como-Sabetti, MPH; Susan Petit, MPH; Mirasol M. Apostol, MPH; Nong Shang, PhD; Chris Van Beneden, MD, MPH; Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA; Infectious Diseases, University of Pittsburgh, Pittsburgh, PA; Emory University School of Medicine, Atlanta, GA; Vanderbilt University School of Medicine, Nashville, TN; New Mexico Department of Public Health, Santa Fe, NM; Oregon Public Health Division, Portland, OR; Minnesota Department of Health, St. Paul, MN; Connecticut Emerging Infections Program, New Haven, CT; California Emerging Infections Program, Oakland, CA; CDC, Atlanta, GA