Nancy M. Bennett

Sustained Reductions in Invasive Pneumococcal Disease in the Era of Conjugate Vaccine

BACKGROUND Changes in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children. METHODS Laboratory-confirmed IPD cases were identified during 1998-2007 by 8 active population-based surveillance sites. We compared overall, age group-specific, syndrome-specific, and serotype group-specific IPD incidence in 2007 with that in 1998-1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations. RESULTS Overall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively (P< .01 all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively (P< .01 for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups (P< .05), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006-2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old. CONCLUSIONS Dramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD.

Bacterial Meningitis in the United States, 1998-2007

BACKGROUND The rate of bacterial meningitis declined by 55% in the United States in the early 1990s, when the Haemophilus influenzae type b (Hib) conjugate vaccine for infants was introduced. More recent prevention measures such as the pneumococcal conjugate vaccine and universal screening of pregnant women for group B streptococcus (GBS) have further changed the epidemiology of bacterial meningitis. METHODS We analyzed data on cases of bacterial meningitis reported among residents in eight surveillance areas of the Emerging Infections Programs Network, consisting of approximately 17.4 million persons, during 1998-2007. We defined bacterial meningitis as the presence of H. influenzae, Streptococcus pneumoniae, GBS, Listeria monocytogenes, or Neisseria meningitidis in cerebrospinal fluid or other normally sterile site in association with a clinical diagnosis of meningitis. RESULTS We identified 3188 patients with bacterial meningitis; of 3155 patients for whom outcome data were available, 466 (14.8%) died. The incidence of meningitis changed by -31% (95% confidence interval [CI], -33 to -29) during the surveillance period, from 2.00 cases per 100,000 population (95% CI, 1.85 to 2.15) in 1998-1999 to 1.38 cases per 100,000 population (95% CI 1.27 to 1.50) in 2006-2007. The median age of patients increased from 30.3 years in 1998-1999 to 41.9 years in 2006-2007 (P<0.001 by the Wilcoxon rank-sum test). The case fatality rate did not change significantly: it was 15.7% in 1998-1999 and 14.3% in 2006-2007 (P=0.50). Of the 1670 cases reported during 2003-2007, S. pneumoniae was the predominant infective species (58.0%), followed by GBS (18.1%), N. meningitidis (13.9%), H. influenzae (6.7%), and L. monocytogenes (3.4%). An estimated 4100 cases and 500 deaths from bacterial meningitis occurred annually in the United States during 2003-2007. CONCLUSIONS The rates of bacterial meningitis have decreased since 1998, but the disease still often results in death. With the success of pneumococcal and Hib conjugate vaccines in reducing the risk of meningitis among young children, the burden of bacterial meningitis is now borne more by older adults. (Funded by the Emerging Infections Programs, Centers for Disease Control and Prevention.).

Population Snapshot of Emergent Streptococcus pneumoniae Serotype 19A in the United States, 2005

BACKGROUND Serotype 19A invasive pneumococcal disease (IPD) increased annually in the United States after the introduction of the 7-valent conjugate vaccine (PCV7). To understand this increase, we characterized serotype 19A isolates recovered during 2005. METHODS IPD cases during 1998-2005 were identified through population-based surveillance. We performed susceptibility testing and multilocus sequence typing on 528 (95%) of 554 serotype 19A isolates reported in 2005. RESULTS The incidence of IPD due to serotype 19A increased from 0.8 to 2.5 cases per 100,000 population between 1998 and 2005 (P < .05), whereas the overall incidence of IPD decreased from 24.4 to 13.8 cases per 100,000 population (P < .05). Simultaneously, the incidence of IPD due to penicillin-resistant 19A isolates increased from 6.7% to 35% (P < .0001). Of 151 penicillin-resistant 19A isolates, 111 (73.5%) belonged to the rapidly emerging clonal complex 320, which is related to multidrug-resistant Taiwan(19F)-14. The remaining penicillin-resistant strains were highly related to other clones of PCV7 serotypes or to isolates within major 19A clonal complex 199 (CC199). In 1999, only CC199 and 3 minor clones were apparent among serotype 19A isolates. During 2005, 11 multiple-isolate clonal sets were detected, including capsular switch variants of a serotype 4 clone. CONCLUSIONS PCV7 ineffectiveness against serotype 19A, antibiotic resistance, clonal expansion and emergence, and capsular switching have contributed to the genetic diversity of 19A and to its emergence as the predominant invasive pneumococcal serotype in the United States.

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.

Geographic diversity and temporal trends of antimicrobial resistance in Streptococcus pneumoniae in the United States.

Resistance of Streptococcus pneumoniae to antibiotics is increasing throughout the United States, with substantial variation among geographic regions. We show that patterns of geographic variation are best explained by the intensity of selection for resistance, which is reflected by differences between the proportions of resistance within individual serotypes, rather than by differences between the frequencies of particular serotypes. Using a mathematical transmission model, we analyzed temporal trends in the proportions of singly and dually resistant organisms and found that pneumococcal strains resistant to both penicillin and erythromycin are increasing faster than strains singly resistant to either. Using the model, we predict that by 1 July 2004, in the absence of a vaccine, 41% of pneumococci at the Centers for Disease Control and Prevention (CDC)s Active Bacterial Core surveillance (ABCs) sites, taken together, will be dually resistant, with 5% resistant to penicillin only and 5% to erythromycin only.

Pulmonary Aspiration in a Long‐term Care Setting: Clinical and Laboratory Observations and An Analysis of Risk Factors

OBJECTIVE: To determine the incidence and risk factors associated with aspiration in a high risk group in a long‐term care setting.

Association Between Use of Statins and Mortality Among Patients Hospitalized With Laboratory-Confirmed Influenza Virus Infections: A Multistate Study

BACKGROUND Statins may have anti-inflammatory and immunomodulatory effects that could reduce the risk of mortality from influenza virus infections. METHODS The Centers for Disease Control and Preventions Emerging Infections Program conducts active surveillance for persons hospitalized with laboratory-confirmed influenza in 59 counties in 10 states. We analyzed data for hospitalized adults during the 2007-2008 influenza season to evaluate the association between receiving statins and influenza-related death. RESULTS We identified 3043 patients hospitalized with laboratory-confirmed influenza, of whom 1013 (33.3%) received statins and 151 (5.0%) died within 30 days of their influenza test. Patients who received statins were more likely to be older, male, and white; to suffer from cardiovascular, metabolic, renal, and chronic lung disease; and to have been vaccinated against influenza that season. In a multivariable logistic regression model, administration of statins prior to or during hospitalization was associated with a protective odds of death (adjusted odds ratio, 0.59 [95% confidence interval, .38-.92]) when adjusting for age; race; cardiovascular, lung, and renal disease; influenza vaccination; and antiviral administration. CONCLUSIONS Statin use may be associated with reduced mortality in patients hospitalized with influenza.

Pneumococcal bacteremia in Monroe County, New York

OBJECTIVES Knowledge of the epidemiology of pneumococcal disease is critical for public health planning, evaluation of preventive strategies, and development of immunization recommendations. METHODS We studied the incidence and case-fatality rates of pneumococcal bacteremia as a proxy for pneumococcal disease in Monroe County, New York, from 1985 through 1989 by reviewing the laboratory and clinical care records of all cases occurring among residents. RESULTS There were 671 cases identified, for an overall yearly rate of 18.8 per 100,000. The rates were highest in the very young, in the very old, and in non-White populations. Age-specific rates were consistently higher in Blacks than in Whites. Predisposing medical conditions were present in 61% of cases. Case-fatality rates were 15% overall, 27% in those with predisposing medical conditions, and approximately 30% in Blacks older than 55 years and Whites older than 65 years. CONCLUSIONS This study documents the incidence of and mortality from pneumococcal bacteremia. It supports previous observations that Black populations have an increased risk of invasive pneumococcal infection and suggests that immunization should be considered for Blacks older than 55 years.

Intervals Between PCV13 and PPSV23 Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP).

Two pneumococcal vaccines are currently licensed for use in the United States: the 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer Inc.]) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax 23, Merck and Co., Inc.]). The Advisory Committee on Immunization Practices (ACIP) currently recommends that a dose of PCV13 be followed by a dose of PPSV23 in all adults aged ≥65 years who have not previously received pneumococcal vaccine and in persons aged ≥2 years who are at high risk for pneumococcal disease because of underlying medical conditions (Table) (1-4). The recommended intervals between PCV13 and PPSV23 given in series differ by age and risk group and the order in which the two vaccines are given (1-4).