Elizabeth R. Zell

Epidemiology of Invasive Group B Streptococcal Disease in the United States, 1999-2005

CONTEXT Group B streptococcus is a leading infectious cause of morbidity in newborns and causes substantial disease in elderly individuals. Guidelines for prevention of perinatal disease through intrapartum chemoprophylaxis were revised in 2002. Candidate vaccines are under development. OBJECTIVE To describe disease trends among populations that might benefit from vaccination and among newborns during a period of evolving prevention strategies. DESIGN AND SETTING Analysis of active, population-based surveillance in 10 states participating in the Active Bacterial Core surveillance/Emerging Infections Program Network. MAIN OUTCOME MEASURES Age- and race-specific incidence of invasive group B streptococcal disease. RESULTS There were 14,573 cases of invasive group B streptococcal disease during 1999-2005, including 1348 deaths. The incidence of invasive group B streptococcal disease among infants from birth through 6 days decreased from 0.47 per 1000 live births in 1999-2001 to 0.34 per 1000 live births in 2003-2005 (P < .001), a relative reduction of 27% (95% confidence interval [CI], 16%-37%). Incidence remained stable among infants aged 7 through 89 days (mean, 0.34 per 1000 live births) and pregnant women (mean, 0.12 per 1000 live births). Among persons aged 15 through 64 years, disease incidence increased from 3.4 per 100,000 population in 1999 to 5.0 per 100,000 in 2005 (chi2(1) for trend, 57; P < .001), a relative increase of 48% (95% CI, 32%-65%). Among adults 65 years or older, incidence increased from 21.5 per 100,000 to 26.0 per 100,000 (chi2(1) for trend, 15; P < .001), a relative increase of 20% (95% CI, 8%-35%). All 4882 isolates tested were susceptible to penicillin, ampicillin, and vancomycin, but 32% and 15% were resistant to erythromycin and clindamycin, respectively. Serotypes Ia, Ib, II, III, and V accounted for 96% of neonatal cases and 88% of adult cases. CONCLUSIONS Among infants from birth through 6 days, the incidence of group B streptococcal disease was lower in 2003-2005 relative to 1999-2001. This reduction coincided with the release of revised disease prevention guidelines in 2002. However, the disease burden in adults is substantial and increased significantly during the study period.

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.).

Epidemiology of invasive group a streptococcus disease in the United States, 1995-1999.

Severe invasive group A streptococcal (GAS) disease is believed to have reemerged during the past 10-20 years. We conducted active, laboratory, population-based surveillance in 5 US states (total population, 13,214,992). From 1 July 1995 through 31 December 1999, we identified 2002 episodes of invasive GAS (3.5 cases per 100,000 persons). Rates varied by age (higher among those <2 or >/=65 years old), surveillance area, and race (higher among black individuals) but did not increase during the study period. The 5 most common emm types (1, 28, 12, 3, and 11) accounted for 49.2% of isolates; newly characterized emm types accounted for 8.9% of isolates. Older age; presence of streptococcal toxic shock syndrome, meningitis, or pneumonia; and infection with emm1 or emm3 were all independent predictors of death. We estimate that 9600-9700 cases of invasive GAS disease occur in the United States each year, resulting in 1100-1300 deaths.

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.

Increasing Burden of Invasive Group B Streptococcal Disease in Nonpregnant Adults, 1990–2007

BACKGROUND Group B Streptococcus (GBS), traditionally considered to be a neonatal pathogen, is an important cause of morbidity and mortality among older adults and among those with underlying medical conditions. We used population-based surveillance to examine trends in adult GBS disease during the period 1990-2007 and to describe the epidemiology of adult GBS disease to guide prevention efforts. METHODS Active Bacterial Core surveillance was conducted in selected counties in 10 US states. A case was defined as isolation of GBS from a normally sterile site in a nonpregnant resident of a surveillance area who was 18 years of age. Rates were calculated using US Census data. Demographic and clinical information was abstracted from medical records. Serotyping and susceptibility testing were performed on isolates collected from a subset of case patients. RESULTS A total of 19,512 GBS cases were identified in nonpregnant adults during 1990-2007 (median patient age, 63 years); the incidence of adult GBS disease doubled from 3.6 cases per 100,000 persons during 1990 to 7.3 cases per 100,000 persons during 2007 (P < .001). The mean difference in incidence between black and white persons was 4.6 cases per 100,000 persons (range, 3.1 cases per 100,000 persons during 1991 to 5.8 cases per 100,000 persons during 1999). Common clinical syndromes in 2007 included bacteremia without focus (39.3%), skin and/or soft-tissue infection (25.6%), and pneumonia (12.6%). Most (88.0%) GBS cases in adults had 1 underlying condition; diabetes was present in 44.4% of cases. Serotypes V, Ia, II, and III accounted for 80.8% of infections during 1998-1999 and 78.5% of infections during 2005-2006. CONCLUSIONS Invasive GBS disease in nonpregnant adults represents a substantial and increasing burden, particularly among older persons, black persons, and adults with diabetes. Prevention strategies are needed.

The Influence of Chronic Illnesses on the Incidence of Invasive Pneumococcal Disease in Adults

Pneumococcal disease is more frequent and more deadly in persons with certain comorbidities. We used 1999 and 2000 data from the Active Bacterial Core surveillance (ABCs) and the National Health Interview Survey (NHIS) to determine rates of invasive pneumococcal disease in healthy adults (> or =18 years old) and in adults with various high-risk conditions. The risks of invasive pneumococcal disease in persons with specific chronic illnesses was compared with that in healthy adults, controlling for age, race, and the other chronic illnesses. Overall incidence rates, in cases/100,000 persons, were 8.8 in healthy adults, 51.4 in adults with diabetes, 62.9 in adults with chronic lung disease, 93.7 in adults with chronic heart disease, and 100.4 in adults who abused alcohol. Among the high-risk groups evaluated, risk was highest in adults with solid cancer (300.4), HIV/AIDS (422.9), and hematological cancer (503.1). Incidence rates increased with advancing age in adults with chronic lung disease, diabetes, and solid cancer. Black adults had higher incidence rates than white adults, both in healthy adults and in adults with chronic illnesses. These data support recommendations to provide pneumococcal vaccine to persons in these at-risk groups and underscore the need for better prevention strategies for immunocompromised persons.

Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial

BACKGROUND Pneumococcal conjugate vaccines (PCVs) prevent vaccine serotype (VT) invasive disease; nonvaccine serotype (NVT) disease increases modestly. The impact of PCV on nasopharyngeal (NP) colonization is essential to understanding disease effects. METHODS We conducted a community-randomized controlled trial with catch-up vaccination through age 2 years investigating the effect of 7-valent PCV (PnCRM7) on NP colonization among American Indian infants and their unvaccinated contacts. Infants receiving blinded vaccine at 2, 4, 6, and 12-15 months of age had NP cultures obtained at age 7, 12, and 18 months. Serotype-specific colonization was detected by immunoblot. RESULTS We enrolled 566 vaccinated and 286 unvaccinated children from 511 households and collected 5157 specimens, of which 3525 (68.4%) had pneumococcus. PnCRM7 vaccinees were less likely to be colonized with VT (odds ratio [OR], 0.40 [95% confidence interval {CI}, 0.23-0.67]) but were more likely to be colonized with NVT pneumococci (OR, 1.67 [95% CI, 1.02-2.78]). PnCRM7 vaccinees were less densely colonized with VT strains than control vaccinees (OR, 0.61 [95% CI, 0.38-0.99]). Day care-attending unvaccinated children in PnCRM7 communities were less likely to have VT colonization than those in control communities (OR, 0.27 [95% CI, 0.07-1.07]). CONCLUSIONS PnCRM7 reduces the risk of VT acquisition and colonization density but increases the risk of NVT acquisition among vaccinees and their household contacts.

Healthcare utilization and cost of pneumococcal disease in the United States

BACKGROUND Streptococcus pneumoniae continues to cause a variety of common clinical syndromes, despite vaccination programs for both adults and children. The total U.S. burden of pneumococcal disease is unknown. METHODS We constructed a decision tree-based model to estimate U.S. healthcare utilization and costs of pneumococcal disease in 2004. Data were obtained from the 2004-2005 National (Hospital) Ambulatory Medical Care Surveys (outpatient visits, antibiotics) and the National Hospital Discharge Survey (hospitalization rates), and CDC surveillance data. Other assumptions regarding the incidence of each syndrome due to pneumococcus, expected health outcomes, and healthcare utilization were derived from literature and expert opinion. Healthcare and time costs used 2007 dollars. RESULTS We estimate that, in 2004, pneumococcal disease caused 4.0 million illness episodes, 22,000 deaths, 445,000 hospitalizations, 774,000 emergency department visits, 5.0 million outpatient visits, and 4.1 million outpatient antibiotic prescriptions. Direct medical costs totaled

Waning Immunity to Pertussis Following 5 Doses of DTaP

3.5 billion. Pneumonia (866,000 cases) accounted for 22% of all cases and 72% of pneumococcal costs. In contrast, acute otitis media and sinusitis (1.5 million cases each) comprised 75% of cases but only 16% of direct medical costs. Patients ≥ 65 years old, accounted for most serious cases and the majority of direct medical costs (