Allen S. Craig

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.

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.).

The Epidemiology of Invasive Group A Streptococcal Infection and Potential Vaccine Implications: United States, 2000–2004

BACKGROUND Invasive group A Streptococcus (GAS) infection causes significant morbidity and mortality in the United States. We report the current epidemiologic characteristics of invasive GAS infections and estimate the potential impact of a multivalent GAS vaccine. METHODS From January 2000 through December 2004, we collected data from Centers for Disease Control and Preventions Active Bacterial Core surveillance (ABCs), a population-based system operating at 10 US sites (2004 population, 29.7 million). We defined a case of invasive GAS disease as isolation of GAS from a normally sterile site or from a wound specimen obtained from a patient with necrotizing fasciitis or streptococcal toxic shock syndrome in a surveillance area resident. All available isolates were emm typed. We used US census data to calculate rates and to make age- and race-adjusted national projections. RESULTS We identified 5400 cases of invasive GAS infection (3.5 cases per 100,000 persons), with 735 deaths (case-fatality rate, 13.7%). Case-fatality rates for streptococcal toxic shock syndrome and necrotizing fasciitis were 36% and 24%, respectively. Incidences were highest among elderly persons (9.4 cases per 100,000 persons), infants (5.3 cases per 100,000 persons), and black persons (4.7 cases per 100,000 persons) and were stable over time. We estimate that 8950-11,500 cases of invasive GAS infection occur in the United States annually, resulting in 1050-1850 deaths. The emm types in a proposed 26-valent vaccine accounted for 79% of all cases and deaths. Independent factors associated with death include increasing age; having streptococcal toxic shock syndrome, meningitis, necrotizing fasciitis, pneumonia, or bacteremia; and having emm types 1, 3, or 12. CONCLUSIONS GAS remains an important cause of severe disease in the United States. The introduction of a vaccine could significantly reduce morbidity and mortality due to these infections.

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.

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.

Emergence of community-associated methicillin-resistant Staphylococcus aureus at a Memphis, Tennessee Children's Hospital.

Background: An epidemiologic investigation was performed because of a perceived increase in infections caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA) among children in the greater Memphis area. Methods: We reviewed medical records of 289 children evaluated from January 2000 to June 2002 at a childrens hospital. Clinical criteria were applied to classify MRSA isolates as community-associated (n=51) or health care-associated (n=138). The relatedness of 33 archived S. aureus isolates was evaluated using pulsed field gel electrophoresis (PFGE) of Sma I-digested genomic DNA; a common pulsed field type was defined as ≥80% similarity based on Dice coefficients. PFGE profiles were compared with those in a national database of MRSA isolates. Results: During the first 18 study months, 46 of 122 MRSA isolates (38%) were community-associated; this proportion increased to 106 of 167 isolates (63%) during the last 12 study months (P < .0001). Community-associated isolates were recovered from normally sterile sites as frequently as were health care-associated isolates (16% versus 13%). PFGE revealed that 15 of 16 community-associated isolates shared a common pulsed field type (USA300) observed in community-associated MRSA infections elsewhere in the United States and characterized by staphylococcal cassette chromosome mec type IV, clindamycin susceptibility and erythromycin resistance mediated by an msr A-encoded macrolide efflux pump. Conclusions: Community-associated MRSA has emerged as a potentially invasive pathogen among children in the greater Memphis area, and this phenomenon is not explained by spread of nosocomial strains into the community.

Incidence of Invasive Pneumococcal Disease among Individuals with Sickle Cell Disease before and after the Introduction of the Pneumococcal Conjugate Vaccine

BACKGROUND We sought to determine the incidence of invasive pneumococcal disease (IPD) among individuals with sickle cell disease (SCD) before and after the introduction of the pneumococcal conjugate vaccine (PCV). METHODS Individuals with SCD who were enrolled in Tennessee Medicaid from January 1995 through December 2004 were identified using SCD-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes. Population-based surveillance data were used to identify individuals with IPD and were linked to patients with SCD in the Tennessee Medicaid database to determine incidence rates of IPD. Clinical data were collected on all subjects with IPD, and antibiotic susceptibility testing and serotyping were performed on all available pneumococcal isolates. RESULTS We identified 2026 individuals with SCD, who constituted 13,687 person-years of follow-up. During the study period, 37 individuals with SCD developed IPD, and 21 of these patients were aged <5 years. In a comparison of the pre-PCV period (1995-1999) with the post-PCV period (2001-2004), the rate of IPD decreased by 90.8% in children aged <2 years (from 3630 to 335 cases per 100,000 person-years; P<.001) and by 93.4% in children aged <5 years (from 2044 to 134 cases per 100,000 person-years; P<.001). Rates of IPD for patients with SCD who were aged >or=5 years decreased from 161 cases per 100,000 person-years during the pre-PCV period to 99 cases per 100,000 person-years during the post-PCV period (P=.36). CONCLUSION The rate of IPD among children with SCD who are aged <5 years has decreased markedly since the introduction of routine administration of PCV to young children.

Revisiting the Need for Vaccine Prevention of Late-onset Neonatal Group B Streptococcal Disease: A Multistate, Population-based Analysis

Background: Intrapartum antibiotic prophylaxis for neonatal group B streptococcal disease (GBS) effectively prevents disease among infants <7 days old, but there are no prevention strategies for late-onset GBS disease (onset on days 7–89 of life). We describe trends in late-onset GBS over a 16-year period to characterize disease burden and estimate vaccine preventability. Methods: We conducted active, population-based surveillance for invasive late-onset GBS disease in 10 states from 1990 to 2005. A case was defined by GBS isolation from a normally sterile site on day 7–89 of life in a surveillance area resident. Incidence rates were calculated per 1000 resident live births. Results: We identified 1726 cases; 26% presented with meningitis, and the case fatality ratio was 4.3%. Incidence was similar throughout the study period. Incidence among black infants was approximately 3 times that among nonblack infants; the disparity persisted when data were stratified by gestational age. We estimate approximately 1300 cases of late-onset GBS occur annually in the United States. Birth at <37 weeks gestation was common among case-infants (49%) and was associated with elevated case fatality (relative risk: 3.8; 95% confidence interval: 1.1–13.2). Of 653 serotyped isolates, serotypes III (53%), IA (24%), and V (13%) predominated. During 2003–2005, 81 (36%) of the 227 cases caused by serotypes III, IA, and V were born before 34 weeks gestation. Conclusions: The late-onset GBS disease burden remains substantial. A trivalent vaccine could be an effective prevention strategy. Because many cases were born preterm, reducing the opportunity for transplacental antibody transfer, adolescent immunization should be considered.

Reduction in High Rates of Antibiotic-Nonsusceptible Invasive Pneumococcal Disease in Tennessee after Introduction of the Pneumococcal Conjugate Vaccine

BACKGROUND Invasive pneumococcal disease (IPD) is a burgeoning problem, with rates of antibiotic-nonsusceptible IPD, in particular, increasing during the past decade. One measure to combat IPD is vaccination with the recently introduced 7-valent pneumococcal conjugate vaccine (PCV). METHODS To evaluate the effects of the introduction of PCV in 2000 on the epidemiology of antibiotic-nonsusceptible IPD, a database of IPD cases from January 1995 through December 2002 identified through active surveillance in 5 Tennessee counties was examined. For each case, clinical data were collected, and antibiotic susceptibility testing and serotyping were performed on available isolates. RESULTS Among children younger than 2 years, IPD rates peaked at 235 cases per 100,000 in 1999 before decreasing, after PCV licensure, to 46 cases per 100,000 in 2002 (P<.001). The proportion of penicillin-nonsusceptible IPD isolates from this age group declined from 59.8% in 1999 to 30.4% in 2002 (P<.01). After 2001, similar decreases in IPD rates and in the proportion of antibiotic-nonsusceptible isolates recovered were seen among persons aged 2 years and older (P<.01). Rates of IPD due to PCV-associated serotypes declined after PCV introduction in all age groups (P<.001), whereas the rate of IPD due to nonvaccine serotypes increased among persons aged 2 years and older. CONCLUSIONS In the 2 years since licensure, widespread PCV vaccination of children has resulted in dramatic declines in the proportion of antibiotic-nonsusceptible isolates in Tennessee. PCV vaccination of children also appears to be a highly effective method for reducing the burden of IPD in adults.