Susan Petit

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.

Health care-associated invasive MRSA infections, 2005-2008.

CONTEXT Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of public health importance; MRSA prevention programs that may affect MRSA transmission and infection are increasingly common in health care settings. Whether there have been changes in MRSA infection incidence as these programs become established is unknown; however, recent data have shown that rates of MRSA bloodstream infections (BSIs) in intensive care units are decreasing. OBJECTIVE To describe changes in rates of invasive health care-associated MRSA infections from 2005 through 2008 among residents of 9 US metropolitan areas. DESIGN, SETTING, AND PARTICIPANTS Active, population-based surveillance for invasive MRSA in 9 metropolitan areas covering a population of approximately 15 million persons. All reports of laboratory-identified episodes of invasive (from a normally sterile body site) MRSA infections from 2005 through 2008 were evaluated and classified based on the setting of the positive culture and the presence or absence of health care exposures. Health care-associated infections (ie, hospital-onset and health care-associated community-onset), which made up 82% of the total infections, were included in this analysis. MAIN OUTCOME MEASURES Change in incidence of invasive health care-associated MRSA infections and health care-associated MRSA BSIs using population of the catchment area as the denominator. RESULTS From 2005 through 2008, there were 21,503 episodes of invasive MRSA infection; 17,508 were health care associated. Of these, 15,458 were MRSA BSIs. The incidence rate of hospital-onset invasive MRSA infections was 1.02 per 10,000 population in 2005 and decreased 9.4% per year (95% confidence interval [CI], 14.7% to 3.8%; P = .005), and the incidence of health care-associated community-onset infections was 2.20 per 10,000 population in 2005 and decreased 5.7% per year (95% CI, 9.7% to 1.6%; P = .01). The decrease was most prominent for the subset of infections with BSIs (hospital-onset: -11.2%; 95% CI -15.9% to -6.3%; health care-associated community-onset: -6.6%; 95% CI -9.5% to -3.7%). CONCLUSION Over the 4-year period from 2005 through 2008 in 9 diverse metropolitan areas, rates of invasive health care-associated MRSA infections decreased among patients with health care-associated infections that began in the community and also decreased among those with hospital-onset invasive disease.

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.

National burden of invasive methicillin-resistant Staphylococcus aureus infections, United States, 2011.

IMPORTANCE Estimating the US burden of methicillin-resistant Staphylococcus aureus (MRSA) infections is important for planning and tracking success of prevention strategies. OBJECTIVE To describe updated national estimates and characteristics of health care- and community-associated invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in 2011. DESIGN, SETTING, AND PARTICIPANTS Active laboratory-based case finding identified MRSA cultures in 9 US metropolitan areas from 2005 through 2011. Invasive infections (MRSA cultured from normally sterile body sites) were classified as health care-associated community-onset (HACO) infections (cultured ≤ 3 days after admission and/or prior year dialysis, hospitalization, surgery, long-term care residence, or central vascular catheter presence ≤ 2 days before culture); hospital-onset infections (cultured >3 days after admission); or community-associated infections if no other criteria were met. National estimates were adjusted using US census and US Renal Data System data. MAIN OUTCOMES AND MEASURES National estimates of invasive HACO, hospital-onset, and community-associated MRSA infections using US census and US Renal Data System data as the denominator. RESULTS An estimated 80,461 (95% CI, 69,515-93,914) invasive MRSA infections occurred nationally in 2011. Of these, 48,353 (95% CI, 40,195-58,642) were HACO infections; 14,156 (95% CI, 10,096-20,440) were hospital-onset infections; and 16,560 (95% CI, 12,806-21,811) were community-associated infections. Since 2005, adjusted national estimated incidence rates decreased among HACO infections by 27.7% and hospital-onset infections decreased by 54.2%; community-associated infections decreased by only 5.0%. Among recently hospitalized community-onset (nondialysis) infections, 64% occurred 3 months or less after discharge, and 32% of these were admitted from long-term care facilities. CONCLUSIONS AND RELEVANCE An estimated 30,800 fewer invasive MRSA infections occurred in the United States in 2011 compared with 2005; in 2011 fewer infections occurred among patients during hospitalization than among persons in the community without recent health care exposures. Effective strategies for preventing infections outside acute care settings will have the greatest impact on further reducing invasive MRSA infections nationally.

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.

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.

Characterization of Methicillin-Resistant Staphylococcus aureus Isolates Collected in 2005 and 2006 from Patients with Invasive Disease: a Population-Based Analysis

ABSTRACT This study characterizes 1,984 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2005 and 2006 from normally sterile sites in patients with invasive MRSA infection. These isolates represent a convenience sample of all invasive MRSA cases reported as part of the Active Bacterial Core surveillance system in eight states in the United States. The majority of isolates were from blood (83.8%), joints (4.1%), and bone (4.2%). Isolates were characterized by pulsed-field gel electrophoresis (PFGE); SCCmec typing; susceptibility to 15 antimicrobial agents; and PCR analysis of staphylococcal enterotoxin A (SEA) to SEH, toxic shock syndrome toxin 1, and Panton-Valentine leukocidin. Thirteen established PFGE types were recognized among these isolates, although USA100 and USA300 predominated, accounting for 53.2% and 31.4% of the isolates, respectively. As expected, isolates from hospital onset cases were predominantly USA100, whereas those from community-associated cases were predominantly USA300. USA100 isolates were diverse (Simpsons discriminatory index [DI] = 0.924); generally positive only for enterotoxin D (74.5%); and resistant to clindamycin (98.6%), erythromycin (99.0%), and levofloxacin (99.6%), in addition to β-lactam agents. USA300 isolates were less diverse (DI = 0.566), positive for Panton-Valentine leukocidin (96.3%), and resistant to erythromycin (94.1%) and, less commonly, levofloxacin (54.6%), in addition to β-lactam agents. This collection provides a reference collection of MRSA isolates associated with invasive disease, collected in 2005 and 2006 in the United States, for future comparison and ongoing studies.

Current Epidemiology and Trends in Invasive Haemophilus influenzae Disease—United States, 1989–2008

BACKGROUND With the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines, there has been a dramatic reduction of Hib disease in young children and the epidemiological trends of invasive H. influenzae have shifted. METHODS Data were collected from active surveillance for invasive H. influenzae disease conducted through Active Bacterial Core surveillance sites during 1989-2008. RESULTS During 1999-2008, the estimated mean annual incidence of H. influenzae infection was 1.62 cases per 100 000 population; 15.3% of cases were fatal. Incidence was higher among adults aged ≥65 years, compared with other age groups. The largest burden of disease among children aged <5 years was in infants aged <1 year; many of these cases occurred during the first month of life in preterm or low-birth weight infants. An estimated 10% of the total burden of disease among children aged <5 years occurred in American Indian and Alaska Native children. During 1989-2008, 7559 cases of H. influenzae disease were reported from Active Bacterial Core surveillance sites. Small increases in the incidence of serotypes a, e, and f were observed during 1989-2008. The largest of these increases was in serotype f and was primarily among adults aged ≥18 years. CONCLUSIONS Since the introduction of Hib conjugate vaccines, the incidence of invasive disease caused by H. influenzae in the United States has decreased dramatically; however, a considerable burden of non-Hib disease is still present in the oldest and youngest age groups. There is no evidence of substantial replacement disease with non-b serotypes in young children in the United States.

Trends in Invasive Methicillin-Resistant Staphylococcus aureus Infections

OBJECTIVE: To describe trends in the incidence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in children during 2005–2010. METHODS: We evaluated reports of invasive MRSA infections in pediatric patients identified from population-based surveillance during 2005–2010. Cases were defined as isolation of MRSA from a normally sterile site and classified on the basis of the setting of the positive culture and presence or absence of health care exposures. Estimated annual changes in incidence were determined by using regression models. National age- and race-specific incidences for 2010 were estimated by using US census data. RESULTS: A total of 876 pediatric cases were reported; 340 (39%) were among infants. Overall, 35% of cases were hospital-onset, 23% were health care–associated community-onset, and 42% were community-associated (CA). The incidence of invasive CA-MRSA infection per 100 000 children increased from 1.1 in 2005 to 1.7 in 2010 (modeled yearly increase: 10.2%; 95% confidence interval: 2.7%–18.2%). No significant trends were observed for health care–associated community-onset and hospital-onset cases. Nationally, estimated invasive MRSA incidence in 2010 was higher among infants aged <90 days compared with older infants and children (43.9 vs 2.0 per 100 000) and among black children compared with other races (6.7 vs 1.6 per 100 000). CONCLUSIONS: Invasive MRSA infection in children disproportionately affects young infants and black children. In contrast to reports of declining incidence among adults, there were no significant reductions in health care–associated MRSA infections in children. Concurrently, the incidence of CA-MRSA infections has increased, underscoring the need for defining optimal strategies to prevent MRSA infections among children with and without health care exposures.