Stephanie J. Schrag

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

BACKGROUNDnGroup 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.nnnMETHODSnActive 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.nnnRESULTSnA 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.nnnCONCLUSIONSnInvasive 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.

Application of TaqMan® Low Density Arrays for Simultaneous Detection of Multiple Respiratory Pathogens

ABSTRACT The large and growing number of viral and bacterial pathogens responsible for respiratory infections poses a challenge for laboratories seeking to provide rapid and comprehensive pathogen identification. We evaluated a novel application of the TaqMan low-density array (TLDA) cards for real-time PCR detection of 21 respiratory-pathogen targets. The performance of the TLDA was compared to that of individual real-time PCR (IRTP) assays with the same primers and probes using (i) nucleic acids extracted from the 21 pathogen strains and 66 closely related viruses and bacteria and (ii) 292 clinical respiratory specimens. With spiked samples, TLDA cards were about 10-fold less sensitive than IRTP assays. By using 292 clinical specimens to generate 2,238 paired individual assays, the TLDA card exhibited 89% sensitivity (95% confidence interval [CI], 86 to 92%; range per target, 47 to 100%) and 98% specificity (95% CI, 97 to 99%; range per target, 85 to 100%) overall compared to IRTP assays as the gold standard with a threshold cycle (CT ) cutoff of 43. The TLDA card approach offers promise for rapid and simultaneous identification of multiple respiratory pathogens for outbreak investigations and disease surveillance.

Household Transmission of 2009 Influenza A (H1N1) Virus after a School-Based Outbreak in New York City, April–May 2009

In April 2009, an outbreak due to infection with the 2009 pandemic influenza A (H1N1) virus (pH1N1) was investigated in a New York City high school. We surveyed household contacts of ill students to characterize the extent of transmission within households, identify contact groups at highest risk for illness, and assess the potential for preventing household transmission. Influenza-like illness (ILI) was reported by 79 of 702 household contacts (11.3% attack rate). Multivariate analysis showed that older age was protective: for each increasing year of age, the risk of ILI was reduced 5%. Additional protective factors included antiviral prophylaxis and having had a household discussion about influenza. Providing care for the index case patient and watching television with the index case patient were risk factors among parents and siblings, respectively. Fifty percent of cases occurred within 3 days of onset of illness in the student. These factors have implications for mitigating the impact of pH1N1 transmission.

Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: Experience in the United States and implications for a potential group B streptococcal vaccine

Group B Streptococcus (GBS) emerged as the leading cause of newborn infection in the United States in the 1970s. In the 1980s clinical trials demonstrated that giving intrapartum intravenous ampicillin or penicillin to mothers at risk was highly effective at preventing invasive GBS disease in the first week of life (early-onset). In 1996, the first national guidelines for the prevention of perinatal GBS disease were issued; these recommended either antenatal screening for GBS colonization and intrapartum antimicrobial prophylaxis (IAP) to colonized women, or targeting IAP to women with certain obstetric risk factors during labor. In 2002, revised guidelines recommended universal antenatal GBS screening. A multistate population-based review of labor and delivery records in 2003-2004 found 85% of women had documented antenatal GBS screening; 98% of screened women had a colonization result available at labor. However, missed opportunities for prevention were identified among women delivering preterm and among those with penicillin allergy, and more false negative GBS screening results were observed than expected. The incidence of invasive early-onset GBS disease decreased by more than 80% from 1.8 cases/1000 live births in the early 1990s to 0.26 cases/1000 live births in 2010; from 1994 to 2010 we estimate that over 70,000 cases of EOGBS invasive disease were prevented in the United States. IAP effectiveness is similar and high among term (91%) and preterm (86%) infants when first line therapy is received for at least 4h. However, early-onset disease incidence among preterm infants remains twice that of term infants; moreover disease among infants after the first week of life (late-onset disease) has not been impacted by IAP. The US experience demonstrates that universal screening and IAP for GBS-colonized women comprise a highly effective strategy against early-onset GBS infections. Maximizing adherence to recommended practices holds promise to further reduce the burden of early-onset GBS disease. Yet there are also inherent limitations to universal screening and IAP. Some of these could potentially be addressed by an efficacious maternal GBS vaccine.

Group B streptococcal disease in infants: Progress in prevention and continued challenges

The burden of early-onset disease caused by group B Streptococcus (GBS) has decreased dramatically in the United States over the past 20 years. Universal culture-based screening at 35 to 37 weeks gestational age and use of intrapartum antibiotic prophylaxis are the cornerstones of prevention measures that have led to this decline. GBS, however, remains the leading cause of early-onset neonatal sepsis in the United States. Revised guidelines for prevention of perinatal GBS are planned for issuance in 2010. This article discusses implementation challenges for clinicians caring for pregnant women and newborns and presents an updated algorithm for neonatal management.

Emergence of Endemic Serogroup W135 Meningococcal Disease Associated with a High Mortality Rate in South Africa

BACKGROUNDnIn the African meningitis belt, Neisseria meningitidis serogroup W135 has emerged as a cause of epidemic disease. The establishment of W135 as the predominant cause of endemic disease has not been described.nnnMETHODSnWe conducted national laboratory-based surveillance for invasive meningococcal disease during 2000-2005. The system was enhanced in 2003 to include clinical data collection of cases from sentinel sites. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing.nnnRESULTSnA total of 2135 cases of invasive meningococcal disease were reported, of which 1113 (52%) occurred in Gauteng Province, South Africa. In this province, rates of disease increased from 0.8 cases per 100,000 persons in 2000 to 4.0 cases per 100,000 persons in 2005; the percentage due to serogroup W135 increased from 7% (4 of 54 cases) to 75% (221 of 295 cases). The median age of patients infected with serogroup W135 was 5 years (interquartile range, 2-23 years), compared with 21 years (range, 8-26 years) for those infected with serogroup A (P<.001). The incidence of W135 disease increased in all age groups. Rates were highest among infants (age, <1 year), increasing from 5.1 cases per 100,000 persons in 2003 to 21.5 cases per 100,000 persons in 2005. Overall case-fatality rates doubled, from 11% in 2003 to 22% in 2005. Serogroup W135 was more likely to cause meningococcemia than was serogroup A (82 [28%] of 297 cases vs. 11 [8%] of 141 cases; odds ratio, 8.9, 95% confidence interval, 2.2-36.3). A total of 285 (95%) of 301 serogroup W135 isolates were identified as 1 clone by pulsed-field gel electrophoresis; 7 representative strains belonged to the ST-11/ET-37 complex.nnnCONCLUSIONSnSerogroup W135 has become endemic in Gauteng, South Africa, causing disease of greater severity than did the previous predominant serogroup A strain.

Incidence and Severity of Invasive Streptococcus pneumoniae, Group A Streptococcus, and Group B Streptococcus Infections Among Pregnant and Postpartum Women

BACKGROUNDnThe epidemiology of streptococcal infection in pregnant and postpartum women is poorly described in recent literature. We used data from multistate surveillance for invasive Streptococcus pneumoniae, group A Streptococcus (GAS), and group B Streptococcus (GBS) infections to estimate disease incidence and severity in these populations.nnnMETHODSnCases were reported through the Centers for Disease Control and Prevention Active Bacterial Core surveillance, an active population- and laboratory-based system. A case was defined as illness in a woman aged 15-44 years with streptococcus isolated from a normally sterile body site during 2007-2009. Pregnant or postpartum status was recorded at the time of culture. Incidence was calculated as cases per 1000 woman-years with use of national Census data; 95% confidence intervals were calculated on the basis of λ distribution. We used multivariable logistic regression to explore associations between pregnant or postpartum status and hospital length of stay, a marker of disease severity.nnnRESULTSnWe identified 1848 cases in women; 6.0% of women were pregnant, and 7.5% were postpartum. Pregnant women had a higher mean incidence of GBS disease, compared with nonpregnant women (0.04 cases per 1000 woman-years [range, 0.03-0.05 cases per 1000 woman-years] vs 0.02 cases per 1000 woman-years [range, 0.02-0.02 cases per 1000 woman-years]). Postpartum women had elevated mean incidence of all 3 pathogens, compared with nonpregnant women (S. pneumoniae: 0.15 cases per 1000 woman-years [range, 0.09-0.25 cases per 1000 woman-years] vs 0.052 cases per 1000 woman-years [range, 0.049-0.056 cases per 1000 woman-years]; GAS: 0.56 cases per 1000 woman-years [range, 0.42-0.70 cases per 1000 woman-years] vs 0.019 cases per 1000 woman-years [range, 0.017-0.021 cases per 1000 woman-years]; GBS: 0.49 cases per 1000 woman-years [range, 0.36-0.64 cases per 1000 woman-years] vs 0.018 [range, 0.016-0.020 cases per 1000 woman-years]). Neither pregnancy nor postpartum status was associated with longer length of stay among women infected with any of the 3 pathogens.nnnCONCLUSIONSnAlthough invasive streptococcal infections do not appear to be more severe in pregnant or postpartum women, postpartum women have a 20-fold increased incidence of GAS and GBS, compared with nonpregnant women.

Emergence of levofloxacin-non-susceptible Streptococcus pneumoniae and treatment for multidrug-resistant tuberculosis in children in South Africa: a cohort observational surveillance study

BACKGROUNDnUse of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa.nnnMETHODSn21,521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003. We screened 19,404 isolates (90% of cases) for ofloxacin resistance and measured levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected.nnnFINDINGSn12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, all in children aged under 15 years. All isolates were rifampicin resistant. Outcome was known for 11 of these patients; five (45%) died. Invasive disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35.78, 95% CI 4.49-285.30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88.96, 19.10-414.29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin.nnnINTERPRETATIONnOur data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae and its nosocomial spread.

Cost-effectiveness of a potential group B streptococcal vaccine program for pregnant women in South Africa

BACKGROUNDnIn low- and middle-income countries neonatal infections are important causes of infant mortality. Group B streptococcus (GBS) is a major pathogen. A GBS polysaccharide-protein conjugate vaccine, the only option that has the potential to prevent both early- and late-onset GBS disease, has completed Phase II trials. Screening-based intrapartum antibiotic prophylaxis (IAP) for pregnant women, an effective strategy in high-income countries, is often not practical in these settings. Risk factor-based IAP (RFB-IAP) for women with risk factors at delivery has had limited success in preventing neonatal infection. We evaluated the cost and health impacts of maternal GBS vaccination in South Africa.nnnMETHODS AND FINDINGSnWe developed a decision-analytic model for an annual cohort of pregnant women that simulates the natural history of GBS disease in their infants. We compared four strategies: doing nothing, maternal GBS vaccination, RFB-IAP, and vaccination plus RFB-IAP. Assuming vaccine efficacy varies from 50% to 90% against covered serotypes and 75% of pregnant women are vaccinated, GBS vaccination alone prevents 30-54% of infant GBS cases compared to doing nothing. For vaccine prices between

Estimates of the Burden of Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children

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