Characteristics of Intracranial Group A Streptococcal Infections in US Children, 1997-2014.

BACKGROUND: Few data on intracranial group A Streptococcus (GAS) infection in children are available. Here, we describe the demographic, clinical, and diagnostic characteristics of 91 children with intracranial GAS infection. METHODS: Cases of intracranial GAS infection in persons ≤18 years of age reported between 1997 and 2014 were identified by the Centers for Disease Control and Prevention's population- and laboratory-based Active Bacterial Core surveillance (ABCs) system. Medical charts were abstracted using a active, standardized case report form. All available isolates were emm typed. US census data were used to calculate rates. RESULTS: ABCs identified 2596 children with invasive GAS infection over an 18-year period; 91 (3.5%) had an intracranial infection. Intracranial infections were most frequent during the winter months and among children aged <1 year. The average annual incidence was 0.07 cases per 100000 children. For 83 patients for whom information for further classification was available, the principal clinical presentations included meningitis (35 [42%]), intracranial infection after otitis media, mastoiditis, or sinusitis (34 [41%]), and ventriculoperitoneal shunt infection (14 [17%]). Seven (8%) of these infections progressed to streptococcal toxic shock syndrome. The overall case fatality rate was 15%. GAS emm types 1 (31% of available isolates) and 12 (13% of available isolates) were most common. CONCLUSIONS: Pediatric intracranial (GAS) infections are uncommon but often severe. Risk factors for intracranial GAS infection include the presence of a ventriculoperitoneal shunt and contiguous infections in the middle ear or sinuses.

Using Hospital Inpatient Discharge Data to Supplement Active Surveillance for Invasive Pneumococcal Disease: Is the Extract Worth the Exertion?

OBJECTIVE: Invasive pneumococcal disease (IPD) surveillance systems monitor morbidity, mortality, and vaccine impact; accurate surveillance is important to detect changes in epidemiology. We evaluated completeness of IPD reporting in New Mexico by comparing data from the Hospital Inpatient Discharge Database (HIDD) and the New Mexico Active Bacterial Core Surveillance (ABCs) program. METHODS: We linked data from the HIDD and the ABCs program. We defined cases of IPD in the HIDD among New Mexico residents with hospitalizations during 2007-2009 as specific (320.1 or 038.2) or nonspecific (481, 320.2, or 041.2) using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. To validate if HIDD records that could not be matched to ABCs data were true IPD cases, we reviewed laboratory data and determined if Streptococcus pneumoniae (S. pneumoniae) had been isolated from a sterile body site. RESULTS: We examined 732 HIDD records for cases that were not matched in the ABCs database; of such records, S. pneumoniae was isolated from a sterile body site in 10 HIDD records. CONCLUSION: ABCs data detected the majority of IPD cases in New Mexico. Laboratory and medical record review is essential when using HIDD data because ICD-9-CM coding alone does not ensure data accuracy. The addition of IPD cases to the ABCs program from the HIDD was minimally beneficial to active surveillance and reporting completeness in New Mexico. States that rely exclusively on passive reporting and that have access to HIDD data might use linkages of pneumococcal and IPD-specific ICD-9-CM-coded HIDD data to improve IPD surveillance and case ascertainment.

Racial disparities in invasive Streptococcus pneumoniae infections, 1998-2009.

BACKGROUND: Before the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), invasive pneumococcal disease (IPD) rates among blacks were twice the rates in whites. We measured the effects of trends in PCV7-type and non-PCV7-type IPD rates on racial disparities in overall IPD and estimated the proportion of IPD caused by serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: We analyzed data from the Active Bacterial Core surveillance system, which performs active, laboratory- and population-based surveillance for IPD for 29.2 million people in the United States, for the period 1998-2009. For patients with unknown race, we multiplied imputed race to calculate age-, race-, and serotype-specific IPD incidence rates. RESULTS: During 1998-2009, 47 449 IPD cases were identified; race was unknown for 5419 (11%). After multiple imputation, 31 981 (67%) patients were considered white and 13 750 (29%) black. PCV7-type IPD rates in all ages in both races decreased to <1 case per 100 000, whereas there were no decreases in overall IPD rates after 2002. By 2009, PCV13 serotypes caused 71% of cases among whites aged <5 years compared with 58% among blacks (P < .01). PCV13 serotypes caused 50% of IPD cases in whites aged ≥5 years compared with 43% among blacks (P < .01). CONCLUSIONS: Despite near elimination of PCV7-type IPD in both races, overall disparities in IPD rates persisted because non-PCV7-type IPD rates are higher among blacks. Whereas PCV13 introduction may reduce racial disparities in IPD, higher valency conjugate vaccines and strategies to directly address underlying causes are needed to eliminate IPD disparities.

Invasive Haemophilus influenzae in the United States, 1999-2008: epidemiology and outcomes.

OBJECTIVES: Introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine has resulted in a dramatic reduction of Hib disease in the U.S. and an increase in the relative importance of infections caused by nontypeable strains. The current project describes the characteristics and clinical outcomes of pediatric and adult patients with invasive H. influenzae (HI) and, through multivariable analysis, identifies risk factors for in-hospital mortality. METHODS: HI cases were identified during 1999-2008 through active surveillance as part of active bacterial core surveillance (ABCs). Multivariable analysis was performed with logistic regression to identify factors predictive of in-hospital death. RESULTS: 4839 cases of HI were identified from 1999-2008. Children accounted for 17.1% of cases and adults 82.9%. Underlying conditions were present in 20.7% of children and 74.8% of adults. In-hospital mortality was highest in cases ≥65 years (21.9%) and <3 months (16.2%). The risk of in-hospital death in children <1 year was higher among those who were prematurely-born (<28 weeks, OR 7.1, 95% CI 3.2-15.6; 28-36 weeks OR 2.1, 95% CI 0.9-4.8) and, among children aged 1-17 years, higher in those with healthcare-associated onset and dialysis (OR 5.66, 95% CI 1.84-17.39; OR 18.11, 95% CI 2.77-118.65). In adults, age ≥40 was associated with death in nontypeable, but not encapsulated, infections. Infections with nontypeable strains increased the risk of death in cases ≥65 years (OR 1.81, 95% CI 1.31-2.52). Healthcare-associated HI, bacteremia without identifiable focus, bacteremic pneumonia, associated cirrhosis, cerebrovascular accident, dialysis, heart failure, and non-hematologic malignancy also increased the risk of death in adults. CONCLUSION: Prematurity in infants, advanced age and certain chronic diseases in adults were associated with an increased risk of in-hospital death. Nontypeable HI was associated with higher mortality in the elderly.

Shiga toxin-producing Escherichia coli, New Mexico, USA, 2004-2007.

Sporadic infection with Shiga toxin-producing Escherichia coli (STEC) in New Mexico increased from 0.9 cases per 100,000 population (95% confidence interval [CI] 0.5-1.36) in 2004 to 1.7 (95% CI 1.14-2.26) in 2007. Non-O157 STEC was more common in nonwhite residents, children <5 years of age, and urban residents.

Evaluation of universal antenatal screening for group B streptococcus.

BACKGROUND: Group B streptococcal disease is one of the most common infections in the first week after birth. In 2002, national guidelines recommended universal late antenatal screening of pregnant women for colonization with group B streptococcus to identify candidates for intrapartum chemoprophylaxis. METHODS: We evaluated the implementation of the guidelines in a multistate, retrospective cohort selected from the Active Bacterial Core surveillance, a 10-state, population-based system that monitors invasive group B streptococcal disease. We abstracted data from the labor and delivery records of a stratified random sample of live births and of all cases in which the newborn had early-onset group B streptococcal disease (i.e., disease in infants <7 days of age) in 2003 and 2004. We compared our results with those from a study with a similar design that evaluated screening practices in 1998 and 1999. RESULTS: We abstracted records of 254 births in which the infant had group B streptococcal disease and 7437 births in which the infant did not. The rate of screening for group B streptococcus before delivery increased from 48.1% in 1998-1999 to 85.0% in 2003-2004; the percentage of infants exposed to intrapartum antibiotics increased from 26.8% to 31.7%. Chemoprophylaxis was administered in 87.0% of the women who were positive for group B streptococcus and who delivered at term, but in only 63.4% of women with unknown colonization status who delivered preterm. The overall incidence of early-onset group B streptococcal disease was 0.32 cases per 1000 live births. Preterm infants had a higher incidence of early-onset group B streptococcal disease than did term infants (0.73 vs. 0.26 cases per 1000 live births); however, 74.4% of the cases of group B streptococcal disease (189 of 254) occurred in term infants. Missed screening among mothers who delivered at term accounted for 34 of the 254 cases of group B streptococcal disease (13.4%). A total of 61.4% of the term infants with group B streptococcal disease were born to women who had tested negative for group B streptococcus before delivery. CONCLUSIONS: Recommendations for universal screening were rapidly adopted. Improved management of preterm deliveries and improved collection, processing, and reporting of culture results may prevent additional cases of early-onset group B streptococcal disease.

The effect of HIV infection on overdose mortality.

OBJECTIVES: To quantify the association of HIV infection with overdose mortality and explore the potential mechanisms. DESIGN: A prospective cohort study. METHODS: A total of 1927 actively injecting drug users who were HIV seronegative at baseline, of whom 308 later HIV seroconverted, were followed semi-annually for death from 1988 to 2001. Survival analyses using marginal structural and standard Cox models were used to evaluate the effect of HIV infection on the risk of overdose mortality. RESULTS: Overdose death rates were higher in HIV-seropositive than HIV-seronegative drug users: 13.9 and 5.6 per 1000 person-years, respectively (P < 0.01). The hazard ratio (HR) was 2.54 [95% confidence interval (CI) 1.47, 4.38] for the marginal structural model and 2.06 (95% CI 1.25, 3.38) for the standard Cox model, both adjusted for demographics, drug injection characteristics, alcohol abuse, substance abuse treatment, and sexual orientation. Adjusting for possible time-varying mediators (i.e. drug use, medical conditions and healthcare access) in extended marginal structural models reduced the effect of HIV on overdose mortality by 30% (HR 1.82, 95% CI 1.01, 3.30). Abnormal liver function was associated with a higher risk of overdose mortality (HR 2.00, 95% CI 1.05, 3.84); adjustment for this further reduced the effect of HIV on overdose mortality. CONCLUSION: HIV infection was associated with a higher risk of overdose mortality. Drug use behavior, systematic disease and liver damage associated with HIV infection appeared to account for a substantial portion of this association. The data suggest a group to target with interventions to reduce overdose mortality rates.

Correlates of unsafe syringe acquisition and disposal among injection drug users in Baltimore, Maryland.

Because multi-person syringe use is the most common vehicle for HIV and hepatitis C virus transmission among injection drug users (IDUs), safe sources of sterile syringes and safe methods of disposal are necessary to curb these epidemics. We examined syringe acquisition and disposal in a cohort of IDUs in Baltimore. Between January 1, 1998 and December 31, 2001, 1034 participants reported on syringe acquisition at 3492 visits, and 953 reported on disposal at 2569 visits. Participants were 69.9% male, 93.9% African-American, and median age was 44. Syringes were acquired exclusively from unsafe sources at 32.3% of visits, while exclusively unsafe disposal was reported at 59.3% of visits. Significant correlates of unsafe acquisition were: attending shooting galleries, anonymous sex, sharing needles, smoking crack, and emergency room visits. Significant correlates of unsafe disposal were: injecting speedball, no methadone treatment, acquiring safely, and frequent injection. Having a primary source of medical care was associated with safe acquisition, but unsafe disposal. IDUs continue to acquire safely but dispose unsafely, especially among those with a primary source of care; this suggests that messages about safe disposal are not being disseminated as widely as those about acquisition. These data suggest the need for a more active program involving pharmacists, an expanded syringe access program, and better efforts to enhance safe disposal.

Prognostic factors for survival differ according to CD4+ cell count among HIV-infected injection drug users: pre-HAART and HAART eras.

To identify prognostic indicators of survival at different CD4 cell levels, independent of highly active antiretroviral therapy (HAART), among injection drug users (IDUs). A community-recruited cohort of injection drug users followed semiannually from 1988 through 2000. Five partially overlapping subcohorts were defined by when participants first reached a CD4 cell level of 351 to 500, 201 to 350, 101 to 200, 51 to 100, or

Mortality in HIV-seropositive versus -seronegative persons in the era of highly active antiretroviral therapy: implications for when to initiate therapy.

BACKGROUND: The optimal time to initiate highly active antiretroviral therapy (HAART) remains unclear. METHODS: Five hundred eighty-three human immunodeficiency virus (HIV)-seropositive and 920 HIV-seronegative injection drug users (IDUs) were followed from 1997 to 2000. HIV-seropositive participants were categorized according to receipt of HAART (either initiated or switched to HAART) and initial CD4 cell count. Survival analysis that included delayed-entry and Cox proportional-hazards models was used to evaluate the effect of HAART, with adjustments for factors associated with access to HAART. RESULTS: Compared with HIV-seronegative participants, overall survival was similar in HIV-seropositive participants who received HAART at >350 CD4 cells/microL, but mortality was higher both in participants with >350 CD4 cells/microL who did not receive HAART and in participants who received HAART at 200-350 CD4 cells/microL (mortality rates, 19.9, 24.0, 43.0, and 50.5/1000 person-years, respectively). In proportional-hazards models in which HIV-seronegative participants were the reference group and in which age, sex, race, frequency of drug use, substance-abuse treatment, and health-care utilization were adjusted for, hazard ratios were 1.01 (95% confidence interval [CI], 0.41-2.45), 2.28 (95% CI, 1.38-3.78), and 2.09 (95% CI, 1.07-4.10) for the latter 3 groups. In HIV-seropositive participants, HAART significantly improved survival when initiated at CD4 cell counts < 200 cells/microL. CONCLUSIONS: Survival of HIV-seropositive participants receiving HAART approximated that of HIV-seronegative participants only when therapy was given at CD4 cell counts > 350 cells/microL. These data, restricted to IDUs, suggest initiating or switching to HAART at higher CD4 cell levels than are currently recommended.

Mortality risk among new onset injection drug users.

AIMS: To characterize mortality experience among those who only recently started injection. DESIGN: Prospective study. SETTING: Independent study clinic within high drug use neighborhoods. PARTICIPANTS: In 1988-1989, we enrolled 256 adult injection drug users (IDUs) recruited through street outreach who had initiated injection within the prior 2 years. MEASUREMENTS: Consenting participants underwent venipuncture for HIV antibody testing and interviews. We prospectively ascertained date and cause of death through follow-up contact and registry linkages. Analyses included standardized mortality ratios (SMRs) with local, state and national mortality data, adjusted for age, gender and race. FINDINGS: Baseline median age was 30 years, 70% were male, 95% were African-American and 90% injected within the prior 6 months. We identified 69 deaths through October 2000; mortality rate was 3.3/100 person-years. The adjusted SMR with the USA (and Baltimore) as the reference for IDUs was 4.40 (2.43) for 1991-1992, which increased to 8.12 (4.13) by 1993-1994, decreased to 4.43 (2.13) by 1997-1998 and increased slightly to 5.35 (2.79) during 1999-2000. Excluding HIV-related mortality, SMRs remained elevated. Decline in SMRs was not linked to drug abuse treatment. CONCLUSIONS: These data demonstrate excess mortality among new-onset IDUs compared with demographically similar peers in the general population, indicating the need for interventions to prevent premature death among young IDUs.

HIV/AIDS risk behaviors and correlates of injection drug use among drug users in Pakistan.

We studied prevalence and correlates of injection drug use, awareness of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and risky behaviors among drug users serviced by a nongovernmental organization catering to drug users in three Pakistani cities (Quetta, Peshawar, and Rawalpindi). Logistic regression analysis was used to identify correlates of injection drug use. Of 608 drug users, 99.8% were male; median age was 32 years, and 44% were married. Most (79.8%) were Pakistani; 15.3% were Afghani. The majority used heroin (98.7%), mostly by inhalation; 15.2% injected drugs. Only 41% had heard of HIV/AIDS, and 30% had been paid for donating blood. Injection drug use and needle sharing were highest in Quetta. Injecting drug users (IDUs) were nearly twice as likely to have donated blood and to have heard about HIV/AIDS compared to other drug users. Interventions to discourage transitions to injection, increase HIV testing, and safeguard the blood supply in Pakistan are urgently needed.