James L. Hadler

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.

Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis.

BACKGROUND Group B streptococcal infections are a leading cause of neonatal mortality, and they also affect pregnant women and the elderly. Many cases of the disease in newborns can be prevented by the administration of prophylactic intrapartum antibiotics. In the 1990s, prevention efforts increased. In 1996, consensus guidelines recommended use of either a risk-based or a screening-based approach to identify candidates for intrapartum antibiotics. To assess the effects of the preventive efforts, we analyzed trends in the incidence of group B streptococcal disease from 1993 to 1998. METHODS Active, population-based surveillance was conducted in selected counties of eight states. A case was defined by the isolation of group B streptococci from a normally sterile site. Census and live-birth data were used to calculate the race-specific incidence of disease; national projections were adjusted for race. RESULTS Disease in infants less than seven days old accounted for 20 percent of all 7867 group B streptococcal infections. The incidence of early-onset neonatal infections decreased by 65 percent, from 1.7 per 1000 live births in 1993 to 0.6 per 1000 in 1998. The excess incidence of early-onset disease in black infants, as compared with white infants, decreased by 75 percent. Projecting our findings to the entire United States, we estimate that 3900 early-onset infections and 200 neonatal deaths were prevented in 1998 by the use of intrapartum antibiotics. Among pregnant girls and women, the incidence of invasive group B streptococcal disease declined by 21 percent. The incidence among nonpregnant adults did not decline. CONCLUSIONS Over a six-year period, there has been a substantial decline in the incidence of group B streptococcal disease in newborns, including a major reduction in the excess incidence of these infections in black infants. These improvements coincide with the efforts to prevent perinatal disease by the wider use of prophylactic intrapartum antibiotics.

Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings.

In October 2001, the first inhalational anthrax case in the United States since 1976 was identified in a media company worker in Florida. A national investigation was initiated to identify additional cases and determine possible exposures to Bacillus anthracis. Surveillance was enhanced through health-care facilities, laboratories, and other means to identify cases, which were defined as clinically compatible illness with laboratory-confirmed B. anthracis infection. From October 4 to November 20, 2001, 22 cases of anthrax (11 inhalational, 11 cutaneous) were identified; 5 of the inhalational cases were fatal. Twenty (91%) case-patients were either mail handlers or were exposed to worksites where contaminated mail was processed or received. B. anthracis isolates from four powder-containing envelopes, 17 specimens from patients, and 106 environmental samples were indistinguishable by molecular subtyping. Illness and death occurred not only at targeted worksites, but also along the path of mail and in other settings. Continued vigilance for cases is needed among health-care providers and members of the public health and law enforcement communities.

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.).

Asthma and Posttraumatic Stress Symptoms 5 to 6 Years Following Exposure to the World Trade Center Terrorist Attack

CONTEXT The World Trade Center Health Registry provides a unique opportunity to examine long-term health effects of a large-scale disaster. OBJECTIVE To examine risk factors for new asthma diagnoses and event-related posttraumatic stress (PTS) symptoms among exposed adults 5 to 6 years following exposure to the September 11, 2001, World Trade Center (WTC) terrorist attack. DESIGN, SETTING, AND PARTICIPANTS Longitudinal cohort study with wave 1 (W1) enrollment of 71,437 adults in 2003-2004, including rescue/recovery worker, lower Manhattan resident, lower Manhattan office worker, and passersby eligibility groups; 46,322 adults (68%) completed the wave 2 (W2) survey in 2006-2007. MAIN OUTCOME MEASURES Self-reported diagnosed asthma following September 11; event-related current PTS symptoms indicative of probable posttraumatic stress disorder (PTSD), assessed using the PTSD Checklist (cutoff score > or = 44). RESULTS Of W2 participants with no stated asthma history, 10.2% (95% confidence interval [CI], 9.9%-10.5%) reported new asthma diagnoses postevent. Intense dust cloud exposure on September 11 was a major contributor to new asthma diagnoses for all eligibility groups: for example, 19.1% vs 9.6% in those without exposure among rescue/recovery workers (adjusted odds ratio, 1.5 [95% CI, 1.4-1.7]). Asthma risk was highest among rescue/recovery workers on the WTC pile on September 11 (20.5% [95% CI, 19.0%-22.0%]). Persistent risks included working longer at the WTC site, not evacuating homes, and experiencing a heavy layer of dust in home or office. Of participants with no PTSD history, 23.8% (95% CI, 23.4%-24.2%) reported PTS symptoms at either W1 (14.3%) or W2 (19.1%). Nearly 10% (9.6% [95% CI, 9.3%-9.8%]) had PTS symptoms at both surveys, 4.7% (95% CI, 4.5%-4.9%) had PTS symptoms at W1 only, and 9.5% (95% CI, 9.3%-9.8%) had PTS symptoms at W2 only. At W2, passersby had the highest rate of PTS symptoms (23.2% [95% CI, 21.4%-25.0%]). Event-related loss of spouse or job was associated with PTS symptoms at W2. CONCLUSION Acute and prolonged exposures were both associated with a large burden of asthma and PTS symptoms 5 to 6 years after the September 11 WTC attack.

Changes in Invasive Pneumococcal Disease among HIV-Infected Adults Living in the Era of Childhood Pneumococcal Immunization

Context Routine pneumococcal conjugate vaccination for infants began in 2000. Its use markedly decreased invasive pneumococcal disease among children, but did it influence rates of disease among HIV-infected adults? Contribution Between 1998 and 2003, invasive pneumococcal disease among adults infected with HIV living in 7 surveillance areas in the United States decreased from 1127 to 919 cases per 100000 adults with AIDS. Disease caused by serotypes in the vaccine decreased 62%, whereas disease caused by nonvaccine serotypes increased 44%. Implications Indirect evidence suggests that pediatric vaccine use is associated with a decreased incidence of pneumococcal disease among HIV-infected adults. The Editors Apneumococcal conjugate vaccine containing 7 serotypes was recommended for routine use in infants in the United States beginning in 2000 (1). Widespread use of the vaccine caused steep declines in invasive pneumococcal disease among young children (2-4) and was associated with decreased disease attributable to vaccine serotypes among adults, for whom the vaccine is not licensed (3). Effects on disease among unvaccinated persons, often called herd effects, are presumably due to reduced transmission from immunized children. Because 90 pneumococcal serotypes cause human disease, there were concerns that the introduction of a conjugate vaccine containing 7 serotypes would lead to increased disease caused by nonvaccine-type organisms, a phenomenon called serotype replacement. Early postintroduction surveillance showed limited serotype replacement disease in the target age group, with no consistent trend toward increasing disease caused by nonvaccine serotypes among adults (3). To our knowledge, the effects of pediatric use of pneumococcal conjugate vaccine on immunocompromised adults, including those infected with HIV, have not previously been investigated. Persons infected with HIV are particularly susceptible to invasive pneumococcal disease, with a 50- to 100-fold higher incidence than the general U.S. population (5, 6). After the introduction of highly active antiretroviral therapy in the mid-1990s, surveillance in 3 geographic areas of the United States showed a 50% reduction in invasive pneumococcal disease among persons with AIDS (7). However, the incidence of pneumococcal disease among persons with AIDS leveled off by mid-1997 and continued to be approximately 35-fold higher in persons with AIDS than in those without HIV infection or AIDS through 2000 (7). We investigated trends in invasive pneumococcal disease among HIV-infected adults to document changes since the use of pneumococcal conjugate vaccine became widespread in children. Methods Active, laboratory-based surveillance for cases of invasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from a normally sterile site, was conducted through Active Bacterial Core surveillance of the Emerging Infections Program network (8). We included cases diagnosed between 1 January 1998 and 31 December 2003 among surveillance-area residents who were 18 to 64 years of age. We limited the analyses to 7 surveillance sites, including California (San Francisco County), Connecticut (entire state), Georgia (8-county Atlanta metropolitan area), Maryland (City of Baltimore and 5 neighboring counties), Minnesota (7-county MinneapolisSt. Paul metropolitan area), Oregon (3-county Portland metropolitan area), and Tennessee (Davidson, Hamilton, Knox, Shelby, and Williamson Counties). Information was systematically collected on the HIV status of case-patients at these sites. In 2003, the resident adult population in these 7 areas was 10.8 million (4.5% of the U.S. population between 18 and 64 years of age) (9) and included 9.5% of the estimated number of adults living with AIDS in the United States (10). Surveillance officers routinely contacted all clinical laboratories in their areas to identify cases and conducted audits of laboratory records to ensure complete ascertainment. Recurrent episodes, defined as invasive pneumococcal disease occurring more than 7 days after a previous case in a surveillance-area resident, were included in this analysis. The race and ethnicity as well as HIV status or previous AIDS diagnosis of case-patients were extracted from medical records by using standardized case report forms. Surveillance in Georgia did not prospectively collect information on HIV infection or AIDS for case-patients until 2000; for case-patients in 1999, we retrospectively reviewed medical records to collect this information. Analyses for 1998 exclude Georgia. Pneumococcal isolates were sent to reference laboratories at the Minnesota Department of Health (for case-patients from Minnesota), the Centers for Disease Control and Prevention, or the University of Texas Health Science Center at San Antonio for susceptibility testing by broth microdilution using standard protocols and quality control procedures (3, 11). Nonsusceptible isolates were defined as those with minimum inhibitory concentrations classified as intermediate or resistant for the antibiotic tested, according to the 2002 definitions of the National Committee for Clinical Laboratory Standards (12). Serotyping by the Quellung reaction was done at the Centers for Disease Control and Prevention or the Minnesota Department of Health (Minnesota cases only). The study personnel are listed in the Appendix. AIDS Surveillance Data For aggregated counties in each of the 7 surveillance areas, we obtained the estimated number of persons 18 to 64 years of age living with AIDS (as outlined in the 1993 Centers for Disease Control and Prevention case definition) (13), according to race and ethnicity and sex, on 30 June of each year. We obtained this number from the Centers for Disease Control and Prevention with permission from state AIDS surveillance coordinators. These estimates are derived from case report data by using a maximum likelihood method to account for delays in reporting new AIDS diagnoses and deaths among persons with AIDS (10), 14. Estimates of the number of persons living with HIV infection, not AIDS, were unavailable from 5 sites (California, Connecticut, Georgia, Maryland, and Oregon) that accounted for more than 80% of adults living with AIDS in the surveillance areas. Statistical Analysis For each surveillance area, we calculated the annual incidence rates of invasive pneumococcal disease among persons with AIDS as follows. We divided the number of cases of pneumococcal disease diagnosed during the calendar year among patients documented as having AIDS by the estimated number of persons 18 to 64 years of age living with AIDS. To calculate incidence among adults not infected with HIV, we used cases of pneumococcal disease in persons without documented HIV infection or AIDS in the numerator. For the denominator, we subtracted the number of adults living with AIDS from the total population of persons 18 to 64 years of age who lived in the surveillance areas; this number was obtained from the U.S. Census Bureau (9). As a proxy for the incidence rates among HIV-infected adults, we calculated a ratio of cases of pneumococcal disease among adults with HIV infection or AIDS to the estimated adult population living with AIDS, multiplied by 100000. Ratios for specific race and ethnicity categories were adjusted, assuming that the distribution of race and ethnicity for case-patients missing these data (3% of cases of pneumococcal disease) was the same as the sex-specific distribution of case-patients within each surveillance area for which race and ethnicity data were available. We adjusted data for selected serotypes (that is, conjugate vaccine or nonvaccine serotypes) or antibiotic-resistant pneumococci on the basis of the percentage of cases with isolates available for testing, assuming the distribution of cases missing serotype (9%) or antibiotic susceptibility data (7%) was the same as that of cases with isolates tested across all sites. We calculated 95% CIs for these ratios by using the standard error of the proportion of cases with isolates tested. To assess changes in the ratio of the number of cases of pneumococcal disease among HIV-infected adults to the number of adults living with AIDS before and after the introduction of the pneumococcal conjugate vaccine for children, we calculated percentage change and exact 95% CIs by comparing the average ratio during 1998 and 1999, called the baseline period, with that during 2002 or 2003. For differences or linear trends in proportions of cases or pneumococcal isolates, we calculated P values using chi-square tests; P values less than 0.05 indicated statistical significance. Statistical analyses were conducted with SAS, version 9.0 for Windows (SAS Institute, Inc., Cary, North Carolina), and EpiInfo, version 6.0 (Centers for Disease Control and Prevention, Atlanta, Georgia). Role of the Funding Source The funding source had no role in the design, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Results From 1998 through 2003, 8582 cases of invasive pneumococcal disease occurred in surveillance-area residents who were 18 to 64 years of age. Of these, 2013 cases occurred in persons with HIV infection or AIDS (Figure 1). When the latter group was excluded, the annual incidence rate in persons who were 18 to 64 years of age during the 1998 to 1999 baseline period averaged 13 cases per 100000 adults without AIDS. By 2003, this rate decreased to 9 cases per 100000, a decrease of 30% (95% CI, 25% to 35%; P< 0.001). Of the 2013 cases of pneumococcal disease among HIV-infected adults, 759 (38%) occurred among adults documented as having AIDS. Based on estimates of the number of adults living with AIDS in the surveillance areas, the incidence of invasive pneumococcal disease among persons with AIDS during the baseline period was 441 cases per 100000 adults. In 2002, the rate was 360 cases per 10000

Declining Incidence of Invasive Streptococcus pneumoniae Infections among Persons with AIDS in an Era of Highly Active Antiretroviral Therapy, 1995—2000

BACKGROUND Our goal was to describe trends in invasive pneumococcal disease incidence among persons with acquired immunodeficiency syndrome (AIDS) since the introduction of highly active antiretroviral therapy (HAART). METHODS We used time-trend analysis of annual invasive pneumococcal disease incidence rates from a population-based, active surveillance system. Annual incidence rates were calculated for 5 July-June periods by use of data from San Francisco county, the 6-county Baltimore metropolitan area, and Connecticut. The numerators were the numbers of invasive Streptococcus pneumoniae infections among persons 18-64 years of age with AIDS; the denominators were the numbers of persons living with AIDS, estimated on the basis of AIDS surveillance data. RESULTS The annual incidence of invasive pneumococcal disease declined from 1094 cases/100,000 persons with AIDS (July 1995-June 1996) to 467 cases/100,000 persons living with AIDS (July 1999-June 2000). The annual percentage changes in incidence were -34%, -29%, -8%, and -1%. Declines were similar by surveillance area, sex, and race/ethnicity. During the final year of the study, the invasive pneumococcal disease incidence in persons with AIDS was half that of the pre-HAART era but was still 35 times higher than that in similarly aged non-HIV-infected adults. CONCLUSIONS In the United States, invasive pneumococcal disease incidence declined sharply across a range of subgroups living with AIDS during the period after widespread introduction of HAART. Despite these gains, persons with AIDS remain at high risk for invasive pneumococcal disease.

Consumer Attitudes and Use of Antibiotics

Recent antibiotic use is a risk factor for infection or colonization with resistant bacterial pathogens. Demand for antibiotics can be affected by consumers’ knowledge, attitudes, and practices. In 1998–1999, the Foodborne Diseases Active Surveillance Network (FoodNet) conducted a population-based, random-digit dialing telephone survey, including questions regarding respondents’ knowledge, attitudes, and practices of antibiotic use. Twelve percent had recently taken antibiotics; 27% believed that taking antibiotics when they had a cold made them better more quickly, 32% believed that taking antibiotics when they had a cold prevented more serious illness, and 48% expected a prescription for antibiotics when they were ill enough from a cold to seek medical attention. These misguided beliefs and expectations were associated with a lack of awareness of the dangers of antibiotic use; 58% of patients were not aware of the possible health dangers. National educational efforts are needed to address these issues if patient demand for antibiotics is to be reduced.

Burden of Self-Reported Acute Diarrheal Illness in FoodNet Surveillance Areas, 1998–1999

To assess trends in the burden of acute diarrheal illness, the Foodborne Diseases Active Surveillance Network (FoodNet) conducted a population-based telephone survey during 1998-1999, using a random-digit-dialing, single-stage Genesys-ID sampling method. During the 12-month study period, 12,755 persons were interviewed; after the exclusion of persons with chronic diarrheal illnesses, 12,075 persons were included in the analysis; 6% (n=645) reported having experienced an acute diarrheal illness at some point during the 4 weeks preceding the interview (annualized rate, 0.72 episodes per person-year). Rates of diarrheal illness were highest among children aged <5 years (1.1 episodes per person-year) and were lowest in persons aged > or =65 years (0.32 episodes per person-year). Twenty-one percent of persons with acute diarrheal illness sought medical care as a result of their illness. Diarrheal illness imposes a considerable burden on the US population and health care system.

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.