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Pneumococcal disease is more frequent and more deadly in persons with certain comorbidities. We used 1999 and 2000 data from the Active Bacterial Core surveillance (ABCs) and the National Health Interview Survey (NHIS) to determine rates of invasive pneumococcal disease in healthy adults (> or =18 years old) and in adults with various high-risk conditions. The risks of invasive pneumococcal disease in persons with specific chronic illnesses was compared with that in healthy adults, controlling for age, race, and the other chronic illnesses. Overall incidence rates, in cases/100,000 persons, were 8.8 in healthy adults, 51.4 in adults with diabetes, 62.9 in adults with chronic lung disease, 93.7 in adults with chronic heart disease, and 100.4 in adults who abused alcohol. Among the high-risk groups evaluated, risk was highest in adults with solid cancer (300.4), HIV/AIDS (422.9), and hematological cancer (503.1). Incidence rates increased with advancing age in adults with chronic lung disease, diabetes, and solid cancer. Black adults had higher incidence rates than white adults, both in healthy adults and in adults with chronic illnesses. These data support recommendations to provide pneumococcal vaccine to persons in these at-risk groups and underscore the need for better prevention strategies for immunocompromised persons. Copyright © 2005 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Influenza causes considerable morbidity and mortality in the United States. Between 2010 and 2020, an estimated 9-41 million cases resulted in 140,000-710,000 hospitalizations and 12,000-52,000 deaths annually (1). As the United States enters the 2021-22 influenza season, the potential impact of influenza illnesses is of concern given that influenza season will again coincide with the ongoing COVID-19 pandemic, which could further strain overburdened health care systems. The Advisory Committee on Immunization Practices (ACIP) recommends routine annual influenza vaccination for the 2021-22 influenza season for all persons aged ≥6 months who have no contraindications (2). To assess the potential impact of the COVID-19 pandemic on influenza vaccination coverage, the percentage change between administration of at least 1 dose of influenza vaccine during September-December 2020 was compared with the average administered in the corresponding periods in 2018 and 2019. The data analyzed were reported from 11 U.S. jurisdictions with high-performing state immunization information systems.* Overall, influenza vaccine administration was 9.0% higher in 2020 compared with the average in 2018 and 2019, combined. However, in 2020, the number of influenza vaccine doses administered to children aged 6-23 months and children aged 2-4 years, was 13.9% and 11.9% lower, respectively than the average for each age group in 2018 and 2019. Strategic efforts are needed to ensure high influenza vaccination coverage among all age groups, especially children aged 6 months-4 years who are not yet eligible to receive a COVID-19 vaccine. Administration of influenza vaccine and a COVID-19 vaccine among eligible populations is especially important to reduce the potential strain that influenza and COVID-19 cases could place on health care systems already overburdened by COVID-19., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: The XALIA and XALIA-LEA prospective, noninterventional studies investigated the safety and effectiveness of rivaroxaban versus standard anticoagulation for venous thromboembolism (VTE) treatment in routine clinical practice across global regions., Objectives: This pooled analysis combined their data to determine the incidence of thromboembolic and bleeding events in both treatment groups and addressed specific bleeding patterns in a broad range of patients., Methods: Patients with objectively confirmed VTE and an indication for ≥3 months' anticoagulation treatment received rivaroxaban or standard anticoagulation (eg, initial treatment with heparin/fondaparinux, followed by a vitamin K antagonist [VKA]). Treatment choice, dose, management, and duration were at the physician's discretion. Primary outcomes (major bleeding, recurrent VTE, and all-cause mortality) were compared between the two treatment groups. Propensity score stratification, and matching were used to reduce bias due to confounding variables., Results: Overall, 7129 patients were enrolled from 36 countries; 6445 and 2714 patients were included in the propensity score-stratified and -matched analyses, respectively. Major bleeding and incidences of recurrent VTE were similar between treatment groups; all-cause mortality was lower with rivaroxaban than with standard anticoagulation. The incidences of genitourinary bleeding were higher with rivaroxaban than with standard anticoagulation therapy (46 and 23 events in the matched analysis, respectively). VKA management in real-world practice was suboptimal., Conclusion: XALIA and XALIA-LEA show similar safety and effectiveness profiles of rivaroxaban and standard anticoagulation for VTE treatment in routine practice in many parts of the world. The observations are consistent with results from the phase III EINSTEIN randomized controlled trials., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

In December 2020, two COVID-19 vaccines (Pfizer-BioNTech and Moderna) were authorized for emergency use in the United States for the prevention of coronavirus disease 2019 (COVID-19).* Because of limited initial vaccine supply, the Advisory Committee on Immunization Practices (ACIP) prioritized vaccination of health care personnel † and residents and staff members of long-term care facilities (LTCF) during the first phase of the U.S. COVID-19 vaccination program (1). Both vaccines require 2 doses to complete the series. Data on vaccines administered during December 14, 2020-January 14, 2021, and reported to CDC by January 26, 2021, were analyzed to describe demographic characteristics, including sex, age, and race/ethnicity, of persons who received ≥1 dose of COVID-19 vaccine (i.e., initiated vaccination). During this period, 12,928,749 persons in the United States in 64 jurisdictions and five federal entities § initiated COVID-19 vaccination. Data on sex were reported for 97.0%, age for 99.9%, and race/ethnicity for 51.9% of vaccine recipients. Among persons who received the first vaccine dose and had reported demographic data, 63.0% were women, 55.0% were aged ≥50 years, and 60.4% were non-Hispanic White (White). More complete reporting of race and ethnicity data at the provider and jurisdictional levels is critical to ensure rapid detection of and response to potential disparities in COVID-19 vaccination. As the U.S. COVID-19 vaccination program expands, public health officials should ensure that vaccine is administered efficiently and equitably within each successive vaccination priority category, especially among those at highest risk for infection and severe adverse health outcomes, many of whom are non-Hispanic Black (Black), non-Hispanic American Indian/Alaska Native (AI/AN), and Hispanic persons (2,3)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing serotypes that are important in low-income and middle-income countries. Vaccine effectiveness estimates are scarce in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the effectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection and in those not infected with HIV., Methods: Cases of invasive pneumococcal disease in children aged 5 years or younger were identified through national laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic regression, we calculated vaccine effectiveness as a percentage, with the equation 1 - [adjusted odds ratio for vaccination] × 100. We included data from an earlier investigation of PCV7 to assess vaccine effectiveness in children exposed to but not infected with HIV and in malnourished children not infected with HIV., Findings: Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study: 240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV, and 283 were controls with HIV infection. The effectiveness of two or more doses of PCV13 against PCV13-serotype invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with HIV and 91% (-35 to 100) among three case-control sets of children with HIV infection. PCV13 effectiveness among 26 case-control sets of children not infected with HIV was 52% (95% CI -12 to 79) against all-serotype invasive pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine effectiveness against PCV7-serotype invasive pneumococcal disease was 87% (95% CI 38 to 97) in children exposed to HIV but uninfected and 90% (53 to 98) in malnourished children not infected with HIV., Interpretation: Our results indicate that PCV13 in a 2 + 1 schedule is effective for preventing vaccine-type pneumococcal infections in young children not infected with HIV, including those who are malnourished or who have been exposed to HIV. Although the point estimate for PCV13 vaccine effectiveness in children infected with HIV was high, it did not reach significance, possibly because of the small sample size. These findings support recommendations for widespread use of pneumococcal conjugate vaccine in low-income and middle-income countries., Funding: Gavi, The Vaccine Alliance., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To compare sentinel and population-based surveillance of the effect of seven-valent pneumococcal conjugate vaccine (PCV7), introduced in 2000, on the hospitalization of children aged under 5 years with invasive pneumococcal disease (IPD) in the United States of America., Methods: Population surveillance data were used to identify children hospitalized between 1998 and 2006 with IPD caused by Streptococcus pneumoniae serotypes. The change from 1998 and 1999 (baseline) to 2006 in the number of hospitalized IPD cases recorded by sentinel surveillance systems involving single hospitals or groups of hospitals was compared with the change in the incidence of hospitalized IPD cases measured by population-based surveillance., Findings: The change in incidence in the eight surveillance areas varied from -37 to -82% for IPD caused by any serotype and from -96 to -100% for IPD caused by serotypes contained in PCV7. All individual sentinel hospitals with more than three cases annually at baseline reported a decrease in cases by 2006. In addition, over 95% of sentinel systems with an average of more than 30 cases annually at baseline recorded a change by 2006 in the number of cases caused by any serotype that fell within the 95% confidence interval for the change in the incidence of hospitalized cases in the corresponding population surveillance area. The change in cases caused by PCV7 serotypes was accurately measured by 93% and 100% of sentinel systems with ≤ 20 and > 20 cases annually at baseline, respectively., Conclusion: Sentinel surveillance can accurately measure the effect of PCV7 on the number of children hospitalized with IPD, provided sufficient cases are detected at baseline. Serotyping increases accuracy.

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.

Randomization of treatment assignment in experiments generates treatment groups with approximately balanced baseline covariates. However, in observational studies, where treatment assignment is not random, patients in the active treatment and control groups often differ on crucial covariates that are related to outcomes. These covariate imbalances can lead to biased treatment effect estimates. The propensity score is the probability that a patient with particular baseline characteristics is assigned to active treatment rather than control. Though propensity scores are unknown in observational studies, by matching or subclassifying patients on estimated propensity scores, we can design observational studies that parallel randomized experiments, with approximate balance on observed covariates. Observational study designs based on estimated propensity scores can generate approximately unbiased treatment effect estimates. Critically, propensity score designs should be created without access to outcomes, mirroring the separation of study design and outcome analysis in randomized experiments. This paper describes the potential outcomes framework for causal inference and best practices for designing observational studies with propensity scores. We discuss the use of propensity scores in two studies assessing the effectiveness and risks of antifibrinolytic drugs during cardiac surgery., (Published by Elsevier Espana.)

Background: The Region of the Americas eliminated measles in 2002 through high first-dose routine measles vaccine coverage and vaccination campaigns every 4-6 years; a second routine dose at school entry was added in some countries. The impact of this second routine dose on measles elimination was evaluated., Methods: Data on socioeconomic factors, demographic characteristics, vaccination coverage, and the estimated proportion of children (<15 years of age) susceptible to measles were compiled. Countries were grouped using propensity score methods, and Kaplan-Meier curves were used to compare time to measles elimination between countries with a 1-dose schedule and those with a 2-dose schedule., Results: One-dose (n = 14) and 2-dose (n = 7) countries did not differ with respect to median routine first-dose measles vaccine coverage, median coverage for 3 measles campaigns, or estimated percentage of susceptible children after routine first vaccination dose and campaigns. Compared with 1-dose countries, 2-dose countries had higher median gross national income per capita (P = .002), percentage of population living in urban areas (P = .04), and female literacy (P = .01), as well as lower infant mortality (P = .007); however, no differences in time to elimination were found., Conclusions: One-dose and 2-dose countries had similar times to measles elimination despite socioeconomic differences between their populations. A second routine dose might not have hastened measles elimination, because threshold immunity needed to eliminate measles was achieved with high first routine dose coverage and vaccination campaigns. Further research will be needed to determine the applicability of these findings to other regions.

Background: The 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., Methods: Cases 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., Results: We 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., Conclusions: Although 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.

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.

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.

Invasive pneumococcal disease (IPD) is 3-5 times more common among Navajo adults than in the general US population. The authors conducted a case-control study to identify risk factors for IPD among Navajo adults. Navajos aged > or =18 years with IPD were identified through prospective, population-based active laboratory surveillance (December 1999-February 2002). Controls matched to cases on age, gender, and neighborhood were selected. Risk factors were identified through structured interviews and medical record reviews. The authors conducted a matched analysis based on 118 cases and 353 controls. Risk factors included in the final multivariable analysis were chronic renal failure (odds ratio (OR) = 2.6, 95% confidence interval (CI): 0.9, 7.7), congestive heart failure (OR = 5.6, 95% CI: 2.2, 14.5), self-reported alcohol use or alcoholism (OR = 2.9, 95% CI: 1.5, 5.4), body mass index (weight (kg)/height (m)(2)) <5th (OR = 3.2, 95% CI: 1.0, 10.6) or >95th (OR = 2.8, 95% CI: 1.0, 8.0) percentile, and unemployment (OR = 2.6, 95% CI: 1.2, 5.5). The population attributable fractions were 10% for chronic renal failure, 18% for congestive heart failure, 30% for self-reported alcohol use or alcoholism, 6% for body mass index, and 20% for unemployment. Several modifiable risk factors for IPD in Navajos were identified. The high prevalence of renal failure, alcoholism, and unemployment among Navajo adults compared with the general US population may explain some of their increased risk of IPD.

Background: Pneumococcal conjugate vaccines (PCVs) prevent vaccine serotype (VT) invasive disease; nonvaccine serotype (NVT) disease increases modestly. The impact of PCV on nasopharyngeal (NP) colonization is essential to understanding disease effects., Methods: We conducted a community-randomized controlled trial with catch-up vaccination through age 2 years investigating the effect of 7-valent PCV (PnCRM7) on NP colonization among American Indian infants and their unvaccinated contacts. Infants receiving blinded vaccine at 2, 4, 6, and 12-15 months of age had NP cultures obtained at age 7, 12, and 18 months. Serotype-specific colonization was detected by immunoblot., Results: We enrolled 566 vaccinated and 286 unvaccinated children from 511 households and collected 5157 specimens, of which 3525 (68.4%) had pneumococcus. PnCRM7 vaccinees were less likely to be colonized with VT (odds ratio [OR], 0.40 [95% confidence interval {CI}, 0.23-0.67]) but were more likely to be colonized with NVT pneumococci (OR, 1.67 [95% CI, 1.02-2.78]). PnCRM7 vaccinees were less densely colonized with VT strains than control vaccinees (OR, 0.61 [95% CI, 0.38-0.99]). Day care-attending unvaccinated children in PnCRM7 communities were less likely to have VT colonization than those in control communities (OR, 0.27 [95% CI, 0.07-1.07])., Conclusions: PnCRM7 reduces the risk of VT acquisition and colonization density but increases the risk of NVT acquisition among vaccinees and their household contacts.

Unlabelled: BACKGROUND. To prevent Streptococcus pneumoniae infection among persons at highest risk for invasive pneumococcal disease (IPD), the pneumococcal polysaccharide vaccine (PPV) is currently recommended for persons >or=65 years old and persons 2-64 years old with certain underlying conditions. Policymakers have considered expanding recommendations for PPV to include persons who are 50-64 years old and additional populations at risk for IPD. Our objectives were to determine the proportion of IPD cases that might have been prevented if all persons with vaccine indications had been vaccinated and to evaluate new indications., Methods: From 2001 to 2003, we performed a case series study of IPD in adults at 6 sites of the Active Bacterial Core surveillance-Emerging Infections Program Network. A case of IPD was defined as isolation of pneumococcus from a normally sterile site from a resident of 1 of the surveillance areas., Results: Among 1878 case patients, 1558 (83%) had at least 1 current vaccine indication; of these, 968 case patients (62%) were unvaccinated. Adherence to existing vaccine recommendations would have prevented 21% of all cases. The proportions of all cases potentially prevented by each new indication were as follows: lowering the universal age of recommended vaccination to 50 years, 5.0%-7.0%; adding new risk-based indications to include current smoking, 1.5%-2.5%; former smoking, 0.4%-0.7%; black race, 1.0%-1.4%; and asthma, 0.3%-0.4%., Conclusions: Increasing vaccine coverage rates among persons with a current indication may prevent more cases than expanding existing indications. Of the potential new indications studied, the strategy that may prevent most cases is lowering the recommended age for universal vaccination to 50 years.

Background: Pneumococcal disease is most prevalent among young children and elderly adults. We explored whether similarities exist in the serotypes that cause disease in these 2 high-risk groups., Methods: With use of US population-based data from 1998-1999 (before the introduction of the 7-valent pneumococcal conjugate vaccine [PCV7] as routine immunization for infants) from the Centers for Disease Control and Prevention's Active Bacterial Core surveillance, we evaluated whether the rate of invasive pneumococcal disease caused by the pediatric serotypes (6B, 9V, 14, 19F, and 23F) increased among elderly persons. We adjusted for potential confounders in multivariable logistic regression., Results: We analyzed 2987 pneumococcal isolates recovered from adults. The risk of infection with pediatric serotypes increased from 32.5% in 35-49-year-old persons to 51.2% in > or = 85-year-old persons (P < .001). Compared with 35-49-year-old persons, the risk of infection with pediatric serotypes was significantly elevated among 65-74-year-old persons (relative risk [RR], 1.68; 95% confidence interval [CI], 1.29-2.20) and increased progressively among persons aged 75-84 years (RR, 1.82; 95% CI, 1.41-2.36) and > or = 85 years (RR, 2.29; 95% CI, 1.72-3.05), with adjustment for sex, race, geographic location, underlying illness, and penicillin resistance. The rate of penicillin resistance was also elevated in the elderly population but was not significant after adjustment for serotype and race., Conclusions: The increased proportion of severe pneumococcal disease caused by pediatric serotypes in the elderly population might indicate opportunities for prevention with use of PCV7.

Community-specific antimicrobial susceptibility data may help monitor trends among drug-resistant Streptococcus pneumoniae and guide empiric therapy. Because active, population-based surveillance for invasive pneumococcal disease is accurate but resource intensive, we compared the proportion of penicillin-nonsusceptible isolates obtained from existing antibiograms, a less expensive system, to that obtained from 1 year of active surveillance for Georgia, Tennessee, California, Minnesota, Oregon, Maryland, Connecticut, and New York. For all sites, proportions of penicillin-nonsusceptible isolates from antibiograms were within 10 percentage points (median 3.65) of those from invasive-only isolates obtained through active surveillance. Only 23% of antibiograms distinguished between isolates intermediate and resistant to penicillin; 63% and 57% included susceptibility results for erythromycin and extended-spectrum cephalosporins, respectively. Aggregating existing hospital antibiograms is a simple and relatively accurate way to estimate local prevalence of penicillin-nonsusceptible pneumococcus; however, antibiograms offer limited data on isolates with intermediate and high-level penicillin resistance and isolates resistant to other agents.

Invasive pneumococcal disease occurs 2-3-fold more often among Navajo adults than among adults in the general United States population. The objective of this observational study was to determine the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) among Navajo adults. Active surveillance identified cases of invasive pneumococcal disease during 1996-1997. Three control patients per case patient were matched according to underlying medical conditions, sex, age, and location of medical care. Effectiveness was calculated by regression analysis of case-control sets and by indirect cohort methodology. Diabetes and alcoholism occurred in 41% and 43% of 108 case patients, respectively; 62% of case patients and 64% of control patients were immunized. Overall vaccine effectiveness was 26% (95% confidence interval [CI], -29% to 58%); 15% (95% CI, -116% to 67%) for patients with diabetes and -5% (95% CI, -141% to 54%) for patients with alcoholism. Overall vaccine effectiveness, as determined by use of the indirect cohort methodology, was 35% (95% CI, -33% to 69%). PPV23 was not significantly effective among Navajo adults and may be inadequate to prevent serious pneumococcal disease in this population.

We collected data during postexposure antimicrobial prophylaxis campaigns and from a prophylaxis program evaluation 60 days after start of antimicrobial prophylaxis involving persons from six U.S. sites where Bacillus anthracis exposures occurred. Adverse events associated with antimicrobial prophylaxis to prevent anthrax were commonly reported, but hospitalizations and serious adverse events as defined by Food and Drug Administration criteria were rare. Overall adherence during 60 days of antimicrobial prophylaxis was poor (44%), ranging from 21% of persons exposed in the Morgan postal facility in New York City to 64% of persons exposed at the Brentwood postal facility in Washington, D.C. Adherence was highest among participants in an investigational new drug protocol to receive additional antibiotics with or without anthrax vaccine--a likely surrogate for anthrax risk perception. Adherence of <60 days was not consistently associated with adverse events.

Treatment of infections with drug-resistant strains of Streptococcus pneumoniae (pneumococcus) may fail; whether drug resistance is associated with an increase in the number of serious infections in the community is unknown. We evaluated the relationship between the proportion of antimicrobial-resistant S. pneumoniae isolates and the number of cases of invasive pneumococcal disease. Linear regression models included 1996 county-level data from 38 counties participating in the US Centers for Disease Control and Prevention's Active Bacterial Core Surveillance. Separate models evaluated hospitalized children aged <5 years, nonhospitalized children aged <5 years, adults aged 18-64 years, and adults aged >64 years. The proportion of isolates resistant to > or =3 drug classes was associated with invasive disease in both hospitalized (P=.06) and nonhospitalized (P=.001) children. The proportion of multidrug-resistant pneumococcal isolates did not predict invasive cases among adults. The increasing prevalence of multidrug-resistant pneumococci among children may be leading to an increase in invasive disease.

Severe invasive group A streptococcal (GAS) disease is believed to have reemerged during the past 10-20 years. We conducted active, laboratory, population-based surveillance in 5 US states (total population, 13,214,992). From 1 July 1995 through 31 December 1999, we identified 2002 episodes of invasive GAS (3.5 cases per 100,000 persons). Rates varied by age (higher among those <2 or >/=65 years old), surveillance area, and race (higher among black individuals) but did not increase during the study period. The 5 most common emm types (1, 28, 12, 3, and 11) accounted for 49.2% of isolates; newly characterized emm types accounted for 8.9% of isolates. Older age; presence of streptococcal toxic shock syndrome, meningitis, or pneumonia; and infection with emm1 or emm3 were all independent predictors of death. We estimate that 9600-9700 cases of invasive GAS disease occur in the United States each year, resulting in 1100-1300 deaths.

We used population-based data to evaluate how often groups of randomly selected clinical laboratories accurately estimated the prevalence of resistant pneumococci and captured trends in resistance over time. Surveillance for invasive pneumococcal disease was conducted in eight states from 1996 to 1998. Within each surveillance area, we evaluated the proportion of all groups of three, four, and five laboratories that estimated the prevalence of penicillin-nonsusceptible pneumococci (%PNSP) and the change in %PNSP over time. We assessed whether sentinel groups detected emerging fluoroquinolone resistance. Groups of five performed best. Sentinel groups accurately predicted %PNSP in five states; states where they performed poorly had high between-laboratory variation in %PNSP. Sentinel groups detected large changes in prevalence of nonsusceptibility over time but rarely detected emerging fluoroquinolone resistance. Characteristics of hospital-affiliated laboratories were not useful predictors of a laboratory's %PNSP. Sentinel surveillance for resistant pneumococci can detect important trends over time but rarely detects newly emerging resistance profiles.

We compared the MRL and the Labsystems Chlamydia pneumoniae microimmunofluorescence (MIF) immunoglobulin G (IgG) kits and the Labsystems enzyme immunoassay (EIA) kit in a blinded study of 83 serum samples in which we evaluated titers, cross-reactivity to other species, and reproducibility. There was no statistically significant difference between the MRL and the Labsystems MIF kits in the endpoint titers of IgG antibody to C. pneumoniae. The correlation between the results obtained with these two MIF kits was excellent (r = 0.95; P = 0.001). The cross-reactivity of the C. pneumoniae-positive sera with C. trachomatis- and C. psittaci-positive sera was assessed for each MIF kit. For C. pneumoniae-positive sera with titers of > or =32, the Labsystems MIF kit exhibited more cross-reactivity to C. psittaci than the MRL kit did. The values obtained with the Labsystems EIA kit represented single dilutions of serum specimens expressed as enzymeimmuno units on a continuous scale. The results obtained with the Labsystems EIA kit correlated moderately well with those obtained with each MIF kit when they were compared for their abilities to detect IgG antibodies to C. pneumoniae (for the MRL MIF kit, r = 0.79 [P = 0.001]; for the Labsystems MIF kit, r = 0.78 [P = 0.001]). The results obtained with the commercial MRL and Labsystems MIF kits and the Labsystems EIA kit tested were reproducible; and the kits were standardized, had quality control reagents, and are suitable for detection of C. pneumoniae antibodies in serum and for use in interlaboratory studies. Validation of the use of these kits for clinical diagnosis still needs further evaluation.

Outbreaks of Mycoplasma pneumoniae (MP) in closed communities can have a high attack rate and can last several months. Azithromycin chemoprophylaxis has not been evaluated as a means of limiting transmission. This randomized, double-blinded placebo-controlled trial of azithromycin was conducted among asymptomatic hospital employees during an MP outbreak. Oropharyngeal swabs were obtained for detection of MP by polymerase chain reaction, and questionnaires were administered to assess clinical illness. Of the 147 employees who were enrolled, 73 received azithromycin and 74 received placebo. Carriage was similar within and between groups at weeks 1 and 6 (9.6% vs. 6.7% and 10.3% vs. 13.2%, respectively). Four episodes of clinically significant respiratory illness occurred in the azithromycin group versus 16 episodes in the placebo group (protective efficacy, 75%; 95% confidence interval, 28%-91%). Use of azithromycin prophylaxis in asymptomatic persons during an MP outbreak in a closed setting may be of value in reducing clinical illness.

The National Immunization Survey (NIS) was designed to measure vaccination coverage estimates for the US, the 50 states, and selected urban areas for children ages 19-35 months. The NIS includes a random-digit-dialed telephone survey and a provider record check study. Data are weighted to account for the sample design and to reduce nonresponse and non-coverage biases in order to improve vaccination coverage estimates. Adjustments are made for biases resulting from nonresponse and nontelephone households, and estimation procedures are used to reduce measurement bias. The NIS coverage estimates represent all US children, not just children living in households with telephones. NIS estimates are highly comparable to vaccination estimates derived from the National Health Interview Survey. The NIS allows comparisons between states and urban areas over time and is used to evaluate current and new vaccination strategies.

Three methods for the recovery of Chlamydia pneumoniae from spiked nasopharyngeal and blood specimens, including extended culture and additional centrifugations, were compared. Additional centrifugations and a 7-day culture time resulted in a 500- to 5, 000-fold increase in the number of detectable inclusion-forming units.

The response to Edmonston-Zagreb vaccine (titer, 5.4 log10 pfu) was evaluated among children in a study of perinatal transmission of human immunodeficiency virus (HIV) in Kinshasa. Acute postvaccination adverse events were monitored for 49 HIV-infected and 376 non-HIV-infected infants, and measles antibody responses were assessed by ELISA for 34 HIV-infected and 255 non-HIV-infected infants. There was no increase in the incidence of common symptoms 7-10 days after vaccination. HIV-infected infants were more likely to have detectable prevaccination measles antibody, and seroconversion after vaccination was somewhat lower in HIV-infected (76.5%) than non-HIV-infected infants (85.5%). Seroconversion rates did not differ among children with or without rhinitis or fever at vaccination. High-titer Edmonston-Zagreb vaccine given at 6 months of age has the potential to provide earlier protection against measles; however, this vaccine is no longer recommended for routine use, and two doses of standard-titer vaccines remains the preferred option for measles vaccination of HIV-infected infants.

The licensure of whole-cell pertussis vaccine combined with diphtheria and tetanus toxoids as DTP in the 1940s--and its widespread use in infants and children--led to a dramatic decline in the incidence of reported pertussis. In the prevaccine era, the average annual incidence and mortality for reported pertussis were 150 cases and six deaths per 100,000 population, respectively. From 1989 to 1991, pertussis cases were reported by state and local health departments to CDC through two distinct national surveillance systems: the National Notifiable Diseases Surveillance System (NNDSS) and the Supplementary Pertussis Surveillance System (SPSS). During the period 1989-1991, 11,446 pertussis cases were reported to the NNDSS (4,157 in 1989; 4,570 in 1990; and 2,719 in 1991), for an unadjusted annual incidence of 1.7, 1.8, and 1.1 cases per 100,000 population in 1989, 1990, and 1991, respectively. For the period 1989-1991, case reports were received through the SPSS on 9,480 (83%) of the 11,446 patients reported to the NNDSS. Age-specific incidence and hospitalization rates were highest among children < 1 year of age and declined with increasing age. Long-term trends suggest an increase in the reported incidence of pertussis in the United States since 1976. The peak in reported pertussis cases in 1990 represents the highest annual incidence of pertussis since 1970. However, the incidence of pertussis declined 41% from 1990 through 1991. Whether the long-term increase in reported pertussis is a true increase in incidence is unclear; the observed increase may be a function of improved surveillance.(ABSTRACT TRUNCATED AT 250 WORDS)

From 1980 through 1989, 27,826 cases of pertussis were reported to the Centers for Disease Control, for an average annual crude incidence of 1.2 cases/100,000 population. The incidence of reported disease increased in all age groups during this period, but the increase was disproportionately large among adolescents and adults. Infants between 1 and 2 months of age were at highest risk for pertussis (average annual incidence, 62.8/100,000). Infants less than 2 months of age had the highest reported rates of pertussis-associated hospitalization (82%), pneumonia (25%), seizures (4%), encephalopathy (1%), and death (1%). Rates of complication were generally higher among unvaccinated children than among those who had received three or more doses of diphtheria-tetanus-pertussis vaccine; 64% of children 3 months to 4 years of age who had reported cases of pertussis had not been immunized appropriately for their age. Whereas control of pertussis in the United States may be further improved through increased levels of diphtheria-tetanus-pertussis vaccination among eligible infants and children, the use of acellular vaccines in adolescents and adults may also be needed to reduce the burden of pertussis in very young infants.

An outbreak of measles among a predominantly unvaccinated and susceptible Amish population in Lebanon County, Pennsylvania, offered the opportunity to test the hypothesis that secondary cases in households are more severe than primary cases because the former have more intense exposure and receive a greater virus inoculum. Of 130 measles cases reported between April and June 1988, 119 (92%) constituted a study of disease severity. Severity was assessed by determining frequency and duration of symptoms, length of any hospitalization, and number of days in bed. In a univariate analysis, fewer secondary cases had conjunctivitis (relative risk [RR], 0.67; 95% confidence interval [CI], 0.48-0.96) and headache (RR, 0.37; CI, 0.15-0.86), but more had earache (RR, 9.69; CI, 1.8-202.9) compared with primary cases. Secondary cases had a shorter mean duration of coryza (4.0 vs. 5.0 days, Student's t test, P = .08). However, a logistic regression model that matched by family and controlled for age and sex indicated that there were no significant differences in measles severity among primary and secondary cases in households.