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Background Influenza virus and SARS-CoV-2 are significant causes of respiratory illness in children. Methods Influenza- and COVID-19–associated hospitalizations among children Results Among children Conclusions In the setting of extensive mitigation measures during the COVID-19 pandemic, the annual COVID-19–associated hospitalization rate during 2020–2021 was higher among adolescents and similar or lower among children

Background Nontypeable Haemophilus influenzae (NTHi) is the most common cause of invasive H. influenzae disease in the United States (US). We evaluated the epidemiology of invasive NTHi disease in the US, including among pregnant women, infants, and people with human immunodeficiency virus (PWH). Methods We used data from population- and laboratory-based surveillance for invasive H. influenzae disease conducted in 10 sites to estimate national incidence of NTHi, and to describe epidemiology in women of childbearing age, infants aged ≤30 days (neonates), and PWH living in the surveillance catchment areas. H. influenzae isolates were sent to the Centers for Disease Control and Prevention for species confirmation, serotyping, and whole genome sequencing of select isolates. Results During 2008–⁠2019, average annual NTHi incidence in the US was 1.3/100 000 population overall, 5.8/100 000 among children aged Conclusions NTHi causes substantial invasive disease, especially among older adults, pregnant/postpartum women, and neonates. Enhanced surveillance and evaluation of targeted interventions to prevent perinatal NTHi infections may be warranted.

We examine airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential using a source-to-dose framework beginning with generation of virus-containing droplets and aerosols and ending with virus deposition in the respiratory tract of susceptible individuals. By addressing 4 critical questions, we identify both gaps in addressing 4 critical questions with answers having policy implications.

Background The 13-valent pneumococcal vaccine (PCV13) was introduced for US children in 2010 and for immunocompromised adults ≥19 years old in series with the 23-valent polysaccharide vaccine (PPSV23) in 2012. We evaluated PCV13 indirect effects on invasive pneumococcal disease (IPD) among adults with and without PCV13 indications. Methods Using Active Bacterial Core surveillance and the National Health Survey, using Active Bacterial Core surveillance and the National Health Interview Survey, we estimated and compared IPD incidence in 2013–2014 and 2007–2008, by age and serotype group (PCV13, PPSV23-unique, or nonvaccine types [NVTs]), among adults with and without PCV13 indications. Results IPD incidence declined among all adults. Among adults 19–64 years, PCV13-type IPD declined 57% (95% confidence interval [CI], −68% to −43%) in adults with immunocompromising conditions (indication for PCV13 use), 57% (95% CI, −62% to –52%) in immunocompetent adults with chronic medical conditions (CMCs, indications for PPSV23 use alone), and 74% (95% CI, −78% to −70%) in adults with neither vaccine indication. Among adults aged ≥65 years, PCV13-type IPD decreased 68% (95% CI, −76% to −60%) in those with immunocompromising conditions, 68% (95% CI, −72% to −63%) in those with CMCs, and 71% (95% CI, −77% to −64%) in healthy adults. PPSV23-unique types increased in adults 19‒64 years with CMCs, and NVTs did not change among adults with or without PCV13 indications. From 2013 to 2014, non-PCV13 serotypes accounted for 80% of IPD. Conclusions IPD incidence among US adults declined after PCV13 introduction in children. Similar reductions in PCV13-type IPD in those with and without PCV13 indications suggest that observed benefits are largely due to indirect effects from pediatric PCV13 use rather than direct use among adults.

BACKGROUND. Following Haemophilus influenzae serotype b (Hib) conjugate vaccine introduction in the 1980s, Hib disease in young children dramatically decreased, and epidemiology of invasive H. influenzae changed. METHODS. Active surveillance for invasive H. influenzae disease was conducted through Active Bacterial Core surveillance sites. Incidence rates were directly standardized to the age and race distribution of the US population. RESULTS. During 2009–2015, the estimated mean annual incidence of invasive H. influenzae disease was 1.70 cases per 100 000 population. Incidence was highest among adults aged ≥65 years (6.30) and children aged

BACKGROUND Antibiotic-nonsusceptible invasive pneumococcal disease (IPD) decreased substantially after the US introduction of the pediatric 7-valent pneumococcal conjugate vaccine (PCV7) in 2000. However, rates of antibiotic-nonsusceptible non-PCV7-type IPD increased during 2004-2009. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7. We assessed the impact of PCV13 on antibiotic-nonsusceptible IPD rates. METHODS We defined IPD as pneumococcal isolation from a normally sterile site in a resident from 10 US surveillance sites. Antibiotic-nonsusceptible isolates were those intermediate or resistant to ≥1 antibiotic classes according to 2012 Clinical and Laboratory Standards Institute breakpoints. We examined rates of antibiotic nonsusceptibility and estimated cases prevented between observed cases of antibiotic-nonsusceptible IPD and cases that would have occurred if PCV13 had not been introduced. RESULTS From 2009 to 2013, rates of antibiotic-nonsusceptible IPD caused by serotypes included in PCV13 but not in PCV7 decreased from 6.5 to 0.5 per 100 000 in children aged

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 PCV7type 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

During 2009–2010, we examined 217 patients hospitalized with laboratory-confirmed pandemic influenza in 9 Influenza Hospitalization Surveillance Network sites and 413 age- and community-matched controls and found that a single dose of monovalent nonadjuvanted influenza A(H1N1)pdm09 vaccine was 50% (95% confidence interval, 13%–71%) effective in preventing hospitalization associated with A(H1N1)pdm09 virus infection.

Background. Certain chronic diseases increase risk for invasive pneumococcal disease (IPD) and are indications for receipt of 23-valent pneumococcal polysaccharide vaccine (PPV23). Since the pediatric introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, incidence of IPD among adults has declined. The relative magnitude of these indirect effects among persons with and without PPV23 indications is unknown. Methods. We evaluated IPD incidence among adults with and without PPV23 indications using populationand laboratory-based data collected during 1998–2009 and estimates of the denominator populations with PPV23 indications from the National Health Interview Survey. We compared rates before and after PCV7 use by age, race, PPV23 indication, and serotype. Results. The proportion of adult IPD cases with PPV23 indications increased from 51% before to 61% after PCV7 introduction (P< .0001). PCV7-serotype IPD declined among all race, age, and PPV23 indication strata, ranging from 82% to 97%. Overall IPD rates declined in most strata, by up to 65%. However, incidence remained highest among adults with PPV23 indications compared with those without (34.9 vs 8.8 cases per 100 000 population, respectively). Apart from age ≥65 years, diabetes is now the most common indication for PPV23 (20% of all cases vs 10% of cases in 1998–1999). Conclusions. Although IPD rates have declined among adults, adults with underlying conditions remain at increased risk of IPD and comprise a larger proportion of adult IPD cases in 2009 compared with 2000. A continued increase in the prevalence of diabetes among US adults could lead to increased burden of pneumococcal disease.

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.Data were collected from active surveillance for invasive H. influenzae disease conducted through Active Bacterial Core surveillance sites during 1989-2008.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 aged5 years was in infants aged1 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 aged5 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.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.

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

Background. We explored the association between antituberculosis drug pharmacokinetics and treatment outcomes among patients with pulmonary tuberculosis in Botswana. Methods. Consenting outpatients with tuberculosis had blood samples collected 1, 2, and 6 h after simultaneous isoniazid, rifampin, ethambutol, and pyrazinamide ingestion. Maximum serum concentrations (Cmax) and areas under the serum concentration time curve were determined. Clinical status was monitored throughout treatment. Results. Of the 225 participants, 36 (16%) experienced poor treatment outcome (treatment failure or death); 155 (69%) were infected with human immunodeficiency virus (HIV). Compared with published standards, low isoniazid Cmax occurred in 84 patients (37%), low rifampin Cmax in 188 (84%), low ethambutol Cmax in 87 (39%), and low pyrazinamide Cmax in 11 (5%). Median rifampin and pyrazinamide levels differed significantly by HIV status and CD4 cell count category. Only pyrazinamide pharmacokinetics were significantly associated with treatment outcome; low pyrazinamide Cmax was associated with a higher risk of documented poor treatment outcome, compared with normal Cmax (50% vs. 16%; ). HIV-infected patients with a CD4 cell count !200 cells/mL P ! .01 had a higher risk of poor treatment outcome (27%) than did HIV-uninfected patients (11%) or HIV-infected patients with a CD4 cell count 200 cells/mL (12%; ). After adjustment for HIV infection and CD4 cell P p .01 count, patients with low pyrazinamide Cmax were 3 times more likely than patients with normal pyrazinamide Cmax to have poor outcomes (adjusted risk ratio, 3.38; 95% confidence interval, 1.84‐6.22). Conclusions. Lower than expected antituberculosis drug Cmax occurred frequently, and low pyrazinamide Cmax was associated with poor treatment outcome. Exploring the global prevalence and significance of these findings may suggest modifications in treatment regimens that could improve tuberculosis cure rates.

BACKGROUND: Beta-hemolytic streptococci of groups other than A and B (NABS) are increasingly recognized as causes of clinically significant disease, but precise information about this heterogeneous group is lacking. We report the incidence of NABS infection and describe the epidemiologic and clinical characteristics. METHODS: Active, population-based surveillance for invasive NABS was performed over a 2-year period in the 8-county metropolitan Atlanta, Georgia, area and the 3-county San Francisco Bay, California, area. Clinical records were reviewed, and available isolates were sent to the Centers for Disease Control and Prevention (Atlanta) for additional microbiologic characterization. Incidences were calculated using year-appropriate US Census Bureau data. RESULTS: A total of 489 cases of invasive NABS infection were identified (3.2 cases per 100,000 population). The median age of patients was 55 years; 64% of patients were males, and 87% had underlying diseases. The incidence was higher among black persons than white persons (4.0 vs. 2.5 cases per 100,000 population; P < .01) and increased with age among all races. Infections were community acquired in 416 cases (85%). Among the 450 patients (94%) with NABS infection who were hospitalized, 55 (12%) died. Of 266 isolates (54%) speciated at the Centers for Disease Control and Prevention, 212 (80%) were Streptococcus dysgalactiae subspecies equisimilis; 46 (17%) were members of the Streptococcus anginosus group. S. dysgalactiae subspecies equisimilis primarily presented as skin and soft-tissue infection in older patients, whereas individuals with invasive S. anginosus group infections were more likely to be younger patients with intra-abdominal infections. CONCLUSIONS: NABS comprise multiple distinct species that cause a significant number of community-acquired invasive infections. Clinical manifestations differ by species. Thus, speciation of invasive NABS may be warranted in clinical settings.

BACKGROUND: Invasive group A Streptococcus (GAS) infection causes significant morbidity and mortality in the United States. We report the current epidemiologic characteristics of invasive GAS infections and estimate the potential impact of a multivalent GAS vaccine. METHODS: From January 2000 through December 2004, we collected data from Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs), a population-based system operating at 10 US sites (2004 population, 29.7 million). We defined a case of invasive GAS disease as isolation of GAS from a normally sterile site or from a wound specimen obtained from a patient with necrotizing fasciitis or streptococcal toxic shock syndrome in a surveillance area resident. All available isolates were emm typed. We used US census data to calculate rates and to make age- and race-adjusted national projections. RESULTS: We identified 5400 cases of invasive GAS infection (3.5 cases per 100,000 persons), with 735 deaths (case-fatality rate, 13.7%). Case-fatality rates for streptococcal toxic shock syndrome and necrotizing fasciitis were 36% and 24%, respectively. Incidences were highest among elderly persons (9.4 cases per 100,000 persons), infants (5.3 cases per 100,000 persons), and black persons (4.7 cases per 100,000 persons) and were stable over time. We estimate that 8950-11,500 cases of invasive GAS infection occur in the United States annually, resulting in 1050-1850 deaths. The emm types in a proposed 26-valent vaccine accounted for 79% of all cases and deaths. Independent factors associated with death include increasing age; having streptococcal toxic shock syndrome, meningitis, necrotizing fasciitis, pneumonia, or bacteremia; and having emm types 1, 3, or 12. CONCLUSIONS: GAS remains an important cause of severe disease in the United States. The introduction of a vaccine could significantly reduce morbidity and mortality due to these infections.

MAJOR ARTICLE Case-Control Study of Shigellosis in San Francisco: The Role of Sexual Transmission and HIV Infection Toma´s J. Arago´n, 1,2 Duc J. Vugia, 3,4 Sue Shallow, 4 Michael C. Samuel, 4 Arthur Reingold, 2,4 Frederick J. Angulo, 5 and Williamson Z. Bradford 4 San Francisco Department of Public Health, City and County of San Francisco, San Francisco, 2 School of Public Health, University of California at Berkeley, Berkeley, 3 California Department of Health Services, Richmond, and 4 California Emerging Infections Program, Oakland, California; and 5 Centers for Disease Control and Prevention, Atlanta, Georgia (See the editorial commentary by Daskalakis and Blaser on pages 335–7) Background. Shigella species infect ∼450,000 persons annually in the United States. Person-to-person trans- mission of Shigella species, which have a low infectious dose, occurs frequently, particularly in areas with poor sanitation and hygiene. Sexual transmission of Shigella species among men who have sex with men (MSM) has been inferred from outbreaks of shigellosis among that population, and limited studies have suggested the im- portance of human immunodeficiency virus (HIV) infection as a risk factor for shigellosis. No population-based study of sporadic shigellosis has evaluated the role of sexual practices (especially among MSM) and HIV infection along with other established risk factors for shigellosis. Methods. We conducted a population-based case-control study of shigellosis in adults in San Francisco, Cal- ifornia, during the period 1998–1999. Cases of Shigella infection were identified through laboratory-based active surveillance conducted by the California Emerging Infections Program. Seventy-six case patients were matched by sex with 146 control subjects. Exposure data were collected on established risk factors, sexual practices, and HIV infection status. Bivariable and multivariable analyses were conducted. Population-attributable fractions were calculated. Results. From the multivariable analysis, for men, shigellosis was associated with MSM (odds ratio [OR], 8.24; 95% confidence interval [CI], 2.70–25.2), HIV infection (OR, 8.17; 95% CI, 2.71–24.6), direct oral-anal contact (OR, 7.50; 95% CI, 1.74–32.3), and foreign travel (OR, 20.0; 95% CI, 5.26–76.3), with population-attributable fractions of 0.72, 0.42, 0.31, and 0.18, respectively. For women, shigellosis was associated only with foreign travel (OR, 21.0; 95% CI, 2.52–899), with a population-attributable fraction of 0.37. Conclusions. Among MSM, shigellosis is predominantly a sexually transmitted disease, with direct oral-anal contact conferring the highest risk and HIV infection likely contributing to increased host susceptibility. Each year, an estimated 450,000 persons in the United States are infected with Shigella species, resulting in 6200 hospitalizations and 70 deaths [1]. Humans and other primates are the only natural reservoirs for Shi- gella species [2]. Shigella species are transmitted by the fecal-oral route, and most infections are transmitted from person to person, reflecting the low infectious dose [3]; as few as 10 viable organisms can result in clinical infection [4]. In areas in which infection is prev- Received 6 September 2006; accepted 27 September 2006; electronically published 29 December 2006. Reprints or correspondence: Dr. Toma´s J. Arago´n, School of Public Health, Div. of Epidemiology, University of California at Berkeley, 140 Warren Hall, MC-7360, Berkeley, CA 94720-7360 (aragon@berkeley.edu). Clinical Infectious Diseases 2007; 44:327–34 2006 by the Infectious Diseases Society of America. All rights reserved. alent, risk for Shigella infection increases with poor hand hygiene, ingestion of contaminated food or water, inadequate sanitation and toileting, overcrowding, and sexual contact [5–13]. Among reported culture-confirmed infections in the United States during the period 1989–2002, 72% were due to Shigella sonnei, 18% were due to Shigella flexneri, 1.6% were due to Shigella boydii, and 0.7% were due to Shigella dysenteriae [3]. Most reported cases occurred in children ! 10 years of age, followed by women 20– 39 years of age; the high rate of infection in the latter group was presumably related to caring for infected children. In the mid-1970s, shigellosis was recognized as a potentially sexually transmitted disease among men who have sex with men (MSM) [7, 14, 15]. In the late 1970s and early 1980s, the increased incidence of S. flexneri infection in men was attributed to the sexual Sexual Transmission of Shigellosis • CID 2007:44 (1 February) • 327

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 those2 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 conducted prospective, active population-based surveillance for candidemia (defined as any Candida species isolated from blood) in Atlanta and San Francisco (total population, 5.34 million) during 1992‐1993. The average annual incidence of candidemia at both sites was 8 per 100,000 population. The highest incidence (75 per 100,000) occurred among infants

Population-based active laboratory surveillance for invasive mycotic infections was conducted during 1992 and 1993 in three California counties: Alameda, Contra Costa, and San Francisco (population, 2.94 million). The cumulative incidence of invasive mycotic infections was 178.3 per million per year. Invasive mycoses were most commonly caused by Candida (72.8 per million per year), Cryptococcus (65.5), Coccidioides (15.3), Aspergillus (12.4), and Histoplasma (7.1). The clinical significance of other, less common fungi was determined by detailed chart review. The cumulative incidence was determined for zygomycosis (1.7 per million per year), hyalohyphomycosis (1.2), and phaeohyphomycosis (1.0). The most common underlying conditions were human immunodeficiency virus infection (47.4%), nonhematologic malignancy (14.7%), diabetes mellitus (9.9%), and chronic lung disease (9.3%). This represents the first population-based epidemiological assessment of invasive mycoses in the United States.

In cases of advanced infection with human immunodeficiency virus, mycobacterial blood cultures are frequently used to diagnose disseminated infection with the Mycobacterium avium complex (MAC). However, no prospectively validated guidelines exist for the use of such cultures. In this study, a two-part model for predicting MAC bacteremia was developed and then validated prospectively. First, a CD4+ cell count of < or = 50/microL was used to predict bacteremia. Then, among patients with < or = 50 CD4+ cells/microL, the documentation of fever on more than 30 days during the preceding 3 months, a hematocrit of < 30%, or a serum albumin concentration of < 3.0 g/dL was used to predict bacteremia. This model had a sensitivity of 89% and positive and negative predictive values of 30% and 98%, respectively, for the identification of patients with bacteremia. Had the model been applied to patients in this study, the number of blood cultures performed would have decreased by 61%, but 11% of the positive cultures would have been missed. In short, this model can predict MAC bacteremia and can potentially guide the use of mycobacterial blood cultures.