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Group B streptococcus (GBS) is an increasing cause of disease in adults. We present long-term trends in incidence of overall infections and identify characteristics of patients with GBS cellulitis, bone and joint infections. Active, population-based surveillance was conducted from 1995-2012 in three California counties and the data were analysed retrospectively. All cases had isolation of GBS from a normally sterile site. Cases of cellulitis were classified based on clinical diagnosis. GBS bone or joint infection was defined as isolation of GBS from a bone or joint or a diagnosis of osteomyelitis or septic arthritis. Medical charts were reviewed for demographic and clinical information. There were 3917 cases of GBS; the incidence of disease increased from 5·8 to 8·3 cases/100 000 persons (P < 0·001) from 1995 to 2012. In adults aged ⩾40 years, the overall incidence of GBS increased from 8·5 to 14·2 cases/100 000 (P < 0·001) persons during the study period. The incidence of cellulitis increased from 1·6 to 3·8 cases/100 000 (P < 0·001), bone infection increased from 0·7 to 2·6 cases/100 000 (P < 0·001), and the incidence of joint infection remained approximately constant at an average rate of 1·0 case/100 000. The highest incidence rates were observed in men, persons aged ⩾80 years, non-Hispanic blacks and Hispanics. Diabetes was the most common underlying condition (51·2% cellulitis cases, 76·3% bone infections, 29·8% joint infections).

To understand the epidemiology of tuberculosis (TB) and HIV co-infection in California, we cross-matched incident TB cases reported to state surveillance systems during 1993-2008 with cases in the state HIV/AIDS registry. Of 57,527 TB case-patients, 3,904

Introduction: Uptake of COVID-19 vaccination remains suboptimal in the United States and other settings. Though early reports indicated that a strong majority of people were interested in receiving the COVID-19 vaccine, the association between vaccine intention and uptake is not yet fully understood. Ourobjective was todescribe predictors of vaccine uptake, and estimate the sensitivity, specificity, and predictive values of self-reported COVID-19 vaccine status compared to a comprehensive statewide COVID-19 vaccine registry., Methods: A cohort of California residents that received a molecular test for SARS-CoV-2 infection during 24 February-5 December 2021 were enrolled in a telephone-administered survey. Survey participants were matched with records in a statewide immunization registry. Cox proportional hazards model were used to compare time to vaccination among those unvaccinated at survey enrollment by self-reported COVID-19 vaccination intention., Results: Among 864 participants who were unvaccinated at the time of interview, 272 (31%) had documentation of receipt of COVID-19 vaccination at a later date; including 194/423 (45.9%) who had initially reported being willing to receive vaccination, 41/185 (22.2%) who reported being unsure about vaccination, and 37/278 (13.3%) who reported unwillingness to receive vaccination.Adjusted hazard ratios (aHRs) for registry-confirmed COVID-19 vaccination were 0.49 (95% confidence interval: 0.32-0.76) and 0.21 (0.12-0.36) for participants expressing uncertainty and unwillingness to receive vaccination, respectively, as compared with participants who reported being willing to receive vaccination. Time to vaccination was shorter among participants from higher-income households (aHR = 3.30 [2.02-5.39]) and who reported co-morbidities or immunocompromising conditions (aHR = 1.54 [1.01-2.36]).Sensitivity of self-reported COVID-19 vaccination status was 82% (80-85%) overall, and 98% (97-99%) among those referencing vaccination records; specificity was 87% (86-89%)., Conclusion: Willingness to receive COVID-19 vaccination was an imperfect predictor of real-world vaccine uptake. Improved messaging about COVID-19 vaccination regardless of previous SARS-CoV-2 infection status may help improve uptake., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Jake M. Pry reports financial support was provided by California Department of Public Health Center for Infectious Diseases.]., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Despite lower circulation of influenza virus throughout 2020-2022 during the COVID-19 pandemic, seasonal influenza vaccination has remained a primary tool to reduce influenza-associated illness and death. The relationship between the decision to receive a COVID-19 vaccine and/or an influenza vaccine is not well understood., Methods: We assessed predictors of receipt of 2021-2022 influenza vaccine in a secondary analysis of data from a case-control study enrolling individuals who received SARS-CoV-2 testing. We used mixed effects logistic regression to estimate factors associated with receipt of seasonal influenza vaccine. We also constructed multinomial adjusted marginal probability models of being vaccinated for COVID-19 only, seasonal influenza only, or both as compared with receipt of neither vaccination., Results: Among 1261 eligible participants recruited between 22 October 2021-22 June 2022, 43% (545) were vaccinated with both seasonal influenza vaccine and >1 dose of a COVID-19 vaccine, 34% (426) received >1 dose of a COVID-19 vaccine only, 4% (49) received seasonal influenza vaccine only, and 19% (241) received neither vaccine. Receipt of >1 COVID-19 vaccine dose was associated with seasonal influenza vaccination (adjusted odds ratio [aOR]: 3.72; 95% confidence interval [CI]: 2.15-6.43); this association was stronger among participants receiving >1 COVID-19 booster dose (aOR = 16.50 [10.10-26.97]). Compared with participants testing negative for SARS- CoV-2 infection, participants testing positive had lower odds of receipt of 2021-2022 seasonal influenza vaccine (aOR = 0.64 [0.50-0.82])., Conclusions: Recipients of a COVID-19 vaccine were more likely to receive seasonal influenza vaccine during the 2021-2022 season. Factors associated with individuals' likelihood of receiving COVID-19 and seasonal influenza vaccines will be important to account for in future studies of vaccine effectiveness against both conditions. Participants who tested positive for SARS-CoV-2 in our sample were less likely to have received seasonal influenza vaccine, suggesting an opportunity to offer influenza vaccination before or after a COVID-19 diagnosis., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: co-author J.A.L. discloses receipt of grants and honoraria from Pfizer, Inc, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The use of face masks or respirators (N95/KN95) is recommended to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Well-fitting face masks and respirators effectively filter virus-sized particles in laboratory conditions (2,3), though few studies have assessed their real-world effectiveness in preventing acquisition of SARS-CoV-2 infection (4). A test-negative design case-control study enrolled randomly selected California residents who had received a test result for SARS-CoV-2 during February 18-December 1, 2021. Face mask or respirator use was assessed among 652 case-participants (residents who had received positive test results for SARS-CoV-2) and 1,176 matched control-participants (residents who had received negative test results for SARS-CoV-2) who self-reported being in indoor public settings during the 2 weeks preceding testing and who reported no known contact with anyone with confirmed or suspected SARS-CoV-2 infection during this time. Always using a face mask or respirator in indoor public settings was associated with lower adjusted odds of a positive test result compared with never wearing a face mask or respirator in these settings (adjusted odds ratio [aOR] = 0.44; 95% CI = 0.24-0.82). Among 534 participants who specified the type of face covering they typically used, wearing N95/KN95 respirators (aOR = 0.17; 95% CI = 0.05-0.64) or surgical masks (aOR = 0.34; 95% CI = 0.13-0.90) was associated with significantly lower adjusted odds of a positive test result compared with not wearing any face mask or respirator. These findings reinforce that in addition to being up to date with recommended COVID-19 vaccinations, consistently wearing a face mask or respirator in indoor public settings reduces the risk of acquiring SARS-CoV-2 infection. Using a respirator offers the highest level of personal protection against acquiring infection, although it is most important to wear a mask or respirator that is comfortable and can be used consistently., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Joseph A. Lewnard discloses receipt of research grants and consulting fees from Pfizer, Inc., unrelated to the current study. No other potential conflicts of interest were disclosed.

By November 30, 2021, approximately 130,781 COVID-19-associated deaths, one in six of all U.S. deaths from COVID-19, had occurred in California and New York.* COVID-19 vaccination protects against infection with SARS-CoV-2 (the virus that causes COVID-19), associated severe illness, and death (1,2); among those who survive, previous SARS-CoV-2 infection also confers protection against severe outcomes in the event of reinfection (3,4). The relative magnitude and duration of infection- and vaccine-derived protection, alone and together, can guide public health planning and epidemic forecasting. To examine the impact of primary COVID-19 vaccination and previous SARS-CoV-2 infection on COVID-19 incidence and hospitalization rates, statewide testing, surveillance, and COVID-19 immunization data from California and New York (which account for 18% of the U.S. population) were analyzed. Four cohorts of adults aged ≥18 years were considered: persons who were 1) unvaccinated with no previous laboratory-confirmed COVID-19 diagnosis, 2) vaccinated (14 days after completion of a primary COVID-19 vaccination series) with no previous COVID-19 diagnosis, 3) unvaccinated with a previous COVID-19 diagnosis, and 4) vaccinated with a previous COVID-19 diagnosis. Age-adjusted hazard rates of incident laboratory-confirmed COVID-19 cases in both states were compared among cohorts, and in California, hospitalizations during May 30-November 20, 2021, were also compared. During the study period, COVID-19 incidence in both states was highest among unvaccinated persons without a previous COVID-19 diagnosis compared with that among the other three groups. During the week beginning May 30, 2021, compared with COVID-19 case rates among unvaccinated persons without a previous COVID-19 diagnosis, COVID-19 case rates were 19.9-fold (California) and 18.4-fold (New York) lower among vaccinated persons without a previous diagnosis; 7.2-fold (California) and 9.9-fold lower (New York) among unvaccinated persons with a previous COVID-19 diagnosis; and 9.6-fold (California) and 8.5-fold lower (New York) among vaccinated persons with a previous COVID-19 diagnosis. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These relationships changed after the SARS-CoV-2 Delta variant became predominant (i.e., accounted for >50% of sequenced isolates) in late June and July. By the week beginning October 3, compared with COVID-19 cases rates among unvaccinated persons without a previous COVID-19 diagnosis, case rates among vaccinated persons without a previous COVID-19 diagnosis were 6.2-fold (California) and 4.5-fold (New York) lower; rates were substantially lower among both groups with previous COVID-19 diagnoses, including 29.0-fold (California) and 14.7-fold lower (New York) among unvaccinated persons with a previous diagnosis, and 32.5-fold (California) and 19.8-fold lower (New York) among vaccinated persons with a previous diagnosis of COVID-19. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These results demonstrate that vaccination protects against COVID-19 and related hospitalization, and that surviving a previous infection protects against a reinfection and related hospitalization. Importantly, infection-derived protection was higher after the Delta variant became predominant, a time when vaccine-induced immunity for many persons declined because of immune evasion and immunologic waning (2,5,6). Similar cohort data accounting for booster doses needs to be assessed, as new variants, including Omicron, circulate. Although the epidemiology of COVID-19 might change with the emergence of new variants, vaccination remains the safest strategy to prevent SARS-CoV-2 infections and associated complications; all eligible persons should be up to date with COVID-19 vaccination. Additional recommendations for vaccine doses might be warranted in the future as the virus and immunity levels change., 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: Reported outbreaks of invasive group A Streptococcus (iGAS) infections among people who inject drugs (PWID) and people experiencing homelessness (PEH) have increased, concurrent with rising US iGAS rates. We describe epidemiology among iGAS patients with these risk factors., Methods: We analyzed iGAS infections from population-based Active Bacterial Core surveillance (ABCs) at 10 US sites from 2010 to 2017. Cases were defined as GAS isolated from a normally sterile site or from a wound in patients with necrotizing fasciitis or streptococcal toxic shock syndrome. GAS isolates were emm typed. We categorized iGAS patients into four categories: injection drug use (IDU) only, homelessness only, both, and neither. We calculated annual change in prevalence of these risk factors using log binomial regression models. We estimated national iGAS infection rates among PWID and PEH., Results: We identified 12 386 iGAS cases; IDU, homelessness, or both were documented in ~13%. Skin infections and acute skin breakdown were common among iGAS patients with documented IDU or homelessness. Endocarditis was 10-fold more frequent among iGAS patients with documented IDU only versus those with neither risk factor. Average percentage yearly increase in prevalence of IDU and homelessness among iGAS patients was 17.5% and 20.0%, respectively. iGAS infection rates among people with documented IDU or homelessness were ~14-fold and 17- to 80-fold higher, respectively, than among people without those risks., Conclusions: IDU and homelessness likely contribute to increases in US incidence of iGAS infections. Improving management of skin breakdown and early recognition of skin infection could prevent iGAS infections in these patients., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Since the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines in the United States, invasive H. influenzae disease epidemiology has changed, and racial disparities have not been recently described., Methods: Active population- and laboratory-based surveillance for H. influenzae was conducted through Active Bacterial Core surveillance at 10 US sites. Data from 2008-2017 were used to estimate projected nationwide annual incidence, as cases per 100 000., Results: During 2008-2017, Active Bacterial Core surveillance identified 7379 H. influenzae cases. Of 6705 patients (90.9%) with reported race, 76.2% were White, 18.6% were Black, 2.8% were Asian/Pacific Islander, and 2.4% were American Indian or Alaska Native (AI/AN). The nationwide annual incidence was 1.8 cases/100 000. By race, incidence was highest among AI/AN populations (3.1) and lowest among Asian/Pacific Islander populations (0.8). Nontypeable H. influenzae caused the largest incidence within all races (1.3), with no striking disparities identified. Among AI/AN children aged <5 years, incidence of H. influenzae serotype a (Hia) was 16.7 times higher and Hib incidence was 22.4 times higher than among White children. Although Hia incidence was lower among White and Black populations than among AI/AN populations, Hia incidence increased 13.6% annually among White children and 40.4% annually among Black children aged <5 years., Conclusions: While nontypeable H. influenzae causes the largest H. influenzae burden overall, AI/AN populations experience disproportionately high rates of Hia and Hib, with the greatest disparity among AI/AN children aged <5 years. Prevention tools are needed to reduce disparities affecting AI/AN children and address increasing Hia incidence in other communities., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background Context: Surgical site infections (SSIs) after spinal fusion surgery increase healthcare costs, morbidity and mortality. Routine measures of obesity fail to consider site specific fat distribution., Purpose: To assess the association between the spine adipose index and deep surgical site infection and determine a threshold value for spine adipose index that can assist in preoperative risk stratification in patients undergoing posterior instrumented lumbar fusion (PILF)., Study Design/setting: Multicenter retrospective case-control study., Patient Sample: We reviewed patients who underwent PILF from January 1, 2010 to December 31, 2018., Outcome Measures: All patients developing a deep primary incisional or organ-space SSI within 90 days of surgery as per US Center for Disease Control and Prevention criteria were identified. We gathered potential pre-operative and intra-operative deep infection risk factors for each patient. A 1:1 match was performed using the following criteria: gender, age (±3 y), ethnicity, date of surgery (± 1 y), and hospital location of surgery. Spine adipose index was measured on pre-operative mid-sagittal cuts of T2 weighted MRI scans. Each measurement was repeated twice by three authors in a blinded fashion, with each series of measurement separated by a period of at least six weeks., Methods: Stepwise binary logistic regression analysis was used to assess the association between SAI and the development of deep SSI. Separate logistic regression models were used for body mass index (BMI) and direct measures of subcutaneous fat thickness. Receiver Operating Characteristic analysis was used to determine the optimal value for SAI, and subsequent risk ratios were calculated using the identified threshold. Intra- and inter-observer reliabilities were assessed using intra-class coefficients., Results: Forty-two patients were included in final analysis, with twenty-one cases and twenty-one matched controls. The spine adipose index was significantly greater in patients developing deep SSI (p=.029), and this relationship was maintained after adjusting for confounders (p=.046). Risk of developing deep SSI following PILF surgery was increased 2.0-fold when the spine adipose index was ≥0.51. The spine adipose index had excellent (ICC >0.9; p<.001) inter- and intra-observer reliabilities., Conclusion: The spine adipose index is a novel radiographic measure and an independent risk factor for developing deep SSI, with 0.51 being the ideal threshold value for pre-operative risk stratification in patients undergoing PILF surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Newly reported hepatitis C virus (HCV) infections in California increased 50% among people 15-29 years of age between 2014 and 2016. National estimates suggest this increase was due to the opioid epidemic and associated increases in injection drug use. However, most of California's 61 local health jurisdictions (LHJs) do not routinely investigate newly reported HCV infections, so these individuals' risk factors for infection are not well understood. We sought to describe the demographics, risk behaviors, and utilization of harm reduction services in California's fastest-rising age group of people with newly reported hepatitis C infections to support targeted HCV prevention and treatment strategies., Methods: California Department of Public Health invited LHJs to participate in enhanced surveillance if they met criteria indicating heightened population risk for HCV infection among people ages 15-29. From June-December 2018, eight LHJs contacted newly reported HCV cases by phone using a structured questionnaire., Results: Among 472 total HCV cases who met the inclusion criteria, 114 (24%) completed an interview. Twenty-seven percent of respondents (n = 31) had ever been incarcerated, of whom 29% received a tattoo/piercing and 39% injected drugs while incarcerated. Among people who injected drugs (PWID)-36% (n = 41) of all respondents-68% shared injection equipment and many lacked access to harm reduction services: 37% knew of or ever used a needle exchange and 44% ever needed naloxone during an overdose but did not have it. Heroin was the most frequently reported injected drug (n = 30), followed by methamphetamine (n = 18). Pre-diagnosis HCV risk perception varied significantly by PWID status and race/ethnicity: 76% of PWID vs. 8% of non-PWID (p < 0.001), and 44% of non-Hispanic White respondents vs. 22% of people of color (POC) respondents (p = 0.011), reported thinking they were at risk for HCV before diagnosis. Eighty-nine percent of all respondents reported having health insurance, although only two had taken HCV antiviral medications., Conclusions: Among young people with HCV, we found limited pre-diagnosis HCV risk perception and access to harm reduction services, with racial/ethnic disparities. Interventions to increase harm reduction services awareness, access, and utilization among young PWID, especially young PWID of color, may be warranted., (© 2021. The Author(s).)

With a population of forty million and substantial geographic variation in sociodemographics and health services, California is an important setting in which to study disparities. Its population (37.5 percent White, 39.1 percent Latino, 5.3 percent Black, and 14.4 percent Asian) experienced 59,258 COVID-19 deaths through April 14, 2021-the most of any state. We analyzed California's racial/ethnic disparities in COVID-19 exposure risks, testing rates, test positivity, and case rates through October 2020, combining data from 15.4 million SARS-CoV-2 tests with subcounty exposure risk estimates from the American Community Survey. We defined "high-exposure-risk" households as those with one or more essential workers and fewer rooms than inhabitants. Latino people in California are 8.1 times more likely to live in high-exposure-risk households than White people (23.6 percent versus 2.9 percent), are overrepresented in cumulative cases (3,784 versus 1,112 per 100,000 people), and are underrepresented in cumulative testing (35,635 versus 48,930 per 100,000 people). These risks and outcomes were worse for Latino people than for members of other racial/ethnic minority groups. Subcounty disparity analyses can inform targeting of interventions and resources, including community-based testing and vaccine access measures. Tracking COVID-19 disparities and developing equity-focused public health programming that mitigates the effects of systemic racism can help improve health outcomes among California's populations of color.

California has a large population of people experiencing homelessness (PEH) that is characterised by a high proportion of people who are unsheltered and chronically homeless. PEH are at increased risk of communicable diseases due to multiple, intersecting factors, including increased exposures, comorbid conditions including substance use disorder and mental illness and lack of access to hygiene and healthcare facilities. Data available for several communicable diseases show that PEH in California experiences an increased burden of communicable diseases compared to people not experiencing homelessness. Public health agencies face unique challenges in serving this population. Efforts to reduce homelessness, increase access to health care for PEH, enhance data availability and strengthen partnerships among agencies serving PEH can help reduce the disparity in communicable disease burden faced by PEH.

Importance: Group B Streptococcus (GBS) is an important cause of invasive bacterial disease. Previous studies have shown a substantial and increasing burden of GBS infections among nonpregnant adults, particularly older adults and those with underlying medical conditions., Objective: To update trends of invasive GBS disease among US adults using population-based surveillance data., Design, Setting, and Participants: In this population-based surveillance study, a case was defined as isolation of GBS from a sterile site between January 1, 2008, and December 31, 2016. Demographic and clinical data were abstracted from medical records. Rates were calculated using US Census data. Antimicrobial susceptibility testing and serotyping were performed on a subset of isolates. Case patients were residents of 1 of 10 catchment areas of the Active Bacterial Core surveillance (ABCs) network, representing approximately 11.5% of the US adult population. Patients were included in the study if they were nonpregnant, were 18 years or older, were residents of an ABCs catchment site, and had a positive GBS culture from a normally sterile body site., Main Outcomes and Measures: Trends in GBS cases overall and by demographic characteristics (sex, age, and race), underlying clinical conditions of patients, and isolate characteristics are described., Results: The ABCs network detected 21 250 patients with invasive GBS among nonpregnant adults from 2008 through 2016. The GBS incidence in this population increased from 8.1 cases per 100 000 population in 2008 to 10.9 in 2016 (P = .002 for trend). There were 3146 cases reported in 2016 (59% male; median age, 64 years; age range, 18-103 years). The GBS incidence was higher among men than women and among blacks than whites and increased with age. Projected to the US population, an estimated 27 729 cases of invasive disease and 1541 deaths occurred in the United States in 2016. Ninety-five percent of cases in 2016 occurred in someone with at least 1 underlying condition, most commonly obesity (53.9%) and diabetes (53.4%). Resistance to clindamycin increased from 37.0% of isolates in 2011 to 43.2% in 2016 (P = .02). Serotypes Ia, Ib, II, III, and V accounted for 86.4% of isolates in 2016; serotype IV increased from 4.7% in 2008 to 11.3% in 2016 (P < .001 for trend)., Conclusions and Relevance: The public health burden of invasive GBS disease among nonpregnant adults is substantial and continues to increase. Chronic diseases, such as obesity and diabetes, may contribute.

Background: Congenital syphilis (CS), the transmission of Treponema pallidum from mother to fetus during pregnancy, can cause adverse birth outcomes. In 2012 to 2014, the CS rate in California increased more than 200% from 6.6 to 20.3 cases per 100,000 live births. Our objectives were to identify characteristics associated with delivering an infant with CS and missed opportunities for prevention among syphilis-infected pregnant women in California., Methods: We linked California Department of Public Health syphilis surveillance records from women aged 15 to 45 years-diagnosed from March 13, 2012, to December 31, 2014-to birth records. We compared characteristics among mothers who delivered an infant with CS (CS mothers) with mothers who delivered an infant without CS (non-CS mothers) by using χ or Fisher exact tests. To visualize gaps in prevention among syphilis-infected pregnant women, we constructed a CS prevention cascade, a figure that shows steps to prevent CS., Results: During the selected period, 2498 women were diagnosed as having syphilis, and 427 (17%) linked to birth records; 164 (38%) were defined as CS mothers and 263 (62%) as non-CS mothers. Mothers with CS were more likely than non-CS mothers to have their first prenatal care visit in the third trimester. High proportions of mothers in both groups reported high-risk sexual behaviors, methamphetamine use, or incarceration (13%-29%). The CS prevention cascade showed decrements of 5% to 11% in prenatal care receipt, testing, and treatment steps; only 62% of potential CS births were prevented., Conclusions: Multifaceted efforts are needed to address gaps in the CS prevention cascade and reduce CS cases in California.

Background: Rates of invasive group B Streptococcus (GBS) disease, obesity, and diabetes have increased in US adults. We hypothesized that obesity would be independently associated with an increased risk of invasive GBS disease., Methods: We identified adults with invasive GBS disease within Active Bacterial Core surveillance during 2010-2012 and used population estimates from the Behavioral Risk Factor Surveillance System to calculate invasive GBS incidence rates. We estimated relative risks (RRs) of invasive GBS using Poisson analysis with offset denominators, with obesity categorized as class I/II (body mass index [BMI] = 30-39.9 kg/m 2 ) and class III (BMI ≥ 40.0 kg/m 2 )., Results: In multivariable analysis of 4281 cases, the adjusted RRs of invasive GBS disease were increased for obesity (class I/II: RR, 1.52; 95% confidence interval [CI], 1.14-2.02; and class III: RR, 4.87; 95% CI, 3.50-6.77; reference overweight) and diabetes (RR, 6.04; 95% CI, 4.77-7.65). The adjusted RR associated with class III obesity was 3-fold among persons with diabetes (95% CI, 1.38-6.61) and nearly 9-fold among persons without diabetes (95% CI, 6.41-12.46), compared with overweight. The adjusted RRs associated with diabetes varied by age and BMI, with the highest RR in young populations without obesity. Population attributable risks of invasive GBS disease were 27.2% for obesity and 40.1% for diabetes., Conclusions: Obesity and diabetes were associated with substantially increased risk of infection from invasive GBS. Given the population attributable risks of obesity and diabetes, interventions that reduce the prevalence of these conditions would likely reduce the burden of invasive GBS infection.

Study Design: Retrospective, descriptive study., Objectives: Managing early surgical site infection following elective lumbar spine surgery remains a challenge with controversy regarding retention of instrumentation and bone graft. Wound closure may also pose considerable challenges. We aim to report on our method of managing deep surgical site infections complicating elective spine surgery with surgeon assembled deep vacuum dressings. Identification of causative organisms with their sensitivities was a secondary objective., Methods: Patients were identified from a prospectively maintained, single-surgeon database from 2003-2015. Patients who had an infective or trauma related diagnosis, cervical procedures, and were younger than 18 years were excluded. Records were reviewed to identify bacteriology, laboratory tests performed, antibiotics administered, and type and frequency of surgical management. One thousand two hundred twenty patients qualified for inclusion, with 19 identified as having developed acute wound sepsis., Results: All patients had surgical debridement on the day of presentation and the majority of wounds were managed with a vacuum dressing. In all but 1 patient was instrumentation retained. Specimens for culture were taken at each debridement and antibiotics changed accordingly. Patients received a minimum 6 weeks of antibiotics., Conclusions: The management of deep surgical site infection is labor intensive and frustrating for both surgeon and patient due to the unexpected prolonged admission. Management goals are identification and eradication of the causative organism with subsequent healing of the surgical wound. This process is enhanced with the use of negative-suction dressings made from theatre stock replaced at regular intervals and allows retention of bone graft and instrumentation in the majority of cases., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Shigella sonnei has caused unusually large outbreaks of shigellosis in California in 2014 and 2015. Preliminary data indicated the involvement of two distinct bacterial populations, one from San Diego and San Joaquin (SDi/SJo) and one from the San Francisco (SFr) Bay area. Whole-genome analysis and antibiotic susceptibility testing of 68 outbreak and archival isolates of S. sonnei were performed to investigate the microbiological factors related to these outbreaks. Both SDi/SJo and SFr populations, as well as almost all of the archival S. sonnei isolates belonged to sequence type 152 (ST152). Genome-wide single nucleotide polymorphism (SNP) analysis clustered the majority of California (CA) isolates to an earlier described lineage III. Isolates in the SDi/SJo population had a novel lambdoid bacteriophage carrying genes encoding Shiga toxin (STX) that were most closely related to that found in Escherichia coli O104:H4. However, the STX genes ( stx1A and stx1B ) from this novel phage had sequences most similar to the phages from Shigella flexneri and S. dysenteriae . The isolates in the SFr population were resistant to ciprofloxacin due to point mutations in gyrA and parC genes and were related to the fluoroquinolone-resistant S. sonnei clade within lineage III that originated in South Asia. The emergence of a highly virulent S. sonnei strain and introduction of a fluoroquinolone-resistant strain reflect the changing traits of this pathogen in California. An enhanced monitoring is advocated for early detection of future outbreaks caused by such strains. IMPORTANCE Shigellosis is an acute diarrheal disease causing nearly half a million infections, 6,000 hospitalizations, and 70 deaths annually in the United States. S. sonnei caused two unusually large outbreaks in 2014 and 2015 in California. We used whole-genome sequencing to understand the pathogenic potential of bacteria involved in these outbreaks. Our results suggest the persistence of a local S. sonnei SDi/SJo clone in California since at least 2008. Recently, a derivative of the original clone acquired the ability to produce Shiga toxin (STX) via exchanges of bacteriophages with other bacteria. STX production is connected with more severe disease, including bloody diarrhea. A second population of S. sonnei that caused an outbreak in the San Francisco area was resistant to fluoroquinolones and showed evidence of connection to a fluoroquinolone-resistant lineage from South Asia. These emerging trends in S. sonnei populations in California must be monitored for future risks of the spread of increasingly virulent and resistant clones.

Background: Invasive group A Streptococcus (GAS) infections are associated with significant morbidity and mortality rates. We report the epidemiology and trends of invasive GAS over 8 years of surveillance., Methods: From January 2005 through December 2012, we collected data from the Centers for Disease Control and Prevention's Active Bacterial Core surveillance, a population-based network of 10 geographically diverse US sites (2012 population, 32.8 million). We defined invasive GAS as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis (NF) or streptococcal toxic shock syndrome (STSS). Available isolates were emm typed. We calculated rates and made age- and race-adjusted national projections using census data., Results: We identified 9557 cases (3.8 cases per 100 000 persons per year) with 1116 deaths (case-fatality rate, 11.7%). The case-fatality rates for septic shock, STSS, and NF were 45%, 38%, and 29%, respectively. The annual incidence was highest among persons aged ≥65 years (9.4/100 000) or <1 year (5.3) and among blacks (4.7/100 000). National rates remained steady over 8 years of surveillance. Factors independently associated with death included increasing age, residence in a nursing home, recent surgery, septic shock, NF, meningitis, isolated bacteremia, pneumonia, emm type 1 or 3, and underlying chronic illness or immunosuppression. An estimated 10 649-13 434 cases of invasive GAS infections occur in the United States annually, resulting in 1136-1607 deaths. In a 30-valent M-protein vaccine, emm types accounted for 91% of isolates., Conclusions: The burden of invasive GAS infection in the United States remains substantial. Vaccines under development could have a considerable public health impact., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Importance: There has been limited surveillance for acute flaccid paralysis in North America since the regional eradication of poliovirus. In 2012, the California Department of Public Health received several reports of acute flaccid paralysis cases of unknown etiology., Objective: To quantify disease incidence and identify potential etiologies of acute flaccid paralysis cases with evidence of spinal motor neuron injury., Design, Setting, and Participants: Case series of acute flaccid paralysis in patients with radiological or neurophysiological findings suggestive of spinal motor neuron involvement reported to the California Department of Public Health with symptom onset between June 2012 and July 2015. Patients meeting diagnostic criteria for other acute flaccid paralysis etiologies were excluded. Cerebrospinal fluid, serum samples, nasopharyngeal swab specimens, and stool specimens were submitted to the state laboratory for infectious agent testing., Main Outcomes and Measures: Case incidence and infectious agent association., Results: Fifty-nine cases were identified. Median age was 9 years (interquartile range [IQR], 4-14 years; 50 of the cases were younger than 21 years). Symptoms that preceded or were concurrent included respiratory or gastrointestinal illness (n = 54), fever (n = 47), and limb myalgia (n = 41). Fifty-six patients had T2 hyperintensity of spinal gray matter on magnetic resonance imaging and 43 patients had cerebrospinal fluid pleocytosis. During the course of the initial hospitalization, 42 patients received intravenous steroids; 43, intravenous immunoglobulin; and 13, plasma exchange; or a combination of these treatments. Among 45 patients with follow-up data, 38 had persistent weakness at a median follow-up of 9 months (IQR, 3-12 months). Two patients, both immunocompromised adults, died within 60 days of symptom onset. Enteroviruses were the most frequently detected pathogen in either nasopharynx swab specimens, stool specimens, serum samples (15 of 45 patients tested). No pathogens were isolated from the cerebrospinal fluid. The incidence of reported cases was significantly higher during a national enterovirus D68 outbreak occurring from August 2014 through January 2015 (0.16 cases per 100,000 person-years) compared with other monitoring periods (0.028 cases per 100,000 person-years; P <.001)., Conclusions and Relevance: In this series of patients identified in California from June 2012 through July 2015, clinical manifestations indicated a rare but distinct syndrome of acute flaccid paralysis with evidence of spinal motor neuron involvement. The etiology remains undetermined, most patients were children and young adults, and motor weakness was prolonged.

Background: Enterovirus D68 was implicated in a widespread outbreak of severe respiratory illness across the USA in 2014 and has also been reported sporadically in patients with acute flaccid myelitis. We aimed to investigate the association between enterovirus D68 infection and acute flaccid myelitis during the 2014 enterovirus D68 respiratory outbreak in the USA., Methods: Patients with acute flaccid myelitis who presented to two hospitals in Colorado and California, USA, between Nov 24, 2013, and Oct 11, 2014, were included in the study. Additional cases identified from Jan 1, 2012, to Oct 4, 2014, via statewide surveillance were provided by the California Department of Public Health. We investigated the cause of these cases by metagenomic next-generation sequencing, viral genome recovery, and enterovirus D68 phylogenetic analysis. We compared patients with acute flaccid myelitis who were positive for enterovirus D68 with those with acute flaccid myelitis but negative for enterovirus D68 using the two-tailed Fisher's exact test, two-sample unpaired t test, and Mann-Whitney U test., Findings: 48 patients were included: 25 with acute flaccid myelitis, two with enterovirus-associated encephalitis, five with enterovirus-D68-associated upper respiratory illness, and 16 with aseptic meningitis or encephalitis who tested positive for enterovirus. Enterovirus D68 was detected in respiratory secretions from seven (64%) of 11 patients comprising two temporally and geographically linked acute flaccid myelitis clusters at the height of the 2014 outbreak, and from 12 (48%) of 25 patients with acute flaccid myelitis overall. Phylogenetic analysis revealed that all enterovirus D68 sequences associated with acute flaccid myelitis grouped into a clade B1 strain that emerged in 2010. Of six coding polymorphisms in the clade B1 enterovirus D68 polyprotein, five were present in neuropathogenic poliovirus or enterovirus D70, or both. One child with acute flaccid myelitis and a sibling with only upper respiratory illness were both infected by identical enterovirus D68 strains. Enterovirus D68 viraemia was identified in a child experiencing acute neurological progression of his paralytic illness. Deep metagenomic sequencing of cerebrospinal fluid from 14 patients with acute flaccid myelitis did not reveal evidence of an alternative infectious cause to enterovirus D68., Interpretation: These findings strengthen the putative association between enterovirus D68 and acute flaccid myelitis and the contention that acute flaccid myelitis is a rare yet severe clinical manifestation of enterovirus D68 infection in susceptible hosts., Funding: National Institutes of Health, University of California, Abbott Laboratories, and the Centers for Disease Control and Prevention., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In summer 2012, an outbreak of hantavirus infections occurred among overnight visitors to Yosemite National Park in California, USA. An investigation encompassing clinical, epidemiologic, laboratory, and environmental factors identified 10 cases among residents of 3 states. Eight case-patients experienced hantavirus pulmonary syndrome, of whom 5 required intensive care with ventilatory support and 3 died. Staying overnight in a signature tent cabin (9 case-patients) was significantly associated with becoming infected with hantavirus (p<0.001). Rodent nests and tunnels were observed in the foam insulation of the cabin walls. Rodent trapping in the implicated area resulted in high trap success rate (51%), and antibodies reactive to Sin Nombre virus were detected in 10 (14%) of 73 captured deer mice. All signature tent cabins were closed and subsequently dismantled. Continuous public awareness and rodent control and exclusion are key measures in minimizing the risk for hantavirus infection in areas inhabited by deer mice.

Objective: National guidelines highlight the roles of early HIV diagnosis and effective comanagement for HIV and tuberculosis (TB) to prevent mortality and morbidity from HIV-related TB. We assessed HIV diagnosis timing and HIV/TB comanagement for California HIV/TB patients., Methods: We reviewed and analyzed public health charts for California HIV/TB patients reported during 2008. HIV diagnoses fewer than three months before TB diagnosis were considered new HIV diagnoses. We determined the proportion of patients with new HIV diagnoses, risk factors for new HIV diagnoses, and proportion of patients receiving recommended CD4 cell count measurements, supervised TB therapy, and antiretroviral therapy (ART)., Results: Of 130 HIV/TB patients, 51% had new HIV diagnoses. Foreign-born patients were more likely than U.S.-born patients to have new HIV diagnoses. Supervised TB therapy and CD4 cell count measurements followed national recommendations for 91% and 74% of patients, respectively. At least 73% of patients started ART before completing TB therapy. Compared with patients who had previous HIV diagnoses, patients with new HIV diagnoses started ART later and had lower CD4 cell counts and higher viral loads at TB diagnosis., Conclusions: Although most HIV/TB patients received the recommended treatment, half had new HIV diagnoses. Compared with patients who had previous HIV diagnoses, patients with new HIV diagnoses had greater immunosuppression at TB diagnosis. A new diagnosis indicates that HIV could have been diagnosed earlier and ART or treatment for latent TB infection could have been initiated to prevent TB development.

Background: Current recommendations for spinal tuberculosis (TB) not requiring open surgery include core needle biopsy to confirm TB and determine drug sensitivity. International figures show the positive culture yield from core needle biopsies is 50 -- 83%.Objectives. To (i) assess the yield of percutaneous needle biopsies; (ii) identify factors that may lead to a negative result; and (iii) determine whether, TB being suspected, needle biopsy is justified., Methods: We conducted a multicentre retrospective review of 44 patients treated for suspected spinal TB between January 2009 and April 2012, who did not require open surgery. Data captured included demographics, relevant history, outcome of investigations and histopathological findings in patients., Results: The overall positive TB culture rate was 59%. Age, duration of symptoms, HIV and neurological status, erythrocyte sedimentation rate and core size had no statistical influence. Of the 7 patients receiving TB treatment at the time of biopsy, 3 were culture-positive. Multidrug resistance was evident in 12% of positive cultures. The positive culture yield was 40% at Tygerberg Hospital and 75% at Groote Schuur Hospital, with no difference in histological yield. This was attributed to the practice of decontaminating specimens prior to culture at Tygerberg Hospital. The highest culture yield (32%) came from samples showing non-necrotising chronic inflammatory changes., Conclusion: Percutaneous biopsy remains an important tool to diagnose and manage spinal TB. The yield of transpedicular biopsies in this study was comparable with international figures. Specimen decontamination prior to culture had a direct negative influence on biopsy culture yield, as did prior TB treatment.

Objectives: Bacterial meningitis is associated with high mortality and long-term complications. This study assessed the impact of Haemophilus influenzae type b (Hib) conjugate vaccine on childhood bacterial meningitis in Ulaanbaatar, Mongolia., Study Design: Prospective, active, population-based surveillance for suspected meningitis in children aged 2-59 months was conducted (February 2002-January 2011) in 6 hospitals. Clinical data, blood, and cerebrospinal fluid were collected. The impact of Hib conjugate vaccine was assessed by comparing Hib and all cause meningitis data in the 3 years preceding pentavalent conjugate vaccine implementation (2002-2004) with 3 years postimplementation (2008-2010)., Results: Five hundred eleven cases of suspected meningitis were identified from 2002-2011. Pentavalent conjugate vaccine coverage in December 2005 in Ulaanbaatar city was 97%. The proportion of suspected cases confirmed as Hib meningitis decreased from 25% (50/201) in the prevaccination era to 2% (4/193) in the postvaccination era (P < .0001). The annual incidence of Hib decreased from 28 cases per 100,000 children in 2002-2005 to 2 per 100,000 in 2008-2010 (P < .0001)., Conclusions: This article demonstrates the marked impact of Hib conjugate vaccine introduction on meningitis in Mongolia. It is important to sustain this surveillance system to monitor the long-term impact of Hib conjugate vaccine, as well as other interventions such as pneumococcal and meningococcal vaccines., (Copyright © 2013. Published by Mosby, Inc.)

Twenty of 37 gonorrhea cases identified during an outbreak were diagnosed at one health care organization that used an out-of-state laboratory. The results were transmitted into electronic medical records without provider notification. Delays in treatment and reporting were identified. Systems should be implemented to ensure provider notification of electronic laboratory results.

To understand the epidemiology of tuberculosis (TB) and HIV co-infection in California, we cross-matched incident TB cases reported to state surveillance systems during 1993–2008 with cases in the state HIV/AIDS registry. Of 57,527 TB case-patients, 3,904 (7%) had known HIV infection. TB rates for persons with HIV declined from 437 to 126 cases/100,000 persons during 1993–2008; rates were highest for Hispanics (225/100,000) and Blacks (148/100,000). Patients co-infected with TB–HIV during 2001–2008 were significantly more likely than those infected before highly active antiretroviral therapy became available to be foreign born, Hispanic, or Asian/Pacific Islander and to have pyrazinamide-monoresistant TB. Death rates decreased after highly active antiretroviral therapy became available but remained twice that for TB patients without HIV infection and higher for women. In California, HIV-associated TB has concentrated among persons from low- and middle-income countries who often acquire HIV infection in the peri-immigration period.

Context: Human immunodeficiency virus (HIV) infection complicates care and contributes to poor outcomes among tuberculosis (TB) patients. The Centers for Disease Control and Prevention recommends that providers test all TB patients for HIV., Objective: We assessed completeness of HIV status determination among TB patients and identified key gaps in adherence., Design: We conducted a retrospective review of public health charts to determine the HIV status for all TB patients reported in California during 2008. We then used logistic regression to determine the factors associated with a known (positive or negative) HIV status. A random sample of TB patients was selected for secondary review to characterize the timing of HIV status determination and the providers who had opportunity to test for HIV., Setting: California TB programs., Participants: All TB patients reported from California in 2008., Main Outcome Measures: Proportion of patients with a known HIV status, adjusted odds ratios for having a known HIV status, proportion of patients with a known HIV status before TB diagnosis, and proportion of patients diagnosed with TB by different provider types., Results: Only 1752 (66%) of 2667 TB patients had a known HIV status. Having a known HIV status was strongly associated with those aged between 15 and 44 years and being managed with any public provider involvement. Of 292 patients in the random sample, 12 patients (4%) had a known HIV status before TB diagnosis. Among the remaining 280 patients, 187 patients (67%) were diagnosed with TB by a private provider., Conclusions: The HIV status determination of TB patients was selective and not routine as recommended. Private providers can play a key role in testing for HIV at TB diagnosis. California TB programs should ensure that all TB patients have an HIV status by promulgating national recommendations, educating private providers on the benefits of testing TB patients for HIV, and monitoring completeness of HIV status determination.

Background: Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay., Methods and Findings: We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults., Conclusions: Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.

Background: Before the widespread use of rotavirus vaccines, rotavirus was a leading cause of gastroenteritis among children. Navajo and White Mountain Apache children suffer a disproportionate burden of severe rotavirus disease compared with the general U.S. population., Methods: We enrolled Navajo and White Mountain Apache infants in a multicenter, double-blind, placebo-controlled trial of pentavalent human-bovine reassortant rotavirus vaccine (PRV). Subjects received 3 doses of vaccine or placebo at 4 to 10 week intervals, with the first dose given between 6 and 12 weeks of age. Gastroenteritis episodes were identified by active surveillance. Disease severity was determined by a standardized scoring system., Results: There were 509 and 494 randomized children who received vaccine and placebo, respectively. Among placebo recipients, the incidence of rotavirus gastroenteritis was 34.2 episodes/100 child-years (95% confidence interval [95% CI]: 25.8-38.9) versus 8.1 episodes/100 child-years (95% CI: 5.4-12.5) in the vaccine group. The percentage of rotavirus episodes caused by serotypes G1, G2, and G3 was 72.3%, 23.4%, and 2.1%, respectively. There were no severe rotavirus episodes among vaccinees and 4 among placebo recipients. PRV was 77.1% (95% CI: 59.7-87.6), 89.5% (95% CI: 65.9-97.9), and 82.9% (95% CI: 61.1-93.6) effective against G1-G4 rotavirus disease, severe and moderate rotavirus disease combined, and outpatient visits for rotavirus disease, respectively. The risk of adverse events was similar for the vaccine and placebo groups., Conclusions: PRV was highly effective in preventing rotavirus disease and related health care utilization in these American Indian infants. Vaccine efficacy and immunogenicity were similar to the overall study population enrolled in the multicenter trial.

Setting: Importation of infectious tuberculosis (TB) threatens TB control in California and the United States., Objective: To assess the effectiveness of an enhanced pre-immigration screening and treatment protocol to prevent the importation of infectious TB., Design: Retrospective analysis of immigrants ≥ 15 years of age with TB suspect classifications who were screened for TB in their countries of origin before (pre-intervention cohort) and after (post-intervention cohort) implementation of enhanced pre-immigration screening. Enhanced pre-immigration screening added sputum cultures to the existing screening system based on sputum smears for persons with abnormal chest radiographs., Results: The pre- and post-intervention cohorts included respectively 2049 and 1430 immigrants. The occurrence of tuberculosis ≤ 6 months after US arrival in this population decreased following the intervention, from 4.2% (86 cases) to 1.5% (22 cases, P < 0.001). Among pre-intervention cohort cases, 14% were sputum acid-fast bacilli (AFB) smear-positive and 81% were sputum culture-positive for TB, compared with 5% sputum AFB smear-positive (P = 0.46) and 68% sputum culture-positive (P = 0.18) among the post-intervention cohort cases., Conclusion: The enhanced pre-immigration screening was associated with a decline in the proportion of immigrants with TB suspect classifications identified with TB within 6 months of arrival in the United States. Continued state and national surveillance is critical to monitor the effectiveness of the revised pre-immigration screening as it is implemented in additional countries.

Background: Recurrent tuberculosis suggests potentially modifiable gaps in tuberculosis treatment and control activities. The frequency of late recurrences following treatment completion has not been well-studied. We determined the frequency of, and risk factors associated with, tuberculosis that recurs at least one year after completion of anti-tuberculosis therapy in California., Methods: The study population included culture-positive, pulmonary tuberculosis patients reported to the California tuberculosis case registry from 1993 to 2007 who completed anti-tuberculosis therapy. A person with late recurrent tuberculosis was defined as an individual that appeared in the registry more than once, determined by match on name and date-of-birth, with at least one year between treatment completion of the first episode and treatment initiation of the second episode., Results: Among 23,517 tuberculosis patients, 148 (0.63%) had a late recurrence. Independent risk factors for recurrence included: infection with a pyrazinamide mono-resistant isolate (adjusted hazard ratio, 2.93; p = 0.019); initiation of an isoniazid- and rifampin-only treatment regimen (adjusted hazard ratio, 2.55; p = 0.0412); sputum smear-positive disease (adjusted hazard ratio, 1.96; p = 0.0003); human immunodeficiency virus infection (adjusted hazard ratio, 1.81; p = 0.0149); and birth in the United States (adjusted hazard ratio, 1.88; p = 0.0002). Infection with an isoniazid mono-resistant isolate was protective (adjusted hazard ratio, 0.25; p = 0.0171)., Conclusions: The low frequency of late recurrent tuberculosis in California suggests that local TB control programs are largely successful at preventing this adverse outcome. Nonetheless, we identified subpopulations at increased risk of late tuberculosis recurrence that may benefit from additional medical or public health interventions.

Streptococcus pneumoniae is a common cause of community-acquired pneumonia (CAP) but existing diagnostic tools have limited sensitivity and specificity. We enrolled adults undergoing chest radiography at three Indian Health Service clinics in the Southwestern United States and collected acute and convalescent serum for measurement of PsaA and PspA titres and urine for pneumococcal antigen detection. Blood and sputum cultures were obtained at the discretion of treating physicians. We compared findings in clinical and radiographic CAP patients to those in controls without CAP. Urine antigen testing showed the largest differential between CAP patients and controls (clinical CAP 13%, radiographic CAP 17%, control groups 2%). Serological results were mixed, with significant differences between CAP patients and controls for some, but not all changes in titre. Based on urine antigen and blood culture results, we estimated that 11% of clinical and 15% of radiographic CAP cases were due to pneumococcus in this population.

To assess the clinical impact of a molecular beacon (MB) assay that detects multidrug-resistant tuberculosis (MDR TB), we retrospectively reviewed records of 127 MDR TB patients with and without MB testing between 2004 and 2007. Use of the MB assay reduced the time to detection and treatment of MDR TB.

Prior to widespread vaccination, Haemophilus influenzae type b was a leading cause of severe childhood bacterial infection, including meningitis, worldwide. Over the last decade the world has taken great strides towards controlling Hib disease through routine use of conjugate vaccines in developed and developing countries. Currently there is no consensus on the appropriate schedule by which to use Hib vaccine. Vaccination schedules around the world vary greatly, particularly between high and low income countries. Questions remain as to the most effective and efficient schedule of primary doses, the need for a booster dose, and the implications of using combination vaccines. Here, we present a synthesis of data supporting various Hib vaccine schedules, with a focus on the implications for developing countries.

Few population-based studies have investigated the epidemiology of adult community-acquired pneumonia (CAP). We aimed to determine the incidence of CAP in a population at high-risk for pneumococcal disease and to evaluate a standardized method for interpreting chest radiographs adapted from the World Health Organization paediatric chest radiograph interpretation guidelines. We reviewed radiology records at the two healthcare facilities serving the White Mountain Apache tribe to identify possible pneumonia cases > or =40 years of age. We categorized patients with clinical criteria and a physician diagnosis of pneumonia as clinical CAP and those with clinical criteria and an acute infiltrate as radiographic CAP. We identified 100 (27/1000 person-years) and 60 (16/1000 person-years) episodes of clinical and radiographic CAP, respectively. The incidence of CAP increased with age. Both radiographic and clinical CAP were serious illnesses with more than half of patients hospitalized. Our case definitions and methods may be useful for comparing data across studies and conducting vaccine trials.

Background: Haemophilus influenzae type b (Hib) is a leading cause of childhood bacterial meningitis, pneumonia, and other serious infections. Hib disease can be almost completely eliminated through routine vaccination. We assessed the global burden of disease to help national policy makers and international donors set priorities., Methods: We did a comprehensive literature search of studies of Hib disease incidence, case-fatality ratios, age distribution, syndrome distribution, and effect of Hib vaccine. We used vaccine trial data to estimate the proportion of pneumonia cases and pneumonia deaths caused by Hib. We applied these proportions to WHO country-specific estimates of pneumonia cases and deaths to estimate Hib pneumonia burden. We used data from surveillance studies to develop estimates of incidence and mortality of Hib meningitis and serious non-pneumonia, non-meningitis disease. If available, high-quality data were used for national estimates of Hib meningitis and non-pneumonia, non-meningitis disease burden. Otherwise, estimates were based on data from other countries matched as closely as possible for geographic region and child mortality. Estimates were adjusted for HIV prevalence and access to care. Disease burden was estimated for the year 2000 in children younger than 5 years., Findings: We calculated that Hib caused about 8.13 million serious illnesses worldwide in 2000 (uncertainty range 7.33-13.2 million). We estimated that Hib caused 371,000 deaths (247,000-527,000) in children aged 1-59 months, of which 8100 (5600-10,000) were in HIV-positive and 363,000 (242,000-517,000) in HIV-negative children., Interpretation: Global burden of Hib disease is substantial and almost entirely vaccine preventable. Expanded use of Hib vaccine could reduce childhood pneumonia and meningitis, and decrease child mortality., Funding: GAVI Alliance and the Vaccine Fund.

Background: Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children worldwide. However, many countries lack national estimates of disease burden. Effective interventions are available, including pneumococcal conjugate vaccine and case management. To support local and global policy decisions on pneumococcal disease prevention and treatment, we estimated country-specific incidence of serious cases and deaths in children younger than 5 years., Methods: We measured the burden of pneumococcal pneumonia by applying the proportion of pneumonia cases caused by S pneumoniae derived from efficacy estimates from vaccine trials to WHO country-specific estimates of all-cause pneumonia cases and deaths. We also estimated burden of meningitis and non-pneumonia, non-meningitis invasive disease using disease incidence and case-fatality data from a systematic literature review. When high-quality data were available from a country, these were used for national estimates. Otherwise, estimates were based on data from neighbouring countries with similar child mortality. Estimates were adjusted for HIV prevalence and access to care and, when applicable, use of vaccine against Haemophilus influenzae type b., Findings: In 2000, about 14.5 million episodes of serious pneumococcal disease (uncertainty range 11.1-18.0 million) were estimated to occur. Pneumococcal disease caused about 826,000 deaths (582,000-926,000) in children aged 1-59 months, of which 91,000 (63,000-102,000) were in HIV-positive and 735,000 (519,000-825,000) in HIV-negative children. Of the deaths in HIV-negative children, over 61% (449,000 [316,000-501,000]) occurred in ten African and Asian countries., Interpretation: S pneumoniae causes around 11% (8-12%) of all deaths in children aged 1-59 months (excluding pneumococcal deaths in HIV-positive children). Achievement of the UN Millennium Development Goal 4 for child mortality reduction can be accelerated by prevention and treatment of pneumococcal disease, especially in regions of the world with the greatest burden., Funding: GAVI Alliance and the Vaccine Fund.

Background: Childhood bacterial meningitis is severe and largely preventable by vaccination. Few data on childhood bacterial meningitis in Northeast and Central Asia exist. Our aim was to determine the incidence and etiology of childhood bacterial meningitis in Ulaanbaatar, Mongolia., Methods: We conducted prospective, population-based, active hospital surveillance for clinical meningitis in children 2 months to 5 years of age. Clinical data, blood, and cerebrospinal fluid were collected according to a standard protocol. Laboratory testing was performed at 2 reference laboratories in Ulaanbaatar., Results: From February 2002 to January 2005, 201 suspected meningitis cases were identified in residents of Ulaanbaatar. The average annual incidence rate for confirmed and probable bacterial meningitis (cases with culture-negative, purulent cerebrospinal fluid) was 68 cases per 100,000 children aged 2 months to 5 years. The average annual incidence rate of confirmed cases was 28 cases per 100,000 children for Haemophilus influenzae type b meningitis, 11 cases per 100,000 children for pneumococcal meningitis, and 13 cases per 100,000 children for meningococcal meningitis. Adjusting for cases without complete cerebrospinal fluid information and culture-negative, probable bacterial cases, the estimated incidence rate was 40 cases per 100,000 children for H. influenzae type b meningitis, 15 cases per 100,000 children for pneumococcal meningitis, and 17 cases per 100,000 children for meningococcal meningitis., Conclusion: H. influenzae type b is the leading cause of childhood bacterial meningitis in Ulaanbaatar, and the incidence rate is higher than that reported from other Asian countries. These data supported the recent introduction of H. influenzae type b conjugate vaccine in Mongolia. Ongoing surveillance will monitor the impact of the vaccine.

Background: Since the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the United States, rates of invasive pneumococcal disease have decreased in both vaccinated and unvaccinated age groups. Reduction of invasive pneumococcal disease in unvaccinated groups has been attributed to reduced transmission of vaccine-type pneumococci in the community. Understanding the impact of PCV7 on carriage among vaccinated and unvaccinated community members is critical to interpreting, predicting, and understanding the impact of PCV7 on disease., Methods: A group-randomized, phase III efficacy trial of PCV7 was conducted among southwestern American Indian communities. Meningococcal conjugate vaccine against serogroup C was used as the control. After the trial was unblinded, we conducted a carriage study of participating communities to evaluate the impact of PCV7 on colonization among trial participants and their unvaccinated household members., Results: Adults and unvaccinated children aged <5 years living in households with a PCV7 vaccinee were less likely to be colonized with vaccine-type pneumococci (odds ratio [OR] for adults, 0.57; 95% confidence interval [CI], 0.33-0.99; OR for children, 0.57; 95% CI, 0.26-0.98) than were those living in a household with a control vaccinee. There was no difference for children aged 5-17 years. Decreases in vaccine-type carriage were offset by increases in carriage of nonvaccine types. Among adults living with a trial participant colonized with vaccine-type pneumococcus, those in the households randomized to receive PCV7 were less likely to be colonized with the same serotype than were those in the households randomized to receive the control vaccine (OR, 0.34; 95% CI, 0.11-0.99)., Conclusions: Vaccine-type pneumococcal carriage was lower among adults and unvaccinated children living with a PCV7 vaccinee. This is attributable to reduced exposure and reduced transmission when exposure occurs.

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.

Whereas members of the Navajo Nation are at high risk for diabetes mellitus, there are no recent published estimates of the burden of end-stage renal disease (ESRD), an important sequela of diabetes, on the Navajo Nation, a 16 million acre area in Arizona, New Mexico, and Utah with more than 200 000 tribal members. We used data from the US Renal Data System to estimate the prevalence and incidence of ESRD among Native American adults (>/=18 years) living on the Navajo Nation. For comparison, we estimated the prevalence and incidence of ESRD among all adults in the US, all Native American adults in the US, and Native American adults living in Arizona, New Mexico, Utah, and Colorado excluding those living on the Navajo Nation. The age-adjusted prevalence of ESRD in the Native American adults on the Navajo Nation was 0.63%, which was higher than in the US adults (0.19%, P<0.0001) and among the Native American adults in the US (0.36%, P<0.0001), but lower than among the other Native American adults in the Southwest (0.89%, P<0.0001). The age-adjusted incidence of ESRD in the Native American adults on the Navajo Nation was 0.11%, which was also higher than in the US adults (0.045%, P<0.0001) and among the Native American adults in the US (0.073%, P<0.0009), but lower than among the other Native American adults in the Southwest (0.17%, P<0.0003). The reasons behind these disparities merit further study.

For over a half of a century, Native American populations have participated in numerous studies regarding the epidemiology, prevention and treatment of infectious diseases. These studies have resulted in measures to prevent morbidity and mortality from many infectious diseases. The lessons learned from these studies and their resultant prevention or treatment interventions have been applied around the world, and have had a major impact in the reduction of global childhood morbidity and mortality.

Background: A 7-valent pneumococcal conjugate vaccine (PnCRM7) has been shown to be highly effective in preventing invasive pneumococcal disease. Pneumococcal conjugate vaccines also protect against nasopharyngeal carriage of vaccine serotypes, but the duration of protection against nasopharyngeal carriage is not known., Methods: A group-randomized efficacy trial of PnCRM7 (vaccine serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) was conducted on the Navajo and White Mountain Apache reservations from April 1997 to October 2000. A group C meningococcal conjugate vaccine was used as the control vaccine. Infants enrolled between 6 weeks and 7 months of age received 3 doses of vaccine 2 months apart and a fourth dose at 12-15 months of age. Vaccinees were enrolled in a nasopharyngeal carriage study from February 2001 to January 2002 to assess the duration of protection against pneumococcal carriage induced by PnCRM7., Results: We included 749 children in the analysis, including 468 children vaccinated with PnCRM7 and 281 children vaccinated with group C meningococcal conjugate vaccine. The median age was 3.3 years (range, 1-7 years), and the median time since last dose of study vaccine was 27 months (range, 12-48 months). Frequencies of overall pneumococcal carriage were similar among PnCRM7 and group C meningococcal conjugate vaccine recipients (63.9% vs. 60.5%, respectively). The absolute frequency of vaccine-type pneumococcal carriage was lower among PnCRM7 recipients (10.3%) than among controls (17.1%; P = .01). This reduction was offset by an increase of nonvaccine-type pneumococcal carriage among PnCRM7 recipients (39.2% vs. 29.8%; P = .01)., Conclusion: Community-wide PnCRM7 vaccination in infancy reduces the prevalence of vaccine-type carriage and increases the prevalence of nonvaccine-type carriage through at least 3 years of age.

Background: Rotavirus is a leading cause of childhood gastroenteritis and death worldwide., Methods: We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events., Results: The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent)., Conclusions: This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.), (Copyright 2006 Massachusetts Medical Society.)

Haemophilus influenzae type b (Hib) is responsible for significant morbidity and mortality worldwide, particularly in children under 5 years of age. In countries where the Hib conjugate vaccine is not routinely used, Hib is a leading cause of childhood pneumonia and meningitis. Routine use of the Hib conjugate vaccines has resulted in a remarkable decline in Hib disease in developed and developing countries. However, Hib conjugate vaccines are not routinely available in most developing countries, many of which have high burdens of Hib disease. This review outlines the pathogenesis and epidemiology of Hib disease, and the various options for prevention.

Background: Before the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, rates of H. influenzae disease among Navajo and White Mountain Apache (WMA) children were among the highest reported worldwide. Routine Hib vaccination has significantly reduced rates of Hib disease in these populations. As Hib disease rates decrease to very low levels, there are concerns that non-type b strains of H. influenzae may emerge as more prevalent causes of invasive disease in children., Methods: We reviewed population-based, active laboratory surveillance data from the period of 1988-2003 for invasive H. influenzae type a (Hia) disease among Navajo and WMA children aged <5 years. Clinical information on cases was collected by chart review. A sample of Hia isolates from Navajo children was typed by pulsed-field gel electrophoresis (PFGE)., Results: During 1988-2003, a total of 76 reported cases of invasive Hia disease occurred among Navajo and WMA children. The overall annual incidence was 20.2 cases per 100,000 population aged <5 years. There was no increase in Hia disease rates after Hib vaccination was introduced. The median age of patients was 12 months. Meningitis (50% of cases) was the most common presentation, followed by pneumonia (27.6%). Two children with Hia disease died. PFGE analysis revealed a limited genetic diversity of Hia strains in this population., Conclusions: Active surveillance data showed high rates of invasive Hia disease among Navajo and WMA children but no increase in the incidence after Hib vaccination was introduced. The presentation of Hia disease is similar to that of Hib disease in the prevaccine era.

High rates of preventable diseases such as pneumococcal disease occur among the Navajo despite their universal health insurance through the Indian Health Service. The objective of this study was to determine the proportion of Navajo adults vaccinated with pneumococcal polysaccharide vaccine and to examine key features of vaccination programs of the Navajo Indian Health Service. For this cross-sectional study, medical charts of Navajo patients with vaccine indications were randomly selected and reviewed to determine who had been vaccinated as of January 1, 1999. Among 480 Navajo>or=65 years old, 73% were vaccinated (95% confidence interval [CI]: 69%-77%). Among 111 Navajo 18-64 years old with vaccine indications, 54% were vaccinated (95% CI: 45% -63%). Vaccination programs utilized extensive public health nursing, home visits, standing orders, and "express lane" clinics. In spite of excellent delivery systems and universal healthcare, the proportion of Navajo persons vaccinated was still below the goals for Healthy People 2010 of having 90% of persons>or=65 years old vaccinated and 60% of high-risk persons 18-64 years old vaccinated.