Lead is an environmental hazard that can cause serious harm to young children. Early childhood lead exposure can damage the brain and nervous system, slow growth and development, and cause hearing and speech problems (1). Screening for elevated blood lead levels (BLL) is essential for routine care of young children. At the onset of the COVID-19 pandemic, substantial disruptions to health care access occurred for routine, preventive care (2). At the onset of the pandemic (January–May 2020), 34% fewer U.S. children aged <6 years received blood lead level testing than during the same months in 2019 (3). The Chicago Department of Public Health (CDPH) characterized patterns of blood lead testing among young children in Chicago from the onset of the pandemic in 2019 through 2022.

The SARS-CoV-2 main protease (M(pro)) has been proven to be a highly effective target for therapeutic intervention, yet only one drug currently holds FDA approval status for this target. We were inspired by a series of publications emanating from the Jorgensen and Anderson groups describing the design of potent, non-peptidic, competitive SARS-CoV-2 M(pro) inhibitors, and we saw an opportunity to make several design modifications to improve the overall pharmacokinetic profile of these compounds without losing potency. To this end, we created a focused virtual library using reaction-based enumeration tools in the Schrödinger suite. These compounds were docked into the M(pro) active site and subsequently prioritized for synthesis based upon relative binding affinity values calculated by FEP+. Fourteen compounds were selected, synthesized, and evaluated both biochemically and in cell culture. Several of the synthesized compounds proved to be potent, competitive M(pro) inhibitors with improved metabolic stability profiles.

Abstract We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for “Unity-aligned” First Few X cases (FFX) and HHTIs published 1 December 2019 to 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review; 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2% to 90% (95% prediction interval: 3%–71%; I2 = 99.7%); I2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.

We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for 'Unity-aligned' First Few X cases (FFX) and HHTIs published between 1 December 2019 and 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review and 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2%-90% (95% prediction interval: 3%-71%; I2=99.7%); I2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

BACKGROUND: Healthcare workers have experienced high rates of morbidity and mortality from coronavirus disease 2019 (COVID-19). METHODS: A prospective cohort study was conducted in three Albanian hospitals between 19 February and 14 December 2021. All participants underwent polymerase chain reaction (PCR) and serological testing at enrolment, regular serology throughout, and PCR testing when symptomatic.Vaccine effectiveness (VE) against COVID-19 and against all severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections (symptomatic or asymptomatic) was estimated. VE was estimated using a Cox regression model, with vaccination status as a time-varying variable. FINDINGS: In total, 1504 HCWs were enrolled in this study; 70% had evidence of prior SARS-CoV-2 infection. VE was 65.1% [95% confidence interval (CI) 37.7-80.5] against COVID-19, 58.2% (95% CI 15.7-79.3) among participants without prior SARS-CoV-2 infection, and 73.6% (95% CI 24.3-90.8) among participants with prior SARS-CoV-2 infection. For BNT162b2 alone, VE was 69.5% (95% CI 44.5-83.2). During the period when the Delta variant was predominant, VE was 67.1% (95% CI 38.3-82.5). VE against SARS-CoV-2 infection for the full study period was 36.9% (95% CI 15.8-52.7). INTERPRETATION: This study found moderate primary series VE against COVID-19 among healthcare workers in Albania. These results support the continued promotion of COVID-19 vaccination in Albania, and highlight the benefits of vaccination in populations with high levels of prior infection.

This article describes perceptions of the COVID-19 vaccine among US adults, and reports that younger adults, women, non-Hispanic Black adults, adults living in nonmetropolitan areas, adults with less education and income, and adults without health insurance have the highest estimates of nonintent to receive vaccination; due to concerns about side effects and safety of the COVID-19 vaccine, lack of trust in the government, and concern that COVID-19 vaccines were developed too quickly are the primary reasons for deferring vaccination. Solid organ transplant candidates and recipients may harbor similar concerns about vaccination, and further, may rely more heavily on herd immunity for protection from COVID-19, since the efficacy of COVID-19 vaccination among immunosuppressed individuals remains ill-defined. Promoting vaccine confidence among transplant candidates, transplant recipients, and the general population will thus be critical to preventing spread of COVID-19.

Background: Healthcare workers (HCWs) have been disproportionally affected by COVID-19. We investigated factors associated with two- and three-dose COVID-19 vaccine uptake and SARS-CoV-2 seropositivity among 1504 HCWs enrolled (19 February-7 May 2021) in a prospective COVID-19 vaccine effectiveness cohort in Albania through a secondary analysis. Methods: We collected sociodemographic, occupational, health, prior SARS-CoV-2 infection, and COVID-19 vaccination data from all HCWs at enrollment. Vaccination status was assessed weekly through June 2022. A serum sample was collected from all participants at enrollment and tested for anti-spike SARS-CoV-2 antibodies. We analyzed HCWs characteristics and outcomes using multivariable logistic regression. Findings: By 11 June 2022, 1337 (88.9%) HCWs had received two COVID-19 vaccine doses, of whom 255 (19.1%) received a booster. Factors significantly associated with receiving three doses (adjusted odds ratio (aOR), 95% CIs) were being ≥35 years (35–44 years: 1.76 (1.05–2.97); 45–54 years: 3.11 (1.92–5.05); ≥55 years: 3.38 (2.04–5.59)) and vaccinated against influenza (1.78; 1.20–2.64). Booster dose receipt was lower among females (0.58; 0.41–0.81), previously infected (0.67; 0.48–0.93), nurses and midwives (0.31; 0.22–0.45), and support staff (0.19; 0.11–0.32). Overall 1076 (72%) were SARS-CoV-2 seropositive at enrollment. Nurses and midwifes (1.45; 1.05–2.02), support staff (1.57; 1.03–2.41), and HCWs performing aerosol-generating procedures (AGPs) (1.40; 1.01–1.94) had higher odds of being seropositive, while smokers had reduced odds (0.55; 0.40–0.75). Interpretation: In a large cohort of Albanian HCWs, COVID-19 vaccine booster dose uptake was very low, particularly among younger, female, and non-physician HCWs, despite evidence demonstrating the added benefit of boosters in preventing infection and severe disease. Reasons behind these disparities should be explored to develop targeted strategies in order to promote uptake in this critical population. SARS-CoV-2 seroprevalence was higher among non-physicians and HCWs performing APGs. A better understanding of the factors contributing to these differences is needed to inform interventions that could reduce infections in the future. Funding: This study was funded by the Task Force for Global Health (US Centers for Disease Control (CDC) cooperative agreement # NU51IP000873) and the World Health Organization, Regional Office for Europe. © 2023 World Health Organization

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (73%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (07%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (914%), moxifloxacin (916%) and ethambutol (933%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

INTRODUCTION: Critical questions remain about COVID-19 vaccine effectiveness (VE) in real-world settings, particularly in middle-income countries. We describe a study protocol to evaluate COVID-19 VE in preventing laboratory-confirmed SARS-CoV-2 infection in health workers (HWs) in Albania, an upper-middle-income country. METHODS AND ANALYSIS: In this 12-month prospective cohort study, we enrolled HWs at three hospitals in Albania. HWs are vaccinated through the routine COVID-19 vaccine campaign. Participants completed a baseline survey about demographics, clinical comorbidities, and infection risk behaviours. Baseline serology samples were also collected and tested against the SARS-CoV-2 spike protein, and respiratory swabs were collected and tested for SARS-CoV-2 by RT-PCR. Participants complete weekly symptom questionnaires and symptomatic participants have a respiratory swab collected, which is tested for SARS-CoV-2. At 3, 6, 9 months and 12 months of the study, serology will be collected and tested for antibodies against the SARS-CoV-2 nucleocapsid protein and spike protein. VE will be estimated using a piecewise proportional hazards model (VE=1-HR). BASELINE DATA: From February to May 2021, 1504 HWs were enrolled. The median age was 44 (range: 22-71) and 78% were female. At enrolment, 72% of participants were seropositive for SARS-CoV-2. 56% of participants were vaccinated with one dose, of whom 98% received their first shot within 4days of enrolment. All HWs received the Pfizer BNT162b2 mRNA COVID-19 vaccine. ETHICS AND DISSEMINATION: The study protocol and procedures were reviewed and approved by the WHO Ethical Review Board, reference number CERC.0097A, and the Albanian Institute of Public Health Ethical Review Board, reference number 156. All participants have provided written informed consent to participate in this study. The primary results of this study will be published in a peer-reviewed journal at the time of completion. TRIAL REGISTRATION NUMBER: NCT04811391.

Outcomes and costs of coronavirus disease (COVID-19) contact tracing are limited. During March-May 2020, we constructed transmission chains from 184 index cases and 1,499 contacts in Salt Lake County, Utah, USA, to assess outcomes and estimate staff time and salaries. We estimated 1,102 staff hours and $29,234 spent investigating index cases and contacts. Among contacts, 374 (25%) had COVID-19; secondary case detection rate was ≈31% among first-generation contacts, ≈16% among second- and third-generation contacts, and ≈12% among fourth-, fifth-, and sixth-generation contacts. At initial interview, 51% (187/370) of contacts were COVID-19-positive; 35% (98/277) became positive during 14-day quarantine. Median time from symptom onset to investigation was 7 days for index cases and 4 days for first-generation contacts. Contact tracing reduced the number of cases between contact generations and time between symptom onset and investigation but required substantial resources. Our findings can help jurisdictions allocate resources for contact tracing.

As of February 8, 2021, 59.3 million doses of vaccines to prevent coronavirus disease 2019 (COVID-19) had been distributed in the United States, and 31.6 million persons had received at least 1 dose of the COVID-19 vaccine (1). However, national polls conducted before vaccine distribution began suggested that many persons were hesitant to receive COVID-19 vaccination (2). To examine perceptions toward COVID-19 vaccine and intentions to be vaccinated, in September and December 2020, CDC conducted household panel surveys among a representative sample of U.S. adults. From September to December, vaccination intent (defined as being absolutely certain or very likely to be vaccinated) increased overall (from 39.4% to 49.1%); the largest increase occurred among adults aged ≥65 years. If defined as being absolutely certain, very likely, or somewhat likely to be vaccinated, vaccination intent increased overall from September (61.9%) to December (68.0%). Vaccination nonintent (defined as not intending to receive a COVID-19 vaccination) decreased among all adults (from 38.1% to 32.1%) and among most sociodemographic groups. Younger adults, women, non-Hispanic Black (Black) persons, adults living in nonmetropolitan areas, and adults with lower educational attainment, with lower income, and without health insurance were most likely to report lack of intent to receive COVID-19 vaccine. Intent to receive COVID-19 vaccine increased among adults aged ≥65 years by 17.1 percentage points (from 49.1% to 66.2%), among essential workers by 8.8 points (from 37.1% to 45.9%), and among adults aged 18-64 years with underlying medical conditions by 5.3 points (from 36.5% to 41.8%). Although confidence in COVID-19 vaccines increased during September-December 2020 in the United States, additional efforts to tailor messages and implement strategies to further increase the public's confidence, overall and within specific subpopulations, are needed. Ensuring high and equitable vaccination coverage across all populations is important to prevent the spread of COVID-19 and mitigate the impact of the pandemic.

Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (β-CTX) in blood have been designated as reference bone turnover markers in osteoporosis by the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The IFCC Committee on Bone Metabolism (C-BM) has examined current commercial assays and performed a multicentre study to examine the agreement between assays for PINP and β-CTX in serum and plasma. The results of these studies will inform our work towards the harmonization of PINP assays and the standardization of β-CTX assays in blood, with the development of common calibrators and reference measurement procedures in collaboration with the reagent manufacturing industry. Successful achievement of these goals will help develop universally acceptable practice guidelines for the management of osteoporosis with the inclusion of common reference intervals and treatment targets for PINP and β-CTX.

International Federation of Clinical Chemistry and Laboratory Medicine and The International Osteoporosis Foundation Joint Committee on Bone Metabolism believes that the harmonization of PINP assays is an achievable and practical goal. INTRODUCTION: In order to examine the agreement between current commercial assays, a multi-center study was performed for PINP in serum and plasma. METHODS: The automated methods for PINP (Roche Cobas and IDS iSYS) gave similar results. A significant proportional bias was observed between the two automated assays and the Orion radioimmunoassay (RIA) for PINP. RESULTS: Results from other published studies comparing PINP values among these three assays broadly support our findings. Taken together, these results confirm that harmonized PINP measurements exist between the two automated assays (Roche Cobas and IDS iSYS) when the eGFR is > 30 mL/min/1.73m(2), but a significant bias exists between the Orion RIA and the two automated assays. CONCLUSION: Therefore, in subjects with normal renal function, PINP results reported by the Roche Cobas and IDS iSYS assays are similar and may be used interchangeably, and similar reference intervals and treatment targets could be applied for the two automated assays. Harmonization between the automated assays and the RIA is potentially possible with the use of common calibrators and the development of a reference method for PINP. This should also help ensure that any new commercial assay developed in the future will attain similar results. IOF and IFCC are committed to working together towards this goal with the cooperation of the reagent manufacturing industry.

BACKGROUND: Long work hours may be associated with adverse outcomes, including cardiovascular disease. We investigated cross-sectional associations of current work hours with coronary artery calcification (CAC). METHODS: Participants (n = 3046; 54.6% men) were from the Multi-Ethnic Study of Atherosclerosis. The number of hours worked in all jobs was obtained by questionnaire and CAC from computed tomography. The probability of a positive CAC score was modeled using log-binomial regression. Positive scores were modeled using analysis of covariance and linear regression. RESULTS: Sixteen percent of the sample worked over 50 hours per week. The overall geometric mean CAC score was 5.2 +/- 10.0; 40% had positive scores. In fully-adjusted models, prevalence ratios were less than 40 hours: 1.00 (confidence interval [CI]: 0.88-1.12), 40:(ref), 41 to 49:1.13 (CI: 0.99-1.30), and >/=50:1.07 (CI: 0.94-1.23) and longer current work hours were not associated with higher mean CAC scores (<40:56.0 [CI: 47.3-66.3], 40:57.8 [CI: 45.6-73.3], 41 to 49:59.2 [CI: 45.2-77.6], >/=50:51.2 [CI: 40.5-64.8]; P = .686). CONCLUSIONS: Current work hours were not independently associated with CAC scores.

During 2017, CDC received 1,521 reports of acute hepatitis A virus (HAV) infections from California, Kentucky, Michigan, and Utah; the majority of infections were among persons reporting injection or noninjection drug use or homelessness. Investigations conducted by local and state health departments indicated that direct person-to-person transmission of HAV infections was occurring, differing from other recent, large HAV outbreaks attributed to consumption of contaminated commercial food products. Outbreaks with direct HAV transmission among persons reporting drug use or homelessness signals a shift in HAV infection epidemiology in the United States, and vaccination of these populations at high risk can prevent future outbreaks.

The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.

The "Know Hepatitis B" campaign was the first national, multilingual communications campaign to promote testing for hepatitis B virus (HBV) among Asian Americans and Pacific Islanders (AAPIs). This population comprises fewer than 5% of the total U.S. population but accounts for more than half of the up to 1.4 million Americans living with chronic HBV infection. To address this health disparity with a national campaign, CDC partnered with Hep B United, a national coalition of community-based partners working to educate AAPIs about hepatitis B and the need for testing. Guided by formative research, the "Know Hepatitis B" campaign was implemented in 2013 with a two-pronged communications strategy. CDC used available Chinese, Korean, and Vietnamese media outlets on a national level and relied on Hep B United to incorporate campaign materials into educational efforts at the local level. This partnership helped facilitate HBV testing among the priority population.

In 2012, CDC issued recommendations calling for those born between 1945 and 1965, or baby boomers, to get tested for the hepatitis C virus. To help implement this recommendation, CDC developed "Know More Hepatitis," a multimedia national education campaign. Guided by behavioral science theories and formative research, the campaign used multiple strategies to reach baby boomers and health-care providers with messages encouraging baby boomers to get tested for hepatitis C. With a limited campaign budget, the "Know More Hepatitis" campaign relied mostly on donated time and space from broadcast and print outlets. Donated placements totaled approximately $14.7 million, which reflected a more than 12-to-1 return on the campaign investment. This effort was supplemented with a small, paid digital advertising campaign. Combining audience impressions from both paid and donated campaign efforts resulted in more than 1.2 billion audience impressions.

BACKGROUND: In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was licensed and recommended in the USA for prevention of invasive pneumococcal disease in children. Licensure was based on immunogenicity data comparing PCV13 with the earlier seven-valent formulation. Because clinical endpoints were not assessed for the new antigens, we did a postlicensure matched case-control study to assess vaccine effectiveness. METHODS: Cases in children aged 2-59 months were identified through active surveillance in 13 sites. Controls were identified via birth registries and matched to cases by age and postal (zip) code. The primary objective was the vaccine effectiveness of at least one dose against the 13 serotypes included in PCV13. Secondary objectives included vaccine effectiveness against all-cause invasive pneumococcal disease, against antibiotic non-susceptible invasive pneumococcal disease, and among children with and without underlying conditions. Vaccine effectiveness was calculated as (1 - matched odds ratio) x 100%. FINDINGS: We enrolled 722 children with invasive pneumococcal disease and 2991 controls; PCV13 serotype cases (217 [30%]) included most commonly serotypes 19A (128 [18%]), 7F (32 [4%]), and 3 (43 [6%]). Vaccine effectiveness against PCV13 serotypes was 86.0% (95% CI 75.5 to 92.3), driven by serotypes 19A and 7F, for which vaccine effectiveness was 85.6% (95% CI 70.6 to 93.5) and 96.5% (82.7 to 100), respectively. We also identified statistically significant effectiveness against serotype 3 (79.5%, 95% CI 30.3 to 94.8) and against antibiotic non-susceptible invasive pneumococcal disease (65.6%, 44.9 to 78.7). Vaccine effectiveness against all-cause invasive pneumococcal disease was 60.2% (95% CI 46.8 to 70.3). Vaccine effectiveness was similar among children with (81.4%, 95% CI 45.4 to 93.6) and without (85.8%, 74.9 to 91.9) underlying conditions. INTERPRETATION: PCV13 appears highly effective against invasive pneumococcal disease among children in the USA in the context of routine and catch-up schedules, although some new vaccine antigens could not be assessed. PCV13 immunisation provides a robust strategy for combating pneumococcal antimicrobial resistance. FUNDING: Centers for Disease Control and Prevention.

OBJECTIVE: This study examines the impact of Family Healthware™ on communication behaviors; specifically, communication with family members and health care providers about family health history. METHODS: A total of 3786 participants were enrolled in the Family Healthware™ Impact Trial (FHITr) in the United States from 2005-7. The trial employed a two-arm cluster-randomized design, with primary care practices serving as the unit of randomization. Using generalized estimating equations (GEE), analyses focused on communication behaviors at 6month follow-up, adjusting for age, site and practice clustering. RESULTS: A significant interaction was observed between study arm and baseline communication status for the family communication outcomes (p's<.01), indicating that intervention had effects of different magnitude between those already communicating at baseline and those who were not. Among participants who were not communicating at baseline, intervention participants had higher odds of communicating with family members about family history risk (OR=1.24, p=0.042) and actively collecting family history information at follow-up (OR=2.67, p=0.026). Family Healthware™ did not have a significant effect on family communication among those already communicating at baseline, or on provider communication, regardless of baseline communication status. Greater communication was observed among those at increased familial risk for a greater number of diseases. CONCLUSION: Family Healthware™ prompted more communication about family history with family members, among those who were not previously communicating. Efforts are needed to identify approaches to encourage greater sharing of family history information, particularly with health care providers.

Vervets, also known as African green monkeys, are a nonhuman primate species widely used in biomedical research. However, there are currently few references available describing techniques and rates of success for pair-housing this species. We present data from four cohorts of vervets from three different facilities: (i) the Wake Forest Vervet Research Colony (VRC; n = 72 female pairs, n= 52 male pairs), (ii) the University of Louisiana at Lafayette-New Iberia Research Center (UL-NIRC; n = 57 female pairs, n = 54 male pairs), (iii) the Tulane National Primate Research Center (TNRPC; n = 18 male pairs), and (iv) a cohort of imported males (n = 18 pairs) at Wake Forest. Compatibility was measured at 14, 30, and 60 days following introduction. Success rates for pair-housing at 14 days ranged from 96% to 98% for females and 96% to 100% for males at the VRC and UL-NIRC but were lower in the smaller imported male cohorts (TNPRC: 50%; WF: 28%). Among the UL-NIRC cohort and VRC male cohort, most of the pair separations after 14 days were due to reasons unrelated to social incompatibility. In contrast, a large proportion of TNPRC and imported male pairs successful at 14 days required separation within 60 days due to incompatibility. Multiple logistic regressions were performed using cohort, mean age of pair and weight difference between pair-mates as potential predictors of compatibility at 14 days. All three predicted the 14-day outcome in males but not females. A separate analysis in the VRC cohort found no evidence that prior familiarity in a group setting influenced outcomes. Variations in success rates across cohorts may have been influenced by introduction methodology. Behavioral differences between vervets and macaques, coupled with our findings, lead us to theorize that the gradual introduction techniques commonly implemented to pair house macaques may not be beneficial or suitable for this species.

BACKGROUND: Studies in the literature have indicated that the timing of seasonal influenza epidemic varies across latitude, suggesting the involvement of meteorological and environmental conditions in the transmission of influenza. In this study, we investigated the link between meteorological parameters and influenza activity in 9 sub-national areas with temperate and subtropical climates: Berlin (Germany), Ljubljana (Slovenia), Castile and Leon (Spain) and all 6 districts in Israel. METHODS: We estimated weekly influenza-associated influenza-like-illness (ILI) or Acute Respiratory Infection (ARI) incidence to represent influenza activity using data from each country's sentinel surveillance during 2000-2011 (Spain) and 2006-2011 (all others). Meteorological data was obtained from ground stations, satellite and assimilated data. Two generalized additive models (GAM) were developed, with one using specific humidity as a covariate and another using minimum temperature. Precipitation and solar radiation were included as additional covariates in both models. The models were adjusted for previous weeks' influenza activity, and were trained separately for each study location. RESULTS: Influenza activity was inversely associated (p<0.05) with specific humidity in all locations. Minimum temperature was inversely associated with influenza in all 3 temperate locations, but not in all subtropical locations. Inverse associations between influenza and solar radiation were found in most locations. Associations with precipitation were location-dependent and inconclusive. We used the models to estimate influenza activity a week ahead for the 2010/2011 period which was not used in training the models. With exception of Ljubljana and Israel's Haifa District, the models could closely follow the observed data especially during the start and the end of epidemic period. In these locations, correlation coefficients between the observed and estimated ranged between 0.55 to 0.91and the model-estimated influenza peaks were within 3 weeks from the observations. CONCLUSION: Our study demonstrated the significant link between specific humidity and influenza activity across temperate and subtropical climates, and that inclusion of meteorological parameters in the surveillance system may further our understanding of influenza transmission patterns.

BACKGROUND: In 2000, seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the USA and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and moderate increases in non-PCV7 type IPD. In 2010, PCV13 replaced PCV7 in the US immunisation schedule. We aimed to assess the effect of use of PCV13 in children on IPD in children and adults in the USA. METHODS: We used laboratory-based and population-based data on incidence of IPD from the Active Bacterial Core surveillance (part of the Centers for Disease Control and Prevention's Emerging Infections Program) in a time-series model to compare rates of IPD before and after the introduction of PCV13. Cases of IPD between July 1, 2004, and June 30, 2013, were classified as being caused by the PCV13 serotypes against which PCV7 has no effect (PCV13 minus PCV7). In a time-series model, we used an expected outcomes approach to compare the reported incidence of IPD to that which would have been expected if PCV13 had not replaced PCV7. FINDINGS: Compared with incidence expected among children younger than 5 years if PCV7 alone had been continued, incidence of IPD overall declined by 64% (95% interval estimate [95% IE] 59-68) and IPD caused by PCV13 minus PCV7 serotypes declined by 93% (91-94), by July, 2012, to June, 2013. Among adults, incidence of IPD overall also declined by 12-32% and IPD caused by PCV13 minus PCV7 type IPD declined by 58-72%, depending on age. We estimated that over 30 000 cases of IPD and 3000 deaths were averted in the first 3 years after the introduction of PCV13. INTERPRETATION: PCV13 reduced IPD across all age groups when used routinely in children in the USA. These findings provide reassurance that, similar to PCV7, PCVs with additional serotypes can also prevent transmission to unvaccinated populations. FUNDING: Centers for Disease Control and Prevention.

BACKGROUND: A clinical trial of mass azithromycin distributions for trachoma created a convenient experiment to test the hypothesis that antibiotic use selects for clonal expansion of pre-existing resistant bacterial strains. METHODS: Mass azithromycin was distributed to 12 communities in Ethiopia every 3 months for 1 year. A random sample of 10 children aged 0-9 years from each community was monitored with nasopharyngeal swabs before mass azithromycin distributions and after 4 mass treatments; S. pneumoniae was isolated and multilocus sequence typing performed. RESULTS: Of 82 pneumococcal isolates identified before treatment, 4 (5%) exhibited azithromycin resistance, representing 3 different sequence types (STs): 177, 6449, and 6494. The proportion of isolates that were classified as one of these 3 STs and were resistant to azithromycin increased after 4 mass azithromycin treatments (14 of 96 isolates; 15%; P=0.04). Using a classification index, we found evidence for a relationship between ST and macrolide resistance after mass treatments (P<0.0001). The diversity of STs-as calculated by the unbiased Simpson's index-decreased significantly after mass azithromycin treatment (P=0.045). CONCLUSIONS: Resistant clones present before mass azithromycin treatments increased in frequency after treatment, consistent with the theory that antibiotic selection pressure results in clonal expansion of existing resistant strains.

BACKGROUND: Limited data are available from Central and Eastern Europe on risk factors for severe complications of influenza. Such data are essential to prioritize prevention and treatment resources and to adapt influenza vaccination recommendations. OBJECTIVES: To use sentinel surveillance data to identify risk factors for fatal outcomes among hospitalized patients with severe acute respiratory infections (SARI) and among hospitalized patients with laboratory-confirmed influenza. METHODS: Retrospective analysis of case-based surveillance data collected from sentinel hospitals in Romania during the 2009/2010 and 2010/2011 winter influenza seasons was performed to evaluate risk factors for fatal outcomes using multivariate logistic regression. RESULTS: During 2009/2010 and 2010/2011, sentinel hospitals reported 661 SARI patients of which 230 (35%) tested positive for influenza. In the multivariate analyses, infection with influenza A(H1N1)pdm09 was the strongest risk factor for death among hospitalized SARI patients (OR: 6.6; 95% CI: 3.3-13.1). Among patients positive for influenza A(H1N1)pdm09 virus infection (n = 148), being pregnant (OR: 7.1; 95% CI: 1.6-31.2), clinically obese (OR: 2.9;95% CI: 1.6-31.2), and having an immunocompromising condition (OR: 3.7;95% CI: 1.1-13.4) were significantly associated with fatal outcomes. CONCLUSION: These findings are consistent with several other investigations of risk factors associated with influenza A(H1N1)pdm09 virus infections. They also support the more recent 2012 recommendations by the WHO Strategic Advisory Group of Experts on Immunization (SAGE) that pregnant women are an important risk group for influenza vaccination. Ongoing sentinel surveillance can be useful tool to monitor risk factors for complications of influenza virus infections during each influenza season, and pandemics as well.

BACKGROUND: After introduction of pneumococcal conjugate vaccine in the U.S. in 2000, increases in antibiotic nonsusceptible non-vaccine serotypes were observed. We sought to understand whether these increases were driven primarily by vaccine or antibiotic use. METHODS: Using active surveillance data, we evaluated geographic and temporal differences in serotype distribution and within-serotype nonsusceptibility during 2000-2009. We compared the proportions of nonsusceptibility to penicillin and erythromycin by study site after standardizing differences across time, place, and serotype by regressing standardized versus crude proportions. A regression slope (RS) approaching zero indicates greater importance of the standardizing factor. RESULTS: We evaluated 31,506 isolates. During 2000-2006, geographic differences in nonsusceptibility were better explained by within-serotype prevalence of nonsusceptibility (RS 0.32, 95%CI 0.08-0.55 for penicillin) than by geographic differences in serotype distribution (RS 0.71, 95%CI 0.44-0.97). From 2007-2009, differences in serotype distribution became more important for penicillin (within-serotype RS 0.52, 95%CI 0.11-0.93; serotype distribution RS 0.57, 95%CI 0.14-1.0). CONCLUSIONS: Differential nonsusceptibility, within individual serotypes, accounts for most geographic variation in nonsusceptibility, suggesting that selective pressure from antibiotic use, rather than differences in serotype distribution, mainly determines nonsusceptibility patterns. Recent trends suggest geographic differences in serotype distribution may be starting to affect the prevalence of nonsusceptibility, possibly due to the decrease in the number of nonsusceptible serotypes.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk of illness and death from invasive pneumococcal disease (IPD). The introduction in 2000 of the 7-valent pneumococcal conjugate vaccine (PCV7) and penicillin prophylaxis for children with SCD has greatly reduced the incidence of IPD in this population. However, a recent report suggested an increase in cases of IPD in children with SCD. METHODS: Using data from Active Bacterial Core Surveillance (ABCs), we analyzed trends in hospitalizations, mortality, and serotype among children with SCD compared with other children. We used neonatal screening data to estimate SCD population denominators for each ABCs site. RESULTS: From 1998-2009, 3,069 cases of IPD occurred among African-American children less than 18 years of age in the ABCs catchment area. Of these, 127 (4.1%) had SCD identified by medical chart review and 185 (6.0%) had one or more IPD risk factors, excluding SCD. Rates of IPD among children with SCD declined by 53% (1,118 versus 530 per 100,000) while the overall rates among African-American children declined by 74% (54 to 14 per 100,000). For all time periods, children with SCD and IPD were more likely to be hospitalized (84%-92% versus 31%-56%) and more likely to die (6%-17% versus 1%-2%) than children with no risk factors. CONCLUSIONS: While the rate of IPD in children with SCD has dropped dramatically since PCV7 introduction, the rate of IPD in children with SCD remains higher than that of the general population of African-American children, pointing to the need for more effective prevention efforts to prevent IPD in children with SCD.

Microsporidia are increasingly recognized as opportunistic pathogens in immunocompromised organ transplant recipients (OTR). Disseminated infection due to Encephalitozoon sp. is reported mainly in human immunodeficiency virus (HIV)-positive patients and rarely in HIV-negative OTR. The clinical spectrum ranges from keratoconjunctivitis, to pneumonitis, to acute kidney injury. The kidney is a common site for disseminated infection; however, specialized techniques are required for definitive diagnosis. We report the first case of disseminated Encephalitozoon cuniculi infection in an HIV-negative lung transplant recipient diagnosed on renal biopsy. Five months after transplant, he presented with fever and a lung infiltrate and developed acute kidney injury. Renal biopsy showed granulomatous interstitial nephritis with gram-positive rod-shaped organisms with a "belt-like stripe" in tubular epithelial cells. Electron microscopy, polymerase chain reaction, and mammalian cell cultures of the urine sediment confirmed E. cuniculi infection. Retrospective review of a previous lung biopsy showed similar organisms. On the basis of electron microscopy findings, the patient was treated with albendazole, and immunosuppressive therapy was reduced. However, the patient expired due to Aspergillus pneumonia and disseminated E. cuniculi infection. Microsporidia should be considered in cases of fever of unknown origin and/or multiorgan infection in HIV-negative OTR when other causes have been excluded, as successful treatment requires early detection.

BACKGROUND: There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. METHODS: We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. RESULTS: The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P<0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (<10%), "intermediate" (10% to <20%), and "high" (≥20%) (P<0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of ≥20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. CONCLUSIONS: In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.).

Hepatitis C virus (HCV) infection is a complex public health problem, characterized by a high prevalence of chronic infection, an increasing burden of HCV-associated disease, low rates of testing and treatment, and the prospect of increasing incidence associated with the epidemic of injection drug use. Three-quarters of chronic HCV infections occur among persons born from 1945 through 1965. Prevention efforts are complicated by limited knowledge among health care professionals, persons at risk and in the public at large. At the Centers for Disease Control and Prevention, efforts to improve primary and secondary prevention effectiveness center on policy development, education and training initiatives, and applied research. This report provides a brief overview of some of these efforts, including the development of testing recommendations for the 1945-1965 birth cohort, research and evaluation studies in settings where persons who inject drugs receive services, and a national viral hepatitis education campaign that targets health care professionals, the public, and persons at risk.