Influenza antiviral treatment is recommended for all persons hospitalized with influenza virus infection. During the 2010-2011 influenza season, antiviral treatment of children and adults hospitalized with laboratory-confirmed influenza declined significantly compared to treatment during the 2009 pandemic (children: 56% versus 77%, p <0.01; adults 77% versus 82%, p<0.01).

BACKGROUND: Case-control studies evaluating post-licensure effectiveness of conjugate vaccines can be laborious and costly. We applied an indirect cohort method to evaluate the effectiveness of seven-valent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) and compared the results to the effectiveness measured using a standard case-control study conducted during the same time period. METHODS: IPD cases among children 2-59 months old were identified through the Active Bacterial Core surveillance system during 2001-2009. We used logistic regression to calculate the odds ratio of vaccination (versus no vaccination) among cases (PCV7-type IPD cases) and non-cases (non-PCV7-type IPD cases), controlling for the presence of underlying conditions. Vaccine effectiveness (VE) was calculated as one minus the adjusted odds ratio. RESULTS: Among 4225 IPD cases reported during 2001-2009, 2680 (63%) had serotype information and vaccine history. Effectiveness of ≥1 dose of PCV7 against PCV7-types was 88%(95% confidence interval (CI) 78-94%) among children with comorbid conditions and 97%(95% CI 92-98%) among healthy children. Among healthy children, VE was higher in 2001-2003 (97%, 95% CI 95-98%) compared to 2004-2009 (81%, 95% CI 64-90%). The annual estimates of VE in 2004-2009 showed great variability and wide confidence intervals due to the small number of PCV7-type cases. CONCLUSIONS: An indirect cohort design using IPD surveillance data confirms the findings of the case-control study and, therefore, appears suitable for estimating PCV7effectiveness. This method would be most useful shortly after vaccine introduction, and less useful in a setting of very high vaccine coverage and fewer vaccine-type cases.

BackgroundMany assumed high morbidity and mortality would accompany the emergence of MRSA USA300 infections as a cause of healthcare-associated infections (HAIs). We evaluated patients with invasive MRSA infections to assess differences in outcomes between infections caused by USA100 and USA300.MethodsPopulation-based data for invasive MRSA infections were used to identify two cohorts:(1) non-dialysis patients with central line-associated bloodstream infections (CLABSI); and (2) patients with community-onset pneumonia (PNEUMO) during 2005-2007 from 6 US metropolitan areas. Medical records of patients with confirmed MRSA USA100 or USA300 were reviewed. Logistic regression and, when appropriate, survival analysis was performed to evaluate mortality, early and late complications, and length of stay.ResultsA total of 236 and 100 patients were included in the CLABSI and PNEUMO cohorts, respectively. USA300 was the only independent predictor of early complications for PNEUMO patients (OR=2.6, P=.02). Independent predictors of CLABSI late complications included intensive care unit (ICU) admission before MRSA culture (aOR=2.1, P=.01) and Charlson comorbidity index (aOR=2.6; P=.003), but not strain type. PNEUMO patients were significantly more likely to die if they were older (P=.02), black (P<.001) or infected with USA100 strain (P=.02); while those with CLABSI were more likely to die if they were older (P<.001), had comorbidities (P<.001) or had an ICU admission before MRSA culture (P=.001).ConclusionsUSA300 was associated with early complications in PNEUMO patients. However, it was not associated with mortality for either PNEUMO or CLABSI patients. Concerns regarding higher mortality from HAIs caused by USA300 may not be warranted.

In response to pandemic (H1N1) 2009, data were collected on work status and industry of employment of 3,365 adults hospitalized with laboratory-confirmed influenza during the 2009-10 influenza season in the United States. The proportion of workers hospitalized for influenza was lower than their proportion in the general population, reflecting underlying protective characteristics of workers compared with nonworkers. The most commonly represented sectors were transportation and warehousing; administrative and support and waste management and remediation services; health care; and accommodation and food service.

Please cite this paper as: Jules et al.(2012) Estimating age-specific influenza-related hospitalization rates during the pandemic (H1N1) 2009 in Davidson Co, TN. Influenza and Other Respiratory Viruses DOI:. 10.1111/j.1750-2659.2012.00343.x. Background  In April 2009, a pandemic caused by a novel influenza strain, the A(H1N1)pdm09 virus, started. Few age-specific estimates of hospitalizations associated with the first year of circulation of the pandemic virus are available. Objectives  To estimate age-specific hospitalization rates associated with laboratory-confirmed A(H1N1)pdm09 virus in Davidson County, TN, from May 2009 to March 2010. Patients/methods  Two separate strategies were applied: capture-recapture and surveillance-sampling methods. For the capture-recapture estimates, we linked data collected via two independent prospective population-based surveillance systems: The Influenza Vaccine Effectiveness Network (Flu-VE) tested consenting county patients hospitalized with respiratory symptoms at selected hospitals using real-time reverse transcriptase polymerase chain reaction (rRT-PCR); the Emerging Infections Program identified county patients with positive influenza tests in all area hospitals. For the surveillance-sampling estimates, we applied the age-specific proportions of influenza-positive patients (from Flu-VE) to the number of acute respiratory illness hospitalizations obtained from the Tennessee Hospital Discharge Data system. Results  With capture-recapture, we estimated 0·89 (95% CI, 0·72-1·49), 0·62 (0·42-1·11), 1·78 (0·99-3·63), and 0·76 (0·50-1·76) hospitalizations per 1000 residents aged <5, 5-17, 18-49, and ≥50 years, respectively. Surveillance-sampling estimated rates were 0·78 (0·46-1·22), 0·32 (0·14-0·69), 0·99 (0·64-1·52), and 1·43 (0·80-2·48) hospitalizations per 1000 residents aged <5, 5-17, 18-49, and ≥50 years, respectively. In all age-groups combined, we estimated approximately 1 influenza-related hospitalization per 1000 residents. Conclusions  Two independent methods provided consistent results on the burden of pandemic virus in Davidson County and suggested that the overall incidence of A(H1N1)pdm09-associated hospitalization was 1 per 1000 county residents.

The metal-responsive transcription factor-1 (MTF-1, also termed MRE-binding transcription factor-1 or metal regulatory transcription factor-1) is a pluripotent transcriptional regulator involved in cellular adaptation to various stress conditions, primarily exposure to heavy metals but also to hypoxia or oxidative stress. MTF-1 is evolutionarily conserved from insects to humans and is the main activator of metallothionein genes, which encode small cysteine-rich proteins that can scavenge toxic heavy metals and free radicals. MTF-1 has been suggested to act as an intracellular metal sensor but evidence for direct metal sensing was scarce. Here we review recent advances in our understanding of MTF-1 regulation with a focus on the mechanism underlying heavy metal responsiveness and transcriptional activation mediated by mammalian or Drosophila MTF-1. This article is part of a Special Issue entitled: Cell Biology of Metals.

Typical enhancers of viral or cellular genes are approx. 100-400 bp long and contain several transcription factor binding sites. Previously we have shown that SV40 genomic DNA that lacks its own enhancer can be used as an "enhancer trap" since it re-acquires infectivity upon incorporation of heterologous enhancers. Here we show that SV40 infectivity can be restored with synthetic enhancers that are assembled by the host cell. We found that several oligonucleotides, co-transfected with enhancerless SV40 DNA into host cells, were incorporated into the viral genome via cellular DNA-end joining. The oligonucleotides tested included MREs (metal response elements), the binding site for the transcription factor MTF-1, which induces gene activity in response to heavy metals. These recombinant SV40 strains showed preferential growth on cells overloaded with zinc or cadmium. We also co-transfected enhancerless SV40 DNA with oligonucleotides corresponding to enhancer motifs of human and mouse cytomegalovirus (HCMV and MCMV). In contrast to SV40 wild type, the viruses with cytomegalovirus-derived patchwork enhancers strongly expressed T-antigen in human HEK293 cells, accompanied by viral DNA replication. Occasionally, we also observed the assembly of functional viral genomes by incorporation of bovine DNA fragments, an ingredient of the fetal calf serum in the medium. These fragments contained, among others, binding sites for AP-1 and CREB transcription factors. Taken together, our studies show that viruses with novel properties can be generated by intracellular incorporation of synthetic enhancer DNA motifs.

Background. Antibiotic postexposure prophylaxis (PEP) following pertussis exposure is recommended but has never been evaluated in healthcare personnel (HCP) vaccinated with acellular pertussis vaccine (Tdap).Methods. Tdap-vaccinated HCP were randomized to receive azithromycin PEP or no PEP following pertussis exposure. Acute and convalescent nasopharyngeal swabs and sera were obtained for pertussis testing by polymerase chain reaction (PCR) and anti-pertussis toxin (PT) immunoglobulin G, respectively. A nasopharyngeal aspirate was also collected for PCR and culture from subjects who reported respiratory symptoms within 21 days following identification of the exposure. Pertussis infection was defined as a positive culture or PCR, a 2-fold rise in anti-PT titer, or a single anti-PT titer of ≥94 enzyme-linked immunosorbent assay units/mL. Daily symptom monitoring without PEP was considered noninferior to PEP after pertussis exposure if the lower limit of the 1-sided 95% confidence interval (CI) for the reduction in pertussis was greater than -7%.Results. During 30 months of study, 86 subjects were randomized following a pertussis exposure. Using the predefined definition of infection, pertussis infection did not develop in 41 (97.6%) of 42 subjects who received azithromycin PEP and 38 (86.4%) of 44 subjects who did not receive PEP (absolute risk difference,-11.3%; lower bound of the 1-sided 95% CI,-20.6%; P =.81). However, no subject developed symptomatic pertussis confirmed with culture or a specific PCR assay, and possibly no subject developed subclinical pertussis infection based upon additional serologic testing.Conclusions. Using the predefined definition of pertussis infection, noninferiority for preventing pertussis following exposure was not demonstrated for daily symptom monitoring of Tdap-vaccinated HCP without PEP when compared with antibiotic PEP. However, the small number of exposed HCP warrants further study of this approach.Clinical Trial Registration. NCT00469274.

Background. Statins may have anti-inflammatory and immunomodulatory effects that could reduce the risk of mortality from influenza virus infections.Methods. The Centers for Disease Control and Prevention's Emerging Infections Program conducts active surveillance for persons hospitalized with laboratory-confirmed influenza in 59 counties in 10 states. We analyzed data for hospitalized adults during the 2007-2008 influenza season to evaluate the association between receiving statins and influenza-related death.Results. We identified 3043 patients hospitalized with laboratory-confirmed influenza, of whom 1013 (33.3%) received statins and 151 (5.0%) died within 30 days of their influenza test. Patients who received statins were more likely to be older, male, and white; to suffer from cardiovascular, metabolic, renal, and chronic lung disease; and to have been vaccinated against influenza that season. In a multivariable logistic regression model, administration of statins prior to or during hospitalization was associated with a protective odds of death (adjusted odds ratio, 0.59 [95% confidence interval,.38-.92]) when adjusting for age; race; cardiovascular, lung, and renal disease; influenza vaccination; and antiviral administration.Conclusions. Statin use may be associated with reduced mortality in patients hospitalized with influenza.