Effects of Multi-Month Dispensing on Clinical Outcomes: Retrospective Cohort Analysis Conducted in Kenya.

Multi-month dispensing (MMD) has been widely adopted by national HIV programs as a key strategy for improving the quality of HIV care and treatment services while meeting the unique needs of diverse client populations. We assessed the clinical outcomes of clients receiving MMD in Kenya by conducting a retrospective cohort study using routine programmatic data in 32 government health facilities in Kenya. We included clients who were eligible for multi-month antiretroviral therapy (ART) dispensing for ≥ 3 months (≥ 3MMD) according to national guidelines. The primary exposure was enrollment into ≥ 3MMD. The outcomes were lost to follow-up (LTFU) and viral rebound. Multilevel modified-Poisson regression models with robust standard errors were used to compare clinical outcomes between clients enrolled in ≥ 3MMD and those receiving ART dispensing for less than 3 months (< 3MMD). A total of 3,501 clients eligible for ≥ 3MMD were included in the analysis, of whom 65% were enrolled in ≥ 3MMD at entry into the cohort. There was no difference in LTFU of ≥ 180 days between the two types of care (aRR 1.1, 95% CI 0.7-1.6), while ≥ 3MMD was protective for viral rebound (aRR 0.1 95% CI 0.0-0.2). As more diverse client-focused service delivery models are being implemented, robust evaluations are essential to guide the implementation, monitor progress, and assess acceptability and effectiveness to deliver optimal people-centered care.

Serum from patients with asthma potentiates macrophage phagocytosis and human mesenchymal stromal cell therapy in experimental allergic asthma.

BACKGROUND/AIMS: Although several studies have demonstrated that mesenchymal stromal cells (MSCs) exhibit beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been controversial. Recent evidence has shown that MSCs modify their in vivo immunomodulatory actions depending on the specific inflammatory environment encountered. Accordingly, we assessed whether the therapeutic properties of human mesenchymal stromal cells (hMSCs) could be potentiated by conditioning these cells with serum (hMSC-serum) obtained from patients with asthma and then transplanted in an experimental model of house dust mite (HDM)-induced allergic asthma. METHODS: hMSC and hMSC-serum were administered intratracheally 24 h after the final HDM challenge. hMSC viability and inflammatory mediator production, lung mechanics and histology, bronchoalveolar lavage fluid (BALF) cellularity and biomarker levels, mitochondrial structure and function as well as macrophage polarization and phagocytic capacity were assessed. RESULTS: Serum preconditioning led to: (i) increased hMSC apoptosis and expression of transforming growth factor-ß, interleukin (IL)-10, tumor necrosis factor-α-stimulated gene 6 protein and indoleamine 2,3-dioxygenase-1; (ii) fission and reduction of the intrinsic respiratory capacity of mitochondria; and (iii) polarization of macrophages to M2 phenotype, which may be associated with a greater percentage of hMSCs phagocytosed by macrophages. Compared with mice receiving hMSCs, administration of hMSC-serum led to further reduction of collagen fiber content, eotaxin levels, total and differential cellularity and increased IL-10 levels in BALF, improving lung mechanics. hMSC-serum promoted greater M2 macrophage polarization as well as macrophage phagocytosis, mainly of apoptotic hMSCs. CONCLUSIONS: Serum from patients with asthma led to a greater percentage of hMSCs phagocytosed by macrophages and triggered immunomodulatory responses, resulting in further reductions in both inflammation and remodeling compared with non-preconditioned hMSCs.

Scale-up of HIV index testing in an urban population: Experiences and achievements from Nairobi County, Kenya.

OBJECTIVE: To describe the implementation strategies of the index testing program across Nairobi County in Kenya, assess outcomes along the HIV index testing cascade (acceptance, elicitation ratio, HIV positivity and linkage to treatment), and assess annual changes along the HIV index testing cascade during the first 2 years of implementation. METHODS: Retrospective analysis of programmatic aggregate data collected from October 2017 to September 2019 after the roll-out of index testing services in 48 health facilities in Nairobi County. Proportions and ratios were calculated for acceptance, elicitation ratio, testing uptake and HIV positivity. We compared these outcomes between years using a chi-squared test, Fisher's exact test or Wilcoxon sign test, and we assessed trends using the Mann-Kendall test. RESULTS: Testing among eligible partners increased from 42.4% (1471/3470) to 74.9% (6114/8159) in the general population, and the positivity yield remained high across both years (25.2% in year 1 and 24.1% in year 2). Index testing positivity yield remained significantly higher than other testing modalities (24.3% vs. 1.3%, p < 0.001). The contribution of index testing services to the total number of HIV-positive individuals identified increased from 7.5% in the first year to 28.6% in the second year (p < 0.001). More men were tested, but the positivity yield was higher among women (30.0%) and those aged 50 years or older (32.4%). Testing eligible partners in key populations (KPs) decreased from 52.4% (183/349) to 40.7% (109/268) (p = 0.674); however, the HIV positivity yield increased from 8.6% to 23.9% (p < 0.001) by the second year of implementation. The HIV positivity yield from index testing remained higher than other testing modalities (14% vs. 0.9%, p < 0.001) for KPs. CONCLUSION: Index testing was well-accepted and effective in identifying individuals living with HIV in a Kenyan urban setting across both general populations and KPs. Ongoing adaptations to the strategies deployed as part of index testing services helped improve most of the outcomes along the index testing cascade.

Achieving HIV Epidemic Control and Improving Maternal Healthcare Services with Community-Based HIV Service Delivery in Zambia: Mixed-Methods Assessment of the SMACHT Project.

Novel community-based approaches are needed to achieve and sustain HIV epidemic control in Zambia. Under the Stop Mother and Child HIV Transmission (SMACHT) project, the Community HIV Epidemic Control (CHEC) differentiated service delivery model used community health workers to support HIV testing, ART linkage, viral suppression, and prevention of mother-to-child transmission (MTCT). A multi-methods assessment included programmatic data analysis from April 2015 to September 2020, and qualitative interviews from February to March 2020. CHEC provided HIV testing services to 1,379,387 clients; 46,138 were newly identified as HIV-positive (3.3% yield), with 41,366 (90%) linked to ART. By 2020, 91% (60,694/66,841) of clients on ART were virally suppressed. Qualitatively, healthcare workers and clients benefitted from CHEC, with provision of confidential services, health facility decongestion, and increased HIV care uptake and retention. Community-based models can increase uptake of HIV testing and linkage to care, and help achieve epidemic control and elimination of MTCT.

Extracellular Vesicles from Different Sources of Mesenchymal Stromal Cells Have Distinct Effects on Lung and Distal Organs in Experimental Sepsis.

The effects of the administration of mesenchymal stromal cells (MSC) may vary according to the source. We hypothesized that MSC-derived extracellular vesicles (EVs) obtained from bone marrow (BM), adipose (AD), or lung (L) tissues may also lead to different effects in sepsis. We profiled the proteome from EVs as a first step toward understanding their mechanisms of action. Polymicrobial sepsis was induced in C57BL/6 mice by cecal ligation and puncture (SEPSIS) and SHAM (control) animals only underwent laparotomy. Twenty-four hours after surgery, animals in the SEPSIS group were randomized to receive saline or 3 × 106 MSC-derived EVs from BM, AD, or L. The diffuse alveolar damage was decreased with EVs from all three sources. In kidneys, BM-, AD-, and L-EVs reduced edema and expression of interleukin-18. Kidney injury molecule-1 expression decreased only in BM- and L-EVs groups. In the liver, only BM-EVs reduced congestion and cell infiltration. The size and number of EVs from different sources were not different, but the proteome of the EVs differed. BM-EVs were enriched for anti-inflammatory proteins compared with AD-EVs and L-EVs. In conclusion, BM-EVs were associated with less organ damage compared with the other sources of EVs, which may be related to differences detected in their proteome.

Testing modality associated with fast-track ART initiation in Botswana.

OBJECTIVES: The aim of this study was to identify community testing modalities associated with fast-track ART initiation in Botswana. METHODS: We conducted a retrospective cohort study that included all Botswana citizens 15 years or older who were newly identified as HIV-positive from 1 May 2017 to 31 January 2019, in Mahalapye and Southern districts. We used Poisson regression with robust error variance and generalised linear mixed models to control for cluster effects to model risk of ART initiation within 7 and 30 days of HIV diagnosis, testing modality factors. RESULTS: A total of 1436 individuals were newly identified HIV-positive, with men accounting for 60% across all testing modalities. 22% of all HIV-positive individuals were initiated on ART within 7 days. Clients diagnosed through index testing were more likely to be started on ART within 7 days (adjusted risk ratio [aRR] = 1.38, 95% CI 1.37-1.38) and 30 days (aRR = 1.17, 95% CI 1.09-1.26) than those diagnosed through mobile/outreach testing. CONCLUSIONS: Community HIV testing can complement facility-based testing by reaching individuals who may be less likely to seek HIV services at a facility, such as men. Monitoring ART initiation by testing modalities is critical to identify the optimal ones and to guide continuous programme improvement.

Re-Engagement into HIV Care: A Systematic Review.

Identifying evidence-based interventions that can optimize the re-engagement into care of people living with HIV is necessary to achieve and sustain HIV epidemic control. We conducted a systematic review of interventions for re-engagement into HIV care to examine the accumulated evidence and to identify similarities and differences across studies. Between January and March 2020, we searched MEDLINE, Embase, CINAHL, and PsycINFO databases for publications from 1996 to 2020. We screened 765 references and selected 125 publications for full-text review. For the nine included studies, the intervention centered on (1) integration of clinic and HIV surveillance data; (2) additional or different levels of support provided by healthcare workers; or (3) multi-component intervention. Irrespective of the interventions, mixed results were found for re-engagement into care or ART re-initiation. None of the studies led to an improvement in viral suppression. Re-engagement in HIV care is critical for longitudinal HIV and national program success. Standardizing definitions for out-of-care and re-engagement would facilitate the comparison of interventions. Rigorous study designs to assess strategies to enhance HIV re-engagement are warranted.

Factors Associated with Retention in HIV Prevention and Treatment Clinical Services Among Female Sex Workers Enrolled in a Sex Workers' Outreach Program (SWOP) in Nairobi, Kenya.

Female sex workers (FSWs) are among the key populations (KP) prioritized for comprehensive HIV programming in Kenya. Retention in the program is critical for prevention of HIV acquisition and transmission among FSWs and their sexual partners. We conducted a retrospective cohort analysis of data collected from FSWs enrolled between October 2016 and September 2017 at seven drop-in centers (DICs) in Nairobi, Kenya, to assess factors associated with retention in HIV prevention and treatment services. We found a 3- and 12- month retention of 24% and 17%, respectively. FSWs aged 20-34 years old were less likely to be retained compared to those 50 years or older. FSWs enrolled in a DIC located in their sub-county of residence or reporting ever using HIV pre- or post-exposure prophylaxis were more likely to be retained. Engaging young FSWs to identify strategies to enhance retention should be prioritized. Strengthening the referral system across DICs may provide opportunities to enhance retention in facilities closer to their residence. Implementation research is needed to gain an additional understanding of the health services needs and preferences among FSWs to optimize retention for this population.

The Greatwall-Endosulfine Switch Accelerates Autophagic Flux during the Cell Divisions Leading to G1 Arrest and Entry into Quiescence in Fission Yeast.

Entry into quiescence in the fission yeast Schizosaccharomyces pombe is induced by nitrogen starvation. In the absence of nitrogen, proliferating fission yeast cells divide twice without cell growth and undergo cell cycle arrest in G1 before becoming G0 quiescent cells. Under these conditions, autophagy is induced to produce enough nitrogen for the two successive cell divisions that take place before the G1 arrest. In parallel to the induction of autophagy, the Greatwall-Endosulfine switch is activated upon nitrogen starvation to down-regulate protein phosphatase PP2A/B55 activity, which is essential for cell cycle arrest in G1 and implementation of the quiescent program. Here we show that, although inactivation of PP2A/B55 by the Greatwall-Endosulfine switch is not required to promote autophagy initiation, it increases autophagic flux at least in part by upregulating the expression of a number of autophagy-related genes.

Nutritional cell cycle reprogramming reveals that inhibition of Cdk1 is required for proper MBF-dependent transcription.

In nature, cells and in particular unicellular microorganisms are exposed to a variety of nutritional environments. Fission yeast cells cultured in nitrogen-rich media grow fast, divide with a large size and show a short G1 and a long G2. However, when cultured in nitrogen-poor media, they exhibit reduced growth rate and cell size and a long G1 and a short G2. In this study, we compared the phenotypes of cells lacking the highly conserved cyclin-dependent kinase (Cdk) inhibitor Rum1 and the anaphase-promoting complex/cyclosome (APC/C) activator Ste9 in nitrogen-rich and nitrogen-poor media. Rum1 and Ste9 are dispensable for cell division in nitrogen-rich medium. However, in nitrogen-poor medium they are essential for generating a proper wave of MluI cell-cycle box binding factor (MBF)-dependent transcription at the end of G1, which is crucial for promoting a successful S phase. Mutants lacking Rum1 and Ste9 showed premature entry into S phase and a reduced wave of MBF-dependent transcription, leading to replication stress, DNA damage and G2 cell cycle arrest. This work demonstrates how reprogramming the cell cycle by changing the nutritional environment may reveal new roles for cell cycle regulators.

Specific Activation In Vivo of HIV-1 by a Bromodomain Inhibitor from Monocytic Cells in Humanized Mice under Antiretroviral Therapy.

Combination antiretroviral therapy (cART) effectively suppresses HIV-1 replication and enables HIV­infected individuals to live long, productive lives. However, the persistence of HIV-1 reservoirs of both T and myeloid cells with latent or low-replicating HIV-1 in patients under cART makes HIV-1 infection an incurable disease. Recent studies have focused on the development of strategies to activate and purge these reservoirs. Bromodomain and extraterminal domain proteins (BETs) are epigenetic readers involved in modulating gene expression. Several bromodomain inhibitors (BETi) are reported to activate viral transcription in vitro in HIV-1 latency cell lines in a P-TEFb (CDK9/cyclin T1)-dependent manner. Little is known about BETi efficacy in activating HIV-1 reservoir cells under cART in vivo Here we report that a BETi (I-BET151) efficiently activated HIV-1 reservoirs under effective cART in humanized mice in vivo Interestingly, I-BET151 during suppressive cART in vivo activated HIV-1 gene expression only in monocytic cells and not in CD4+ T cells. We further demonstrate that BETi preferentially enhanced HIV-1 gene expression in monocytic cells rather than in T cells and that whereas CDK9 was involved in activating HIV-1 by I-BET151 in both monocytic and T cells, CDK2 enhanced HIV-1 transcription in monocytic cells but inhibited it in T cells. Our findings reveal a role for CDK2 in differential modulation of HIV-1 gene expression in myeloid cells and in T cells and provide a novel strategy to reactivate monocytic reservoirs with BETi during cART.IMPORTANCE Bromodomain inhibitors have been reported to activate HIV-1 transcription in vitro, but their effect on activation of HIV-1 reservoirs during cART in vivo is unclear. We found that BETi (I-BET151) treatment reactivated HIV-1 gene expression in humanized mice during suppressive cART. Interestingly, I-BET151 preferentially reactivated HIV-1 gene expression in monocytic cells, but not in CD4 T cells, in cART-treated mice. Furthermore, I-BET151 significantly increased HIV-1 transcription in monocytic cells, but not in HIV-1-infected CD4 T cells, via CDK2-dependent mechanisms. Our findings suggest that BETi can preferentially activate monocytic HIV-1 reservoir cells and that a combination of reservoir activation agents targeting different cell types and pathways is needed to achieve reactivation of different HIV-1 reservoir cells during cART.

Preventing Viral Contamination: Effects of Wipe and Spray-based Decontamination of Gloves and Gowns.

We conducted a laboratory simulation to evaluate the contamination of environmental surfaces when using wipe vs spray methods of personal protective equipment (PPE) decontamination. We did not observe any environmental contamination with the bacteriophage MS-2 when bleach solution spray or wipes were used for PPE disinfection.

Down-regulation of Cdk1 activity in G1 coordinates the G1/S gene expression programme with genome replication.

Cell division is regulated by cyclin-dependent kinases (Cdks) and requires the periodic activation and inactivation of transcription factors that generate waves of gene expression in different cell-cycle phases. In fission yeast, the MCB-binding transcription factor (MBF) is activated at the end of G1 and regulates the expression of a set of genes that encode for proteins involved in the G1/S transition and DNA replication. Here, we review the importance of controlling MBF by Cdk activity at the onset of S phase. Furthermore, we emphasize that MBF regulation by Cdk is particularly critical under conditions in which G1 is extended, such as in nitrogen-poor environments, where down-regulation of Cdk activity in G1 is crucial to generate a proper wave of MBF-dependent transcription at the end of G1, which is critical to promote a successful S phase.

Greatwall-Endosulfine: A Molecular Switch that Regulates PP2A/B55 Protein Phosphatase Activity in Dividing and Quiescent Cells.

During the cell cycle, hundreds of proteins become phosphorylated and dephosphorylated, indicating that protein kinases and protein phosphatases play a central role in its regulation. It has been widely recognized that oscillation in cyclin-dependent kinase (CDK) activity promotes DNA replication, during S-phase, and chromosome segregation, during mitosis. Each CDK substrate phosphorylation status is defined by the balance between CDKs and CDK-counteracting phosphatases. In fission yeast and animal cells, PP2A/B55 is the main protein phosphatase that counteracts CDK activity. PP2A/B55 plays a key role in mitotic entry and mitotic exit, and it is regulated by the Greatwall-Endosulfine (ENSA) molecular switch that inactivates PP2A/B55 at the onset of mitosis, allowing maximal CDK activity at metaphase. The Greatwall-ENSA-PP2A/B55 pathway is highly conserved from yeast to animal cells. In yeasts, Greatwall is negatively regulated by nutrients through TORC1 and S6 kinase, and couples cell growth, regulated by TORC1, to cell cycle progression, driven by CDK activity. In animal cells, Greatwall is phosphorylated and activated by Cdk1 at G2/M, generating a bistable molecular switch that results in full activation of Cdk1/CyclinB. Here we review the current knowledge of the Greatwall-ENSA-PP2A/B55 pathway and discuss its role in cell cycle progression and as an integrator of nutritional cues.

Risk Factors and Outcomes Associated with Multidrug-Resistant Acinetobacter baumannii upon Intensive Care Unit Admission.

Multidrug-resistant (MDR) Acinetobacter baumannii, associated with broad-spectrum antibiotic use, is an important nosocomial pathogen associated with morbidity and mortality. This study aimed to investigate the prevalence of MDR A. baumannii perirectal colonization among adult patients upon admission to the intensive care unit (ICU) over a 5-year period and to identify risk factors and outcomes associated with colonization. A retrospective cohort analysis of patients admitted to the medical intensive care unit (MICU) and surgical intensive care unit (SICU) at the University of Maryland Medical Center from May 2005 to September 2009 was performed using perirectal surveillance cultures on admission. Poisson and logistic models were performed to identify associated risk factors and outcomes. Four percent of the cohort were positive for MDR A. baumannii at ICU admission. Among patients admitted to the MICU, those positive for MDR A. baumannii at admission were more likely to be older, to have received antibiotics before ICU admission, and to have shorter length of stay in the hospital prior to ICU admission. Among patients admitted to the SICU, those colonized were more likely to have at least one previous admission to our hospital. Patients positive for MDR A. baumannii at ICU admission were 15.2 times more likely to develop a subsequent positive clinical culture for A. baumannii and 1.4 times more likely to die during the current hospitalization. Risk factors associated with MDR A. baumannii colonization differ by ICU type. Colonization acts as a marker of disease severity and of risk of developing a subsequent Acinetobacter infection and of dying during hospitalization. Therefore, active surveillance could guide empirical antibiotic selection and inform infection control practices.

Intraoperative red blood cell transfusion, delayed graft function, and infection after kidney transplant: an observational cohort study.

BACKGROUND: Kidney transplant patients are frequently anemic and at risk for red blood cell (RBC) transfusion. Previous studies suggest that pre-transplant RBC transfusion may improve kidney transplant outcomes; however, RBC transfusion is also associated with infection. The purpose of our study was to characterize the relationships between intraoperative RBC transfusion, delayed graft function (DGF), postoperative surgical site infection (SSI), and sepsis. METHODS: Analysis was performed on a historical cohort of adult kidney transplant patients from a single medical center during a two-year period. Crude odds ratios for DGF, superficial and deep SSI, and sepsis were calculated for transfused patients and multivariate regression was used to control for potential confounders when significant relationships were identified. RESULTS: Four hundred forty-one patients had kidney transplant during the study period; 27.0% had RBC transfusion, 38.8% had DGF, 7.0% had superficial SSI, 7.9% had deep SSI, and 1.8% had sepsis. High dose RBC transfusion was associated with improved graft function, but this was negated after adjusting for confounders (OR = 0.86, 95% CI 0.26 to 2.88). There was no association between RBC transfusion and SSI. RBC transfusion was independently associated with sepsis (OR = 8.98, 95% CI 1.52 to 53.22), but the confidence interval was wide. CONCLUSIONS: Intraoperative RBC transfusion during kidney transplant is not associated with improved allograft function or incisional SSI, but is associated with postoperative sepsis. RBCs should not be liberally transfused during kidney transplant surgery to improve graft outcomes.

Regulatory T Cells Contribute to HIV-1 Reservoir Persistence in CD4+ T Cells Through Cyclic Adenosine Monophosphate-Dependent Mechanisms in Humanized Mice In Vivo.

Background: Regulatory T cells (Tregs) suppress T-cell immune activation and human immunodeficiency virus type 1 (HIV-1) replication, but the role of Tregs in HIV-1 reservoir persistence is poorly defined. Methods: Tregs were depleted by denileukin diftitox in humanized mice with chronic HIV-1 infection. Viral replication in lineage cells was determined by p24 expression. Levels of HIV-1 RNA and DNA in human cells, as well as replication-competent-virus-producing cells, were measured to quantified viral replication and reservoirs. Results: Treg depletion resulted in a blip of HIV-1 replication in T cells but not in myeloid cells. The major activated reservoir cells were memory CD4+ T cells in vivo. Interestingly, the transient activation of viral replication led to HIV-1 reservoir reduction after viremia resuppression, as indicated by the quantity of HIV-1 DNA and replication-competent-virus-producing cells. Furthermore, we demonstrated that Tregs use cyclic adenosine monophosphate (cAMP)-dependent protein kinase A pathway to inhibit HIV-1 activation and replication in resting conventional T cells in vitro. Conclusion: Tregs suppress HIV-1 replication in T cells and contribute to HIV-1 reservoir persistence. cAMP produced in Tregs is involved in their suppression of viral gene activation and expression. Treg depletion combined with combination antiretroviral therapy provides a novel strategy for HIV-1 cure.

Transmission of Resistant Gram-Negative Bacteria to Health Care Worker Gowns and Gloves during Care of Nursing Home Residents in Veterans Affairs Community Living Centers.

The objectives of the study were to estimate the risk of transmission of antibiotic-resistant Gram-negative bacteria (RGNB) to gowns and gloves (G&G) worn by health care workers (HCWs) when providing care to nursing home residents and to identify the types of care and resident characteristics associated with transmission. A multicenter, prospective observational study was conducted with residents and HCWs from Veterans Affairs (VA) nursing homes. Perianal swabs to detect RGNB were collected from residents. HCWs wore G&G during usual care activities, and the G&G were swabbed at the end of the interaction in a standardized manner. Transmission of RGNB from a colonized resident to G&G by type of care was measured. Odds ratios (ORs) associated with type of care or resident characteristics were estimated. Fifty-seven (31%) of 185 enrolled residents were colonized with ≥1 RGNB. RGNB transmission to HCW gloves or gowns occurred during 9% of the interactions (n = 905): 7% to only gloves and 2% to only gowns. Bathing the resident and providing hygiene and toilet assistance were associated with a high risk of transmission. Glucose monitoring and assistance with feeding or medication were associated with a low risk of transmission. In addition, antibiotic use by the resident was strongly associated with greater transmission (OR, 2.51; P < 0.01). RGNB were transferred to HCWs during ∼9% of visits. High-risk types of care were identified for which use of G&G may be prioritized. Antibiotic use was associated with 2.5 times greater risk of transmission, emphasizing the importance of antibiotic stewardship. (This study has been registered at ClinicalTrials.gov under registration no. NCT01350479.).

What Transmission Precautions Best Control Influenza Spread in a Hospital?

Influenza is a significant problem within hospitals, leading to extended hospital stays, excess morbidity and mortality, and economic loss. Prevention and control strategies are generally "bundled"; therefore, the individual effects of particular strategies and the value of combined strategies cannot be determined directly, making it difficult to discern the optimal strategy. To quantify the individual and joint effectiveness of several known influenza infection control measures used in general hospitals, we simulated influenza transmission at a hypothetical hospital in Ann Arbor, Michigan, during a 1-year seasonal epidemic (June 2012-June 2013), using a susceptible-exposed-infected-recovered (SEIR) compartmental model. The hospital population comprised patients and health-care workers, interacting with its larger community population. Parameter ranges and values were determined from the literature (both national and local to Ann Arbor) and took into account coverage levels and effects of vaccination. The most effective individual strategies, based on percent reduction of cases, were: hand-washing (11%-27%), health-care worker vaccination (6%-19%), prevaccination of patients (4%-17%), patient isolation (5%-16%), antiviral treatment (4%-14%), and use of face masks (3%-10%). Use of all strategies together with ideal levels of compliance could potentially halve the number of observed hospital cases of influenza; under a more realistic scenario, an almost 40% reduction could be achieved. A multifaceted approach is imperative to control and prevent nosocomial influenza in health-care settings.