Increased Age-Dependent Risk of Death Associated With lukF-PV-Positive Staphylococcus aureus Bacteremia

Abstract Background Panton-Valentine leucocidin is a Staphylococcus aureus virulence factor encoded by lukF-PV and lukS-PV that is infrequent in S aureus bacteremia (SAB), and, therefore, little is known about risk factors and outcome of lukF-PV/lukS-PV-positive SAB. Methods This report is a register-based nationwide observational cohort study. lukF-PV was detected by polymerase chain reaction. Factors associated with the presence of lukF-PV were assessed by logistic regression analysis. Adjusted 30-day hazard ratios of mortality associated with lukF-PV status were computed by Cox proportional hazards regression analysis. Results Of 9490 SAB cases, 129 were lukF-PV-positive (1.4%), representing 14 different clonal complexes. lukF-PV was associated with younger age, absence of comorbidity, and methicillin-resistant S aureus. In unadjusted analysis, mortality associated with lukF-PV-positive SAB was comparable to SAB. However, lukF-PV-positive SAB nonsurvivors were significantly older and had more comorbidity. Consequently, by adjusted analysis, the risk of 30-day mortality was increased by 70% for lukF-PV-positive SAB compared with SAB (hazard ratio, 1.70; 95% confidence interval, 1.20–2.42; P = .003). Conclusions lukF-PV-positive SAB is rare in Denmark but associated with a significantly increased risk of mortality. Although the risk of lukF-PV-positive SAB was highest in the younger age groups, >80% of deaths associated with lukF-PV-positive SAB occurred in individuals older than 55 years.

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1067. Comparative Effectiveness of Nafcillin or Oxacillin, Cefazolin, and Piperacillin/Tazobactam in Methicillin-Sensitive Staphylococcus aureus Bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.904 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S319-S319

Author(s):

Maya Beganovic ◽

Jaclyn Cusumano ◽

Vrishali Lopes ◽

Kerry LaPlante ◽

Aisling Caffrey

Keyword(s):

Staphylococcus Aureus ◽

Nearest Neighbor ◽

Proportional Hazards ◽

Final Analysis ◽

Cox Proportional Hazards ◽

Inpatient Mortality ◽

Staphylococcus Aureus Bacteremia ◽

Hazard Ratios ◽

Ocean Spray ◽

Research Grant

Abstract Background β-Lactam antibiotics are recommended as first line for treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. The objective of this study was to compare effectiveness among β-lactam therapies in MSSA bacteremia patients that were exclusively treated with one antibiotic. Methods This was a retrospective cohort study of patients hospitalized at Veterans Affairs (VA) medical centers with MSSA bacteremia from January 1, 2002 to October 1, 2015. Patients were included if they were treated exclusively with nafcillin, oxacillin, cefazolin, or piperacillin/tazobactam (i.e., monotherapy with no changes in therapy). The primary outcome was 30-day mortality, and secondary outcomes were time to discharge, inpatient mortality, 30-day readmission, and 30-day S. aureus reinfection. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using unadjusted, quintile adjusted, and propensity-score (PS) matched (nearest neighbor, 0.05 caliper) Cox proportional hazards regression. Results A total of 326 patients were included in the final analysis. When comparing nafcillin (n = 75)/oxacillin (n = 30) with cefazolin (n = 108), 30-day mortality was similar between groups (PS matched n = 40, HR 4.0, 95% CI 0.45–35.79), as were rates of the other outcomes assessed. When combining nafcillin/oxacillin with cefazolin, and comparing to piperacillin/tazobactam (n = 113), 30-day mortality was significantly lower in the nafcillin/oxacillin/cefazolin group (PS matched n = 66, HR 0.29, 95% CI 0.09–0.87). Inpatient mortality and 30-day mortality were significantly lower with nafcillin/oxacillin/cefazolin in PS-adjusted analyses (HR 0.29, 95% CI 0.11–0.73 and HR 0.23, 95% CI 0.10–0.50, respectively). Conclusion In hospitalized patients with MSSA bacteremia, no difference in mortality was observed between nafcillin/oxacillin and cefazolin in patients that were exclusively treated with these monotherapies. However, higher mortality was observed with piperacillin/tazobactam as compared with nafcillin/oxacillin/cefazolin, suggesting that it may not be as effective as other monotherapies for MSSA bacteremia. Disclosures K. LaPlante, Merck: Grant Investigator, Research grant. Pfizer Pharmaceuticals: Grant Investigator, Research grant. Allergan: Scientific Advisor, Honorarium. Ocean Spray Cranberries, Inc.: Grant Investigator and Scientific Advisor, Honorarium and Research grant. Achaogen, Inc.: Scientific Advisor, Honorarium. Zavante Therapeutics, Inc.: Scientific Advisor, Honorarium. A. Caffrey, Merck: Grant Investigator, Research grant. The Medicine’s Company: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant.

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Abstract 2429: ICD Efficacy In Patients Who Developed New Onset Atrial Fibrillation After Enrollment In The MADIT-II Trial

Circulation ◽

10.1161/circ.116.suppl_16.ii_533-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Anant K Vyas ◽

Ilan Goldenberg ◽

Wojciech Zareba ◽

Scott McNitt ◽

Arthur J Moss

Keyword(s):

Atrial Fibrillation ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Functional Class ◽

Icd Therapy ◽

Risk Of Death ◽

Hazard Ratios ◽

Increased Risk ◽

Madit Ii ◽

New Onset

Introduction: In the Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II), the presence of atrial fibrillation (AF) at baseline was associated with an increased risk of death, and these patients received a substantial benefit from ICD therapy. In the current study, we evaluated the risk of death and the efficacy of ICD therapy in patients who developed new-onset AF after enrollment in the MADIT-II study. Methods/Results: Hazard ratios (HR) were determined using multivariate Cox proportional hazards method. Age ≥ 65 (HR 3.02, p < 0.01), QRS duration > 120 ms (HR 2.30, p < 0.01), and NYHA functional class ≥ 2 (HR 1.78, p = 0.03) were independent predictors of new-onset AF. In both treatment arms, there was a significant increase in the risk of death after developing new-onset AF (Post-AF) (n = 25 in conventional arm, n = 51 in ICD arm) than among patients before or without AF (Pre-AF) (n = 416 in conventional arm, n = 624 in ICD arm) as shown in the Mantel-Byar graphs. After adjusting for relevant covariates (including age, BUN, EF, and beta-blocker use), ICD therapy was associated with a greater reduction in the risk of death in patients who developed new-onset AF (HR 0.31, p = 0.013) compared to patients with no interim AF (HR 0.73, p = 0.055) [p = 0.085 for interaction between interim AF and ICD therapy]. Conclusions: The development of new-onset AF is associated with a significant increase in mortality and this group may be a target for closer follow-up and more aggressive treatment. ICD therapy was highly effective in reducing mortality in MADIT-II patients who developed new-onset AF after enrollment in the trial.

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Adaptive metabolic and inflammatory responses identified using accelerated aging metrics are linked to adverse outcomes in severe SARS-CoV-2 infection

The Journals of Gerontology Series A ◽

10.1093/gerona/glab078 ◽

2021 ◽

Author(s):

Alejandro Márquez-Salinas ◽

Carlos A Fermín-Martínez ◽

Neftalí Eduardo Antonio-Villa ◽

Arsenio Vargas-Vázquez ◽

Enrique C. Guerra ◽

...

Keyword(s):

Critical Illness ◽

Proportional Hazards ◽

Inflammatory Responses ◽

Age Groups ◽

Accelerated Aging ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Adaptive Responses ◽

Predictive Capacity ◽

Risk Of Death

Abstract Background Chronological age (CA) is a predictor of adverse COVID-19 outcomes; however, CA alone does not capture individual responses to SARS-CoV-2 infection. Here, we evaluated the influence of aging metrics PhenoAge and PhenoAgeAccel to predict adverse COVID-19 outcomes. Furthermore, we sought to model adaptive metabolic and inflammatory responses to severe SARS-CoV-2 infection using individual PhenoAge components. Methods In this retrospective cohort study, we assessed cases admitted to a COVID-19 reference center in Mexico City. PhenoAge and PhenoAgeAccel were estimated using laboratory values at admission. Cox proportional hazards models were fitted to estimate risk for COVID-19 lethality and adverse outcomes (ICU admission, intubation, or death). To explore reproducible patterns which model adaptive responses to SARS-CoV-2 infection, we used k-means clustering using PhenoAge components. Results We included 1068 subjects of whom 222 presented critical illness and 218 died. PhenoAge was a better predictor of adverse outcomes and lethality compared to CA and SpO2 and its predictive capacity was sustained for all age groups. Patients with responses associated to PhenoAgeAccel>0 had higher risk of death and critical illness compared to those with lower values (log-rank p<0.001). Using unsupervised clustering we identified four adaptive responses to SARS-CoV-2 infection: 1) Inflammaging associated with CA, 2) metabolic dysfunction associated with cardio-metabolic comorbidities, 3) unfavorable hematological response, and 4) response associated with favorable outcomes. Conclusions Adaptive responses related to accelerated aging metrics are linked to adverse COVID-19 outcomes and have unique and distinguishable features. PhenoAge is a better predictor of adverse outcomes compared to CA.

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Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

Journal of Clinical Medicine ◽

10.3390/jcm10071514 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1514

Author(s):

Hilde Espnes ◽

Jocasta Ball ◽

Maja-Lisa Løchen ◽

Tom Wilsgaard ◽

Inger Njølstad ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Pressure Management ◽

Reference Models ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

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Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study

Cancers ◽

10.3390/cancers13051177 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1177

Author(s):

In Young Choi ◽

Sohyun Chun ◽

Dong Wook Shin ◽

Kyungdo Han ◽

Keun Hye Jeon ◽

...

Keyword(s):

Breast Cancer ◽

Metabolic Syndrome ◽

Proportional Hazards ◽

Screening Program ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Health Screening Program ◽

Design And Methods

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

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Comorbidity between types of eating disorder and general medical conditions

The British Journal of Psychiatry ◽

10.1192/bjp.2021.104 ◽

2021 ◽

pp. 1-8

Author(s):

Natalie C. Momen ◽

Oleguer Plana-Ripoll ◽

Cynthia M. Bulik ◽

John J. McGrath ◽

Laura M. Thornton ◽

...

Keyword(s):

Eating Disorders ◽

Eating Disorder ◽

Proportional Hazards ◽

Medical Condition ◽

Detailed Examination ◽

Cox Proportional Hazards ◽

Medical Conditions ◽

Relative Risks ◽

Hazard Ratios ◽

Increased Risk

Background Comorbidity with general medical conditions is common in individuals with eating disorders. Many previous studies do not evaluate types of eating disorder. Aims To provide relative and absolute risks of bidirectional associations between (a) anorexia nervosa, bulimia nervosa and eating disorders not otherwise specified and (b) 12 general medical conditions. Method We included all people born in Denmark between 1977 and 2010. We collected information on eating disorders and considered the risk of subsequent medical conditions, using Cox proportional hazards regression. Absolute risks were calculated using competing risks survival analyses. We also considered risks for prior medical conditions and subsequent eating disorders. Results An increased risk was seen for almost all disorder pairs (69 of 70). Hazard ratios for those with a prior eating disorder receiving a subsequent diagnosis of a medical condition ranged from 0.94 (95% CI 0.57−1.55) to 2.05 (95% CI 1.86−2.27). For those with a prior medical condition, hazard ratios for later eating disorders ranged from 1.35 (95% CI 1.26–1.45) to 1.98 (95% CI 1.71–2.28). Absolute risks for most later disorders were increased for persons with prior disorders, compared with reference groups. Conclusions This is the largest and most detailed examination of eating disorder–medical condition comorbidity. The findings indicate that medical condition comorbidity is increased among those with eating disorders and vice versa. Although there was some variation in comorbidity observed across eating disorder types, magnitudes of relative risks did not differ greatly.

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Accelerated aging and mortality in long-term survivors of childhood cancer: A report from the St. Jude Lifetime Cohort (SJLIFE).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10045 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10045-10045

Author(s):

AnnaLynn M. Williams ◽

Jeanne S. Mandelblatt ◽

Mingjuan Wang ◽

Kirsten K. Ness ◽

Gregory T. Armstrong ◽

...

Keyword(s):

Childhood Cancer ◽

Proportional Hazards ◽

Accelerated Aging ◽

Cox Proportional Hazards ◽

Premature Aging ◽

Self Report ◽

Deficit Accumulation ◽

Risk Of Death ◽

Increased Risk ◽

Survivors Of Childhood Cancer

10045 Background: Survivors of childhood cancer have functional limitations and health-related morbidity consistent with an accelerated aging phenotype. We characterized aging using a Deficit Accumulation Index (DAI) which examines the accumulation of multiple aging-related deficits readily available from medical records and self-report. DAI’s are used as surrogates of biologic aging and are validated to predict mortality in adult cancer patients. Methods: We included childhood cancer survivors (N = 3,758, mean age 30 [SD 8], 22 [9] years post diagnosis, 52% male) and community controls (N = 575, mean age 34 [10] 44% male) who completed clinical assessments and questionnaires and who were followed for mortality through December 31st, 2018 (mean follow-up 6.1 [3.1] years). Using the initial SJLIFE clinical assessment, a DAI score was generated as the proportion of deficits out of 44 items related to aging, including chronic conditions (e.g. hearing loss, hypertension), psychosocial and physical function, and activities of daily living. The total score ranged 0 to 1; scores > 0.20 are robust, while moderate and large clinically meaningful differences are 0.02 and 0.06, respectively. Linear regression compared the DAI in survivors and controls with an age*survivor/control interaction and examined treatment associations in survivors. Cox-proportional hazards models estimated risk of death associated with DAI. All models were adjusted for age, sex, and race. Results: Mean [SD] of DAI was 0.17 [0.11] for survivors and 0.10 [0.08] for controls. 32% of survivors had a DAI above the 90th percentile of the control distribution (p < 0.001). After adjustment for covariates, survivors had a statistically and clinically meaningfully higher DAI score than controls (β = 0.072 95%CI 0.062, 0.081; p < 0.001). When plotted against age, the adjusted DAI at the average age of survivors (30 years) was 0.166 (95% CI 0.160,0.171), which corresponded to 60 years of age in controls, suggesting premature aging of 30 years. The mean difference in DAI between survivors and controls increased with age from 0.06 (95% CI 0.04, 0.07) at age 20 to 0.11 (95% CI 0.08, 0.13) at age 60, consistent with an accelerated aging phenotype (p = 0.014). Cranial radiation, abdominal radiation, cyclophosphamide, platinum agents, neurosurgery, and amputation were each associated with a higher DAI (all p≤0.001). Among survivors, a 0.06 increase in DAI was associated with a 41% increased risk of all-cause mortality (HR 1.41 95%CI 1.32, 1.50; p < 0.001). Conclusions: Survivors of childhood cancer experience significant age acceleration that is associated with an increased risk of mortality; longitudinal analyses are underway to validate these findings. Given the ease of estimating a DAI, this may be a feasible method to quickly identify survivors for novel and tailored interventions that can improve health and prevent premature mortality.

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Supper Timing and Cardiovascular Mortality: The Japan Collaborative Cohort Study

Nutrients ◽

10.3390/nu13103389 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3389

Author(s):

Jingyun Tang ◽

Jia-Yi Dong ◽

Ehab S. Eshak ◽

Renzhe Cui ◽

Kokoro Shirai ◽

...

Keyword(s):

Hemorrhagic Stroke ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Stroke Mortality ◽

Hazard Ratios ◽

Risk Of Mortality ◽

Increased Risk ◽

Study Participants

Evidence on the role of supper timing in the development of cardiovascular disease (CVD) is limited. In this study, we examined the associations between supper timing and risks of mortality from stroke, coronary heart disease (CHD), and total CVD. A total of 28,625 males and 43,213 females, aged 40 to 79 years, free from CVD and cancers at baseline were involved in this study. Participants were divided into three groups: the early supper group (before 8:00 p.m.), the irregular supper group (time irregular), and the late supper group (after 8:00 p.m.). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for stroke, CHD, and total CVD according to the supper time groups. During the 19-year follow-up, we identified 4706 deaths from total CVD. Compared with the early supper group, the multivariable HR of hemorrhagic stroke mortality for the irregular supper group was 1.44 (95% confidence interval [CI]: 1.05–1.97). There was no significant association between supper timing and the risk of mortality from other types of stroke, CHD, and CVD. We found that adopting an irregular supper timing compared with having dinner before 8:00 p.m. was associated with an increased risk of hemorrhagic stroke mortality.

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Relationship of lycopene intake and consumption of tomato products to incident CVD

British Journal Of Nutrition ◽

10.1017/s0007114512005417 ◽

2013 ◽

Vol 110 (3) ◽

pp. 545-551 ◽

Cited By ~ 54

Author(s):

Paul F. Jacques ◽

Asya Lyass ◽

Joseph M. Massaro ◽

Ramachandran S. Vasan ◽

Ralph B. D'Agostino Sr

Keyword(s):

Repeated Measures ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Supporting Evidence ◽

Inverse Association ◽

Cvd Risk ◽

Stroke Incidence ◽

Hazard Ratios ◽

Increased Risk

Evidence for cardioprotective effects of lycopene is inconsistent. Studies of circulating lycopene generally report inverse associations with CVD risk, but studies based on lycopene intake do not. The failure of dietary studies to support the findings based on biomarkers may be due in part to misclassification of lycopene intakes. To address this potential misclassification, we used repeated measures of intake obtained over 10 years to characterise the relationship between lycopene intake and the incidence of CVD (n314), CHD (n171) and stroke (n99) in the Framingham Offspring Study. Hazard ratios (HR) for incident outcomes were derived from Cox proportional hazards regression models using logarithmically transformed lycopene intake adjusted for CVD risk factors and correlates of lycopene intake. HR were interpreted as the increased risk for a 2·7-fold difference in lycopene intake, a difference approximately equal to its interquartile range. Using an average of three intake measures with a 9-year follow-up, lycopene intake was inversely associated with CVD incidence (HR 0·83, 95 % CI 0·70, 0·98). Using an average of two intake measures and 11 years of follow-up, lycopene intake was inversely associated with CHD incidence (HR 0·74, 95 % CI 0·58, 0·94). Lycopene intake was unrelated to stroke incidence. The present study of lycopene intake and CVD provides supporting evidence for an inverse association between lycopene and CVD risk; however, additional research is needed to determine whether lycopene or other components of tomatoes, the major dietary source of lycopene, are responsible for the observed association.

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Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis

Viruses ◽

10.3390/v10110658 ◽

2018 ◽

Vol 10 (11) ◽

pp. 658 ◽

Cited By ~ 2

Author(s):

Paul Blair ◽

Maryam Keshtkar-Jahromi ◽

Kevin Psoter ◽

Ronald Reisler ◽

Travis Warren ◽

...

Keyword(s):

Proportional Hazards ◽

Clinical Laboratory ◽

Cynomolgus Macaque ◽

The United States ◽

Cox Proportional Hazards ◽

Marburg Virus ◽

Time To Death ◽

Risk Of Death ◽

Published Evidence ◽

Increased Risk

Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model.

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