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      Assessment of Risk Factors and Outcomes of Severe Ehrlichiosis Infection

      research-article
      , MD 1 , 2 , , , MD, MPH 3 , , MD, PhD 4 , , PhD 5 , 6 , , MD, MPH 3 , 6 ,
      JAMA Network Open
      American Medical Association

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          Key Points

          Question

          What risk factors are associated with severe ehrlichiosis?

          Findings

          This cross-sectional study including 155 patients identified a delay in doxycycline therapy as a significant factor associated with severe ehrlichiosis. Documentation of tick exposure was independently associated with a decreased need for intensive care unit admission, and a change toward a decreased need for intensive care unit admission among immunosuppressed persons was identified.

          Meaning

          In this study, delay in initiation of empirical doxycycline therapy appears to be a risk factor for severe ehrlichiosis; education focused on early recognition and treatment may decrease morbidity associated with this infection.

          Abstract

          Importance

          Ehrlichiosis cases in the US have increased more than 8-fold since 2000. Up to 57% of patients with ehrlichiosis require hospitalization and 11% develop a life-threatening complication; however, risk factors for serious disease are not well documented.

          Objective

          To examine risk factors associated with severe ehrlichiosis.

          Design, Setting, and Participants

          An analytic cross-sectional study of patients diagnosed with ehrlichiosis by polymerase chain reaction (PCR) between January 1, 2007, and December 31, 2017, was conducted in a single tertiary-care center in a region endemic for ehrlichiosis. Analysis was performed from February 27, 2018, to September 9, 2020. A total of 407 positive Ehrlichia PCR results were identified from 383 unique patients, with 155 unique patients meeting study criteria. Patients hospitalized at other institutions who had a positive Ehrlichia PCR performed as a reference test (n = 222) were excluded as no clinical data were available. Electronic medical record review was performed to collect demographic, clinical, laboratory, treatment, and outcomes data. Cases were excluded when there were insufficient clinical data to assess the severity of illness (n = 3) and when the clinical illness did not meet the case definition for ehrlichiosis (n = 3).

          Exposures

          Date of presentation, onset of symptoms, date of PCR testing, date of treatment initiation, site of care, age, birth sex, race/ethnicity, Charlson Comorbidity Index, trimethoprim with sulfamethoxazole use within the prior 2 weeks, and immunosuppression.

          Main Outcomes and Measures

          Requirement for intensive care unit (ICU) admission.

          Results

          Of the 155 patients who met inclusion criteria, 99 patients (63.9%) were men, and 145 patients (93.5%) identified as non-Hispanic White; median age was 50 years (interquartile range, 23-64 years). Intensive care unit admission was indicated in 43 patients (27.7%), 94 patients (60.6%) were hospitalized on general medical floors, and 18 patients (11.6%) received care as outpatients. In adjusted analysis, time to treatment initiation was independently associated with an increased risk for ICU admission (adjusted prevalence ratio [aPR], 1.09; 95% CI, 1.04-1.14; P < .001). Documentation of tick exposure was independently associated with a decreased risk for ICU admission (aPR, 0.54; 95% CI, 0.34-0.86; P = .01). There appeared to be a nonsignificant change toward a decreased need for ICU care among immunosuppressed persons (aPR, 0.51; 95% CI, 0.26-1.00; P = .05).

          Conclusions and Relevance

          This study suggests that delay in initiation of doxycycline therapy is a significant factor associated with severe ehrlichiosis. Increased recognition of infection by front-line clinicians to promote early treatment may improve outcomes associated with this increasingly common and life-threatening infection.

          Abstract

          This cross-sectional study examines risk factors associated with severity of infection in patients with ehrlichiosis.

          Related collections

          Most cited references42

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          A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation

          The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
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            A modified poisson regression approach to prospective studies with binary data.

            G Zou (2004)
            Relative risk is usually the parameter of interest in epidemiologic and medical studies. In this paper, the author proposes a modified Poisson regression approach (i.e., Poisson regression with a robust error variance) to estimate this effect measure directly. A simple 2-by-2 table is used to justify the validity of this approach. Results from a limited simulation study indicate that this approach is very reliable even with total sample sizes as small as 100. The method is illustrated with two data sets.
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              Is Open Access

              Vital Signs : Trends in Reported Vectorborne Disease Cases — United States and Territories, 2004–2016

              Introduction Vectorborne diseases are major causes of death and illness worldwide. In the United States, the most common vectorborne pathogens are transmitted by ticks or mosquitoes, including those causing Lyme disease; Rocky Mountain spotted fever; and West Nile, dengue, and Zika virus diseases. This report examines trends in occurrence of nationally reportable vectorborne diseases during 2004–2016. Methods Data reported to the National Notifiable Diseases Surveillance System for 16 notifiable vectorborne diseases during 2004–2016 were analyzed; findings were tabulated by disease, vector type, location, and year. Results A total 642,602 cases were reported. The number of annual reports of tickborne bacterial and protozoan diseases more than doubled during this period, from >22,000 in 2004 to >48,000 in 2016. Lyme disease accounted for 82% of all tickborne disease reports during 2004–2016. The occurrence of mosquitoborne diseases was marked by virus epidemics. Transmission in Puerto Rico, the U.S. Virgin Islands, and American Samoa accounted for most reports of dengue, chikungunya, and Zika virus diseases; West Nile virus was endemic, and periodically epidemic, in the continental United States. Conclusions and Implications for Public Health Practice Vectorborne diseases are a large and growing public health problem in the United States, characterized by geographic specificity and frequent pathogen emergence and introduction. Differences in distribution and transmission dynamics of tickborne and mosquitoborne diseases are often rooted in biologic differences of the vectors. To effectively reduce transmission and respond to outbreaks will require major national improvement of surveillance, diagnostics, reporting, and vector control, as well as new tools, including vaccines.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                17 November 2020
                November 2020
                17 November 2020
                : 3
                : 11
                : e2025577
                Affiliations
                [1 ]Section of Infectious Disease, Renown Health, Reno, Nevada
                [2 ]Department of Medicine, School of Medicine, University of Nevada, Reno
                [3 ]Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
                [4 ]Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
                [5 ]Vector-Borne Disease Section, Tennessee Department of Health, Nashville
                [6 ]Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee
                Author notes
                Article Information
                Accepted for Publication: September 16, 2020.
                Published: November 17, 2020. doi:10.1001/jamanetworkopen.2020.25577
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Kuriakose K et al. JAMA Network Open.
                Corresponding Authors: Kevin Kuriakose, MD, Section of Infectious Disease, Renown Health, 75 Pringle Way, Ste 512, Reno, NV 89502 ( kkuriakose6@ 123456gmail.com ); Karen C. Bloch, MD, MPH, Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, A-2200 Medical Center N, 1161 21st Ave S, Nashville, TN 37232 ( karen.bloch@ 123456vumc.org ).
                Author Contributions: Drs Kuriakose and Bloch had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Kuriakose, Schmitz, Bloch.
                Acquisition, analysis, or interpretation of data: All authors.
                Drafting of the manuscript: Kuriakose, Schmitz, Moncayo.
                Critical revision of the manuscript for important intellectual content: All authors.
                Statistical analysis: Pettit.
                Administrative, technical, or material support: Moncayo, Bloch.
                Supervision: Schmitz, Bloch.
                Conflict of Interest Disclosures: Dr Schmitz reported receiving grants from the Centers for Disease Control and Prevention, the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases, and the NIH/National Institute of Allergies and Infectious Diseases; consulting fees from the US Department of Justice; and stock options (not exercised) from Discitis Dx, all outside the submitted work. No other disclosures were reported.
                Funding/Support: This work was supported in part by grant P30 AI110527 from the NIH-funded Tennessee Center for AIDS Research.
                Role of the Funder/Sponsor: The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Article
                zoi200836
                10.1001/jamanetworkopen.2020.25577
                7672514
                33201233
                82ff975c-874b-42d3-a795-dd431dcca0e5
                Copyright 2020 Kuriakose K et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 27 May 2020
                : 16 September 2020
                Categories
                Research
                Original Investigation
                Online Only
                Infectious Diseases

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