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      Outcomes among children and adults at risk of severe dengue in Sri Lanka: Opportunity for outpatient case management in countries with high disease burden

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          Abstract

          Background

          Healthcare systems in dengue-endemic countries are often overburdened due to the high number of patients hospitalized according to dengue management guidelines. We systematically evaluated clinical outcomes in a large cohort of patients hospitalized with acute dengue to support triaging of patients to ambulatory versus inpatient management in the future.

          Methods/Principal findings

          From June 2017- December 2018, we conducted surveillance among children and adults with fever within the prior 7 days who were hospitalized at the largest tertiary-care (1,800 bed) hospital in the Southern Province, Sri Lanka. Patients who developed platelet count ≤100,000/μL (threshold for hospital admission in Sri Lanka) and who met at least two clinical criteria consistent with dengue were eligible for enrollment. We confirmed acute dengue by testing sera collected at enrollment for dengue NS1 antigen or IgM antibodies. We defined primary outcomes as per the 1997 and 2009 World Health Organization (WHO) classification criteria: dengue hemorrhagic fever (DHF; WHO 1997), dengue shock syndrome (DSS; WHO 1997), and severe dengue (WHO 2009). Overall, 1064 patients were confirmed as having acute dengue: 318 (17.4%) by NS1 rapid antigen testing and 746 (40.7%) by IgM antibody testing. Of these 1064 patients, 994 (93.4%) were adults ≥18 years and 704 (66.2%) were male. The majority (56, 80%) of children and more than half of adults (544, 54.7%) developed DHF during hospitalization, while 6 (8.6%) children and 22 (2.2%) adults developed DSS. Overall, 10 (14.3%) children and 113 (11.4%) adults developed severe dengue. A total of 2 (0.2%) patients died during hospitalization.

          Conclusions

          One-half of patients hospitalized with acute dengue progressed to develop DHF and a very small number developed DSS or severe dengue. Developing an algorithm for triaging patients to ambulatory versus inpatient management should be the future goal to optimize utilization of healthcare resources in dengue-endemic countries.

          Author summary

          In countries where dengue is prevalent, hospitals are often overwhelmed due to the high numbers of patient admissions during dengue epidemics. We studied 1064 children and adults hospitalized with acute dengue in Sri Lanka to determine the prevalence of severe disease outcomes to support the development of a system which can limit hospitalizations in the future. We found that only half of patients developed severe disease outcomes during hospitalization and only a small minority of patients developed life-threatening disease. For dengue-prevalent countries, developing systems to identify patients with acute dengue who can be managed without hospital admission should be a priority.

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          Most cited references23

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          The global distribution and burden of dengue

          Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes 1 . For some patients dengue is a life-threatening illness 2 . There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread 3 . The contemporary worldwide distribution of the risk of dengue virus infection 4 and its public health burden are poorly known 2,5 . Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanisation. Using cartographic approaches, we estimate there to be 390 million (95 percent credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of clinical or sub-clinical severity). This infection total is more than three times the dengue burden estimate of the World Health Organization 2 . Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help guide improvements in disease control strategies using vaccine, drug and vector control methods and in their economic evaluation. [285]
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            The global economic burden of dengue: a systematic analysis.

            Dengue is a serious global burden. Unreported and unrecognised apparent dengue virus infections make it difficult to estimate the true extent of dengue and current estimates of the incidence and costs of dengue have substantial uncertainty. Objective, systematic, comparable measures of dengue burden are needed to track health progress, assess the application and financing of emerging preventive and control strategies, and inform health policy. We estimated the global economic burden of dengue by country and super-region (groups of epidemiologically similar countries).
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              Differences in dengue severity in infants, children, and adults in a 3-year hospital-based study in Nicaragua.

              To investigate age-related differences in dengue severity, 114 infants, 1,211 children, and 346 adults with laboratory-confirmed dengue virus (DEN) infections presenting to three hospitals in major urban centers in Nicaragua were recruited from 1999 to 2001. The age distribution of dengue cases and the circulating serotype (predominantly DEN2) were representative of national data. Similar results were obtained when either dengue hemorrhagic fever/dengue shock syndrome or its principal manifestations (vascular permeability, internal hemorrhage, marked thrombocytopenia, and/or shock) were analyzed in relation to age and immune status. The burden of disease and of severe dengue was found predominantly in infants 4-9 months of age and in children 5-9 years old, and secondary DEN infection was a risk factor for severity in children. Age-related differences were identified in the prevalence of specific clinical manifestations as well as in their association with a confirmed DEN diagnosis. This represents one of the few comprehensive studies to analyze characteristics of dengue in infants, children, and adults in the same population and highlights age-related differences in dengue severity.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: Project administrationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: Project administrationRole: Writing – review & editing
                Role: Project administrationRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                28 December 2021
                December 2021
                : 15
                : 12
                : e0010091
                Affiliations
                [1 ] Department of Medicine, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka
                [2 ] Duke Global Health Institute, Durham, North Carolina, United States of America
                [3 ] Duke-Ruhuna Collaborative Research Centre, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka
                [4 ] Department of Microbiology, Faculty of Medicine, Galle, Sri Lanka
                [5 ] Department of Pediatrics, Faculty of Medicine, Galle, Sri Lanka
                [6 ] Institute for Medical Research, Durham, North Carolina, United States of America
                [7 ] Teaching Hospital, Karapitiya, Galle, Sri Lanka
                [8 ] Faculty of Medicine, General Sir John Kotelawala Defence University, Ratmalana, Sri Lanka
                [9 ] Department of Family Medicine and Community Health, Duke University, Durham, North Carolina, United States of America
                [10 ] Department of Medicine, Duke University, Durham, North Carolina, United States of America
                Centre hospitalier de Cayenne, FRANCE
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-1339-1883
                https://orcid.org/0000-0003-3942-4575
                https://orcid.org/0000-0002-8330-3597
                https://orcid.org/0000-0002-8438-8086
                https://orcid.org/0000-0001-5488-8293
                https://orcid.org/0000-0003-4730-432X
                https://orcid.org/0000-0001-9517-3876
                https://orcid.org/0000-0002-1917-6845
                https://orcid.org/0000-0002-9783-4313
                https://orcid.org/0000-0001-5291-9543
                https://orcid.org/0000-0001-7240-2453
                https://orcid.org/0000-0001-6012-7271
                Article
                PNTD-D-21-01500
                10.1371/journal.pntd.0010091
                8746768
                34962920
                c74d4b0f-73bd-429d-bc83-5cf721b4f190
                © 2021 Bodinayake et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 October 2021
                : 14 December 2021
                Page count
                Figures: 0, Tables: 5, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100008982, National Science Foundation;
                Award ID: RPHS/2016/D 04
                Award Recipient :
                This study was funded by a grant from the Sri Lanka National Science Foundation (RPHS/2016/D04) to ADSN. http://www.nsf.ac.lk The funder did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Medical Conditions
                Tropical Diseases
                Neglected Tropical Diseases
                Dengue Fever
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Viral Diseases
                Dengue Fever
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Blood Plasma
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                Blood
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                Physiology
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                Asia
                Sri Lanka
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                Biology and Life Sciences
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                Medicine and Health Sciences
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                Custom metadata
                vor-update-to-uncorrected-proof
                2022-01-10
                Data cannot be shared publicly because of restrictions by the ethics committees. Data are available from the Faculty of Medicine, University of Ruhuna, Ethics Committee Committee (contact via ethics@ 123456med.ruh.ac.lk ) for researchers who meet the criteria for access to confidential data.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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