Original Research
20 June 2023

Clinical Characteristics and Outcomes Among Travelers With Severe Dengue: A GeoSentinel Analysis

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Publication: Annals of Internal Medicine
Volume 176, Number 7
Visual Abstract. Clinical Characteristics and Outcomes Among Travelers With Severe Dengue
In this retrospective review of travel-associated dengue reported to GeoSentinel, complicated dengue occurred in 95 of 5958 (2%) patients. The most common laboratory findings and signs were thrombocytopenia, elevated aminotransferase, bleeding, and plasma leakage. Clinicians should monitor patients with dengue for warning signs that may indicate progression to severe disease.

Abstract

Background:

Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited.

Objective:

To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue).

Design:

Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022.

Setting:

20 of 71 international GeoSentinel sites.

Patients:

Returning travelers with complicated dengue.

Measurements:

Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue.

Results:

Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n = 27 [31%]) and Southeast Asia (n = 20 [23%]). Frequent reasons for travel were tourism (45%) and visiting friends and relatives (30%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2), and neurologic symptoms (n = 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG−) and 12 as secondary (IgM−/IgG+) dengue.

Limitations:

Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited.

Conclusion:

Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study.

Primary Funding Source:

Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.

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Supplemental Material

Supplement. Complicated Dengue Questionnaire

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 176Number 7July 2023
Pages: 940 - 948

History

Published online: 20 June 2023
Published in issue: July 2023

Keywords

Authors

Affiliations

Department of Infectious Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Verona, Italy (R.H.)
Division of Global Migration and Quarantine, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia (K.M.A.)
CIWEC Hospital and Travel Medicine Center, Kathmandu, Nepal (B.A.)
J.D. MacLean Centre for Tropical Diseases, McGill University Health Centre, Montreal, Quebec, Canada (S.B.)
Elizabeth D. Barnett, MD
Section of Pediatric Infectious Diseases, Boston Medical Center, Boston, Massachusetts (E.D.B., M.L.)
Emmanuel Bottieau, MD, PhD https://orcid.org/0000-0002-5868-7760
Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium (E.B.)
Hannah Emetulu, MPH
International Society of Travel Medicine, Atlanta, Georgia (H.E., A.R.)
Infectious and Tropical Diseases Unit and CIC Inserm 1424, Centre Hospitalier de Cayenne, Cayenne, French Guiana (L.E.)
Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Geneva, Switzerland (G.E.)
Line Medebb, PhD
Aix Marseille University, AP-HM, IHU-Méditerranée Infection, Marseille, France (L.M.)
Federico Gobbi, MD, PhD
Department of Infectious Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Verona, and Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (F.G.)
Martin P. Grobusch, MD, PhD https://orcid.org/0000-0002-0046-1099
Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Amsterdam University Medical Center, Amsterdam, the Netherlands (M.P.G.)
Oula Itani, MD
Institut Pasteur, Centre Médical, Centre d’Infectiologie Necker-Pasteur, Paris, France (O.I.)
Sabine Jordan, MD
Division of Tropical Medicine, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, and Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany (S.J.)
Paul Kelly, MD
BronxCare Hospital Center, Bronx, New York (P.K.)
School of Public Health and Preventive Medicine, Monash University, and Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Victoria, Australia (K.L.)
Marta Díaz-Menéndez, MD, PhD https://orcid.org/0000-0002-9427-5237
Tropical Medicine Department, Hospital Universitario La Paz-Carlos III, IdIPAz, and CIBERINFECT, Madrid, Spain (M.D.)
Center Hospital of the National Center for Global Health and Medicine, Shinjuku City, Tokyo, Japan (N.O.)
Aisha Rizwan, MPH
International Society of Travel Medicine, Atlanta, Georgia (H.E., A.R.)
Camilla Rothe, MD
Department of Infectious Diseases and Tropical Medicine, Ludwig-Maximilians-Universität München, Munich, Germany (C.R.)
Doctor's Plaza, Nairobi Hospital, Nairobi, Kenya (M.S.)
Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia (J.W.)
Yokohama Municipal Citizen's Hospital, Yokohama, Kanagawa, Japan (Y.Y.)
Section of Pediatric Infectious Diseases, Boston Medical Center, Boston, Massachusetts (E.D.B., M.L.)
Department of Global Health, Boston University School of Public Health, Section of Infectious Diseases, Boston University School of Medicine, Center for Emerging Infectious Disease Policy and Research, Boston University, and National Emerging Infectious Disease Laboratory, Boston, Massachusetts (D.H.H.)
Eli Schwartz, MD
The Center of Geographical Medicine and Tropical Diseases, Sheba Medical Center, Tel HaShomer, and Ramat Gan & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.S.).
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Acknowledgment: The authors thank Christophe Burm at the Institute of Tropical Medicine, Antwerp, Belgium, for his valuable contributions to managing the electronic data collection.
Financial Support: This project was funded through a Cooperative Agreement between the Centers for Disease Control and Prevention and the International Society of Travel Medicine (Federal Award Number: 1 U01CK000632-01-00). Public Health Agency of Canada also provides a grant to the International Society of Travel Medicine. The analysis was cofunded by the GeoSentinel Foundation.
Reproducible Research Statement: Study protocol: This project has a nonresearch determination at the Centers for Disease Control and Prevention. The project protocol is available by e-mailing [email protected]. Statistical code: Available on request from Dr. Angelo (e-mail, [email protected]). Data set: The data collected is that of the individual GeoSentinel sites and cannot be released.
Corresponding Author: Ralph Huits, MD, PhD, Department of Infectious Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 5, 37024 Negrar, Verona, Italy; e-mail, [email protected].
Correction: This article was amended on 21 June 2023 to correct the number of patients with severe dengue mentioned in the Discussion section. This article was amended on 15 August 2023 to correct reporting errors. None of these revisions substantively changed the results or conclusions of this article. A correction has been published (doi:10.7326/L23-0297).
Author Contributions: Conception and design: K.M. Angelo, E.D. Barnett, D.H. Hamer, R. Huits, M. Libman, A. Rizwan, E. Schwartz.
Analysis and interpretation of the data: K.M. Angelo, S. Barkati, E.D. Barnett, E. Bottieau, L. Epelboin, F. Gobbi, M.P. Grobusch, D.H. Hamer, R. Huits, S. Jordan, K. Leder, M. Libman, E. Schwartz, J. Waggoner.
Drafting of the article: K.M. Angelo, D.H. Hamer, R. Huits, M. Libman, A. Rizwan.
Critical revision of the article for important intellectual content: B. Amatya, K.M. Angelo, S. Barkati, E.D. Barnett, E. Bottieau, M. Díaz-Menéndez, L. Epelboin, F. Gobbi, M.P. Grobusch, D.H. Hamer, R. Huits, O. Itani, S. Jordan, P. Kelly, K. Leder, M. Libman, N. Okumura, A. Rizwan, C. Rothe, E. Schwartz, J. Waggoner.
Final approval of the article: B. Amatya, K.M. Angelo, S. Barkati, E.D. Barnett, E. Bottieau, M. Díaz-Menéndez, H. Emetulu, L. Epelboin, G. Eperon, F. Gobbi, M.P. Grobusch, D.H. Hamer, R. Huits, O. Itani, S. Jordan, P. Kelly, K. Leder, M. Libman, L. Meddeb, N. Okumura, A. Rizwan, C. Rothe, M. Saio, E. Schwartz, J. Waggoner, Y. Yoshimura.
Provision of study materials or patients: E.D. Barnett, E. Bottieau, M.P. Grobusch, R. Huits, O. Itani, S. Jordan, M. Libman, M. Saio.
Statistical expertise: K.M. Angelo, R. Huits.
Obtaining of funding: K.M. Angelo, D.H. Hamer, R. Huits, M. Libman.
Administrative, technical, or logistic support: K.M. Angelo, H. Emetulu, D.H. Hamer, R. Huits, A. Rizwan.
Collection and assembly of data: B. Amatya, S. Barkati, E.D. Barnett, E. Bottieau, M. Díaz-Menéndez, F. Gobbi, M.P. Grobusch, R. Huits, O. Itani, S. Jordan, P. Kelly, K. Leder, M. Libman, L. Meddeb, N. Okumura, A. Rizwan, C. Rothe, E. Schwartz.
This article was published at Annals.org on 20 June 2023.

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Ralph Huits, Kristina M. Angelo, Bhawana Amatya, et al. Clinical Characteristics and Outcomes Among Travelers With Severe Dengue: A GeoSentinel Analysis. Ann Intern Med.2023;176:940-948. [Epub 20 June 2023]. doi:10.7326/M23-0721

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