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Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012-2015.
PLoS Negl Trop Dis. 2017 Sep; 11(9):e0005859.PN

Abstract

Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1-4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1-4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3-5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management.

Authors+Show Affiliations

Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico, United States of America.Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico, United States of America.Ponce Health Sciences University/Saint Luke's Episcopal Hospital, Ponce, Puerto Rico, United States of America.Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico, United States of America.Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico, United States of America.Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico, United States of America.Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico, United States of America.Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico, United States of America.Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico, United States of America.Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico, United States of America.Bacterial Special Pathogens Branch, Zoonoses and Select Agent Laboratory, CDC, Atlanta, Georgia, United States of America.Bacterial Special Pathogens Branch, Zoonoses and Select Agent Laboratory, CDC, Atlanta, Georgia, United States of America.Bacterial Special Pathogens Branch, Zoonoses and Select Agent Laboratory, CDC, Atlanta, Georgia, United States of America.Polio and Picornavirus Laboratory Branch, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, CDC, Atlanta, Georgia, United States of America.Polio and Picornavirus Laboratory Branch, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, CDC, Atlanta, Georgia, United States of America.Polio and Picornavirus Laboratory Branch, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, CDC, Atlanta, Georgia, United States of America.Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, CDC, Atlanta, Georgia, United States of America.Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, CDC, Atlanta, Georgia, United States of America.Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, CDC, Atlanta, Georgia, United States of America.Ponce Health Sciences University/Saint Luke's Episcopal Hospital, Ponce, Puerto Rico, United States of America.Ponce Health Sciences University/Saint Luke's Episcopal Hospital, Ponce, Puerto Rico, United States of America.Ponce Health Sciences University/Saint Luke's Episcopal Hospital, Ponce, Puerto Rico, United States of America.Saint Luke's Episcopal Hospital, Guayama, Puerto Rico, United States of America.Saint Luke's Episcopal Hospital, Guayama, Puerto Rico, United States of America.Saint Luke's Episcopal Hospital, Guayama, Puerto Rico, United States of America.Ponce Health Sciences University/Saint Luke's Episcopal Hospital, Ponce, Puerto Rico, United States of America.Office of the Director, Division of Vector-Borne Diseases, CDC, Fort Collins, Colorado, United States of America.Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), San Juan, Puerto Rico, United States of America.Ponce Health Sciences University/Saint Luke's Episcopal Hospital, Ponce, Puerto Rico, United States of America.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28902845

Citation

Tomashek, Kay M., et al. "Clinical and Epidemiologic Characteristics of Dengue and Other Etiologic Agents Among Patients With Acute Febrile Illness, Puerto Rico, 2012-2015." PLoS Neglected Tropical Diseases, vol. 11, no. 9, 2017, pp. e0005859.
Tomashek KM, Lorenzi OD, Andújar-Pérez DA, et al. Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012-2015. PLoS Negl Trop Dis. 2017;11(9):e0005859.
Tomashek, K. M., Lorenzi, O. D., Andújar-Pérez, D. A., Torres-Velásquez, B. C., Hunsperger, E. A., Munoz-Jordan, J. L., Perez-Padilla, J., Rivera, A., Gonzalez-Zeno, G. E., Sharp, T. M., Galloway, R. L., Glass Elrod, M., Mathis, D. L., Oberste, M. S., Nix, W. A., Henderson, E., McQuiston, J., Singleton, J., Kato, C., ... Alvarado, L. I. (2017). Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012-2015. PLoS Neglected Tropical Diseases, 11(9), e0005859. https://doi.org/10.1371/journal.pntd.0005859
Tomashek KM, et al. Clinical and Epidemiologic Characteristics of Dengue and Other Etiologic Agents Among Patients With Acute Febrile Illness, Puerto Rico, 2012-2015. PLoS Negl Trop Dis. 2017;11(9):e0005859. PubMed PMID: 28902845.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012-2015. AU - Tomashek,Kay M, AU - Lorenzi,Olga D, AU - Andújar-Pérez,Doris A, AU - Torres-Velásquez,Brenda C, AU - Hunsperger,Elizabeth A, AU - Munoz-Jordan,Jorge Luis, AU - Perez-Padilla,Janice, AU - Rivera,Aidsa, AU - Gonzalez-Zeno,Gladys E, AU - Sharp,Tyler M, AU - Galloway,Renee L, AU - Glass Elrod,Mindy, AU - Mathis,Demetrius L, AU - Oberste,M Steven, AU - Nix,W Allan, AU - Henderson,Elizabeth, AU - McQuiston,Jennifer, AU - Singleton,Joseph, AU - Kato,Cecilia, AU - García Gubern,Carlos, AU - Santiago-Rivera,William, AU - Cruz-Correa,Jesús, AU - Muns-Sosa,Robert, AU - Ortiz-Rivera,Juan D, AU - Jiménez,Gerson, AU - Galarza,Ivonne E, AU - Horiuchi,Kalanthe, AU - Margolis,Harold S, AU - Alvarado,Luisa I, Y1 - 2017/09/13/ PY - 2017/05/08/received PY - 2017/08/07/accepted PY - 2017/9/14/entrez PY - 2017/9/14/pubmed PY - 2017/9/20/medline SP - e0005859 EP - e0005859 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 11 IS - 9 N2 - Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1-4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1-4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3-5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/28902845/full_citation L2 - https://dx.plos.org/10.1371/journal.pntd.0005859 DB - PRIME DP - Unbound Medicine ER -