Tomashek Kay M, Lorenzi Olga D, Andújar-Pérez Doris A, Torres-Velásquez Brenda C, Hunsperger Elizabeth A, Munoz-Jordan Jorge Luis, Perez-Padilla Janice, Rivera Aidsa, Gonzalez-Zeno Gladys E, Sharp Tyler M, Galloway Renee L, Glass Elrod Mindy, Mathis Demetrius L, Oberste M Steven, Nix W Allan, Henderson Elizabeth, McQuiston Jennifer, Singleton Joseph, Kato Cecilia, García Gubern Carlos, Santiago-Rivera William, Cruz-Correa Jesús, Muns-Sosa Robert, Ortiz-Rivera Juan D, Jiménez Gerson, Galarza Ivonne E, Horiuchi Kalanthe, Margolis Harold S, Alvarado Luisa I
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.
PLoS Negl Trop Dis. 2017 Sep 13;11(9):e0005859. doi: 10.1371/journal.pntd.0005859. eCollection 2017 Sep.
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.
由于临床表现不具特异性且诊断手段有限，确定急性发热性疾病（AFI）的病因颇具挑战性。前瞻性AFI研究提供了一种按年龄和病因描述该综合征的方法，这些研究结果可用于制定病例定义和多重诊断方法，以优化治疗管理。我们在波多黎各进行了一项为期3年的前瞻性AFI研究。对发热≤7天的患者进行招募，并在入组时以及出院或随访时收集临床数据和样本。采用逆转录聚合酶链反应（RT-PCR）和免疫诊断方法对血液及口鼻咽样本进行检测，以确定是否感染登革病毒（DENV）1-4型、基孔肯雅病毒（CHIKV）、甲型和乙型流感病毒（FLU A/B）、其他12种呼吸道病毒（ORV）、肠道病毒、钩端螺旋体属以及类鼻疽伯克霍尔德菌。将感染DENV的参与者的临床表现和实验室检查结果与感染CHIKV、FLU A/B和ORV的参与者进行比较。根据年龄和发病后天数（DPO）确定与所有其他AFI病因相比，实验室确诊登革热的临床预测因素。在2012年5月7日至2015年5月6日招募的8996名参与者中，超过一半（54.8%，4930人）检测到病原体。最常检测到的病原体为CHIKV（1635例，18.2%）、FLU A/B（1074例，11.9%）、DENV 1-4型（970例，10.8%）和ORV（904例，10.3%）。与其他诊断的参与者相比，感染DENV的参与者就诊时间较晚，且住院比例更高（感染ORV的为27.3%，感染FLU A/B的为18.8%，感染CHIKV的为11.2%，而感染DENV的为46.7%）。发病<3天就诊的参与者中，登革热的预测因素包括白细胞减少、血小板减少、头痛、眼痛、恶心和头晕，而烦躁和流涕为阴性预测因素。发病3-5天就诊的参与者中，登革热的预测因素为白细胞减少、血小板减少、面部/颈部红斑、恶心、眼痛、循环不良体征和腹泻；流涕、咳嗽和结膜充血提示非登革热AFI。通过在临床表现时招募发热患者，我们确定了与AFI其他常见病因相比，实验室确诊登革热的无偏倚预测因素。这些研究结果可用于协助早期识别登革热患者，并提供直接的预期指导以及及时启动正确的临床管理。
