Rosenberger Kerstin D, Phung Khanh Lam, Tobian Frank, Chanpheaktra Ngoun, Kumar Varun, Lum Lucy Chai See, Sathar Jameela, Pleités Sandoval Ernesto, Marón Gabriela M, Laksono Ida Safitri, Mahendradhata Yodi, Sarker Malabika, Rahman Ridwanur, Caprara Andrea, Souza Benevides Bruno, Marques Ernesto T A, Magalhaes Tereza, Brasil Patrícia, Amaral Calvet Guilherme, Tami Adriana, Bethencourt Sarah E, Dong Thi Hoai Tam, Nguyen Tan Thanh Kieu, Tran Van Ngoc, Nguyen Tran Nam, Do Chau Viet, Yacoub Sophie, Nguyen Van Kinh, Guzmán María G, Martinez Pedro A, Nguyen Than Ha Quyen, Simmons Cameron P, Wills Bridget A, Geskus Ronald B, Jaenisch Thomas
Section Clinical Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany; Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, Cologne, Germany.
Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Viet Nam.
Lancet Glob Health. 2023 Mar;11(3):e361-e372. doi: 10.1016/S2214-109X(22)00514-9.
Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management.
In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values.
Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only.
Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook.
EU's Seventh Framework Programme.
For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section.
登革热早期诊断的改进迫在眉睫，尤其是在资源有限的环境中，登革热与其他发热性疾病的区分对患者管理至关重要。
在这项前瞻性观察研究（IDAMS）中，我们纳入了来自八个国家（孟加拉国、巴西、柬埔寨、萨尔瓦多、印度尼西亚、马来西亚、委内瑞拉和越南）26个门诊机构的5岁及以上初诊时患有未分化发热的患者。我们使用多变量逻辑回归来研究发热（即发病日）后第2天至第5天临床症状和实验室检查与登革热及其他发热性疾病之间的关联。我们构建了一组候选回归模型，包括临床和实验室变量，以反映采用综合方法与简约方法的必要性。我们通过诊断价值的标准指标评估这些模型的性能。
2011年10月18日至2016年8月4日期间，我们招募了7428名患者，其中2694名（36%）被诊断为实验室确诊的登革热，2495名（34%）患有（非登革热）其他发热性疾病且符合纳入标准，并被纳入分析。纳入分析的5189名患者中，2703名（52%）年龄小于15岁，2486名（48%）年龄为15岁及以上，2179名（42%）为女性，3010名（58%）为男性。血小板计数、白细胞计数以及这些变量与前一天疾病状态的变化与登革热密切相关。咳嗽和鼻炎与其他发热性疾病密切相关，而出血、厌食和皮肤潮红通常与登革热相关。疾病第2天至第5天模型性能有所提高。综合模型（18个临床和实验室预测指标）的敏感性为0.80至0.87，特异性为0.80至0.91，而简约模型（8个临床和实验室预测指标）的敏感性为0.80至0.88，特异性为0.81至0.89。一个包含易于测量的实验室指标（如血小板计数或白细胞计数）的模型优于仅基于临床变量的模型。
我们的结果证实了血小板和白细胞计数在诊断登革热中的重要作用，以及后续几天连续测量的重要性。我们成功量化了涵盖登革热早期的临床和实验室指标的性能。所得算法在区分登革热与其他发热性疾病方面比已发表的方案表现更好，并考虑了随时间的动态变化。我们的结果为包括《儿童疾病综合管理》手册在内的指南更新提供了关键信息。
欧盟第七框架计划。
摘要的孟加拉语、印度尼西亚语、葡萄牙语、高棉语、西班牙语和越南语翻译见补充材料部分。
