Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study

• Published in: The Lancet global health Vol. 11; no. 3; pp. e361 - e372
• Main Authors: 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, Hasan, Zabir, Wanderley Lopes Gomes, Kilma, Soares Mesquita, Lyvia Patricia, Braga, Cynthia, Castanha, Priscila M.S., Cordeiro, Marli T., Damasceno, Luana, Chuop, Bophal, Ouk, Sonyrath, Sin, Reaksmey, Sun, Sopheary, Alvarez Vera, Mayling, Barahona, Guillermo, Cruz, Bladimir, Beck, Dorothea, Gaczkowski, Roger, Junghanss, Thomas, Morales, Ivonne, Wirths, Marius, Natkunam, Santha Kumari, Ho, Bee Kiau, AbuBakar, Sazaly, Abd-Jamil, Juraina, Syed Omar, Sharifah Faridah, Lizarazo, Erley F., Vincenti-González, María F., Tovar, Robert, Cao Thi, Tam, Dinh Thi Tri, Hong, Huynh Le Anh, Huy, Huynh Thi Le, Duyen, Lai Thi Cong, Thanh, Nguyen Thi Hong, Van, Nguyen Thi My, Linh, Tran Thi Nhu, Thuy, Truong Thi Thu, Thuy, Banh Thi, Nuoi, Huynh Lam Thuy, Trinh, Nguyen Thi Thu, Hiep, Tran Thi Kim, Van, Vo Thanh, Luan, Dang Thi, Bich, Dinh Thi Thu, Huong, Dinh Van, Huy, Nguyen Nguyen, Huyen, Vu Thi Thu, Huong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-03-2023; Elsevier
• Subjects: Asia; Bangladesh; Biomarkers; Female; Fever - diagnosis; Fever - etiology; Humans; Latin America - epidemiology; Male; Prospective Studies; Asia; Bangladesh; Latin America
• ISSN: 2214-109X; 2214-109X
• 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.