The Lancet Global Health (Mar 2023)

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

  • Kerstin D Rosenberger, PhD,
  • Lam Phung Khanh, MD PhD,
  • Frank Tobian, MSc,
  • Ngoun Chanpheaktra, MD,
  • Varun Kumar, MD,
  • Lucy Chai See Lum, ProfMRCP,
  • Jameela Sathar, MD,
  • Ernesto Pleiteés Sandoval, MD,
  • Gabriela M Maroén, MD,
  • Ida Safitri Laksono, MD PhD,
  • Yodi Mahendradhata, MD PhD,
  • Malabika Sarker, ProfMD PhD,
  • Ridwanur Rahman, ProfFCPS,
  • Andrea Caprara, ProfMD PhD,
  • Bruno Souza Benevides, MD PhD,
  • Ernesto T A Marques, ProfMD PhD,
  • Tereza Magalhaes, PhD,
  • Patrícia Brasil, ProfMD PhD,
  • Guilherme Amaral Calvet, MD PhD,
  • Adriana Tami, MD PhD,
  • Sarah E Bethencourt, PhD,
  • Tam Dong Thi Hoai, MD PhD,
  • Kieu Nguyen Tan Thanh, MPharm,
  • Ngoc Tran Van, MD,
  • Nam Nguyen Tran, MD,
  • Viet Do Chau, MD,
  • Sophie Yacoub, MD PhD,
  • Kinh Nguyen Van, ProfMD PhD,
  • María G Guzmán, ProfMD PhD,
  • Pedro A Martinez, MD PhD,
  • Quyen Nguyen Than Ha, PhD,
  • Cameron P Simmons, ProfPhD,
  • Bridget A Wills, ProfFRCPCH,
  • Ronald B Geskus, PhD,
  • Thomas Jaenisch, MD PhD,
  • Zabir Hasan,
  • Kilma Wanderley Lopes Gomes,
  • Lyvia Patricia Soares Mesquita,
  • Cynthia Braga,
  • Priscila M.S. Castanha,
  • Marli T. Cordeiro,
  • Luana Damasceno,
  • Bophal Chuop,
  • Sonyrath Ouk,
  • Reaksmey Sin,
  • Sopheary Sun,
  • Mayling Alvarez Vera,
  • Guillermo Barahona,
  • Bladimir Cruz,
  • Dorothea Beck,
  • Roger Gaczkowski,
  • Thomas Junghanss,
  • Ivonne Morales,
  • Marius Wirths,
  • Santha Kumari Natkunam,
  • Bee Kiau Ho,
  • Sazaly AbuBakar,
  • Juraina Abd-Jamil,
  • Sharifah Faridah Syed Omar,
  • Erley F. Lizarazo,
  • María F. Vincenti-González,
  • Erley F. Lizarazo,
  • Robert Tovar,
  • María F. Vincenti-González,
  • Tam Cao Thi,
  • Hong Dinh Thi Tri,
  • Huy Huynh Le Anh,
  • Duyen Huynh Thi Le,
  • Thanh Lai Thi Cong,
  • Van Nguyen Thi Hong,
  • Linh Nguyen Thi My,
  • Thuy Tran Thi Nhu,
  • Thuy Truong Thi Thu,
  • Nuoi Banh Thi,
  • Trinh Huynh Lam Thuy,
  • Hiep Nguyen Thi Thu,
  • Van Tran Thi Kim,
  • Luan Vo Thanh,
  • Bich Dang Thi,
  • Huong Dinh Thi Thu,
  • Huy Dinh Van,
  • Huyen Nguyen Nguyen,
  • Huong Vu Thi Thu

Journal volume & issue
Vol. 11, no. 3
pp. e361 – e372

Abstract

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Summary: Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: EU's Seventh Framework Programme. Translations: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section.