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

Rosenberger KD 1 , Phung Khanh L 2 , Tobian F 3 , Chanpheaktra N 4 , Kumar V 5 , Lum LCS 6 Show all authors , Sathar J 7 , Pleités Sandoval E 8 , Marón GM 9 , Laksono IS 10 , Mahendradhata Y 11 , Sarker M 12 , Rahman R 13 , Caprara A 14 , Souza Benevides B 15 , Marques ETA 16 , Magalhaes T 17 , Brasil P 18 , Amaral Calvet G 18 , Tami A 19 , Bethencourt SE 20 , Dong Thi Hoai T 2 , Nguyen Tan Thanh K 2 , Tran Van N 21 , Nguyen Tran N 22 , Do Chau V 22 , Yacoub S 23 , Nguyen Van K 24 , Guzmán MG 25 , Martinez PA 25 , Nguyen Than Ha Q 2 , Simmons CP 26 , Wills BA 23 , Geskus RB 23 , Jaenisch T 27 , International Research Consortium on Dengue Risk Assessment, Management, and Surveillance Investigators

Affiliations 

  • 1 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
  • 2 Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Viet Nam
  • 3 Section Clinical Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany
  • 4 Angkor Hospital for Children, Siem Reap, Cambodia
  • 5 Angkor Hospital for Children, Siem Reap, Cambodia; East Tennessee State University Quillen College of Medicine, Johnson City, TN, USA
  • 6 University of Malaya, Medical Centre, Kuala Lumpur, Malaysia
  • 7 Ampang Hospital, Ministry of Health, Kuala Lumpur, Malaysia
  • 8 Hospital Nacional de Niños Benjamin Bloom, San Salvador, El Salvador
  • 9 Hospital Nacional de Niños Benjamin Bloom, San Salvador, El Salvador; St Jude Children's Research Hospital, Memphis, TN, USA
  • 10 Center for Tropical Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; Department of Child Health, Dr Sardjito General Hospital, Yogyakarta, Indonesia
  • 11 Center for Tropical Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • 12 Heidelberg Institute of Global Health, Heidelberg University Hospital, Heidelberg, Germany; James P Grant School of Public Health, BRAC University, Dhaka, Bangladesh
  • 13 Shaheed Suhrawardy Medical College and Hospital, Dhaka, Bangladesh
  • 14 Universidade Estadual Do Ceará, Fortaleza, Brazil
  • 15 Universidade Estadual Do Ceará, Fortaleza, Brazil; Centro Universitário Christus-Unichristus, Fortaleza, Brazil; Centro Universitário Fametro-Unifametro, Fortaleza, Brazil
  • 16 Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Pernambuco, Brazil; Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
  • 17 Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Pernambuco, Brazil; Departamento de Medicina Preventiva e Social, Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil; Department of Entomology, Texas A&M University, College Station, TX, USA
  • 18 Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
  • 19 Facultad de Ciencias de la Salud, Universidad de Carabobo, Valencia, Venezuela; Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • 20 Facultad de Ciencias de la Salud, Universidad de Carabobo, Valencia, Venezuela
  • 21 Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam
  • 22 Children's Hospital Number 2, Ho Chi Minh City, Viet Nam
  • 23 Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK
  • 24 National Hospital for Tropical Diseases, Hanoi, Viet Nam
  • 25 Institute of Tropical Medicine "Pedro Kouri" (IPK), Havana, Cuba
  • 26 Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Viet Nam; Institute of Vector-borne Disease, Monash University, Melbourne, VIC, Australia
  • 27 Section Clinical Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute of Global Health, Heidelberg University Hospital, Heidelberg, Germany; Center for Global Health, Colorado School of Public Health, Aurora, CO, USA; Paediatric Infectious Diseases, Colorado School of Medicine, Aurora, CO, USA. Electronic address: [email protected]
Lancet Glob Health, 2023 Mar;11(3):e361-e372.
PMID: 36796983 DOI: 10.1016/S2214-109X(22)00514-9

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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