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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
K D Rosenberger PhD, F Tobian MSc, T Jaenisch MD PhD) and Heidelberg Institute of Global Health (Prof M Sarker MD PhD, T Jaenisch), Heidelberg University Hospital, Heidelberg, Germany; Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, Cologne, Germany (K D Rosenberger); Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Viet Nam (L Phung Khanh MD PhD, T Dong Thi Hoai MD PhD, K Nguyen Tan Thanh MPharm, S Yacoub MD PhD, Q Nguyen Than Ha PhD, Prof C P Simmons PhD, Prof B A Wills FRCPCH, R B Geskus PhD); Angkor Hospital for Children, Siem Reap, Cambodia (N Chanpheaktra MD, V Kumar MD); East Tennessee State University Quillen College of Medicine, Johnson City, TN, USA (V Kumar); University of Malaya, Medical Centre, Kuala Lumpur, Malaysia (Prof L C S Lum MRCP); Ampang Hospital, Ministry of Health, Kuala Lumpur, Malaysia (J Sathar MD); Hospital Nacional de Niños Benjamin Bloom, San Salvador, El Salvador (E Pleités Sandoval MD, G M Marón MD); St Jude Children’s Research Hospital, Memphis, TN, USA (G M Marón); Center for Tropical Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia (I S Laksono MD PhD, Y Mahendradhata MD PhD); Department of Child Health, Dr Sardjito General Hospital, Yogyakarta, Indonesia (I S Laksono); James P Grant School of Public Health, BRAC University, Dhaka, Bangladesh (Prof M Sarker); Shaheed Suhrawardy Medical College and Hospital, Dhaka, Bangladesh (Prof R Rahman FCPS); Universidade Estadual Do Ceará, Fortaleza, Brazil (Prof A Caprara MD PhD, B Souza Benevides MD PhD); Centro Universitário ChristusUnichristus, Fortaleza, Brazil (B Souza Benevides); Centro Universitário FametroUnifametro, Fortaleza, Brazil (B Souza Benevides); Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Pernambuco, Brazil (Prof E T A Marques MD PhD, T Magalhaes PhD); Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA (Prof E T A Marques); Departamento de Medicina Preventiva e Social, Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil (T Magalhaes); Department of Entomology, Texas A&M University, College Station, TX, USA (T Magalhaes); Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil (Prof P Brasil MD PhD, G Amaral Calvet MD PhD); Facultad de Ciencias de la Salud, Universidad de Carabobo, Valencia, Venezuela (A Tami MD PhD, S E Bethencourt PhD); Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, Netherlands (A Tami); Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam (N Tran Van MD); Children’s Hospital Number 2, Ho Chi Minh City, Viet Nam (N Nguyen Tran MD, V Do Chau MD); Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK (S Yacoub, Prof B A Wills, R B Geskus); National Hospital for Tropical Diseases, Hanoi, Viet Nam (Prof K Nguyen Van MD PhD); Institute of Tropical Medicine “Pedro Kouri” (IPK), Havana, Cuba (Prof M G Guzmán MD PhD, P A Martinez MD PhD); Institute of Vector-borne Disease, Monash University, Melbourne, VIC, Australia (Prof C P Simmons); Center for Global Health, Colorado School of Public Health, Aurora, CO, USA (T Jaenisch); Paediatric Infectious Diseases, Colorado School of Medicine, Aurora, CO, USA (T Jaenisch) Correspondence to: Dr Thomas Jaenisch, Heidelberg Institute of Global Health (HIGH), Heidelberg University Hospital, Heidelberg 69120, Germany.
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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.
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Elsevier
Citation
ROSENBERGER, Kerstin D. et al. Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study. The Lancet Global Health, v. 11, p. 1-12, Mar. 2023.DOI
10.1016/S2214-109X(22)00514-9ISSN
2214-109XNotes
Patricia Brasill - Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brazil.K D Rosenberger PhD, F Tobian MSc, T Jaenisch MD PhD) and Heidelberg Institute of Global Health (Prof M Sarker MD PhD, T Jaenisch), Heidelberg University Hospital, Heidelberg, Germany; Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, Cologne, Germany (K D Rosenberger); Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Viet Nam (L Phung Khanh MD PhD, T Dong Thi Hoai MD PhD, K Nguyen Tan Thanh MPharm, S Yacoub MD PhD, Q Nguyen Than Ha PhD, Prof C P Simmons PhD, Prof B A Wills FRCPCH, R B Geskus PhD); Angkor Hospital for Children, Siem Reap, Cambodia (N Chanpheaktra MD, V Kumar MD); East Tennessee State University Quillen College of Medicine, Johnson City, TN, USA (V Kumar); University of Malaya, Medical Centre, Kuala Lumpur, Malaysia (Prof L C S Lum MRCP); Ampang Hospital, Ministry of Health, Kuala Lumpur, Malaysia (J Sathar MD); Hospital Nacional de Niños Benjamin Bloom, San Salvador, El Salvador (E Pleités Sandoval MD, G M Marón MD); St Jude Children’s Research Hospital, Memphis, TN, USA (G M Marón); Center for Tropical Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia (I S Laksono MD PhD, Y Mahendradhata MD PhD); Department of Child Health, Dr Sardjito General Hospital, Yogyakarta, Indonesia (I S Laksono); James P Grant School of Public Health, BRAC University, Dhaka, Bangladesh (Prof M Sarker); Shaheed Suhrawardy Medical College and Hospital, Dhaka, Bangladesh (Prof R Rahman FCPS); Universidade Estadual Do Ceará, Fortaleza, Brazil (Prof A Caprara MD PhD, B Souza Benevides MD PhD); Centro Universitário ChristusUnichristus, Fortaleza, Brazil (B Souza Benevides); Centro Universitário FametroUnifametro, Fortaleza, Brazil (B Souza Benevides); Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Pernambuco, Brazil (Prof E T A Marques MD PhD, T Magalhaes PhD); Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA (Prof E T A Marques); Departamento de Medicina Preventiva e Social, Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil (T Magalhaes); Department of Entomology, Texas A&M University, College Station, TX, USA (T Magalhaes); Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil (Prof P Brasil MD PhD, G Amaral Calvet MD PhD); Facultad de Ciencias de la Salud, Universidad de Carabobo, Valencia, Venezuela (A Tami MD PhD, S E Bethencourt PhD); Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, Netherlands (A Tami); Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam (N Tran Van MD); Children’s Hospital Number 2, Ho Chi Minh City, Viet Nam (N Nguyen Tran MD, V Do Chau MD); Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK (S Yacoub, Prof B A Wills, R B Geskus); National Hospital for Tropical Diseases, Hanoi, Viet Nam (Prof K Nguyen Van MD PhD); Institute of Tropical Medicine “Pedro Kouri” (IPK), Havana, Cuba (Prof M G Guzmán MD PhD, P A Martinez MD PhD); Institute of Vector-borne Disease, Monash University, Melbourne, VIC, Australia (Prof C P Simmons); Center for Global Health, Colorado School of Public Health, Aurora, CO, USA (T Jaenisch); Paediatric Infectious Diseases, Colorado School of Medicine, Aurora, CO, USA (T Jaenisch) Correspondence to: Dr Thomas Jaenisch, Heidelberg Institute of Global Health (HIGH), Heidelberg University Hospital, Heidelberg 69120, Germany.
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