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Updated: May 5, 2026
Multiplexed Isothermal Amplification Based Diagnostic Platform to Detect Zika, Chikungunya, and Dengue 1
Published on: March 13, 2018
A comparative analysis of dengue, chikungunya, and Zika in a pediatric cohort over 18 years
Insights
Dengue, chikungunya, and Zika virus infections in children have overlapping symptoms. This study identified key distinguishing features for each disease, including abdominal pain for dengue, joint pain for chikungunya, and rash for Zika, aiding in diagnosis.
Area of Science:
- Pediatric infectious diseases
- Clinical epidemiology
- Arbovirology
Background:
- Dengue, chikungunya, and Zika virus infections are significant public health concerns.
- Diagnosing these arboviruses in children is challenging due to overlapping clinical presentations.
- Limited research directly compares these three diseases in pediatric populations.
Purpose of the Study:
- To identify distinct clinical characteristics of dengue, chikungunya, and Zika in children and adolescents.
- To improve differential diagnosis of these febrile illnesses in pediatric patients.
- To provide updated insights into arbovirus manifestations in young individuals.
Main Methods:
- Analysis of laboratory-confirmed pediatric cases (2-<18 years) from a longitudinal cohort study in Nicaragua (2006-2023).
- Collection and analysis of clinical records and laboratory results within the first 10 days of illness.
- Utilized generalized additive models, day-and-disease-specific prevalence estimates, and machine learning for data analysis.
Main Results:
- Characterized 1,405 dengue, 517 chikungunya, and 522 Zika cases.
- Dengue cases showed higher prevalence of abdominal pain, leukopenia, nausea, vomiting, and basophilia.
- Chikungunya cases were distinguished by arthralgia and absence of leukopenia; Zika cases by rash and absence of fever/lymphocytopenia.
- Afebrile dengue cases were identified, presenting similarly to afebrile Zika cases.
Conclusions:
- Clinical features like arthralgia, basophilia, and fever absence are key differentiators for chikungunya, dengue, and Zika, respectively.
- Findings enhance understanding of arbovirus disease in children and improve diagnostic capabilities.
- The existence of afebrile dengue necessitates a review of current international case definitions and diagnostic guidelines.
Background:
Dengue, chikungunya, and Zika are diseases of major human concern. Differential diagnosis is complicated in children and adolescents by their overlapping clinical features (signs, symptoms, and complete blood count results). Few studies have directly compared the three diseases. We aimed to identify distinguishing pediatric characteristics of each disease.
Methods:
Data were derived from laboratory-confirmed cases (symptomatic infections) aged 2-<18 years enrolled in a longitudinal cohort study in Managua, Nicaragua, and attending a primary health care center from January 19, 2006, through December 31, 2023. We collected clinical records and laboratory results across the first 10 days of illness. Data were analyzed with generalized additive models, day-and-disease-specific prevalence estimates, and machine learning models.
Findings:
We characterized 1,405 dengue, 517 chikungunya, and 522 Zika pediatric cases. We included 1,165 (47·7%) males and 1,279 (52·3%) females, with a median age of 10·0 (IQR 7·0-12·7) years. The prevalence of many clinical features exhibited by dengue, chikungunya, and Zika cases differed substantially overall, by age, and by day of illness. Dengue cases were differentiated most by abdominal pain (Prevalence difference (PD) 19·1%, 95% confidence interval (CI): 15·7%, 22·9%), leukopenia (PD 41·1%, 95% CI: 36·2%, 45·6%), nausea (PD 15·5%, 95% CI: 12·2%, 19·2%), vomiting (PD 21·9%, 95% CI: 17·9%, 26·1%), and basophilia (PD 42·3%, 95% CI: 37·4%, 47·0%); chikungunya cases were differentiated most by arthralgia (PD 60·5%, 95% CI: 56·3%, 64·2%) and the absence of leukopenia (PD -32·0%, 95% CI: -36·7%, -27·1%) and papular rash (PD -14·9%, 95% CI: -17·2%, -12·7%); and Zika cases were differentiated most by rash (PD 31·8%, 95% CI: 27·0%, 36·2%) and the lack of fever (PD -37·3%, 95% CI: -41·7%, -33·0%) and lymphocytopenia (PD -41·9%, 95% CI: -46·6%, -37·1%). Dengue and chikungunya cases exhibited similar temperature dynamics during acute illness, and their temperatures were higher than Zika cases. Sixty-two laboratory-confirmed afebrile dengue cases, which would not be captured by any widely used international case definition, presented very similarly to afebrile Zika cases, though some exhibited warning signs of disease severity. The presence of arthralgia, the presence of basophilia, and the absence of fever were the most important model-based distinguishing predictors of chikungunya, dengue, and Zika, respectively.
Interpretations:
These findings substantially update our understanding of dengue, chikungunya, and Zika in children while identifying various clinical features that could improve differential diagnoses. The occurrence of afebrile dengue warrants reconsideration of current guidance.
Funding:
US National Institutes of Health R01AI099631, P01AI106695, U01AI153416, U19AI118610.
