Scoring systems for prediction of malaria and dengue fever in non-endemic areas among travellers arriving from tropical and subtropical areas

Abstract

Background: Fever is a common symptom among travellers returning from tropical/subtropical areas to Europe, and promptly distinguishing severe illnesses from self-limiting febrile syndromes is important but can be challenging due to non-specific clinical presentation.

Methods: A cross-sectional study enrolled adults and children who sought care during 2015-2020 at Karolinska University Hospital, Stockholm, Sweden with fever within 2 months after returning from travel to a tropical/subtropical area. Data on symptoms and laboratory parameters were prospectively and retrospectively collected. Two separate scoring systems for malaria and dengue were developed based on backward elimination regressions.

Results: In total, 2113 adults (18-94 years) and 202 children (1-17 years) were included, with 112 (4.8%) confirmed malaria by blood thick smear and 90 (3.9%) PCR/serology dengue-positive cases. Malaria was more likely in a patient who had visited sub-Saharan Africa and presented with combination of thrombocytopenia, anaemia and fever ≥39.5°C. Leucopenia, muscle pain and rash after travelling to Asia or South/Latin America indicated high probability of dengue. Two scoring systems with points between 0 and 7 for prediction of malaria or dengue were created based on the above predictors. Scores ≥3 indicated >80% sensitivity and specificity for malaria and >90% specificity for dengue in children and adults (area under the curve (AUC) for dengue: 0.92 in adults (95% CI 0.90 to 0.95) and 0.95 in children (95% CI 0.88 to 1.0); AUC for malaria: 0.93 in adults (95% CI 0.91 to 0.96) and 0.88 in children (95% CI 0.78 to 0.99)). Internal validation of optimism and overfitting was managed with bootstrap.

Conclusion: The presented scoring systems provide novel tools for structured assessment of patients with tropical fever in a non-endemic area and highlight clinical signs associated with a potential severe aetiology to direct the need for microbial investigation.

Keywords: clinical management; management; pediatric emergency medicine; tropical medicine.

Figure 1

OR of predictors* for malaria and dengue in children and adults estimated by univariate logistic regression. Only the predictors that were statistically significant in any diagnosis and age group are presented (for the 95% CI, see online supplemental table 7). *Total 24 clinical predictors and 6 regions included: cough, vomiting, diarrhoea, abdominal pain, nausea, malaise, pulse, saturation, RR, headache, rash, muscle pain, urinary symptoms, confusion, anaemia, leucocytes, thrombocytes, neutrophils, lymphocytes, CRP, ASAT, ALAT, creatinine and fever measured at the ED. Regions: sub-Saharan Africa, Asia & Pacific, South/Latin America, Middle East/North Africa, South Europe, North America. ALAT, alanine aminotransferase; ASAT, aspartate transaminase; CRP, C reactive protein.

Figure 2

ROC curve of malaria scoring system for adults (A) and children (B) and dengue scoring system for adults (C) and children (D). ROC curves for clinical chemistry and visited region/symptoms as separate comparing curves. *Clinical chemistry=thrombocytopenia, anaemia, lymphocytopenia, neutropenia. ROC, receiver operating characteristic.