Dengue is the world’s most common arboviral infection, with almost 4 billion people estimated to be living at risk of dengue infection. A recently introduced vaccine is currently recommended only for seropositive individuals in a restricted age range determined by transmission intensity. With no effective dengue vaccine for the general population or any antiviral therapy, dengue control continues to rely heavily on vector control measures. Early and accurate diagnosis is important for guiding appropriate management and for disease surveillance to guide prompt dengue control interventions. However, major uncertainties exist in dengue diagnosis and this has important implications for all three. Dengue can be diagnosed clinically against predefined lists of signs and symptoms and by detection of dengue-specific antibodies, non-structural 1 antigen or viral RNA by reverse transcriptase–polymerase chain reaction. All of these methods have their limitations. This review aims to describe and quantify the advantages, uncertainties and variability of the various diagnostic methods used for dengue and discuss their implications and applications for dengue surveillance and control.

Infants in neonatal intensive care units frequently experience clinically necessary painful procedures, which elicit a range of behavioral, physiological, and neurophysiological responses. However, the measurement of pain in this population is a challenge and no gold standard exists. The aim of this study was to investigate how noxious‐evoked changes in facial expression, reflex withdrawal, brain activity, heart rate, and oxygen saturation are related and to examine their accuracy in discriminating between noxious and non‐noxious stimuli. In 109 infants who received a clinically required heel lance and a control non‐noxious stimulus, we investigated whether combining responses across each modality, or including multiple measures from within each modality improves our ability to discriminate the noxious and non‐noxious stimuli. A random forest algorithm was used to build data‐driven models to discriminate between the noxious and non‐noxious stimuli in a training set which were then validated in a test set of independent infants. Measures within each modality were highly correlated, while different modalities showed less association. The model combining information across all modalities had good discriminative ability (accuracy of 0.81 in identifying noxious and non‐noxious stimuli), which was higher than the discriminative power of the models built from individual modalities. This demonstrates the importance of including multiple modalities in the assessment of infant pain.

Background Dengue is the world’s most common mosquito-borne virus but remains diagnostically challenging due to its nonspecific presentation. Access to laboratory confirmation is limited and thus most reported figures are based on clinical diagnosis alone, the accuracy of which is uncertain. This systematic review assesses the diagnostic accuracy of the traditional (1997) and revised (2009) WHO clinical case definitions for dengue fever, the basis for most national guidelines. Methodology/Principal findings PubMed, EMBASE, Scopus, OpenGrey, and the annual Dengue Bulletin were searched for studies assessing the diagnostic accuracy of the unmodified clinical criteria. Two reviewers (NR/SL) independently assessed eligibility, extracted data, and evaluated risk of bias using a modified QUADAS-2. Additional records were found by citation network analysis. A meta-analysis was done using a bivariate mixed-effects regression model. Studies that modified criteria were analysed separately. This systematic review protocol was registered on PROSPERO (CRD42020165998). We identified 11 and 12 datasets assessing the 1997 and 2009 definition, respectively, and 6 using modified criteria. Sensitivity was 93% (95% CI: 77–98) and 93% (95% CI: 86–96) for the 1997 and 2009 definitions, respectively. Specificity was 29% (95% CI: 8–65) and 31% (95% CI: 18–48) for the 1997 and 2009 definitions, respectively. Diagnostic performance suffered at the extremes of age. No modification significantly improved accuracy. Conclusions/Significance Diagnostic accuracy of clinical criteria is poor, with significant implications for surveillance and public health responses for dengue control. As the basis for most reported figures, this has relevance to policymakers planning resource allocation and researchers modelling transmission, particularly during COVID-19.