Tourniquet Test for Dengue Diagnosis: Systematic Review and Meta-analysis of Diagnostic Test Accuracy

Abstract

Background: Dengue fever is a ubiquitous arboviral infection in tropical and sub-tropical regions, whose incidence has increased over recent decades. In the absence of a rapid point of care test, the clinical diagnosis of dengue is complex. The World Health Organisation has outlined diagnostic criteria for making the diagnosis of dengue infection, which includes the use of the tourniquet test (TT).

Purpose: To assess the quality of the evidence supporting the use of the TT and perform a diagnostic accuracy meta-analysis comparing the TT to antibody response measured by ELISA.

Data sources: A comprehensive literature search was conducted in the following databases to April, 2016: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, BIOSIS, Web of Science, SCOPUS.

Study selection: Studies comparing the diagnostic accuracy of the tourniquet test with ELISA for the diagnosis of dengue were included.

Data extraction: Two independent authors extracted data using a standardized form.

Data synthesis: A total of 16 studies with 28,739 participants were included in the meta-analysis. Pooled sensitivity for dengue diagnosis by TT was 58% (95% Confidence Interval (CI), 43%-71%) and the specificity was 71% (95% CI, 60%-80%). In the subgroup analysis sensitivity for non-severe dengue diagnosis was 55% (95% CI, 52%-59%) and the specificity was 63% (95% CI, 60%-66%), whilst sensitivity for dengue hemorrhagic fever diagnosis was 62% (95% CI, 53%-71%) and the specificity was 60% (95% CI, 48%-70%). Receiver-operator characteristics demonstrated a test accuracy (AUC) of 0.70 (95% CI, 0.66-0.74).

Conclusion: The tourniquet test is widely used in resource poor settings despite currently available evidence demonstrating only a marginal benefit in making a diagnosis of dengue infection alone.

Registration: The protocol for this systematic review was registered at

Prospero: CRD42015020323.

Fig 1. Flow chart of systematic review process.

Fig 2. Quality Assessment of Diagnostic Accuracy Studies II.

Fig 3. Forest plot for individual studies and pooled sensitivity and specificity for Dengue x ELISA.

Q: chi-squared statistic; df: degrees of freedom; I²: inconsistency of studies’ results; Dashed line means the mean number found across studies.

Fig 4. RoC curve for all three comparisons conducted in the study.

A = Dengue x ELISA; B = Dengue fever x ELISA, C = Dengue haemorrhagic fever x ELISA.

Fig 5. Forest plot for individual studies and pooled sensitivity and specificity for Dengue Fever x ELISA.

Q: chi-squared statistic; df: degrees of freedom; I2: inconsistency of studies’ results; Dashed line means the mean number found across studies.

Fig 6. Forest plot for individual studies and pooled sensitivity and specificity for Dengue Haemorragic Fever x ELISA.

Q: chi-squared statistic; df: degrees of freedom; I2: inconsistency of studies’ results; Dashed line means the mean number found across studies.

Fig 7. Forest plot for individual studies and pooled sensitivity and specificity for Dengue x ELISA in children and adolescents aged from 6 months to 15 years.

Q: chi-squared statistic; df: degrees of freedom; I2: inconsistency of studies’ results; Dashed line means the mean number found across studies.

Fig 8. Forest plot for individual studies and pooled sensitivity and specificity for Dengue x ELISA cut-off points reported ≥20 petechiae per one square inch.

Q: chi-squared statistic; df: degrees of freedom; I2: inconsistency of studies’ results; Dashed line means the mean number found across studies.

Fig 9. Forest plot for individual studies and pooled sensitivity and specificity for Dengue x ELISA removing six studies with high risk for selection bias.

Q: chi-squared statistic; df: degrees of freedom; I2: inconsistency of studies’ results; Dashed line means the mean number found across studies.

Fig 10. Publication bias presentation using funnel plot for Dengue x ELISA.