Scrub typhus point-of-care testing: A systematic review and meta-analysis

Background: Diagnosing scrub typhus clinically is difficult, hence laboratory tests play a very important role in diagnosis. As performing sophisticated laboratory tests in resource-limited settings is not feasible, accurate point-of-care testing (POCT) for scrub typhus diagnosis would be invaluable for patient diagnosis and management. Here we summarise the existing evidence on the accuracy of scrub typhus POCTs to inform clinical practitioners in resource-limited settings of their diagnostic value. Methodology/principal findings: Studies on POCTs which can be feasibly deployed in primary health care or outpatient settings were included. Thirty-one studies were identified through PubMed and manual searches of reference lists. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). About half (n = 14/31) of the included studies were of moderate quality. Meta-analysis showed the pooled sensitivity and specificity of commercially available immunochromatographic tests (ICTs) were 66.0% (95% CI 0.37–0.86) and 92.0% (95% CI 0.83–0.97), respectively. There was a significant and high degree of heterogeneity between the studies (I2 value = 97.48%, 95% CI 96.71–98.24 for sensitivity and I2 value = 98.17%, 95% CI 97.67–98.67 for specificity). Significant heterogeneity was observed for total number of samples between studies (p = 0.01), study design (whether using case-control design or not, p = 0.01), blinding during index test interpretation (p = 0.02), and QUADAS-2 score (p = 0.01). Conclusions/significance: There was significant heterogeneity between the scrub typhus POCT diagnostic accuracy studies examined. Overall, the commercially available scrub typhus ICTs demonstrated better performance when ‘ruling in’ the diagnosis. There is a need for standardised methods and reporting of diagnostic accuracy to decrease between-study heterogeneity and increase comparability among study results, as well as development of an affordable and accurate antigen-based POCT to tackle the inherent weaknesses associated with serological testing. Author summary: Scrub typhus is a disease caused by a mite-transmitted bacterium, Orientia tsutsugamushi. Aside from fever and necrotic skin lesion at the site of mite inoculation (eschar), scrub typhus has virtually no distinctive clinical features, making diagnosis without laboratory tests difficult. However, the laboratory tests often have limited diagnostic accuracy and are generally in limited supply in resource-limited or outpatient settings. In those settings, point-of-care testing (POCT) can be useful in making a quick diagnosis. In this study, the authors reviewed the available evidence on the diagnostic value of scrub typhus POCT. A meta-analysis, focusing on commercially available immunochromatography tests (ICTs), was done. The pooled sensitivity and specificity were 66.0% (95% CI 0.37–0.86) and 92.0% (95% CI 0.83–0.97), respectively. This indicates better performance when ‘ruling in’ a positive diagnosis rather than ‘ruling out’ a negative diagnosis. As ICTs have low false positive rates, confidence in interpreting a positive result can be high. The studies reviewed displayed wide variation in both methodology and quality, indicating a need to develop standards for study methodology and reporting.