Tools for the Diagnosis of Herpes Simplex Virus 1/2: A Systematic Review of Studies Published Between 2012-2018 (Preprint)

BACKGROUND: Herpes simplex virus (HSV)-1 and HSV-2 are common infections affecting the global population, with HSV-1 estimated to affect 67% of the global population. HSV can have rare but severe manifestations, such as encephalitis and neonatal herpes, necessitating the use of reliable and accurate diagnostic tools for the detection of the viruses. Currently used HSV diagnostic tools require highly specialized skills and availability of a laboratory setting but may lack sensitivity. The numerous recently developed HSV diagnostic tools need to be identified and compared in a systematic way to make the best decision about which diagnostic tool to use. The diagnosis of HSV is essential for prompt treatment with antivirals. To select the best test for a patient, knowledge of the performance and limitations of each test is critical. OBJECTIVE: This systematic review has summarized recent studies evaluating HSV-1 and HSV-2 diagnostic tools. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, selection criteria, data extraction, and data analysis were determined before the commencement of the study. Studies assessing the specificity/sensitivity of HSV-1 or HSV-2 diagnostic tools published between 2012 and 2018 were included. Quality assessment of included studies was performed using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. RESULTS: Searches of the PubMed database yielded 264 studies; 11 studies included 11 molecular assays, and 8 studies included 19 different serological assays for the detection of HSV-1, HSV-2, or both. A greater proportion of molecular assay-based tools are being developed by commercial entities. Studies that tested molecular assays mostly focused on cutaneous and mucosal HSV infections (n=13); 2 studies focused on ocular disease, whereas only 1 study focused on the central nervous system manifestations. The Simplexa HSV 1 & 2 Direct is currently the only Food and Drug Administration-approved device for use on cerebrospinal fluid. No tools focused on prenatal screening. We also present performance metrics of tests for benchmarking of future technology. Most of the included studies had a high risk of bias rating in half of the QUADAS-2 tool risk of bias domains. CONCLUSIONS: The use of serologic tests to diagnose genital lesions is inappropriate because positive results may be due to chronic infection, whereas negative results may overlook recent infection. The incidence of acute infections is rising. As these infections present the greatest risk to fetuses, work needs to be done to prevent vertical transfer. Prenatal screening for primary infection and subsequent medical intervention will assist in lowering the rate of neonatal herpes. In conclusion, HSV diagnosis is moving away from culture-based methods to serology-based or polymerase chain reaction-based methods. Sensitive, rapid, and efficient HSV diagnostic tools should be adopted for the prevention of acute infections and neonatal herpes.