Maximizing Human Rabies Case Detection: Understanding the Diagnostic Sensitivity of Antemortem Testing From 35 Years of US Data

Le résumé fourni par la source

BACKGROUND: Human rabies underdetection is a global challenge due in part to under-testing. Antemortem diagnosis obviates challenges associated with postmortem testing and is critical to timely clinical and public health decision-making. This study aimed to characterize diagnostic sensitivity associated with specific antemortem sample types and timing of collection. METHODS: Confirmed human rabies cases reported to the US Centers for Disease Control and Prevention (CDC) from 1990 through 2024 with antemortem testing on at least one of four recommended sample types (saliva, nuchal skin, serum, CSF) were included. Samples were tested primarily at CDC using standard protocols. Diagnostic test performance was stratified by sample type and time since symptom onset; regression models estimated percent positivity over time. RESULTS: Analyses included 69 human rabies cases, from which 382 antemortem samples were tested. After symptom onset, median time to first positive sample collection and to death were 8 and 16 days, respectively. Among cases with 4 antemortem sample types tested, combined diagnostic sensitivity was 100% and the risk of false negative results was <2%. Among cases with fewer antemortem sample types tested, diagnostic sensitivity was lower (<65% with one sample type tested). The probability of detecting virus (saliva and nuchal skin samples) was higher in early illness; the probability of detecting antibody (serum and CSF samples) was higher in later illness. CONCLUSIONS: Antemortem human rabies testing is highly sensitive when conducted per CDC recommendations. Understanding antemortem test sensitivity per sample type and timing of collection is critical to interpretation of test results.

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