ANTEMORTUM human rabies testing detects infection when sample types are collected across the course of illness.
Human rabies remains underdetected in part because patients are not always tested before death, and when they are, limited sampling can compromise case detection. In this 35-year U.S. analysis, investigators evaluated the diagnostic sensitivity of antemortem human rabies testing by sample type and timing, focusing on how clinicians can interpret both positive and negative results during suspected encephalitis.
Study Overview and Methods
The study included 69 confirmed human rabies cases reported to the U.S. Centers for Disease Control and Prevention between 1990 and 2024, with at least one antemortem test on saliva, nuchal skin, serum, or cerebrospinal fluid. In total, 382 antemortem samples were tested using standard protocols. Investigators stratified diagnostic performance by individual sample type and by time from symptom onset, and used regression models to estimate the probability of positivity over the illness course. Median time from symptom onset to first positive sample was 8 days, and median time to death was 16 days, underscoring the narrow window for clinical and public health decision making.
Antemortem Human Rabies Testing Performance
Among cases in which all four recommended antemortem sample types were collected, combined diagnostic sensitivity reached 100 percent and the risk of false negative results was under 2 percent. In contrast, when only a single sample type was tested, overall diagnostic sensitivity fell below 65 percent, highlighting the vulnerability of relying on limited specimens for human rabies case detection. Virus detection in saliva and nuchal skin was more likely earlier in illness, whereas antibody detection in serum and cerebrospinal fluid increased later, reflecting evolving host response.
Clinical Interpretation and Timing
For clinicians evaluating suspected human rabies or rabies encephalitis, the findings reinforce that the diagnostic yield of antemortem testing depends on both sample selection and timing. Negative results from one early sample type cannot reliably exclude infection if other recommended samples are not obtained or if testing occurs at a suboptimal time. Aligning local practice with CDC guidance to collect all four sample types across the illness course can maximize diagnostic sensitivity and support timely clinical management, infection prevention, and public health response. Understanding how sensitivity varies by sample type and day from symptom onset is therefore central to interpreting antemortem human rabies testing results.
Reference: Swedberg C et al. Maximizing Human Rabies Case Detection: Understanding the Diagnostic Sensitivity of Antemortem Testing from 35 Years of U.S. Data. Clin Infect Dis. 2025;doi:10.1093/cid/ciaf666.
