Rabies is a deadly viral disease that is spread through the bite or scratch of an infected animal. Once symptoms appear, rabies is almost always fatal. However, if treatment is given early, before symptoms develop, the disease can be prevented. One way to determine if a person has been exposed to rabies is through a blood test. Blood tests can detect rabies antibodies or antigens and help guide whether post-exposure prophylaxis is needed.
What is rabies and how is it transmitted?
Rabies is caused by a virus in the genus Lyssavirus. It infects the central nervous system of mammals, including humans. Rabies is most commonly spread through the bite or scratch of an infected animal. Infected saliva introduced through broken skin or mucous membranes is how the rabies virus typically enters the body.
The rabies virus travels from the site of infection to the peripheral nerves and then spreads to the central nervous system. It causes inflammation of the brain and spinal cord once there. All mammals can get rabies, but it is most commonly seen in wild animals like raccoons, skunks, bats, coyotes, and foxes in the United States.
Rabid animals usually exhibit abnormal behavior. They may appear tamer than usual or aggressively attack without reason. However, rabies can only be confirmed post-mortem by laboratory testing of brain tissue.
What are the symptoms of rabies in humans?
Rabies in humans has an incubation period that averages 1-3 months but can range from <5 days to >6 years. The incubation period depends on factors like the location of the bite/exposure and how much virus was introduced. Those bitten on the head or neck tend to have shorter incubation periods.
Rabies progresses through 2 clinical phases:
– Prodromal phase: Lasting 2-10 days. Flu-like symptoms like fever, headache, nausea may occur. There may also be itching, pain, or tingling at the exposure site.
– Neurologic phase: The disease progresses to anxiety, agitation, hallucinations, hypersalivation, trouble swallowing, hydrophobia (fear of water), and insomnia. As the infection spreads in the central nervous system, symptoms advance leading to seizures, paralysis, coma, and ultimately death within a few days.
Once clinical signs appear, rabies is nearly 100% fatal. However, the disease is preventable if post-exposure prophylaxis (PEP) is given early, before the onset of symptoms.
Can blood tests diagnose rabies?
Blood tests can be used to detect a rabies infection. Testing provides critical information to assess the need for lifesaving PEP treatment after an exposure. There are two main types of blood tests for rabies:
Antibody titers
These blood tests check for the presence of antibodies to the rabies virus. Antibodies are proteins produced by plasma cells (a type of white blood cell) in response to an infection.
During a primary exposure, it takes approximately 1 week to several months for detectable rabies virus antibodies to appear. Checking for antibody titers can determine:
– If an exposure occurred: Positive antibody levels indicate a person was exposed to rabies and triggered an immune response. However, these tests cannot determine precisely when the infection occurred or distinguish between vaccination and exposure.
– Response to vaccination: Testing 2 weeks after receiving the rabies vaccine series checks for an appropriate antibody response. This is done to confirm immunity, especially for people at high-risk of exposure like veterinarians, animal handlers, and laboratory workers.
Antigen detection
These tests detect the presence of the rabies virus itself within a sample, rather than the antibodies triggered by infection.
Samples to directly identify the virus can include:
– Saliva – Can detect virus in saliva during the first 7-10 days of symptoms
– Spinal fluid – Can find viral RNA in cerebrospinal fluid during neurological disease
– Skin samples – Can detect viral antigens at the nape of the neck during the early stage of symptoms
– Brain biopsy – Can detect the virus post-mortem in brain tissue
Finding viral components through antigen testing confirms an active or recent rabies infection. However, its utility in blood samples remains experimental. Ongoing research aims to develop rapid point-of-care blood tests that could identify rabies virus antigens or RNA to support clinical diagnosis and prompt PEP.
When should rabies blood tests be performed?
Blood tests play an important role in determining if PEP is needed following a potential rabies exposure. Testing may be considered in two scenarios:
After a possible exposure
If someone is bitten by or exposed to an animal suspected of having rabies, blood can be drawn to determine if:
– The person has pre-existing rabies antibodies from prior vaccination
– The person develops new antibodies during the incubation period, indicating they may have contracted rabies
In the United States, public health officials typically recommend starting PEP first, then performing antibody testing 3-7 days after the first vaccine dose. If adequate rabies antibody levels are present, PEP can be discontinued. If the person lacks antibodies, completing the vaccine series is recommended.
To monitor immunization response
People at occupational risk of rabies exposure should have blood drawn 2-4 weeks after completing their initial vaccine series. Testing is repeated every 6 months to 2 years to ensure antibody levels remain protective through routine titer checks. If titers decline, a booster shot is given.
For the general public with potential exposures, routine antibody testing is often not needed outside of the first PEP series. But it may provide information in special circumstances.
What test methods detect rabies antibodies?
Several laboratory techniques are used to identify and quantify rabies virus antibodies:
Rapid fluorescent focus inhibition test (RFFIT)
– This is considered the gold standard test for measuring protective rabies antibody levels.
– It is a virus neutralization assay – patient serum is incubated with live rabies virus and then inoculated into cell cultures.
– If rabies antibodies are present, they will neutralize the virus. This prevents infected cells from forming.
– A fluorescent rabies antibody is added later to detect any non-neutralized virus.
– Antibody titers are reported in IU/mL, with ≥0.5 IU/mL indicating an appropriate response to vaccination.
Fluorescent antibody virus neutralization (FAVN) test
– Similar to RFFIT, uses cells inoculated with serum and live virus.
– Quantifies virus neutralization based on fluorescent staining signals instead of counting foci.
– Results are consistent with RFFIT values. A titer ≥0.5 IU/mL is considered positive.
Enzyme-linked immunosorbent assay (ELISA)
– An ELISA detects binding between rabies virus proteins and patient antibodies.
– It offers automated, high-throughput testing for population-level antibody screening.
– Provides quantitative titers but is less sensitive than neutralization assays.
– Positive cutoff varies based on kit used, often ≥0.5 IU/mL.
Lateral flow assays
– Rapid immunochromatographic tests that give a visual positive or negative result for rabies antibodies.
– Use a paper strip with test/control regions coated with viral antigen that bind antibodies.
– Mainly used for point-of-care qualitative screening to assess PEP need.
What are normal and abnormal rabies antibody levels?
Reference ranges for rabies antibodies:
– Unvaccinated people: Less than 0.1 IU/mL is negative indicating susceptibility.
– Previously vaccinated: 0.5 IU/mL or higher indicates immunity due to past vaccination. Levels may decrease over time without boosters.
– Recent vaccination: Should see antibody levels of at least 0.5 IU/mL in a blood sample drawn 2-4 weeks after finishing post-exposure prophylaxis.
– Past exposure: May have elevated titers due to natural infection, often well above 10 IU/mL. Cannot distinguish whether antibodies are from vaccination or exposure based on levels alone.
A four-fold or greater rise in antibody titers taken at two different time points strongly suggests a recent rabies infection. For example, if antibodies were first undetectable, then rose to 1.5 IU/mL on follow-up testing. Response to the rabies vaccine, in contrast, usually elevates titers less than four-fold.
How accurate are rabies blood tests?
Accuracy of rabies serology depends on the test method:
– Virus neutralization assays (RFFIT/FAVN) offer the highest sensitivity and specificity, greater than 95%.
– ELISA has good specificity (>90%) but is less sensitive, missing about 30% of low-positive samples.
– Lateral flow assays have marginal sensitivity (50-70%) compared to lab-based quantification but can rapidly indicate serostatus.
False positive results are rare but can occur due to:
– Testing errors
– Cross-reactivity with antibodies against other pathogens
– Non-specific binding of serum proteins
Factors causing potential decreased sensitivity include:
– Very early testing before an antibody response fully develops
– Immunosuppression that inhibits antibody production
– Only a local antibody reaction in the nerves, not yet detectable systemically
Overall, rabies neutralization assays remain the gold standard method for confirming seroconversion. A rise in titers provides the strongest evidence of infection when paired samples are tested. PCR and viral antigen tests of infected tissue offer better indication of active infection than serology.
What is the role of blood tests in making a rabies diagnosis?
Rabies blood tests play an adjunctive role and have limitations:
– Cannot make a definitive rabies diagnosis alone – direct virus detection in tissues is required for confirmation
– Cannot determine when infection occurred or distinguish vaccine-induced antibodies
– May miss very early or immunosuppressed infections with low antibody levels
However, rabies serology still provides valuable information for PEP decisions:
– Helps identify exposures by revealing specific antibody response
– Monitors vaccine-induced immunity in people at occupational risk
– Guides need for passive immunization in exposed individuals lacking antibodies
– Aids initiation of PEP in appropriate post-bite timeframe
– Confirms seroconversion to vaccine in immunosuppressed patients
Overall, blood tests provide supportive data and identify who should receive PEP, but suspected rabies exposures still warrant prophylaxis based on animal interactions. Clinical observation is needed given limitations of current serology. Improved antigen detection in easily accessible fluids like blood remains a future goal.
Can blood tests rule out rabies infection?
Negative blood test results cannot definitively rule out rabies infection. Key reasons antibody titers may be negative in an infected person include:
– Too early – Antibodies take 1-2 weeks after exposure to develop and may not be detectable in the initial days. Repeat testing is advised.
– Localized antibodies – The infected individual may only mount an immune response in nerve tissue, not systemically.
– Immunosuppression – Conditions like HIV/AIDS, immunosuppressive drugs, and chemotherapy impair antibody production.
– Fast disease progression – In very rapid cases, patients may die before measurable antibody levels appear.
– Unusual variants – New viral strains or isolated cases with mutated surface proteins may not bind/get neutralized by lab antibodies.
For these reasons, anyone with a known high-risk exposure should receive PEP regardless of negative serology. Monitoring for antibody response and clinical signs during incubation time is critical, as a normal titer alone cannot rule out rabies.
Conclusion
While blood tests can support rabies infection diagnosis, they have limitations. Antibody titers cannot fully confirm or exclude rabies. However, checking for seroconversion guides proper PEP use after exposures. Virus neutralization assays provide the most sensitive and specific results. ELISA techniques also deliver quantitative titers, while rapid immunochromatographic tests allow point-of-care antibody screening.
Negative serology does not rule out rabies, particularly early after exposure. But positive and rising titers indicate the need for treatment in exposed individuals. Blood tests add helpful data but require a cautious interpretation based on timing and clinical context. More rapid, standardized blood diagnostics detecting viral antigens or nucleic acids could improve confirmation and treatment in the future. For now, neutralizing antibody detection aids clinical decisions to deliver life-saving post-exposure prophylaxis when it is most effective.