Home › Microbiology › Diagnosis and Prevention of Rabies

Diagnosis and Prevention of Rabies

For medical students2 min readUpdated 2026-10-10

Rabies diagnosis is most often performed post-mortem by detecting specific inclusions in brain tissue—Negri bodies—along with viral antigens. Disease prevention includes immediate wound care, emergency post-exposure vaccination, and, when indicated, administration of rabies immunoglobulin.

Case Fatality RateOnce clinical symptoms appear, the prognosis is universally fatal.

Viral MarkerNegri bodies (cytoplasmic inclusions in brain neurons).

ObservationThe biting animal must be quarantined and observed for 10 days.

Wound CarePrimary closure (suturing) of the wound should be avoided for the first 3 days.

Microbiological Diagnosis

Due to the 100% fatality rate of the infection, laboratory confirmation is most often performed post-mortem. Main methods:

Microscopic Examination. Smear imprints or tissue sections of the hippocampus, cerebellum (Purkinje cells), and cerebral cortex are examined for specific cytoplasmic inclusions—Negri bodies. Stains such as Romanowsky-Giemsa, Turevich, Mann, or Muromtsev are utilized.
Rapid Diagnostics. Allows for the swift detection of viral antigens in brain tissue or submandibular salivary glands using the direct fluorescent antibody (DFA) test.
Biological Assay. Involves intracerebral inoculation of suckling mice. Animals are monitored for up to 28 days, though death typically occurs within a week. For subsequent agent identification, ELISA or neutralization tests using rabies immunoglobulin are applied.

In rare instances, antemortem diagnosis is attempted in patients. Specimens include skin biopsies or corneal imprints (analyzed via DFA). Viral isolation from cerebrospinal fluid, tears, or saliva via mouse inoculation, as well as antibody detection via complement fixation and ELISA, are also possible.

Emergency Prophylaxis and First Aid

No specific treatment exists for clinical rabies—only supportive care is available. Timely prophylaxis is the only intervention capable of saving an infected individual. Success relies on active post-vaccination immunity developing prior to the end of the incubation period.

Wound Management Protocol:

Immediate and thorough flushing of the wound with soapy water.
Antiseptic treatment of the wound edges with alcohol or iodine solutions.
Surgical debridement of wound margins.
Crucial rule: do not suture the wound for the first 3 days.

The biting animal (if known) must be placed under mandatory veterinary observation for 10 days to rule out or confirm rabies.

Vaccination (Specific Prophylaxis)

Specific immunoprophylaxis is divided into pre-exposure prophylaxis (indicated for veterinarians and animal handlers) and post-exposure prophylaxis (administered after a potential exposure).

Vaccines. Modern regimens utilize cell-culture inactivated vaccines (inactivated via UV or gamma irradiation). Recombinant vaccines containing glycoprotein G are also under development. Vaccination stimulates cellular immunity, antibody production, and interferon synthesis.
Passive Immunization. Severe exposures or multiple bites require immediate protection. In such cases, rabies immunoglobulin is administered to establish passive immunity, safeguarding the patient until active post-vaccination antibodies are produced.

Historically, the first rabies vaccine was developed by Louis Pasteur in 1885. He derived the so-called "fixed" virus through 133 consecutive passages of "street" virus through rabbit brains. The pathogen lost its virulence for humans, and its incubation period shortened to 7 days. Attenuation was achieved by drying the spinal cords of infected rabbits over potassium hydroxide.

Mnemonic

To remember the locations of Negri bodies: "Brain, Cortex, Hippocampus" — BCH (Cerebellum [Purkinje cells], Cerebral cortex, Hippocampus).

Frequently asked questions

What are the strict indications for passive immunization with rabies immunoglobulin?

Strict indications for passive immunization with rabies immunoglobulin include severe injuries and high-risk exposures with a short incubation period. These comprise:

High-risk anatomical locations — bites in densely innervated areas (head, face, neck, hands, fingertips, perineum, genitals).
Severe wounds — multiple, deep lacerations, transdermal bites, or bleeding scratches.
Mucosal contamination — any saliva contact with mucous membranes or broken skin.
Special exposures — injuries inflicted by wild carnivores, farm animals, bats, and rodents.

What are the main differences between the fixed rabies virus and the wild street virus?

The primary differences involve altered incubation periods and loss of virulence following serial passage.

Feature	"Street" Virus	"Fixed" Virus
Incubation Period	Baseline (variable)	Shortened to ~7 days
Virulence	Baseline (pathogenic)	Lost for species other than rabbits
Origin	Wild field strain	Serial passage through rabbit brains (133 passages)

What is the schedule (days of administration) for emergency post-exposure rabies vaccination?

Emergency post-exposure rabies prophylaxis follows a strict regimen of intramuscular injections. The vaccine is administered in 1.0 mL doses on the following days post-exposure:

Day 0 — first injection;
Day 3;
Day 7;
Day 14;
Day 30;
Day 90 — booster dose.

The course may be discontinued early (after the third injection) if the animal remains healthy throughout the 10-day observation period or if laboratory testing confirms the animal is rabies-free.

Which specific commercial rabies vaccine preparations are used in medical practice?

Reference materials frequently cite purified, concentrated, inactivated cell-culture rabies vaccines (such as CCV preparations). The vaccine is administered intramuscularly and can be used alone or combined with rabies immunoglobulin for high-risk exposures.

The disease is universally fatal once clinical symptoms develop. Antemortem diagnosis is difficult, and the primary confirmatory sign (Negri bodies) is identified in brain tissue.

The disease is universally fatal once clinical symptoms develop. Antemortem diagnosis is difficult, and the primary confirmatory sign (Negri bodies) is most reliably detected in brain tissue post-mortem.

What is the rationale behind post-exposure prophylaxis?

It involves administering the rabies vaccine (and immunoglobulin for severe bites) following exposure to the infection source. Protection successfully develops because of the virus's prolonged incubation period.

How many days must a biting animal be observed?

Animal observation lasts for exactly 10 days.

Why is the wound left open during the first few days?

Surgical sutures are avoided during the first 3 days post-exposure to minimize the risk of infection within a closed cavity and to allow adequate drainage.

Go deeper

Mechanisms of cellular immunity generation during vaccination
Differences between Pasteur's 'fixed' virus and 'street' viral strains
Role of glycoprotein G in the development of recombinant vaccines
Special staining techniques for Negri bodies (Turevich, Muromtsev)