Theory of Rabies

“Theory of Rabies” : Written by Jihei Tanakamaru, Edited by Kiyoshi Shiga

Published in April, 1917 (Taisho 6)

In 1885, Louis Pasteur developed a post-exposure vaccine that made it possible to prevent the onset of rabies even after being bitten by a rabid dog.

As a result, diagnosis is required more rapidly than ever before.

▶ Clinical Diagnosis

Dogs that have bitten humans should be captured alive for rabies diagnosis and should be diagnosed within 8 days by showing the symptoms characteristic of rabies.

Stage 1 (1–3 days after onset) : Abnormal excitement. Anxiety. Loss of appetite. Biting foreign objects.

Stage 2 (2–4 days after onset) : Paroxysmal mania. Biting people. Difficulty in swallowing. Difficulty walking.

Stage 3 : Paralysis begins in the lower legs. Wrinkled barking. Lethargy.

▶ Postmortem Diagnosis

Rabies was diagnosed by detecting Negri bodies in the brain tissue of a dead dog, or by inoculating the brain into mice or guinea pigs to see if they would develop rabies.

◎Negri body staining method

The following methods were used to stain Negri bodies.

Bohne method

After treatment with acetone for 30 to 40 minutes, the sections were embedded in paraffin.

・Mann staining

Methyl blue and eosin are used to stain the cytoplasm blue, the Negri body dark red, and the erythrocytes bright red.

Lents staining

With the Mann staining , it was difficult to differentiate the nucleolus of the ganglion cell nucleus from the Negri bodies. It is also difficult to examine the fine structure of the nucleolus because the interior of the Negri bodies is vacuolated and the ganglion cells are stained too strongly.

Therefore, in addition to staining with methyl blue and eosin, Lugol’s solution was used to improve the staining and decolorization methods.

Glial tissue is stained pale rose or colorless, ganglion cell nuclei are stained light dark, nucleoli/ ganglion cells/ leukocytes/ capillary walls are stained dark to pale blue, red blood cells are stained vermilion red, and Negri bodies are stained scarlet red.

It was used to detect fixed viruses in which Negri bodies are difficult to form.

Stutser staining method

Methylene blue and tannic acid are used to stain Negri bodies reddish purple and neurons blue.

This is an excellent staining method because the structure of the Negri bodies is clear and the technique is simple.

Van Gieson staining

Negri bodies are stained red with Rosaniline Violet and methylene blue.

This is a simple and effective method for diagnosis.

◎Animal Inoculation Method

Since 1897, the national laboratory of Infectious Diseases has conducted tests using a method based on the animal inoculation method published by Pasteur.

・A brain emulsion of the test animal is inoculated subdurally into the parietal of the rabbit.

・If the specimen is positive, the disease develops after the incubation period of 10 to 20 days and dies within 2 to 3 days.

In 1902, Oshida devised a method of inoculating the brain base through the optic foramen from the lower part of the eye.

▶ Clinical Symptoms

There are two types of manifestations of rabies, manic insanity (today’s furious rabies) and static insanity (today’s paralytic rabies), each with the following symptoms.

◎Manic Insanity

1.Incubation Period:The incubation period averages 60 days after the bite.

2. Melancholy Period:Usually lasts from half a day to three days.

Behavior changes drastically, becoming either melancholy or cheerful.

The  is very easily startled and has an inherent state of anxious excitement.

Itching and licking at the bite site.

Appetite is unchanged in the beginning, but gradually becomes extremely anorexic and eats foreign objects such as wood chips, straw, paper, feather stones, etc.

The animal becomes hyperactive and sniffs and licks the pubic area of its own or other dogs.

Eye conjunctivae become bloodshot, pupils dilate, breathing increases, and difficulty walking and loss of energy occur.

3. Manic phase:

The dog becomes more symptomatic in response to stimuli and exhibits the symptoms characteristic of rabies.

The dog will attempt to escape from the fenced area, and if not tethered, will leave the house and escape without a plan.

Seizures occur sporadically, and if a stick is inserted into the captive dog, the dog becomes enraged and bites. When other dogs are introduced, it becomes ferocious and bites them on the face and head. It also does not appear to be fatigued at all.

Escaped or wandering dogs run away in a straight line when they have a seizure, bite objects when they hit them, and move many kilometers in a short time, causing damage to many people and livestock. When at rest, they lie down as if they are limp. The face, in particular, is markedly tonic.

As the disease progresses, the tonicity extends to the whole body, often with convulsions, and a captive rabid dog can be triggered by external light or sound.

Swallowing is difficult, but there is no water avoidance seizure as seen in humans at the onset of the disease.

The seizures last 3–4 days, and the dog becomes collapses.

4. Paralytic phase:

When paralytic symptoms develop, the hind limbs become frail, the dog hesitates to walk, and the tail droops.

Paralysis gradually progresses to the front of the body, breathing increases and becomes irregular, and the tongue comes out of the mouth with foamy saliva mixed with blood. At this time, the animal already has no biting power and cannot bark.

The pulse becomes weak and convulsions occur in parts of the body or all over the body.

The dog often dies within 3–6 days. In rare cases, the animal survives for 7–8 days, but there have been no cases of abnormal survival for 10 days.

◎Static Frenzy

Lack of excitability of the nerve centers and paralysis of the mandible are characteristic of this disease.

This symptom appears early on, resulting in the inability to bite and eat or drink.

The mandible is completely paralyzed and droops, the tongue hangs out of the oral cavity, and food and drink are vomited out.

As in the manic insanity, Saliva is always secreted in large quantities, and the barking changes, disturbance of consciousness, and rapid progression of the disease are the same as in the manic episode.

Weakness begins in the hind limbs and extends to the brainstem, causing local and generalized convulsions that often lead to death within 2 to 3 days after onset.