NAME OF DISEASE:     Rabies
                                        Hydrophobia

ETIOLOGICAL AGENT:     Rabies virus (a rhabdovirus)

THE DISEASE:

    This is primarily a viral infection of non-human carnivores. Transmission to man is rare and is usually effected through a bite. Clinical evidence of involvement of the CNS appears after an extremely variable period of incubation. A deep-seated fear of rabies is almost instinctual despite the actual rarity of the infection in man, perhaps reflecting a primordial knowledge of the virtual certainty of death once disease is overt.

PATHOLOGY:

    The rabies virus is usually transmitted to man by a bite that implants saliva containing an infective dose of virus in muscle and near nerve tissue. The virus may undergo a limited amount of reproduction in the muscle cells at the site of inoculation. The virus travels along the nerves from the point of inoculation to the CNS. The dense concentration of sensory nerve endings in the head, face, neck and fingers accounts for the higher fatality rate observed when these areas are exposed. Similarly, the more extensive or severe the bite wounds, the higher the mortality, because more nerve tissue is exposed to an infective dose of rabies virus. After entering the CNS, the virus replicates in the neurons of the gray matter before traveling centrifugally along nerves from the CNS to invade a variety of organs and tissues. Humans and animals dying of rabies commonly exhibit characteristic cytoplasmic inclusion bodies in neurons of the brain; these are called Negri bodies. The presence of Negri bodies is pathognomonic of rabies infection, but their absence does not preclude the disease. In humans who have died from rabies, Negri bodies are prominent in ganglion cells, particularly in the hippocampus and cerebellum. Other changes also present in the CNS include edema, hemorrhage, congestion, and perivascular cuffing in all parts, but most severe in the pons and medulla. In the cranial, spinal, and sympathetic ganglia, there are actual foci of necrosis with neuronophagia and infiltration with lymphocytes. The severity of the histopathologic changes in the spinal cord often corresponds to the site of bite - for example, the lumbar cord is most extensively affected when the bite is on the foot. Gross changes are inconspicuous.

DIAGNOSIS:

    Where there is a history of bite by a known rabid animal and the bitten person shows typical symptoms, the clinical diagnosis of rabies is usually evident. In many instances, a history of exposure is lacking, and the diagnosis of rabies may be missed unless revealed by postmortem laboratory tests.

    The manifestations of rabies begins in man anywhere from 10-240 days after exposure. However, the incubation period is usually 30-90 days. The length of this incubation period is a function of:

    1.     The number of sensory nerves ending in the bitten area

    2.     The dose of virus

    3.     The severity of the bite wounds

    4.     The distance from the bite wound to the CNS

    There are three clinical phases of the disease:

    1.     Prodromal phase - the onset of clinical rabies in man includes 2-4 days of prodromal
            manifestations, most of which are non-specific. A low fever, malaise, headache, anorexia,
             nausea and sore throat are common. There may also be increasing nervousness, anxiety,
            irritability and depression and melancholia, with or without a sense of impending death.
            Hyperesthesia, an increased sensitivity to bright light and loud noise, excessive salivation,
            lacrimation and perspiration have been noted. The general muscle tone may be increased,
            and facial expression can be overactive. Dilated pupils, an increased pulse rate and shallow
            respirations are seen. However, by far, the most significant symptoms are abnormal
            sensations referred to the site of inoculation; noted by 80% of patients, these include pain
            (local or radiating), a sensation of cold, pruritus (itching) and tingling.

    2.     Excitation phase - the excitation phase begins gradually and may persist to death. It may be
            punctuated at any time by depression and paralysis. There usually are increasing anxiety,
            apprehension and a sense of impending doom. Although the tone of the somatic musculature
            is increased, there may be weakness of the muscle groups around the location of the bite.
            Cranial nerve malfunctions result in ocular palsies with:

            a.     Strabismus - failure of the eyes to follow one another in any movement. This is due to
                    incoordination of the extra-ocular muscles.

            b.     Dilation or constriction of the pupils that may be asymmetric and associated with:

                    (1)     Hippus (abnormal exaggeration of the rhythmic contraction and dilation of the
                              pupil, independent of changes in illumination or in fixation of the eyes).

                    (2)     Nystagmus (continuous rolling of eyeball)

                    (3)     Diplopia

            c.     Absence of corneal reflexes

            d.     Weakness of facial muscles

            e.     Hoarseness

            f.     Babinski and Chaddock signs

            g.     Papilledema

            There may be tachycardia or bradycardia (slow heart beat), cyclic respiration, urinary
             retention and constipation.

            Hydrophobia, the classical diagnostic manifestation of rabies, is an affliction of the excitatory
            phase of the disease. When the patient attempts to swallow liquids, forceful, painful
            expulsion occurs as a consequence of spasmodic contraction of the muscles of swallowing
            and respiration. Once experienced, the sight, sound or smell of liquids may provoke the
            syndrome. The ensuing choking may cause severe apnea (temporary cessation of breathing)
            and cyanosis. Death frequently occurs during the course of such a convulsive attack.
            Dehydration is a common consequence.

    3.     Paralytic phase - hydrophobia, if present, disappears and swallowing becomes possible,
            although difficult, as the paralytic phase sets in. A progressive, general, flaccid paralysis
            develops. Apathy shades into stupor, progressing to coma. There is urinary incontinence.
            Peripheral vascular collapse ensues and death follows.

            Definitive diagnosis of rabies depends on laboratory procedures:

            1.     Isolation of the virus from saliva, CSF, urine, nerve tissue

            2.     Fluorescent rabies antibody (FRA) test on brain tissue

            3.     Presence of Negri bodies

PROGNOSIS:

    Only 6 people have ever recovered from rabies. CNS sequelae are common.

TREATMENT:

    The most important immediate treatment includes:

    1.     Washing the wound with copious amounts of soap and water.

    2.     Apply 1% quaternary ammonium compounds after all traces of soap have been removed.

    3.     Apply antirabies serum by careful instillation into the wound and by infiltration around the
            wound. Administer serum systemically.

    4.     Postpone suturing the wound.

    5.     Institute antitetanus procedures

    6.     Start administration of vaccine pending autopsy of animal involved in the bite. Stop
            treatment  if animal is normal.

    7.     If rabies symptoms ensue give extensive supportive care (treat symptoms as they appear):

            a.     Tracheostomy to prevent hypoxia

            b.     Careful tracheal suctioning

            c.     Use of supplemental oxygen

            d.     Relieve intracranial pressure by insertion of a CSF reservoir connected to the lateral
                    ventricle (cavity in the forebrain, one in each cerebral hemisphere)

            e.     Control focal seizures with anticonvulsant therapy

VACCINES AVAILABLE:

    1.     Rabies vaccine

            a.     Semple - type of nerve tissue vaccine - no longer commercially available in U.S.
                    Causes severe immune reactions against the neural tissue.

            b.     Duck embryo vaccine - hypersensitivity to eggs may result in a reaction to this vaccine.
                    This may include:

                    (1)     Abdominal cramps

                    (2)     Nausea

                    (3)     Vomiting

                    (4)     Transient urticaria (skin reaction)

                    (5)     Anaphylactoid reactions

                    Generally, however, the reactions are only local erythema and induration.

                    Dose (minimum) - 1 ml/day subcutaneous for 14 days; (maximum) - 23 doses
                    (requires 7-10 days for response).

            c.     Attenuated virus vaccine grown in human diploid cells. Injected IM in any part of the
                    body. 1 ml dose. 5 injections at 3,7,14 and 28 days after first injection.

            d.     Recombinant vaccine - vaccinia virus with rabies glycoprotein gene. (1 vaccination)

    2.     Antirabies antiserum

            a.     Heterologous (equine origin) - given IM around the wound and in the buttocks. Serum
                    sickness may result from the use of this product.

            b.     Homologous (human origin) - fewer side effects but much more expensive.