Rabies Virus

Dr. Hala Al Daghistani

Rabies is an acute fatal viral illness of the central nervous system (CNS). It can affect all mammals and is transmitted between them by infected secretions, most often by bite.

The rabies virus is a bullet-shaped, enveloped, single-stranded RNA virus of the rhabdovirus group. antigenic differences in surface glycoproteins have indicated strain heterogeneity among rabies virus isolates.

Rabies involves the development of severe neurologic symptoms and signs in apatient who was previously bitten by an animal. The neurologic abnormalities are very characteristic, with agitation, hallucinations, and salivation. The neurologic abnormalities are explained by spread of the virus from the bite wound into the CNS and then to the autonomic nervous system.

EPIDEMIOLOGY An occasional case has resulted from aerosol exposure (eg, bat caves and no

bite). the occurrence of human rabies is estimated to be about 15,000 cases per

year, with the highest attack rates in Southeast Asia, the Philippines, and the Indian subcontinent.

Pathogenesis

The essential first event in human or animal rabies infection is the inoculation of virus through the epidermis, usually as a result of an animal bite. Rabies virus first replicates in striated muscle tissue at the site of inoculation. Immunization at this time can prevent migration of the virus into neural tissues.In the absence of immunity, the virus then enters the peripheral nervous system at the neuromuscular junctions and spreads to the CNS, where it replicates exclusively within the gray matter. It then passes centrifugally along autonomic nerves to reach other tissues, including the salivary glands, adrenal medulla, kidneys, and lungs. Passage into the salivary glands in animals facilitates further transmission of the disease by infected saliva. The neuropathology of rabies include infiltration of lymphocytes and plasma cells into CNS tissue and nerve cell destruction. The pathognomonic lesion is the Negri body, an eosinophilic cytoplasmic inclusion distributed throughout the brain, particularly in the cerebral cortex, cerebellum, and dorsal spinal ganglia.

The incubation period ranges from 10 days to a year, depending on- the amount of virus introduced- the amount of tissue involved- the host immune mechanisms- the innervation of the site- the distance the virus must travel from the site of inoculation to the CNS.

R A B I E S : C L I N I C A L A S P E C T SManifestations

Rabies in humans usually presents as an acute, fulminant, fatal encephalitis; human survivors have been reported only occasionally. After an average incubation period of 20 to 90 days the disease begins as a nonspecific illness marked by fever, headache, malaise, nausea, and vomiting. Abnormal sensations at or around the site of viral inoculation occur frequently and probably reflect local nerve involvement. The onset of encephalitis is marked by periods of excess motor activity and agitation. Hallucinations, combativeness, increased salivation, muscle spasms, signs of meningeal irritation, seizures, and focal paralysis occur. Brainstem and cranial nerve dysfunction is characteristic, with double vision, facial palsies, and difficulty in swallowing. ” Hydrophobia, involuntary contractions of the diaphragm and accessory respiratory.

DIAGNOSIS The CSF of a rabies patient shows minimal to no abnormalities with some

patients exhibiting a lymphocytic pleocytosis (5 to 30 cells/mm3).

The test of choice in a live patient is detection of rabies antigen by immunofluorescent stain of a nape of the neck biopsy.

PCR of CSF or saliva may supplant the neck biopsy. Laboratory diagnosis of rabies in animals or deceased patients is accomplished

by demonstration of virus in brain tissue. Viral antigen can be demonstrated rapidly by immunofluorescence procedures.

Histologic examination of their brain tissue shows Negri bodies in 80% of cases; electron microscopy may demonstrate both Negri bodies and rhabdovirus particles.

Treatment Human hyperimmune antirabies globulin, Interferon, and Vaccine do

not alter the disease once symptoms have developed.

Prevention It is now believed that vaccination induces antibody that is either

neutralizing or inhibits cell to cell spread of virus. Currently, the prevention of rabies is divided into preexposure and

postexposure prophylaxis. Preexposure prophylaxis consists of two subcutaneous injections of vaccine given 1 month apart, followed by a booster dose several months later. Postexposure prophylaxis requires careful evaluation and judgment. The physician must consider (1) whether the individual came into physical contact with saliva or another

substance likely to contain rabies virus(2) whether there was significant wounding or abrasion(3) whether rabies is known or suspected in the animal species and area

associated with the exposure(4) whether the bite was provoked or unprovoked (i.e., the circumstances

surrounding the exposure)(5) whether the animal is available for laboratory examination.

Arboviruses Arbovirus is a term used to refer to any viruses that is transmitted by arthropod vectors . Arboviruses can affect both animals, including humans, and plants. In humans, symptoms of Arbovirus infection generally occur 3–15 days after exposure to the virus and last 3 or 4 days. The most common clinical features of infection are fever, headache, and malaise, but encephalitis and hemorrhagic fever may also occur. Some arboviruses cause severe inflammation of the brain (encephalitis) with damage or destruction of neural cells that may be fatal or lead to permanent neurologic damage in survivors.

EPIDEMIOLOGYUrban As the term suggests, the urban cycle is favored by the presence of relatively large numbers of humans living in close proximity to arthropod (usually mosquito) species capable of virus transmission. Examples of this cycle include urban dengue, urban yellow fever, and occasional urban outbreaks of St. Louis encephalitis.SylvaticIn the sylvatic cycle a single nonhuman vertebrate reservoir may be involved. In this situation, the human, is not important in maintaining the infection cycle. An example of this cycle is jungle yellow fever.

In sylvatic cycles, multiple vertebrate reservoirs may be involved: Examples include western equine encephalitis, eastern equine encephalitis, and California viruses.

PathogenesisThere are three major manifestations of Arbovirus diseases in humans associated with different tropisms of various viruses for human organs, although overlap can occur.

In some, the central nervous system (CNS) is primarily affected, leading to aseptic meningitis or meningoencephalitis.

A second syndrome involves many major organ systems, with particular damage to the liver, as in yellow fever.

The third is manifested by hemorrhagic fever, in which damage is particularly severe to the small blood vessels, with skin petechiae and intestinal and other hemorrhages.

Infection of the human by a biting, infected arthropod is followed by viremia, which is apparently amplified by extensive virus replication in the RES and vascular endothelium. After replication the virus becomes localized in various target organs, depending on its tropism, and illness results. The viruses produce cell necrosis with resultant inflammation which leads to fever in nearly all infections.

If the major viral tropism is for the CNS, virus reaching this site by crossing the blood–brain barrier or along neural pathways can cause meningeal inflammation (aseptic meningitis) or neuronal dysfunction (encephalitis). The CNS pathology consists of meningeal and perivascular mononuclear cell infiltrates; degeneration of neurons with neuronophagia; and occasionally, destruction of neurons.

ARBOVIRUS DISEASE: SPECIFIC ARBOVIRUSES

Western Equine Encephalitis الشرقي الخيلي الدماغ التهابThe agent that causes western equine encephalitis is prevalent in the central valley of California, eastern Washington, Colorado, and Texas. Horses and humans represent blind-end hosts; both are susceptible to infection and illness, commonly manifested as encephalitis.The disease spectrum may range from mild, nonspecific febrile illness to aseptic meningitis or severe encephalitis. Mortality is estimated at 5% for cases of encephalitis. It is a very serious disease in infants less than 1 year of age; as many as 60% of survivors have permanent neurologic impairment.

Eastern Equine Encephalitis الغربي الخيلي الدماغ التهاب

The eastern equine encephalitis virus is largely confined to the Atlantic Seaboard states from New England down the coasts of Central America and South America. The mosquito vector generally restricts its feeding to horses and birds, although occasional outbreaks among humans have occurred.The virus can cause severe encephalitis in horses and also in wild birds. The mortality among humans is estimated at 50% for individuals of all ages,

St. Louis EncephalitisThe St. Louis encephalitis virus is a major cause of Arbovirus encephalitis in the United States. Its geographic distribution and major mosquito vector are similar to those of western equine encephalitis It infects but causes no disease in horses. The disease spectrum in humans is similar to that of western equine encephalitis, but the major morbidity and mortality, as well as the highest attack rates, are among adults more than 40 years of age.

West Nile VirusThere were at least 3600 human cases reported in the United States, with 212 deaths. The virus is antigenically related to St. Louis encephalitis and Japanese encephalitis. Transmission is from infected mosquitoes to birds, humans and horses, and clinical illness leading to death can result from infections in any of these hosts. Transmission among humans via blood transfusions, breast milk, or organ transplants is also possible. Crows الغربان are particularly affected Clinical illness often included muscle weakness and flaccid paralysis, and encephalitis.

Japanese B Encephalitis

The flavivirus species that causes Japanese B encephalitis is prevalent in Japan, Taiwan, Indonesia, and in India. Its transmission cycle resembles that of the St. Louis encephalitis and western equine encephalitis viruses. A high proportion of human infections are subclinical, especially in children; when encephalitis does develop it is severe and often fatal.

C L I N I C A L A S P E C T SDIAGNOSIS

Laboratory animals: The arboviruses may be isolated in various culture systems including intracerebral inoculation of newborn mice, which often results in encephalitis and death.

Most infections asymptomatic found in the blood (viremia) from a few days before onset of symptoms

Virus is not present in the stool and is rarely found in the throat; viral recovery from cerebrospinal fluid (CSF) is also unusual.

Serology: Early rapid presumptive diagnosis can sometimes be made by the detection of IgM-specific antibodies that often appear within a few days of onset

Vaccines are available for immunization of horses against western, eastern, and Venezuelan equine encephalitis virus infections, and the latter has also been used for some laboratory personnel who work with the virus.