Rabies And Its Effect On Human Health Biology Essay
Rabies is a zoonotic viral disease usually transferred from a bite of an infected dog, but any mammal may also be a transmitter. Rabies, along with several other lyssaviruses of bats, is classified under the Order Mononegavirales, Family Rhabdoviridae, and Genus Lyssavirus. Transmission to humans occur by direct contact through transfer of virus laden saliva through biting of an animal, though licking of fresh wounds may also be a mode of entry.
Upon successful infection, incubation period varies in humans from as early as ten days to as long as 15 years depending on the site of inoculation. However in dogs, signs and symptoms usually appear as early as 7 to 14 days. This is very helpful in the tentative diagnosis of rabies in animals, which may be used in the programming of treatment modalities in humans. If left untreated and the animal is found to be rabid, the human may suffer from slight headache to as severe as circulatory and respiratory failure which may eventually lead to death.
There are two distinguished rabies cycles: urban, which is maintained in dogs, and rural, which is maintained in wild animals such as raccoons, foxes, and bats. Natural infection occurs in almost all domestic and wild mammals, although different species show distinct degrees of susceptibility. Animal hosts that maintain rabies virus in nature are carnivores and bats. Herbivores and other non-biting animals, rodent, and lagomorphs do not play any role in the epidemiology of the disease.
Figure 1. Geographic distribution of rabies infection in humans.
Lyssaviruses of terrestrial (non-flying) mammals have been isolated all over the world. Only a few countries are free of terrestrial rabies. This includes: New Zealand, Australia, Japan, United Kingdom, Ireland, Scandinavia and Iceland. In countries where canine rabies has been controlled or eradicated and where wild rabies exists, the number of human cases has been reduced to a very low level.
Rabies incidence in the Philippines is estimated to about 300 to 600 deaths per million Filipinos/year. Ranking fourth highest in the world, this remains to be a major public health concern in the country.
Through wounds or direct contact with mucous membranes
Muscles and nervous tissues
Anorexia, nausea, pain in area of bite, hydrophobia and ptyalism
Virus isolation, fluorescent rabies antibody or histopathology of dog’s brain
Neural necrosis and presence of Negri bodies
Respiratory and circulatory failure
Rabies virus belongs to the order Mononegavirales, viruses with a nonsegmented, negative-stranded RNA genomes. Within this group, viruses with a distinct "bullet" shape are classified in the Rhabdoviridae family, which includes at least three genera of animal viruses, Lyssavirus, Ephemerovirus, and Vesiculovirus.
The genus Lyssavirus, has seven genotypes (Gt), and is maintained in reservoir mammals, mainly carnivores (dogs) and bats. Genotype 1 comprises the classical rabies virus (RV) strains which are found in almost every country in the world. Genotypes 2 to 7 include the rabies-related viruses (RRV), more specifically, as follows:
· Lagos bat virus (LBV), (Gt2)
· Mokola (MOK) virus, (Gt3)
· Duvenhage virus (Gt4)
· European bat lyssavirus 1 (EBLV-1), (Gt5)
· European bat lyssavirus 2 (EBLV-2), (Gt6)
· Australian bat lyssavirus (ABLV), (Gt7)
Four recent isolates of bat Lyssavirus in Central Asia, East Siberia and Caucasian region need to be characterized as new genotypes: Aravan virus or ARAV, Khujland virus or KHUV, Irkut virus or IRKV and West Caucasian bat virus or WCBV.
Mode of Transmission
Rabies virus entry occurs through wounds or direct contact with mucosal surfaces. It is important to note that the virus cannot cross intact skin and that, the virus remains at the site of inoculation for a variable period of time without propagating.
Once inside, the virus then either replicates in non-nervous tissues or directly enters peripheral nerves and travels by retrograde axoplasmic flow to the central nervous system (CNS). Both motor and sensory fibers may be involved depending on the animal species. The incubation period varies from 2 weeks to 6 years (average 2 to 3 months) depending on the amount of virus in the inoculum and site of inoculation.
The proximity of the site of virus entry to the CNS increases the likelihood of a short incubation period. The estimated speed of virus migration is 15 to 100 mm per day. The virus then moves from the CNS via anterograde axoplasmic flow within peripheral nerves, leading to infection of some of the adjacent non-nervous tissues: for example, secretory tissues of salivary glands.
The appearance of rabies virus in saliva is of special interest in the epidemiology, since biting is the main mode of transmission of infection. In most cases, elimination in saliva begins with the start of disease but appearance of the agent in saliva has been confirmed in animals of many species before clinical symptoms were observed.
The virus is widely disseminated throughout the body at the time of clinical onset. The first clinical symptom is usually neuropathic pain at the wound site. This is caused by virus replication in dorsal root ganglia and ganglionitis. Major clinical signs are related to the virus-induced encephalomyeloradiculitis. Two major clinical presentations are observed: furious and paralytic forms that cannot be correlated with any specific anatomical localization of rabies virus in the CNS. Nevertheless, peripheral nerve dysfunction is responsible for weakness in paralytic rabies. In furious rabies electrophysiological studies indicate anterior horn cell dysfunction even in the absence of clinical weakness. Without intensive care, death occurs within a few days (1 to 5 days) of the development of neurological signs. Rabies is inevitably fatal.
Organs and Systems Affected
Signs and Symptoms
The incubation period is from 2 to 8 weeks, but it may vary from 10 days to 8 months or more. The disease begins with a feeling of anxiety, cephalalgia, a small increase in body temperature, malaise and indeifinite sensory changes, frequently around the site of the bite.
The patient usually feels pain and irritation in the region of the wound. The excitation phase that follows includes hyperesthesia and extreme sensitivity to light and sound, dilation of the pupils, and an increase in salivation. As the disease progresses, there are spasms of the deglutitory muscles and liquids are violently rejected by muscular contraction. This swallowing dysfunction is seen in most patients, many of whom experience spasmodic laryngopharyngeal contractions simply when looking a liquid and stop swallowing their own saliva ("hydrophobia”).
Postmortem Diagnosis for Animals and Humans
The fluorescent antibody (FA) technique is the gold standard, for rabies diagnosis; however, the accuracy of this test depends upon the expertise of the examiner, and the quality of anti-rabies conjugate and the fluorescence microscope. The' test is based; upon microscopic examination under ultraviolet light of impressions, smears or frozen sections of tissue after they have been treated with anti-rabies serum or globulin conjugated with fluorescein isothiocyanate. The diagnostic conjugate should be high quality and the appropriate working dilution must be determined in order to detect the different genotypes of lyssavirus. Impressions (or smears) of tissue samples from brainstem thalamus, cerebellum, and the hippocampus (Ammon's horns) are recommended for increased sensitivity of the test.
Detection of lyssavirus nucleocapsid antigen by enzyme-linked immunosorbent assay (ELISA) has been described and used for many years in some laboratories. It is rapid and can be useful for epidemiological surveys. However, at present this test is not commercially available.
Virus isolation may be necessary to confirm the results of antigen detection tests and for further characterization of the isolate. Virus isolation can be performed on neuroblastoma cells or upon intracranial inoculation of mice. Where cell culture facilities are not available, mouse inoculation should be used.
Detection by Molecular Techniques
The use of the polymerase chain reaction (PCR) and other amplification techniques is not currently recommended for routine postmortem diagnosis of rabies. However, these molecular techniques can be applied for epidemiological surveys in laboratories with strict quality control procedures in place and that have experience and expertise with these techniques.
Techniques for Intra Vitam Diagnosis of Rabies in Humans
The sensitivity of techniques for rabies diagnosis varies greatly according to the stage of the disease, antibody status, intermittent nature of viral shedding and the training of the technical staff. While a positive result is indicative of rabies, a negative result does not necessarily rule out the infection. Brain biopsy taken solely for the diagnosis of rabies is not recommended.
Viral antigen may be detected by using the FA test on skin biopsies from patients with clinical rabies. Skin biopsies are usually taken from the nuchal area of the neck, with hair follicles containing peripheral nerves. Examination of at least 20 sections is required to detect rabies nucleocapsid inclusions around the base of hair follicles. Though sensitive, this technique may not be practical in all settings, because of the need for a cryostat to prepare frozen tissue sections. FA testing on corneal impressions is rarely reliable in most clinical settings and is therefore not recommended.
Rabies virus isolation can be performed using neuroblastoma cells or the intracranial inoculation of mice. Virus isolation is preferably performed on saliva samples or other biological fluids such as tears and cerebrospinal fluid. The success rate depends upon the antibody status (more positive results are obtained in antibody-negative patients) and on the intermittence of viral shedding. Liquid specimens conserved as such or in swabs should be maintained frozen after collection. The contents of the swab should be expelled into the collection medium. Under no circumstances should preservatives be added to the collection medium. It should be noted that infectious virus may be absent from these specimens even during the late stage of the disease.
Neutralizing antibodies in the serum or cerebrospinal fluid of non-vaccinated patients can be measured using a virus neutralization test such as the rapid fluorescent focus inhibition test (REFIT) or the fluorescent antibody virus neutralization (FAVN) test: Virus-neutralizing antibodies in serum tend to appear on average 8 days after clinical symptoms appear. Rabies antibodies are infrequently found in cerebrospinal fluid.
Molecular detection by polymerase chain reaction and nucleic acid sequence based amplification techniques has the highest level of sensitivity but requires standardization and very stringent quality control. Rabies virus RNA can be detected in several biological fluids and samples (e.g. saliva, .cerebrospinal fluid, tears, skin biopsy sample and urine). Serial samples of fluids (e.g. saliva and urine) should be tested, owing to intermittent shedding of virus. Such techniques can produce false positive or false negative results, and should only be used in combination with other conventional techniques.
Description of Pathology of Organs and Systems
1. Rabies virus causes widespread changes throughout the CNS.
2. This consists of neural necrosis and mononuclear cellular infiltration specially in the thalamus, hypothalamus, pons, and medulla.
3. The cranial nerve nuclei are extensively damaged.
4. Neural changes are present in the spinal cord especially in the posterior horns.
5. Negri bodies are most abundant in the hypocampus, basal ganglia, pons, and medulla, and are found in the degenerating neurons of the salivary glands (pathologic sign forrabies).
Complications and Cause of Death
There may also be spasms of the respiratory muscles and generalized convulsions. The excitation phase may persist until death, or it may be replaced by a generalized paralysis. In some cases the excitation phase is very short with the paralytic symptomatology predominating throughout most of the disease course. The. disease lasts from 2 to 6 days although sometimes longer, and almost invariably ends death.
Common Medications and Treatment
1. Isolate the patient.
2. Give emotional and spiritual support.
3. Provide optimum comfort.
4. Darken the room and provide a quiet environment.
5. Patient should not be bathed and there should not be any running water in the room or within the hearing distance of the patient.
6. If IV fluid has to be given it should be wrapped and needle should be securely anchored in the vein to avoid dislodging in times of restlessness.
7. Concurrent and terminal disinfection should be carried out.
Prevention and Control
Prophylaxis prior to exposure is limited to groups exposed to high risk, such as laboratory workers, personnel of city animal pounds and of rabies control programs, veterinarians and naturalists.
The prevention of rabies after exposure consists basically of local treatment of the wound and passive and active immunization of the individual.
Local treatment of the wound is extremely important and on its own can prevent many cases of rabies by eliminating or inactivating the inoculated virus. The wound should be washed as soon as possible under a strong jet of water and cleaned with soap or detergent and water, followed by application of 40-70% alcohol, tincture of iodine, iodized alcohol, or 0.1% quaternary ammonium compounds. The wound should not be sutured immediately.
Postexposure prophylactic immunization. Because of the long incubation period typical of most cases of human rabies, immunization is possible. Vaccination must be started as soon as possible to ensure that the individual will be immunized before the rabies virus reaches the central nervous system. Combined administration of serum and vaccine is the most effective method of antirabies prophylaxis. It may be used in all cases, but is especially indicated when severe exposures are involved. The sera used may be heterologous (obtained by hyperimmunization of various animal species such as horses and rabbits) or homologous rabies immunoglobulin (of human origin). It is important to note that heterologous serum may cause an anaphylactic reaction; before administration, an intradermal or ophthalmic sensitivity test should be done. Complications with homologous serum are rare, but unfortunately this serum is costly to produce and not readily available.
Postexposure prophylaxis of human patient may be discontinued if the animal involved remains healthy after the prescribed observation period (10-14 days) after the exposure occurred; or if the animal is humanely killed and proven to be negative for rabies by a reliable diagnostic laboratory using a prescribed test. If the animal inflicting the wound is suspected of being rabid and is not apprehended, post-exposure prophylaxis should be instituted immediately. When animal bites occur in a rabies-free area where adequate rabies surveillance is in effect, post exposure prophylaxis may not be required depending upon the outcome of a risk assessment conducted by a medical expert knowledgeable in the epidemiology of rabies in the area and the proper requirements for assessing the risk involved. In areas where canine or wildlife rabies is enzootic, adequate laboratory surveillance is in place and data from laboratory and field experience indicate that there is no infection in the species involved, local health authorities may not recommended anti-rabies prophylaxis.
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