CLINICAL SYMPTOMS AND MANAGEMENTS OF RABIES

Rabies CaseRabies is a communicable disease that deaden for it’s suffer which it be caused by RNA virus that can be grouped in Rhabdoviridae family. This disease always has a fatal consequence i.e. death for sufferer who has been contacted   by infection and don’t get vaccination. Rabies has spread in all of world particularly in the developing states.

Rabies or crazy dog disease is a zoonosis disease which most important in Indonesia because of: widely of rabies area in Indonesia, the more of animal biting cases with rabies suspected, the character of crazy dog disease on human or animal that always be finished by death. Rabies constitutes a disease that appearing the significant health problem in Asia, where occur death rate hundreds until thousands per year.  Rabies has highest case fatality rate of all infection diseases that are present. Rabies virus can infect all hot bleed animal, so human and bird. Spreading a big party is happened by animal bite from many types of reservoir animal like as: god, cat, wolf, cave bat and others. So it can spread accordance with aerosol particularly on many types of cave bat in America. In America and Canada tackling of Rabies cause problem and heavy economic burden where the governments of those states spend average of 20, 5 million dollars every year. Dog is as the main reservoir of rabies in Asia with 94 – 98% of death is caused by dog bite, highest of bite being present in Bangladesh, India and Pakistan.

Rabies ReservoirRabies be known as strategic animal disease which has high externality, its mean has impact widely loss and with characteristic spreading, spread by fast with high morbidity and high mortality along with has potential to threaten of public health. Restraint and eradication of communicable animal disease which zoonosis characteristic get priority because be seen as part of protection anticipation toward of public health.

Rabies disease be caused by rabies virus that in classification be included on group V negative-strand RNA genome, order of: mononegalovirales, family of: rhabdoviridae, genus of: lyssavirus, species of: rabies virus. The measure of this virus around of long: 180 nm and width 75 nm which be arranged by five types of proteins i.e.: nucleoprotein (N), Phospoprotein (P), matrices protein (M), glycoprotein (G), and polymerase (L). Generally Rhabdoviridae consist of two basic components: rhibonucleoprotein (RNP) on center part and be covered by envelope on outer part. RNP be shaped by nucleoprotein and be coupled by phopoprotein and polymerase (L-protein). Whereas glycoprotein shape the spike on outer surface area (envelope/membrane) and virus with long of around 10 nm with function as main antigen that it inducted and bind up of neutralizing viral antibody, it very important for immune system. Whereas envelope with RNP be coupled with matrices protein (M). The genome of rabies virus is single chain, antisense; none segmented RNA with long around of 12 kb.

bat_rabies reservoirReplication of virus in host cell be begun by fusion of envelope with membrane cell host, and then occur absorption interaction between glycoprotein with specific receptor of cell host surface be followed by penetration of virus to cytoplasm with endocytosis mechanism. Occur virion aggregation with vesicle on cytoplasm (endosome) and then viral membrane will fusion with endosome membrane with consequence RNP virus free moving into cytoplasm (un coating). Because this virus has single and linier RNA genome, then be needed mRNA (messenger RNA) to record in order virus has replication. This recording will be followed by printing process of protein accordance with ordering that had be recorded a while ago on free ribosome in cytoplasm cell (translation). This process will be completed on endoplasm reticulum and Golgi body. After that occurs process of duplication of virus.

PATHOGENESIS

Rabies virus has characteristic very neurotropic, Rabies virus go in the body pass through wound of animal bite spreader of rabies or direct contact with mucosa membrane. Virus cannot go in pass through intact skin. Glycoprotein of virus will bundle with nicotinic receptor (acethycholine receptor) on nerve cell surface. Virus will duplicate itself in inoculation place, spread in accordance with centripetal pass through motorist and sensoric nerve cell go to central nerve system with speed 50 – 100 mm/day and infect brain stem, diencephalon and hippocampus. Spreading pass through lumbar segment of medulla spinals and transportation to brain use nerve circuit which long be included of rubrospinale, corticospinale, spino-olivary, vestibulospinale, spinoreticular, spinocelebelum, and columna dorsal circuit. After arrive to central nerve system the virus will spread accordance with centrifuge go to multiple organs pass through somatic and autonomic nerve arrangement particularly engage parasymphatic strip which responsible toward infection on saliva gland, cornea, skin, heart, pancreas, medulla adrenal and other organ. Viral infection can appear the infiltrate and necrosis of cellular.

Sensitivity toward infection and incubation period be depended of genetic background, virus strain that mixed up with, viral receptor concentration, amount of inoculums, severe of laceration, and distance that be passed through by virus to spread to central nerve system. The symptoms faster appear and incubation period shorter if bite location on face or head.

CLINICAL SYMPTOMS

Incubation period in generally between 30-90 days, but it has variation from 4 days until some years. It depends of location of bite.

Early sign of rabies infection: itchiness and pain on area of wound or bite trace, fever, tremble, weakness, faster in feeling tired, headache, muscle pain, anxiety, depression, nervous, symptom of respiration nerve disorder or symptom of digestive nerve disorder, and after some days will appear acute neurologist symptoms manifestation.

Acute neurologist symptoms: be differenced of encephalitis rabies or furious rabies and paralytic rabies or dumb rabies depends of where organ dominant be infected, brain or medulla spinal. Encephalitis is constitute a symptom that often be found on rabies sufferer about 80%. Sufferer show hyper excitability episode which reflect of brain infection imaging, be signed by confusion episode, hallucination, agitation and aggressive behavior going on some minutes be followed by quiet phase. Hyper excitability symptom occurs spontaneously or appears by sensory irritation provocation (auditory, visual, and olfactory). A big part of sufferer show hydrophobic symptom with trias: inspiration muscle spasm, larynx spasm, and swallow anxiety.

Paralytic Rabies be found about 20% cases, be signed by paralyzed more particularly, shaped as pareses of all extremities and with sphincter anus disorder. The symptoms that appear some time resemble Guillain Barre Syndrome. Some cases be followed by hydrophobic and spasm of larynx muscle on terminal phase.

Coma, without supportive therapy 1/3 cases of rabies will pass away at the first day hydrophobic, 2/3 cases of rabies will fall in coma with or without paralysis and seldom be present hold out longer than one week without intensive care.

DIAGNOSIS

Diagnosis of rabies is building on clinical signs very difficult except be found specific clinical signs i.e. hydrophobic and be present of dog bite wound history. According to clinical experts the classical sign of involvement of brain on this disease are spasm on tactile responds, visual or stimulation olfactory after with full conscious period, agitation, confused, and signs of autonomic dysfunction. Definite diagnosis of rabies only is found by laboratory examination.

Fluorescent Antibody (FA) technique is a sensitive method to diagnostic rabies on animal and human. FA technique is constitute god standard to diagnostic rabies, but the accuracy of this test be depended of examination experience of anti rabies conjugate quality, and fluorescent microscope that be used. Nuclei cap side detection by ELISA has been used by some laboratory, this test fast and can be used on epidemic survey, but until this time that test are no provided commercially yet.

Antigen detection, viral antigen can be detected through skin biopsy which content hair follicle and nerve tissue, usually sample be taken in nape of neck, and require at least 20 samples to detect the rabies nucleocapside, this method is very sensitive but cannot be used in all situation because its require crysostat to make the frozen section. Antibody detection using serum or cerebrospinal fluid is not always giving positive result because the new antibody is formed on the eighth after the clinical symptoms appear.

Virus isolation: using the cells neuroblastome from saliva, tears and cerebrospinal fluid. The success of this method depends upon the representative sampling, antibody status and attachment of the virus on the receptor.

MANAGEMENT

The management of rabies therapy to human is not satisfied, especially if the disease has shown it symptoms. Until now, there is no case report which is the patient can survive after the disease manifestation manifest. Lots of therapy test done, but no one showing a good result. Antiviral or interferon (IFN) therapy that used in single or combination therapy is not fare well yet. Jackson et.al, 2003 recommending the rabies management of early symptom with combination therapy as following: rabies vaccine intradermisly to accelerate the immune respond; rabies immunoglobulin to stop the infection process; ribavirin and alpha-interferon intravenously and intraventricularly. High concentration of Ketamin given intravenously is proven in vitro can inhibit the virus replication. This regiment is still in controversion and requires further verifications because those combination therapies not give satisfaction result after tested in some other country. Wilde H,et al (2008) recommending that it need further researches based on pathogenesis to find effective therapy to rabies patient. Usage of steroid is not recommended in rabies case because in some cases, steroid can accelerate dead and shorten the incubation period. Symptomatic treatment to relieve patient complains can be done by using sedative, narcotic analgesic, anti convulsion and neuromuscular blocker.

The care should be done in isolation room. And to prevent infection from the patient, the doctor and staff should use gloves, goggle and mask when handle this case and the patient fixated in bed. Remember of the end condition of this disease is death as consequence of breathing muscle paralysis so  then be considered using breathing help tool.

Rabies disease can be prevented by immunization. If we find the present case of bite animal suspected of rabies then be done efforts to kill or reduce virus rabies by wash the bite wound by water flow and soap or detergent during 10-15 minutes and next be given antiseptic. The wound of animal bite is not righted to be sewn, except situation sewing. If it needs to be sewn, the wound should be infiltrated by ARS (Anti Rabies serum). Along with be considered giving anti tetanus, antibiotic and analgesic. Giving immunization to prevent rabies is done by two methods i.e.: after contact immunization and before contact immunization.

Therapy after be infected by virus rabies can be done by giving vaccine anti rabies (VAR) only or the SAR. VAR be given if present animal bite with wound which is not dangerous (laceration, excoriation) around of hand or foot. And then giving VAR with SAR if occur animal bite with dangerous wound, wound on mucosa tissues, wound above of shoulder (face, head, neck), wound on arm area, leg, genital, deep wound or multiple wound of animal bite.

Giving Vaccine Anti Rabies (VAR) procedure as below:

Purified Vero Rabies Vaccine (PVRV), be given post exposure Treatment, constitute frozen dry vaccine, formed as virus rabies (Wistar RaBIES PM/WI 38-1503 M Strain). Recommended dosage on adult same with children i.e.: at the first visiting be given two dosages each with 0, 5 ml on deltoid right and left. At the seven days more be given 0, 5 ml intramuscular of deltoid. The same dosage more be repeated at the twenty one days. If it wants to give with the Serum Anti Rabies (SAR) then the giving of anti rabies is repeated on the ninety days, with dosage 0, 5 ml.

Giving Serum Anti Rabies (SAR) procedure as below:

Heterolog serum:

This serum is created from horse serum, before injection be done skin test early. Injection is done by infiltration on wound more and more, and remaining be injected accordance with intramuscular. Extending dose is 40 IU/kg body weight or be given by similar with extending of VAR the first day visit.

Homolog serum:

This serum is created from human blood serum. Injection is done by infiltration on wound more and more, and remaining be injected accordance with intramuscular. Extending dose is 20 IU/kg body weight or be given by similar with extending of VAR the 1st day visit.

If   we want to do prevention of rabies infection before be bitten could be done vaccination with PVRV. Giving by intramuscular on deltoid area 0, 5 ml at 1st day visit, be continued 0, 5 ml at 28th day is followed with revaccination one year after 1st giving by the same dosage. Be given back every 3 years. This prevention particularly is indicated for community with high risk like as for peoples whose work on research center of rabies, domesticated animal doctor, breeder, employee zoo, and employee forestry.

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