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    1 : Rabies Dr. Rabie Zahran. Tropical M. Consultant. Damietta Fever Hospital. Egypt
    2 : *Rabies is a zoonotic viral disease of the CNS. *It infect both domestic & wild animals. *It is one of the oldest & most feared diseases reported in medical text. Introduction
    3 : Introduction Practicing physicians must have a good idea about : * The biology, *Pathogenesis, *Epidemiology of the disease. *Detailed knowledge regarding post-exposure prophylaxis
    4 : Rabies is a global problem *Rabies is widely distributed across the globe. *More than 55 000 people die of rabies each y. *Human rabies cases have been documented in all continents except Australia and Antarctic. * 95% of human deaths occur in Asia & Africa.
    5 : Rabies is a global problem *Most human deaths follow a bite from an infected dog. *Between 30% to 60% of the victims of dog bites are children under the age of 15.
    6 : Rabies in Egypt
    7 : History * Rabies virus was recognized in Egypt before 2300 B.C. and was described by Aristotle ancient Greece. Who said, “Dogs suffer from the madness. This causes them to become irritable and all animals they bite to become diseased.”
    8 : * Dog bites are the causes for over 90% of all human post-exposure treatment in Egypt. Rabies in Egypt.
    9 : There is annual occurrence of stray dogs or wild canines bites for human. * No laboratory confirmation for the suspected cases. *All the bitten individuals are subjected to prophylactic treatment against Rabies including vaccination. Rabies in Egypt.
    10 : Control of stray dog population * The dog population is estimated at more than 3 million dogs. * The ratio of stray dogs to owned dogs is estimated to be 15 : 1 . Accordingly, the control measures are aimed mostly to eliminate stray dogs.
    11 : Control of stray dog population cont. * The current system for control of stray dog population is the elimination by poisoning with strychnine or by cartridge shooting. * These procedures create many problems with animal welfare organizations.
    12 : Causative agent
    13 : Causes Rabies is transmitted by contact with rabies virus. Most rabies viruses belong to: genus Lyssa-virus . family Rhabdo-viridae . (Greek word : Rhabdos =Road )
    14 : Rabies virus Bullet shaped virus Size is 180 x 75 nm Has Lipoprotein envelop Knob like spikes /Glycoprotein S Genome unsegmented Linear negative sense RNA.
    15 : Its nucleocapsid material comprises the Negri bodies observed in the cytoplasm of infected neurons.
    16 :
    17 : Rabies virus is sensitive to : *Ethanol. *Iodine. *Soap / Detergents. *Ether. *Chloroform. *Acetone. Destroyed at 500 c in 1 hour at 600 c in 5 minutes.
    18 : reservoir for rabies Any mammal can get rabies.
    19 : Dog is one of best human friends but can spread Rabies if not vaccinated
    20 : Dogs cats reservoir
    21 : reservoir Donkey Horse
    22 : Foxes Skunks reservoir ???????
    23 : Raccoons reservoir Bats
    24 : cattle ferrets reservoir ?????
    25 : Rodents seldom carry rabies. NB. their bites generally do not require post-exposure prophylaxis.
    26 : lagomorphs (eg , hares) seldom carry rabies their bites generally do not require post-exposure prophylaxis. ??????? ??????
    27 : Woodchucks are an exception and have been shown to carry rabies. So post-exposure prophylaxis is required
    28 : Those not mammals & so don’t carry rabies bird bees tick snake turtle
    29 : Rabies is transmitted through: Bite wound (5-80% of cases). Scratched , being licked over an open wound or mucus membrane, exposure to brain tissue or cerebrospinal fluid (CSF) of a rabid animal. Intact skin contact with urine, blood, or feces of an animal has not been shown to constitute exposure, except in bats. Where respiratory exposure from bats is a growing concern. Transmission
    30 : Direct human-to-human transmission of rabies has not been documented. However, 8 cases have been reported in which people died of rabies after transplantation of corneas from people who were diagnosed with the disease. All 8 occurred in transplanted corneas in 5 countries.
    31 : Incubation period Average : 20-90 days. Rarely : as long as 19 years. In > 90% of cases IP. <1 year. This depend upon : 1) size of inoculum . 2) size and depth of bite. 3) proximity to CNS.
    32 :
    33 : Pathogenesis
    34 : After inoculation, viral glycoprotein attaches to the nicotinic acetylcholine receptor of skeletal muscle. Initial replication occurs in myocytes. Pathogenesis
    35 : Pathogenesis *The virus then enters the nervous system via unmyelinated sensory and motor terminals. At this point, the virus is sequestered from the immune system, SO vaccination can no longer be effective. * The exact time course of these events is unknown because IP. may take years.
    36 : Pathogenesis *Rabies virus spreads via retrograde axoplasmic flow at 8-20 mm/d until it reaches the spinal cord. *Paresthesia then may begin at the wound site. *Rabies continues to spread throughout the CNS. undergoing centrifugal spread.
    37 : centrifugal spread along peripheral nerves to : *the skin, *Intestine, *salivary glands, where it is shed in saliva. * Cornea & shed in tears . Pathogenesis
    38 : PATHOGENESIS Live virus? Epidermis, Mucus membrane Peripheral nerve CNS ( gray matter ) Other tissue (salivary glands,…) centripetally centrifugally
    39 :
    40 : Signs in animals that may suspect to be rabid Unusual behavior. Wild animals that appear friendly. Nocturnal animals active during the day An increase in drool or saliva. Animals that act very sick. Animals that have difficulty moving or are dead
    41 : Rabid dog
    42 : Rabid dog with dripping saliva
    43 : two dogs afflicted with dumb rabies, manifested as depression, and an attempt at self-imposed isolation
    44 : Rabid fox in wooded area
    45 : Depressed rabid fox
    46 : Clinical
    47 : Clinical presentation (Leads the clues in Diagnosis) 1) history of or evidence of : *an animal bite, *death of the biting animal, *incomplete or no vaccination following exposure. 2) clinical symptoms and signs,
    48 : Broad category - Presentations Furious Rabies Dumb ( Rage tranquille ) (Landry/Guillain-Barre Syndrome
    49 : Once symptoms of rabies develop it is fatal to both animal and human
    50 : Clinical Course * Rabies progresses over 7 to 14 days . * The mean time between initial presentation and death is 16.2 days.
    51 : Clinical Course Non specific Prodrome : 1 - 2 days ? 10 days. Fever, headache, sore throat Anorexia, nausea, vomiting, Agitation, depression Paresthesias or fasciculation at or Around the site of inoculation of virus.
    52 : Clinical Course The only symptom that specifically arias the Red Flag of rabies diagnosis is Paresthesias and pain at the site of bite or scratch during the Prodrome.
    53 : Acute Neurologic Encephalitis(symptoms) 1 – 2 days to < 1 week Excessive motor activity, Excitation, Agitation Confusion, Hallucinations, Delirium, Bizarre aberrations of thought, Seizures, Muscle spasms, Meningismus , Opisthotonic posturing Mental aberration ( Lucid period ? coma ) Hyper salivation, Aphasia, Pharyngeal spasms Incordination , Hyperactivity Clinical Course
    54 : Acute Neurologic Encephalitis(signs) Fever T > 40.6 Dilated irregular pupils Lacrimation , Salivation & Perspiration Upper motor neuron paralysis Deep tendon reflexes Extensor plantar responses ( as a rule ) Hydrophobia or Aerophobia (50 -70% ) Clinical Course
    55 : Late symptoms : Hypotension. Coma. DIC. Cardiac arrhythmias. Cardiac arrest. Clinical Course
    56 : Rabies can present as Grave condition
    57 :
    58 : Clinical diagnosis in humans. Classical signs of brain involvement include : spasm in response to stimuli either : * Tactile. * Auditory. * Visual. *Olfactory. e g : aerophobia and hydrophobia.
    59 : Clinical diagnosis in humans. Periods of lucidity, agitation , confusion, Signs of autonomic dysfunctions. Spontaneous inspiratory spasms until death (there presence facilitate clinical diagnosis). At early paralytic rabies myoedema is noted at percussion sites on the chest , deltoid and thigh.
    60 : Atypical or non classic rabies is being increasingly recognized and may be responsible for underreporting.
    61 : Role of imaging: 1: MRI of brain: Abnormal , ill-defined , mildly hyper signal T2 images of the brain are suggestive of rabies. 2: CT of brain : Is of no diagnostic value.
    62 : Lab . Studies 1: CSF : * may be normal . * protein may be elevated. * mild increase of CSF white blood cells. * Isolation of rabies virus from CSF (also from saliva ). * Rabies neutralizing antibody titer in the CSF (or serum) is higher than 5 in unvaccinated people.
    63 : Common confirmatory test 1)The standard pre-mortem test is Direct fluorescent antibody test to demonstrate the presence of viral antigen. 2)The standard post-mortem test is biopsy of the patient's brain and examination for Negri b. Autopsies are rarely performed.
    64 : Negri bodies – A gold standard in Diagnosis Inclusion bodies called Negri bodies are 100% diagnostic for rabies infection, but found only in 20% of cases
    65 : Negri bodies in Brain Tissue Negri bodies  round or oval inclusion bodies seen in the cytoplasm and sometimes in the processes of neurons of rabid animals after death. Negri bodies are Eosino-philic, sharply outlined, (2-10 µm in diameter) pathognomonic for diagnosis.
    66 : DIFFERENTIAL DIAGNOSIS Other viral encephalitis Hysteria reaction to animal bite Landry/ Guillan - barre syndrome Poliomyelitis Allergic encephalomyelitis ( rabies vaccine )
    68 : PREVENTION Pre-exposure Prophylaxis Post-exposure Prophylaxis
    69 : 1st Vaccine for Rabies Prepared by Pasteur by drying various periods pieces of spinal cord of Rabbits infected with fixed virus 1885 Joseph Meister 9 year boy vaccinated 13 injections were given Patient saved
    70 : Cell culture Vaccines in – commonly prescribed 1 Human diploid cell vaccine. 2 Purified chick embryo cell vaccine 3.Purified Vero cell vaccine
    71 : Human Diploid Cell Vaccine Koprowsky, Viktor, Plokin discovered Inactivated in Betaproprionate. No serious side effects. Human Diploid cell vaccines purified . Sub Unit vaccines in progress/developed.
    72 : Pre-exposure vaccination Indicated for : 1) Laboratory workers. 2) Veterinarians. 3) technical staff. 4) Bat handlers. 5) International travelers (who are likely to come in contact with animals in parts of the world where rabies is common.)
    73 : Human Diploid Cell Vaccines Inactivated forms of virus that promote immunity by inducing an active immune response. * Pre-exposure prophylaxis ( 3 doses ) 0 – 7 – 21 or 28 days A booster after 1 year, Repeat once in 5 days, Given IM or SC in the Deltoid region. Don't inject in Gluteal region.
    74 : Vaccination is the best way to prevent infection and properly vaccinated animals stand very little chance of contracting the disease. While rabies vaccination for dogs is mandatory for all states, it is estimated that up to half of all dogs are not vaccinated
    75 : Post-exposure care Prophylaxis
    76 : The good news is that if post-exposure treatment is given correctly and in time, it is 100% effective in preventing rabies disease.
    77 : Post-exposure care :
    78 : Post-exposure care :
    79 : * don't suture . * Use local antiseptics or tincture of Iodine. * Inform your doctor immediately Post-exposure care :
    80 : Once the diagnosis of rabies is confirmed : Considering the hopelessness of rabies in man TTT. Should centre on comfort care: 1: the patient should receive adequate sedation & comfort in a private room with suitable emotional and physical support . 2: Repeated IV . Morphine is effective in reliving severe agitation, anxiety and phonic spasms. 3: Invasive procedures should be avoided.
    81 : Post-exposure Prophylaxis
    82 : Category - WHO Category I: touching or feeding suspect animals, but skin is intact. Category II: minor scratches without bleeding from contact, or licks on broken skin . Category III: one or more bites, scratches, licks on broken skin, or other contact that breaks the skin; or exposure to bats
    83 : Anti rabies vaccine should be given for: category II & III exposures as soon as possible according to WHO. Recognized regimen.
    84 : Anti rabies immunoglobulin( antibodies ) should be given (with 1st dose anti-rabies vaccine ) to : Category III exposures . Category II ( if the patient is immunocopromized.)
    85 : This Passive antibody provides protection for 1-2 weeks until the vaccine elicits protective antibody.
    86 : Identify and capture the animal involved . Post exposure prophylaxis should start immediately and can be stopped if the animal remains healthy after 10 days In case of category III exposure :
    87 : Human Diploid Cell Vaccines *Post exposure Prophylaxis: 5 doses at : 0 -3 -7-14 – 28 days. Given IM or SC in the Deltoid region. Don't inject in Gluteal region.
    88 : A person who has been previously vaccinated should get 2 doses of rabies vaccine At 0 & 3rd day * Rabies Immune Globulin is not needed
    89 : Pregnancy & Rabies vaccine
    90 : Pregnancy is not a contraindication to post-exposure prophylaxis against rabies, which is warranted to protect the life of the fetus and mother. *No adverse pregnancy outcomes have been documented with post-exposure prophylaxis. *No mother-to-fetus transmission has been described;
    91 : *thus, neither rabies exposure nor diagnosis of rabies in the mother is an indication for pregnancy termination

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