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Rabies
- 5. Man’s best friend but not vaccinatedMan’s best friend but not vaccinated
- 10. World Rabies Day • …… to reduceto reduce the sufferingthe suffering from rabiesfrom rabies
- 11. At the end of session you will learnAt the end of session you will learn • Rabies: an invariably fatalRabies: an invariably fatal encephalitisencephalitis • Only mammals affectedOnly mammals affected • Always endemic in the wildAlways endemic in the wild • VirusVirus descendsdescends from brain to salivary glandsfrom brain to salivary glands • 90% are from rabid dog90% are from rabid dog • Bats spread it byBats spread it by aerosolaerosol • It can be prevented (100%)It can be prevented (100%) • Bangladesh stands 2Bangladesh stands 2ndnd in mortalityin mortality
- 12. Key factsKey facts • Globally >Globally >60k deaths/60k deaths/yy in >in >150150 countriescountries • 1111thth biggest c/of deathbiggest c/of death • 95% in Asia Africa95% in Asia Africa • 50% children50% children • India: (~30k)India: (~30k) • Wound cleansing & immunization can prevent itWound cleansing & immunization can prevent it • Bangladesh: mBangladesh: most people are unprotectedost people are unprotected • Rabies costs theRabies costs the world $124 billion/yworld $124 billion/y
- 13. What is Rabies?What is Rabies? • .. a zoonosis c/by.. a zoonosis c/by rabiesrabies virusvirus • Infects both domestic & wild animalsInfects both domestic & wild animals • Causes ac. EncephalitisCauses ac. Encephalitis Symptomatic rabies:Symptomatic rabies: 100% fatal100% fatal
- 14. Rhabdo/lyssa viruses • Bullet shaped.Bullet shaped. RNARNA • EnvelopedEnveloped • Killed byKilled by ethanol ether, iodine,ethanol ether, iodine, soap/detergents,soap/detergents, chloroform, acetone, heatchloroform, acetone, heat (60(6000 cc x5 min)x5 min) Lyssa means rageLyssa means rage
- 15. EpidemiologyEpidemiology • Fixed virusFixed virus (lab virus)(lab virus):: R. virus after serial passage throughR. virus after serial passage through rabbits to stabilize its virulence & IPrabbits to stabilize its virulence & IP • Street virus:Street virus: wild viruswild virus • Primary reservoirs:Primary reservoirs: wild mammalswild mammals • OnlyOnly mammalsmammals affected; exceptaffected; except mice !mice ! • ManMan, dogs, raccoons, skunks, foxes, bats, cats, cattle, dogs, raccoons, skunks, foxes, bats, cats, cattle commonlycommonly affectedaffected • It is endemic in many countriesIt is endemic in many countries except Australia, Malaysia,except Australia, Malaysia, Japan, Bhutan, NepalJapan, Bhutan, Nepal IP: incubation periodIP: incubation period
- 17. Distribution of rabies reservoirsDistribution of rabies reservoirs
- 18. RaccoonsRaccoons
- 19. Skunks; a major reservoir of rabies in USASkunks; a major reservoir of rabies in USA
- 21. • Bites, abrasionsBites, abrasions • Scratches,Scratches, aerosol (bats)aerosol (bats) • Mucosal exposureMucosal exposure • RarelyRarely • eating infected meateating infected meat • corneal transplantationcorneal transplantation TransmissionTransmission
- 22. PathogenesisPathogenesis • IP:IP: 9-90d9-90d (several years):(several years): depends on:depends on: • InoculumInoculum • SiteSite • Wound severityWound severity • InnervationInnervation • Untreated:Untreated: 50% rabid bites will develop R:50% rabid bites will develop R: • virulence, dosevirulence, dose • route, site, age, host defenseroute, site, age, host defense
- 23. Pathogenesis ..Pathogenesis .. • RV replicates in muscles: enters nerves & ascends toRV replicates in muscles: enters nerves & ascends to CNS (CNS (3 mm/h)3 mm/h) • Spread within CNS is rapidSpread within CNS is rapid • Then spreads centrifugally by nerves to salivary g., eyes,Then spreads centrifugally by nerves to salivary g., eyes, kidneys, breastskidneys, breasts • This time the classic CF developThis time the classic CF develop RV: rabies virusRV: rabies virus
- 24. Pathogenesis ..Pathogenesis .. Live virusLive virus skin: mucosa: muscleskin: mucosa: muscle Peripheral nervePeripheral nerve CNS (gray matter)CNS (gray matter) Salivary, eyes, breast, kidneysSalivary, eyes, breast, kidneys moves centripetally moves centrifugally
- 25. HistopathologyHistopathology • EncephalomyelitisEncephalomyelitis • Perivascular inflammatory cellsPerivascular inflammatory cells • Neuronal cytoplasmic inclusion (Negri bodies)Neuronal cytoplasmic inclusion (Negri bodies) esp. in pyramidal cellsesp. in pyramidal cells • Inclusion bodiesInclusion bodies (elementary bodies):(elementary bodies): are nuclear/cytoplasmic aggregates; usuallyare nuclear/cytoplasmic aggregates; usually proteins: typically represent sites of viral replication & consist of viral capsidproteins: typically represent sites of viral replication & consist of viral capsid • Pyramidal neurons (pyramidal cells):Pyramidal neurons (pyramidal cells): found infound in c. cortex, hippocampus, & amygdalac. cortex, hippocampus, & amygdala.. They are primary excitation units of mammalian prefrontal cortex &They are primary excitation units of mammalian prefrontal cortex & corticospinal tractcorticospinal tract
- 26. Early CF: (often vague)Early CF: (often vague) • Flu-like:Flu-like: malaise, F:malaise, F: 38C or above38C or above, chills, HA, f, chills, HA, fatigue,atigue, problems sleeping, anorexiaproblems sleeping, anorexia • Anxiety, irritability, sore throatAnxiety, irritability, sore throat • Discomfort/ paresthesiaDiscomfort/ paresthesia at bite site (50%)at bite site (50%) • BBizarre behavior, fear of death!izarre behavior, fear of death! On progression:On progression: neuro-symptoms:neuro-symptoms:
- 27. Neuro-symptoms:Neuro-symptoms: bbroad categoryroad category • Furious rabies (80%)Furious rabies (80%) • Dumb or paralytic rabiesDumb or paralytic rabies (GBS) 20%(GBS) 20%
- 28. Furious rabiesFurious rabies • anxiety, confusion, insomnia, nervousness, seizure,anxiety, confusion, insomnia, nervousness, seizure, aggressivenessaggressiveness,, hallucinations, delirium, fear of deathhallucinations, delirium, fear of death • biting,biting, delusions, HGF, hyperhydrosis, goose skin, priopism,delusions, HGF, hyperhydrosis, goose skin, priopism, hypersalivation, dysphagia,hypersalivation, dysphagia, hydro-phobiahydro-phobia (50%),(50%), aero-, photo-: aaero-, photo-: a few days later coma & deathfew days later coma & death Dumb/paralytic rabiesDumb/paralytic rabies • S/of partial/full paralysisS/of partial/full paralysis usually begins in limbs & spreadsusually begins in limbs & spreads all overall over • Hydrophobia isHydrophobia is unusualunusual • Progress to coma & death (heart or lung failure)Progress to coma & death (heart or lung failure)
- 29. A rabid dog displayingA rabid dog displaying the classic form ofthe classic form of paralytic R, cranial-paralytic R, cranial- nerve deficits &nerve deficits & hypersalivationhypersalivation
- 30. Routine rabies tests:Routine rabies tests: • Direct fluorescent Ab. test (dFA:) (only post mortem)Direct fluorescent Ab. test (dFA:) (only post mortem) • Biopsy:Biopsy: NegriNegri bodies. Immunohistochemistry (IHC). EMbodies. Immunohistochemistry (IHC). EM Importance:Importance: • For timely post-exposure prophylaxis (PEP) orFor timely post-exposure prophylaxis (PEP) or • avoid unnecessary physical & psychological traumaavoid unnecessary physical & psychological trauma Diagnosis in AnimalsDiagnosis in Animals
- 31. dFAdFA detects RVdetects RV • Ideal tissue is nerve (brain)Ideal tissue is nerve (brain) • Fl. anti-rabies Ab incubated with brain tissue fixes RV; seenFl. anti-rabies Ab incubated with brain tissue fixes RV; seen by Fl. MC. Unbound Ab can be washed awayby Fl. MC. Unbound Ab can be washed away IHCIHC • Like dFA, IHC uses sp. Ab to detect RV inclusions in tissues.Like dFA, IHC uses sp. Ab to detect RV inclusions in tissues. More sensitive than histopathologyMore sensitive than histopathology Fl: fluorescence. MC: microscopeFl: fluorescence. MC: microscope
- 32. DFA negativeDFA negative DFA positiveDFA positive
- 33. • Negri bodiesNegri bodies are pathognomonic incl. bodies in cytoplasmare pathognomonic incl. bodies in cytoplasm of certain nerves (of certain nerves (only in 20%)only in 20%)
- 34. Rabies Dx in HumansRabies Dx in Humans • No test available before cl. diseaseNo test available before cl. disease • Confirmed pre- & post mortem by detecting RV, viral Ag inConfirmed pre- & post mortem by detecting RV, viral Ag in brain, skin, urine, salivabrain, skin, urine, saliva • Saliva is tested by reverse transcription followed by PCR (RT-Saliva is tested by reverse transcription followed by PCR (RT- PCR)PCR) • Antibody: serum, CSFAntibody: serum, CSF Ag: antigenAg: antigen
- 35. PreventionPrevention • Vaccinating pet & killing stray dogsVaccinating pet & killing stray dogs • Vaccine for at risk personsVaccine for at risk persons • Care of biteCare of bite • No contact with stray/wild animals. Don’t capture orNo contact with stray/wild animals. Don’t capture or provoke stray animalsprovoke stray animals • Not touching animal carcassesNot touching animal carcasses • Secure garbageSecure garbage • Cover chimneys & other entrancesCover chimneys & other entrances
- 36. • If bitten by bats, skunks, foxes, other carnivoresIf bitten by bats, skunks, foxes, other carnivores • regard as rabid unless the area is R free or until animalregard as rabid unless the area is R free or until animal is negative by lab testingis negative by lab testing • immediate immunization & HRIGimmediate immunization & HRIG • Bites by squirrel, gerbil, hamster, G. pig, rat, mice, otherBites by squirrel, gerbil, hamster, G. pig, rat, mice, other rodents, rabbits, hare almost never require anti-R Rxrodents, rabbits, hare almost never require anti-R Rx HRIG: human rabies immunoglobulinHRIG: human rabies immunoglobulin Prevention …Prevention …
- 38. VaccinationVaccination Killed R virus vaccine PreexposurePreexposure PostexposurePostexposure Animal vaccinationAnimal vaccination 15million vaccines are15million vaccines are pushed worldwidepushed worldwide
- 39. Who should get the Vaccine?Who should get the Vaccine? Pre-exposurePre-exposure • High-risk people:High-risk people: vets., animal handlers, R. lab. workers,vets., animal handlers, R. lab. workers, cave/wild explorers, forestry workers,cave/wild explorers, forestry workers, travelers intravelers in endemic areas,endemic areas, people having frequent contact with R.people having frequent contact with R. virusvirus • 3 doses: 0-7-21/283 doses: 0-7-21/28thth d d BenefitsBenefits • No need of HRIG, less post-expo. vax. dosesNo need of HRIG, less post-expo. vax. doses • Post exposure Rx might be delayedPost exposure Rx might be delayed • Protects from inapparent exposures to R.Protects from inapparent exposures to R. • For repeated exposure screen for boosterFor repeated exposure screen for booster
- 40. Post-exposurePost-exposure • Bitten by an animal, or contactBitten by an animal, or contact • 4 doses: 0-3-7-144 doses: 0-3-7-14thth daysdays • They should also get HRIG with first dose vax.They should also get HRIG with first dose vax. • Pre-vaccinated person get 2 doses: 0-3Pre-vaccinated person get 2 doses: 0-3rdrd d; no HRIGd; no HRIG • Should the animal be kept for 10 d?Should the animal be kept for 10 d?
- 42. Cell culture VaccinesCell culture Vaccines Human diploid cell vaccine (HDCV)Human diploid cell vaccine (HDCV) Purified chick embryo cell vaccine (PCEC)Purified chick embryo cell vaccine (PCEC) Purified Vero cell vaccine (PVRV)Purified Vero cell vaccine (PVRV) Purified duck embryo vaccine (PDEV)Purified duck embryo vaccine (PDEV) Vaccines in BD: Vaccines in BD: Rabipur (PCEC)Rabipur (PCEC) Verorab (PVRB)Verorab (PVRB) Rabix Rabix ,, ,,
- 43. Future Rabies VaccinesFuture Rabies Vaccines • Vax. under dev. may be safe, potent & cheaperVax. under dev. may be safe, potent & cheaper • DNA vaccinesDNA vaccines, recombinant vaccines, recombinant vaccines • Plant biotechnology for making AgPlant biotechnology for making Ag • Neutralizing monoclonal antibodyNeutralizing monoclonal antibody
- 44. Adverse ReactionsAdverse Reactions Less in childrenLess in children • Adults: local reactions (25%), systemic- (20%)Adults: local reactions (25%), systemic- (20%) • HA, nausea, AP, aches & dizziness (5-40%)HA, nausea, AP, aches & dizziness (5-40%) • Very rare:Very rare: illness like GBSillness like GBS • Immune-complex with boosters: hives, arthralgia, F (6%)Immune-complex with boosters: hives, arthralgia, F (6%) • Different brands differDifferent brands differ • Anaphylaxis, Anaphylaxis, if any, occurs within a min- to an hr. withif any, occurs within a min- to an hr. with dyspnoea, hoarseness, wheeze, throat swelling, hives,dyspnoea, hoarseness, wheeze, throat swelling, hives, pallor, weakness, tachycardia, or dizzinesspallor, weakness, tachycardia, or dizziness
- 45. Human Rabies IG (HRIG)Human Rabies IG (HRIG) • Category iii bite:Category iii bite: 20iu/kg20iu/kg with vax. but different siteswith vax. but different sites • ½ at the site (infiltrate the½ at the site (infiltrate the wound); ½ IMwound); ½ IM
- 46. Basic Care in Animal BitesBasic Care in Animal Bites • Immediate thorough toileting x15min with soapImmediate thorough toileting x15min with soap water, detergent, povidone iodinewater, detergent, povidone iodine • Don't suture!Don't suture! • Categorize the bite:Categorize the bite: • Post- exposure prophylaxisPost- exposure prophylaxis
- 48. Bite CategoryBite Category ((WHO)WHO) • Category I: 1.Category I: 1. touching/feeding suspect animalstouching/feeding suspect animals 2.2. licks on intact skinlicks on intact skin • Category II: 1.Category II: 1. nibbling of skinnibbling of skin 2.2. scratches/abrasionsscratches/abrasions, but no hge., but no hge. 3.3. licks on broken skinlicks on broken skin • Category III:Category III: 1 or more1 or more bites/scratches, licks with hge.;bites/scratches, licks with hge.; mucosal contamination with saliva, contacts with batsmucosal contamination with saliva, contacts with bats
- 49. Category ICategory I no treatmentno treatment Category IICategory II wound disinfectionwound disinfection vaccine onlyvaccine only
- 50. Category III bite:Category III bite: bites withbites with bleedingbleeding
- 51. Category IIICategory III wound cleansing, HRIG & vaccinewound cleansing, HRIG & vaccine • Animal observation in our country is not practical:Animal observation in our country is not practical: frequent bitesfrequent bites • Delay Rx only ifDelay Rx only if • Species unlikely to be infectedSpecies unlikely to be infected • Lab Dx in 48hrLab Dx in 48hr • Dog >1yr old with current vaccination (observe forDog >1yr old with current vaccination (observe for 10d)10d)
- 54. To date only 6 cases survivedTo date only 6 cases survived • Once clinical, rabies is always fatalOnce clinical, rabies is always fatal • Rx is only supportiveRx is only supportive • Typically life ends after 2-10 d (6d)Typically life ends after 2-10 d (6d) No danger of nursing R pts with precautionsNo danger of nursing R pts with precautions PrognosisPrognosis
- 55. DDDD Other encephalitisOther encephalitis Hysteria reaction to animal biteHysteria reaction to animal bite GBSGBS PoliomyelitisPoliomyelitis Allergic encephalomyelitis ( rabies vaccine )Allergic encephalomyelitis ( rabies vaccine )
- 56. Shots for Dogs Would Save PeopleShots for Dogs Would Save People • Mass vaccination for dogs could eliminate it in humanMass vaccination for dogs could eliminate it in human • R. is rare in HICsR. is rare in HICs • Lack of international commitment is among the reasonsLack of international commitment is among the reasons why rabies in people persistswhy rabies in people persists
- 57. MCQMCQ • Most rabies are from bite by rabid dogsMost rabies are from bite by rabid dogs • Most of rabid-dog bites develop into rabiesMost of rabid-dog bites develop into rabies • HDCV is at present the best ARVHDCV is at present the best ARV • Rabies is not transmitted by contaminated corneal graftRabies is not transmitted by contaminated corneal graft • Rabies is always endemic in the forestRabies is always endemic in the forest • India has the greatest rabies deathsIndia has the greatest rabies deaths • Bangladesh stands second in mortalityBangladesh stands second in mortality
- 58. MCQMCQ • Vaccinating pet dogs is essential to control rabiesVaccinating pet dogs is essential to control rabies • Everyone should be vaccinated against rabiesEveryone should be vaccinated against rabies • Rabies virus spread to CNS via bloodRabies virus spread to CNS via blood • It can be transmitted by foodIt can be transmitted by food • Saliva contains R virus after brain involvementSaliva contains R virus after brain involvement • Rabies can be eradicatedRabies can be eradicated
- 61. THANK YOU
Hinweis der Redaktion
- Bats possible source of rabies
- The reservoirs vary based on geographic location; commonly dogs, bats, raccoons, foxes, cats, & skunks. The primary cause of human rabies worldwide is from dogs In the US, dogs are vaccinated, the primary c/of R in humans is from wildlife (particularly bats)
- Transmission of R usually begins when infected saliva of a host is passed to an uninfected animal. Various routes have been documented: mucosa (eyes, nose, mouth), aerosol, & corneal transplantations. The most common is bite. Following primary infection, the virus enters an eclipse phase in which it cannot be easily detected within the host. This phase may last for several days or months. Investigations have shown both direct entry of virus into peripheral nerves at the site of infection & indirect entry after viral replication in nonnervous tissue (muscle cells). During the eclipse phase, the host immune defenses may confer CMI against viral infection as R virus is a good Ag. The uptake of virus into PN is important for progressive infection to occur. After uptake into PN, R virus is transported to CNS via retrograde axoplasmic flow. Typically this occurs via sensory & motor nerves at the initial site of infection. IP may vary from a few days to several years, but is typically 1-3 mo. Dissemination of virus within the CNS is rapid, & includes early involvement of limbic system neurons. Active cerebral infection is followed by passive centrifugal spread of virus to peripheral nerves. The amplification of infection within the CNS occurs through cycles of viral replication & cell-to-cell transfer of progeny virus. Centrifugal spread of virus may lead to the invasion of highly innervated sites of various tissues, including the salivary glands. During this period of cerebral infection, the classic behavioral changes associated with rabies develop
- Pathology R is typically encephalitis & myelitis. Perivascular infiltration with lymphocytes, polymorphs & plasma cells can occur throughout entire CNS. R frequently causes cytoplasmic eosinophilic inclusion bodies (Negri bodies) in neuronal cells, esp. pyramidal cells of the hippocampus & Purkinje cells of cerebellum. These are areas of active replication. Several factors may affect outcome: virus variant, inoculum, route & location of exposure, as well as individual age & immune defenses
- Hydrophobia is a set of symptoms in later stages of R: difficulty swallowing, panic when presented with liquids to drink, & the pt. can't quench its thirst Aerophobia: pathological aversion or sensitivity to air or its movement, especially as a symptom of R.
- Rabies diagnosis in humans The importance of routine rabies tests Essential characteristics for routine rabies tests Laboratory tests for rabies Direct fluorescent antibody test (dFA) Antigen detection by dFA General histopathology Negri bodies Immunohistochemistry (IHC) Ultrastructure Amplification methods New standard DFA protocol for rabies Rabies diagnosis in animals The direct fluorescent antibody test (dFA) is the test most frequently used to diagnose rabies. This test requires brain tissue from animals suspected of being rabid. The test can only be performed post-mortem Rabies diagnosis in humans Several tests are necessary to diagnose rabies ante-mortem (before death) humans; no test sufficient. Tests are performed on samples of saliva, serum, CSF, & skin biopsies of hair follicles at the nape of the neck. Saliva can be tested by virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR). Serum & spinal fluid are tested for antibodies to rabies virus. Skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of hair follicles. The importance of routine rabies tests Rapid & accurate laboratory diagnosis of rabies in humans & other animals are essential for timely administration of postexposure prophylaxis. Within a few hours, a diagnostic laboratory can determine whether or not an animal is rabid & inform the responsible medical personnel. The laboratory results may save a patient from unnecessary physical & psychological trauma, & financial burdens, if the animal is not rabid. In addition, identification of positive rabies cases may aid in defining current epidemiologic patterns of disease & provide appropriate information for the development of rabies control programs. Essential characteristics for routine rabies test The nature of rabies disease dictates that laboratory tests be standardized, rapid, sensitive, specific, economical, & reliable. Laboratory tests for rabies The standard test for rabies testing is dFA. This test has been thoroughly evaluated for more than 40 years, & is recognized as the most rapid & reliable of all the tests available for routine use. All rabies laboratories in the United States perform this test (post-mortem) on animals suspected of having rabies. Other tests for diagnosis & research, such as electron microscopy (EM), histologic examination, immunohistochemistry (IHC), RT-PCR, & isolation in cell culture are useful tools for studying the virus structure, histopathology, typing, & virulence of rabies viruses. Direct fluorescent antibody test (dFA) The dFA test is based on the observation that animals infected by rabies virus have rabies virus proteins (antigen) present in their tissues. Because rabies is present in nervous tissue (& not blood like many other viruses), the ideal tissue to test for rabies antigen is brain. The most important part of a dFA test is flouresecently-labelled anti-rabies antibody. When labelled antibody is incubated with rabies-suspect brain tissue, it will bind to rabies antigen. Unbound antibody can be washed away & areas where antigen is present can be visualized as fluorescent-apple-green areas using a fluorescence microscope. If rabies virus is absent there will be no staining. Antigen detection by dFA The rabies antibody used for the dFA test is primarily directed against the nucleoprotein (antigen) of the virus (see The Virus section on viral structure). Rabies virus replicates in the cytoplasm of cells, & infected cells may contain large round or oval inclusions containing collections of nucleoprotein (N) or smaller collections of antigen that appear as dust-like fluorescent particles if stained by the dFA procedure.
- Despite evidence that control of dog rabies through programs of animal vaccination & elimination of stray dogs can reduce the incidence of human rabies, exposure to rabid dogs is still the cause of over 90% of human exposures to rabies & of over 99% of human deaths worldwide.
- Purpose of PrEP: First, although it does not eliminate the need for additional medical attention after a exposure, it simplifies therapy by eliminating the need for HRIG & decreasing the number of vaccine doses needed – a point of particular importance for persons at high risk of being exposed to rabies in areas where immunizing products may not be available, & it minimizes SE to multiple doses of vaccine. Second, it may enhance immunity in persons whose postexposure Rx might be delayed. Finally, it may provide protection to persons with inapparent exposures to rabies. It consists of 3 doses: on days 0, 7, & 21 or 28
- RIG: Rabies Immune Globulin
- Vero cells are used in cell cultures; first isolated from kidney epith cells from an African green monkey in 1962 They are used for: screening toxin of E coli ("Vero toxin“ or "Shiga-like toxin“), for growing virus; testing for rabies virus, growth of viral stocks for research purposes, host cells for eukaryotic parasites. The Vero cell lineage is continuous & aneuploid meaning an abnormal number of chromosomes. Vero cells are interferon-deficient; they do not secrete interferon when infected by viruses though they have Interferon receptor
- Local treatment of the wound: Removing the RV at the site by chemical or physical means is an effective means of protection, prompt local treatment of all bite wounds & scratches that may be contaminated with RV is important. Immediate & thorough flushing & washing of the wound for a minimum of 15 min with soap & water, detergent, povidone iodine or other substances that kill the rabies virus
- Signs & symptoms The first symptoms of rabies may be nonspecific flu-like signs — malaise, fever, or headache, which may last for days. There may be discomfort or paresthesia at the site of exposure (bite), progressing within days to symptoms of cerebral dysfunction, anxiety, confusion, agitation, progressing to delirium, abnormal behavior, hallucinations, & insomnia. The acute period of disease typically ends after 2 to 10 days (6). Once clinical signs of rabies appear, the disease is nearly always fatal, & treatment is typically supportive. Disease prevention is entirely prophylactic & includes both passive antibody (immune globulin) & vaccine. Non-lethal exceptions are extremely rare. To date only six documented cases of human survival from clinical rabies have been reported & each included a history of either pre- or postexposure prophylaxis.