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Rhabdoviruses. G. Jamjoom. VIRAL ZOONOSES. PART I I VERTEBRATE VECTORS. HUMAN RABIES. >50,000 DEATHS PER YEAR WORLD WIDE. Rabies Virus. Structure of rabies virus (Source: CDC). Rabies virus particles. RABIES VIRUS. Rhabdoviridae family Lyssavirus genus helical, enveloped
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Rhabdoviruses G. Jamjoom
VIRAL ZOONOSES PART I I VERTEBRATE VECTORS
HUMAN RABIES • >50,000 DEATHS PER YEAR WORLD WIDE
Rabies Virus Structure of rabies virus (Source: CDC) Rabies virus particles
RABIES VIRUS • Rhabdoviridae family • Lyssavirus genus • helical, enveloped • ss RNA, -VE sense
Rabies Virus • member of the Lyssavirus genus of the Rhabdoviridae. • ssRNA enveloped virus, characteristic bullet-shaped appearance with 6-7 nm spike projections. • virion 130-240nm * 80nm • -ve stranded RNA codes for 5 proteins; G, M, N, L, S • Exceedingly wide range of hosts. • There are 5 other members of Lyssavirus : Mokola, Lagosbat, Duvenhage, EBL-1, and EBL-2. • Duvenhage and EBL-2 have been associated with human rabies.
TRANSMISSION • BITE - USUAL ROUTE • CORNEAL AND OTHER TRANSPLANTS • MUCOSAL MEMBRANES, WOUND • AEROSOL (RARE)
Note: no viremia Murray et al., Medical Microbiology
NERVE MAN CDC
Epidemiology Rabies is a zoonosis which is prevalent in wildlife. The main animals involved differs from continent to continent. Europe fox, bats Middle East wolf, dog Asia dog Africa dog, mongoose, antelope N America foxes, skunks, raccoons, insectivorous bats S America vampire bats , dog
INCUBATION PERIOD • ~2 weeks to ~18 months • average about two months • post-exposure prophylaxis
Pathogenesis • The commonest mode of transmission in man is by the bite of a rabid animal, usually in Asia a dog. Rabies is an acute infection of the CNS which is almost invariably fatal. • Following inoculation, the virus replicates in the striated or connective tissue at the site of inoculation and enters the peripheral nerves through the neuromuscular junction. • It then spreads to the CNS in the endoneurium of the Schwann cells. • Terminally, there is widespread CNS involvement but few neurons infected with the virus show structural abnormalities. The nature of the profound disorder is still not understood.
SYMPTOMS • Variable, often misdiagnosed • Tingling, paresthesia at bite site • Fever, headache, malaise, anorexia • Nausea, vomiting, myalgia, hydrophobia • Confusion, hallucinations, seizures, paralysis • Coma, respiratory failure, death
DIAGNOSIS • neutralizing antibodies in serum or CSF • direct fluorescence antibody • corneal smear, nuchal biopsy, brain biopsy • RT-PCR saliva • post-mortem staining of brain slice • Negri bodies • direct flouresent Ab test ( more sensitive)
FLUORESCENT ANTI-RABIES NUCLEOPROTEIN ANTIBODY rabies virus infected uninfected CDC
rabies virus infected (Negri body) uninfected CDC
HUMAN RABIES • SINGLE SEROTYPE • >95% WORLDWIDE DEATHS ASSOCIATED WITH CANINE RABIES • CANINE RABIES PREVALENT IN LATIN AMERICA, ASIA, AFRICA • USA 1990-2004 ~75% BAT-ASSOCIATED • 39 cases • 29 cases bat-associated strain • 1 case raccoon-associated strain • 9 cases dog/coyote (8 acquired outside US)
RABIES AND RODENTS • Small rodents - rarely infected but can occur - esp. woodchucks
HUMAN RABIES • IN U.S.A. MOST OF RECENT CASES ASSOCIATED WITH BAT RABIES CDC silver-haired bat
HUMAN RABIES • HUMAN-TO-HUMAN • surgically - via transplants • no direct human-to-human ever documented
POST-EXPOSURE PROPHYLAXIS • CLEAN WOUND • Include soap and water, alcohol or benzyl alkonium chloride etc. • STATE HEALTH DEPARTMENT • determine risk, examine animal (if available) • VACCINATION • Human Diploid Cell Vaccine • fetal rhesus lung cell vaccine • Purified Chicken Embryo Cell vaccine • HUMAN RABIES IMMUNE GLOBULIN • HRIG • infiltrate up to half around wound, rest IM
PRE-EXPOSURE PROPHYLAXIS • VETERINARIANS AND STAFF • WILDLIFE OFFICERS ETC LIKELY TO CONTACT RABID ANIMALS • Cave Explorers • TRAVELERS • RABIES RESEARCH WORKERS
TREATMENT • ONCE SYMPTOMS DEVELOP, TREATMENT VIRTUALLY ALWAYS UNSUCCESSFUL • INTENSIVE SUPPORTIVE CARE • ONLY 3 CASES DOCUMENTED RECOVERY
Control of Rabies • Urban - canine rabies accounts for more than 99% of all human rabies. Control measures against canine rabies include; • stray dog control. • Vaccination of dogs • quarantine of imported animals • Wildlife - this is much more difficult to control than canine rabies. However, there are on-going trials in Europe where bait containing rabies vaccine is given to foxes. Success had been reported in Switzerland.