1 Rhabdoviruses G. Jamjoom

2 VIRAL ZOONOSES PART I I VERTEBRATE VECTORS

3 HUMAN RABIES >50,000 DEATHS PER YEAR WORLD WIDE

4 Rabies Virus Structure of rabies virus (Source: CDC) Rabies virus particles

5 RABIES VIRUS Rhabdoviridae family Lyssavirus genus helical, enveloped ss RNA, -VE sense

6 Rabies Virus member of the Lyssavirus genus of the Rhabdoviridae. ssRNA enveloped virus, characteristic bullet-shaped appearance with 6-7 nm spike projections. virion nm * 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.

7 TRANSMISSION BITE - USUAL ROUTE CORNEAL AND OTHER TRANSPLANTS MUCOSAL MEMBRANES, WOUND AEROSOL (RARE)

8 Murray et al., Medical Microbiology Note: no viremia

9 NERVE MAN CDC

10 Epidemiology Rabies is a zoonosis which is prevalent in wildlife. The main animals involved differs from continent to continent. Europe fox, bats Middle Eastwolf, dog Asiadog Africadog, mongoose, antelope N Americafoxes, skunks, raccoons, insectivorous bats S Americavampire bats, dog

11 INCUBATION PERIOD ~2 weeks to ~18 months average about two months post-exposure prophylaxis

12 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.

13 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

14 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)

15 CDC rabies virus infected uninfected FLUORESCENT ANTI-RABIES NUCLEOPROTEIN ANTIBODY

16 CDC rabies virus infected (Negri body) uninfected

17 HUMAN RABIES SINGLE SEROTYPE >95% WORLDWIDE DEATHS ASSOCIATED WITH CANINE RABIES –CANINE RABIES PREVALENT IN LATIN AMERICA, ASIA, AFRICA USA ~75% BAT-ASSOCIATED –39 cases –29 cases bat-associated strain – 1 case raccoon-associated strain – 9 cases dog/coyote (8 acquired outside US)

18 RABIES AND RODENTS Small rodents - rarely infected but can occur - esp. woodchucks

19 HUMAN RABIES IN U.S.A. MOST OF RECENT CASES ASSOCIATED WITH BAT RABIES CDC silver-haired bat

20 HUMAN RABIES HUMAN-TO-HUMAN –surgically - via transplants –no direct human-to-human ever documented

21 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

22 PRE-EXPOSURE PROPHYLAXIS VETERINARIANS AND STAFF WILDLIFE OFFICERS ETC LIKELY TO CONTACT RABID ANIMALS Cave Explorers TRAVELERS RABIES RESEARCH WORKERS

23 TREATMENT ONCE SYMPTOMS DEVELOP, TREATMENT VIRTUALLY ALWAYS UNSUCCESSFUL INTENSIVE SUPPORTIVE CARE ONLY 3 CASES DOCUMENTED RECOVERY

24 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.