The African lyssaviruses
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1 Animal rabies: BATS Primary reservoirs for all except Mokola Wide diversity of species, large numbers, widespread, often protected Human rabies bat origin only in Americas Rupprecht Lancet Infect Dis : : Messenger Clin Infect Dis : :
2 The African lyssaviruses Lagos bat, Mokola, Duvenhage Epidemiology poorly studied Human case numbers small,? underreported Last human case Duvenhage S Africa 2006: scratch face by bat, no medical attention, died Rupprecht Lancet Infect Dis : : Paweska Emerg Infect Dis : :
3 European bat lyssaviruses EBLV 1 predominant Geographic variability eg Germany only type 1; UK only type 2 Spillover from bats to mammals inc livestock, humans, wildlife but no reservoir roles 4 human cases (1997 +) Ukraine, Russia (EBLV 1); Finland, Scotland (EBLV 2) all died 3 bat bites, 1 bat conservationist; no vaccination Kappelar Rabies Bull Eur : : 12-3; Muller Arch Virol : : ; Brooks Emerg Infect Dis : : 572-8; Fookes Epidemiol Infect : :
4 Australian bat lyssavirus Pteropus alecto (black flying fox) 1996 Ag in brains of 7% of bats submitted for testing following human contact Seropositivity rates 6-7%: 6 Qld Rabies found in bats in Philippines with cross- reactivity to ABL Two human cases: Qld & NSW occupational & bite (27 mos earlier!) Fraser Emerg Infect Dis : : ; 31; Warrilow Curr Top Microbiol Immunol : : 25-44; McCall Emerg Infect Dis : : ; Warrilow Emerg Infect Dis : : 262-4; Arguin Emerg Infect Dis : : ; Allworth Commun Dis Intell : : 504; Hanna Med J Aust : :
5 ABL in the Philippines Neutralizing antibody 22/1998 bats One species Miniopterus schreibersi No active infections found (350 cases human rabies yearly) Arguin Emerg Infect Dis : :
6 Rabies transmission Bite from rabid dog or bat Scratch or lick: broken skin or mucosa Not always a clear history (20/32 in USA) Aerosolization: lab accidents 2 human cases; experimental in bats & mice Organ donor: 4 recipients kidneys, liver and arterial graft all died [donor SAH; rabies antibodies, bat bite] ; CDC MMWR : : 183-4; Winkler JAMA : : ; 21; Davis J Infect Dis : ; Srinivasan NEJM : :
7 Lyssavirus lab diagnosis Culture: saliva, CSF neuroblastoma cell line or ic inoculation of mice [several] Direct FAT using anti-n N antibody, corneal impressions & skin biopsies. Animals. Immunohistochemistry of skin biopsies RT-PCR (real time) using N gene: saliva, CSF, skin. Epidemiologic investigations. Serum/CSF antibody in unvaccinated (neut( neut,, IFA) Brain FAT, Negri bodies, immunohistochem,, culture, RT- PCR Woldehiwet 2005 Clin Chim Acta 351: : 49-63; Heaton J Clin Micro : ; 6; Black J Virol Meth : : 25-35; Smith J Clin Virol : ; Wakeley J Clin Micro : : ; Gould Virus Res : 1-28; Kuzmin Virus Res : : 28-43
8 Clinical features: rabies Incubation months, up to 6 years Prodromal flu-like, like, several days +/- local pain, itch, paresthesiae Encephalitic: : salivation, spasms, LOC, convulsions, coma, death Paralytic: : Guillain Barre-like, sphincter loss, sensory preservation, myoedema Atypical: : neuropathic pain, sensory/motor, chorea, brainstem, cranial ns, myoclonus, psychiatric disturbance Rupprecht Lancet Infect Dis : : ; Warrell Lancet : ; Smith NEJM : :
9 Clinical features: other lyssaviruses Not well characterized Lagos bat virus no human disease EBLV (4 pts) local pain/itch/paresthesiae with encephalitic sequelae ABLV (2 pts) encephalitis, 1st case initial weakness arm Fookes Epidemiol Infect : : ; Allworth Commun Dis Intell : : 504; Hanna Med J Aust : : 597-9
10 Rabies: 6 survivors (1) [Highest case fatality of any ID in humans] Dog (3), bat (2), lab accident (1) USA (3), Mexico, Argentina, India 9 yo boy complete recovery; others significant sequelae; 1 died 23 ys later 5 received vaccine prior to onset of symptoms; none received RIG Warrell Lancet : : ; Willoughby NEJM : :
11 Rabies: 6 survivors (2) 15 yo girl Wisconsin, no vaccine, coma induced by ketamine + amantidine, ribavirin Acquired rabies antibodies Residual choreoathetosis, dysarthria, ataxia Subsequent Thai pt similar treatment without vaccine died Willoughby NEJM : : Hemachudha Neurovirol : : 407-9
12 Prevention in animals 50 million dogs vaccinated/year public health programmes or by private owners Vaccination effective eg Morocco, Tunisia, Sri Lanka Oral live vaccines advocated by WHO eg foxes & coyotes Europe & N America Fertility control; clearance of rubbish Wandeler Rev Sci Tech : : 51-71
13 Prevention in humans Pre-exposure exposure prophylaxis Post-exposure prophylaxis Wound care: soap and water reduces mortality (Kaplan Bull WHO : : ) 75) Australian Immunisation Handbook. NHMRC 9 th Ed
14 Pre-exposure exposure (1) No rabies deaths reported following admin of appropriate vaccine regimen Obviates need for RIG Boosting recommended with monitoring of neut Ab levels; 1 y boost assoc Ab for 10 y ID route immunogenic but lower Ab levels & involves use of multi-dose vials Reduced response in HIV pos children Warrell Lancet : : ; Strady J Infect Dis : : ; Madhusudana Hum Vacc : : 200-4; Thisyakorn Clin Infect Dis : : 218
15 Pre-exposure exposure (2) HDCV & others from genotype 1 Not protective Lagos bat, Mokola, Duvenhage Protective EBLV 1, partially EBLV 2 HDCV 79% protective vs ABLV challenge in mouse model [100% RABV & EBLV] ABLV vaccine likely to be more successful if local strains used in development Encouraging results for new Eurasian strains Lafon Vaccine : : 362-8; Fekadu Vaccine : : ; Hanlon Virus Res : : 44-54; Brooks Vaccine : : ; Hooper 1997 Bull Inst Pasteur 95: :
16 Post-exposure (1) RIG: : human source Horse, sheep, goat rodent sources Monoclonal products in development Rupprecht Lancet Infect Dis : ; Goutsmit J Infect Dis : : ; Prozniak J Infect Dis : : HDCV Chick embryo, duck embryo, rhesus cell & vero cell vaccines considered equivalent DNA or recombinant vaccines + use of plant technology in future Aust Imun Handbook ; Rupprecht Lancet Infect Dis : :
17 Post-exposure (2) Failures usually assoc with deviations from protocol or poor availability or quality: Thai study 7/15 represented true failures No failures of RIG + vacc for EBLV; animal studies: neutralizing effect of RIG variable ABLV more closely related to rabies than EBLV so RIG + vacc hopefully effective Wilde Vaccine : : ; Warrell Lancet : : ;
18 The number of annual human deaths from rabies in the world is: 25,000 35,000 45,000 55,000 65,000
19 Rabies: true/false Transmitted as a lab accident in 1 person: 2 Transmitted from cornea of an organ donor: kidneys, liver, arterial graft There have been only 4 survivors: 6 Axonal transmission occurs at 20 mm/day: Phylogenetic classification is based on G protein: N protein
20 European bat lyssavirus: true/false Has been found in a human in northern England: Scotland Only 5 human cases have been described: 4
21 Where outside Australia has ABL New Zealand New Caledonia Papua New Guinea Malaysia Vietnam Philippines been found?
22 Advances Virology: proteins, virulence, pathogenesis Neuroinvasiveness Transmission Diagnostic tools Global surveillance of animals and humans Reduction in animal cases in some countries Effectiveness of preventive measures
23 However. 55,000 humans/ year develop rabies They almost all die Prophylactic measures very effective The old problem between rich and poor countries applies
24 Acknowledgements Ina and Greg Smith, Public Health Virology, Coopers Plains Alex Hyatt, AAHL, Geelong Scott Hamer,, American Society for Microbiology: Emerging Infectious Diseases 8 th edition
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