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rabies virus; rabies disease; epidemiology; zombie
Human rabies disease is caused by Rabies Lyssavirus, a virus belonging to Rhabdoviridae family. The more frequent means of contagion is through bites of infected mammals (especially dogs, but also bats, skunks, foxes, raccoons and wolves) which, lacerating the skin, directly inoculate virus-laden saliva into the underlying tissues. Immediately after inoculation, the Rabies virus enters neural axons and migrates along peripheral nerves towards the central nervous system, where it preferentially localizes and injuries neurons of brainstem, thalamus, basal ganglia and spinal cord. After an initial prodromic period, the infection evolves towards two distinct clinical entities, encompassing encephalitic (i.e., “furious”; ~70-80% of cases) and paralytic (i.e., “dumb”; ~20-30% of cases) rabies disease. The former subtype is characterized by fever, hyperactivity, hydrophobia, hypersalivation, deteriorated consciousness, phobic or inspiratory spasms, autonomic stimulation, irritability, up to aggressive behaviours. The current worldwide incidence and mortality of rabies disease are estimated at 0.175×100,000 and 0.153×100,000, respectively. The incidence is higher in Africa and South-East Asia, nearly double in men than in women, with a higher peak in childhood. Mortality remains as high as ~90%. Since patients with encephalitic rabies remind the traditional image of “Zombies”, we need to think out-of-the-box, in that apocalyptic epidemics of mutated Rabies virus may be seen as an imaginable menace for mankind. This would be theoretically possible by either natural or artificial virus engineering, producing viral strains characterized by facilitated human-to-human transmission, faster incubation, enhanced neurotoxicity and predisposition towards developing highly aggressive behaviours.
2. Davis BM, Rall GF, Schnell MJ. Everything You Always Wanted to Know About Rabies Virus (But Were Afraid to Ask). Annu Rev Virol 2015;2:451-71.
3. Schnell MJ, McGettigan JP, Wirblich C, Papaneri A. The cell biology of rabies virus: using stealth to reach the brain. Nat Rev Microbiol 2010;8:51-61.
4. Hemachudha T, Laothamatas J, Rupprecht CE. Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges. Lancet Neurol 2002;1:101-9.
5. Vaidya SA, Manning SE, Dhankhar P, Meltzer MI, Rupprecht C, Hull HF, Fishbein DB. Estimating the risk of rabies transmission to humans in the U.S.: a Delphi analysis. BMC Public Health 2010;10:278.
6. Wacharapluesadee S, Hemachudha T. Ante- and post-mortem diagnosis of rabies using nucleic acid-amplification tests. Expert Rev Mol Diagn 2010;10:207-18.
7. Helmick CG, Tauxe RV, Vernon AA. Is there a risk to contacts of patients with rabies? Rev Infect Dis 1987;9:511-8.
8. Dutta JK, Dutta TK, Das AK. Human rabies: modes of transmission. J Assoc Physicians India 1992;40:322-4.
9. Fekadu M, Endeshaw T, Alemu W, Bogale Y, Teshager T, Olson JG. Possible human-to-human transmission of rabies in Ethiopia. Ethiop Med J 1996;34:123-7.
10. Kolars JC. Should contacts of patients with rabies be advised to seek postexposure prophylaxis? A survey of tropical medicine experts. J Travel Med 2003;10:52-4.
11. Zhu JY, Pan J, Lu YQ. A case report on indirect transmission of human rabies. J Zhejiang Univ Sci B 2015;16:969-70.
12. Lu XX, Zhu WY, Wu GZ. Rabies virus transmission via solid organs or tissue allotransplantation. Infect Dis Poverty 2018;7:82.
13. Gongala G, Mudhusudanab SM, Sudarshanc MK, Mahendrad BJ, Hemachudhae T, Wildee H. What is the risk of rabies transmission from patients to health care staff? Asian Biomed 2012;6:937-939.
14. Mrak RE, Young L. Rabies encephalitis in humans: pathology, pathogenesis and pathophysiology. J Neuropathol Exp Neurol 1994;53:1-10.
15. Jackson AC. Diabolical effects of rabies encephalitis. J Neurovirol 2016;22:8-13.
16. Warrell M, Warrell DA, Tarantola A. The Imperative of Palliation in the Management of Rabies Encephalomyelitis. Trop Med Infect Dis. 2017 Oct 4;2(4). pii: E52. doi: 10.3390/tropicalmed2040052.
17. Nugent C, Berdine G, Nugent K. The undead in culture and science. Proc (Bayl Univ Med Cent) 2018;31:244-9.
18. Awasthi M, Parmar H, Patankar T, Castillo M. Imaging findings in rabies encephalitis. AJNR Am J Neuroradiol 2001;22:677-80.
19. Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2017 (GBD 2017) Results. Seattle, United States: Institute for Health Metrics and Evaluation (IHME), 2018. Available at: http://ghdx.healthdata.org/gbd-results-tool. Last accessed, January 10, 2020.
20. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392:1789-858.
21. Dupont JR, Earle KM. Human rabies encephalitis. A study of forty-nine fatal cases with a review of the literature. Neurology 1965;15:1023-34.
22. Hueffer K, Khatri S, Rideout S, Harris MB, Papke RL, Stokes C, Schulte MK. Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS. Sci Rep 2017;7:12818.
23. Verran J, Reyes XA. Emerging Infectious Literatures and the Zombie. Condition Emerg Infect Dis 2018;24:1774-8.
24. Littlewood R, Douyon C. Clinical findings in three cases of zombification. Lancet 1997;350:1094-6.
25. Adams AJ, Banister SD, Irizarry L, Trecki J, Schwartz M, Gerona R. "Zombie" Outbreak Caused by the Synthetic Cannabinoid AMB-FUBINACA in New York. N Engl J Med 2017;376:235-242.
26. Centers for Disease Control and Prevention. Zombie Preparedness. Available at: https://www.cdc.gov/cpr/zombie/index.htm. Last accessed, January 10, 2020.
27. Headquarters United States Strategic Command. Counter-Zombie Dominance. Available at: https://web.archive.org/web/20170328232114/http://www.cubadebate.cu/wp-content/uploads/2014/05/CONPLAN-8888.pdf. Last accessed, January 10, 2020.
28. Sartin JS. Contagious Horror: Infectious Themes in Fiction and Film. Clin Med Res 2019;17:41-46.
29. Mahadevan A, Suja MS, Mani RS, Shankar SK. Perspectives in Diagnosis and Treatment of Rabies Viral Encephalitis: Insights from Pathogenesis. Neurotherapeutics 2016;13:477-92.
30. Rothe K, Tsokos M, Handrick W. Animal and Human Bite Wounds. Dtsch Arztebl Int 2015;112:433-42.
31. Manning SE, Rupprecht CE, Fishbein D, Hanlon CA, Lumlertdacha B, Guerra M, Meltzer MI, Dhankhar P, Vaidya SA, Jenkins SR, Sun B, Hull HF; Advisory Committee on Immunization Practices Centers for Disease Control and Prevention (CDC). Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2008;57:1-28.
32. Wang W, Ma J, Nie J, Li J, Cao S, Wang L, Yu C, Huang W, Li Y, Yu Y, Liang M, Zirkle B, Chen XS, Li X, Kong W, Wang Y. Antigenic variations of recent street rabies virus. Emerg Microbes Infect 2019;8:1584-1592.
33. Faber M, Faber ML, Papaneri A, Bette M, Weihe E, Dietzschold B, Schnell MJ. A single amino acid change in rabies virus glycoprotein increases virus spread and enhances virus pathogenicity. J Virol 2005;79:14141-8.
34. van Aken J, Hammond E. Genetic engineering and biological weapons. New technologies, desires and threats from biological research. EMBO Rep 2003;4 Spec No:S57-60.
35. Lippi G, Mattiuzzi C. Severe Acute Respiratory Sindrome (SARS): a new and intriguing diagnostic challenge. Biochim Clin 2003;27:177-85.
36. Boulton F. Which bio-weapons might be used by terrorists against the United Kingdom? Med Confl Surviv 2003;19:326-30.
37. Fisher CR, Streicker DG, Schnell MJ. The spread and evolution of rabies virus: conquering new frontiers. Nat Rev Microbiol 2018;16:241-255.
38. Than K. "Zombie Virus" Possible via Rabies-Flu Hybrid? National Geographic, 2010. Available at: https://www.nationalgeographic.com/news/2010/10/1001027-rabies-influenza-zombie-virus-science/: Last accessed, January 10, 2020.
39. Koch C, Crick F. The zombie within. Nature 2001;411:893.
40. Alemi AA, Bierbaum M, Myers CR, Sethna JP. You can run, you can hide: The epidemiology and statistical mechanics of zombies. Phys Rev E Stat Nonlin Soft Matter Phys 2015;92:052801.
41. Warrell MJ. Developments in human rabies prophylaxis. Rev Sci Tech 2018;37:629-647.
42. Fisher CR, Schnell MJ. New developments in rabies vaccination. Rev Sci Tech 2018;37:657-672.