Viruses, continued

Man-Arthropod-Man Cycle e.g. dengue, urban yellow fever. Reservoir may be in either man or arthropod vector. In the latter transovarial transmission may take place. 4

Animal-Arthropod-Man Cycle e.g. Japanese encephalitis, EEE, WEE, jungle yellow fever. The reservoir is in an animal. The virus is maintained in nature in a transmission cycle involving the arthropod vector and animal. Man becomes infected incidentally. 5

Zoonotic Viruses Zoonoses are diseases of vertebrate animals that can be transmitted to man: either directly or indirectly through an insect vector. When an insect vector is involved, the disease is also known as an arboviral disease. However, not all arboviral diseases are zoonosis: where the transmission cycle takes place exclusively between insect vector and human e.g. dengue and urban yellow fever. Examples of viral zoonoses that can be transmitted to man directly include rabies, hantaviruses, lassa and ebola fevers.

Rabies Virus member of the Lyassavirus 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 Lyassavirus : Mokola, Lagosbat, Duvenhage, EBL-1, and EBL-2 Duvenhage and EBL-2 have been associated with human rabies.

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

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 dog, vampire bats

Spongiform Encephalopathies and Prions

Prion Smaller than smallest known virus Not yet completely characterized Most widely accepted theory Prion = Proteinaceous infectious particle Normal Protein PrPC (C for cellular) Glycoprotein normally found at cell surface inserted in plasma membrane Prions are smaller than the smallest known virus and have not yet been completely characterized. The most widely accepted theory is that prions are mutated proteins, although not all scientists accept they are the cause of disease. Professor Stanley Prusiner, the Nobel prize winning scientists who first proposed that prion proteins could cause disease, says that today "a wealth of experimental and clinical data" proves his ideas were right. The idea of a protein-only infectious agent was first proposed by Griffiths in 1967. However, it was only after the co purification of the prion protein with hamster scrapie infectivity that Prusiner was able to distinguish it from a virus. The normal protein is designated as PrPC the C stands for cellular. The glycoprotein is normally found at the cell surface and is inserted in the plasma membrane.

Normal protein Secondary structure dominated by alpha helices Easily soluble Easily digested by proteases Encoded by PRNP gene (in humans) Located on human chromosome 20 The secondary structure of the normal protein is dominated by alpha helices. There are likely three of these structures. The normal protein is easily soluble and digested by proteases. This gene in humans is designated PRNP and located on our chromosome 20. Image from www.prionics.ch, shows normal cellular prion protein.

Abnormal Protein Insoluble in all but strongest solvents Highly resistant to digestion by proteases Survives in tissues post-mortem Extremely resistant Heat, normal sterilization processes, sunlight No detectable immune response The abnormal protein is insoluble in all but the strongest solvents and is highly resistant to digestion by proteases. It survives in tissues post-mortem and is not destroyed by various rendering processes. The abnormal form of the protein is extremely resistant to heat, normal sterilization processes and sunlight. It is also very resistant to most disinfectants and is stable at a wide range of pH. The abnormal protein also does not evoke a detectable immune or inflammatory response in its host so the body does not react to it as an invader.

spongiform encephalopathies of humans and other animals Kuru (Fore people in New Guinea) Creutzfeldt-Jakob disease (CJD) Gerstmann-Straussler-Scheinker (GSS) fatal familial insomnia new variant CJD

transmissible spongiform encephalopathies of humans and other animals Scrapie exotic ungulate encephalopathy bovine spongiform encephalopathy (BSE) transmissible mink encephalopathy feline spongiform encephalopathy chronic wasting disease (CWD)

BSE in Britian CJD, nvCJD in Britian

the prion hypothesis conversion instead of replication PrP PrPSc abnormal protein normal protein conversion instead of replication PrP PrPSc

(Re)Emerging Pathogens

Emerging and re-emerging pathogens (during the last 20 years) 175 new species 77 viruses and prions 53 bacteria and rickettsiae 19 fungi 16 protozoans 10 helminths

Scientific advances Advance in analytical techniques Molecular biological methods (PCR) Flow cytometry (FACS) Implementation of effective monitoring system US: MMWR (Morbidity and Mortality Weekly Report): CDC, State Health Departments World: WER (Weekly Epidemiological Record): WHO

Microbial adaptation (I) “Will to Survive” To change themselves Viruses: Mutation RNA viruses (Influenza, SARS) Bacteria: Mobile genomic elements (plasmids, transposons) Virulence factor (E. coli O157:H7) Antibiotic resistance (MRSP (Multi-drug Resistant Streptococcus pneumoniae), VRE (vancomycin-resistant Enterococci)) Morphologic change (V. cholerae O139 (capsule))

Microbial adaptation (II) To find susceptible populations the elderly, organ transplant/cancer patient, AIDS patients Cryptosporidium parvum, Mycobacterium avium complex

Microbial adaptation (III) To find a new niche (habitat) Legionnaire's disease (Air conditioning system: Legionella pnuemophila) Mycobacterium avium complex (Water distribution system)

Vulnerable situation Population expansion/urbanization 50 % of world populations in cities Slums: high density, poor sanitation, malnutrition War, civil unrest, and natural disaster Breakdown of public health infrastructure International travel and commerce 690 million international travels in 2001

Review Questions (So far)? (Exposure routes; Epi Terms?) QOTDs? (RR v. OR; Reduvids/Chagas

Basic Epidemiological Concepts and Terms Risk- The number of individuals who are exposed and become ill divided by the number of those exposed Relative Risk- The risk of illness for individuals exposed divided by the risk of illness for those not exposed

Example What Are Relative Risks for Each Food Item???

Basic Epidemiological Concepts and Terms Odds for Cases- Number of cases exposed to a factor divided by the number of cases not exposed to the factor Odds for Controls- Number of controls exposed to a factor divided by the number of controls not exposed to the factor Odds Ratio- Odds for cases divided by odds for controls OR = Ocases/Ocontrols

Example What is Odds Ratio??? OR = (a/c)/(b/d) = ad/bc