1. Viruses, continued

2. 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

3. 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

4. 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.

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

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

7. 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

8. Spongiform Encephalopathies and Prions

9. 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 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.

10. 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 shows normal cellular prion protein.

11. 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.

12. 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

13. 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)

15. BSE in
Britian
CJD,
nvCJD in
Britian

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

17. (Re)Emerging Pathogens

18. 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

19. 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

20. 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))

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

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

23. 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

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

25. 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

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

27. 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

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