1. Predicting the Future: Emerging Pathogens and Infectious Disease Risk Samuel L. Stanley, Jr., M.D.

2. What is the threat? Emerging infectious diseases –HIV –Avian/Variant Influenza –Hepatitis C –SARS –West Nile Virus –Dengue Fever –Monkeypox –Parvovirus –Nipah –Ebola –Prions

3. Why are they inevitable? Mutability Adaptability Cross species transmission “Human encroachment” Increased susceptible populations Improved discovery techniques X-factor

4. Why are they inevitable? Mutability Adaptability Cross species transmission “Human encroachment” Increased susceptible populations Improved discovery techniques X-factor

5. Why are they inevitable? Mutability Adaptability Cross species transmission “Human encroachment” Increased susceptible populations Improved discovery techniques X-factor

6. Why are they inevitable? Mutability Adaptability Cross species transmission “Human encroachment” Increased susceptible populations Improved discovery techniques X-factor

7. Parvovirus Single stranded DNA viruses Prefer to infect and lyse rapidly dividing cells. Erythema infectiosum (slapped cheek syndrome or Fifth disease) Aplastic crises in individuals with underlying immunosuppression or hematologic disorders. Hydrops fetalis and fetal death with intrauterine Highly resistant to inactivation protocols

8. Dogs are Dying 1978—outbreak of a new disease in dogs in the United States. Disease characterized by decreased appetite, fever, diarrhea (bloody), anemia, myocarditis. High fatality rate in puppies. Spread worldwide. Estimates of 100K to 1M dogs died worldwide.

9. What was the agent? There was a known canine parvovirus, but it was not associated with disease. A feline parvovirus caused feline panleukopenia disease (aka feline distemper). –Fevers; diarrhea; dehydration; hematologic abnormalities. High mortality in kittens.

10. From cat to dog Feline parvovirus— mutations in capsid protein led to ability to infect dogs. No natural resistance in dogs—rapid global epidemic. Stopped by subsequent development of new vaccine as well as use of feline vaccine.

11. Lesson Viruses (RNA or DNA) can alter “host specificity” proteins and jump across species. Disease may be more virulent in new host until virus can adapt. There are parvoviruses or related viruses in other species (e.g. pigs). Could they make the jump to humans? Parvoviruses difficult to eliminate; frequently contaminate animal products (e.g. trypsin, serum ).

13. A Malaysian Mystery Sudden outbreak of encephalitis. Initially suspected to be Japanese B Encephalitis virus. Patients presented with relatively acute onset of fever, headache, dizziness and vomiting. More than 50% of cases had reduced consciousness and evidence for brain stem dysfunction. –Segmental myoclonus, areflexia, hypertension, tachycardia. Abnormal CSF (increased protein/WBC) in 75% of encephalitic patients.

14. Disease Characteristics Initially 28 cases reported-all individuals with contact with pigs. Disease had been preceded by an outbreak of respiratory disease in pigs. Illness spread throughout Malaysia. Pigs, then humans infected. 265 cases of acute encephalitis/105 deaths.

15. Isolation of a new virus Paramyxovirus family (measles and mumps) Resembled Hendra Virus (megamyxovirus genus)— associated with bats, capable of causing disease in horses and humans. Named Nipah for village in Malaysia where isolate obtained.

17. Follow up on Nipah Outbreaks in Bangladesh in 2001 and 2003 caused by Nipah. Fatality rates of 40% and 60% respectively in symptomatic patients. Source unclear—Nipah (+) bats were found. ? Person to person transmission

18. Lessons from Nipah Urbanization/deforestation leads to new contacts between animals and humans. Piggeries next to orchards exacerbated bat/pig contact. Intermediary animals (pigs) may play a key role in disease transmission.

19. Circoviruses ss circular DNA viruses –3 kb genomes –Non-enveloped Multiple members –PCV –TTV –CAV Extraordinary diversity

20. Human Circoviruses High prevalence in human populations Some individuals infected with multiple genotypes Can be transmitted via transfusion; fecal oral also possible; mother-child Association with disease unclear

21. Why worry? Plasticity Pathogens within animal hosts –PCV2 causes severe disease in piglets –Others associated with immunosuppression or anemia Very hearty—resistant to standard measures, including irradiation

22. Lessons from Circoviruses New class of transmissable agent recognized. High variation for DNA virus Extraordinarily resistant What are the consequences of long term infection?

23. Why are emerging infections inevitable? Mutability Adaptability Cross species transmission “Human encroachment” Increased susceptible populations Improved discovery techniques X-factor

24. New frontiers in biology –Reverse transcription –Prion disease Risks/biology that we simply do not recognize yet…

25. How do we respond to this threat?