Emerging Infectious Diseases (EID).

Where do they
originate? What do we do? Why do we care?

Global richness map of the geographic origins of EID

events from 1940 2004. http://www.ucsd.tv/search-details.aspx?showID=23137

The Realities in Global Trends

EIDs are a significant burden on global economies &
public health.
EID emergence thought to be driven by socio-economic
environmental & ecological factors.

http://www.prweb.com/releases/2005/03/prweb220610.htm

Definition of a Pandemic: Tracking

Swine Flu using Google Maps
http://www.gadgetlite.com/2009/04/27/tracking-swine-flu-pandemic-google/

pandemic occurring over wide geographical

area and affecting an exceptionally high
proportion of the population.

zoonotic diseases or zoonosis: infectious

diseases that can be transmitted from other vertebrate
animals to humans. May be direct or via a vector.

http://www.avma.org/onehealth/appendix_c.asp

Zoonotic Diseases: Five Stages through which pathogens

of animals evolve to cause disease in humans.
Critical transitions:
Stage 1 to Stage 2:
from animal to human
Stages 3 & 4:
pathogens ability to
sustain cycles of human
to human transmissions
Ex. modern Ebola
outbreaks are stage 3.

2007 Nature 447, 279-283.

Global Trends Results

EIDs events have risen significantly over time.
Peak 1980s attributed to HIV.
EIDs dominated by zoonoses (60.3%).
71.8% of zoonoses originate in
wildlife (SARs, Ebola) and this
trend is increasing.
54.3% caused by bacteria or
rickettsia.
25.4% by viruses or prions.
Drug-resistant microbes are
Increasing.
Data reveal substantial risk
of zoonotic & vector-borne EIDs
at lower altitudes (below equator)
where reporting effort low.

2008 Nature 451, 990-994

List of NIAID Emerging and Re-emerging Diseases

Group IPathogens Newly Recognized in the Past Two
Decades
Acanthamebiasis
Australian bat lyssavirus
Babesia, atypical
Group IIRe-emerging
Bartonella henselae
Pathogens
Ehrlichiosis
Enterovirus 71
Encephalitozoon cuniculi
Clostridium difficile
Encephalitozoon hellem
Mumps virus
Enterocytozoon bieneusi
Streptococcus, Group A
Helicobacter pylori
Staphylococcus aureus
Hendra or equine morbilli virus
Hepatitis C
Hepatitis E
Human herpesvirus 8
Human herpesvirus 6
Lyme borreliosis
Parvovirus B19

Why are many EIDs linked to Viruses?

Viruses have
High rate of mutation, contact between species, spread from
isolated populations.
RNA viruses unusually high rates of mutation
lack the proofreading mechanisms seen in DNA replication
Examples of RNA virus EIDs: common cold, measles, mumps, polio
HIV or AIDs
Ebola hemorrhagic fever
West Nile & other emerging viruses causing encephalitis
SARS severe acute respiratory syndrome (2002-2003)
Examples of DNA virus EIDs:
hepatitis, chicken pox, herpes infections

Ebola virus

Infectious Disease Cycle

& Persistence

Resistance
Spread
Outbreak

Dependent on duration of
infectivity in host.
Rate of infection of new hosts.
Rate of development of host
protective immunity
Population density, size, and
structure: may eradicate
locally but persists regionally.

HowdoesanInfluenzaPandemic
Occur?
Video

youtube copy

Experts predict next epidemic will start in animals.

USA Today. October 22, 2008.
First known case Swine Flu (H1N1): March 28, 2009.
First known case US: April 17, 2009
April 26th: New Zealand, France, Israel, Brazil, Spain report cases.
86 deaths in Mexico attributed to swine flu.
June 11th: Pandemic declared by WHO. The first influenza pandemic in the
last 40 years.
July 14th: WHO authorizes pharmacy companies to manufacture vaccines.
August 27th: US colleges see spike in number of cases.
September 4th: WHO announced 625 deaths in the last week.
October 5th: vaccine ready.
October 24: President declares a national emergency.

Attendance exercise:
Why did the President declare a national
emergency concerning swine flu?
What is the greatest fear of scientists and policy
makers?

Swine Flu or H1N1 is an influenza A virus

containing 11 viral genes.

Genome consists of
8 segments of single
stranded RNA.
Genes encoded include:
polymerase PB2
polymerase PB1& PB1-F2
polymerase PA
hemagglutinin HA
nuclear protein NP
neuraminidase NA
matrix proteins M1 & M2
nonstructural proteins NS1 & 2

Neumann et al. 2009. Nature 459, 931-939.

Schematic diagram of the influenza

viral life cycle.

Animation: Influenza Vi
rus Replication

Figure 2: G Neumann et al.

Nature 459, 931-939 (2009)

Where did most recent H1N1 come from?

Original reservoir was birds
1918: human influenza A
(H1N1) pandemic transfer
from chickens
1918: Cedar Rapids Swine
Show influenza A transmitted to
pigs from humans.
1931: documented infectious
transmission
1933: used ferret model to
document transmissibility for
human & swine viruses.
1918-present: evolution of virus
in humans.
1957: H1N1 abruptly
disappeared from humans.

Morens et al. 2009. NEJM 361. 225-229.

Genesis of 2009 Swine-origin H1N1 Influenza Viruses.

Neumann et al. 2009. Nature 459, 931-939.

MonitoringforInfluenzaviruses
MSNBC Video: H1N1 Virus

We can watch virus evolution.

This requires large-scale sequencing of viruses isolated from
patients.
After this, bioinformatic analysis shows which ones are evolving
most rapidly. These are, on evolutionary principles, the most
likely to be problematic in the future.

video backup link

US Vaccine Evaluation Centers

Prevention and Control

Possibility #1

Prevention and Control

Possibility #2
A

Antiviral drugs interfere with viral

specific proteins:
adamantanes: block ion channel
formed by M proteins (M proteins
used for escape from
endosome).
Oseltamivir (Tamiflu) and
aznamivir: neuraminidase
inhibitors block release of new
virus particles.

M protein with 2
adamantanes bound

Attendance exercise:
Why did the President declare a national
emergency concerning swine flu?
What is the greatest fear of scientists and policy
makers?

Dengue Fever on the watch list. Why?

Video from ABC News
(copy of the Video link)

Caused by one of 4 different, but related viruses.

Carried by mosquito, Aedes aegypti
4-6 days for symptoms to appear.
Often referred to as break-back fever

++

Why?

Local copy of the video

Antibiotic resistance: MRSA Infections

Methicillin-resistant Staphylococcus aureus.
Resistant to broad range of antibiotics.
Harmless unless enters body through cut or wound.
Deadly to those with weakened immune systems.
Hospitals, assisted living facilities.
Teams, locker rooms.
2M people/year infected in hospitals. ~100,000 deaths.

Kellen Winslow, Oct 21, 2008

MRSA Infections RPI News: August 16, 2010

Develop antimicrobial coatings for hospital surfaces
Carbon nanotube-enzyme conjugates made with
Lysostaphin, a cell wall degrading enzyme
Lysostaphin from non-pathogenic strains of Staph bacteria
had >99% MRSA killed within 2 hours.

R Pangule et al. JS Dordick

2010 ACS Nano 4, 3993-4000.

Antibiotics: An Uphill Battle

www.CEN-ONLINE.org April 14, 2008

Short period of effectiveness.

Emerging drug-resistant pathogens.
Cost of R&D without promise of profit margin.
Mother nature more clever than humans!
Focus on natural products- novel compounds

The Need for New Ideas

Focus on Under Developed Nations
Focus on Tuberculosis- second most lethal infectious disease
Bill and Melinda Gates Foundation October 21, 2008

X PRIZE to fight tuberculosis worldwide-effective diagnosis