Download Emerging diseases and Global Health Risks

Communicable Diseases,
Nosocomial Diseases,
Emerging and Re-Emerging
Diseases
Biology 447 - Environmental Microbiology
Introduction
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In 2001, a review of the scientific literature identified 1415
species of infectious organisms known to be pathogenic to
humans, including:
–
–
–
–
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217 viruses and prions,
538 bacteria and rickettsiae,
307 fungi,
66 protozoa and
287 helminths.
Of these, 61% were zoonotic and 12% were associated with
diseases considered to be emerging
(Taylor, Latham & Woolhouse, 2001).
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Communicable Diseases: Definition
•
Defined as
• “any condition which is transmitted directly or indirectly to a person from an
infected person or animal through the agency of an intermediate animal, host, or
vector, or through the inanimate environment”.
•
Transmission is facilitated by the following:
– more frequent human contact due to
• Increase in the volume and means of transportation (affordable international air
travel),
• globalization (increased trade and contact)
– Microbial adaptation and change
– Breakdown of public health capacity at various levels
– Change in human demographics and behavior
– Economic development and land use patterns
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CD- Modes of transmission
•
Direct
•
•
•
•
•
Blood-borne or sexual – HIV, Hepatitis B,C
Inhalation – Tuberculosis, influenza, anthrax
Food-borne – E.coli, Salmonella,
Contaminated water- Cholera, rotavirus, Hepatitis A
Indirect
• Vector-borne- malaria, onchocerciasis, trypanosomiasis
• Formites
•
Zoonotic diseases – animal handling and feeding practices (Mad cow
disease, Avian Influenza)
•
Nosocomial Infections- physician or health care worker induced
diseases
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Importance of Communicable Diseases
Significant burden of disease especially in low and middle income
countries
– Social impact
– Economic impact
– Potential for rapid spread
– Human security concerns
– Intentional use
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Communicable Diseases account for a significant
global disease burden
• In 2005, CDs accounted for about 30% of the global Burden of
Disease and 60% of the BoD in Africa.
• CDs typically affect LIC and MICs disproportionately.
• Account for 40% of the disease burden in low and middle
income countries
• Most communicable diseases are preventable or treatable.
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Communicable Disease Burden Varies Widely Among Continents
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Communicable Disease Burden Varies Widely Among Continents
67%
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Communicable disease burden in Europe
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Communicable disease burden in Europe
3%
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Nosocomial Infections
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Nosocomial Infection
Any infection that is acquired from being in a hospital or other
healthcare institution (e.g., nursing home)
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• 44,000 - 98,000 preventable deaths occur in
U.S. hospitals every year
• 17-29 billion healthcare dollars “wasted”
because of medical errors
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Burden of Nosocomial Infection in U.S. Hospitals
• 1.7 - 2 million nosocomial infections/year
• Results in 80,000-100,000 deaths/year
– Medication errors cause ~7,000 deaths
• Cost: 5-6 billion dollars/year
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Emerging Drug Resistance in Bacteria
• MRSA = Methicillin-Resistant Staphylococcus aureus
• VRE
= Vancomycin-resistant enterococcus
• 3CRKP = Klebsiella pneumoniae resistant to 3rd generation
cepalosporins
• FQRPA = Pseudomonas aeruginosa resistant to fluoroquinolones
• Clostridium difficile (NAP1) resistant to fluoroquinolones
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Methicillin-Resistant Staphylococcus aureus (MRSA)
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Staphylococcus aureus is commonly carried on the skin or in the nose of
healthy people. Approximately 25% to 30% of the population is colonized (when
bacteria are present, but not causing an infection) in the nose.
•
It is one of the most common causes of skin infections but most of are minor
(such as pimples and boils) and can be treated without antibiotics. It also can
cause serious infections (such as surgical wound infections, bloodstream
infections, and pneumonia).
Who is susceptible to MRSA infection?
•
•
MRSA usually infects hospital patients who are elderly or very ill. You may be
at more risk if you have had frequent, long-term, or intensive use of antibiotics.
Intravenous drug users and persons with long-term illnesses or who are
immuno-suppressed are also at increased risk.
The infection can develop in an open wound such as a bedsore or when there
is a tube such as a urinary catheter that enters the body. MRSA rarely infects
healthy people.
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Methicillin-Resistant Staphylococcus aureus (MRSA)
•
Staphylococcus aureus is commonly carried on the skin or in the nose of
healthy people. Approximately 25% to 30% of the population is colonized (when
bacteria are present, but not causing an infection) in the nose.
•
It is one of the most common causes of skin infections but most of are minor
(such as pimples and boils) and can be treated without antibiotics. It also can
cause serious infections (such as surgical wound infections, bloodstream
infections, and pneumonia).
Who is susceptible to MRSA infection?
•
•
MRSA usually infects hospital patients who are elderly or very ill. You may be
at more risk if you have had frequent, long-term, or intensive use of antibiotics.
Intravenous drug users and persons with long-term illnesses or who are
immuno-suppressed are also at increased risk.
The infection can develop in an open wound such as a bedsore or when there
is a tube such as a urinary catheter that enters the body. MRSA rarely infects
healthy people.
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Note:
•
Staphylococcus aureus and MRSA can also cause illness in persons
outside of hospitals and healthcare facilities.
•
MRSA infections that are acquired by persons who have not been
recently (within the past year) hospitalized or had a medical procedure
(such as dialysis, surgery, catheters) are know as CommunityAcquired-MRSA infections (CA-MRSA
•
Data from a prospective study in 2003, suggests that 12% of clinical
MRSA infections are community-associated, but this varies by
geographic region and population.
•
CDC has investigated clusters of CA-MRSA skin infections among
athletes, military recruits, children, Pacific Islanders, Alaskan Natives,
Native Americans, men who have sex with men, and prisoners.
Factors that have been associated with the spread of MRSA skin
infections include: close skin-to-skin contact, openings in the skin
such as cuts or abrasions, contaminated items and surfaces, crowded
living conditions, and poor hygiene.
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Note:
•
Staphylococcus aureus and MRSA can also cause illness in persons
outside of hospitals and healthcare facilities.
•
MRSA infections that are acquired by persons who have not been
recently (within the past year) hospitalized or had a medical procedure
(such as dialysis, surgery, catheters) are know as CommunityAcquired-MRSA infections (CA-MRSA
•
Data from a prospective study in 2003, suggests that 12% of clinical
MRSA infections are community-associated, but this varies by
geographic region and population.
•
CDC has investigated clusters of CA-MRSA skin infections among
athletes, military recruits, children, Pacific Islanders, Alaskan Natives,
Native Americans, men who have sex with men, and prisoners.
Factors that have been associated with the spread of MRSA skin
infections include: close skin-to-skin contact, openings in the skin
such as cuts or abrasions, contaminated items and surfaces, crowded
living conditions, and poor hygiene.
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Vancomycin-resistant enterococci
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Enteroccocci are bacteria that are normally present in the human
intestines and in the female genital tract and are often found in the
environment. These bacteria can sometimes cause infections.
•
Vancomycin is an antibiotic that is often used to treat infections
caused by enterococci. In some instances, enterococci have become
resistant to this drug and thus are called vancomycin-resistant
enterococci (VRE). Most VRE infections occur in hospitals.
•
In the last decade enterococci have become recognized as leading
causes of nosocomial bacteremia, surgical wound infection, and
urinary tract infection
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Enterococci are readily recovered outdoors from vegetation and
surface water, probably because of contamination by animal
excrement or untreated sewage. In humans, typical concentrations of
enterococci in stool are up to 108 CFU per gram
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Vancomycin-resistant enterococci
•
Enteroccocci are bacteria that are normally present in the human
intestines and in the female genital tract and are often found in the
environment. These bacteria can sometimes cause infections.
•
Vancomycin is an antibiotic that is often used to treat infections
caused by enterococci. In some instances, enterococci have become
resistant to this drug and thus are called vancomycin-resistant
enterococci (VRE). Most VRE infections occur in hospitals.
•
In the last decade enterococci have become recognized as leading
causes of nosocomial bacteremia, surgical wound infection, and
urinary tract infection
•
Enterococci are readily recovered outdoors from vegetation and
surface water, probably because of contamination by animal
excrement or untreated sewage. In humans, typical concentrations of
enterococci in stool are up to 108 CFU per gram
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Vancomycin-resistant enterococci
•
Enteroccocci are bacteria that are normally present in the human
intestines and in the female genital tract and are often found in the
environment. These bacteria can sometimes cause infections.
•
Vancomycin is an antibiotic that is often used to treat infections
caused by enterococci. In some instances, enterococci have become
resistant to this drug and thus are called vancomycin-resistant
enterococci (VRE). Most VRE infections occur in hospitals.
•
In the last decade enterococci have become recognized as leading
causes of nosocomial bacteremia, surgical wound infection, and
urinary tract infection
•
Enterococci are readily recovered outdoors from vegetation and
surface water, probably because of contamination by animal
excrement or untreated sewage. In humans, typical concentrations of
enterococci in stool are up to 108 CFU per gram
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• Among several phenotypes for vancomycin-resistant
enterococci, VanA (resistance to vancomycin and teicoplanin)
and VanB (resistance to vancomycin alone) are most common.
• In the United States, VanA and VanB account for approximately
60% and 40% of vancomycin-resistant enterococci (VRE)
isolates, respectively.
• Enterococci are intrinsically resistant to many antibiotics.
Unlike acquired resistance and virulence traits, which are
usually transposon or plasmid encoded, intrinsic resistance is
based in chromosomal genes, which typically are
nontransferrable
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CDC’s National Nosocomial Infection Surveillance (NNIS) System, 1989 - 2004
MRSA
VRE
3CRKP
FQRPA
Proportion of Resistant Isolates (%)
70
MRSA = methicillin-resistant Staphylococcus aureus
60
50
FQRPA = Pseudomonas aeruginosa resistant to fluoroquinolones
40
30
VRE = vancomycin-resistant enterococcus
20
10
3CRKP = Klebsiella pneumoniae resistant to 3rd generation
cephalosporins
0
89
90
91
92
93
94
95
96
97
98
99
00
01
02
03
04
Year
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3CRKP and FQRPA
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Clostridium difficile (NAP1)
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Potential Bioterrorism Agents
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Complete List of Potential Bioterrorism Agents from the
Center for Disease Control, Atlanta, Georgia, USA
From: http://emergency.cdc.gov/agent/agentlist.asp
•Anthrax (Bacillus anthracis)
•Arenaviruses
•Bacillus anthracis (anthrax)
•Botulism (Clostridium botulinum toxin)
•Brucella species (brucellosis)
•Brucellosis (Brucella species)
•Burkholderia mallei (glanders)
•Burkholderia pseudomallei (melioidosis)
•Chlamydia psittaci (psittacosis)
•Cholera (Vibrio cholerae)
•Clostridium botulinum toxin (botulism)
•Clostridium perfringens (Epsilon toxin)
•Coxiella burnetii (Q fever)
•Ebola virus hemorrhagic fever
•E. coli O157:H7 (Escherichia coli)
•Emerging infectious diseases such as Nipah virus and
hantavirus
•Epsilon toxin of Clostridium perfringens
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Complete List of Potential Bioterrorism Agents from the CDC
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Escherichia coli O157:H7 (E. coli)
Food safety threats (e.g., Salmonella species, Escherichia
coli O157:H7, Shigella)
Francisella tularensis (tularemia)
Glanders (Burkholderia mallei)
Lassa fever
Marburg virus hemorrhagic fever
Melioidosis (Burkholderia pseudomallei)
Plague (Yersinia pestis)
Psittacosis (Chlamydia psittaci)
Q fever (Coxiella burnetii)
Ricin toxin from Ricinus communis (castor beans)
Rickettsia prowazekii (typhus fever)
Salmonella species (salmonellosis)
Salmonella Typhi (typhoid fever)
Salmonellosis (Salmonella species)
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Complete List of Potential Bioterrorism Agents from the CDC
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Shigella (shigellosis)
Shigellosis (Shigella)
Smallpox (variola major)
Staphylococcal enterotoxin B
Tularemia (Francisella tularensis)
Typhoid fever (Salmonella Typhi)
Typhus fever (Rickettsia prowazekii)
Variola major (smallpox)
Vibrio cholerae (cholera)
Viral encephalitis (alphaviruses [e.g., Venezuelan equine
encephalitis, eastern equine encephalitis, western equine
encephalitis])
Viral hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg]
and arenaviruses [e.g., Lassa, Machupo])
Water safety threats (e.g., Vibrio cholerae, Cryptosporidium
parvum)
Yersinia pestis (plague)
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Complete list of potential bioterrorism agents (CDC)
•
Anthrax (Bacillus anthracis)

Arenavirues

Bacillus anthracis (anthrax)

Botulism (Clostridium botulinum toxin)

Brucella species (brucellosis)

–
Plague (Yersinia pestis)
–
Psittacosis (Chlamydia psittaci)
–
Q fever (Coxiella burnetii)
–
Ricin toxin from Ricinus communis (castor
beans)
Brucellosis (Brucella species)
–
Rickettsia prowazekii (typhus fever)

Burkholderia mallei (glanders)
–
Salmonella species (salmonellosis)

Burkholderia pseudomallei (melioidosis)
–
Salmonella Typhi (typhoid fever)

Chlamydia psittaci (psittacosis)
–
Salmonellosis (Salmonella species)

Cholera (Vibrio cholerae)
–
Shigella (shigellosis)

Clostridium botulinum toxin (botulism)
–
Shigellosis (Shigella)

Clostridium perfringens (Epsilon toxin)
–
Smallpox (variola major)

Coxiella burnetii (Q fever)
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Staphylococcal enterotoxin

Ebola virus hemorrhagic fever
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Tularemia (Francisella tularensis)

E. coli O157:H7 (Escherichia coli)
–
Typhoid fever (Salmonella Typhi)
Emerging infectious diseases such as Nipah virus and
hantavirus
–
Typhus fever (Rickettsia prowazekii)
–
Variola major (smallpox)
–
Vibrio cholerae (cholera)
–
Viral encephalitis (alphaviruses [e.g.,
Venezuelan equine encephalitis, eastern
equine encephalitis, western equine
encephalitis])
–
Viral hemorrhagic fevers (filoviruses [e.g.,
Ebola, Marburg] and arenaviruses [e.g.,
Lassa, Machupo])
–
Water safety threats (e.g., Vibrio cholerae,
Cryptosporidium parvum)
–
Yersinia pestis (plague)


Epsilon toxin of Clostridium perfringens

Escherichia coli O157:H7 (E. coli)

Food safety threats (e.g., Salmonella
species,scherichia coli O157:H7, Shigella)

Francisella tularensis (tularemia)

Glanders (Burkholderia mallei)

Lassa fever
•
Marburg virus hemorrhagic fever
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Melioidosis (Burkholderia pseudomallei)
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Neglected Diseases
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Neglected diseases
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Cause over 500,000 deaths and 57 million DALYs annually.
•
Include the following
– Helminthic infections
• Hookworm (Ascaris, trichuris), lymphatic filariasis, onchocerciasis,
schistosomiasis, dracunculiasis
– Protozoan infections
• Leishmaniasis, African trypanosomiasis, Chagas disease
– Bacterial infections
• Leprosy, trachoma, buruli ulcer
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Mapping Emerging Diseases
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Emerging diseases on rise
Date: 21/02/2008
•
An international research team has provided the first scientific
evidence that deadly emerging diseases have risen steeply across the
world, and has mapped the outbreaks' main sources.
•
They say new diseases originating from wild animals in poor nations
are the greatest threat to humans.
•
Expansion of humans into shrinking pockets of biodiversity and
resulting contacts with wildlife are the reason, they say. Meanwhile,
richer nations are nursing other outbreaks, including multidrugresistant pathogen strains, through overuse of antibiotics, centralised
food processing and other technologies.
•
The study appears in the Feb. 21 2008 issue of the leading scientific
journal Nature. Emerging diseases-defined as newly identified
pathogens, or old ones moving to new regions--have caused
devastating outbreaks already.
•
The HIV/AIDS pandemic, thought to have started from human contact
with chimps, has led to over 65 million infections; recent outbreaks of
SARS originating in Chinese bats have cost up to $100 billion.
Outbreaks like the exotic African Ebola virus have been small, but
deadly.
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Emerging diseases on rise
Date: 21/02/2008
•
An international research team has provided the first scientific
evidence that deadly emerging diseases have risen steeply across the
world, and has mapped the outbreaks' main sources.
•
They say new diseases originating from wild animals in poor nations
are the greatest threat to humans.
•
Expansion of humans into shrinking pockets of biodiversity and
resulting contacts with wildlife are the reason, they say. Meanwhile,
richer nations are nursing other outbreaks, including multidrugresistant pathogen strains, through overuse of antibiotics, centralised
food processing and other technologies.
•
The study appears in the Feb. 21 2008 issue of the leading scientific
journal Nature. Emerging diseases (defined as newly identified
pathogens, or old ones moving to new regions) have caused
devastating outbreaks already.
•
The HIV/AIDS pandemic, thought to have started from human contact
with chimps, has led to over 65 million infections; recent outbreaks of
SARS originating in Chinese bats have cost up to $100 billion.
Outbreaks like the exotic African Ebola virus have been small, but
deadly.
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•
Despite three decades of research, previous attempts to explain these
seemingly random emergences were unsuccessful.
•
In the new study, researchers from four institutions analysed 335
emerging diseases from 1940 to 2004, then converted the results into
maps correlated with human population density, population changes,
latitude, rainfall and wildlife biodiversity.
•
They showed that disease emergences have roughly quadrupled over
the past 50 years. Some 60% of the diseases travelled from animals to
humans (such diseases are called zoonoses) and the majority of those
came from wild creatures.
•
With data corrected for lesser surveillance done in poorer countries,
"hot spots" jump out in areas spanning sub-Saharan Africa, India and
China; smaller spots appear in Europe, and North and South America.
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•
Despite three decades of research, previous attempts to explain these
seemingly random emergences were unsuccessful.
•
In the new study, researchers from four institutions analysed 335
emerging diseases from 1940 to 2004, then converted the results into
maps correlated with human population density, population changes,
latitude, rainfall and wildlife biodiversity.
•
They showed that disease emergences have roughly quadrupled over
the past 50 years. Some 60% of the diseases travelled from animals to
humans (such diseases are called zoonoses) and the majority of those
came from wild creatures.
•
With data corrected for lesser surveillance done in poorer countries,
"hot spots" jump out in areas spanning sub-Saharan Africa, India and
China; smaller spots appear in Europe, and North and South America.
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Emerging diseases on rise -
Date: 21/02/2008
•
"We are crowding wildlife into ever-smaller areas, and human
population is increasing. The meeting of these two things is a recipe
for something crossing over." - Marc Levy, a global-change expert at
the Center for International Earth Science Information Network
(CIESIN)
•
The main sources are mammals.
•
Some pathogens may be picked up by hunting or accidental contact;
others, such as Malaysia's Nipah virus, go from wildlife to livestock,
then to people.
•
Humans have evolved no resistance to zoonoses, so the diseases
can be extraordinarily lethal. The scientists say that the more wild
species in an area, the more pathogen varieties they may harbour.
•
About 20 percent of known emergences are multidrug-resistant
strains of previously known pathogens, including tuberculosis.
•
Increasing use and reliance on modern antibiotics has helped breed
such dangerous strains
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Emerging diseases on rise -
Date: 21/02/2008
•
"We are crowding wildlife into ever-smaller areas, and human
population is increasing. The meeting of these two things is a recipe
for something crossing over." - Marc Levy, a global-change expert at
the Center for International Earth Science Information Network
(CIESIN)
•
The main sources are mammals.
•
Some pathogens may be picked up by hunting or accidental contact;
others, such as Malaysia's Nipah virus, go from wildlife to livestock,
then to people.
•
Humans have evolved no resistance to zoonoses, so the diseases
can be extraordinarily lethal. The scientists say that the more wild
species in an area, the more pathogen varieties they may harbour.
•
About 20 percent of known emergences are multidrug-resistant
strains of previously known pathogens, including tuberculosis.
•
Increasing use and reliance on modern antibiotics has helped breed
such dangerous strains
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Emerging diseases on rise
Date: 21/02/2008
•
More diseases emerged in the 1980s than any other decade-likely due
to the HIV/AIDS pandemic, which led to other new diseases in
immune-compromised victims.
•
In the 1990s, insect-transmitted diseases saw a peak, possibly in
reaction to rapid climate changes that started taking hold then.
•
"The world's public-health resources are misallocated. Most are
focused on richer countries that can afford surveillance, but most of
the hotspots are in developing countries. If you look at the highimpact diseases of the future, we're missing the point."
•
"We need to start finding pathogens before they emerge," said
Daszak.
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Emerging diseases on rise
Date: 21/02/2008
•
More diseases emerged in the 1980s than any other decade-likely due
to the HIV/AIDS pandemic, which led to other new diseases in
immune-compromised victims.
•
In the 1990s, insect-transmitted diseases saw a peak, possibly in
reaction to rapid climate changes that started taking hold then.
•
"The world's public-health resources are misallocated. Most are
focused on richer countries that can afford surveillance, but most of
the hotspots are in developing countries. If you look at the highimpact diseases of the future, we're missing the point."
•
"We need to start finding pathogens before they emerge," said
Daszak.
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Nature 451, 990-993 (21 February 2008)
Global trends in emerging infectious diseases
Kate E. Jones, Nikkita G. Patel, Marc A. Levy, Adam Storeygard, Deborah Balk,
John L. Gittleman & Peter Daszak2
Institute of Zoology, Zoological Society of London, Regents Park, London NW1
4RY, UK
Consortium for Conservation Medicine, Wildlife Trust, 460 West 34th Street, 17th
Floor, New York, New York 10001, USA
Center for International Earth Science Information Network, Earth Institute,
Columbia University, 61 Route 9W, Palisades, New York 10964, USA
Odum School of Ecology, University of Georgia, Athens, Georgia 30602, USA
Present addresses: Department of Economics, Brown University, Providence,
Rhode Island 02912, USA (A.S.); School of Public Affairs, Baruch College, City
University of New York, 1 Bernard Baruch Way, Box D-0901, New York, New
York 10010, USA (D.B.).
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Nature 451, 990-993 (21 February 2008)
Summary:
1.
2.
3.
4.
5.
6.
Emerging infectious diseases (EIDs) are a significant burden on global economies and
public health.
Their emergence is thought to be driven largely by socio-economic, environmental and
ecological factors, but no comparative study has explicitly analysed these linkages to
understand global temporal and spatial patterns of EIDs.
Here we analyse a database of 335 EID 'events' (origins of EIDs) between 1940 and 2004,
and demonstrate non-random global patterns. EID events have risen significantly over time
after controlling for reporting bias, with their peak incidence (in the 1980s) concomitant
with the HIV pandemic. EID events are dominated by zoonoses (60.3% of EIDs): the
majority of these (71.8%) originate in wildlife (for example, severe acute respiratory virus,
Ebola virus), and are increasing significantly over time.
We find that 54.3% of EID events are caused by bacteria or rickettsia, reflecting a large
number of drug-resistant microbes in our database.
Our results confirm that EID origins are significantly correlated with socio-economic,
environmental and ecological factors, and provide a basis for identifying regions where
new EIDs are most likely to originate (emerging disease 'hotspots').
They also reveal a substantial risk of wildlife zoonotic and vector-borne EIDs originating at
lower latitudes where reporting effort is low. We conclude that global resources to counter
disease emergence are poorly allocated, with the majority of the scientific and surveillance
effort focused on countries from where the next important EID is least likely to originate.
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Global distribution of relative risk of an EID event
A
B
C
D
Caption: Global distribution of relative risk of an EID event. Maps are derived for EID events caused by a, zoonotic pathogens
from wildlife, b, zoonotic pathogens from nonwildlife, c, drug-resistant pathogens and d, vector-borne pathogens. The relative
risk is calculated from regression coefficients and variable values in Table 1 (omitting the variable measuring reporting effort),
categorized by standard deviations from the mean and mapped on a linear scale from green (lower values) to red (higher
values).
Credit: Jones et. al., Nature
10/24/2008
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Geographic Origins of EID events from 1940 to 2004
Caption:
Global
richness
map
the
geographicorigins
origins of
2004.
The
map
is is
derived
for for EID
Caption:
Global
richness
map
of of
the
geographic
of EID
EID events
eventsfrom
from1940
1940toto
2004.
The
map
derived
EID events caused by all pathogen types. Circles represent one degree grid cells, and the area of the circle is
events caused by all pathogen types. Circles represent one degree grid cells, and the area of the circle is proportional
proportional
to events
the number
ofcell.
events
in the Jones
cell. Credit:
to the
number of
in the
Credit:
et. al.,Jones
Natureet. al., Nature
10/24/2008
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Emerging Diseases in the
United States
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Emerging and re-emerging Diseases in the USA
Chlamydia
Diphtheria *
Encephalitis
West Nile
St. Louis
E. coli
N gonorrhea
H. Influenzae
Hantavirus
Hepatitis A-G (A and B*)
Human herpes viruses
HHV 1-8
HIV/AIDS
Human papilloma viruses *
Influenza * Emerging strains
Legionella pneumophila
Lyme Disease *
Measles *
Meningococcus
MRSA
Pertussis *
Poliomyelitis *
Rabies
Rocky Mountain Spotted Fever
Rubella *
SARS (Severe Acute Respiratory Syndrome)
Salmonellosis
Shigellosis
S. pneumoniae
Syphilis
Tetanus *
Toxic-Shock Syndrome
Tuberculosis *
* Vaccination possible
10/24/2008
58
Emerging / Re-emerging – Diseases - Continued
•
•
•
•
•
HIV/AIDS/Opportunistic infections
Hepatitis A-G, Other ?
Herpes, Flu, Other viral diseases
Candiaiasis, Other fungal diseases
Bacterial/Drug resistant bacterial:
– E. coli 015.7:H7
– Other food/H2O-borne
– S. pneumonia, MRSA, VRSA
– Vancomycin resistant Enterococcus (VRE)
– Multiple-drug resistant TB (MDRTB)
– Bio-engineered agents
Malaria – drug-resistant
10/24/2008
59
Why are these mainly “older” diseases “re-emerging”
in the USA ?
• Change in vaccination patterns and percentage coverage of
population
• Lack of herd immunity
• New strains of organisms
• Faster transmission
• Hygiene and general health?
• Overuse of antibiotics (in humans and animals)
• Immuno-compromised individuals (AIDS, cancer treatment
patients, children, etc)
• Breakdown in public health or control
• Human demographics, behaviour
• Ecological changes
10/24/2008
60
Why are these mainly “older” diseases “re-emerging”
in the USA ?
• Change in vaccination patterns and percentage coverage of
population
• Lack of herd immunity
• New strains of organisms
• Faster transmission
• Hygiene and general health?
• Overuse of antibiotics (in humans and animals)
• Immuno-compromised individuals (AIDS, cancer treatment
patients, children, etc)
• Breakdown in public health or control
• Human demographics, behaviour
• Ecological changes
10/24/2008
61
Why are these mainly “older” diseases “re-emerging”
in the USA ?
• Change in vaccination patterns and percentage coverage of
population
• Lack of herd immunity
• New strains of organisms
• Faster transmission
• Hygiene and general health?
• Overuse of antibiotics (in humans and animals)
• Immuno-compromised individuals (AIDS, cancer treatment
patients, children, etc)
• Breakdown in public health or control
• Human demographics, behaviour
• Ecological changes
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62
Diseases in the USA
preventable by vaccination
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63
Vaccine Preventable Diseases
•
•
•
•
•
•
•
•
•
•
•
•
•
Adults
Mumps*
Pneumococcus**
Polio
Rubella*
Tetanus**
Varicella*
Diphtheria**
Hepatitis A
Hepatitis B
Influenza**
Lyme Disease
Measles*
Haemophilis influenza type B (Hib)
www.cdc.gov, 2/4/2002
10/24/2008
64
Vaccine Preventable Diseases - Adults - Continued
•
•
•
•
•
•
•
•
•
•
•
•
•
10/24/2008
Diphtheria**
Hepatitis A
Hepatitis B
Influenza**
Lyme Disease
Measles*
Haemophilis influenza type B (Hib)
Mumps*
Pneumococcus**
Polio
Rubella*
Tetanus**
Varicella*
65
Vaccine Preventable Diseases of children
•
•
•
•
•
•
10/24/2008
Diphtheria
Hepatitis A
Hepatitis B
Pertussis
Measles*
Haemophilis influenza type B (Hib)
66
Vaccines for Potential Bioterrorism Agents
• Anthrax
– Cell-free culture of an avirulent, non-encapsulated,
derivative of a bovine isolate-V770
• 2-dose efficacy in monkeys
• Estimated > 90% effective against cutaneous anthrax
• Botulism
– Pentavalent toxoid (A-E)
• 3 doses 100% effacicious in primates
• Tuleraemia
– Live attenuated vaccine - 80% protection
• Plague
– Suspension of killed Yersinia pestis - Questionable immunity
• Smallpox
– Vaccinia vaccine; Effective in one dose; Side effects
• Viral Hemorrhagic Fevers
– No vaccine available
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67
Increasing Antibiotic Resistance
10/24/2008
68
Global Emerging and Re-emerging Diseases
10/24/2008
69
Enlarged View on next 2
pages
10/24/2008
70
10/24/2008
71
Continued:
From: WHO – Emerging Issues in Water and Infectious disease
ISBN 92 4 159082 3 (LC/NLM classification: QW 80) ISSN 1728-2160
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72
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73
Global Diseases
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74
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75
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76
HIV/AIDS
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77
Emerging viral diseases
AIDS
• First reported 6/5/81 by CDC
Epidemiologic Notes and Reports
• Pneumocystis Pneumonia --- Los Angeles
• In the period October 1980-May 1981, 5 young men,
all active homosexuals, were treated for biopsy-confirmed
Pneumocystis carinii pneumonia at 3 different hospitals in Los
Angeles, California. Two of the patients died. All 5 patients had
laboratory-confirmed previous or current cytomegalovirus
(CMV) infection and candidal mucosal infection.
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78
1982: Term AIDS replaces GRID
1983: Universal precautions introduced
MMWR 1983;32:101
 The virus that causes AIDS identified
Gallo- HTLV III; Montagnier-LAV
Name changed to human immunodeficiency virus (HIV)
1985: First serologic test for HIV licensed by FDA
 Rock Hudson died of AIDS on 10/2/85
1986: AZT approved by FDA
Record approval time of 6 months
10/24/2008
79
HIV
•
•
•
•
•
•
Very dynamic virus
109 viral particles/day
Loss of 108-109 CD4 cells/day
Replicate every two days
680,000 viral particles produced and cleared daily
95% of virus produced from newly infected cells
CD4 - A glycoprotein on the surface of helper T cells that serves
as a receptor for HIV. CD4 A type of protein molecule in human
blood that is present on the surface of 65% of human T cells.
CD4 is a receptor for the HIV virus. When the HIV virus infects
cells with CD4 surface proteins, it depletes the number of T
cells, B cells, natural killer cells, and monocytes in the patient's
blood. Most of the damage to an AIDS patient's immune system
is done by the virus' destruction of CD4+ lymphocytes. CD4 is
sometimes called the T4 antigen.
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80
1989: U.S. AIDS cases reported at 100,000
1991: Estimated HIV infected in USA 1.5 million
 Magic Johnson announces he is HIV positive
1993: Multiple drugs fail in clinical trials
 Period of extreme pessimism for HIV infected
1995: First protease inhibitor approved:
Inverase,saquinivir
 HIV kinetics reported at 10 billion virions/day
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81
1996:
• HIV viral load testing
– Becomes major method to assess ART
• Mellors J; Ann Intern Med 1997;126:946
• ACTG 076 shows benefit of AZT in reducing
perinatal transmission
• NEJM 1996;335:1621
• Initial reports of benefit of HAART (highly active antiretroviral
therapy )
– Ritonavir and indinavir approved
– Fisrt NNRTI, nevirapine approved
– First triple combination HAART study
• Eradication of HIV might be possible with HAART
– Dr. David Ho Time “Man of the Year”
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82
1997: 13% decrease in AIDS deaths
– 60-80% reduction in new AIDS-defining conditions,
hospitalizations and deaths
• Palella et al, NEJM 1998;338:853,
• Mocroft at al, Lancet 1998;352:1725
1999: HIV spread to humans from chimpanzees
– Occurred in Africa decades before recognition (maybe even
longer)
2000: AIDS pandemic raging in “Third World”
– 36.1 million people infected with HIV
– 21.8 million deaths
– 14,000-16,000 new infections/day
2001: Two distinct epidemics
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83
HIV Natural History
• Clinical Latent Period:
Asymptomatic - May have PGL; Viral set point at 6 month:
Equilibrium between immune system and HIV; Persists for
years; Gradual, relentless degradation of immune function
• Early Symptomatic HIV Infection:
CD4 < 500; Opportunistic Infection(s)
• AIDS: CD4 < 200; AIDS Defining Illness(s)
• Advanced HIV Infection: CD4 < 50; Serious
opportunistic Infection(s); Death
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84
How Is HIV Spread?
Routes of Transmission:
– Sexual
– Intravenous Drug Use
Inhalation drug abuse
– Exposure to blood/blood products
Occupational exposure
– Mother to child
Breast feeding
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85
Mother-to-Child Transmission
Global Situation
• Estimated 2.4 million HIV-positive women give
birth annually to 600,000 HIV-positive babies
– 1800 new infections each day
90% in sub-Saharan Africa
<1% (1000) in USA and Europe
• Transmission rates
USA/Europe: 13–30% without ART,
approaching 1–3% with ART
Developing countries: 20–43% without ART, lower rates with
ART, even with short-course therapy
• Breast feeding for 6 months
Additional 5–10% infections, with the highest rates of
transmission occurring in the first and second months postpartum
Wiktor SZ, et al. XIIIth IAC, Durban, 2000. Abstract 354
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86
HIV/AIDS
• In 2005, 38.6 million people worldwide were living with HIV, of
which 24.7 million (two-thirds) lived in SSA
– 4.1 million people worldwide became newly infected
– 2.8 million people lost their lives to AIDS
• New infections occur predominantly among the 15-24 age
group.
• Previously unknown about 25 years ago. Has affected over 60
million people so far.
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87
HIV Co-infections
•
Impact of TB on HIV
– TB considerably shortens the survival of people with HIV/AIDS.
– TB kills up to half of all AIDS patients worldwide.
– TB bacteria accelerate the progress of AIDS infection in the patient
•
HIV and Malaria
– Diseases of poverty
– HIV infected adults are at risk of developing severe malaria
– Acute malaria episodes temporarily increase HIV viral load
– Adults with low CD4 count more susceptible to treatment failure
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88
Global HIV Burden
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89
Adults and Children With HIV/AIDS, 12/31/02
Eastern Europe & Central \Asia
North America
Western Europe
980,000
570,000
Caribbean
440,000
1,200,000
North Africa &
Middle East
550,000
Latin America
Sub Saharan Africa
1,500,000
29,400,000
East Asia & Pacific
1,200,000
South & South-East Asia
6,000,000
Australia
& New
Zealand
15,000
People living with HIV/AIDS
..........................
42 million
New HIV infections in 2002
...........................
5 million
Deaths due to HIV/AIDS in 2002 ....................
10/24/2008
3.1 million
90
HIV/AIDS
• Interventions depend on
– Epidemiology – mode of transmission, age group
– Stage of epidemic –concentrated vs. generalized
• Elements of an effective intervention
• Strong political support and enabling environment.
• Linking prevention to care and access to care and treatment
• Integrate it into poverty reduction and address gender
inequality
• Effective monitoring and evaluation
• Strengthening the health system and Multisectoral approaches
• Challenges in prevention and scaling up treatment globally
include
•
•
•
•
10/24/2008
Constraints to access to care and treatment
Stigma and discrimination
Inadequate prevention measures.
Co-infections (TB, Malaria)
91
Malaria
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92
Malaria
•
Every year, 500 million people become severely ill with malaria
• causes 30% of Low birth weight in newborns globally.
•
>1 million people die of malaria every year. One child dies from it
every 30 seconds
•
40% of the world’s population is at risk of malaria. Most cases and
deaths occur in SSA.
•
Malaria is the 9th leading cause of death in LICs and MICs
• 11% of childhood deaths worldwide attributable to malaria
• SSA children account for 82% of malaria deaths worldwide
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93
Annual Reported Malaria Cases by Country (WHO 2003)
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94
Global malaria prevalence
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95
Malaria Control
•
Malaria control
– Early diagnosis and prompt treatment to cure patients and reduce
parasite reservoir
– Vector control:
• Indoor residual spraying
• Long lasting Insecticide treated bed nets
– Intermittent preventive treatment of pregnant women
•
Challenges in malaria control
– Widespread resistance to conventional anti-malaria drugs
– Malaria and HIV
– Health Systems Constraints
• Access to services
• Coverage of prevention interventions
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96
Hepatitis
10/24/2008
97
Hepatitis and Liver Disease
•
500-1000 therapeutic agents implicated in hepatitis
•
15-20 million Americans are alcoholics
•
Tenth leading cause of death in USA
•
–
25,000 deaths/year
–
1% of all deaths
40 % of chronic liver disease HCV-related
–
–
–
10/24/2008
8-10,000 deaths/year.
HCV associated end stage liver disease is the
most frequent indication for liver transplant
As HCV population ages incidence of chronic
liver disease could increase substantially
98
Hepatitis
•
Asymptomatic - anicteric
•
Mild symptomatic - anicteric
•
Classic icteric infection (pertaining to or affected with jaundice)
•
Fulminant hepatitis (sudden, flaring up type)
•
Chronic hepatitis
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99
Viral Hepatitis - Overview
Type of Hepatitis
A
Source of
virus
Route of
transmission
Chronic
infection
Prevention
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feces
fecal-oral
no
B
C
D
blood/ blood-derived/body fluids
Percutaneous/permucosal
yes
yes
E
feces
fecal-oral
yes
no
ensure safe
pre/postpre/postblood donor
pre/postexposure
exposure
screening;
exposure drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification
100
Viral Hepatitis
GENOME
HAV
VIRAL
CLASS
Picoravirus
RNA
Enteric
HBV
Hepadana
DNA
Parenteral
40-120 Days
5-10 %
HCV
Flavivirus
RNA
Parenteral
15-90 Days
> 85 %
HDV
Satellite
RNA
Parenteral
25-75 Days
2-70 %
HEV
Calci-Like
RNA
Enteric
20-80 Days
None
HGV
Flavivirus
RNA
Parenteral
Unknown
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SPREAD
INCUBATION
15-45 Days
CHRONICITY
None
Probable
101
Human Herpesviruses
• Alpha Herpesviruses:
– Herpes Simplex Virus Type 1 (HSV-1)
– Herpes Simplex Virus Type 2 (HSV-2)
– Varicella Zoster Virus (HZV)
• Beta Herpesviruses:
– Cytomegalovirus (CMV)
– Human Herpesvirus Type 6 (HHV-6)
– Human Herpesvirus Type 7 (HHV-7)
The Herpes Simplex
Virus type 1 (HSV1),
which is the cause of
cold sores, has an
icosahedral capsid
shown here at 13 Å
resolution.
• Gamma Herpesviruses:
– Epstein-barr Virus (EBV)
– Human Herpesvirus Type 8 (HHV-8)
• Kaposi’s Sarcoma Asso. Herpesvirus
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Viruses - Herpes; HSV-1 & 2
• HSV-1:
–
–
–
–
–
–
–
Oral/genital/mucocutaneous lesions;
Acute gingivostomatitis;
Pharyngitis;
Herpes labialis;
Keratoconjunctivitis;
Encephalitis;
Herpetic Whitlow;
• HSV-2:
–
–
–
–
10/24/2008
Oral/genital/mucocutaneous lesions;
At least 1:4 persons > 12 y.o. infected;
70-90% asymptomatic shedding;
Only about 20% of HSV-2 Ab+ know they are infected
103
Herpes Viruses
• EBV:
–
–
–
–
–
Epstein-Barr virus (EBV) occurs
world-wide and infects most people
at some point in their lives. Children
are largely immune to its effects, but
infection in older people can cause a
condition called infectious
mononucleosis.
Long-term infection is, in very rare
cases, linked to the development of
some forms of cancer.
Infects > 85% of population;
Agent of infectious mononucleosis
Cause of oral hairy leukoplakia;
Oncogenic: Burkitt’s Lymphoma;
Linked to Hodgkin’s Disease/ other malignancies
• CMV:
–
–
–
–
Problematic in immumocomp. pts; Retinitis, enteritis;
Linked to vasculopathies, CAD?
Role in organ transplant rejection;
Other graft/host involvement
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Varicella-Zoster (VZV)
• Chickenpox: Ubiquitous infection of childhood
– Primary infection results in the characteristic disseminated
cutaneous lesions.
– The virus then establishes lifelong latency in dorsal root
ganglia from whence it may reactivate to cause localized
cutaneous eruptions known as herpes zoster or shingles.
• Herpes zoster usually occurs later in life as a consequence of
immunosuppressive illness or immunosuppressive medical
therapy.
• Declining VZV-specific immunity later in life is associated with
an increased risk of herpes zoster.
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Human Papillomavirus
• Most common viral STD
– Infects about 1/3 of sexually active
population in USA
– >60 strains have been identified
– 25 strains associated with genital
tract infections/cancer
• Strongly associated with:
– Cervical cancer
• Causative agent
– Oral cancer
– Peri-anal/testicular cancer
– Especially severe in HIV infected
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Papilloma; Focal Epithelial Hyperplasia (FEH)
• Etiological agent:
– Human papilloma virus (HPV)
– “Wart”
• Clinical appearance:
– Flat (FEH)
– Siky
– Cauliflower-like
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Avian Influenza
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108
Avian Influenza
• Seasonal influenza causes severe illness in 3-5 million people
and 250000 – 500000 deaths yearly
• 1st H5N1 avian influenza case in Hong Kong in 1997.
• By October 2007 – 331 human cases, 202 deaths.
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109
Avian Influenza
•
Control depends on the phase of the epidemic
– Pre-Pandemic Phase
• Reduce opportunity for human infection
• Strengthen early warning system
– Emergence of Pandemic virus
• Contain and/or delay the spread at source
– Pandemic Declared
• Reduce mortality, morbidity and social disruption
• Conduct research to guide response measures
•
Antiviral medications – Oseltamivir, Amantadine
•
Vaccine – still experimental under development.
• Can only be produced in significant quantity after an outbreak
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Confirmed human cases Avian Influenza
10/24/2008
111
Migratory pathway for birds and Avian influenza
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112
The Spread of Avian Flu -- Status as of the Summer 2008
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113
West Nile Virus
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114
WNV
In USA
12/11/02
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115
• Spread by mosquitoes, which transmit it from infected birds.
Mosquito species does make some difference.
• -Alligators have WNV titers as high as birds, thus they can
serve as a reservoir too.
• -Certain titers need to be reached in order to infect mosquitoes.
Horses and humans do not have high titers.
• -300 captive alligators that died in 2002 in Florida, necropsies
showed the alligators had high viral loads of WNV.
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116
West Nile Virus
•
Clinical Presentation
Incubation period 3 - 14 days
– 20% develop “West Nile fever”
– 1 in 150 develop meningoencephalitis
– Advanced age primary risk factor for
severe neurological disease and death
•
Mild dengue-like illness of sudden onset
– Duration 3 - 6 days
– Fever, lymphadenopathy, headache,
abdominal pain, vomiting, rash, conjunctivitis,
eye pain, anorexia
– Symptoms of West Nile fever in contemporary
outbreaks not fully studied
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• Suspect WNV when:
–
–
–
–
Symptoms consistent with WNV
Unexplained bird or horse deaths
Mosquito season
Age > 50 years
• Symptoms:
– Most cases asymptomatic or mild dengue-like illness
• Incubation period usually 5 (3) to 15 days
–
–
–
–
Fever, lymphadenopathy, headache
Abdominal pain, vomiting, rash, conjunctivitis
Muscle weakness and /or flaccid paralysis, hyporeflexia
EMG/NCV showing axonal neuropathy
Lymphocytopenia
MRI:
• Shows enhancement of leptomeninges and/or periventricular area
– CNS involvement and death in minority of cases
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118
West Nile Virus Human Cases in the US
1999 -62 cases with 7 deaths in New York only
1999 -21 cases with 2 deaths in 12 states
2000 -66 cases with 9 deaths in 10 states
2001 -4156 cases with 284 deaths in 40 states
2002 -9862 cases with 264 deaths in 46 states
2004 -2539 cases with 100 deaths in 42 states
2005 -3000 cases with 119 deaths in 44 states
2006 -4269 cases with 177 deaths in 44 states
2007 -3630 cases with 124 deaths in 43 states
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119
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120
U.S. cases of West Nile for 2002
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121
U.S. cases of West Nile for 2004
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122
U.S. cases of West Nile for 2005
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123
U.S. cases of West Nile for 2007
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124
African Trypanosomiasis
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125
African Trypanosomiasis
•Called Sleeping Sickness, vector is the tsetse fly
•Classical example of an emerging infection, 1890-1930
•Leading public health problem in Africa during that
time, colonialism brought it to new areas
•Nearly eliminated by 1960 using population screening,
case treatment, chemoprophylaxis
•Re-emerging infection in central Africa
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126
African Trypanosomiasis, cont.
West African
Agent:
Vector:
Distribution:
Reservoir:
Disease:
Mortality:
At risk:
10/24/2008
T. brucei gambiense
riverine tsetse fly
west/central Africa
human
chronic (years)
100%
rural persons
East African
T. brucei rhodesiense
savanna tsetse fly
east/south Africa
antelope/cattle
rapid progression: 1-4 weeks
100%
rural, visitors to game reserves
127
10/24/2008
128
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129
Problems Estimating Disease Burden
• 60 million people at risk, but <2 million screened
• No health facilities in many areas at risk
• Conflict or insecurity in epidemic foci
• Outbreaks in 2004 reported in DRC, Angola
• Clinical diagnosis is difficult until late in disease
-intermittent fever
-lymph node swelling
-headaches and sleep disturbance
-weight lose (they look like AIDS)
-lab diagnosis is hard (antigenic variation)
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130
Prevalence of trypanosomiasis
• In 1986, WHO est. that 70 million people lived in
transmission areas.
•
• In 1998, 40,000 cases were reported, but it was
estimated that 300,000 to 500,000 cases were
undiagnosed.
• Villages in the Congo, Angola, and Sudan,
prevalence has reached 50%.
• By 2005, surveillance had been reinforced and new
cases dropped.
• 1998-2004 cases fell from 40,000 to 18,000.
• The estimated cases is currently between 50,000 and
70,000.
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131
Management of Trypanosomias
Disease management in three steps:
1) Screening for potential infection. Serological tests
and/or checking for swollen cervical glands.
2) Diagnosis shows whether the parasite is present.
3) Staging to determine the disease progression.
Examination of cerebro-spinal fluid by lumbar puncture
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Treatments for Trypanosomias
First stage treatments:
Pentamidine: discovered in 1941, used against T.b. gambiense.
Despite a few undesirable effects, it is well tolerated by
patients.
Suramin: discovered in 1921, used against T.b. rhodesiense.
Effects in the urinary tract and allergic reactions.
Second stage treatments:
Melarsoprol: discovered in 1949, used against both forms.
Arsenic derivative with many side effects. Fatal encephalopathy
(3% to 10%). 1997 resistance up to 30%.
Eflornithine: was registered in 1990. Only effective against T.b.
gambiense. Less toxic alternative to melarsoprol, but the
regimen is strict and difficult to apply.
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133
SARS
(Severe Acute Respiratory Syndrome)
10/24/2008
134
10/24/2008
135
Severe Acute Respiratory Syndrome (SARS)
The Initial Epidemic
• Outbreak of atypical pneumonia in Hong Kong in March 2003
– Between 03/11/03 and 03/25/03 156 patients
were hospitalized with SARS
– 138 were identified as secondary or tertiary
cases as a result of exposure to index case(s)
• 112 secondary cases
• 26 tertiary cases
– Includes 69 HCWs
• 20 MDs
• 34 Nurses
• 15 Allied HCWs
– 54 patients on ward or visitors
• 16 medical students
• 32 of the 138 patients (23.2%) had severe respiratory failure
– 5 patients died (3.6%)
• All had been hospitalized with a major medical condition
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136
Severe Acute Respiratory Syndrome (SARS)
The Clinical Presentation- Initial 138 Cases
• Incubation period was 2-10 days from initial
exposure to onset of fever
– Median incubation period was 6 days
• The most common clinical symptoms were:
– Fever (100%) > 100.50
– Chills, rigors or both (73.2%)
– Myalgia (60.9%)
– Cough (57.3%)
– Headache (55.8%)
– Dizziness (42.8%)
• Less common symptoms included:
– Sore throat, sputum production, coryza (cold symptoms),
nausea, vomiting, and diarrhea
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137
Routes of Transmission:
• The principal way SARS appears to be spread is through
droplet transmission
– Namely, when a SARS patient coughs or sneezes droplets
into the air and someone else breathes them in.
• It is possible that SARS can be transmitted through the air or
from objects that have become contaminated.
• People at risk:
– Direct close contact with an infected person
– Sharing a household with a SARS patient
– HCWs who did not use infection control
procedures while caring for a SARS patient.
• In the United States, there is no indication
of community transmission at this time.
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138
Spread of SARS
From New York Times
10/24/2008
139
10/24/2008
140
Severe Acute Respiratory Syndrome (SARS)
Cause of SARS
• Scientists at CDC and other laboratories have detected a
previously unrecognized coronavirus in patients with SARS.1-4
– Confirmed as causative agent by WHO on 04/16/03
– Virus a member of the coronavirus family, never before
seen in humans
1. http://www.cdc.gov/ncidod/sars/casedefinition.htm
2. Peiris J et al, Lancet 2003 http://image.thelancet.com/extras/03art3477web.pdf
3. Drosten C et al. NEJM 2003 www.nejm.org
4. Ksiazek T et al. NEJM 2003 www.nejm.org
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141
•
http://en.wikipedia.org/wiki/SARS
SARS is a novel coronavirus.
An art model of CoV, modified from Dr. Kathryn. V. Holmes [N Engl J Med. 2003; 348(20):1948-51]
by Prof. Yi Xue LI and Ye CHEN of Bioinformation Center, Shanghai Institutes for Biological
Sciences, CAS.
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142
Hantavirus
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Hantavirus Pulmonary Syndrome (HPS)
• An outbreak of unexplained illness occurred in May 1993 an
area of the Southwest shared by NM, AZ, CO, and UT (Four
Corners).
– A number of previously healthy young adults suddenly
developed acute respiratory symptoms; about half soon
died.
– A hantavirus, which is transmitted by rodents, was
suspected.
– The virus named Sin Nombre virus (SNV) and its principal
carrier, the deer mouse were positively identified.
• A "bumper crop" of rodents there, due to heavy rains during
the spring of 1993.
• Determined that person to person transmission of SNV was
unlikely.
• SNV had actually been present, but unrecognized, at least as
early as 1959.
• Since the discovery in 1993, hantavirus pulmonary syndrome
(HPS) has been identified in over half of the states of the U.S.
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Influenza
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Influenza
Influenza virus particle
Image from:
www.drugdevelopment-technology.com
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Influenza
•
Acute, febrile illness, usually self limited
– Headache, malaise, myalgias
– Fever - 104oF-106oF (days 1-3)
– URI symptoms
•
• Nasal discharge, sore throat, cough (days 2-7)
• Cervical adenopathy (children > adults) and rhonchi
Attack rate: 10 - 40%
– Viral shedding:
One day before - until 10 days after symptom onset
Peak day 3-4
Shedding is prolonged in young children
 Transmission:
Person to person via small particle aerosols
Virus is relatively stable and favors low humidity
and cool temperatures
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Influenza virus
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Cold virus
149
• Influenza (flu) is a serious disease
– Flu is not a cold!
• It is far more dangerous than a bad cold
– The virus infects the lungs.
• It can lead to pneumonia/other sequellae.
• Every year in the USA approximately:
– 114,000 people are hospitalized
– 20,000 people die because of the flu.
• Most who die are over 65 years old. But small children less
than 2 years old are as likely as those over 65 to have to go to
the hospital because of the flu.
http://www.cdc.gov/nip/Flu/Public.htm#Facts
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Tuberculosis
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Tuberculosis (TB)
TB is not on the decline.
One third of the world's population is infected with TB
– In 1999 TB caused 8,000 deaths/day
– 7- 8 million people become infected with TB/year
– 5-10 % of these people will develop active TB
– Between 1993 and 1996, TB increased 13 %
– TB accounts for more than 1/4 of all preventable adult
deaths the developing world. Someone is newly infected
with TB every second !
–
–
–
–
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TB is the leading killer of women
TB outranks all causes of maternal mortality
TB creates more orphans than any other infectious disease
TB is the leading cause of death among HIV-positive
individuals
152
Global Prevalence of TB cases (WHO)
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Tuberculosis
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Tuberculosis Control
•
Challenges for tuberculosis control
–
–
–
–
•
MDR-TB - In most countries. About 450000 new cases annually.
XDR-TB cases confirmed in South Africa.
Weak health systems
TB and HIV
The Global Plan to Stop TB 2006-2015.
–
–
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an investment of US$ 56 billion, a three-fold increase from 2005. The estimated
funding gap is US$ 31 billion.
Six step strategy: Expanding treatment; Health Systems Strengthening; Engaging all
care providers; Empowering patients and communities; Addressing MDR TB,
Supporting research
156
Tuberculosis Transmission
• Caused by Mycobacterium tuberculosis
• Spread by:
- Airborne route
- Droplet nuclei
• Affected by:
– Infectiousness of patient
– Environmental conditions
– Duration of exposure
• Most persons exposed do not become infected
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First-Line Treatment
of Tuberculosis for DrugSensitive TB
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Pathogenesis - Latent M.tuberculosis Infection
• Inhaled droplet nuclei with M. tuberculosis :
- Reach alveoli
- Are taken up by alveolar macrophages
- Reach regional lymph nodes
- Enter bloodstream and disseminate
• Chest radiograph may have transient abnormalities
• Specific cell-mediated immune response controls further
spread
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Ebola Virus
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Nipah Virus
• 265 patients with viral encephalitis, 105 died (40% case fatality
rate)
• From bat reservoir:
– 1994 – Hendra virus
– 1997 – Australian Lyssavirus
– 1997 – Menangle virus
– 1999 – Nipah virus
– 2004 – SARS-like CoV
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Hendra Virus
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Summary
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•
Why do there seem to be more emerging and re-emerging
diseases in the past few decades?
• One reason is certainly better detection, monitoring and
surveillance systems….
• Another set of reasons may be the changes that have
happened in the recent past………….
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Why are there more emerging or re-emerging diseases?
1.
2.
1.
4.
5.
1.
7.
1.
2.
3.
4.
5.
6.
Human demographics and behavior
Technology and Industry
Economic development and land use
International travel and commerce
Microbial adaptation and change
Breakdown of public health measures
Human vulnerability
Climate and weather
Changing ecosystems
Poverty and social inequality
War and famine
Lack of political will
Intent to harm
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1. Human demographics and behavior
• More people, more crowding an aging population in many parts
of the world (high AIDS infections rates change that age
distribution)
• Changing sexual mores (HIV, STDs)
• Injection drug use (HIV, Hepatitis C)
• Changing eating habits: out more, more produce (food-borne
infections)
• More populations with weakened immune system: elderly,
HIV/AIDS, cancer patients and survivors, persons taking
antibiotics and other drugs
• More children in daycare (infection spread)
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2. Technology and Industry
•
Mass food production (Campylobacter, E.coli O157:H7, etc…)
•
Use of antibiotics in food animals (antibiotic-resistant bacteria)
•
More organ transplants and blood transfusions (Hepatitis C, WNV,…)
•
New drugs for humans (prolonging immuno-suppression)
•
People live longer but then have weakened immune systems
•
Water and food supply systems larger and more complex and prone to
“single site of failure”
•
Industrial pollution (TB)
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3. Economic development and land use
•
Changing ecology influencing waterborne, disease transmission (e.g.
dams, deforestation)
•
Contamination of watershed areas by cattle (Cryptosporidium)
•
More exposure to wild animals and vectors (Lyme disease,
erhlichiosis, babesiosis, HPS,…)
•
Logging in rain forest exposes workers to new vectors
•
New standing water from construction (mosquito and other vectors
increase)
•
Some developments (Aswan High dam in Egypt) lead to higher
infection rates (Schistosomiasis) – reforestation in the US has led to
increase in Lyme disease
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4. International travel and commerce
•
Persons infected with an exotic disease anywhere in the world can be
into major US city within hours (SARS)
•
400 million people a year travel internationally. Circumnavigation of
the world used to take 365 days, now 36 hours – quarantine of
travellers is not feasible.
•
Foods from other countries imported routinely into other countries
(Cyclospora,….)
•
Cruise ship travel (single source epidemics)
•
Transportation of food products very widespread and facilitates
spread of vectors and carriers. Vectors hitchhiking on imported
products (Asian tiger mosquitoes on lucky bamboos,….)
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6
Days to Circumnavigate (
the Globe
350
5
300
4
250
200
3
150
2
100
50
1
0
0
1850
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)
400
1900
Year
1950
World Population in billions (
)
Speed of Global Travel in Relation to World Population Growth
2000
170
5. Microbial adaptation and change
•
Increased antibiotic resistance with increased use of antibiotics in
humans and food animals (VRE, VRSA, penicillin- and macrolideresistant Strep pneumonia, multidrug-resistant Salmonella,….)
•
Many patients making antibiotics do NOT complete the full course of
treatment – leads to resistant microorganisms
•
In the US it is estimated that 30% of antibiotic prescriptions are for
diseases that are viral or willl not respond to anti-bacterial antibiotics
(Why do doctors still prescribe them?)
•
Increased virulence (Group A Strep?)
•
Jumping species from animals to humans (avian influenza, HIV?,
SARS?)
•
New (or previously unknown) organisms can be produced by contacts
between microorganisms
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From: Murphy and Nathanson. Semin. Virol. 5, 87, 1994
CDC
171
Emerging Vancomycin-resistant Enterococcal Infections*
% Resistant
Emerging Vancomycin-resistant Enterococcal Infections*
* in U.S. NNIS Hospitals
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CDC
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6. Breakdown of public health measures
• Lack of basic hygienic infrastructure (safe water, safe foods,
etc..)
• Inadequate vaccinations (measles, diphtheria)
• Discontinued mosquito control efforts (dengue, malaria)
• Lack of monitoring and reporting (SARS)
• Lack of basic medical facilities in many parts of the world (the
Ebola outbreak in Kitwit continued with high mortality for
weeks or months before anyone outside heard about it – many
victims were medical personnel)
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7. Human vulnerability
Increased vulnerability with malnutrition or water shortages
Decreased immunity with many other infections (eg AIDS)
Increased number of immuno-compromised and elderly patients
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8. Climate and Weather
• With increased global temperature (global warming or global
climate change) there will be increased rainfall that will:
» increase breeding grounds for mosquitoes
» increase vegetation and rodent numbers
» increase runoff into reservoirs (with contamination a
likely result)
• Higher ocean temperatures may stimulate growth of Vibrio spp.
• And many other possibilities……………………..
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9. Changing ecosystems
• Ecological or ecosystem changes can alter the pattern of distribution of
both pathogens and vectors (of the 10 emerging diseases targeted by the
WHO, 7 have arthropod vectors)---- Malaria in Canada?
• It can also alter human or animal distribution as populations migrate
• Destruction of rainforest can increase humidity
• Urban development can increase particulate matter and temperatures in
the area.
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10. Poverty and social inequality
• Mortality from infectious diseases is very closely linked with
income level
• Lower income levels correlate with:
•
•
•
•
•
Lack of clean water and sanitation
Poor housing
Lack of access to medical treatment
Lack of transportation
Exposure to higher pollutant levels (often, but not always in
rural environments)
• The lowest income group is increasing the fastest
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11. War and famine
• About 1% of the worlds population are war refugees
• They are exposed to new, often poor conditions and
microorganisms and disease vectors.
• Famine and war are often closely linked (of 16 food emergencies
in 2001, 9 were linked to civil unrest)
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12. Lack of political will
• A global political commitment is difficult to achieve – but the
Millenium Declaration of the countries of the UN is a start.
• Long-term commitments (10 to 20 years) required to solve
many of these problems are difficult for most governments with
a 3 to 5 year lifetime before elections.
• Also needs long-term commitment from donors, governments,
health care professionals and patients.
• Development of new treatments and antibiotics for the most
common developing world diseases (AIDS, malaria, etc) is not
as profitable as for developed world “diseases” such as heart
conditions, depression and cancer.
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13. Intent to harm
• Bioterrorism: mailings of “weaponized” Anthrax in US 2001
• Bio-Crimes: Salmonella in OR, Shigella in TX (deliberate
contamination of food)
• Potential agents: Smallpox, Anthrax. Botulism toxin, Plague,
Tularemia, and others ….
Aum Shinrikyo (responsible for the Sarin nerve gas attack on the Tokyo
subway) had tried botulinum toxin, anthrax and had sent people to
Zaire to get Ebola virus.
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Prevention of Emerging Infectious Diseases Will Require Action
in Each of These Areas
 Surveillance and Response
Detect, investigate, and monitor emerging, the diseases they cause, and the factors
influencing their emergence, and respond to problems as they are identified.
 Applied Research
Integrate laboratory science and epidemiology to increase the effectiveness of public
health practice.
CDC
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 Infrastructure and Training
 Strengthen public health infrastructures to support surveillance,
response, and research and to implement prevention and control
programs
 Provide the public health work force with the knowledge and tools it
needs.

Prevention and Control
 Ensure prompt implementation of prevention strategies and
enhance communication of public health information about
emerging diseases
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Sources of Information and slides:
• Center for Disease Control – www.cdc.gov
• Louis G. DePaola, DDS, MS Dental School, University of
Maryland
• Duc J. Vugia, M.D., M.P.H. Division of Communicable Disease
Control, California Department of Health Services
• WHO – http://www.who.int/en/
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The End
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