Emerging Diseases

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					 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:

                      –   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)‫‏‬

•    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 Community-
     Acquired-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 Community-
     Acquired-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
•    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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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
                                                    70


                                                              MRSA = methicillin-resistant Staphylococcus aureus
             Proportion of Resistant Isolates (%)




                                                    60


                                                    50


                                                    40                                                  FQRPA = Pseudomonas aeruginosa resistant to fluoroquinolones


                                                    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



             •   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

             •   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)
                                                              –   Plague (Yersinia pestis)
      Arenavirues
                                                              –   Psittacosis (Chlamydia psittaci)
      Bacillus anthracis (anthrax)
                                                              –   Q fever (Coxiella burnetii)
      Botulism (Clostridium botulinum toxin)
                                                              –   Ricin toxin from Ricinus communis (castor
      Brucella species (brucellosis)                             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)                            –   Staphylococcal enterotoxin
      Ebola virus hemorrhagic fever                          –   Tularemia (Francisella tularensis)
      E. coli O157:H7 (Escherichia coli)                     –   Typhoid fever (Salmonella Typhi)
      Emerging infectious diseases such as Nipah virus and   –   Typhus fever (Rickettsia prowazekii)
       hantavirus
                                                              –   Variola major (smallpox)
      Epsilon toxin of Clostridium perfringens
                                                              –   Vibrio cholerae (cholera)
      Escherichia coli O157:H7 (E. coli)
                                                              –   Viral encephalitis (alphaviruses [e.g.,
      Food safety threats (e.g., Salmonella                      Venezuelan equine encephalitis, eastern
       species,scherichia coli O157:H7, Shigella)                 equine encephalitis, western equine
      Francisella tularensis (tularemia)                         encephalitis])
      Glanders (Burkholderia mallei)                         –   Viral hemorrhagic fevers (filoviruses [e.g.,
                                                                  Ebola, Marburg] and arenaviruses [e.g.,
      Lassa fever
                                                                  Lassa, Machupo])
 •     Marburg virus hemorrhagic fever
                                                              –   Water safety threats (e.g., Vibrio cholerae,
 •     Melioidosis (Burkholderia pseudomallei)                    Cryptosporidium parvum)
                                                              –   Yersinia pestis (plague)
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             Neglected Diseases




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Neglected diseases

•    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 multidrug-
             resistant 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 multidrug-
             resistant 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 high-
             impact 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 high-
             impact diseases of the future, we're missing the point."

•            "We need to start finding pathogens before they emerge," said
             Daszak.




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                                                                                     52
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.    Emerging infectious diseases (EIDs) are a significant burden on global economies and
     public health.
2.   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.
3.   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.
4.   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.
5.   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').
6.   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).
  10/24/2008                                       Credit: Jones et. al., Nature                                              55
 Geographic Origins of EID events from 1940 to 2004




Caption: Global richness map of of the geographicorigins of EID events from 1940 toto 2004. The map is derived for EID
    Caption: Global richness map the geographic origins of EID events from 1940 2004. The map is derived for
    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
to the number of events in the cell. Credit: Jones et. al.,Jones et. al., Nature
    proportional to the number of events in the cell. Credit: Nature

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                                                                                                                56
             Emerging Diseases in the
              United States




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                                        57
 Emerging and re-emerging Diseases in the USA
Chlamydia                      Measles *
Diphtheria *                   Meningococcus
Encephalitis                   MRSA
     West Nile                 Pertussis *
     St. Louis                 Poliomyelitis *
E. coli                        Rabies
N gonorrhea                    Rocky Mountain Spotted Fever
H. Influenzae                  Rubella *
Hantavirus                     SARS (Severe Acute Respiratory Syndrome)
Hepatitis A-G (A and B*)       Salmonellosis
Human herpes viruses           Shigellosis
     HHV 1-8                   S. pneumoniae
HIV/AIDS                       Syphilis
Human papilloma viruses *      Tetanus *
Influenza * Emerging strains   Toxic-Shock Syndrome
Legionella pneumophila         Tuberculosis *
Lyme Disease *

                        * Vaccination possible

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                                                                    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



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                                                   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
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                                                              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
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                                                              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
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                                                                         64
Vaccine Preventable Diseases - Adults - Continued


             •   Diphtheria**
             •   Hepatitis A
             •   Hepatitis B
             •   Influenza**
             •   Lyme Disease
             •   Measles*
             •   Haemophilis influenza type B (Hib)
             •   Mumps*
             •   Pneumococcus**
             •   Polio
             •   Rubella*
             •   Tetanus**
             •   Varicella*




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                                                      65
Vaccine Preventable Diseases of children



               •   Diphtheria
               •   Hepatitis A
               •   Hepatitis B
               •   Pertussis
               •   Measles*
               •   Haemophilis influenza type B (Hib)




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                                                    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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Increasing Antibiotic Resistance




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                                   68
      Global Emerging and Re-emerging Diseases




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                                             69
             Enlarged View on next 2
                     pages




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                                70
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             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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             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


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                                                                      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 post-
              partum

                                   Wiktor SZ, et al. XIIIth IAC, Durban, 2000. Abstract 354


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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                          1,200,000
              980,000                     570,000                                     East Asia & Pacific

                                               North Africa &
                                                                                         1,200,000
               Caribbean
                                                Middle East
               440,000                                                              South & South-East Asia
                                                550,000                                  6,000,000
                 Latin America              Sub Saharan Africa
                 1,500,000                    29,400,000                                          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 ....................              3.1 million


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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
             •   Constraints to access to care and treatment
             •   Stigma and discrimination
             •   Inadequate prevention measures.
             •   Co-infections (TB, Malaria)
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             Malaria




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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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             Hepatitis




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                         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
       –     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

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                                                             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             B             C             D          E
Source of           feces           blood/ blood-derived/body fluids     feces
virus


Route of
transmission      fecal-oral         Percutaneous/permucosal           fecal-oral

Chronic
infection            no            yes           yes           yes         no

Prevention                                                            ensure safe
                   pre/post-    pre/post-  blood donor      pre/post-
                   exposure     exposure     screening;    exposure drinking
                 immunization immunization risk behavior immunization; water
                                            modification risk behavior
                                                          modification
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Viral Hepatitis


               VIRAL       GENOME   SPREAD       INCUBATION    CHRONICITY
               CLASS
HAV          Picoravirus    RNA     Enteric       15-45 Days     None

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        Probable




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                                                                        101
Human Herpesviruses


• Alpha Herpesviruses:
       – Herpes Simplex Virus Type 1 (HSV-1)
       – Herpes Simplex Virus Type 2 (HSV-2)
       – Varicella Zoster Virus (HZV)
                                                    The Herpes Simplex

• Beta Herpesviruses:                               Virus type 1 (HSV1),
                                                    which is the cause of
                                                      cold sores, has an
       – Cytomegalovirus (CMV)                       icosahedral capsid
                                                     shown here at 13 Å
       – Human Herpesvirus Type 6 (HHV-6)                 resolution.

       – Human Herpesvirus Type 7 (HHV-7)
• 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:
       –     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


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                                                                  103
 Herpes Viruses



• EBV:                                                  Epstein-Barr virus (EBV) occurs

    –    Infects > 85% of population;                   world-wide and infects most people
                                                        at some point in their lives. Children
                                                        are largely immune to its effects, but
    –    Agent of infectious mononucleosis              infection in older people can cause a
                                                        condition called infectious

    –
                                                        mononucleosis.
         Cause of oral hairy leukoplakia;               Long-term infection is, in very rare
                                                        cases, linked to the development of
    –    Oncogenic: Burkitt’s Lymphoma;                 some forms of cancer.


    –    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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                                             106
Papilloma; Focal Epithelial Hyperplasia (FEH)‫‏‬


• Etiological agent:
   – Human papilloma virus (HPV)
   – “Wart”
• Clinical appearance:
   – Flat (FEH)
   – Siky
   – Cauliflower-like




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                                                 107
             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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                                                                                110
Confirmed human cases Avian Influenza




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                                        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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                                                           117
• 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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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                East African

Agent:               T. brucei gambiense    T. brucei rhodesiense
Vector:              riverine tsetse fly    savanna tsetse fly
Distribution:        west/central Africa    east/south Africa
Reservoir:           human                  antelope/cattle
Disease:             chronic (years)        rapid progression: 1-4 weeks
Mortality:           100%                   100%
At risk:             rural persons          rural, visitors to game reserves




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   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)




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                                               134
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             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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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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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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Spread of SARS

From New York Times




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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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                                                             •   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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             Hantavirus




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                          143
 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 !
      –      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
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       Global Prevalence of TB cases (WHO)




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             Tuberculosis




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                            154
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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.
       –     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




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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 Drug-
             Sensitive 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.   Human demographics and behavior
2.   Technology and Industry
1.   Economic development and land use
4.   International travel and commerce
5.   Microbial adaptation and change
1.   Breakdown of public health measures
7.   Human vulnerability
1.   Climate and weather
2.   Changing ecosystems
3.   Poverty and social inequality
4.   War and famine
5.   Lack of political will
6.   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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        Speed of Global Travel in Relation to World Population Growth

                            0
                           40
                                                                   6
)




                                                                        )
                            5
                           30
                                                                   5
                            0
                           30
Days to Circumnavigate (




                                                                        World Population in billions (
                           20
                            5                                      4
        the Globe




                            0
                           20
                                                                   3
                            5
                           10
                                                                   2
                            0
                           10
                           50                                      1

                            0                                      0
                                15
                                 80   10
                                      90        15
                                                 90       00
                                                         20
                                           er
                                           Ya


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5. Microbial adaptation and change
•   Increased antibiotic resistance with increased use of antibiotics in
    humans and food animals (VRE, VRSA, penicillin- and macrolide-
    resistant 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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                                                                             171
             From: Murphy and Nathanson. Semin. Virol. 5, 87, 1994
                      Emerging Vancomycin-resistant Enterococcal Infections*
        Emerging Vancomycin-resistant Enterococcal Infections*
 % Resistant




               * in U.S. NNIS Hospitals
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                                                                                172
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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                                                                   173
  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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                                                                           178
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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                                                                    179
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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                                                                     180
   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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                                                                                                   181
 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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