Communicable Diseases, Nosocomial Diseases, Emerging and ReEmerging Diseases

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Communicable Diseases, Nosocomial Diseases,
Emerging and Re-Emerging Diseases

• Biology 447 - Environmental Microbiology

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Outline

• Communicable Diseases
• Nosocomial Infections (hospital-acquired)?
• Antibiotic Resistance
• Bioterrorism Agents
• Mapping Emerging Diseases
• Neglected Diseases
• Emerging Diseases in the US
• Diseases preventable by vaccination
• Global Emerging and Re-emerging Diseases
• - HIV - Hepatitis - Influenza
• - Malaria - Herpes
  - Ebola
• - Tuberculosis - HPV - SARS
• - Avian Influenza - West Nile virus -
  Trypanosomiasis
• - Others
• Summary

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• Communicable Diseases

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• 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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(No Transcript)
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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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Causes of Death Vary Greatly by Country Income
Level
Sierra Leone - Age distribution at death (2005)?
Denmark - Age distribution at death (2005)?
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CDs have a significant social impact

• Disruption of family and social networks
• Child-headed households, social exclusion
• Widespread stigma and discrimination
• TB, HIV/AIDS, Leprosy
• Discrimination in employment, schools, migration
  policies
• Orphans and vulnerable children
• Loss of primary care givers
• Susceptibility to exploitation and trafficking
• Interventions such as quarantine measures may
  aggravate the social disruption

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CDs have a significant economic impact in
affected countries

• At the macro level
• Reduction in revenue for the country (e.g.
  tourism)?
• Estimated cost of SARS epidemic to Asian
  countries 20 billion (2003) or 2 million per
  case.
• Drop in international travel to affected
  countries by 50-70
• Malaria causes an average loss of 1.3 annual GDP
  in countries with intense transmission
• The plague outbreak in India cost the economy
  over 1 billion from travel restrictions and
  embargoes
• At the household level
• Poorer households are disproportionately affected
• Substantial loss in productivity and income for
  the infirmed and caregiver
• Catastrophic costs of treating illness

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International boundaries are disappearing

• Borders are not very effective at stopping
  communicable diseases
• With increasing globalization
• interdependence of countries more trade and
  human/animal interactions
• The rise in international traffic and commerce
  makes challenges even more daunting
• Other global issues affect or are affected by
  communicable diseases.
• climate change
• migration
• Change in biodiversity

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Human Security concerns

• Potential magnitude and rapid spread of
  outbreaks/pandemics. e.g. SARS outbreak
• No country or region can contain a full blown
  outbreak of Avian influenza
• Bioterrorism and intentional outbreaks
• Anthrax, Small pox
• New and re-emerging diseases
• Ebola, TB (MDR-TB and XDR-TB), Hantvirus, etc

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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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Staphylococcus aureus growth
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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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CDCs National Nosocomial Infection Surveillance
(NNIS) System, 1989 - 2004
MRSA methicillin-resistant Staphylococcus
aureus VRE vancomycin-resistant
enterococcus
FQRPA Pseudomonas aeruginosa resistant to
fluoroquinolones 3CRKP Klebsiella
pneumoniae resistant to 3rd generation
cephalosporins
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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/agen
t/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 O157H7 (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 O157H7 (E. coli)?
• Food safety threats (e.g., Salmonella species,
  Escherichia coli O157H7, 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)?
• Arenavirues
• 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 O157H7 (Escherichia coli)?
• Emerging infectious diseases such as Nipah virus
  and hantavirus
• Epsilon toxin of Clostridium perfringens
• Escherichia coli O157H7 (E. coli)?
• Food safety threats (e.g., Salmonella
  species,scherichia coli O157H7, Shigella)?

• 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)?
• Shigella (shigellosis)?
• Shigellosis (Shigella)?
• Smallpox (variola major)?
• Staphylococcal enterotoxin
• 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)?

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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

50

• 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

51

• 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.

52

• 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.

53

• 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
• 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
56
Geographic Origins of EID events from 1940 to 2004
Caption Global richness map of the geographic
origins of EID events from 1940 to 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 proportional to the
number of events in the cell. Credit Jones et.
al., Nature
Caption Global richness map of the geographic
origins of EID events from 1940 to 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 proportional to the
number of events in the cell. Credit Jones et.
al., Nature
57

• Emerging Diseases in the United States

58
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
59
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 015.7H7
• Other food/H2O-borne
• S. pneumonia, MRSA, VRSA
• Vancomycin resistant Enterococcus (VRE)?
• Multiple-drug resistant TB (MDRTB)?
• Bio-engineered agents
• Malaria drug-resistant

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

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

62

• 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

63

• Diseases in the USA preventable by vaccination

64
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
65
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

66
Vaccine Preventable Diseases of children

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

67
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 gt 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

68
Increasing Antibiotic Resistance
69

• Global Emerging and Re-emerging Diseases

70
Enlarged View on next 2 pages
71
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72
Continued
From WHO Emerging Issues in Water and
Infectious disease ISBN 92 4 159082 3 (LC/NLM
classification QW 80) ISSN 1728-2160
73
(No Transcript)
74

• Global Diseases

75
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76
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77

• HIV/AIDS

78
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.

79

• 1982 Term AIDS replaces GRID
• 1983 Universal precautions introduced
• MMWR 198332101
• 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

80
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.
81

• 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

82

• 1996
• HIV viral load testing
• Becomes major method to assess ART
  
• Mellors J Ann Intern Med 1997126946
• ACTG 076 shows benefit of AZT in reducing
  perinatal transmission
• NEJM 19963351621
• 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

83

• 1997 13 decrease in AIDS deaths
• 60-80 reduction in new AIDS-defining conditions,
  hospitalizations and deaths
• Palella et al, NEJM 1998338853,
• Mocroft at al, Lancet 19983521725
• 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

84
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 lt 500
  Opportunistic Infection(s)?
• AIDS CD4 lt 200 AIDS Defining Illness(s)
• Advanced HIV Infection CD4 lt 50 Serious
  opportunistic Infection(s) Death

85
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

86
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
• lt1 (1000) in USA and Europe
• Transmission rates
• USA/Europe 1330 without ART,
  approaching 13 with ART
• Developing countries 2043 without ART, lower
  rates with ART, even with short-course therapy
• Breast feeding for 6 months
• Additional 510 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
87
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.

88
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

89
Global HIV Burden
90
Adults and Children With HIV/AIDS, 12/31/02
Eastern Europe Central \Asia 1,200,000
North America 980,000
Western Europe 570,000
East Asia Pacific 1,200,000
North Africa Middle East 550,000
Caribbean 440,000
South South-East Asia 6,000,000
Latin America 1,500,000
Sub Saharan Africa 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
91
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)?

92

• Malaria

93
Malaria

• Every year, 500 million people become severely
  ill with malaria
• causes 30 of Low birth weight in newborns
  globally.
• gt1 million people die of malaria every year. One
  child dies from it every 30 seconds
• 40 of the worlds 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

94
Annual Reported Malaria Cases by Country (WHO
2003)?
95
Global malaria prevalence
96
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

97

• Hepatitis

98
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

99

• Hepatitis
• Asymptomatic - anicteric
• Mild symptomatic - anicteric
• Classic icteric infection (pertaining to or
  affected with jaundice)?
• Fulminant hepatitis (sudden, flaring up type)?
• Chronic hepatitis

100
Viral Hepatitis - Overview


Type of Hepatitis
A
B
C
D
E
Source of
feces
blood/ blood-derived/body fluids
feces
virus
Route of
Percutaneous/permucosal
fecal-oral
fecal-oral
transmission
Chronic
no
yes
yes
yes
no
infection
ensure safe
Prevention
pre/post-
pre/post-
blood donor
pre/post-
drinking
exposure
exposure
screening
exposure
immunization
immunization
risk behavior
immunization
water
modification
risk behavior
modification
101
Viral Hepatitis
102
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)?
• Gamma Herpesviruses
• Epstein-barr Virus (EBV)?
• Human Herpesvirus Type 8 (HHV-8)
  
  
• Kaposis Sarcoma Asso. Herpesvirus

The Herpes Simplex Virus type 1 (HSV1), which is
the cause of cold sores, has an icosahedral
capsid shown here at 13 Å resolution.
103
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 14 persons gt 12 y.o. infected
  
  
• 70-90 asymptomatic shedding
  
• Only about 20 of HSV-2 Ab know they are
  infected

104
Herpes Viruses

• EBV
  
  
• Infects gt 85 of population
  
  
• Agent of infectious mononucleosis
  
• Cause of oral hairy leukoplakia
  
  
  
• Oncogenic Burkitts Lymphoma
  
• Linked to Hodgkins Disease/ other malignancies
• CMV
  
  
• Problematic in immumocomp. pts Retinitis,
  enteritis
• Linked to vasculopathies, CAD?
  
  
• Role in organ transplant rejection
  
  
• Other graft/host involvement

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.
105
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.

106
Human Papillomavirus

• Most common viral STD
• Infects about 1/3 of sexually active
  population in USA
• gt60 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

107
Papilloma Focal Epithelial Hyperplasia (FEH)?

• Etiological agent
  
• Human papilloma virus (HPV)?
• Wart
• Clinical appearance
• Flat (FEH)?
• Siky
  
• Cauliflower-like

108

• Avian Influenza

109
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.

110
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

111
Confirmed human cases Avian Influenza
112
Migratory pathway for birds and Avian influenza
113
The Spread of Avian Flu -- Status as of the
Summer 2008
114

• West Nile Virus

115
WNV In USA
12/11/02
116

• 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.

117
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

118

• Suspect WNV when
• Symptoms consistent with WNV
• Unexplained bird or horse deaths
• Mosquito season
• Age gt 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

119
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
120
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121
U.S. cases of West Nile for 2002
122
U.S. cases of West Nile for 2004
123
U.S. cases of West Nile for 2005
124
U.S. cases of West Nile for 2007
125

• African Trypanosomiasis

126
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 brou