INFECTIOUS DISEASES

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INFECTIOUS DISEASES
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IMPACT OF INFECTIOUS DISEASES

• 14th century - Europe - plague kills 20-45 of
  the
• worlds population
• 1831 - Cairo - 13 of population
  succumbs to cholera
• 1854-56 - Crimean war deaths due to
• dysentery were 10 times higher than
  deaths due to casualties
• 1899-1902 - Boer War deaths due to
  dysentery were 5 times higher
• than deaths due to casualties

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Infectious disease is one of the few genuine
adventures left in the world. The dragons are
all dead and the lance grows rusty in the chimney
corner . . . About the only sporting proposition
that remains unimpaired by the relentless
domestication of a once free-living human species
is the war against those ferocious little fellow
creatures, which lurk in the dark corners and
stalk us in the bodies of rats, mice and all
kinds of domestic animals which fly and crawl
with the insects, and waylay us in our food and
drink and even in our love. - (Hans
Zinsser,1934 quoted in Murphy 1994)
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• One can think of the middle of the 20th century
  as the end of one of the most important social
  revolutions in history, the virtual elimination
  of the infectious diseases as a significant
  factor in social life
• Sir Macfarland Burnet

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Ongoing West Nile Outbreak Being Called The Largest Ever In The US As of August 22, CDC is reporting 1,118 cases of West Nile virus infections in 38 states with 41 deaths. It is the largest West Nile virus outbreak to occur in the US since first reported in 1999. Lyle Petersen, CDCs vector-borne disease specialist, told the media that the peak usually occurs in mid-August and that he expects many more cases as it takes a couple of weeks for people to develop illness. The cause for the record number of cases this year is unknown but Petersen speculated that unusually warm weather conditions could have made it easier for transmission to humans to occur. Texas has been at the epicenter of the epidemic with approximately half of the cases (586) and half of the deaths (21). To protect themselves, Americans are being urged to fight the bite by using mosquito repellent with DEET, dressing in long pants and sleeves, being extra careful at dusk and dawn, and draining any standing water around their premises. 
Epidemiology News Briefs - August 23, 2012
LA Times, 14 August 2012
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LA Times, 13 August 2012
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LA Times, Sept 2012
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Direct economic impact of selected infectious
disease outbreaks, 1990-2003
Heymann DL. Emerging and re-emerging infections.
In Oxford Textbook of Public Health, 5th ed,
2009, p1267.
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Factors in Promotion of Infectious Disease

• Agent Host
  
• ?
• Environment
• Agent virus, bacteria, parasite, prion, etc.
• Host genetic profile, immune capacity, poverty,
  nutritional status
• Environment biologic and chemical pollution,
  climate change, deforestation

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DISEASE EMERGENCE ANDRE-EMERGENCE CAUSES

• GENETIC/BIOLOGIC FACTORS
• Host and agent mutations
• Increased survival of susceptibles
• HUMAN BEHAVIOR
• POLITICAL
• SOCIAL
• ECONOMIC
• PHYSICAL ENVIRONMENTAL FACTORS
• crowding
• ECOLOGIC FACTORS
• Climatic changes
• Deforestation
• Etc.

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THE CHAIN OF INFECTION

• Etiologic agent
• Reservoir
• Humans
• Animals
• Environment (e.g. soil)
• Portal of exit
• Mode of transmission
• Direct
• Indirect
• Intermediate host
• Portal of entry
• Susceptible host

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PORTALS OF ENTRY/EXIT OF INFECTIOUS AGENTS

• Respiratory influenza, common cold agents,
  measels
• Genitourinary sexually transmitted agents
• Alimentary track (gut) Campylobacter, cholera,
  salmonella
• Skin streptococci,
• Percutaneous (vector borne diseases e.g.
  arboviruses)
• Eye C. trachomatis
• Transplacental cytomegalovirus, HIV
• Route of entry and exit not necessarily the
  same for a single agent e.g. HIV, schistosomaisis

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MICROBIAL THREATS (1)

• Newly recognized agents (SARS, acinetobacter)
• Mutation of zoonotic agents that cause human
  disease (e.g., H5N1, H1N1)
• Resurgence of endemic diseases (malaria,
  tuberculosis)
• Persisting diseases (measles, polio)

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MICROBIAL THREATS (2)

• Development of drug-resistant agents
  (tuberculosis, gonorrhea)
• Recognition of etiologic role in chronic diseases
  (Chlamydia causing respiratory and heart disease
  HIV and heart disease)
• Use of infectious agents for terrorism and
  warfare (anthrax)

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Multidrug resistant
National Academies Press http//www.nap.edu/books/
0309071844/html/13.html
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NEWLY IDENTIFIED INFECTIOUS DISEASES AND
PATHOGENS (1)

• Year Disease or Pathogen
• 1993 Hantavirus pulmonary syndrome (Sin
  Nombre
• virus)
• 1992 Vibrio cholerae O139
• 1991 Guanarito virus
• 1989 Hepatitis C
• 1988 Hepatitis E human herpesvirus 6
• 1983 HIV
• 1982 Escherichia coli O157H7 Lyme
  borreliosis
• human T-lymphotropic virus type 2
• 1980 Human T-lymphotropic virus

Source Workshop presentation by David Heymann,
World Health Organization, 1999
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NEWLY IDENTIFIED INFECTIOUS DISEASES AND
PATHOGENS (2)

• Year Disease or Pathogen
• MERS-CoV
• 2009 H1N1
• 2004 Avian influenza (human cases)
• 2003 SARS
• 1999 Nipah virus
• 1997 H5N1 (avian influenza A virus)
• 1996 New variant Creutzfelt-Jacob disease
• Australian bat lyssavirus
• 1995 Human herpesvirus 8 (Kaposis sarcoma
  virus)
• 1994 Savia virus Hendra virus

Source Workshop presentation by David Heymann,
World Health Organization, 1999
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Principles of Infectious Diseases
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Microbiological Classification of Infectious
Diseases

• Disease is a disturbance in the state of health
• Microbes cause disease in the course of stealing
  space, nutrients, and/or living tissue from their
  symbiotic hosts (e.g., us)
• To do this, microbes do most of the following
• Gain access to the host (contamination)
• Adhere to the host (adherence)
• Replicate on the host (colonization)
• Invade tissues (invasion)
• Produce toxins or other agents that cause host
  harm (damage)

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BIOLOGIC CHARACTERISTICS OF INFECTIOUS AGENTS

• Infectivity the ability to infect a host
• Pathogenicity the ability to cause disease in
  the host
• Virulence the ability to cause severe disease
  in the host
• Immmunogenicity the ability to induce an immune
  response in the host

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Infectious Disease Terms

• Infectious dose number of organisms needed to
  successfully infect
• Latent period - exposure to infectiousness
  interval
• Incubation period interval from exposure to
  clinical symptoms
• Infectious period interval during which host
  can transmit infection
• Reproductive rate ability of an agent to spread
  in populations
• Virulence
• Pathogenicity
• Immunogenicity
• Outbreak limited spread
• Endemic usually present steady prevalence
• Epidemic rapid spread
• Pandemic occurring across countries and in
  multiple populations

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Important Terms Used for Infectious Diseases (1
of 2)
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Important Terms Used for Infectious Diseases (2
of 2)
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MODES OF TRANSMISSION

• Direct
• Droplet
• Aerosol
• Skin to skin
• Indirect
• Fomites (clothes, blankets, door handles etc)
• Vectors (e.g. mosquitoes)
• Food and water
• Intermediate hosts (e.g. snails)

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CLINICAL RESPONSES TO INFECTION BY AN AGENT

• Inapparent infection no clinical symptoms
  generated
• Carrier state usually no clinical symptoms but
  host can transmit infection for long periods
• Clinical symptoms
• Mild disease
• Severe disease
• Residual impairment
• death

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CLASSIFICATION OF INFECTIOUS AGENTS (1 of 2)

• Bacteria survive on appropriate media, stain
  gram-positive or -negative
• Viruses obbligate intracellular parasites which
  only replicate intracellularly (DNA, RNA)
• Fungi non-motile filamentous, branching
  strands of connected cells
• Metazoa multicellular animals (e.g.parasites)
  with complicated life cycles often involving
  several hosts

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CLASSIFICATION OF INFECTIOUS AGENTS (2 of 2)

• Protozoa single cell organisms with a
  well-defined nucleus
• Rickettsia very small bacteria spread by ticks
• Prions unique proteins lacking genetic
  molecules
• Chlamydia bacteria lacking cell walls

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Size Comparison of Microbes
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Bacterial Cell Structure
James D. Dick, PhD, Johns Hopkins University
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Taxonomy of Bacteria
Strain
O157H7
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Microbiological Classification of Infectious
Diseases

• Bacteria are classified by their Gram stain
  characteristics.
• Gram staining is the application of a crystal
  violet dye to a culture of bacteria. Bacteria
  that retain the color of the dye are called Gram
  positive bacteria that don't are Gram negative.
• The Gram stain attaches to peptidoglycan in the
  bacterial cell wall.
• In Gram-negative bacteria, the peptidoglycan
  layer is protected by an outer membrane.

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Microbiological Classification of Infectious
Diseases
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Microbiological Classification of Infectious
Diseases
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Microbiological Classification of Infectious
Diseases

• Viruses are acellular, obligate intracellular
  organisms.
• The complete infectious virus is termed a virion.
• The virion consists of the specific nucleic acid
  (DNA or RNA) surrounded by a protein coat
  (capsid).
• Some viruses are enveloped which means that they
  possess a lipoprotein coat that surrounds the
  capsid and is acquired from infected host cell
  membrane.
• Viruses that lack an envelope are naked.

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Microbiological Classification of Infectious
Diseases

• Viruses are typically classified by
• Genetic material (DNA vs. RNA)
• Strandedness (single vs. double)
• Size and shape of the capsid and whether its
  enveloped or non-enveloped
• Method of replication

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Microbiological Classification of Infectious
Diseases
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Microbiological Classification of Infectious
Diseases
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Microbiological Classification of Infectious
Diseases
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VirusesEntry into the Host Cell with an Envelope
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VirusesEntry into the Host Cell with an Envelope
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Microbiological Classification of Infectious
Diseases

• All fungi are chemoheterotrophs
• Pathogenic fungi have two forms yeasts
  (unicellular) and molds (multicellular)
• Some fungi are dimorphic (this is particularly
  true for the pathogenic fungi)
• Molds grow as filamentous, branching strands of
  connected cells known as hyphae

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Microbiological Classification of Infectious
Diseases

• Types of Parasites
• Protozoa Single-celled, microscopic organisms
  that can perform all necessary functions of
  metabolism and reproduction. Some protozoa are
  free-living, while others parasitize other
  organisms for their nutrients and life cycle.
• The morphology of protozoa varies widely and
  includes oval, spherical and elongated cells that
  can range in size from 5-10 to 1-2 mm.
• Structurally, the protozoa resemble other
  eukaryotic cells and possess a cytoplasmic
  membrane that encloses cytoplasm containing
  membrane-bound nuclei, mitochondria, 80s
  ribosomes and a variety of organelles.

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Microbiological Classification of Infectious
Diseases

• Types of Parasites
• Helminths A large, multicellular organism (worm)
  that is generally visible to the naked eye in its
  adult stages.
• Helminths can be free-living or parasitic.
• Nematodes Roundworms
• Trematodes Flukes
• Cestodes Tapeworms

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Microbiological Classification of Infectious
Diseases

• Prions are abnormal, transmissible agents that
  are able to induce abnormal folding of normal
  cellular prion proteins in the brain, leading to
  brain damage and the characteristics signs and
  symptoms of the disease.
• Prion diseases are usually rapidly progressive
  and always fatal.

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WHATS AHEAD?

• Microbes and vectors swim in the evolutionary
  stream, and they swim faster than we do.
  Bacteria reproduce every 30 minutes. For them, a
  millennium is compressed into a fortnight. They
  are fleet afoot, and the pace of our research
  must keep up with them, or they will overtake us.
  Microbes were here on earth 2 billion years
  before humans arrived, learning every trick for
  survival, and it is likely that they will be here
  2 billion years after we depart (Krause 1998).

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The Immune Response
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Immune System Characteristics

• Distinguishes between self and non-self
• Remembers pathogens (memory)
• Responds to specific antigens (subunits/ epitopes)

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Immune Cells and Immune Responses
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Types of Cell-Mediated Immunity

• Cellular
• Innate non-specific immediate response
• Adaptive specificity and memory require days to
  weeks
• Humoral Specificity and memory requires days to
  weeks to produce immune globulins (antibodies)
• Cells
• Monocytes precursors of macrophages
• Macrophages ingest and eliminate (innate)
  present antigens (adaptive)
• Dendritic cells induce innate immunity present
  antigens (adaptive) and stimulate cytokine
  production
• Lymphocytes
• T cells mature in the thymus
• B cells mature in the bone marrow
• Natural killer cells

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Immune Cells

• T cells
• CD4 activate other cells of the immune system
• CD8 inhibit or kill infected cells
• B cells
• Produce specific antigen-binding immune globulins
• Enhance phagocytosis (innate)
• NK cells
• Respond initially to immune challenges

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Humoral Immunity (B cells)

• Production of immune globulin (antibodies)
• Adaptive response requires days to weeks
• Types of immune globulins produced
• IgM early response (3-6 months)
• IgG later response, persists as memory
• IgA secreted by mucosal tissue and in blood
• IgE responds to parasites, small percentage
• Specific response each antibody recognizes
  (responds) to only one epitope (sub-component of
  an antigen)

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Immune System Components (1 of 3)

• Antigens trigger an immune response
• Epitopes subunit of an antigen (amino acids,
  sugars, lipids or nucleotides) that bind with
  specific immune receptors
• Antigen receptors on immune cells, bind only
  one epitope, which activates the immune response

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• Immune Activation of Cells
• Binding of antigen to cells receptor
• Stimulates cell proliferation
• Releases regulatory and effector molecules
  (cytokines) recognized by other immune cells

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• To activate a T cell you need
• Foreign antigen
• Antigen-presenting cell (APC)

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T Cell Activation
Anergic T Cell
CD3 Stimulation
Activated T Cell
Co-Stimulation
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Immune System Components (2 of 3)

• B cells recognize raw antigens
• T cells recognize only antigens processed by
  antigen-presenting cells to epitopes and attach
  the correct MHC protein to it
• MHC molecules (human leukocyte antigens (HLA))

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Immune System Components (3 of 3)

• Class I (A, B, C) expressed on nucleated cells
  - trigger CD8 killing
• Class II (DR, DP) expressed on cells of the
  immune system trigger CD4 cells
• Cytokines chemicals that facilitate
  communication between different types of cells

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• Natural Killer (NK) cells
• Killer inhibitory receptors (KIR) on NK cells
• Down-regulation of MHC class I molecules by
  virally infected cells reduces KIR and activates
  NK cells

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Cytokines (Immune Communicators)

• Hormone-like proteins
• Released by cell activation
• Affect immune responses from own and other cells
• Regulate cell activity
• Cytokine receptors bind cytokines and trigger
  action
• Antigen-independent
• One cytokine can have multiple roles
• Chemokine a cytokine produced by immune and
  non-immune cells that attracts cells to site of
  infection and also inhibits some immune responses