infectious diseases
DESCRIPTION
INFECTIOUS DISEASES. IMPACT OF INFECTIOUS DISEASES. 14 th century- Europe - plague kills 20-45% of the world’s population 1831 - Cairo - 13% of population succumbs to cholera 1854-56- Crimean war – deaths due to - PowerPoint PPT PresentationTRANSCRIPT
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INFECTIOUS DISEASESINFECTIOUS DISEASES
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IMPACT OF INFECTIOUS IMPACT OF INFECTIOUS DISEASESDISEASES
• 14th century - Europe - plague kills 20-45% of the
world’s 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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LA Times, 14 August 2012
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, CDC’s 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
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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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National Academies Presshttp://www.nap.edu/books/0309071844/html/13.html
Multidrug resistant
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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 O1391991 Guanarito virus1989 Hepatitis C1988 Hepatitis E; human herpesvirus 61983 HIV1982 Escherichia coli O157:H7; 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
2012 MERS-CoV2009 H1N12004 Avian influenza (human cases)2003 SARS1999 Nipah virus1997 H5N1 (avian influenza A virus)1996 New variant Creutzfelt-Jacob disease; Australian bat lyssavirus1995 Human herpesvirus 8 (Kaposi’s 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 TermsInfectious 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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Strain O157:H7
Taxonomy of Bacteria
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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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WHAT’S 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 CharacteristicsDistinguishes between self and non-selfRemembers 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 ImmunityCellularInnate – non-specific immediate responseAdaptive – specificity and memory require days to weeksHumoral – Specificity and memory requires days to weeks to produce immune globulins (antibodies)
CellsMonocytes – precursors of macrophagesMacrophages – ingest and eliminate (innate) present antigens (adaptive)Dendritic cells – induce innate immunity present antigens (adaptive) and stimulate cytokine productionLymphocytes
T cells – mature in the thymusB cells – mature in the bone marrowNatural killer cells
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Immune CellsT cells
CD4 – activate other cells of the immune systemCD8 – inhibit or kill infected cells
B cellsProduce specific antigen-binding immune globulins
Enhance phagocytosis (innate)
NK cellsRespond 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 CellsBinding of antigen to cells receptor:Stimulates cell proliferationReleases 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
ActivatedT Cell
CD3
Quiescent
CD28
T Cell
CD3
Quiescent
CD28
T Cell
CD3 Stimulation
Co-Stimulation
Anergic T Cell
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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) cellsKiller 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