Transcript disease emergence and re-emergence

INFECTIOUS DISEASES
IMPACT OF INFECTIOUS
DISEASES
• 14th century
• 1831
• 1854-56
• 1899-1902
- Europe - plague kills 20-45% of the
world’s population
- Cairo - 13% of population
succumbs to cholera
- Crimean war – deaths due to
dysentery were 10 times higher
than deaths due to casualties
- Boer War – deaths due to
dysentery were 5 times higher
than deaths due to casualties
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)
• “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
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
LA Times, 14 August 2012
LA Times, 13 August 2012
LA Times, Sept 2012
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.
Factors in Promotion of
Infectious Disease
Agent

Environment
Host
Agent – virus, bacteria, parasite, prion, etc.
Host – genetic profile, immune capacity,
poverty, nutritional status
Environment – biologic and chemical pollution,
climate change, deforestation
DISEASE EMERGENCE AND
RE-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.
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
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
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)
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)
Multidrug resistant
National Academies Press
http://www.nap.edu/books/0309071844/html/13.html
NEWLY IDENTIFIED INFECTIOUS
DISEASES AND PATHOGENS (1)
Year
Disease or Pathogen
1993
Hantavirus pulmonary syndrome (Sin Nombre
virus)
Vibrio cholerae O139
Guanarito virus
Hepatitis C
Hepatitis E; human herpesvirus 6
HIV
Escherichia coli O157:H7; Lyme borreliosis;
human T-lymphotropic virus type 2
Human T-lymphotropic virus
1992
1991
1989
1988
1983
1982
1980
Source: Workshop presentation by David Heymann, World Health Organization, 1999
NEWLY IDENTIFIED INFECTIOUS
DISEASES AND PATHOGENS (2)
Year
Disease or Pathogen
2012
2009
2004
2003
1999
1997
1996
MERS-CoV
H1N1
Avian influenza (human cases)
SARS
Nipah virus
H5N1 (avian influenza A virus)
New variant Creutzfelt-Jacob disease;
Australian bat lyssavirus
Human herpesvirus 8 (Kaposi’s sarcoma virus)
Savia virus; Hendra virus
1995
1994
Source: Workshop presentation by David Heymann, World Health Organization, 1999
Principles of Infectious Diseases
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)
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
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
Important Terms Used for
Infectious Diseases (1 of 2)
Important Terms Used for
Infectious Diseases (2 of 2)
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)
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
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
CLASSIFICATION OF
INFECTIOUS AGENTS (2 of 2)
• Protozoa – single cell organisms with a welldefined nucleus
• Rickettsia – very small bacteria spread by ticks
• Prions – unique proteins lacking genetic
molecules
• Chlamydia – bacteria lacking cell walls
Size Comparison of Microbes
Bacterial Cell Structure
James D. Dick, PhD, Johns Hopkins University
Taxonomy of Bacteria
Strain
O157:H7
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.
Microbiological Classification of
Infectious Diseases
Microbiological Classification of
Infectious Diseases
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.”
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
Microbiological Classification of
Infectious Diseases
Microbiological Classification of
Infectious Diseases
Microbiological Classification of
Infectious Diseases
Viruses
Entry into the Host Cell with an Envelope
Viruses
Entry into the Host Cell with an Envelope
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
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 510 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.
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
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.
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).
The Immune Response
Immune System Characteristics
Distinguishes between self and non-self
Remembers pathogens (memory)
Responds to specific antigens (subunits/
epitopes)
Immune Cells and Immune Responses
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
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
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)
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
Immune Activation of Cells
Binding of antigen to cells receptor:
Stimulates cell proliferation
Releases regulatory and effector molecules
(cytokines) recognized by other immune cells
To activate a T cell you need:
 Foreign antigen
 Antigen-presenting cell (APC)
T Cell Activation
CD3
Quiescent
T Cell
Anergic
T Cell
CD3 Stimulation
CD28
CD3
Quiescent
T Cell
CD28
Co-Stimulation
Activated
T Cell
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))
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
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
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