INFECTIOUS DISEASESINFECTIOUS DISEASES

IMPACT OF INFECTIOUS IMPACT OF INFECTIOUS DISEASESDISEASES

• 14th century - Europe - plague kills 20-45% of theworld’s population

• 1831 - Cairo - 13% of population succumbs to cholera

• 1854-56 - Crimean war – deaths due todysentery were 10 times higherthan deaths due to casualties

• 1899-1902 - Boer War – deaths due to dysentery were 5 times higherthan 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

LA Times, 14 August 2012

Ongoing West Nile Outbreak Being Called The Largest Ever In The USAs 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, 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 Host•

Environment

Agent – virus, bacteria, parasite, prion, etc.Host – genetic profile, immune capacity, poverty, nutritional statusEnvironment – biologic and chemical pollution, climate change, deforestation

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.

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)

National Academies Presshttp://www.nap.edu/books/0309071844/html/13.html

Multidrug resistant

NEWLY IDENTIFIED INFECTIOUS DISEASES AND PATHOGENS (1)

Year Disease or Pathogen

1993 Hantavirus pulmonary syndrome (Sin Nombrevirus)

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 21980 Human T-lymphotropic virus

Source: Workshop presentation by David Heymann, World Health Organization, 1999

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

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 TermsInfectious dose – number of organisms needed to successfully infectLatent period - exposure to infectiousness intervalIncubation period – interval from exposure to clinical symptomsInfectious period – interval during which host can transmit infectionReproductive rate – ability of an agent to spread in populationsVirulencePathogenicityImmunogenicityOutbreak – limited spreadEndemic – usually present; steady prevalenceEpidemic – rapid spreadPandemic – 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 well-defined 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

Strain O157:H7

Taxonomy of Bacteria

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 capsidand 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

VirusesEntry into the Host Cell with an Envelope

VirusesEntry 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 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.

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 CharacteristicsDistinguishes between self and non-selfRemembers pathogens (memory)Responds to specific antigens (subunits/ epitopes)

Immune Cells and Immune Responses

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

Immune CellsT cells

CD4 – activate other cells of the immune systemCD8 – inhibit or kill infected cells

B cellsProduce specific antigen-binding immune globulinsEnhance phagocytosis (innate)

NK cellsRespond initially to immune challenges

Humoral Immunity (B cells)Production of immune globulin (antibodies)Adaptive response – requires days to weeksTypes 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 CellsBinding of antigen to cells receptor:Stimulates cell proliferationReleases 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

ActivatedT Cell

CD3

Quiescent

CD28

T Cell

CD3

Quiescent

CD28

T Cell

CD3 Stimulation

Co-Stimulation

AnergicT 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) cellsKiller 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