Principles of DiseasePrinciples of DiseaseMicrobiology 2314

• Every disease is a race between a pathogen trying to gain a foothold and the host defenses trying to prevent the pathogen from doing so.

DiseaseDisease

• Is a Process

• Is a State of Being Not In Good Health

• Involves Many Factors

- Age

- Nutrition

- Gender

- Race

• We tend to equate one pathogen with one disease, but it is more complicated than that.

• It is actually much more complicated than that.

Definitions: ParasiteDefinitions: Parasite

• Refers to Protozoans and Worms

Definition: PathogenDefinition: Pathogen

• Refers to Bacteria / Virus / Fungus

• An organism with the potential to cause disease.

• Infection

A pathogen growing in or on the host

• Virulence

The degree or intensity of pathogenicity

• Invasiveness

Ability to spread to other tissues

• Infectivity

Ability to secrete toxins

• Septicemia

Blood infection

More Definitions:More Definitions:

• Pathology

Scientific study of disease• Etiology

Cause of disease• Pathogenesis

Development of disease• Host

Organism that shelters and

supports the growth of

pathogens.

DiseaseDisease• An abnormal process in which part or all

of the body is not properly adjusted or is incapable of performing normal functions often because of infection by pathogens.

Relationships Between Relationships Between Microorganisms and ManMicroorganisms and Man

David Vetter the “Bubble Boy”

Usually germ-free in utero

Microorganisms begin colonization in and on the surface of the body during and after birth

We require these organisms

Germ-free organisms are less healthy than organisms with normal microbiota

Body Regions Have Characteristic Body Regions Have Characteristic FloraFlora

• Skin 1012

• Mouth 1010

• GI Tract 1014

Normal Flora Are Found MostlyNormal Flora Are Found Mostly

– on the skin – in the eyes – in the nose – in the mouth – in the upper throat – in the lower urethra – in the lower intestine – especially in the large intestine

• Note that this list basically includes all of the body surfaces exposed to the external environment.

Microbial AntagonismMicrobial Antagonism• Normal Microbiota establish permanent colonies

inside or on the body without producing disease• Symbiosis• Three Types

1. Commensalism

2. Mutualism

3. Parasitism• Transient microbiota are members of the normal flora

that are not always present or are present for only a few days, weeks, or months before disappearing.

Nitrogen Fixation -- MutualismNitrogen Fixation -- Mutualism

Ruminants and Resident Microbes – MutualismRuminants and Resident Microbes – Mutualism

Lichen Symbiosis Lichen Symbiosis

-- Mutualism-- Mutualism

Ascaris Worms / Ascaris Worms / ParasitismParasitism

• The upper respiratory tract consists of the nostrils, nasal cavities and throat.  It contains a number of commensalistic inhabitants including:  Staphylococcus epidermidis.

Out of all types of symbiotic bacteria, commemsalists are the least studied.  The reason for this is simple; if a bacteria is not causing harm or benefit to a host there is simply not much reasons to studying it.

Microbial AntagonismMicrobial AntagonismMicrobial Antagonism or Colonization inhibition: A process by which pathogenic microorganisms are inhibited by normal florafrom colonizing healthy organisms (a form of symbiosis)

Antagonism between the fungus Paraconyothyrium variabile and Fusarium oxysporum

• Mechanisms by which this inhibition occurs includes: 1. competing with pathogenic microorganisms

for nutrients

2. competing with pathogenic microorganisms for space

3. producing toxins that are harmful to some pathogenic microorganisms

Remember!Remember!

• Categorizing symbiotic relationships is convenient, but keep in mind that under certain circumstances the relationship can change.

Question?

• A colonic microorganism which bores into its host and by doing so does it damage, competes with its host for nutrients, but is the sole supplier of an organic growth factor without which the host could not survive. This symbiotic relationship is an example of (chose the best answer):

a. commensalism b. mutualismc. parasitism

Question?

• A colonic microorganism which bores into its host and by doing so does it damage, competes with its host for nutrients, and is the sole supplier of an organic growth factor without which the host could not survive. This symbiotic relationship is an example of (chose the best answer):

a. commensalism b. mutualismc. parasitism

Question?

• A bacteria is attached to the intestinal wall via its pili, causes its host no harm, and secretes an antibacterial poison which limits colonization of the intestine by other, unrelated bacteria. With regard to the prevention of disease, what process specifically is this bacteria effecting?

Microbial Antagonism

Question?

• Microbial antagonism (choose best answer) a. is a parasitic interaction between two

organisms b. describes generally the harm done by a

microorganism to a host c. can be an example of mutualism d. can be an example of parasitism e. all of the above Ab. none of the above

Question?

• Microbial antagonism (choose best answer) a. is a parasitic interaction between two

organisms b. describes generally the harm done by a

microorganism to a host c. can be an example of mutualism d. can be an example of parasitism e. all of the above Ab. none of the above

Question?

• A colonic microorganism which bores into its host and by doing so does it damage. This organism has no additional redeeming characteristics. You would describe the symbiotic relationship it has with its host as an example of (choose the best answer):

a. commensalism b. mutualism c. microbial antagonism d. parasitism e. none of the above

Question?

• A colonic microorganism which bores into its host and by doing so does it damage. This organism has no additional redeeming characteristics. You would describe the symbiotic relationship it has with its host as an example of (choose the best answer):

a. commensalism b. mutualism c. an effector of microbial antagonism d. parasitism e. none of the above

Question?

• Which is not a member of the normal flora of a plant or an animal? (assume all are obligate colonizers of the plant or animal host organism)

a. a bacterium b. a virus c. a fungus d. a protozoa e. all are equally likely to be members of normal flora

Question?

• Which is not a member of the normal flora of a plant or an animal?

a. a bacterium b. a virus c. a fungus d. a protozoa e. all are equally likely to be

members of normal flora

Question?

• Name a part of the body that you would not expect to have an associated normal flora.

StomachKidneyLiverEtc.

Anything Basically That Is Internal

• Transient microbiota are members of the normal flora that are not always present or are present for only a few days, weeks, or months before disappearing.

Transient MicrobiotaTransient Microbiota

Opportunistic MicroorganismsOpportunistic Microorganisms• Do not cause disease under normal conditions but

can cause disease under special conditions.

Staph Infection

Cooperation Among Cooperation Among MicroorganismsMicroorganisms

• One of the organizing principles of life on Earth is that cells cooperate.

• This is evident in the case of multicellular organisms, from nematodes to humans, but it also appears to apply widely among single-celled organisms such as bacteria, fungi, and amoeba.

• A well-studied example of intraspecies cooperation concerns the cyanobacterium Anabaena, which grows in long chains, in which approximately one cell out of ten differentiates into a heterocyst that provides fixed nitrogen for the neighboring cells

This Cellular Cooperation Can This Cellular Cooperation Can Increase the Virulence of a Increase the Virulence of a

MicroorganismMicroorganism

Example:

Strep Infection Scarlet Fever Rheumatic Fever

The Etiology of Infectious DiseaseThe Etiology of Infectious DiseaseKoch’s Postulates Koch’s Postulates

• Robert Koch played an important role in determining that specific microbes were associated with specific diseases.

• Four Postulates

1. Same pathogen must be present in every case of the disease.

2. Pathogen must be isolated in pure culture.

3. Pathogen isolated from pure culture must cause the same disease in lab animal.

4. Pathogen must be re-isolated from inoculated lab animal.

Exceptions to Koch’s PostulatesExceptions to Koch’s Postulates

• Inability to grow on artificial media (Syphilis)

Exceptions to Koch’s PostulatesExceptions to Koch’s Postulates

• Unequivocal signs and symptoms (Tetanus)

Exceptions to Koch’s PostulatesExceptions to Koch’s Postulates

• Diseases caused by variety of organisms (Pneumonia)

• Pathogens causing variety of diseases (Streptococcus pyogenes)

Exceptions to Koch’s PostulatesExceptions to Koch’s Postulates• Diseases that occur in humans only (Smallpox)

Classifying Infectious DiseasesClassifying Infectious Diseases

• Symptoms

Subjective Changes

Cannot Be Measured

• Signs

Objective Changes

Measurable Changes

Sign or Symptom?Sign or Symptom?

• Pain

• Temperature

• Nausea

• Swelling

• Discomfort

• Blood Pressure

Classifying Infectious DiseasesClassifying Infectious Diseases• Syndrome

A specific group of symptoms or signs

that always accompany a specific disease.

What is the Syndrome?What is the Syndrome?

• Flu• Measles• Anthrax• Legionnaires• Mumps• Carbuncles• Smallpox• West Nile Virus

Communicable DiseasesCommunicable Diseases• Transmitted Directly or Indirectly From

One Host to Another Host

Chickenpox

Measles

Genital Herpes

Contagious DiseasesContagious Diseases• A communicable disease that is spread

easily from one individual to another

Name a Communicable Disease that is Not Contagious.

http://162.129.70.33/images/Leprosy_Stigmata_1_040325.jpg

Noncontagious DiseasesNoncontagious Diseases

• Caused by microorganisms that normally grow outside the human body and are not transmitted from one host to another.

Tetanus

Anthrax

The Occurrence of DiseaseThe Occurrence of Disease• Incidence

Number of New Cases of Disease in a

Given Population.

The Risk of Disease• Prevalence

Number of Existing Cases of Disease in

a Given Population at Any One Time

The Burden of Disease

Question?

• Assume a classroom of 50 students exposed to a new strain of three-day influenza.

• Before exposure, the prevalence and incidence in this population are both zero.

• If within one week, 5 out of the 50 students contract the flu, what is the incidence?

• What is the prevalence for that one week period?

Continue?

• If after one more week, 5 more students become infected, what is the point prevalence?

• What is the overall prevalence?

• What is the incidence?

Trends

• Changes in incidence and prevalence are usually followed over a seasonal, yearly, and long-term basis and are helpful in predicting trends.

• Statistics of concern to epidemiologists are the rates of disease with regard to sex, race, and geographic region.

What We SeeWhat We See

• Infectious Diseases

High Incidence

Low Prevalence

• Chronic Diseases

Low Incidence

High Prevalence

Classification of DiseaseClassification of Disease

• Sporadic

Only an Occasional Case (Typhoid Fever)• Endemic

Constantly Present at an Expected Level (Common Cold)

• Epidemic

Above the Normal Expected Frequency (Flu)

• Pandemic

World Wide Epidemic (AIDs)

Scope of DiseaseScope of Disease

• Acute

Develops Rapidly

Short Lifespan

Usually Severe Symptoms

Example: Flu, Measles

• Chronic

Develops Slowly

Continual, Long Lasting, or Reoccurring

Usually Less Severe

Example: Osteoporosis

• Latent

Causative Agent Remains Inactive for a

Time – Then Becomes Active and

Produces Symptoms.

Chicken Pox to Shingles

HIV to AIDS

Herd Herd ImmunityImmunity

• The presence of immunity to a disease in most of the population.

• Normally due to Vaccination.

Herd Immunity is the Reason we Vaccinate!

The way herd immunity works is by isolating potential hosts and reducing virus’ opportunities to be passed on. For herd immunity to be effective I need to vaccinate at least 90% of the susceptible population.

If I drop below a 90% vaccination rate, the chances of passing infection increase and I get small clusters of disease occurring.

Emerging Infectious DiseasesEmerging Infectious Diseases

• New diseases with increasing incidence.

1. SARS

2. Ebola

3. West Nile Virus

4. Bird Flu

5. Monkeypox

Emerging Infectious DiseasesEmerging Infectious DiseasesEIDsEIDs

• EIDs Can Result From

1. Overuse of Antibiotics

2. Overuse of Pesticides

3. Climatic Changes

4. Travel

5. Lack of Necessary Vaccinations

The CDC, NIH and WHO are responsible for surveillance and responses to EIDs and the world’s health.

Re-emerging Infectious DiseasesRe-emerging Infectious DiseasesRIDsRIDs

• Old diseases that are occurring with increasing incidence.

1. Tuberculosis

2. Hantavirus

3. Plague

The Extent of Host Involvement The Extent of Host Involvement Local InfectionLocal Infection

• A local infection affects a small area of body

• Boil or Acne

Systemic InfectionSystemic Infection• Infection spread throughout the body via the

circulatory system• Mumps • Systemic Infections often lead to Focal Infections.• What is a Focal Infection?

Secondary InfectionSecondary Infection

• After the host is weakened from a primary infection, it is easier for them to become infected with a secondary infection due to a compromised immune system.

Unapparent or Subclinical InfectionUnapparent or Subclinical Infection• An apparently healthy individual carries the disease

organism and passes it on to others without expressing any symptoms of the illness.

• Poliovirus• Hepatitis A• HIV

Reservoirs of Reservoirs of InfectionInfection

For a disease to perpetuate itself, there must be continual organisms available and a source providing appropriate conditions.

Birds are Reservoirs for WNV

• Marine shellfish are the main reservoir of Cholera

ZoonosesZoonoses

• Diseases that affect wild and domestic animals and can be transmitted to humans.

• Lyme Disease

• Rabies

• Anthrax

• West Nile Virus

Transmission of ZoonosesTransmission of Zoonoses• Direct Contact with Infected Animals

• Direct Contact with Animal Waste

• Contamination of Food and Water

• Contaminated Hides, Fur, and Feathers

• Consuming Infected Animal Products

• Insect Vectors

Some Diseases Result from Pathogenic Some Diseases Result from Pathogenic Microorganisms Growing in or on Microorganisms Growing in or on

Nonliving Reservoirs Such as Soil and Nonliving Reservoirs Such as Soil and Water or ObjectsWater or Objects

• Ringworm

• Botulism

• Tetanus

Transmission of Transmission of DiseaseDisease

• Direct Transmission Indirect Transmission1. Close Personal Contact 1. Fomites

2. Touching, Kissing, etc. 2. Droplets/Airborne

3. Vehicles

4. Vectors

Direct Transmission

1. Personal Contact

2.Touching

Kissing

Sex

Etc.

Indirect TransmissionIndirect Transmission

• Fomites

Inanimate Objects

Tissues, Drinking Glasses, Needles

AIDS, Hepatitis

Indirect TransmissionIndirect Transmission• Transmission by a Medium

Water, Food, Air

Plague, Cholera

Indirect TransmissionIndirect Transmission

• Droplet Transmission

Saliva and Mucus

Coughing, Sneezing, Laughter

Less than 1 Meter

Indirect TransmissionIndirect Transmission

• Airborne Transmission

Carried on Water/Mucus Droplets

Greater than 1 Meter

Indirect TransmissionIndirect Transmission

• Vectors (Often Arthropod)1. Mechanical Means

Passive ProcessPathogens are on the body of the vector.Ex. Fly landing on food

Can you name a Disease Transmitted by this this Process?

Indirect Indirect Transmission Transmission

• Vectors (Often Arthropod)

2. Biological Means Active Process Vector must bite or scratch or sting. Ex. Mosquito Bite

Can you name a Disease Transmitted

by this process?

Routes of TransmissionRoutes of Transmission1. Vertical

Mother to Offspring- Transplacental: Rubella, Toxoplasma (Note: Humans only have two layers of

separation)- Perinatal: Listeria, Gonorrhea, Chlamydia- Breastfeeding: HIV

2. Horizontal Person to Person

- Contact Spread- Common Vehicle- Airborne- Vector-borne

Portals of Exit (Preferred Ways to Leave Portals of Exit (Preferred Ways to Leave the Body and Spread Infection)the Body and Spread Infection)

• Respiratory Tract

(Coughing or Sneezing)• Gastrointestinal Tract

(Saliva or Feces)• Urogenital Tract

(Secretions from the Vagina or Penis)

Arthropods and Syringes provide a portal of exit for microbes in blood.

Nosocomial InfectionsNosocomial Infections

• An infection that is acquired during the course of stay in a health facility.

• 2 million NI Yearly• 5-15% of All

Patients Acquire NI• 90,000 Die

The Rate of Nosocomial Infections Is Increasing

Trends in Nosocomial InfectionsTrends in Nosocomial Infections

• 1940’s – 1950’s Gram + S. aureus

• 1970’s Gram – E. coli

• 1980’s Gram + A.R. S. aureus

• 1990’s Both

• 2000’s No Relief in Sight

Frequency of Nosocomial Frequency of Nosocomial InfectionsInfections

Large Number of Skin Infections Due to Newborns

The Compromised Host is Most The Compromised Host is Most at Riskat Risk

1. Burns (Broken Skin)

2. Surgical Wounds (Broken Skin)

3. Suppressed Immune Systems (Due to Ill Health)

The Body Defends UsThe Body Defends Us

• Skin and Mucus Membranes• T-Lymphocytes Kill Pathogens• B-Lymphocytes Produce Antibodies

• Their Effectiveness if Altered By Many Things

- Drugs- Radiation- Steroids- Burns- Diabetes- Stress- Poor Nutrition

Chain of Transmission:Chain of Transmission:Nosocomial Infections Are Transmitted Nosocomial Infections Are Transmitted

By Direct Contact Between Staff By Direct Contact Between Staff Members and PatientsMembers and Patients

Fomites such as catheters, syringes, and respiratory devices can transmit nosocomial infections.

Control of Nosocomial InfectionsControl of Nosocomial Infections

1. Handwashing #1

2. Disinfect Equipment

3. Necessary Antibiotics Only

4. Infection Control Team

Could a copper door handle help to beat MRSA (2009 Study)?

• Doorknobs, bath taps, toilet handles and 'grab rails' will be ripped out and replaced with copper versions at Birmingham's Selly Oak hospital in a bid to beat MRSA

• MRSA has proven resistant to even the most powerful antibiotics. But hospital superbugs may finally have met their match - in copper door handles.

• Copper, used in medicines for 4,000 years, has been shown to be highly effective in killing off pathogens such as MRSA.

• In the trial study, copper grew 95% less bacteria.

Predisposing FactorsPredisposing Factors

• Gender

• Climate

• Age

• Fatigue

• Poor Nutrition

• Low Vitamin D

A Factor that Makes the Body More Susceptible A Factor that Makes the Body More Susceptible to Disease or Alters the Course of an Illness.to Disease or Alters the Course of an Illness.

EpidemiologyEpidemiology

• The study of the distribution and determination of health related events within a given population.

• The study of the transmission, incidence, and frequency of disease

1. Descriptive Epidemiology

2. Analytical Epidemiology

3. Experimental Epidemiology

Descriptive EpidemiologyDescriptive Epidemiology• Data about infected people are collected

and analyzed in descriptive epidemiology.

• Who, What, When, Where, How, etc.

Analytical EpidemiologyAnalytical Epidemiology

• A group of infected people is compared with an uninfected group.

• Analytical epidemiology aims to research and study risk and protector factors of diseases.

Relative Risk of Death on the Relative Risk of Death on the TitanicTitanic

308 154

142 709

Alive Dead

Female

Male

462

851

308 154

142 709

Alive Dead

Female

Male

462

851

Probability of Death for Females is 154 / 462 = .333 or 33%

Probability of Death for Males is 709 / 851 =.833 or 83%

RR = .833 / .333 = 2.5

There is a 2.5 greater probability of death for males than for females.

Experimental EpidemiologyExperimental Epidemiology• Use of controlled experiments designed to test

hypotheses are performed in experimental epidemiology.

• Example: In these studies normal guinea pigs were exposed to tuberculosis cage mates in two different degrees of crowding, some in ordinary cages, where the food became contaminated with the excreta, laden with tubercle bacilli, of the inoculated animals, and some in special cages with wire-mesh floors, where these excreta were largely excluded as a source of contagion.

Clinical TrialClinical Trial

HistoryHistory

• John Snow

• London Cholera Epidemic

• Broadstreet Pump

The CDC is the Main Source of The CDC is the Main Source of Epidemiological Information in the Epidemiological Information in the

United StatesUnited States