Exam 2 Clinical Microbiology

Predisposing Factors in a Host

• Nutrition

• Sex (UTIs vs pneumonia / meningitis)

• Genetic inheritance (HIV, cholera, COVID-19)

• Climate (respiratory illness)

• Environment (pollution, radiation)

• Vaccination

• Age (influenza)

• Lifestyle / behaviors (tobacco use, sedentary lifestyle, unsafe sexual practices / drug use)

• Compromised host (immunosuppression, pregnancy, “barrier disruption” ie burns, cuts)

Development of Diseases (periods)

1. Incubation Period

2. Prodromal Period

3. Period of Illness

4. Period of Decline

5. Period of Convalescence

Incubation Period

Infection to appearance of signs or symptoms

Prodromal Period

Early, mild symptoms (difficult to diagnose by these typically non-specific symptoms)

Period of Illness

Most severe disease condition; patient either overcomes diseases or dies

Period of Decline

Symptoms and signs decrease in severity

Period of Convalescence

Patient regains strength and recovers to pre-diseased state

Reserviors

Continual source of a microbe / virus

Examples of Reserviors

• Humans

• Animals

• Nonliving

Human Reserviors

• People with S&S

• Can also have inapparent infections or latent dz

Human Reserviors: Carriers

Have the pathogen and can transmit it

Human Reserviors: Incubating Carriers

Disease is in incubation period

Human Reserviors: Convalescent Carriers

Transmit during recovery

Human Reserviors: Chronic Carriers

Fully recovered but still transmit

Human Reserviors: Passive Carriers

Are not infected themselves but transmit pathogen accidentally from patient-to-patient

Animal Reserviors

• Zoonoses

• Malaria, Rabies, Lyme dz

Zoonoses

Diseases primarily in the wild and domestic animals that can be transmitted to humans

Nonliving Reserviors

• Soil (manure as fertilizer)

• Water (feces contamination = cholera)

• Foods (“food poisoning”, Salmonellosism botulism)

Duration of Disease

• Depends on the type of dz

• The average time that people have the disease (from the diagnosis until they are either cured or die)

Types of Disease Transmission

• Direct Contact Transmission

• Congenital Transmission

• Indirect Contact Transmission

• Droplet Transmission

• Vehicle Transmission

• Vector Transmission

Direct Contact Transmission

• Person-to-person

• No intermediate is needed

• Ex. Touching, kissing, sex, congenital transmission (childbirth)

Congenital Transmission

During childbirth

Indirect Contact Transmission

• Reservoir - Nonliving object - susceptible host

• Ex. Contaminated syringes, diapers, bedding, tissues, etc

Droplet Transmission

• Mucus droplets that travel through the air before falling

• Drop nuclei - 3 feet

• Aerosol - 6 feet

• Ex. COVID-19, influenza, pneumonia, whooping cough

Vehicle Transmission

• Airborne

• Waterborne

• Foodborne (ex. bacteria in meet, egg, etc come into contact with food that won’t be cooked)

Vector Transmission

• Arthropods, especially fleas, ticks, and mosquitos (bite into animal (reservoir) and bring to a new host)

• Transmit disease by mechanical or biological transmission

Vector Transmission: Mechanical Transmission

Arthropod carries pathogen on its feet

Vector Transmission: Biological Transmission

Pathogen reproduces in the vector; transmitted via bites or feces

Pathogenicity

The ability to cause dz

Virulence

The degree of pathogenicity

Portals of Entry

• Mucous membranes

• Skin

• Parental route

Portals of Entry: Mucous Membranes

• Lining of respiratory tract, digestive canal, genital systems, urinary system, and conjunctiva

Portals of Entry: Skin

• Sweat glands or hair follicles

• Hookworm larvae can bore through the skin

• Fungi may live on the keratin or infect skin

Portals of Entry: Parental Route

Deposited directly into tissues (beneath skin or mucous membranes) when barriers are penetrated

Portals of Exit

• Respiratory Tract

• Digestive Tract

• Genital System

• Skin

• Infected blood

What determines if a dz occurs?

1. Route of exposure

2. Number of invading microbes

3. Adherence

How does host damage occur?

• Siderophores

• Direct Damage

• Toxins: exotoxins and endotoxins

• Cytopathic effects

How do pathogens evade host defenses?

• Get inside cells

• Prevent phagocytosis

• Switch antigens

• Biofilm

• Break down defense against everything

How do pathogens penetrate host infections?

1. Capsules

2. Cell wall components

3. Enzymes (proteins that allow a rxn to happen)

4. Antigenic variation

5. Penetration into host

6. Biofilms

Pathogens Penetrate Host Infections: Capsule

• Resist phagocytosis

Pathogens Penetrate Host Infections: Enzymes

• Coagulates: cause blood to clot

• Kinases: break down blood clots

• Hyaluronidases: Dissolve cxns between human cells in CT

• Collagenases: Dissolve cxns between humans cells in CT

• IgA Proteases: Destroy antibodies produced by host

Pathogens Penetrate Host Infections: Antigenic Variation

A change in the antigens (molecules recognized by host immune system, specifically antibodies)

Pathogens Penetrate Host Infections: Penetration into the host

• Cause changes to the host cell which allows for bacterium to enter

• Prevents digestion of the microbe upon entering the host cell

Pathogens Penetrate Host Infections: Biofilms

• Resistance to disinfectants or antibiotics

• Prevent phagocytosis

Exotoxins

• Bacterial Source:

• Chemistry:

• Heat Stability:

• Toxicity:

• Fever-Producing:

• Immunology:

• Lethal Dose:

• Representative Diseases:

• Bacterial Source: Gram +

• Chemistry: Protein, usually with 2 parts (A-B)

• Heat Stability: Unstable, 60-80 C

• Toxicity: High

• Fever-Producing: No

• Immunology: Can be converted to toxoids to immunize against toxin; neutralized by antitoxin

• Lethal Dose: Small

• Live or Dead: Alive

• Representative Diseases: Gas gangrene, tetanus, botulism, diphtheria, scarlet fever

Endotoxins

• Bacterial Source:

• Chemistry:

• Heat Stability:

• Toxicity:

• Fever-Producing:

• Immunology:

• Lethal Dose:

• Representative Diseases:

• Bacterial Source: Gram -

• Chemistry: Lipid portion (lipid A) of LPS outer membrane

• Heat Stability: Stable, can withstand autoclaving 121 C for 1 hr

• Toxicity: Low

• Fever-Producing: Yes

• Immunology: Not easily neutralized by antitoxin, therefore, effective toxoids cannot be made to immunize against toxin

• Lethal Dose: Considerably larger

• Live or Dead: Alive or Dead

• Representative Diseases: Typhoid fever, UTIs, and meningococcal meningitis

IFR

• Estimates this proportion of deaths among all infected individuals

• Smaller than CFR

• Less lethal

CFR

• Estimates this proportion of deaths among identified confirmed cases. 

• # of deaths divided by # of infected people

• Within a certain period of time

• Have to be diagnosed

• More narrow

ID50

• Infectious Dose 50

• # of microbes required to cause an infection in 50% of a population of people

• Infection

LD50

• Lethal Dose 50

• The number of microbes required to kill 50% of a population

• Toxin

How to interpret data for ID50 and LD50

A smaller # means a more pathogenic or lethal microbe

What factors influence the normal microbiota?

• Nutrients that are available to the microbes

• Physical and chemical factors

• Host defenses

• Mechanical forces

How do normal microbial residents keep local condition in check to prevent the growth of pathogenic microbes?

• Competing for nutrients

• Secreting antimicrobial substances

• Maintaining pH

• Affecting oxygen levels

Relationship between Organisms: Symbiosis

2 organisms living together

Relationship between Organisms: Commensalism

1 organism benefits and the other is unaffected

Relationship between Organisms: Mutualism

Both organisms benefit

Relationship between Organisms: Parasitism

1 organism benefits at the expense of the other

Infection

• Invasion of colonization of a body

• Can be due to a microbe colonizing a location in the body that it normally doesn’t inhabit

Disease

The abnormal state brought on by a pathogenic organism

Exceptions to Koch’s Postulates

• Some microbes cannot be cultured

• Virus

• Some conditions are caused by multiple organisms

• Some infectious diseases are poorly defined

• Some pathogen can cause multiple disease conditions

Acute Dz

Disease develops rapidly, but short duration

Chronic Dz

Disease develops slowly, and duration is long

Subacute Dz

Disease develops more slowly than acute but faster than chronic

Latent Dz

Causative agent remains inactive for long period before causing illness

Herd Immunity

• Individuals get vaccinated or disease-induced immunity

• Leads to protecting children, those with immune disorders, and some cancer patients

Systemic Infection

Spread throughout the body by blood or lymph

Focal Infection

Systemic infection that started as a local infection but entered blood or lymph

Septicemia

Pathogens multiplying in the blood

Bacteremia

Bacteria in the blood

Toxemia

Bacterial toxins in the blood

Viremia

Viruses in the blood

Primary Infection

Acute, initial illness

Secondary Infection

Opportunistic pathogen gains access due to effects of primary infection

Sequence of Events for Infection and Disease

• Reservoir Exits

• Transmission to susceptible host

• Invasion

• Pathogenesis

What causes HAI’s?

1. Microbes in hospital

2. Compromised hosts

3. Chain of transmission

Compromised Hosts

• Broken skin or mucus membranes

• Immunocompromised

• Invasive procedures

Reasons for EID’s appearance (or increased frequency)

• Genetic exchange between organisms

• Evolution of an organism

• Antibiotic use and pesticide use

• Genetic instability, especially for RNA viruses

• Global warming

• Geographic import

• Insect vector import

• Ecological encroachment by people

• Animal control

• Decreased vaccine uptake

• Bioterrorism

Types of Epidemiology: Descriptive

Seeks to characterize the past or predict the future of a disease

Types of Epidemiology: Analytical

Seeks to determine the risk factors by matching groups

Types of Epidemiology: Experimental

Tests hypotheses, including clinical trials

Single Blind Study

Test individuals do not know if they get placebo or test substance / treatment

Double Blind Study

Test individual and clinician both do not know who gets placebo or treatment

Morbidity

Incidence of specific notifiable dz

Mortality

Number of deaths from notifiable dz

If a pathogen can evade the host’s first line of defense, they can cause damage by four ways:

1. Disrupts host cell fxn

2. Uses host cell nutrients

3. Produces waste produces

4. Multiples in host cells and causes ruptures

A-B Toxins: B

Binds to host cell receptor (protein on surface)

A-B Toxins: A

• Causes the activity of the toxin

• Enters the cell and alters cell physiology

• Chemical run

Membrane-disrupting Toxins

Host cells break open which hinders the host’s ability to prevent an infection

Superantigens

Cause a massive immune overreaction to an invading microbe, potentially leading to shock and / or death

Cardio

Heart

Hepato

Liver

Neuro

Nerve

Leuko

White

Erythro

Red

Geno

DNA

Cyte

Cell

Entero

Intestinal

What is shock?

A life-threatening decrease in blood pressure

Septic Shock

Caused by bacteria

Plasmids

• Small, circular DNAs that can carry genes that produce proteins for antibiotic resistance or virulence factors

• Easily transferrable from one bacterium to another which allows for a quick spread of antibiotic resistant or increased virulence