Infection, Infectious Diseases, and Epidemiology

Chapter 14

Mammals have elaborate physical, chemical, and immunological defenses that protect against disease-causing microbes.

However, every fortress has its weakness.

Pathogenic microbes exploit those weaknesses, and the result is disease.

The fundamental question of microbial pathogenesis is this:

How an organism too small to be seen with the naked eye can kill a human a million times larger.

Introduction

Symbiotic Relationships Between Microbes and Their Hosts

• Symbiosis means "to live together"

• We have symbiotic relationships with countless microorganisms

• Types of symbiosis

• Mutualism

• Commensalism

• Parasitism

Normal Microbiota in Hosts

Organisms that colonize the body's surfaces without normally causing disease

Also termed normal flora and indigenous microbiota

Two types:

Resident microbiota

Transient microbiota

Bacterial flora benefit host by preventing overgrowth of harmful microbes – microbial antagonism

Endogenous infections – occur when normal flora is introduced to a site that was previously sterile

Normal Microbiota in Hosts

Resident microbiota

Are a part of the normal microbiota throughout life

Are mostly commensal

Less influenced by hygiene

Transient microbiotaRemain in the body for short period

Found in the same regions as resident microbiota

Competition from other microorganisms

Elimination by the body's defense cells

Influenced by hygiene

Acquisition of normal microbiota

Development in womb free of microorganisms

Microbiota begin to develop during birthing process

Much of one's resident microbiota established during first months of life

How Normal Microbiota Become Opportunistic Pathogens

Opportunistic pathogens: Normal microbiota that cause disease under certain circumstances

Conditions that provide opportunities for pathogens

1) Introduction of normal microbiota into unusual site in body

2) Immune suppression

3) Changes in the normal microbiota

4) Changes in relative abundance may allow opportunity for a member to thrive and cause disease

Reservoirs of Infectious Diseases of Humans

Most pathogens cannot survive for long outside of their host

Reservoirs of infection: Sites where pathogens are maintained as a source of infection

Three types of reservoirs:

1) Animal reservoir

2) Human carriers

3) Nonliving reservoir

Animal Reservoirs

Zoonoses: Diseases naturally spread from animal host to humans

Acquire zoonoses through various routes:

1) Direct contact with animal or its waste

2) Eating animals

3) Bloodsucking arthropods (Also review pages 372-373 in chapter 12)

Humans are usually dead-end host to zoonotic pathogens

Impossible to eradicate

Human Carriers

Asymptomatic infected individuals can be infective to others

Some individuals eventually develop illness while others never get sick

Healthy carriers may have defensive systems that protect them

Typhoid Mary (Mary Mallon)

Source: PBS/NOVA

Article in New York American, June 20, 1909

http://www.pbs.org/wgbh/nova/typhoid/

http://www.pbs.org/wgbh/nova/body/disease-detective.html

Nonliving Reservoirs

Soil, water, and food can be reservoirs of infection

Presence of microorganisms often due to contamination by feces or urine

Airborne – droplet nuclei, aerosols

Vehicle – inanimate material, food, water, biological products, fomites

Fomites consist of both porous and nonporous surfaces or objects that can become contaminated with pathogenic microorganisms and serve as vehicles in transmission

Exposure to Microbes: Contamination and Infection

Contamination: The mere presence of microbes in or on the body

Infection: When organism evades body's external defenses, multiplies, and becomes established in the body

Infectious disease: an infection that causes damage or disruption to tissues and organs

Endogenous agents

normal flora

Exogenous agents

originate from source outside the body

Morbidity: diseased stateMortality: death

Contact

Invasion

Infection

Colonization with

microbiota

Effects of microbes

resulting in injury or tissue

damage

Immune defense prevails

Morbidity/Mortality can occur

Immunity/Damage repair

Carrier state

Concept of an infectious dose (ID)

Infectious dose: Minimum number of microbes required for successful infection

Microbes with small IDs have greater virulence

Lack of ID will not result in infection

www.mass.gov

Portals of Entry

Portal of entry: Sites through which pathogens enter the body

Three major pathways:

1) Skin

2) Mucous membranes

3) Placenta

Entry via the parenteral route circumvents the usual portals

Portals of Entry : Skin

Outer layer of dead skin cells acts as a barrier to pathogens

Some pathogens can enter through openings or cuts

Others enter by burrowing into or digesting outer layers of skin

Line the body cavities that are open to the environment

Provide a moist, warm environment hospitable to pathogens

Respiratory tract is the most common site of entry

Entry is through the nose, mouth, or eyes

Gastrointestinal tract may be route of entry

Must survive the acidic pH of the stomach

Portals of Entry : Mucous membranes

Typically forms effective barrier to pathogens

Pathogens may cross the placenta and infect the fetus

Can cause spontaneous abortion, birth defects, premature birth

Portals of Entry : Placenta

STORCH - Syphilis, Toxoplasmosis, Other diseases (hepatitis B, HIV-1/AIDS

and chlamydia), Rubella, Cytomegalovirus and Herpes simplex virus

Pathogens that infect during pregnancy

http://phil.cdc.gov/

N Engl J Med 2010; 362:833

Not a true portal of entry

Means by which portals of entry can be circumvented

Pathogens deposited directly into tissues beneath the skin or mucous membranes

Portals of Entry : Parenteral route

The Role of Adhesion in Infection

Process by which microorganisms attach themselves to cells

Required to successfully establish colonies within the host

Uses adhesion factors

Specialized structures

Attachment proteins

The Role of Adhesion in Infection

Attachment proteins help in adhesion and found on viruses and many bacteria

Viral or bacterial ligands bind host cell receptors

Interaction can determine host cell specificity

Changing/blocking a ligand or its receptor can prevent infection

Inability to make attachment proteins or adhesins renders microorganisms avirulent

Some bacterial pathogens attach to each other to form a biofilm

The Nature of Infectious Disease

Infection is the invasion of the host by a pathogen

Disease results if the invading pathogen alters normal body functions

Disease is also referred to as morbidity

Manifestations of Disease: Symptoms, Signs, and Syndromes

Symptoms: Subjective characteristics of disease felt only by the patient

Signs :Objective manifestations of disease observed or measured by others

Syndrome: Symptoms and signs that characterize a disease or abnormal condition

Asymptomatic, or subclinical infections lack symptoms but may still have signs of infection

Causation of Disease: Etiology

Etiology: Study of the cause of disease

Diseases have various causes

Using Koch's postulates to determine etiology

Germ theory of disease

Infections by pathogenic microorganisms cause disease

Robert Koch developed a set of postulates one must satisfy to prove a particular pathogen causes a particular disease

Koch’s postulates

1. Find evidence of a particular microbe in every case of a disease

2. Isolate that microbe from an infected subject and cultivate it artificially in the laboratory

3. Inoculate a susceptible healthy subject with the laboratory isolate and observe the resultant disease

4. Re-isolate the agent from this subject

Exceptions to Koch's postulates

Some pathogens can't be cultured in the laboratory

Diseases caused by a combination of pathogens and other cofactors

Diseases can be caused by more than one pathogen

Ethical considerations prevent applying Koch's postulates to pathogens that require a human host

Virulence Factors of Infectious Agents

Pathogenicity: Ability of a microorganism to cause disease

Virulence: Degree of pathogenicity

Virulence factors contribute to virulence

1) Adhesion factors

2) Biofilms

3) Extracellular enzymes

4) Toxins

5) Antiphagocytic factors

Virulence Factors: Extracellular enzymes

Secreted by the pathogen

Dissolve structural chemicals in the body

Help pathogen maintain infection, invade, and avoid body defenses

Important to virulence of the pathogen

Mutant species that do not secrete the enzymes are often avirulent

Chemicals that harm tissues or trigger host immune responses that cause damage

Toxemia refers to the presence of toxins in the bloodstream

The toxins are carried beyond the site of infection

Two types: Exotoxins and Endotoxins

Virulence Factors: Toxins

A-B Exotoxins

The A (active) component is attached to the B (binding)component

The A component inhibits a cellular protein to cause the damage

Toxin precursor (inactive)

A chain

B chain

A

B

Binding site

B chain attaches to receptor

A

B

Host cell membrane with specific receptor

Endocytosis

Vacuole formation

A

B

B

A

A portion of toxin is released from vacuole

Toxin acts on ribosomes and blocks protein synthesis; causes cell death

Virulence Factors: ExotoxinsPLAY

Virulence Factors: Exotoxins

Virulence Factors: EndotoxinsPLAY

Virulence Factors: Endotoxins

Factors prevent phagocytosis by the host's phagocytic cells

Allow pathogens to remain in a host for longer time

Bacterial capsule

Composed of chemicals not recognized as foreign

Slippery and difficult for phagocytes to engulf

Antiphagocytic chemicals

Prevent fusion of lysosome and phagocytic vesicles

Leukocidins directly destroy phagocytic white blood cells

Virulence Factors: Antiphagocytic factors

Phagocytosis: Microbes That Evade ItPLAY

Phagocytosis: Microbes That Evade It

The Stages of Infectious Disease

The disease process occurs following infection

Many infectious diseases have five stages following infection

1)Incubation period

2) Prodromal period

3) Illness

4) Decline

5)Convalescence

The Movement of Pathogens Out of Hosts: Portals of Exit

Pathogens leave host through portals of exit

Many portals of exit are the same as portals of entry

Pathogens often leave hosts in materials the body secretes or excretes

Modes of Infectious Disease Transmission

Transmission is from a reservoir or a portal of exit to another host's portal of entry

Three groups of transmission:

1) Contact transmission

2) Vehicle transmission

3) Vector transmission

Contact TransmissionDirect contact transmission

Usually involves body contact between hosts

Transmission within a single individual can also occur

Indirect contact transmission

Pathogens are spread from host to host by fomites

Droplet transmission

Spread of pathogens in droplets of mucus by exhaling, coughing, and sneezing

Fomites consist of both porous and nonporous surfaces or objects that can become contaminated with pathogenic microorganisms and serve as vehicles in transmission

Vehicle Transmission

Airborne transmission

When pathogens travel more than 1 meter via an aerosol

Aerosols can occur from various activities

Sneezing, coughing, air-conditioning systems, sweeping

Waterborne transmission

Important in the spread of many gastrointestinal diseases

Fecal-oral infection

Foodborne transmission

Spread of pathogens in and on foods

Inadequately processed, cooked, or refrigerated foods

Foods may become contaminated with feces

Bodily fluid transmission

Bodily fluids such as blood, urine, saliva can carry pathogens

Prevent contact with conjunctiva or breaks in the skin or mucous

membranes

Vehicle Transmission

Vector Transmission

Biological vectors

Transmit pathogens and serve as host for some stage of the pathogen's life cycle

Biting arthropods transmit many diseases to humans

Mechanical vectors

Passively transmit pathogens present on their body to new hosts

Classification of Infectious DiseasesLocalized infection

(boil)Systemic infection (influenza)

Focal infection

Frequency of Disease

Track occurrence of diseases using two measures

Incidence

Number of new cases of a disease in a given area during a given period of time

Prevalence

Number of total cases of a disease in a given area during a given period of time

Occurrence also evaluated in terms of frequency and geographic distribution

Different terms for the occurrence of disease.

Pandemic – epidemic across continents

Sporadic – when occasional cases are reported at irregular intervals

Epidemic – when prevalence of a disease is increasing beyond what is expected

Endemic – disease that exhibits a relatively steady frequency over a long period of time in a particular geographic locale

Epidemiological Studies: Descriptive epidemiology

Careful tabulation of data concerning a disease

Record location and time of the cases of disease

Collect patient information

Try to identify the index case of the disease

Seeks to determine the probable cause, mode of transmission, and methods of prevention

Useful in situations when Koch's postulates can't be applied

Often retrospective

Investigation occurs after an outbreak has occurred

Epidemiological Studies: Analytical epidemiology

Test a hypothesis concerning the cause of a disease

Application of Koch's postulates

Epidemiological Studies: Experimental epidemiology

Hospital Epidemiology: Nosocomial Infections

Types of nosocomial infections

Exogenous: Pathogen acquired from the health care environment

Endogenous: Pathogen arises from normal microbiota due to factors within the health care setting

Iatrogenic: Results from modern medical procedures

Superinfections: Use of antimicrobial drugs reduces competition from some resident microbiota – other microbes may thrive

The interplay of factors that result in nosocomial infections.

Control of nosocomial infections

Requires aggressive control measures

Handwashing is the most effective way to reduce nosocomial infections

Universal precautions - stringent measures to prevent the spread ofnosocomial infections from patient to patient, from patient to worker, and from worker to patient

Based on the assumption that all patient specimens could harbor infectious agents, so must be treated with the same degree of care

Epidemiology and Public Health

Sharing of data among public health organizations

Agencies at the local, state, national, and global level share information concerning disease

The United States Public Health Service

National public health agency: CDC is one branch

World Health Organization (WHO):Coordinates public health efforts worldwide

Role of public health agencies in interrupting disease transmission

Public health agencies work to limit disease transmission

• Monitor water and food safety

• Work to reduce disease vectors and reservoirs

• Establish and enforce immunization schedules

• Locate and treat individuals exposed to contagious pathogens

• Establish isolation and quarantine measures

Public health education

Public health agencies campaign to educate the public on healthful choices to limit disease

http://www.cdc.gov/tuskegee/timeline.htm