INFECTIOUS DISEASE 1. Symbiotic Relationships Between Microbes and Their Hosts Symbiosis means “to...

INFECTIOUS DISEASE

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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

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Infection

• Commensual: Equal advantage to host and pathogen. They both benefit, but not because of the other.

• Indifference: Advantage to one, no disadvantage to the other.

• Parasitism: Advantage to one, disadvantage to the other.

• Symbiosis: Synergistic Commensualism (Both have advantage that neither can have alone.

• Normal Flora: Organism is always on or in us; GI, GU, oral mucosa.

• Sterile areas of the body: Blood, CSF. Any organism here indicates something is wrong. The first indicator is decreased glucose, increased protein

• Opportunistic Pathogens: A normal flora organism that becomes a pathogen when the host’s immune defense decreases.

• Trauma, Surgery, Burns: overcomes barriers of defense• Catheterization: allows increased access and decreased

defense• Chemotherapy: e.g. ablative (for CA) destroys bone marrow, therefore myeloid and lymphoid immunity goes down.• Co-infection: e.g. haemophilic influenza is 2° to viral influenza.

Tissue Tropism

• Tissue Tropism (organisms are selective of tissues they infect): influenza does not affect your hand; gonorrhea only effects mucosa. Tropism can also be species, organ, or non-specific.

• HIV integrates a provirus into our chromosome. Antibodies actually assist the HIV organisms because opsinization helps to internalize the virus. Because of almost no cell mediated immunity (T-cells are infected), AIDS patients die from TB, cytomegalovirus (CMV), Candida, pneumocystis. When a person has a second infection, it is called a CO-INFECTION.

OBLIGATE PATHOGENS

• Will always cause infection and disease whenever and wherever they are encountered (e.g. Yersinia pestis plague, anthrax, smallpox) unless you are immune. However, they don’t want to kill their host.

Virulence• VIRULENCE: Ability to cause infection and disease. • MULTIPLICITY OF INFECTION (INNOCULUM): the number of organisms

needed to cause disease. There is an inverse relationship between virulence and Multiplicity of Infection.

• Obligate pathogens are virulent, even with a low inoculum, because they are effective. Most innoculum needs 103-5 organisms. Only 10 organisms can form an innoculum in a virulent organism such as anthrax.

• Anthrax avoids immune defenses by exploiting the very mechanisms used to fight it. It becomes activated after phagocytosis.

• Mycobacterium will coat the wall of vacuoles so lysozymes can’t fuse.• Rickettsia is on a timer, and escapes the vacuole to invade the nucleus.

PORTALS OF ENTRY (POE)

• CEPHALIC (7 PORTALS): Mouth, nose, eyes, ears.

• CORPOREAL: Mammary, Vaginal, Urethral, Rectal

• TRAUMA/MEDICAL: Burn, Compound Fracture, surgical/catheter, injury/IVDA, abnormal mucosa (CA chemo).

MODES OF TRANSMISSION (MOT)

• AEROSOL: Airborne micro-particles (soil aerosol containing endospores)

• DROPLET NUCLEI: Mucoid micro-droplet via cough or sneeze, durable on surfaces, mainly transmitted by contact.

• DIRECT CONTACT: Direct object/tissue-to-tissue contact.• CASUAL TRANSMISSION: handshake, clothing• ASPIRATION: inhalation or oral, GI, or food-borne

organisms• FECAL-ORAL: autoinoculation or contamination (poor hygiene)• SEXUAL TRANSMISSION (STD): sexual/bodily fluid contact

AGENTS OF TRANSMISSION

• VECTOR: a living organism that spreads disease from one host to another.

(mosquitoes, ticks, rats, humans)• FOMITE: inanimate object that spreads

disease from one host to another. (toothbrush, water glass, toys, handles)

HOST-PATHOGEN RELATIONSHIP (HPR)

• INFECTION: presence of organism• DISEASE: adverse symptoms due to infection• NORMAL FLORA: organism typically found on health individual• PATHOGEN: organism causing disease (etiologic agent)• IMMUNOCOMPROMISED: suppressed or deficient immunity• NOSOCOMIAL: acquired in hospital setting• COMMUNITY-ACQUIRED: acquired in routine, day-to-day activities• OPPORTUNISTIC PATHOGEN: normal flora + compromised pathogen• OBLIGATE PATHOGEN: always causes Dz if present• PATHOGENESIS (Px): events leading to Dz (POEDz)• MULTIPLICITY OF INFECTION (MOI): inoculum required for infxn• INCUBATION (INC): time from transmission to Dz• VIRULENCE: measure of Dz capability• VIRULENCE FACTOR (VF): ultrastructure, exoenzyme, or exotoxin

BACTERIAL SYMPTOM TERMINOLOGY

• BACTEREMIA: bacteria in bloodstream• BACTERURIA: bacteria in urine (normal or pathogenic flora)• SEPTICEMIA: Gram negative bacteremia• PYEMIA: Gram + bacteremia• PURULENT: pus-producing, reaches an opening to drain out• PYROGENIC: fever-producing infection or bacterial components• PYOGENIC: pus producing; infxn where neutrophils are 1° immune cells

GRANULOMATOUS: infxn where macrophages are 1° immune cells (no pus)• DIFFERENTIAL DIAGNOSIS: all possible causes of the disease.• UROSEPSIS: Septicemia from UTI; requires organism to be present.• FACULTATIVE INTRACELLULAR PARASITES: are not obligate

pathogens. They can survive temporarily in white cells, such as PMN’s, Monocytes, Macrophages, and super-killer macrophages.

• EXOTOXINS: e.g. pesticin, hemolysins, shigatoxins, choleragen, enterotoxins, plasminogen activating factor, coagulase, etc.

• ENDOTOXINS: e.g. unusual LPS and LOS.


• Normal Microbiota in Hosts– Also termed normal flora and indigenous

microbiota– Organisms that colonize the body’s surfaces

without normally causing disease– Two types

• Resident microbiota• Transient microbiota

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– Resident microbiota• Are a part of the normal microbiota throughout life• Are mostly commensal

– Transient microbiota• Remain in the body for short period• Found in the same regions as resident microbiota• Cannot persist in the body

– Competition from other microorganisms– Elimination by the body’s defense cells– Chemical or physical changes in the body

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– Acquisition of normal microbiota• Development in womb free of microorganisms

(axenic)• Microbiota begin to develop during birthing

process• Much of one’s resident microbiota established

during first months of life

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• How Normal Microbiota Become Opportunistic Pathogens– Opportunistic pathogens

• Normal microbiota that cause disease under certain circumstances

– Conditions that provide opportunities for pathogens

• Introduction of normal microbiota into unusual site in body

• Immune suppression• Changes in the normal microbiota

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

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Inflammation

Host defense summary

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Cell surface markers

• Designated as “CD”– Cluster of Differentiation– used to identify specific structures on a cell– ~200 different designations

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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– Animal reservoir– Human carriers– Nonliving reservoir

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Reservoirs of Infectious Diseases of Humans

• Animal Reservoirs– Zoonoses

• Diseases naturally spread from animal host to humans

– Acquire zoonoses through various routes• Direct contact with animal or its waste• Eating animals• Bloodsucking arthropods

– Humans are usually dead-end host to zoonotic pathogens

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• Human Carriers– Infected individuals who are asymptomatic but

infective to others– Some individuals eventually develop illness while

others never get sick– Healthy carriers may have defensive systems that

protect them

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• Nonliving Reservoirs – Soil, water, and food can be reservoirs of infection

• Presence of microorganisms often due to contamination by feces or urine

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The Movement of Microbes into Hosts: Infection

• 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

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• Portals of Entry – Sites through which pathogens enter the body– Four major pathways

• Skin• Mucous membranes• Placenta• Parenteral route

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Routes by which humans acquire parasitic infections

Figure 23.1

Routes of entry for invading pathogens

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Portals of exit

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• 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

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• Portals of Entry

– Mucous membranes• 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

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• Portals of Entry

– Placenta• Typically forms effective barrier to pathogens• Pathogens may cross the placenta and infect the fetus

– Can cause spontaneous abortion, birth defects, premature birth

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• Portals of Entry – Parenteral route

• Not a true portal of entry• Means by which the portal of entry can be

circumvented• Pathogens deposited directly into tissues beneath the

skin or mucous membranes

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• 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

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• The Role of Adhesion in Infection – Attachment proteins help in adhesion

• 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

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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

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The Nature of Infectious Disease • 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

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• Cause of Disease: Etiology– Study of the cause of disease– Germ theory of disease

• Disease caused by infections of pathogenic microorganisms

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

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Koch’s Postulates

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• Causation of Disease: Etiology– Exceptions to Koch’s postulates

• Some pathogens can’t be cultured in the laboratory• Diseases caused by a combination of pathogens and

other cofactors• Ethical considerations prevent applying Koch’s

postulates to pathogens that require a human host

– Difficulties in satisfying Koch’s postulates• Diseases can be caused by more than one pathogen• Pathogens that are ignored as potential causes of

disease

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• Virulence Factors of Infectious Agents– Pathogenicity

• Ability of a microorganism to cause disease– Virulence

• Degree of pathogenicity• Virulence factors contribute to virulence

– Adhesion factors– Biofilms– Extracellular enzymes– Toxins– Antiphagocytic factors

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• Virulence Factors of Infectious Agents– Extracellular enzymes

• Secreted by the pathogen• Dissolve structural chemicals in the body• Help pathogen maintain infection, invade, and avoid

body defenses

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• Virulence Factors of Infectious Agents– Toxins

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

• Toxemia refers to toxins in the bloodstream that are carried beyond the site of infection

• Two types– Exotoxins– Endotoxins

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• Virulence Factors of Infectious Agents– Antiphagocytic factors

• Factors prevent phagocytosis by the host’s phagocytic cells

– Bacterial capsule » Composed of chemicals not recognized as foreign» Slippery; difficult for phagocytes to engulf bacteria

– Antiphagocytic chemicals» Prevent fusion of lysosome and phagocytic vesicles» Leukocidins directly destroy phagocytic white blood cells

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• The Stages of Infectious Disease– The disease process occurs following infection– Many infectious diseases have five stages

following infection• Incubation period• Prodromal period• Illness• Decline• Convalescence

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The stages of infectious disease

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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

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Portals of exit

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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– Contact transmission

• Direct, indirect, or droplet

– Vehicle transmission• Airborne, waterborne, or foodborne

– Vector transmission• Biological or mechanical

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Classification of Infectious Diseases

• Diseases can be classified in number of ways– The body system they affect– Taxonomic categories– Their longevity and severity– How they are spread to their host– The effects they have on populations (rather than

on individuals)

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Classification of Infectious Diseases• Terms used to classify infectious disease

– Acute disease– Chronic disease– Subacute disease– Latent disease– Communicable– Contagious

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EPIDEMIOLOGY

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Epidemiology of Infectious Diseases

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INFECTION: Presence of microbeDISEASE: Symptomatic consequence of 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

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The incidence and estimated prevalence of AIDS

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Epidemiologists report data in a number of ways

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Different terms for the occurrence of disease

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Epidemics Defined Relative to Expected Number of Cases

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• 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 (or first case) of the disease

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• Epidemiological Studies– Analytical epidemiology

• Seeks to determine the probable cause (etiology), 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

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• Epidemiological Studies– Experimental epidemiology

• Involves testing a hypothesis concerning the cause of a disease

• Application of Koch’s postulates is experimental epidemiology

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• 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

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The interplay of factors that result in nosocomial infections

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• Hospital Epidemiology: Nosocomial Infections– Control of nosocomial infections

• Precautions designed to reduce factors that result in disease

• Hand washing is the most effective way to reduce nosocomial infections

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• Epidemiology and Public Health– Agencies at the local, state, national, and global

level share information concerning disease• The United States Public Health Service• World Health Organization (WHO)

– Public health agencies work to limit disease transmission

• Monitor water and food safety– Public health agencies campaign to educate the

public on healthful choices to limit disease

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Basic Principles of Microbial Control

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