reflection

The Progress of an Infection • Pathogen:

• A microbe whose relationship with its host is parasitic and results in infection and disease.

• Disease: any deviation from health • Infectious disease: disruption of

a tissue or organ caused by microbes and their products

• Type and severity of infection depends on the pathogenicity of the organism and the condition of the host.

The Progress of Infection (cont’d) • Pathogenicity: an organism’s

potential to cause infection or disease • True pathogens: capable of causing

disease in healthy persons with normal immune defenses:

• Generally associated with a specific, recognizable disease

• May vary in severity from mild to severe to fatal

• Examples include the influenza virus, plague bacillus, and malarial protozoan.

The Progress of Infection (cont’d) • Opportunistic Pathogens:

• Cause disease when the host’s defenses are compromised or when they become established in a part of the body that is not natural to them

• Not considered pathogenic to a normal, healthy person

• Do not possess well-developed virulence properties

• Examples include Pseudomonas species and Candida albicans.

Primary Vs Secondary

• Primary pathogen is a virus, bacteria, fungi, or any other biological entity that causes a disease when it gains entry into a victim's body.

• The disease caused by the primary pathogen is usually one that stresses the victim's immune system. ...

• Secondary or opportunistic pathogens refers to this group of micro-organisms

The Progress of Infection • Virulence:

• The relative severity of a disease caused by a particular microbe

• The degree of pathogenicity • Virulence of a microbe is determined

by its ability to: • Establish itself in a host • Cause damage

• Virulence factor: any characteristic or structure of the microbe contributes to its ability to establish itself in the host and cause damage

What Kind of Infection? • Which is it? • Ebola • Staphylococcus aureus • Clostridium difficile • Bordatella pertussis • E. coli • Mycobacterium tuberculosis • Influenza • Candida albicans

Step One: Becoming Established – Portals of Entry

• Portal of entry: the route that a microbe takes to enter the tissues of the body to initiate an

infection • Exogenous: microbe originating

from a source outside the body from the environment or another person or animal

• Endogenous: microbe already existing on or in the body – normal biota or a previously silent infection

Portals of Entry

• The majority of pathogens have adapted to a specific portal of entry

• If certain pathogens enter the “wrong” portal, they will not be infectious.

• Inoculation of the nasal mucosa with the influenza virus will result in infection, but if the virus contacts the skin, no infection occurs.

• Occasionally, an infectious agent can enter by more than one portal:

• Mycobacterium tuberculosis can enter through both the respiratory and gastrointestinal tracts.

• Streptococcus and Staphylococcus can enter through the skin, urogenital tract, and the respiratory tract.

The Size of The Inoculum • Infectious Dose (ID):

• The minimum number of microbes necessary to cause an infection to proceed

• Microorganisms with smaller infectious doses have greater virulence.

• ID for rickettsia is a single cell. • ID for tuberculosis, giardiasis, and

coccidioidomycosis is about 10 cells. • ID for gonorrhea is 1,000 cells. • ID for typhoid fever is 10,000 cells. • ID for cholera is 1,000,000,000 cells.

Step Two: Becoming Established – Attaching to Host Cells

• Adhesion: • Process by which microbes gain a

more stable foothold on host tissues

• Dependent on binding between specific molecules on both the host and pathogen

• Pathogen is limited to only those cells (and organisms) to which it can bind.

• Firm attachment is almost always a prerequisite for causing disease, since the body has so many mechanisms for flushing microbes from tissues.

Step Three: Becoming Established – Surviving Host Defenses

• Phagocytes: cells that engulf and destroy host pathogens by means of enzymes and antimicrobial chemicals

• Antiphagocytic Factors: • Virulence factors that help

pathogens to avoid phagocytes • Leukocidins: kill phagocytes

outright (slime or capsule) makes it difficult for the phagocyte to engulf the pathogen

• Extracellular slime or capsule: makes it difficult to for phagocytes to engulf microbes

• Some bacteria survive inside the phagocyte.

Step Four: Causing Disease

• Virulence factors are simply adaptations a microbe uses to establish itself in a host.

• Three ways that microorganisms cause damage (disease) to their host:

• Directly through the action of enzymes

• Directly through the action of toxins (both endotoxins and exotoxins)

• Indirectly by inducing the host’s defenses to respond excessively or inappropriately

Extracellular Enzymes

• Exoenzymes: • Enzymes secreted by microbes that

break down and inflict damage on tissues

• Dissolve the host’s defense barriers to promote the spread of disease to other tissues

• Examples of Exoenzymes: • Mucinase: digests the protective

coating on mucous membranes • Hyaluronidase: digests the ground

substance that cements animal cells together

• Coagulase: causes clotting of blood or plasma

• Kinase: dissolves fibrin clots

Bacterial Toxins: A Potent Source of Cellular Damage

• Toxin: a specific chemical product of microbes, plants, and some animals that is poisonous to other organisms

• Toxins are named according to their target:

• Neurotoxins act on the nervous system.

• Enterotoxins act on the intestines. • Nephrotoxins damage the

kidneys. • Hemolysins disrupt the

cytoplasmic membrane of red blood cells.

Bacterial Toxins: A Potent Source of Cellular Damage

• Exotoxins: • Can cause damage to

the host by destroying cells or disrupting normal cellular metabolism

• Can be secreted or released during lysis of the cell

• Many different mechanisms

Exotoxins

• Mechanisms: • Aid in spreading

• Act on the extracellular matrix of connective tissue

• Collagenase by Clostridium perfringens

• Hyluronidase by S. aureus and S. pyogens

• DNAase by S. aureus and S. pyogens

• Exfoliative toxin by S. aureus

• Damage membranes • Either act as lipases or digest

phospholipids or form membrane pores

• Lecithinase by Clostridium perfringens

• Alpha toxin and delta toxin of S. aureus

• Hemolysins and leucocidin produced by S. pyogens

Exotoxins

• Mechanisms • Block protein synthesis

– Diptheria toxin produced by Mycobacterium diptheriae

– Exotoxin A produced by Pseudomonas aeroguinosa

• Block nerve function – Tetanus toxin (tetanospasmin) produced

by Clostridium tetani – Botulinium toxin produced by Clostridium

botulinium • Enterotoxins

– Cholera toxin produced by Vibrio cholerae – Shiga toxin produced by Shigella

dysenteriae – Shiga-like toxins produced by

Enterohemorraghic E. coli • Superantigens

– Toxic Shock Syndrome Toxin produced by S. aureus

– Enterotoxin produced by S. aureus – Streptococcal Pyrogenic Exotoxins

produced by S. pyogenes

Bacterial Toxins: A Potent Source of Cellular Damage

• Endotoxin: • Lipopolysaccharide (LPS), part

of the outer membrane of gram- negative cell walls

• Has a variety of systemic effects on tissues and organs

• Causes fever, inflammation, hemorrhage, and diarrhea

• Blood infections by Salmonella, Shigella, Neisseria meningitidis, and Escherichia coli are particularly dangerous.

The Process of Infection and Disease

• Establishment, Spread, and Pathologic Effects: • Microbes eventually settle in a particular target organ and cause damage

at the site: • Host tissues are weakened as a result of the multiplication of the

pathogen. • Pathogens obstruct tubular structures such as blood vessels,

lymphatic channels, fallopian tubes, and bile ducts. • Necrosis: accumulated damage due to pathogens leading to cell

and tissue death • Viruses destroy cells by multiplying and lysing them.

Necrosis

• Death of most or all of the cells in an organ or tissue due to disease, injury, or failure of the blood supply.

• When bacteria are involved it is called Necrotizing Fasciitis

• MRSA,Group A Streptococcus (group A strep), Klebsiella, Clostridium, Escherichia coli, Staphylococcus aureus, and Aeromonas hydrophila, Vibrio vulnificus

• Some viruses can mimic these symptoms as well

• Haemolytic viral diseases

Necrosis • Types

– Coagulative necrosis. – Liquefactive necrosis. – Caseous necrosis. – Fat necrosis. – Fibroid necrosis. – Gangrenous necrosis.

This Photo by Unknown Author is licensed under CC BY-NC-ND

Necrosis

• Coagulative Necrosis - accidental cell death typically caused by ischemia or infarction. In coagulative necrosis the architecture of dead tissue is preserved for at least a couple of days. ... Like most types of necrosis if enough viable cells are present around the affected area regeneration will usually occur

Necrosis Liquefactive Necrosis - (or colliquative necrosis) is a type of necrosis which results in a transformation of the tissue into a liquid viscous mass. Often it is associated with focal bacterial or fungal infections

Necrosis

Caseous Necrosis - is a form of cell death in which the tissue maintains a cheese-like appearance. The dead tissue appears as a soft and white proteinaceous dead cell mass. Often associated with TB infections

Necrosis

• Fat necrosis is characterized by the action upon fat by digestive enzymes

• Lipase releases fatty acids from triglycerides. The fatty acids then complex with calcium to form soaps. These soaps appear as white chalky deposits.It is usually associated with trauma of the pancreas or acute pancreatitis It can also occur in the breast, the salivary glands and in neonates after a traumatic delivery.

Necrosis

Fibrous Necrosis - in which there is accumulation of amorphous, basic, proteinaceous material in the tissue matrix with a staining pattern reminiscent of fibrin. It is associated with conditions such as immune vasculitis (e.g. polyarteritis nodosa), malignant hypertension, preeclampsia, or hyperacute transplant rejection.

Necrosis Gangrenous Necrosis - • Dry Gangrene occurs in the

absence of superimposed microbial infection and histologically manifests as Coagulative Necrosis.

• Wet Gangrene occurs when there is a superimposed microbial infection and histologically manifests as coagulative necrosis with certain areas taking on a morphology more akin to Liquifactive Necrosis

Signs and Symptoms: Warning Signals of Disease

• Sign: objective evidence of disease as noted by an observer

• Symptom: subjective evidence of disease as sensed by the patient

• Syndrome: a disease identified by a certain complex of signs and symptoms

Signs and Symptoms of Inflammation

• Signs: • Edema: the accumulation of fluid in afflicted

tissue • Granulomas and abscesses: walled-off

collections of inflammatory cells and microbes in the tissues

• Lymphadenitis: swollen lymph nodes • Symptoms:

• Fever • Pain • Soreness • Swelling

Signs of Infection in the Blood • Signs:

• Leukocytosis: increase in white blood cell levels

• Leukopenia: decrease in white blood cell levels

• Septicemia: a general state in which microorganisms are multiplying in the blood and are present in large numbers

• Bacteremia or viremia: bacteria or viruses are present in the blood but not multiplying

Infections That Go Unnoticed

• No noticeable symptoms are produced.

• Microbe is present in host tissues. • Host does not seek medical

attention. • These infections are known as

asymptomatic, subclinical, or inapparent.

Step Five: Vacating the Host – Portals of Exit

• Portal of Exit: • Specific avenue by which

pathogens exit • Shed through secretion,

excretion, discharge, or sloughed tissue

• High number of microbes in these materials increases the likelihood that the pathogen will reach other hosts.

• Portal of exit is usually the same as the portal of entry, but some pathogens use a different route.

The Persistence of Microbes and Pathologic Conditions • Latency: a dormant state of microbes

in certain chronic infectious diseases: • Viral latency: herpes simplex,

herpes zoster, hepatitis B, AIDS, Epstein-Barr

• Bacterial/protozoan latency: syphilis, typhoid fever, tuberculosis, malaria

• Sequelae: long-term or permanent damage to tissues or organs caused by infectious disease

• Meningitis: deafness • Strep throat: rheumatic heart

disease • Lyme disease: arthritis • Polio: paralysis

What Happens in Your Body

• Incubation period: • The time from initial contact with the infectious

agent to the appearance of symptoms • Agent is multiplying at the portal of entry but

has not caused enough damage to elicit symptoms.

• Varies according to host resistance, degree of virulence, and distance between the target organ and the portal of entry.

• Ranges from several hours to several years. • Majority of infections range from 2 and 30

days.

What Happens in Your Body

• Prodromal Stage: • 1 – 2 day period when the earliest

notable symptoms of infection appear

• Vague feeling of discomfort: head and muscle aches, fatigue, upset stomach, general malaise

• Period of Invasion: • Infectious agent multiplies at high

levels, exhibits greatest toxicity, becomes well established in host tissue

• Marked by fever and other prominent and specific signs and symptoms

• Extremely variable in length of period

What Happens in Your Body • Illness

• Presentation of some or all of the classical signs and symptoms of the disease are present in the sick individual

What Happens in Your Body • Convalescent Period:

• Patient begins to respond to the infection and symptoms decline.

• Patient’s strength and health gradually return due to the healing nature of the immune response.

• Many patients stop taking antibiotics during this period, even though pathogens are still in their system leading to antibiotic resistance.

What Happens in Your Body

• Transmissibility of Microbes:

• Incubation period: measles released during this period

• Invasive period: Shigella released during this period

• All periods: hepatitis B

Reservoirs: Where Pathogens Persist

• Reservoir: • Primary habitat in the natural

world from which a pathogen originates

• Often a human or animal carrier

• Also soil, water, and plants • Transmitter: individual or object

from which an infection is acquired • Syphilis: reservoir and

transmitter are the same • Hepatitis A: reservoir is a

human, transmitter is food

Living Reservoirs

• A great number of infections that affect humans have their reservoirs in other humans. Persons or animals with symptomatic infection are obvious sources.

• Carrier: an individual who inconspicuously shelters a pathogen, spreads it to others without any notice, and who may not have experienced disease due to the microbe.

Animals as Reservoirs and Sources

• The majority of animal reservoir agents are arthropods such as fleas, mosquitoes, flies, and ticks.

• Biological vector: actively participates in a pathogen’s life cycle, serving as a site in which it can multiply or complete its life cycle

• Mechanical vector: carries the microbe more or less accidentally on its body parts

• Larger animals can also spread infection: • Mammals: rabies • Birds: psittacosis • Lizards: salmonellosis

Animals as Reservoirs and Sources • Zoonosis: an infection indigenous to

animals but naturally transmissible to humans

• Humans are essentially dead-end hosts that do not contribute to the natural persistence of the microbe.

• Some zoonotic infections have multihost involvement.

• Some have complex life cycles in the wild.

• Zoonotic spread of disease is promoted by close associations between humans and animals.

Animals as Reservoirs and Sources

• Zoonosis (cont’d): • Make up a full 70% of all new

emerging diseases worldwide • Impossible to eradicate without

also eradicating the animal reservoir

• Attempts have been made to eradicate mosquitoes and certain rodents

• In 2004, China slaughtered thousands of civet cats thought to be the reservoir of SARS.

Nonliving Reservoirs • Most microbes that thrive in the soil

and water are saprobic and cause little harm and considerable benefit to humans.

• Some are opportunists and a few are regular pathogens.

• Because humans are in regular contact with environmental sources, acquisition of pathogens from natural habitats is important in diagnosis of disease and epidemiological studies.

The Acquisition and Transmission of Infectious Agents

• Communicable: a disease in which an infected host can transmit the infectious agent to another host and establish infection in that host

• Infectious is synonymous with communicable. • Contagious: a disease that is highly communicable,

especially through direct contact • Influenza and measles are highly contagious. • Hansen’s disease (leprosy) is only weakly

communicable.

The Acquisition and Transmission of Infectious Agents (cont’d)

• Noncommunicable: an infectious disease that does not arise through transmission of the infectious agent from host to host

• Compromised person is invaded by their own microbiota.

• Individual has accidental contact with a microbe that exists in a nonliving reservoir.

• Infected persons do not become a source of disease to others.

Patterns of Transmission in Communicable Diseases

• Direct or indirect contact with animate or inanimate objects

• Horizontal transfer: disease is spread through a population from one infected individual to another

• Vertical transfer: disease is transmitted from parent to offspring

• Two major modes of transmission: • Direct contact • Indirect transmission in which

some vehicle is involved

Patterns of Transmission in Communicable Diseases

• Biting vectors of infectious disease can transmit disease through:

• Injecting infected saliva into the blood (mosquito)

• Defecate around the bite wound (flea) • Regurgitate blood into the wound (tse

tse fly) • Mechanical vectors:

• Not necessary to the life cycle of the infectious agent

• External body parts of the animal become contaminated when they come into physical contact with a source of pathogens.

• Agent is transferred to humans indirectly by an intermediate such as food.

Healthcare-Associated Infections

• Healthcare-associated or nosocomial infections:

• Infections acquired or developed during a hospital stay

• From 0.1 – 20% of all admitted patients, with an average of 5%

• 2 – 4 million cases a year, resulting in 90,000 deaths

• 8 million in additional days of hospitalization and an increased cost of $5 – 10 billion

Healthcare-Associated Infections • Factors tied to healthcare-

associated infections: • Compromised patients • Collection point for pathogens • Lowered defenses permit

normal biota to enter the body • Infections acquired directly or

indirectly from fomites, medical equipment, other patients, medical personnel, visitors, air, and water

Healthcare-Associated Infections

• Healthcare processes that lead to healthcare- associated infections:

• Treatments using reusable instruments such as respirators and thermometers

• Indwelling devices such as catheters, prosthetic heart valves, grafts, drainage tubes, and tracheostomy tubes form ready portals of entry

• High proportion of the hospital population receives antimicrobial therapy, drug- resistant microbes are selected for at a much higher rate

Healthcare- Associated Infections

• Most common healthcare-associated infections:

• Urinary tract, respiratory tract, surgical incisions

• Gram-negative intestinal biota (Escherichia coli, Klebsiella, Pseudomonas) cultured in more than half of the patients with nosocomial infections

• Gram-positive bacteria (staphylococci and streptococci) and yeasts make up the rest.

• True pathogens such as Mycobacterium tuberculosis, Salmonella, hepatitis B, and influenza can be transmitted as well.

Healthcare-Associated Infections

• Control of healthcare-associated infections: • Medicaid and Medicare no longer reimburse hospitals for

catheter-related UTIs, vascular catheter-associated infections, and surgical site infections.

• Infection control officer: implements proper practices and procedures, tracks potential outbreaks, identifies breaches in asepsis, and trains health care workers in aseptic techniques

• Nurses and caregivers are regularly exposed to needlesticks, infectious secretions, blood, and physical contact with patients; they need to be especially aware of infection control

Universal Blood and Body Fluid Precautions

• Health care worker precautions: • Health care workers with active,

draining skin or mucous membrane lesions must refrain from handling patients or equipment that will come into contact with patients.

• Pregnant health care workers risk infecting their fetuses and must pay attention to these guidelines.

• Personnel should be protected by vaccination whenever possible.

Which Agent Is the Cause? Using Koch’s Postulates

• Etiologic/causative agent: the cause of infection and disease

• Koch’s postulates: • A series of proofs that

became the standard for determining causation of infectious disease

• Continue to play an essential role in modern epidemiology

• Reliable for many diseases, but cannot be completely fulfilled in certain situations

Which Agent Is the Cause? Using Koch’s Postulates

• Exceptions to Koch’s postulates: • Some infectious agents

cannot be readily isolated or grown in the laboratory.

• Some infections cannot be elicited in animals; viruses have a limited host range, human viruses will only cause disease in humans, etc.

• Not possible to determine causation in polymicrobial diseases