Microbio Lecture 4 Notes

Pathogen

Disease-causing microbe

Pathogenicity

Ability of an infectious agent to cause a disease

Pathogenesis

Sequential steps involved in the development of a disease

Colonization

Initial act of a microbe establishing its presence in the host

Infection

Multiplication and invasion of a pathogen resulting in illness

What are the 2 categories of illnesses that pathogens can cause in humans?

Infectious diseases or Microbial intoxications

Infectious disease

Illness that occurs after a pathogen colonizes the body and subsequently invades host tissues

Microbial intoxication

Illness that occurs after a person ingests a toxin that has been produced by a pathogen in vitro

Microbial antagonism

Human microbiota may inhibit the growth of foreign microbes

Infectious Disease Phases

1. Incubation period

2. Prodromal period

3. Period of illness

4. Convalescent period

Incubation period

Time between entry of the pathogen and onset of signs/ symptoms

• Influenced by the type and number of pathogens that enter the host, as well as the overall health and nutritional status of the host

• May be short (1-3 days for influenza), intermediate (2-3 weeks for chickenpox) or long (months for HIV)

Prodromal period

Time during which a patient feels like they are “coming down with something”

• Characterized by non-specific signs/symptoms such as mild fever, fatigue, body ache, and headache

Period of illness

Time during which a patient experiences typical signs/symptoms

• Characterized by tissue damage and inflammation

• Signs/symptoms aid in diagnosis (e.g. fever and sore throat in influenza, blistering red rash in chickenpox)

• Communicable diseases are easily transmitted

Convalescent period

Time during which a patient recovers (if disease is not fatal)

• Varies in duration and is characterized by progressive elimination of the pathogen, repair of damaged tissues, and resolution of signs/symptoms

Signs

Objective evidence of disease

• Observed by a healthcare professional and measured through physical exams or lab tests

• Ex. Elevated blood pressure, abnormal heart sounds, elevated body temperature, abnormal pulse rate, enlarged liver or spleen

Symptoms

Subjective evidence of disease

• Experienced by a patient and subsequently reported to a healthcare professional

• Ex. Aches or pains, ringing in the ears, blurry vision, nausea, dizziness, chills

Localized infections

Confined to a single organ or region of the body

• Some pathogens are site-specific and are restricted in their capacity to invade other tissues

• Helicobacter pylori causes peptic ulcers but has not been implicated in other disorders

Systemic infections

Widespread and affect the entire body

• Some pathogens can spread by gaining access to the blood or lymphatic channels

• Mycobacterium tuberculosis can disseminate from the lungs to the liver, spleen, kidneys, and skin

What’s an example of a localized infection?

Peptic ulcer is a mucosal break or erosion in the stomach or duodenum - Usually measures 5mm or larger in diameter

What is an example of a systemic infection?

Cutaneous lesions of disseminated tuberculosis in a child - Appear as small red spots that can develop into ulcers and abscesses

Primary infection

First disease (because sometimes one infectious disease may follow another infectious disease)

Secondary infection

Second disease

General Steps in Pathogenesis

1. Penetration of the skin or mucous membranes - (ex. Clostridium tetani through skin wounds, HIV through the genital mucosa)

2. Introduction directly into the blood - (ex. hepatitis B or C viruses through sharing contaminated needles to inject drugs)

3. Inoculation into body tissues - (ex. Plasmodium vivax through the bite of an infected female Anopheles mosquito)

4. Inhalation - (ex. influenza viruses through droplet inhalation)

5. Ingestion - (ex. hepatitis A virus through drinking contaminated water)

Virulence

Expresses the degree of pathogenicity

• Some pathogens are more virulent than others, ex. they are better able to cause a disease

Shigella and Salmonella

• 10 Shigella cells are sufficient to cause shigellosis, but >100 Salmonella cells are needed to cause salmonellosis

• Conclusion - Shigella is more virulent than Salmonella

Streptococcus pyogenes

“Flesh-eating” strains are more virulent than those that cause acute pharyngitis (strep throat)

Virulence factors

Attributes of pathogen that enable them to attach to host cells, invade tissues, escape destruction, and cause disease

Virulence factors can be grouped into what groups?

1. Adhesion factors

2. Invasion factors

3. Evasion factors

4. Toxins

Adhesion Factors

Enable pathogens to attach to and colonize specific host cells at different anatomical sites

Adhesins

Special molecules on the surface of pathogens that help them recognize and bind to specific host cell receptors

Ex. Attachment of HIV to CD4+ helper T cells

Pili (fimbriae)

Hair-like flexible structures composed of piling that enable bacteria to anchor themselves to body surfaces

Fimbriated strains

Can attach to the inner walls of the urethra and cause urethritis

Non-fimbriated strains

Cannot attach and are flushed out during urination

Invasion Factors

Facilitate the penetration of anatomical barriers and cause damage to the host tissues

Exoenzymes

Enzymes released by pathogens (as opposed to end-enzymes which remain within cells to catalyze intracellular reactions)

Necrotizing enzymes

Some proteases and lipases can cause extensive tissue destruction

Necrotizing fasciitis

Rapid destruction of soft tissues

Evasion Factors

Enable pathogens to evade (i.e. escape) normal host defense mechanisms

Capsules

Protect bacterial cells from being engulfed by phagocytes

Antigenic variation

Mechanism by which some pathogens can alter their surfaces molecules (proteins, carbohydrates, or lipids) in order to evade a host immune response

• Mechanism also allows pathogens to cause re-infection of hosts (who might have developed immunity after the original infection) as the altered surface antigens are not recognized by the host’s immune system

Drifts

Minor antigenic variations

Shifts

Major antigenic variations

Toxins

Poisonous substances produced by pathogens

Toxins can be categorized as what?

Endotoxins or exotoxins

Endotoxins

• Lipopolysaccharides that constitute an integral part of the cell wall structure of Gram-negative bacteria

• Passively released during cell lysis and can cause serious, adverse effects in humans

Septicemia

Septicemia is a systemic illness following the invasion of the bloodstream by virulent Gram-negative bacteria

• Characterized by fever, chills, and extreme exhaustion that may progress to life threatening septic shock

Exotoxins

• Proteins that are actively secreted by pathogens

• Cause damage to the host by disrupting normal cellular metabolism and destroying cells

Enterotoxins

Exotoxins that affect the GI tract and cause diarrhea or vomiting

Neurotoxins

Exotoxins that affect the CNS and block the transmission of nerve impulses

Opisthotonus

Abnormal posture seen in severe tetanus where the back becomes extremely arched due to muscle spasms

How can you properly diagnose infectious diseases?

Proper diagnosis of infectious diseases requires:

• Taking a complete patient history

• Conducting a thorough physical exam

• Evaluating a patient’s signs and symptoms

• Implementing the appropriate selection, collection, transport, and processing of clinical specimens

What are clinical specimen?

Biological materials collected from patients for processing in a lab. Ex. – Blood, urine, cerebrospinal fluid (CSF), sputum, throat swabs, wound specimens, fecal specimens

What needs to be exercised during clinical specimen collection?

Caution needs to be exercised during the collection, transport, and processing of clinical specimens

• Requires a close working relationship among members of the healthcare team

• Lab professionals conduct tests for pathogens and generate test results

  • Findings assist clinicians to correctly diagnose infectious diseases and initiate treatment

Clinical Specimen Quality

High-quality specimens are required to achieve accurate, clinically relevant lab results for proper diagnoses of infectious diseases

Improper specimen selection, collection, or transport may result in:

• Inability to find the pathogen due to its absence or its destruction

• Masking of the pathogen due to an overgrowth of human microbiota

• Inability to correctly identify the pathogen due to contamination

Specimen Selection

Appropriate type of specimen should be collected for the diagnosis of a suspected infectious disease

Specimen Collection

• Specimen should be obtained preferably before initiating antimicrobial therapy

• Specimen should be obtained from a site where the suspected pathogen is most likely to be found

• Sufficient quantity of the specimen should be obtained for all required lab tests

• Care should be taken to avoid discomfort

• Specimen should be collected in a sterile, disposable container to prevent contamination

• Specimen container should be properly labeled and accompanied by a lab test requisition form

Specimen transport

• Specimen should be protected from excessive heat or cold and promptly delivered to the lab

• Hazardous specimens must be handled with even greater care to avoid contamination of couriers, patients, and healthcare professionals

Blood is made up of what?

Cellular components (45%) + Plasma (55%)

What is hematology?

Study of blood

Bacteremia

Presence of bacteria in the bloodstream

• May or may not be a sign of disease

• Can occur temporarily after vigorous brushing of teeth, tooth extraction, or oral surgery

• Can also occur during certain stages of some infectious diseases (e.g. pneumonia, typhoid fever)

  Bacteremia is not the same as septicemia!

Phlebotomy

Procedure in which a needle is used to draw blood by puncturing a vein

Urine

Urine is normally sterile in the bladder, but becomes contaminated by microbiota of the distal urethra during voiding

Contamination can be reduced by collecting what?

Clean-catch midstream urine specimen

“Clean-catch”

Area around the external opening of the urethra is cleaned with an antiseptic wipe or using soap and water to remove the resident microbiota

“Midstream”

Initial stream of urine is directed into the toilet rather than the specimen collection container to flush out the resident microbiota from the distal urethra

Cerebrospinal fluid

Cerebrospinal fluid is a clear filtrate of blood plasma in the:

• Four ventricles of the brain

• Central canal of the spinal cord

• Intracranial subarachnoid space

• Spinal subarachnoid space

• CSF acts as a cushion and serves as a medium for the diffusion of nutrients, electrolytes, and metabolic wastes

Lumbar puncture (spinal tap)

Procedure in which a needle is used to collect CSF into a sterile tube

• Technically complex procedure in which a needle is inserted into the subarachnoid space between L3 and L4 (below the level of the spinal cord)

STAT specimens

Abbreviation of the Latin word “static” which means “immediately”.

• CSF specimens should be transported to the lab within 15 minutes to initiate an immediate workup

Sputum

Pus that accumulates deep within the lungs of a patient with pneumonia, tuberculosis, or any other lower respiratory tract infection

• Specimens labeled “sputum” are often just saliva

Throat Swabs

Throat swabs are often used to test for acute pharyngitis caused by S. pyogenes

• Signs and symptoms - Pain while swallowing, fever, and swollen tonsils (in absence of cough)

Wounds

• Swabs are used to obtain specimens from shallow wounds

• Needles and syringes are used to aspirate pus from deeper wounds

• Need to specify the type of wound

  • Dog bite? Burn wound? Surgical wound?

Feces

• Fecal specimens should be collected at the lab and processed immediately

• Combination of direct microscopic examination,

  culture, biochemical tests, and immunologic tests may be performed

  • Helps in the identification of Gram negative and Gram- positive bacteria, fungi, intestinal protozoa, and intestinal helminths

Clinical health

Deals with personal healthcare issues (at the individual level)

• Examples of professions – Nurses, dentists, physicians, surgeons, physical therapists

• Focuses on treatment

Public health

Deals with health issues from the perspective of populations (not individuals)

• Examples of professions – Epidemiologists, behavioral health scientists, biostatisticians, environmental health scientists, health policy professionals

• Focuses on prevention

Epidemiology (simple definition)

Branch of public health that deals with studying the spread and control of diseases in populations

Epidemiology (formal definition)

Study of the distribution and determinants of health-related states or events in specified populations and the application of this study to control health problems

Distribution

Person (who?), place (where?), time (when?)

Determinants

Risk factors, protective factors

Descriptive epidemiology

Descriptive epidemiology deals with the distribution of disease

• Descriptive studies estimate disease frequency and evaluate time trends but do not provide strong evidence for or against causal relationships

Analytic epidemiology

Analytic epidemiology deals with the determinants of disease

• Analytic studies test hypotheses in order to evaluate potential causal relationships

Who is Austin Bradford Hill?

• British epidemiologist and statistician

• 1950 – Demonstrated the link between smoking and lung cancer with Sir Richard Doll

• 1965 – Presented a group of nine criteria to deduce whether a causal relationship exists between an exposure and a disease

• Note – Criteria work together, not in isolation

What were Bradford Hill’s Criteria?

• Strength of association - How strong is the relationship?

• Consistency - Have other studies found similar results?

• Specificity - Does one exposure lead to one disease?

• Temporality - Does the exposure precede the disease?

• Biological gradient - Is there a dose-response effect?

• Plausibility - Is there a reasonable biological explanation?

• Coherence - Do new findings align with accepted facts about the disease?

• Experimentation - Does cessation of the exposure result in resolution of the disease?

• Analogy - Has an analogous relationship been observed between similar exposures and similar diseases?

How can we get a measure of association? (risk ratio)

• Research studies have shown that over a 10-year period:

• 11% of individuals with evidence of H. pylori infection develop peptic ulcers

• 0.8% of individuals without evidence of H. pylori infection develop peptic ulcers

• Dividing these figures gives us a measure of association: Risk ratio = 11/0.8 = 13.75

What is so special about temporality?

Perhaps the only criterion that is required to establish a causal relationship

Dose-response effect

Does the disease severity increase with increasing levels of exposure?

Incidence

New cases of a disease (or other health condition) in a specified population that develop over a period of time

Two commonly used measures - risk and rate

Prevalence

Existing cases of a disease (or other health condition) in a specified population over a certain period of time

Mortality

Deaths due to a disease in a specified population that occur over a period of time

Endemic

Usual level or the constant presence of a disease within a specified population or geographic area (ex. chickenpox among young school children)

Epidemic

Occurrence of disease at a higher level than what is normally expected in a population (ex. cholera in London in 1854)

Pandemic

Epidemic simultaneously occurring across countries or continents (ex. COVID-19 across the world in 2020)

Epidemiologic Triad

Basic model to study health problems

3 factors:

1. Host - age, race, sex, previous diseases, family history, etc

2. Environment - temperature, altitude, crowding, housing, neighborhood, food, etc

3. Agent - biologic (bacteria, viral), chemical (poison, alcohol, smoke), physical (trauma, fire), nutrition (lack, excess)

   Disease is produced by exposure of a susceptible host to an noxious agent in the presence of environmental factors that aid or hinder agents of disease

Chain of Infection

1. Source of infection (the pathogen)

2. Reservoir

3. Portal of exit

4. Mode of transmission

5. Portal of entry

6. Susceptible host

Reservoirs

Principal habitats of pathogens

Living reservoirs

Humans, animals, and arthropods

Non-living reservoirs

Air, soil, dust, contaminated water and foods, and fomites

Humans

Individuals with current infection – People who have an infectious disease in whom the pathogen is surviving and multiplying

Carriers – People who are colonized with a particular pathogen which is not currently causing an infectious disease but can be transmitted to others

Zoonotic diseases or Zoonoses

Humans can acquire infectious diseases from animal sources

• May be acquired by direct contact (ex. rabies virus is transmitted through a dog bite or a cat bite)

• May be acquired by inhalation or ingestion (ex. anthrax spores dispersed in the air or in undercooked meat)

Arthropods

Insects (ex. fleas, mosquitoes) and arachnids (ex. mites, ticks) can serve as reservoirs