Infectious disease principle (EXAM 2)

What are infectious diseases

diseases caused by pathogens (bacteria, viruses, fungi, parasites, and prions)

**prions are the worst theres no defense against them

how are infections spread

person to person, insects/animals (vector), contaminated food/water, fomites (furniture)

what are the first symptoms of infectious diseases

fever and fatigue

who are most vulnerable to infectious diseases

very young, elderly, immunocompromised, poor socioeconomic status

how is an infection established

microorganism enters host and multiples which results in tissue injury (directly though cytotoxins and indirectly through inflammatory response)

first line of defense against establishment of infection

physical and chemical barriers

inflammation

Physical barriers to infection

squamous epithelium (first line)

mucous membranes containing lysozymes

chemical barriers to infection

innate immunity activated by foreign proteins

Vascular response to inflammation

vasodilation and increased capillary blood flow (causing heat and redness)

increased vascular permeability; accumulation of fluid in tissues (swelling, pain, and Impaired function)

infiltration of leukocytes

when are plasma derived mediators activated

during inflammatory response

the kinin system

plasma derived mediator

activated by coagulation factor XII

increases vascular permeability (MC bradykinin) leading to vasodilation

bradykinin results in pain and itching

the clotting system

plasma derived mediators

converts plasma protein to fribrinogen then fibrin (component of exudate, crusting, discharge)

Fibrinolytic system

plasma derived mediator

forms plasmin which breaks down fibrin (gets rid of scab)

the complement system

plasma derived mediators

helps our immune system

protein, chemotactic for neutrophils, increase vascular permeability, stimulate release of histamine from mast cells and adhere to surface of bacteria

C3a, c5A, C4a

in the complement system

activate mast cells to release histamine

C3b

in complement system

opsonin (opsonization)

tags making more susceptible for phagocytosis

C5a

in complement system

vasodilation, inc vascular permeability, neutrophil activation

MAC (membrane attack complex) (C5b-C9)

lipid dissolving agent (cell lysis)

help break down cells

part of complement system

histamine

cell derived mediators

mast cells and basophils (when injured)

triggers vasodilation and vascular permeability

serotonin

cell derived mediators

from platelets

increase vascular permeability and vasodilation

prostaglandins

vascular permeability

pain and fever

cell derived mediator

Leukotrienes

vascular permeability

migrate neutrophils

cell derived mediator

Lysosomal compounds

from neutrophils

increase vascular permeability

cell derived mediator

platelet activating factor

platelet aggregation and vasodilation

cell derived mediator

cytokines

secreted from immune cells

inflammation mainly produced by T helper cells and macrophages

cell derived mediator

nitric oxide and oxygen

pro inflammatory mediator

produced by macrophages

toxic to bacteria

cell derived mediator

what is the goal of the inflammatory response

to remove foreign protein and limit the extent of tissue damage

first line and nonspecific

doesn't require prior contact

can be triggered bu infections and non-infections (trauma)

steps in the inflammatory response

acute phase: cells release histamine; vascular permeability and vasodilation and vasodilation

Subacute proliferative phase: inflammation phase; clotting factors and enzymes contrast and plug injuries blood vessels to prevent blood from entering injuries site; signs of inflammation begin

Proliferative phase: blood platelets send chemical signals to move cells in for healing; cells produce collagen to form scar tissue

Remodeling phase: decreased inflammation, complete healing

acute inflammation

first symptoms is redness and heat due to vasodilation

pain and swelling follow

chronic inflammation

response of macrophages and lymphocytes instead of neutrophils

fibroblast proliferation rather than exudates

granuloma formation (associated with fb)

subclinical carrier

asymptomatic carrier

no clinical findings

subacute patient presentation

mild symptoms (not as acute as acute)

acute patient presentation

clinical disease with specific signs and symptoms

anything from self limiting to severe disease

chronic patient presentation

continuous, long term with exacerbations and remission

colonization

presence of microorganisms in or on a host with growth and multiplication but without tissue invasion or damage

commensalism

A relationship between two organisms in which one organism benefits and the other is unaffected

mutualism

A relationship between two species in which both species benefit

(ex: e.coli)

Parasitic

A relationship between two organisms of different species where one benefits and the other is harmed

saprophytes

organisms that live on dead organic matter

virulence

ability to infect and cause a disease

capsule increases virulence

pathogen

very virulent

normal flora

bacteria that colonize skin and mucous membranes w/o causing infection

prevent pathogen colonization

synthesize vitamins

potentially harmful (endogenous disease)

opportunistic pathogen

endogenous organism that is normally commensal that can cause disease and become a pathogen when the hosts resistance is altered

eukaryotes

chromosomes contained in distinct nucleus

prokaryotes

single celled organism without a distinct nucleus with a membrane nor other specialized organelles

virus

cannot replicate on their own

not eukaryotes or prokaryotes

most common infections

respiratory infections (flu, adenovirus, RSV)

meningitis/encephalitis

life cycle of viruses

Attachment via a specific protein on the capsid, to a receptor on the host cell

Viral entry via fusion, endocytosis and release of contents into host cell

Once inside the cell the viral genome is copied, viral proteins produced. The mRNA encoding viral genes are translated into viral proteins using host ribosomes. The viral proteins produced vary from virus to virus and include capsid proteins, envelope proteins, proteins that can block host defenses or assist with viral replication

Viral particles are assembled from the viral proteins and copies of the viral genome.

Complete viral particles are released from the cell and infect other cells.

retrovirus

▪ After entry into host cell viral RNA translated into DNA by viral enzyme reverse transcriptase. Viral DNA is integrated into host chromosome and exists latently

▪ Reactivation requires reversal of this process.

▪ Ex/ Human retroviruses: HIV-1 and HIV-2

oncogenic viruses (oncoviruses)

▪ transform host cells into malignant cells on replication. Ex/ retroviruses and DNA viruses such as herpesviruses ex/HPV (human papillomaviruses) and cervical cancer , EBV and lymphoma

RNA viruses

▪ the common cold, influenza, hepatitis C, West Nile fever, polio and measles, rotavirus

viral diseases

▪ Stop synthesis of normal cell proteins: RNA and DNA

▪ Some weaken cell membranes and lysosomal membranes

▪ Some viral proteins are toxic to cells, immune defenses also may kill virus-infected cells.

parasite advantage

▪ Parasite has advantage (nutrients); presence is usually detrimental to the host. Transmission usually fecal-oral

protozoa

▪ microscopic, unicellular eukaryotes, motile

malaria

Plasmodium Protozoa; transmitted by mosquitos. Reside within RBC; reoccurring cycles of fevers, chills, and other non-specific symptoms

Babesiosis

▪ spread by Ixodes scapularis tick. Infects RBCs. Fever, chills, sweating, headache, body aches, loss of appetite, nausea, fatigue, hemolytic anemia.

Toxoplasmosis (Toxoplasma Gondii)

▪ can lead to brain abscesses in HIV patients with a CD4 T Cell count <200. Transmission: undercooked pork, exposure to cat feces. MRI or CT scan show ring enhancing lesions

Trypanosoma cruzi

trypanosomiasis (Chagas disease, African Sleeping Sickness)

Tape worms (cestodes)

flat bodies with hooks or mouths for attachment

Flukes (trematodes)

▪ Flat bodies with mouth or hooks for attachment: intestinal and urinary: Burrow in skin, travel to lungs, liver, bladder, GI tract

Ascaris lumbricoides (nematode)

type of round worm

fecal oral, common worldwide: Swallow food/water contaminated with eggs, larvae hatch, go to liver, then lungs and alveoli, crawl to trachea, swallowed, travel to small intestine, develop into worms and release eggs, colonic obstruction, biliary obstruction, intestinal perforation

Helminths

parasitic worms

▪ Multicellular: three main life-cycle stages: eggs, larvae, adults

▪ Drugs that kill helminths are frequently very toxic to human cells

arthropods

Presence of an exoskeleton, jointed appendages, and a body composed of specialized regional segments

(ex: ticks, mosquitos)

Ectoparasites

▪ infest body surface, localized tissue damage and inflammation due to bite or burrowing of arthropod

▪ Present with erythematous, edematous eruptions with papules and urticaria common with bites and stings.

▪ Toxic venom can result in systemic autonomic instability, neurotoxicity, organ failure

bacteria

contain circular double stranded DNA and cell walls (except mycoplasma)

have plasmid to increase virulence and resistance

Cocci divide in chains called streptococci, divide in pairs (diplococci), clusters (staphylococci)

Community of bacteria=biofilm; make antibitocs to work harder

growth parameters for fastidious, anaerobes, aerobes, and facultative anaerobe

Fastidious: strict growth; cannot live outside human body (ex: neisseria gonorrhea)

Anaerobes: cannot survive in oxygen rich environment

Aerobes: require oxygen to survive

Facultative anaerobe: adapt metabolism to aerobic or anaerobic conditions: Fermentation , aerobic cellular respiration

how are bacteria identified

gram stain (purple-gram positive)

acid fast stain (membrane resists decolorization of primary stain when treated with acid alcohol.) (ex: TB mycobacteria)

gram positive vs gram negative

Gram +: thick peptidoglycan layer that holds the crystal violet stain

Gram - cannot hold crystal violet stain, counterstained by safranin (red). Have antibiotic-inactivating enzymes. Endotoxins are in outer cell wall especially worry in sepsis (usually gram negative)

How bacteria are identified (review chart)

types of gram stains

giemsa stain; usually stains fungus but also bacteria; stain blood cells and bone marrow samples, can stain chromosomes, parasites; stains nuclei dark blue/pink by binding to DNA; is perfered for malaria

india ink; stain is not taken up by polysaccharide capsule ; transparent halo; good for any encapsulated species

silver stain; used for fungi and bacteria and psuedomonis; turns black

Bacteria: Spirochetes

gram negative coiled rods

anaerobic

Leptospira: Transmitted from infected urine to humans through mucus membranes and can produce fatal Weil syndrome (jaundice, renal, hemorrhage).

Treponema : transmission is direct contact with Treponema pallidum (syphilis)

Borrelia: transmission is animal to human through bite of vector (lice/ticks). (relapsing fever (Borrelia recurrentis), Lyme disease (Borrelia Burgdorferi)

Bacteria - Mycoplasma

Prokaryote, absence of cell wall, flexible cell membrane containing cholesterol

Not visible on gram stain, resistant to beta lactam antibiotics, glycopeptide antibiotics (penicillin and cephalosporins)

Limited metabolic activity, not culturable on standard culture media, requires specialized media with sterols

Can grow under aerobic, anaerobic conditions (facultative)

Primarily affects the respiratory tract by attaching to respiratory epithelium, atypical pneumonia.

Smallest free-living organism; doesn’t live in the cell

diagnosed by PCR

overview of bacterial infections (need to know bacteria and where it causes infection) (image)

gram negative bacteria (chart need to know)

▪ Names by genus followed by species

▪ H2S: hydrogen sulfide producing organism

▪ Oxidase positive: aerobic

▪ Lactose fermenting: produce acidic byproducts

gram positive bacteria (chart need to know)

▪ Catalase positive: enzyme that converts hydrogen peroxide to water and oxygen gas: (sample will bubble)

▪ Coagulase positive: ability to clot blood plasma. Coagulase-positive staphylococci are the most pathogenic species S aureus. (increases virulence)

▪ Acid fast: bacterium have ability to resist decolorization by acids during staining procedures.

Rickettsia and Chlamydia

▪ Vector borne, obligate intracellular pathogen

▪ Have a rigid peptidoglycan cell wall, reproduce by cellular division, contain RNA and DNA like bacteria (don’t gram stain well), depend on host for nutrition

▪ Rickettsiae: transmission to humans via arthropods (fleas/ticks) bites, Ex/ Rickettsia rickettsii: Rocky Mountain spotted fever

▪ Chlamydiae: does not require arthropod vector

Chlamydia trachomatis: genitourinary sexually transmitted disease, ocular infections and pneumonia in newborns. (not usual in eyes and lungs)

Chlamydia pneumoniae: chlamydia pneumonia in those with underlying pulmonary disease (immunocompromised)

prions

▪ Protein without DNA or RNA. No reproductive and metabolic functions (antibiotics don’t work)

▪ Degeneration of neurons; slowly progressive, non-inflammatory results in loss of coordination (ataxia), dementia, death: spongiform encephalopathies (holes in brain) (neurodegenerative disease)

▪ No treatment

▪ Prion associated disease: Creutzfeldt-Jakob disease (CJD): in humans; rapid neurodegeneration causing brain to develop holes

fungi (mycotic)

▪ Primary occur in immunocompetent, and those that occur in immunocompromised. Can be local (skin related; ringworm or vaginal; yeast infection) or systemic (mainly immunocompromised).

▪ Eukaryotic

▪ Yeast

unicellular fungi, reproduce by budding, reproduce slower than bacteria

-Buds that do not separate form long chains of yeast cells called pseudohyphae

-Ex/ Candida albicans forms pseudohyphae

▪ Mold

-multicellular colonies, clumps of intertwined branching hyphae grow by longitudinal extension and produce spores (aspergillosis)

▪ Dimorphic fungi

-Can grow as yeast or mold depending on the environmental conditions: usually grow as a yeast at body temperature and mold at colder temperatures:

-Ex/ Histoplasma, Blastomyces, Coccidioides

Fungi

▪ Inhalation of fungal spores into lungs or direct contact

▪ Dermatophytes: superficial infections in immunocompetent patients; incapable of growing at core body temp, infection limited to cooler cutaneous surfaces. Ringworm, athlete’s foot

▪ Rigid cell wall with non-peptidoglycan layer so PCN does not work

▪ Rarely causes clinical syndromes in immunocompetent hosts. Self-limited infections of skin and subcutaneous tissue(puncture wounds or inhalation): opportunistic infection; found in immunosuppressed patients

Fungi Morphology

▪ Spores: reproductive structure of molds, Coccidioidomycosis and histoplasmosis are transmitted by inhalation of asexual species

▪ Hyphae: long, threadlike, branching, filamentous, tubular structure composed of fungal cells attached end to end, grow by extending from the ends of the tubules

▪ Cell membrane: innermost layer contains ergosterol which is analogous to cholesterol: amphotericin B and nystatin (antifungals) bind to ergosterol, ketoconazole inhibits ergosterol synthesis

▪ Cell wall: surrounds cell membrane, contains complex carbohydrates; explains calcification in chronic infections. can become potent allergen.

▪ Capsule: polysaccharide coating surrounding the cell wall, capsule increases virulence. visualized with India ink stain

Where is Candida, aspergillosis, Tinea, histoplasma/cryptococcus, cryptococcal meningitis found

▪ Candida: found in skin, GI tract (esophagus), lungs

▪ Aspergillosis: found in lungs

▪ Tinea: skin

▪ Histoplasma, Cryptococcus: lungs

▪ Cryptococcal meningitis : meningitis in AIDS patients

Prevalence and incidence

▪ Prevalence: total number of people in a specific group population who have a certain disease, condition; existing cases

▪ Incidence: proportion or rate of persons who develop a condition during a particular time period.

disease occurrence

▪ Endemic: Incidence (new cases) and prevalence (existing cases) are as expected and stable.

▪ Epidemic: abrupt and unexpected increase in the incidence over endemic rates.

▪ Pandemic: epidemic that has spread over several countries or continents, usually affecting a large number of people Morbidity

reasons for an epidemic

▪ Increased virulence of the agent

▪ Introduction of agent into a new setting where it has not been before

▪ Enhanced mode of transmission

▪ Change in susceptibility of the host response to the agent

▪ Increased host exposure

stages of infectious disease

Incubation: Pathogen begins active replication, asymptomatic. Timing can be short (Salmonella food poisoning 6-24 hours vs HIV can be years); dependent on host immune system, dose, and method of infection

Prodrome: Initial appearance of non-specific symptoms in host. Constitutional symptoms (infectious disease): mild fever, myalgia, headache, fatigue (inflammatory response)

Acute stage: Rapid proliferation of pathogen. Immune response results in tissue damage and inflammation. (max impact; specific symptoms)

Convalescent stage: progressive elimination and tissue repair.

Resolution: complete elimination fo the pathogen; no residual symptoms

barriers to resolution (abscess and Biomedical implants)

▪ Abscess: host can contain the infection however unable to eradicate. Usually require surgical drainage.

▪ Biomedical implants: catheters, artificial heart valves, prosthetic bone implants. Infectious agent colonizes surface of implant and creates a biofilm. Usually needs to be removed because antibiotics don’t work against biofilm.

site specific symptoms (-itis in tissue and -emia in the blood)

tissue

▪ Nose: rhinitis

▪ Pharynx: pharyngitis

▪ bronchioles: bronchitis

▪ Intestine: gastroenteritis,

▪colon: colitis

▪ bladder/urethra: cystitis/urethritis

▪ Meninges: meningitis (headache)

▪Brain: Encephalitis

▪ Heart: Carditis

blood

▪ Bacteremia, Viremia, Fungemia, Sepsis or septicemia: microbial toxins in the blood

chain of infection (picture)

How we spread infection

In order for infection to spread we need an infectious agent; next reservoir to transmit pathogen (food, water, people, etc.); next portal of exit (sneeze, cough, etc.); mode of transmission (airborne, contact, etc.); portal of entry (breathing it in, wounds, etc.); susceptible host (immunocompromised, age, etc.)

goal: infectious control; breaking the chain

sources of infection (exogenous, endogenous, zoonoses, other)

▪ Exogenous: acquired from external environment: water, food, soil, air, human

▪ Endogenous: acquired from hosts own microbial flora: opportunistic infections

▪ Other: direct contact: person to person, congenital (placenta), inanimate objects (fomites: toys, door), vector (animals, insects)

▪ Zoonoses: from animals to human (ex/white foot mouse is an animal reservoir for the bacteria Borrelia burgdorferi (Lyme disease). Ixodes ticks is an insect vector; tick larva feed on an infected mouse, become infected and transmit to human blood stream through saliva

Healthcare associated infections

▪ “healthcare-associated infections”: both hospitalized patients and community patients

▪ Often resistant to multiple antibiotics

▪ Colonization progresses to infection (symptomatic). Ex/ long term hospitalization often colonized with gram-negative bacteria: risk for pseudomonas pneumonia and sepsis.

direct vs indirect mode of transmission

▪ Direct: transferred from a reservoir to a susceptible host

▪ Direct contact: occurs through skin-to-skin contact, kissing, and sexual intercourse.

▪ Droplet: spray with large, short-range aerosols produced by sneezing, coughing, or talking

▪ Indirect: refers to the transfer of an infectious agent from a reservoir to a host by suspended air particles,

▪ Vehicle: food, water, biologic products (blood), and fomites

▪ Vector: mosquitoes, fleas, and ticks

Susceptible host (chain of infection)

▪ Depends on genetic factors, specific immunity, and factors that affect an individual’s ability to resist infection (ex: sickle cell pts protected from malaria).

▪ Specific immunity: protective antibodies directed against a specific agent in response to infection, vaccine, toxoid (toxin that has been deactivated and retains its capacity to produce antibodies), acquired by transplacental transfer, injection of antitoxin or immune globulin

▪ Nonspecific factors: intact skin, mucus membranes, gastric acidity, cilia in respiratory tract, cough reflex

▪ Factors that may increase susceptibility: steroids, comorbidities, malnutrition, immunocompromised

what can we do to break the chains of infection? (standard precautions and for patient's infected with pathogens)

▪ Standard Precautions: everyone follows

▪ Respiratory hygiene/cough etiquette, handwashing

▪ Safe injection techniques

▪ Use of masks during sterile procedures

▪ For patients infected with pathogens to control transmission:

▪ Early identification, Early isolation, Early treatment

▪ Appropriate isolation of patients infected with communicable disease: contact, airborne, or droplet

do we sterilize our hands

no we disinfect hands

subclinical

▪ symptoms are either very mild or asymptomatic

clinical disease

▪ same as acute stage; specific signs and symptoms

carrier/ chronic carrier

▪ can pass disease on to others. No clinical response to presence of pathogen

latent infection

▪ infected but not symptomatic (dormant)

chronic infectious disease

continuous long term with exacerbations and remissions (HIV, herpes)