Tuesday, June 5, 2012

Microbiology 1 Final Notes

Origin Of Pathogens - Where do bacteria come from?

Reservoir - A place where the pathogen ultimately originates, its habitat, such as a human, animal, water, plant, etc. 

Source - The immediate Origin of an infections agent 

Carrier - An individual that inconspicuously shelters a pathogen and spreads it to others

Asymptomatic carrier - An infected individual with no obvious symptoms (gonorrhea and genital warts)

Convelescent carrier - recovering patients without symptoms with viable microbe shedding (Diphtheria, up to 30 days)

Chronic Carrier - Carriage of the microbe for a long period after recovery (Tuberculosis, salmonella, typhi -several years) 

Passive carrier - Uninfected individual that carry infections agents from infected persons to uninfected ones by hands or instrument.  

Acquisition of infection - Communicable infectious disease.  When pathogen is transmitted from host to host directly or indirectly.  
  • Gram negative rods such as E. Coli, Klebsiella, and Pseudomonas are most often cultured from patient specimens followed by staph and strep.  
Reportable/ notifiable disease - Disease that, by law, must be reported to authorities.
  • The CDC and WHO keep track of infectious diseases at the levels of local, district, state, and international.  
Koch’s Postulates

Robert Koch proved the germ theory of disease by developing a standard for determining causative agents.

1- Find evidence of a particular microbe in every case of disease.
2- Isolate that microbe from infected subject and cultivate it artificially in a lab.
3- Inoculate a susceptible healthy subject with lab isolate and observe the resultant
    disease
4- Re-isolate the agent from this subject

Koch’s Postulates - Click to enlarge


Establishment of Pathogen

By virulence factors microbe settle in a particular organ and continue to cause damage.
The scope of injuries during this accounts for the typical stages of infection.



Stages in the Course of Infection and Disease

1. Incubation time - the time when you become infected with a
microbe; there are no symptoms during this time. Incubation periods
are different for different bacteria.

2. Prodromal Stage - the time when the microbe begin to multiply and
the signs and symptoms begin to occur.

3. Period of Invasion - period when the microbes are growing and there
are maximal signs and symptoms.

4. Convalescent Period - time of recovery for the body as the number of
bacteria decrease.

5. Terminal Stage - does not occur if there was a convalescent period.
If, however, our body could not recover then we become terminal and
die.

      
Stages in the course of infection and disease - Click to enlarge


Pattern of Infection

1. Localized infection - the bacteria remain limited to one area of the body.

2. Generalize or Systemic infection - the bacterial infection gets to the fluid
(blood etc) and spread to several areas.

3. Focal Infection - the bacterial infection spreads from one area to one
other area.

4. Mixed infection - infection by more than one type of microbe (two
different bacteria or bacteria and virus etc.).

5. Acute Infection - the type of infection which is very severe. The period
of the infection is very short.

6. Chronic Infection - the severity is low and the timing is long. Gradual
increase in severity.

7. Subacute Infection - midway between acute and chronic.

The occurrence of infections with regard to location and sequence - click to enlarge


Warning Signals of Disease

1. Sign - any measurable evidence of the infection which can be seen by an
observer. Ex. temperature, antibody's in the blood, number of blood
cells etc.

2. Symptom - something that is felt or seen but cannot be measured.                              
    Ex: headache.

3. Syndrome - collection of symptoms.


4. Blood Signs:
a) Leukocytosis - increase in the number of white blood cells
b) Leukopenia - decrease in the number of white blood cells
c) Septicemia - multiplication of microbe in the blood.
d) Bacteremia - presence of bacteria in the blood.
e) Viremia - presence of virus in the blood.

Microbial Nutrition
Nutrition is a process by which all organisms (micro/macro) obtain substances from their environment to convert to metabolic uses.
All microorganisms require six bioelements:
                     Carbon
                     Hydrogen
                     Oxygen
                     Nitrogen
                     Phosphorus
                     Sulfur
To survive, grow and reproduce.

Microbial Nutrient
Nutrient categorized by:
A.  Amount
B.  Chemical Structure
C.  Importance to the Organism

A.  Amount
1. Macronutrients: Large amounts required and have principal roles in bacterial cells structure and metabolism.
2. Microelements: Small amount required for maintenance of bacterial structure and function.
B. Chemical Structure
1. Organic
 Composed of Carbon, and Hydrogen.
2. Inorganic
Simple molecule that is composed of other elements beside C, and H2. 
C. Importance to the organism
1. Essential
Nutrients are  essential for bacterial growth and survival.
2. Non-Essential
Nutrients are not essential for bacterial growth and survival.

 Microorganisms are classified by chemical form of their nutrient.
a. Hetrotrophs
Microorganisms obtain carbon in the form of organic matter from the bodies of other organisms.
b. Autotrophs
Microorganisms obtain carbon from inorganic gas (carbon dioxide) and have the special capacity to convert CO2 into organic compounds.

 Epidemiology:

Epidemiology- The study of disease in a population

Surveillance- Rate of occurrence, mortality, morbidity and transmission of infections

Prevalence- Total number of existing cases with respect to the entire population

Incidence- Number of new cases over a certain time over healthy population

Endemic- A constant number of cased during a long period of time in a specific geographic locale

Sporadic- A few isolated cased in a wide spread locale (unpredictable)

Epidemic- Prevalence of cases increased unexpectedly, number of cases increase

Pandemic- The spread of epidemic all over the world ex (AIDS)


Defense Mechanism of the Host

The interaction and cooperation of three lines of defense provide complete protection against infection

First line of defense: (general function- same type of protection for all bacteria)

Any barrier that block invasion at the portal entry (skin)

Natural immunity is the result of the first line of defense and it is nonspecific

Three different kind of barrier may involved in the first line of defense

Ex. Skin and mucous membrane

1- Physical: Structure of tissue will protect us and not allow bacteria to come in and cause infection. If skin has damage infection can occur

2- Chemical: Secretion of chemicals to protect (Silvia protection in mouth; acid production in stomach; tears has lysozyome that protect eye sockets from bacteria)

3- Genetics: Genetic differences in susceptibility or resistance

Second Line of defense: (general function)

This line is non specific and is composed of more sensitive system for protective cells and fluids that includes inflammation and phagocytosis:


Phagocytosis:                                                                  

Microorganisms that enter the host are engulfed by any variety of phagocytic cells. The main function of  phagocytic include:

1- Chemotaxis- Attraction due to chemical stimulate phagostic cell , phagoctic cell will be attracted and begin to migrate

2- Migration- Move to microbe

3- Ingestion

4-Microbial killing- Lysozome kills bacteria


Microbes that enter the lymphatic, lung, bone marrow or blood stream are engulfed by any of variety of phagocytic cells

Most Common type of phagocytoic cells:

Polymorphonuclear leukocytes (PMN)
PMN  are Granulocyte and phagocytic
Moncyte = macrophage
Many microorganisms elaborate chemotactic factors that attract phagocytic cells

Monocyte- Make the macrophage
Neutrophil- Most present (55%)
Eosinophil- Can also perform phagocytosis
Basophil-  can not do perform phagocytosis and  Involve in inflammatory response

Factors affecting phagocytosis:

1- Presence of antibodies (opsonins) that coat the surface of bacteria, facilitate their ingestion by phagocytosis

Opsonization
Attachment of antibodies to the microbial surface call opsonization that assist phagocytosis by forming a physicochemical handle which the phagocyte can immediately recognize and grasp

2- Hyperosmolarity inhibits phagocytosis


Inflammatory response:

Injury to the tissue following multiplication of microorganism, elicit an inflammatory reaction

After tissue damage, histamine is produced (histamine is proceeds by tissue damage)

Steps in inflammatory response:
Dilation of local capillaries
Escape of plasma
Fluid accumulation (edema) in the area
Formation of fibrin network- Limiting the spreads of microorganism
Migration (chemotaxis) of PMN FROM ENGULFING OF MICROORGANISM BY PHAGOCYTE

Third line of function (specific function)

It is acquired as each foreign substance is encountered by specially adopted cells called lymphocytes

Line is specific and provides long term immunity
Four main body compartments that dominate in immune function

  
B cells and T- cells are involved
Located in spleen and lymph nodes

Bone marrow→ Spleen → Lymph nodes

 B Cells function- Humoral immunity or anti-mediated responses; result is production of antibody

1- Must be activated; phagocytic cells involved (this occurs in the second line of defense)
2- B-cells multiply and form plasma cells and create antibody (does not stay effective in the body for a long time)
3- Memory cells created, has longest life span (several years) protect against exposure to infection that has occurred before

T- Cells function – Cell mediated or cellular mediated immunity

Lymphocyte- Make B and T cells involved in third line of defense (20-35%)

Mechanism of Specific Host Response
Very specific and includes:

1- Surveillance (search for marker, performed by phagocytic cells)
2-Recognize
3- Destroy

The cells of immune system can recognize what is self and what is not

Self- Cell- Carries distinctive molecules (marker) that identify it as self. The body’s immune defenses do not normally attack tissue that carries a self   marker

Immune Response:
A complex variety of response
1- Antibody- mediated response (humoral)
2- Cell mediated response (cellular)
3- Combination of both

 Fever Notes- General Knowledge (not testing)
Low Fever- 99-100
Medium Fever- 100-103
High Fever- above 103

- Fever protects against bacteria, bacteria is sensitive to the heat. Slows rate of growth
- Low iron will also slow down growth rate of bacteria


Antibody mediated response

B cells undergoes blast formation and several division of blast cells from plasma cell that secret antibody and memory cells that can react to the same antigen

Antigen (Ag)- Antibody (Ab) reactions:

1- Opsonization- (Ab) tags the (Ag) to make it more accessible for phagocytosis

2- Neutralization- Attack to an active site of toxin or a receptor of a virus

3- Aggregate (clumping) Ag; kill microbe

4- Fix (binding) complement and cause destruction of cells



Characteristics of Antigen: (part of bacteria that can bind to the antibody)
a. Foreignness--- non self; not similar to components of the body

b. Molecular size large protein MW>10,000 (less that 1,000 can not function as an antigen);<1,000 MW (haptens) are not antigenic

c. Chemical & Structural complexity
Certain amount of complexity; made from several things to make them complex (ex protein)

d. Antigenic determinants (epitope)
The smallest unit of a complex antigen that is able to bind to an antibody


Antibody structure
1- Antibody is an immunoglobulin
2- Light (L) & heavy (H) polypeptide chains
3- The amino terminal of H chain participate in the antigen in binding sites
4- The simplest antibody molecule has a Y shaped molecule; contain two identical parts (Fab) and Fe





Types of Antibody

 IGG (memory cells make IGG)

A. IGG- simplest form of antibody; in blood circulation

2- secondary response (memory cells)- exposed to

3- Important defense against bacteria and viruses

4- Pass through placenta

B. IgM ( Plasma cells create IgM)

Most effective ( f times for effective) type of antibody, and heaviest

1- Five H2L2 units
2- Primary response
3- Important in agglutination, complement, fixation, & in defense mechanism against bacteria and viruses
4- Can be produced by a fetus with a infection
5- Has highest activity


C. IgA

1- Two H2L2
2- Main immunoglobulin in secretion (milk, saliva, tear)
3- Protect mucous membrane from attack by bacteria and viruses

D. IgE
1- Antigen- antibody complex
2- Allergic response


E. IgD
- A receptor on B cells
-Act as antigen receptor on the surface of certain B cells
-Monoclonal, and Polyclonal Ab:
-Monoclonal antibody arises by fusing a B cell with a single clone of cancer cells (ab with single specificity to Ag)
- Polyclonal antibodies arisen  in an animal in response to a single complex Ag.

Antibodies in serum (antiserum)



Cell medeiated immunity (CMI): Function of the T cells.

A direct attack of T cell upon a variety of foreign cells and cell markers

Steps in CMI:
1- Presentation of a Ag by macrophage; just like - Bcells
2- Sensitization of T cell and blast formation
3- Formation of:
a. T- Helper cells assist other T and B cells
b. T-suppressor cells (limit the action of other T and B cells; regulate function of T cells)
c. Cytotoxic or killer cells (destroy large, complex foreign and abnormal cells)
d. Delayed hypersensitivity cells (reactions with foreign antigens cause a form of allergy)

4- T Cells secrete a series of chemicals called lympokinse the destroy antigen or stimulate reaction

Reference 21-13 and 21-12 for examples

Complement or factor C: (Blood Protein)

Complex chemical defense system that destroys certain pathogens and act as an
immune mediating system

1- Composed of 20-30 blood proteins; inside 9 compartments (in order of when they were discovered)
2- Operates on cascade reaction (one component activated, then second; so on and so fourth)
Cascade reaction:
Once component activates the next in line, which activate the next

3- Originates from liver cells keratocyte, lymphocyte, and monocyte
4- Two major pathways:

a. Classical pathway involves activation of complement by specific antibody (It is initiated when antibody, called complement fixing antibody attached to antigen on the surface of a membrane.

b. Alternative pathway involves non-specific reaction to infections (can be initiated to wide variety of microbes, tumors and cell walls of bacteria). Starts from C3 and goes to C9

5- Result of complement activation is a huge enzyme called, the membrane attack complex. Those can k kill bacteria cells and viruses by digesting holes in their other membrane
6- Numbered C1-C9 in order of their discovered


Having memory cells mean the body have become immune to an infection

Resistant and Immunity
 
The term immunity indicates that those properties of the those that confer resistance to a specific infectious agent


Innate or Native Immunity - Resistance state at the time of birth; based on your genetic make up

- Species immunity
- Racial   immunity
- Individual immunity


Acquired Immunity- The resistance obtained during the life of the individual
- Natural: An immune state obtained by natural means (ex. infection or placental transfer)

- Artificial: Immune state produced by the introduction of immunizing materials (active) or of immunoglobulins (antibodies) that have been prepared for this purpose (passive)

- Active- antibodies are produced by the individual’s immune mechanism

- Passive- antibodies are received from an outside source (e.g. colostrums or placental transmission from the mother to her off spring, breast feeding)                                     

Immunization-Producing immunity by medical intervention (general term)


Vaccination- Production of a long lasting immunity following an antigenic stimulus; (active immunity, body is exposed to the antigen)


1- Killed cell or inactivated cell (used as the vaccine) entire cell used
2- Live or attenuated cells bad method weak; bacteria can get strong again
3-Subunit or part of microbe only part of cell used- ex:  viral surface protein
4-Neutralized toxin- Passive vaccine, antibody against toxin (ex. Tetanus shot) passive
5-Cloned Ag or recombinant attenuated microbes- cloning of proteins (best vaccine )

Immune testing:

1- Agglutination test
Ab cross linked whole cell antigen, forming three dimensional complexes that settle our and form visible clump

2- Double diffusion precipitation test Diffusion of Ags and Abs in a soft agar gel
Diffusion of Ags and Abs in a soft agar gel forming zone of precipitation where they met


Hypersensitivity or Allergy

Immune response results in reactions that are harmful to the host
Function of the immune systems harms host (over reaction of the immune system)


Types of Hypersensitivity

Type I
Immediate (anaphylactic) hypersensitivity:

Fast within a few minutes (very fast)
First exposure, no symptoms
Second exposure, host experience symptoms IgE procuded


An Ag induces IgE with bind to basophyls mediator
Histamine and prostaglandin

Atopy:

1- Hay Fever- Seasonal reaction to pollen
2- Asthma
3- Atopic dermatitis eczema
4- Food allergy
5- Drug allergy

Anaphylaxis
1- Cutaneous
2- Systemic

Type II – Cytotoxic Hypersensitivity
Ab directed at cell surface antigens activates C to damage the cells
IgG or IgM and C are the primary mediator of this type of hypersensitivity

B cells is involved
Ex. Blood transfusion, body reaction when bad blood is received

Type- III
Immune complex hypersensitivity
Deposition of immune complex which activate the complement and cause inflammations

IgG involved; production of IgG will bind to antigen and form the complex.
Binding can occur in heart, joints and kidney; comes from blood that contains complement
Function of immune system causes problem
Ex: Complication following Strep infection -Rheumatic fever,
Acute   Glomerulnephritis


Type IV
Cell mediated (delayed) Hypersensitivities

A Function of T lymphocyte (B cell is not involved)
    It starts hours or days after contact with Ag

Activated by the T -Cells
Ex.(1) Poison Oak, Poison ivy,(2) rejection of organ

Medically Important Cocci
Pyogenic cocci: (cause pus forming infection )

3 Types:

1- Syaphyloccocci ( gram positive)
2- Streptoccocci ( gram positive)
3-Neisseria ( gram negative)

Staphylococcus

Characteristic:
1- non-motile
 2-non-spore forming
 3-irregular clusters
 4-faculative anaerobe
 5-salt tolerant
 6- Catalase- positive
 7- Fermentative
 8- pigmented  arge colonies

Staphylococcus aureus (most pathogen of group)

Virulence factors
1- Coagulase- Coagulates plasma and blood( MOST USEFUL DIAGNOSTIC ENZAYME )
2- Halurindiase- Digests ground substance around the cells (dissolve cement of cells)
3- Staphylokinase- Digests blood clots
4- Nuclease- attack DNA
5-Cytotoxin:

-Hemolysin- Lyse red blood cells X toxin; B hemolysis
-Luekocidin- Alter the permeability of neutrophils , can kill with blood cells (phagocytic cells)

- Entrotoxin- act upon gastronintestinal tract, (cause food poisoning)

-Toxic shock syndrome toxin-toxemia in women due to infection of vagina associated with wearing tampons (tampon allow bacteria that cause bacteria to grow faster)

- Exfoliative toxin- separates the epidermal layer from the dermis

Target of infection: Skin and gland
Systemic infection:
 Bone and joint
Epidemiology:
Common human associates

Poor hygiene and nutrition, tissue injury, persisting primary infections, diabetes mellitus and immunodeficiency states increase

 S. aureus infections

Clinical manifestations
1- Local or contiguous infections

Skin
- folliculitis denotes a superficial infection ( the mildest skin infection)
- a boil or furuncle extends into the subcutaneous area (more severe than folliculitis)
- a carbuncle invades dipper tissue; it tends to be multiple and contiguous especially in the neck and upper back ( most sever skin infection)

- impetigo involve encrusted pustules on superficial layers skin; it is highly contagious and occurs mostly in preschool children (streptococci also may cause impetigo)

Eye
- conjunctivitis

Lungs
-pneumonia (common in children under age 1)

Wounds
-trauma or surgical sites, especially in the abdomen

Disseminated infections

(1) Blood stream or lymphatic disseminated infections (infection spread all over the body)
- occur away from the infection site
- are chronic and difficult to cure
 (a) Osteomyelitis, especially in the diaphysis of long bones
 (b) Pyoarthritis with permanent cartilage damage, especially in the hip
 (c)  Acute bacterial endocarditis in drug  abuser or within 2 months after heart surgery

(2) Toxin-associated infections
(a) Scalded skin syndrome due to an exfoliative toxin that splits the epidermis at the stratum granulosum

(b) Toxic shock syndrome due to pyogenic toxins (TSST); occurs mostly in females using tampons is characterized by high fever with vomiting and diarrhea, collapse of peripheral circulation, and scarli form rash

(c ) Food poisoning due to an enterotoxin preformed in food to 6 hours after ingestion of contaminated food (local infection)

(e) Enterocolitis; following broad spectrum antibiotic therapy for other bacterial infections cause cramps, diarrhea, fever, and dehydration


1- Treatment

-Isolate orgamisms and perform antibiotic sensitivity tests (because widespread resistance)

- Give oral antibiotics for 10 days for localized infections
-Give parental antibiotics for 4 to 6 weeks for disseminated infection
-Drain abscesses; remove any foreign body, if possible
-Severe toxic shock syndrome may require intravenous(IV) fluids measures to elevate blood pressure
- food poisoning is self-limiting within 24 hours; no treatment is required


2- S. epidermidis
- cause urinary tract infections, primarily in the elderly
-may cause subacute bacterial endocarditis at least two months after heart surgery of after gastrointestinal instrumentation or dental work when person is not wearing gloves ( blood transmission)
- usually normal flora of the skin


2- Prevention
- Hand washing is a key to prevention in a hospital environment
-Hospital problems occur primarily in operating rooms and nurseries



Streptocpccus
Normal resident or agent of disease in human or animal

Characteristic:
1. Spherical Shape
2. Long bead like chains
e. Non spore forming and none motile
 f. Facultative anaerobes
g. Ferment sugar with the production of lactic acid
h. Colonies usually small, and non-pigmented
i  Catalase- negative
h. A peroxidase system for inactivation of hydrogen peroxide

Calassification:

Rebecca Lancefield (1930)
Cell wall Carbohydrates                                                   abs WITH DIFFERING SPECIFICTIES

Another classification on the base of their reaction in blood agar

A, B, C and some D are Beta HEMOLYTIC
Streptoccoccus pneumoniae
Viridians (mitis and pneumoniae)
Are alpha hemolysis producer

Group A
Streptoccoccus pyogenes (B hemolytic)
Cause throat infection
Inhabitait of the throat,nasopharynx and skin of humans


Virulance factors:
1- Capsule
2- C- carbohydrate- protect bacterium from being dissolved by the host lysozyme
3- M protein- main component of fimbriae

All are antiphagocyitic and adherence factor

4- Streptolysin O (SLO) and streptolysin S (SLS)
Both produce B hemolysis

5- Erythogenic or pyogenic toxin
Responsible for scarlet fever and induces fever and red rashes

6- Streptokinase
Digest in the fibrin clot and may play a role in invasion

7- Hyalurinidase
Promote the spreading of bacteria by digestion of intracellular glue                                    

Targets of infection
1- Skin or the mucus membranes of the throat primary lesion ( skin infection- strep impetigo or pyoderma = itching papules  that break open  and form a highly contagious yellow crust) 
Pharyngitis or tonsillitis (strep throat)
Redness, edema, enlargement of tonsils
2- Lymph and blood (systemic infections)
3- Vagina (puerperal fever)
4- Join, heart, and subcutaneous tissues (delayed inflammatory reaction- rheumatic fever)
5- Kidney (acute gomerulonephritis)
6- Tissue between skin and muscle Necrotising  Faceitis
(Flesh eating disease)


Treatment:
Penicillin and its derivatives
Erythromycin or cephalosporin

Alpha Hemolytic Streptococci: The Viridan Group

Most numerous and residents of the oral cavity
S. mits, S. mutans, and S. sanguis
Dental procedures can lead to:
Bacteremia
Meningitis
Abdominal infection
Sinusitis
Wound infections
And subacute endocarditis
Dental caries because of streptococci mutans
And streptococci sanguis

Streptococcus pneumoniae:
Significant human pathogen

Characteristics:
Encapsulated
Capsules contain a polysaccharide antigen called the specific soluble substance (SSS) that varies chemically between the pneumococcal types and stimulates different Abs of varying specificity


Target of Infection:
Adult:
1-pharynx
2-Lung (lovar peumoniae)
Symptoms: chills, shaking, fever

Young children:
1- Upper respiratory tract
2- Meninges (meningitis)
3 middle ear (otitis media)

Treatement:
Penicillin, clindamycin, erythromycin and cephalosporin

Neisseriaceae:
Resident of the mucous membrane of worm blooded animals
Two species are primary human pathogens
1- Neisseria
2- Moraxella

Neisseria:
-Distinguishing feature is the morphology
-Bean-shaped and paired
-Capsule on the pathogens
-Pilli (slow down phag)
-Strict parasite
-Aerobic
-Catalase positive



Neisseria gonirrhaeae
-Sexually transmitted disease (STD)
Albert Neisser 1879

Site of infection:
Genital tract, eye, rectum and throat
Symptom: Yellow creamy pus with painful urination

Virulence;
Pilli-promote attachment of cocci to each other an epithelial tissue to each other and       epithelial tissue
Pilli also seem to slow pahgocytosis by macrophage and neutrophiles
-Protease-cleaves the secretory antibody( IgA)

Epidemiology and pathology
Strictly human pathogen
Rank in top 5 STD
600,000 to 700,000/ year in the USA
Several categories of gonorrhea male, female and children

Treatment
1- Intramuscular injection of procaine pencillin G
2- Oral ampicillin and probenecid

Gonorrhea is  reportable


Neisseria meningoccous:
Neisseia meningitides is a serious human pathogen

Important virulence factors:
1- a polysaccharide capsule( nine different strains of a capsular antigens exist, serotypes A,B, and C are responsible for most infections
2- Pilli
3- IgA protease
4-Lippoplysaccharide (endotoxin) released for cell wall

Epidemiology and Pathogenesis :
The continuing reservoir of infection is human Neisseria meingitidis is the second most
frequent cause of meningitis in young children

Serious complication due to meningococcemia bacteria entering the blood vessel rapidly permeate the meninges and produces symptoms of meningitis

Symptoms:
Fever,weakness, headace, stiff neck. Convulsions and vomiting


Treatment:
Penecillin G
Prevention therapy with rifamphin or tetracycline

Other gram negative cocci:
1- Branhamella catarrhlis-common member of throat flora, and can cause opportunistic infection
2- Moraxella, a short rods that colonies mammalian mucous membrane


Bacilli of Medical Importance

Gram positive bacilli:

a. Aerobic: Bacillus
b. Anaerobic: Clostridium
2- Non spore-forming
    
Gram positive spore-forming bacilli:
Motile
Rod-shape
Endospore
Extreme resistance to heat, drying and radiation
Ex. Bacillus, Clostridium
Bacillus anthracis:
Blocked-shaped angular rods
Largest bacteria
Zoonatic disease of domesticated animal
Central spore

Virulence factors:
Capsule
Exotoxins
Very important in medical microbiology

Robert kock used this organism for developing his postulate, and Louis Pasteur used the disease to prove the usefulness of vaccination.

Depending upon the portal entry
1- Cutaneous anthrax---skin---through small cut
2- Pulmonary anthrax---inhaling airborne spores
Exotoxins produce a toxemia with cardiovascular shock

Treatment
Penicillin or tetracycline

Bacillus cereus:
A common air-borne and dust- borne contaminant
Multiply in cooked food (starchy food and meet )
Spore survive short periods of heating
Spore germinates and release entrotoxins
Ingestion of toxin containing food causes nausea, vomiting, abdominal cramps and diarrhea

No specific treatment

The Genus Clostridium:

Gram positive
Spore forming
Heat resistant
Requirement of oxygen
Catalase
Inhabitant of human and animals
Single, pair and chain arrangement
Exotoxins play an important role in various clostridial disease
Several species are important


Types of infections

1- Wound and tissue infections, including myonerosis, antibiotic-associated colitis and tetanus
2- Food intoxication of the perfringens and botulism varieties

Clostridium Prifringes----soft tissue and wound infection (Gas gangeria)
Extent and symptom of infection

Two forms: (wound infection)
1- Anaerobic cellulites:

Target—previously injured necrotic tissue
Toxin and gas production
Localized infection

2- Myonecrosis:
Most distractive
Target--- injured tissue (often large muscle)
Diffuse into nearby tissue and cause necrosis there. This damage tissue then be a source continuation of growth of bacteria

Treatment
Removing of the infected tissue (this is very difficult in the intestine or body cavity infection)
Large dose of a broad-spectrum cephalosporin
Passive immunization with polyvalent antitoxin

Clostridium tetani:
Common resident of cultivated soil and gastrointestinal tracts of humans and animals

Spore usually enter the body through accidental cut
Tetanus neuromascular disease--- Lockjaw

Spores cannot become established unless tissue at the site of the wound is necrotic and poorly supplied with the blood

Neurotoxin (tetanospasmin) responsible for the major symptoms


Treatment:
1. Immediately receives antitoxin therapy with Human tetanus Immune Golbulin (TIGH). Tetanus antitoxin from a horse is also acceptable with a chance of allergic reaction
2. Remove the infected tissue
3. Control the infection with Penicillin
4. Administration of muscle relaxants

Clostriduim food poisoning:

C. perfringens- Bacteria is eaten with uncooked meat and fish, producing toxin in the intestine, not usually fatal

C. botulinum (improperly home- canned food)
Spore withstands food processing and germinates in stored food and produce Toxin (botulin)

Food poisoning
a. Caused by poisonous plants animals
b. Caused by microbes

1- Food toxication (toxin) 
2- Food infection (bacteria)

Most common food poisoning in the USA is Staphylococcal food intoxication
Other common: Salmonella, Clostriduim perferingen, Shigella


Irregular, non spore forming bacilli:

Corynobacterium
Mycobacteria
Nocardia

Corynebacterium
Corynebacterium diphtheriae
Aerobic curved rod and palisade arrangement
Epidemiology
400 years ago---significant cause of mortality and morbidity
Today mortality declined to 0.1% in 1,000,000
Many healthy human carrier

Pathology:
The main pathogenicity factor is production of diphtherotoxin

This exotoxin is produced only by strains of C diphtheriae that carry the gene for toxin  production that obtained from bactriophage during transduction

Clinical disease:

Diphteria--- a disease occurs in two stages
a. local infection---
Toxin absorbed into the mucous membrane of upper respiratory tracts (tonsils, pharynx, larynx, and trachea) causes destruction of epithelium and causes superficial inflammatory response and formation of a grayish “pseudo membrane)

Other symptoms—low grade- fever, sore throat, nausea, vomiting and sever edema of the entire neck

b. Systemic infection:
Toxin is absorbed from the throat to the blood - to heart  ( myocarditis and nerve( paralysis ); patient could die from this infection

Treatments
Pseudo membrane can be removed
Penicillin and Erythromycin
DPT ( toxoid vaccine -prevention

Acid fast Bacteria (wax layer in the cell wall)
Mycolic acid and waxes
Strict aerobes
Filamentous rod
Resistant to environment

Mycobacteria:
Several species are important

Mycobacterium tuberculosis


1- Generally we get infected easily, and develop resistance to disease (95%)
2- 5% of population will develop disease
3- 85% of 5% population will develop lung infection

Lung infection- lesion- lesion in regional lymph nodes- Ghon complex-,healthy people will recover from infection by fibrosis—calcification, and healing.
Unhealthy people will develop TB through blood circulation


Diagnosis:
1- Chest X ray
2- Isolation Acid Fast bacteria from Sputum

3- Tuberculin Skin Test (Mantoux test)-
Exposure to small amount of purified protein derivative (PPD)
4- Lab cultivation and Diagnosis


Gram Negative Rod:
Non- spore former
Cell walls contain lypopolysacharide that is endotoxin

1. Aerobic non spore forming:

Pseudomonas aerugionsa
Opportunistic pathogens
May attack lung, skin, burns, urinary tract eye and ear

2-Facultative Anaerobic rods
:
Enterobacteriaceae:
Small, ofter motile,
Found in intestine----enteric
1- Coliforms---E.Coli,serratia (ferment lactose)
 Normal flora that are rapid lactose fermenters (coliform)
Non- coliforms
Do not or only weakly ferment lactose (Proteus)

Coliform Bacteira: (can produce sugar from lactic acid; non pathogen)
Ecoli
Klebsiella
Entrobacter
Citrobacter
Serratina

Non- Coliform Bacteria (non- pathogen)
Proteus vulgaris
Morganella

Pathogen:
Salmonella---salmonelosis (Typhoid Fever)
Shigella---- Sigellosis (Bacillary dysentery)
Yersinia—Bubnic plague

Virulence factor:
Flagella, Capsule, and Firbriae

E. Coli

Most common in gut and harmless
Pathogenic strains:

Virulence factor:
Toxin and fimbriae
Causes sever diarrhea illness
Agent of infantile diarrhea (greatest cause of mortality in babies) most common cause of Travelers diarrhea

E coli type 157
Newest pathogenic strain
Mild gastroenteritis with fever to bloody diarrhea
Can cause kidney damage and failure
High risk in your children, elderly and immune-compromised people
first discovered on 1982

The Spirochetes:
Long Rod
Spiral and motile
1. Treponema
Gram negative cell wall with axial filament
Causes syphilis, bejel, yaws, and pinta




Ttreponema palidum
A. Acquired Syphilis:
Limited to human host
Sensitive bacteria to environmental condition and transmitted by sexual contact
Involve all tissues of the body
Multiply at the sit of entry--- spread to nearby lymph nodes—blood stream
2-10 weeks—hard chance (an ulcer with a clean, hard base at the site of entry- primary lesion)
2-10 weeks later—secondary lesion—red rash anywhere on the body

Both primary and secondary lesions are highly infectious. Contagious lesion may recur within 3-5 years after infection but thereafter the infected individual is not infectious

- 30% remain latent
-In the remainder, disease progresses to tertiary stage, characterized to the development of glaucomatous lesion in the skin, bones, liver and degenerative changed in CNS, and cardiovascular system

B. Congenial syphilis: A pregnant woman can transmit infection to the fetus during 10th -15th week gestation
Some of the infected fetus may die

Misscarriages
Problem  with eye, teeth,  nose and CNS

Treatment: Penecillin G
Prevention use of condom

2. Borrelia ( Arthoropod- borne spirochete)
Borrelia burgdorferi—lyme disease
Human---accidental host
Principal host--- mouse and deer

Transmission by tick
Symptom:
Early—skin lesion  in 70% of infected patient -called erythema chromicum migrans and flue like symptoms ( fever, chills, headache)

Late—Arthralgia and arthritis
Neurological manifestation—meningitis

Cardiac disease
Treatment: Tetracycline, and penicillin

3. Vibrio (curved gram negative)
Spread by water and food
Uncommon in USA
Sporadic out break along of Gulf of Mexico
Sometimes isolated from shellfish
Vibro parahaemolyticus in sea food

Microbiology of Drinking Water

Water need to be free of pathogen. Water can pick up pathogen through ordinary exposure to air, soil, etc.

Most common pathogen in water:

                   Salmonella
                   Sigella
Bacteria      Vibrio               
                   Mycobacterium
                  Campylobacter

Virus          Hepatitis A
                   Norwalk Virus ( reovirus)

Fecal contamination :
Most common source of pathogens in drinking water.



Monitoring Water

Water constantly surveyed for certain indicator bacteria.

Indicator Bacteria - 
Intestinal residents of birds and mammals that can be identified more readily than individual pathogens

 Most useful enteric bacteria for monitoring:

                        Coliforms

                        Streptococci

These bacteria survive in water without multiplication.

High numbers indicate high levels of fecal contamination.


Environmental Protection Agency (EPA)
Standard for water sanitation based on the levels of coliforms.


Water Quality Assays:

1- Standard plate count

2- Measurement of dissolved oxygen

3- Colifrm Enumeration
     a. Most Probable Number( MPN )
     b. Membrane filter                 
            
Water and Sewage Treatment

Water Purification
Storage, Sedimentation, Settling, Aeration and disinfection

Sewage Treatment:
Sewage processed to remove solid matter, dangerous chemical and microorganism.

Bioremediation:
Using microorganisms to breakdown or remove toxic waste in water and soil

Most important bioremedial microbes: Pseudomonas, Bacillus and toxic - eating Fungi  

Medically important Bacteria of unique Morphology

Helicobacter Pylori
Rickettsias
Chlamydia
Mycoplasma


Helicobacter Pylori

Unusuall Spiral in human and animal
Microaerophilic
Pollar fellagella
Grow in acidic environment
Causes inflammation of lining of Stmomach called gastritis
Implicated in 90% of stomach and duodenalulcer
Cofactor in the decelopment of a common type of stomch cancer called adenocarcinoma

Transmision: person to person by oral- oral or oral – fecal

Treatment: antibiotic and antiacid

Rickettsias:
Gram negative rod or cocci 

Obligate intracellular

Transmission by insect

Rickettsia rickettsii:

Gram negative rod, multiply in endothelial cells of lining of blood vessel , causing necrosis
Rocky Mountain spotted fever
Zoonosis carried by dog and wood tick
Symptoms: Spotted, migratory rash, Fever, chills, headache

Complications:
Hemorrhage, heart damage, CNS damage

Treatment: Tetracycline

Rickettsia prowazekii:

Typhus
Carried by lice
Symptoms: High fever, chills, headache,
Rush
Treatment: Tetracycline

Chlamydia:

Gram negative coccobacilli
Obligate intracellular
2 forms:
Elementary body which is infectious
Intracellular reticular body – reproductive form and pathological effect

Chlamydia trachomatis:

Eye infection and STD
Eye disease is the infection of eyelid and cornea, can cause blindness
STD is non gonococcal urethritis in male and cervicitis and infertility in female


Chlamydia psittaci:

Cause disease in bird (parrots)
Cause human respiratory infection
(Parrots Fever)

Mycoplasma:

Lack cell, wall have strole and highly pleomorphic
Not obligate parasite but require special lipids from host membrane

Mycoplasma pneumonia:
  
Contain sterols for protection
Causes atypical pneumonia
Symptoms:
Fever chest pain and sore throat

 Viruses in infection and disease:

Virus Particle- Needs cell to live;

Structure of virus:
Consists of Covering and Central Core
Covering: Capsid, envelope not found in all viruses
Central Core: Nucleic acid molecule DNA or RNA and Matrix Proteins enzumes; not found in all viruses           

DNA-double stranded except parvovirus   (or)
RNA-single strand except reovirus
- will only have DNA or RNA will not have both

Target cell
Scope of infections
Latency/ oncogencity (can cause cancer)



Viral Replication
1- Adsorption: Virus attaches to hose
2- Penetration-
Lysogeny (Latent) State- Virus go to bacterial DNA and become dormiant will not damage cell; can come out and begin to grow
Lytic State- grow and burst out of the cell
3.Synthesus  structural parts
4-Assembly-
5- Release


DNA viruses:
Enveloped
1-Pox virus
2- Herpes virus
3- Hepanavirus

Non enveloped:
1- Adenovirus
2-Papovavirus
3-Parvoirus

Pox virus—Infect epithelial of respiratory tracts circulation and lymph nodes
Skin pustules----pock or pox
Largest virus
Symptoms: fever, malaise, later rash in pharynx and

Small pox, and variola
Minor—mild
Major – 25 times more virulent
Vaccine—cow pix virus


The Herpesviruses: (herpes viruse hominis)
Herpes= Creeping

Herpes simplex type 1 (Fever blister)
- hide in the Ganglion area, until activated

Type 2= Genital infections
- Latent in the ganglion of the lumbosacral spinal nerve trunk

Herpes zoster = Chickenpox and shingle
Cytomegalovirus= salivary glands
Epstein-Barr Virus= Lymphoid tissue
Herpus virus 6= T Cell and B cell
Herpus virus 7- T cell
Herpus virus 8- T cells

Herpes simplex type 1 & type 2
Enveloped
Structrue:
Large virus –150-200 nm diameter
Envelope with glycoprotein spike
Icosahedral capsid
Core—double strand DNA
Replication in host nucleus
Viral release by cell budding

The exact mechanisms of latency are not known, the virus remain inside trigeminal  ganglion ( type 1 ) and Lumbar sacral ganglion( type -2)  in a non-dividing stage for a variable time , recurrent infection is triggered by different stimuli:
Fever
UV radiation
Menstrusation
Stress
And mechanical injury
After reactivation virus migrates to the body sites and produce local skin or membranes lesion

Types of HSV-1 infection:

1. Gingivostomatitis- most primary infection; infection of the oropharynx- inflammation of the oral mucosa (gum, tounge,soft palate and lips)

2. Herpes labialis- fever blister or cold sore on the lips or adjacent skin

Herpes Keratitis (ocular herpes)
Primary and recurrent infection of eye
Cornea is the site of infection
The chronic case can lease to visual loss

Encephalitis- complication in newborns infected at birth – brain infection
Severe CNS damage
Fatal of neonate and fetus (50%-80%)

Disseminated herpes- inpatient with immunodeficiency

Herpetic Whitlow
Finger tip infection

Diagnosis and Treatment
Tissue culture for virus cytopathic effect is essential for diagnosis
Acyclovir ( can stop the growth of virus)

Varicella-Zoster Virus (VZV)
Chickenpox (varicella) and zoster (shingles) chickenpox is the primary infection, and zoster is the later recurrence of infection by latent virus

a- Vesicular rash on the fact and truck (primary)
b- Latency in the dorsal ganglia
c-the one site pattern in shingle (reactivation)

Transmission by droplets

Treatment:
Uncomplicated is self limited
Drug for systemic disease is intravenous
Acyclovir, interferon, and vidarabine

The use of aspirin is not recommended because of the risk of Reye syndrome ( a disease that strikes the brain, liver and kidney fatalities are common.  Children given aspirin therapy have a higher risk for the disease)

Cytomegalovirus (CMV):
Named from the characteristic cytopathic
Effects (nuclear and cytoplasmic inclusion bodies)

High infection rate in children, pregnant woman and drug abuser
Spread with close contact with saliva, mucus, urine, and semen

Congenital infection causes disturbance of liver, spleen, brain, and eyes
Disseminated disease in AIDS and transplant patients

Treatment: If you are healthy immune will cure; if you have low immunity
 Treatment: Gancyclover; best for treatment of chickenpox

Epstein- Barr Virus (EBV)
Infect lymphoid and glandular tissue

Transmitted by saliva, oral contact
95% of all persons develop some kind of infection asymptomatic
Cause of monoucleosis a “kissing disease
Common in college students
Can cause cancer

None enveloped  DNA virus
Adenovirus:
Transmission:
         Transmitted by fecal to oral contact, waterborne transmission and inhalation of aerosols also possible.
         There are many different types of adenovirus and they all survive adverse conditions from chemicals and pH levels and rely on the host for survival and replication
         Examples: conjunctivitis,
    ear infections, tonsillitis,
    and croup
Pathology:
         Most cases involve respiratory tract, GI tract and eye
         Most people are infected with some type of strain before the age of 15
         50 to 80 percent of tonsils removed contain some form of adenovirus
         In some cases the virus can live inside the host for up to 2 years, it can be excreted from the stool and urine
Diagnosis:
         viral culture, adenovirus-specific viral antigen assays and polymerase chain reaction assays are most commonly used

Prevention:
Hand hygiene is the most important preventative measure along with adequate amounts of chlorine in swimming pools

RNA virus
More kinds of RNA virus than DNA virus
Segmented-
Non- Segmented virus

Postitive Sense
Negative Sense

Retroviruses:
1- Most unusual virus
2- Oncogenic (some viruses are transforming agent regulate certain genes and convert normal cells into cancer cells
3- Capable of reprogramming a hosts DNA
4- Unusual enzyme called reverse transcriptase which can convert a singe stranded RNA into double stranded viral DNA


RNA- AIDS virus
Enzyme can change RNA into DNA ( reverse transcriptase  enzyme )

Classification:
Human T- cell leukemia virus (HTLV)
HTLV I, II and III
Type I & II are associated with human leukemia or lymphoma, and type III is the agent of AIDS
Type III- agent of AIDS

Since it was determine that HTLV III LYMPHADENOPATHY VIRUS (LAV) AND (AIDS) retrovirus (ARV) are all the same virus, a unified names HIV-1

Epidemiology:
AIDS have been reported in every country (30-40 million)
1 million in the USA

Transmission:
Sexual Intercourse
Transfer of blood of blood products
The virus can be isolated from urine, tears, sweat, and saliva, but these fluids are considered an unlikely source of infection
The mother milk can be a source of neonatal infection


AIDS is defined as severe immunodeficiency Disease arising from infection with HIV-1

Symptoms:
Opportunistic infections, persistent fever,

ARC (AIDS related complex) is considered a stave in the development of the disease
  
AIDS Pathology

1- HIV initially enter special cells on the membranes called dendritic cells
2- It grows and she from the cells with out killing them
3- It can multiply in a macrophages, skin, lymph organ, bone marrow, and blood
4- Infect and destroys many of cells need to destroy microbes including the helper

Class of lymphocytes, monocytes, macrophages and even B lymphocytes
Can infect brain cells, macrophage,

Diagnosis and Treatment
1- Secondary infection and cancers
2- The enzyme- linked immunabsorbent assay (ELISA) is highly sensitive but can lead to false positive
3- Western blot, which is most specific test and can rule out false positive

There is no cure for AIDS. The available therapies prolong life or diminish symptoms by stopping the growth of virus .
Drug:
AZT (retrovir) blocks the replication of virus
DDI (videx)
Both drugs are synthetic nucleotide and incorporate into the DNA molecules during reverse transcription

Rhabdovirus- Rabies

         The Rhabdovirus is a negative stranded RNA genome that is uniquely bullet shaped.
         The name is derived from the Greek word rhabdos meaning rod referring to the shape of the virus.
         They typically carry genes for five proteins.    
         Rhabdoviruses have a broad host range affecting both animal and plant kingdoms.
         Rhabdoviruses infect cells and generally enter via a bite or a wound infected with saliva. 
Rabies:
         Rabies is a viral disease that causes acute encephalitis (inflammation of the brain) in warm-blooded animals Initially, the virus replicates at the site and then infects the CNS tissue.
         Rhabdovirus causes lethal encephalitis resulting in approximately 50,000 human deaths per year. The rabies virus is classified as Lyssavirus genus, in the family Rhabdoviridae.
          

Orthomyxovirus-Influenza Virus:

All orthomyxovirus are viruses, isolated strains and are named after the virus type (A,B,C), the host and location of initial isolation, the year of isolation, and the antigenic designation of the hemagglutinin and neuraminidase

         Influenza is an acute respiratory tract infection that usually occurs as epidemic by influenza virus                           
         Just three types of influenza virus are known : A,B and C
                                                                      
         Major outbreaks of influenza
          are associated with influenza virus type A or B.
         Infection with type B influenza is usually milder than type A.
         Type C virus is associated with minor symptoms.

Antigenic Drift and Shift
Type A: antigenic shift
Type B: antigenic Drift

 Slow Infections
Virus like agent---

Prions- atypical chemical and physical properties
10- 20 years before you feel symptom
Agents of spongiform Encephalopathies or neurodegenerative dementias

Human diseases with prions:
1- Kuru
2- Creutzfeldt- Jacob disease
3. Gerstmann Straussler- Scheinker disease
4. Faal Familial Isomina (FFI)
Aminal disease with prions:
Scrapie--- found in sheep and goats












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