READ THE POEM BY W. H. AUDEN: "FOR CREATURES YOUR SIZE..."
INTRODUCTION:
HEALTHY INDIVIDUALS ARE INFECTED AND ARE BEING INFECTED ANEW CONSTANTLY
MAKE A DISTINCTION BETWEEN
NORMAL FLORA
TRANSIENT FLORA
SOME OF THESE ORGANISMS MAYBE PATHOGENS (MORE FREQUENTLY AMONG THE TRANSIENT FLORA GROUP). SOME AMONG THE NORMAL FLORA MAY BE OPPORTUNISTS.
OUR RELATIONSHIP WITH MICROBES IS VERY DYNAMIC:
THERE IS A BALANCE BETWEEN:
THE DISEASE CAUSING PROPERTIES OF THE MICROBES
<<<<------------>>>>> AND THE ANTIMICROBIAL DEFENSES OF THE HOST.
INFECTION AND DISEASE ARE NOT SYNONYMOUS TERMS. INFECTION IS REALLY A NEUTRAL TERM.
INFECTIOUS DISEASE IS DISEASE CAUSED BY PATHOGENIC MICROORGANISMS
{definition: pathogenic = disease causing}
{definition: disease = abnormal state, deviation from a state of wellness or health}
INFECTIOUS DISEASES ARE OFTEN CATCHY BUT THEY DON'T HAVE TO BE:
COMMUNICABLE DISEASES - CONTAGIOUS, EASILY CAUGHT: ex.: INFLUENZA, COMMON COLD, TUBERCULOSIS, SEXUALLY TRANSMITTED DISEASES. (NOT ALL COMMUNICABLE DISEASES ARE EQUALLY CONTAGIOUS. CONTAGIOUSNESS DEPENDS ON SEVERAL FACTORS. ANALYZE THE ABOVE LIST AND DESCRIBE THE FACTORS WHICH RELATE TO THE SPREAD OF THESE DISEASES.
INFECTIOUS DISEASES WHICH ARE GENERALLY CONSIDERED NON-COMMUNICABLE - THESE ARE NOT COMMONLY TRANSMITTED: ex.: TETANUS, SUBACUTE BACTERIAL ENDOCARDITIS
WHETHER OR NOT YOU WILL CATCH A DISEASE DEPENDS ON
(1) YOU: YOUR HEALTH, NUTRITION, IMMUNE STATUS
(2) THE PATHOGEN'S VIRULENCE
(A) HOW TOXIC THE ORGANISM IS
(B) HOW INVASIVE THE ORGANISM IS
THE NORMAL FLORA
THE HUMAN ADULT IS ESTIMATED TO HAVE 1013 HUMAN CELLS AND 1014 BACTERIAL CELLS.
SEE TORTORA pg. 368 - diagram of human body sites and pg. 369 - chart of normal human flora organisms and their locations.
WE ARE A CYLINDER WITH A HOLE THEROUGH THE CENTER. JUST ABOUT EVERY SURFACE IS COLONIZED. THERE ARE SPARSE AREAS:
THE STOMACH - WAS THOUGHT TO BE FREE OF ORGS -- BUT RECENTLY SHOWN THAT SOME ORGANISMS CAN SURVIVE--- HELICOBACTER PYLORI---- THIS IS PROBABLY NOT CONSIDERED NORMAL FLORA SINCE IT IS NOW KNOWN TO CAUSE ULCERS.
THE BLADDER AND THE LOWER REACHES OF THE RESPIRATORY TRACT. THESE AREAS CAN BE TRANSIENTLY INFECTED BUT NORMAL CLEARANCE MECHANISMS EXIST TO GET RID OF THE INTRUDERS.
WE ARE COLONIZED AT BIRTH WITH LACTOBACILLUS.
OVER TIME WE ACQUIRE AND ESTABLISH POPULATIONS OF:
COLIFORMS - (Escherichia coli and other enteric gram negative rods) - intestines
Staphylococcus aureus, Staphylococcus epidermidis, Proprionibacterium acnes and other diptheroids - skin
Streptococci (viridans and pneumoniae) as well as some anaerobes - mouth
Lactobacilli - vagina
BENEFICIAL EFFECTS OF THE NORMAL FLORA
ANTAGONISM
COMPETITION AND THE PRODUCTION OF INHIBITORS
IF NORMAL FLORA IS DESTROYED ex.:
STAPHYLOCOCCAL ENTERITIS - S. AUREUS; PSEUDOMEMBRANOUS COLITIS - CLOSTRIDIUM DIFFICILE;
CANDIDA INFECTIONS - THRUSH, VAGINITIS CAUSED BY ANTIBIOTICS AND DOUCHES AND DEODORANTS;
INCREASED SENSITIVITY TO SALMONELLA AND SHIGELLA INFECTIONS.
PRODUCTION OF NUTRIENTS - VITAMINS B AND K IN THE INTESTINES
STIMULATE THE IMMUNE SYSTEM
THE ABOVE ARE EXAMPLES OF MUTUALISM
REVIEW SYMBIOSIS, COMMENSALISM, MUTUALISM, PARASITISM
IMPOSED ON THIS IS THE IDEA OF OPPORTUNISM
OPPORTUNISTS - THESE ARE ORGANISMS THAT NORMALLY DON'T CAUSE DISEASE BUT WILL IF GIVEN AN OPPORTUNITY:
AS IN SECONDARY INFECTIONS
IF RESISTANCE IS LOW
IF THEY GET INTO THE WRONG PLACE
E. COLI - NORMALLY IN THE INTESTINE, BUT IF IN THE BLADDER OR PERITONEAL CAVITY - BIG PROBLEM. SUCH AS WHEN ONE SEES PERITONITIS AFTER A RUPTURED APPENDIX. ALSO WITH E. COLI ONE HAS FRANKLY PATHOGENIC VARIANTS SUCH AS O157:H7 - THIS IS EHEC OR ENTEROHEMORRHAGIC E. COLI WHICH PRODUCES POWERFUL TOXINS RESPONSIBLE FOR HEMOLYTIC UREMIC SYNDROME.
ORAL STREPTOCOCCI - MAY CAUSE TOOTH DECAY
PNEUMOCYSTIS CARINII - PNEUMONIA IN IMMUNOCOMPROMISED INDIVIDUALS
NEISSERIA MENINGITIDIS - MENINGITIS IN CHILDREN, 5 - 15% CARRIAGE RATE IN APPARENTLY HEALTHY PEOPLE.
STREPTOCOCCUS PNEUMONIAE - PNEUMONIA AFTER INFLUENZA OR OTHER RESPIRATORY TRACT INFECTION PARTICULARLY IN ELDERLY PEOPLE.
CANDIDA ALBICANS - VAGINITIS AND THRUSH
PSEUDOMONAS AERUGINOSA - INFECTIONS OF BURNS AND INFECTIONS OF THE LUNGS IN CYSTIC FIBROSIS
STAPHYLOCOCCUS AUREUS - SKIN INFECTIONS AND TOXIC SHOCK SYNDROME
CLOSTRIDIUM DIFFICILE - PSEUDOMEMBRANOUS COLITIS
TORTORA DISCUSSES HOW TO DETERMINE IF AN ORGANISM IS THE ETIOLOGIC AGENT OF DISEASE
REVIEW KOCH'S POSTULATES: (TORTORA pg. 370)
ORGANISM ALWAYS PRESENT AND ISOLATABLE
DISEASE CAN BE TRANSMITTED WITH THAT ORGANISM IN AN EXPERIMENTAL ANIMAL
ORGANISM CAN BE REISOLATED FROM THE EXPERIMENTAL ANIMAL
THERE ARE EXCEPTIONS:
HIV AND AIDS
MYCOBACTERIUM LEPRAE
TREPONEMA PALLIDUM
SPREAD OF INFECTION IN A POPULATION
NEED TO KNOW THE RESERVOIR AND MODE OF TRANSMISSION
RESERVOIR
CAN THINK OF THE RESERVOIR AS THE SOURCE OF THE ORGANISM
HUMAN SOURCE:
SICK HUMAN -- ACUTE ILLNESS (RAPIDLY DEVELOPING AND OFTEN RAPID RESOLUTION - GET BETTER OR DIE. ex. influenza, chicken pox, cholera, strep throat.
CARRIER HUMAN -- INAPPARENT INFECTIONS, SUBCLINICAL INFECTION, CHRONIC INFECTION.
MARY MALLON -- TYPHOID MARY
ex.: tuberculosis, epstein-barr infection (mononucleosis), syphilis, HIV infection, Hepatitis B
ANIMAL SOURCE: WILD ANIMAL (SYLVATIC)? DOMESTIC?
ZOONOSIS -- PRIMARILY AN ANIMAL DISEASE AND THEN SPREAD TO HUMANS.
EXAMPLES OF DISEASES WITH A SIGNIFICAN ANIMAL RESERVOIR: rabies, plague, leptospirosis, lyme disease, toxoplasmosis, psittacosis, salmonella food poisoning
NON-LIVING SOURCE:
SOIL HARBORS ORGANISMS THAT CAUSE A VARIETY OF INFECTIOUS DISEASES
ex.: tetanus, botulism, anthrax, Pseudomonas infections, a variety of fungi.
WATER IS OFTEN CONTAMINATED AND CAN SERVE AS A VEHICLE OF INFECTION.
ex. giardiasis, typhoid fever, amebiasis, leptospirosis -- note that water is easily contaminated by human and animal feces.
MODE OF TRANSMISSION
PHYSICAL CONTACT
DIRECT CONTACT -- TOUCH, KISS, SEX, ANIMALS
INDIRECT -- FOMITES (INANIMATE OBJECTS THAT SERVE AS MEANS OF SPREAD) -- DOORKNOBS, TOWELS, PHONES, NEEDLES AND OTHER MEDICAL EQUIPMENT
DROPLET AND AEROSOLS-- BREATHE IN SUSPENDED INFECTIOUS PARTICLES - IMPORTANT IN MANY RESPIRATORY INFECTIONS (see picture Tortora pg. 376)
INGESTION -- EAT INFECTIOUS MATERIAL - ORAL-FECAL TRANSMISSION
ONE CAN SOMETIMES DESCRIBE TRANSMISSION AS CAUSED BY A COMMON VEHICLE -- THIS CAN BE FOOD, IV PRODUCTS AND BLOOD PRODUCTS, DRUGS, WATER, AN AIR SUPPLY.
VECTOR -- AN INFECTED ANIMAL (usually an insect) THAT TRANSMITS TO HUMANS
BIOLOGICAL TRANSMISSION -- THE ANIMAL HOST IS NEEDED BY THE MICROBE FOR SOME METABOLIC OR OTHER ESSENTIAL PROCESS. ex.: malaria protozoan- mosquito; Lyme disease spirochete -- tick; sleeping sickness protozoan -- tsetse fly; the plague bacterium -- flea and rodent (rat)
MECHANICAL TRANSMISSION -- THE ANIMAL HOST PICKS UP THE MICROBES AND MOVES THEM AROUND. ex.: flies landing on feces or dead animals. cockroaches and lizards rats can do the same thing.
HOSPITAL ACQUIRED INFECTIONS -- 5-15% OF ALL INPATIENTS WILL SUFFER THESE.
NOSOCOMIAL INFECTIONS
IATROGNIC INFECTIONS
HOSPITAL ACQUIRED INFECTIONS ARE ESPECIALLY FEARSOME BECAUSE:
MANY HOSPITAL ORGANISMS ARE RESISTANT TO ANTIBIOTICS
PATIENTS ARE COMPROMISED BY DISEASE, INJURY AND CHEMOTHERAPY
THERE ARE MANY INVASIVE PROCEDURES
READ TORTORA FOR: EPIDEMIOLOGY, TYPES OF INFECTION (local, systemic, focal, bacteremia, septicemia, viremia, primary infection, secondary infection, superinfection, pneumonia, meningitis, gastroenteritis, hepatitis), PATTERNS OF DISEASE and PREDISPOSING FACTORS.
THE VIRULENCE FACTORS OF MICROORGANISMS
THIS INVOLVES INVASIVE FACTORS AND TOXICITY FACTORS
ORGANISMS HAVE TO GET IN FIRST (HOW?) -- THE PORTALS OF ENTRY:
MUCOUS MEMBRANES - MOUTH, NOSE, EYES, RESPIRATORY, GI, GU.
BREAKS IN THE SKIN
BREAKS INTO THE TISSUES BELOW THE SKIN INTO THE TISSUES, VEINS OR ARTERIES -- PARENTERAL
ORGANISMS HAVE TO ADHERE -- THEY HAVE ADHESINS
CAPSULE -- HELPS TO ATTACH BUT ALSO IMPEDES PHAGOCYTOSIS. ex.: Streptococcus pneumoniae, Klebsiella pneumoniae, Streptococcus mutans - dextran and tooth decay.
FIMBRIAE (PILI) -- ARE OFTEN TISSUE SPECIFIC.
ex.: E.coli strain differences in tissue specificity due to different types of fimbriae - urinary tract strains differ from enteropathogenic strains in the type of pili they make. Whooping cough bacterium - Bordetella pertusis attaches specifically to repiratory epithelium cilia.
Neisseria gonorrhea - has pili and outer membrane proteins that allow it to stick to urethral and vaaginal epithelium, non-ciliated fallopian tube cells, sperm cells and neutrophils; Streptococcus pyogenes - protein F attaches to pharyngeal epithelium, protein M attaches to keratinocytes in the skin both proteins are are part of the fimbriae of these organisms.
THE CELL WALLS OF SOME BACTERIA HAVE VIRULENCE PROMOTING PROPERTIES
ex.: Streptococcus pyogenes - protein G binds to the back end of antibodies preventing their normal function - this is a CLOAKING DEVICE for the bacterial cell and it helps the cell avoid phagocytosis. Staphylococcus aureus has protein A - which works the same way. Mycobacterium tuberculosis has wax D and sulfolipids which inhibit the killing mechanisms of phagocytes.
THE OUTER MEMBRANE OF GRAM NEGATIVE ORGANISMS (endotoxin, LPS, contains lipid A).
THIS STRUCTURE IS SLOUGHED OFF DURING THE LIFE OF THE ORGANISM AND IS SHED IN LARGE SCALE WHEN THE ORGANISM DIES. HAS PROFOUND TOXIC EFFECTS ON THE HUMAN. CAN RESULT IN FEVER, WEAKNESS, ACHES, SHOCK, HEMORRHAGE, MISCARRIAGE, DISSEMINATED INTRAVASCULAR COAGULATION. THESE EFFECTS ARE CAUSED BY THE RELEASE OF INTERLEUKIN-1 (IL-1) AND TUMOR NECROSIS FACTOR (TNF) BY MACROPHAGES IN AN APPARENT OVER-REACTION. THESE ARE CYTOKINES WHICH AFFECT MANY ASPECTS OF THE INFLAMMATORY AND IMMUNE RESPONSES.
BACTERIAL ENZYMES ASSOCIATED WITH VIRULENCE - MANY ARE EXOENZYMES OR SECRETED ENZYMES.
LEUKOCIDINS -- DESTROY PHAGOCYTIC LEUKOCYTES, WHICH THEN RELEASE THEIR OWN DIGESTIVE ENZYMES ONTO THE TISSUES. S. aureus and S. pyogenes.
HEMOLYSIN -- DESTROY RBC'S -- S. aureus, S. pyogenes and C. perfringes
COAGULASE -- MAKESA FIBRIN CLOT AROUND THE ORGANISM. -- S. aureus
BACTERIAL KINASES -- DIGEST FIBRIN CLOTS -- streptokinase and staphylokinase. can be used therapeutically to dissolve blood clots.
HYALURONIDASE -- DISSOLVES HYALURONIC ACID
COLLAGENASE (GELATINASE) -- DISSOLVES COLLAGEN
SIDEROPHORES -- SCAVENGE IRON
BACTERIAL TOXINS -- EXOTOXINS (MANY ARE ENZYMES)
CAN BE CLASSIFIED AS CYTOTOXINS, NEUROTOXINS, ENTEROTOXINS.
DIPTHERIA TOXIN -- PHAGE WITH TOX GENE. TOXIN INHIBITS PROTEIN SYNTHESIS IN EUCARYOTIC CELLS
ERYTHROGENIC TOXIN -- THIS IS A SUPERANTIGEN -- HOST REPONSE CAUSES FEVER AND RASH AND DAMAGE TO CAPILLARIES
BOTULINUM TOXIN -- HITS THE NEUROMUSCULAR JUNCTION - NO ACETYLCHOLINE RELEASE - FLACCID PARALYSIS.
TETANUS TOXIN (TETANOSPASM) -- HITS THE CENTRAL NERVOUS SYSTEM - INHIBITS THE FIRING OF THE INHIBITORY MOTOR NEURONS - SPASTIC PARALYSIS.
CHOLERA TOXIN (CHOLERAGEN) -- STIMULATES ADENYL CYCLASE IN THE ENTEROCYTES - WHICH THEN DUMP WATER AND ELECTROLYTES INTO THE SMALL INTESTINE.
E. COLI ENTEROTOXIN -- VERY SIMILAR TO CHOLERA TOXIN
S. AUREUS ENTEROTOXIN -- HAS CHOLERAGEN LIKE ACTIVITY BUT IS ALSO A SUPERANTIGEN -- ACTIVATES T-CELLS TO RELEASE ALOT OF INTERLEUKIN-2 (IL-2) AND TUMOR NECROSIS FACTOR (TNF).
SOME BACTERIA HAVE ENZYMES AND PROPERTIES THAT ALLOW THEM TO SURVIVE INSIDE PHAGOCYTIC CELLS. THESE INCLUDE MYCOBACTERIUM TUBERCULOSIS, SALMONELLA TYPHI, AND NEISERRIA GONORRHEA