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Germs 201: Microbes And GERMS 201:MICROBES vs. MAN RICHARD S. NEIMAN, M.D. “THE GERM” • A MIGHTY CREATURE IS THE GERM, ‘THO SMALLER THAN A PACHYDERM • ITS CUSTOMARY PLACE IS DEEP WITHIN THE HUMAN RACE • ITS CHILDISH PRIDE IT OFTEN PLEASES BY GIVING PEOPLE STRANGE DISEASES • DO YOU, MY POPPET, FEEL INFIRM? • YOU PROBABLY CONTAIN A GERM! OGDEN NASH HANS ZINSSER, “RATS, LICE AND HISTORY” • “INFECTIOUS DISEASE IS ONE OF THE FEW GENUINE ADVENTURES LEFT IN THE WORLD. THE DRAGONS ARE ALL DEAD AND THE LANCE GROWS RUSTY IN THE CHIMNEY CORNER. ABOUT THE ONLY SPORTING PROPOSITION THAT REMAINS UNIMPAIRED BY THE RELENTLESS DOMESTICATION OF A ONCE FREE-LIVING HUMAN SPECIES IS THE WAR AGAINST THOSE FEROCIOUS LITTLE CREATURES WHICH LURK IN THE DARK CORNERS AND STALK US IN THE BODIES OF RATS, MICE AND ALL KINDS OF DOMESTIC ANIMALS; WHICH FLY AND CRAWL WITH THE INSECTS, AND WAYLAY US IN OUR FOOD AND DRINK AND EVEN IN OUR LOVE.” THE MIGHTY CREATURE MICROBES HAVE BEEN RESPONSIBLE FOR MORE HUMAN DEATHS THROUGHOUT HISTORY THAN ALL THE WARS COMBINED. MORE COMBATANTS DIED OF INFECTIOUS DISEASES THAN ENEMY ACTION IN ALL U.S. WARS UNTIL WWII. IN WWII IN THE ASIAN THEATER ALONE THERE WERE OVER 500 THOUSAND CASES OF MALARIA IN US TROOPS. WHY ARE INFECTIOUS DISEASES SO IMPORTANT IN HUMAN HISTORY? • THEY CAN, BY DEFINITION, SPREAD. • THEY DISPROPORTIONALLY INFECT PREVIOUSLY UNEXPOSED PEOPLES. • THEIR PREVENTION AND CONTROL DEPENDS UPON INTERNATIONAL COOPERATION. “THE MICROBE THAT FELLED ONE CHILD IN A DISTANT CONTINENT YESTERDAY COULD REACH YOURS TODAY AND SEED A GLOBAL PANDEMIC TOMORROW” JOSHUA LEDERBERG GERM SYNONYMS: • MICROBE • MICROORGANISM • MICROSCOPIC ORGANISM • INCLUDES BACTERIA, VIRUSES, PROTOZOA AND FUNGI VIRUS • A MICROSCOPIC INFECTIVE AGENT, TOO SMALL TO BE SEEN BY A CONVENTIONAL MICROSCOPE, CONSISTING OF A NUCLEIC ACID MOLECULE (EITHER DNA OR RNA) IN A PROTEIN COAT. • IT IS ABLE TO MULTIPLY ONLY WITHIN THE LIVING CELLS OF A HOST BACTERIUM • A ONE-CELLED ORGANISM THAT HAS A CELL WALL AND AN ORGANIZED NUCLEUS. • MOST BACTERIA ARE HARMLESS TO MAN, OTHERS CAN CAUSE DISEASE IN OTHER ANIMALS ONLY, AND STILL OTHERS CAUSE DISEASE IN MAN. PROTOZOAN • A SINGLE-CELLED ORGANISM EITHER FREE- LIVING OR PARASITIC, THAT FEEDS ON ORGANIC MATTER SUCH AS OTHER MICROORGANISMS OR ORGANIC TISSUE OR DEBRIS. IT FREQUENTLY HAS A COMPLEX LIFE CYCLE. AN EXAMPLE OF SUCH AN ORGANISM IS PLASMODIUM, THE MALARIA PARASITE. FUNGUS • A GROUP OF ORGANISMS INCLUDING MOLDS , MILDEWS, MUSHROOMS AND RUSTS THAT PARASITIZE LIVING ORGANISMS OR FEED UPON DEAD ORGANIC MATERIAL. THEY LACK CHLOROPHYLL, ROOTS, STEMS AND LEAVES AND REPRODUCE BY MEANS OF SPORES. THERAPY OF MICROORGANISMS • BACTERIA—MANY EFFECTIVE DRUGS AVAILABLE; PROBLEM OF DRUG RESISTANCE GROWING. • VIRUSES—FEW DRUGS AVAILABLE. • PROTOZOA—DRUGS AVAILABLE, BUT MANY TOXIC. • FUNGI—SOME DRUGS AVAILABLE. HISTORICAL THEORIES OF INFECTIOUS DISEASE • GOD’S PUNISHMENT FOR SIN • IMBALANCE OF BODILY HUMORS (BLOOD, BLACK BILE, YELLOW BILE, PHLEGM)(“CHOLERA”) • UNCLEANLINESS • FETID OR POLLUTED AIR (“MALARIA”) • COSMIC FORCES (“INFLUENZA DELLE STELLE”) EPIDEMICS: HATE AND COMPASSION FROM THE PLAGUE OF ATHENS TO AIDS COHN, S.K. JR. THE MICROBE IS SO VERY SMALL YOU CANNOT MAKE HIM OUT AT ALL BUT MANY SANGUINE PEOPLE HOPE TO SEE HIM THROUGH A MICROSCOPE HILLAIRE BELLOC GERM THEORY • “MANY DISEASES ARE CAUSED BY MICROORGANISMS THAT INVADE HUMANS, ANIMALS OR OTHER HOSTS”. • FIRST PROPOSED BY FRACASTORO IN 1546 AND EXPANDED UPON BY VON PLENCIZ IN 1762, BUT WAS NOT ACCEPTED UNTIL PROVEN BY THE WORK OF PASTEUR AND KOCH IN THE 1880s KOCH’S POSTULATE • TO POSTULATE THAT A GIVEN ORGANISM IS THE CAUSE OF A GIVEN DISEASE, IT IS NECESSARY TO ISOLATE IT FROM A PATIENT (OR EXPERIMENTAL ANIMAL) WITH THAT SPECIFIC DISEASE, AND REINTRODUCE IT INTO ANOTHER, THEREBY CAUSING THE SAME DISEASE. QUESTIONS • HOW HAS THE SOCIAL EVOLUTION OF MAN FROM HUNTER-GATHERER TO MEGALOPOLIS- DWELLER AFFECT THE NATURE, EXTENT AND SEVERITY OF INFECTIOUS DISEASES? • HOW DO EPIDEMICS AND PANDEMICS BECOME ENDEMIC, AND VICE-VERSA? • WHY HAS MAN’S CONQUEST OF CERTAIN INFECTIOUS DISEASES BEEN PROBLEMATIC? • WHAT IS IN STORE IN THE FUTURE? FACTORS AFFECTING INCIDENCE AND SEVERITY OF EPIDEMICS • POPULATION AND ITS DENSITY • LIVING CONDITIONS • WARS • EASE OF TRAVEL • HEALTH OF EXPOSED POPULATION(S) (HERD IMMUNITY) • EFFECTIVENESS OF PREVENTIVE MEASURES • MEDICAL PREPAREDNESS • MEDICAL ADVANCES FACTORS AFFECTING SEVERITY OF AN INFECTIOUS ILLNESS • GENERAL HEALTH OF INDIVIDUAL • NUTRITIONAL STATUS • AGE • IMMUNOLOGIC STATUS • STRAIN (SUBTYPE) OF OFFENDING ORGANISM (VIRULENCE) • SIZE OF INITIAL “DOSE” OF ORGANISM • PAST EXPOSURE DARWINIAN QUANDRY • HOW CAN A PATHOGENIC MICROORGANISM SURVIVE IF IT KILLS ITS HOSTS OR RENDERS THEM IMMUNE FROM FUTURE INFECTION? • MICROORGANISMS HAVE EVOLVED MANY WAYS TO SOLVE THIS PROBLEM ENDEMIC vs. EPIDEMIC • ENDEMIC IS A MORE STABLE PATTERN OF INFECTION, LESS DESTRUCTIVE TO HUMAN HOSTS AND MORE SECURE FOR THE MICROBE, SINCE ALL HOSTS DO NOT DIE OR BECOME IMMUNE, AND THERE IS A FRESH CROP OF HUMAN HOSTS TO INFECT EACH YEAR ( PEDIATRIC INFECTIONS). CHARTACTERISTICS OF THE IDEAL PATHOGEN • BE HIGHLY CONTAGEOUS • REPLICATE (MULTIPLY) QUICKLY • MUTATE FREQUENTLY • CONSIST OF MANY IMMUNOLOGICALLY DISTINCT SUBTYPES • DO NOT KILL HOST (IF DO, NOT QUICKLY) • HAVE A PLACE TO HIDE (RESERVOIR, VECTOR, SPORULATION) • RESIST THERAPY • RESIST VACCINE EFFECTIVENESS WEAPONS USED BY PATHOLOGIC ORGANISMS TO SURVIVE • SPREAD EASILY—” LIKE SOFT BUTTER” • EXAMPLES: INFLUENZA, CHOLERA,YELLOW FEVER, MOST “CHILDHOOD DISEASES” WEAPONS USED BY PATHOLOGIC ORGANISMS TO SURVIVE • MULTIPLY LIKE CRAZY AND MUTATE WHEN THE HOST DEVELOPS IMMUNITY (“DAMN THE TORPEDOES, FULL SPEED AHEAD”) • EXAMPLE: INFLUENZA WEAPONS USED BY PATHOLOGIC ORGANISMS TO SURVIVE • HIDE IN WATER, THEN AMBUSH • EXAMPLES: CHOLERA POLIO TYPHOID MECHANISMS FOR PATHOLOGIC ORGANISMS TO SURVIVE • HIDE YOUR RESERVE FORCES IN ANOTHER ORGANISM TO USE FOR A RAINY DAY (RESERVOIR),(VECTOR) • EXAMPLES: LEPROSY PLAGUE MALARIA TYPHUS ANTHRAX YELLOW FEVER DENGUE MECHANISMS FOR PATHOLGIC ORGANISMS TO SURVIVE • FORTIFY YOURSELF IN AN IMPREGNABLE FORTRESS (FORM SPORES) • EXAMPLES: ANTHRAX BOTULISM (CLOSTRIDIUM) GAS GANGRENE DISEASES IN THIS COURSE • VIRAL: • BACTERIAL: • DENGUE • TYPHUS • YELLOW FEVER • TYPHOID • MEASLES(RUBEOLA) • SALMONELLOSIS • MUMPS • DIPHTHERIA • CHICKENPOX • BRUCELLOSIS • GERMAN MEASLES • GONORRHEA • (RUBELLA) • ANTHRAX • HEPATITIS (ALL TYPES) • PERTUSSIS (WHOOPING • COUGH).
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