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3: Brief History of Infectious Diseases

Homework:

-explore efforts to track emergence of new human diseases by doing online search with key words “Nathan Wolfe and  jungle viruses video”   http://www.gvfi.org/

Origin of parasitism: the “Food Fight”

We have discussed how a pathogen/parasite invades another organism (the host) and causes harm/infectious disease. We might ask “Why does a pathogen behave this way?”

Some people think of pathogens as being “evil”, (note on pages ___ in _______ use of adjectives ______), but the real explanation is much less sinister.

Historian William McNeil suggests that a search for food by pathogens might be at the bottom of infectious diseases.

Disease and parasitism play a pervasive role in all life. A successful search for food on the part of one organism becomes for its host a nasty infection or disease.   All animals depend on other living things for food, and human beings are no exception. Problems of finding food and the changing ways human communities have done so are familiar enough in economic histories.  The problems of avoiding becoming food for some other organism are less familiar, largely because from very early times human beings ceased to have much to fear from large-bodied animal predators like lions and wolves. Nevertheless,, one can properly think of most human lives as caught in a precarious equilibrium between the microparasitism of disease organisms and the macroparasitism of large-bodied predators, chief among which have been other human beings.”

McNeil describes microparasites as “tiny organisms”, the viruses, bacteria and protozoa we have discussed earlier. He describes macroparasites as larger parasites, also of great diversity. He continues to describe how the skills of early human hunters “outclassed their rival predators. Humanity thus emerged at the top of the food chain*….Later when food production became a way of life…a modulated macroparasitism** became possible. A conqueror could seize food from those who produced it, and by consuming it himself become a parasite of a new source….Early civilizations were built upon the possibility of taking only a part of the harvest from subjected communities, leaving enough behind to allow the plundered community to survive indefinitely….”

Source: People and Plagues p5-6 William H. McNeil Anchor Books

(*we might argue that pathogens are truly at the top of the food chain)

(**When working on your infectious disease project , you might want to consider what type of “modulated macroparasitism” still occurs in the world, and how this form of parasitism ALSO contribute to the prevalence of infectious diseases, part of the “political ecology” of infectious diseases).

What does food have to do with diseases and pathogens?   What is the “goal” of living organisms, of pathogens? From a biologist’s perspective, the simplest goal would be to grow and reproduce. To grow and reproduce, all organisms require a source of  “building blocks”. We generally refer to the source of these building blocks as “food”. For pathogens, we humans represent a wonderful source of “fast food”.

Infectious diseases are the products of “food fights”. Pathogens invade hosts and cause disease, not because the pathogens are “evil”, but because they require a food source to grow and replicate.  While the pathogen benefits from the food fight, the host suffers, the classic example of parasitism.

Early examples of  “food fights” or simple predator-prey relationships

  • predator:  the hunter
  • prey:  what is being hunted, what will end up as “food” for the predator
  • phagocytosis: literally “cell eating”, a means of bringing large particles into a cell in a membrane-bound vesicle

Phagocytosis and early predator-prey interactions

Predator-prey relationships probably developed soon after the first unicellular cells evolved. Larger unicellular protozoa “hunted” and “ate” smaller bacteria. The process by which the protozoa “ate” their bacterial prey is called phagocytosis (“cell eating”).

Phagocytosis occurs when the “prey” is enclosed in a membrane-lined “sac” or vesicle ( a “phagosome” = “eating body”) by the predator.  Eventually lysosomal digestive enzymes will kill and break-down the prey. The predator then absorbs the nutrients released from the digested prey.

 

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Bacterium is enclosed in a membrane-bound “phagosome”; lysosome fuses with phagosome and delivers hydrolytic enzymes

 

Bacterium is killed and digested

 

 

 

 

 

 

 

 

 

 

Fig 1: Phagocytosis of a bacterium by a phagocytic cell (see fig 18.10 p479 Belk’s Biology)

Modern examples of phagocytosis

The process of phagocytosis is still carried out by “modern” protozoa. It is also used by many of your immune cells (phagocytic cells called macrophages and neutrophils) to capture and destroy invading pathogens

“Multicellular predator”-prey relationships

 Multicellular organisms also developed predator-prey relationships. Carnivores such as lions and cheetahs would hunt prey animals such as gazelle. Humans slowly evolved skills which permitted them to hunt a wide variety of prey animal (including other predators). These skills permitted humans to reach the top of the food chain (maybe).  One could argue that pathogens are truly at the top of the food chain, using humans as a source of nutrients.

Infectious disease as a modern example of “predator-prey” relationship:

Microbial pathogens are obviously too small to phagocytize us, their hosts. However this does not stop them from stealing nutrients from us and frequently causing great harm in the process.  In this case, we would be considered the prey and the tiny microbes would be considered the predators. (note: size then does not ensure success!)

Ancient Infectious Diseases, Jared Diamond and “The Lethal Gift of Livestock”

Agriculture predisposes humans to new zoonotic and “crowd diseases”

In exploring the origins of ancient human infectious diseases, Jared Diamond in Guns, Germs and Steel states that the earliest human infectious diseases were shared with humans’ nearest relative, the great apes.

As hunter-gatherers living in small groups and constantly on the move, humans were not at great risk for pathogens spread through feces-contaminated food or water. Compared to their farmer descendants, these early hunter-gatherers had low exposure to pathogens carried by animals.

Diamond states that development of agriculture predisposed humans to new “crowd infectious diseases” and to new diseases transferred from animals to humans (zoonotic diseases, zoonoses).  Increased, reliable food production led to increased birth rates, sedentary lifestyles and thus increased population density (which pathogens love!). If a disease outbreak occurred, it was easier for a pathogen to be spread to a new host if the hosts were crowded together in towns/cities. Increasing population density caused problems with sanitation/sewage disposal. Humans started living in their own feces and thus were exposed to all the pathogens feces carries for example intestinal viruses, bacteria, protozoa and worms. Feces could contaminate food and water which could then quickly spread pathogens (fecal-oral transmission). Feces and urine were also used to fertilize fields thus increasing farmers exposure to pathogens and increasing fecal contamination of food. (Diamond)

(Hopefully in class we can see clip from “Guns, Germs and Steel”)

 

Diamond and Garrett : Progress, Modern “Mega Cities” and  Diseases

Both Diamond and Garrett report that urbanization increased human susceptibility to “crowd” infectious diseases. Increased population growth and crowding, lack of housing, and inadequate nutrition led to ideal conditions for the spread of pathogens within cities.  Within cities, tremendous sanitation problems arose. Feces and garbage are havens for pathogens, rodents and vectors. 

Diamond provides examples of epidemic disease which throughout history have decimated urban populations. (see Table 1).

Table 1: Disease decimating urban populations throughout history; “crowd diseases”    

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            1. Epidemic typhus: Rickettsia prowazeki; body louse vector

            2. Plague (bubonic and pneumonic plague): Yersinia pestis; fleas, aerosols

            3. Cholera: Vibrio cholerae; fecal contaminated water, food

            4. Tuberculosis: Mycobacterium tuberculosis: aerosols (also food=gi TB)

            5. Typhoid: Salmonella typhi: fecal contaminated food, water

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Domestication of animals and zoonotic diseases

Domestication of animals triggered the appearance of new zoonoses (zoonoses=human disease in which pathogen maintains an animal reservoir). Humans began living closely with their animals which increased human exposure to animal pathogens carried in milk, blood, saliva, urine and feces.  This intimate contact also increased human exposure to parasites carried by animals which could act as arthropod vectors carrying animal pathogens (for example fleas, ticks and lice).  Some of the animal pathogens were capable of adapting to life in new human hosts. For example, a mutation in the surface structure of a microbial animal pathogen might permit the pathogen to bind to human cells, resulting in a new zoonoses (the pathogen “jumped hosts”). Some of the animal pathogens adapted so well to life in humans they lost their ability to live in animal hosts over time.   Other animal pathogens were more flexible and retained their ability to infect both humans and animals. Thus animals became reservoirs for these pathogens. (Diamond; see table 2 below)

Agriculture and increased food production attracted rodents to human settlements. Stored food attracted rodents which became important sources of vectors and pathogens for humans. ( e.g. Buboninc Plague)

 

Table 2: Examples of animal pathogen “ancestors” of human pathogens as described by Diamond

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Human disease/pathogen<------------  Animal disease/pathogen most closely related

 

1. Measles (paramyxovirus)  ß        Rinderpest of cattle (not zoonotic) 

                       

2. Tuberculosis (bacterium)   ß        Tuberculosis of cattle

 

3. “Whooping cough”/pertussis ßKennel cough” of dogs; atrophic rhinitis of pigs

   (bacterium)

 

4. Smallpox (virus)                 ß        Cowpox of cattle; provides protective immunity in                                                                          humans against smallpox

 

5. HIV                                      ß        SIV

 

6. Human Influenza               ß        Influenza of birds, pigs, horses (zoonotic;

(orthomyxovirus)                                            recombination in birds, pigs

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Modern examples  of animals as reservoirs of human pathogens

            1. Contamination of animal food products by pathogens

                        E.coli o157:H7, Salmonella, Campylobacter, Listeria monocytogenes,                                 prions…

            2. Contamination of drinking water with pathogens from animal feces

                        Cryptosporidium, Giardia, Cyclospora…

            3. “Wild” animal reservoirs

                        Hantavirus, Lyme Disease, Bubonic Plague…

 

4. Animal reservoirs as “recombination vessels” for human-animal pathogens

                        Example: Influenza viruses

“Modern EID’s”,  Emerging Infectious Diseases

Many of the factors leading to new human diseases throughout history are still at work and continue to contribute to the emergence of new infectious diseases. Changes in human behavior and destruction of natural habitats, pollution and over use of antimicrobials have fueled the emergence of new infectious diseases. Some of the factors contributing to EID’s are discussed below.

-Sexually transmitted infections, ‘STI’s”

Garrett describes how economic changes triggered a mass migration of men from the countryside into cities. Alone and lonely, some of these men practiced multiple partner, “anonymous” sex in the cities.  Sexually transmitted pathogens causing sexually transmitted infections or “STI’s” thus spread rapidly within the new “megacities”. Many of these men were married and would return to their wives and families on weekends or every few months. The men thus acted as human “vectors” of STI’s, spreading the pathogens to their wives in rural areas.

-Bush Meat and EIDS

See  Nathan Wolfe:   http://www.gvfi.org/

http://www.gvfi.org/projects_viral_discovery.html

 

Additional factors contributing to Emerging Infectious Diseases

Source: Emerging Infectious Diseases by Stuart Hill. 2006. Michael A Palladino, ed. Benjamin Cummings Special topics in Biology Series.

factor

disease

 

1. Emergence caused by environmental change

  • Lyme Disease (1970’s)
  • Venezuelan Hemorrhagic Fever(1980’s)
  • Korean Hemorrhagic Fever/Hantavirus/Sin nombre Virus (1990’s)
  • intrusion of humans into rodent-deer ecosystems; home construction in natural habitats
  • agricultural disruption of natural habitats, conversion forest to ag land
  • weather pattern changes, El Nino effects cause increase in pinenuts, then population explosion infected deermice, invasion of human homes

2. Emergence caused by human behavior

-Dengue Fever, Dengue Hemorrhagic Fever

 

 

 

-West Nile Fever

 

 

-cholera, dysentery, polio

 

 

-Bacterial meningitis

-increased population growth, urbanization, mass migration, war, shanty towns, crowding, nonexistent sanitation, mosquito breeding grounds, rapid transportation

 

-overcrowding in cities, mosquito habitats around human dwellings

 

-large, transient populations, refugee camps, poor sanitation

 

--crowding in college dormitories, exchange of body fluids

3. Emergence associated with international travel and commerce

 

 

 

 

 

-SARS (2002)

-STI’s: HIV, herpes, gonorrhea, chlamydia

-bacterial meningitis

-cholera

-BSE, “Mad Cow Disease”

-Ehrlichiosis

-Hepatitis A

-Cyclospora

-Monkeypox

-rapid spread from China globally

-global spread STI’s

-religious pilgrimages

-transported in contaminated ship ballast water to the Americas from Asia

-importation of infected animals

-importation of infected dogs, adaptation to humans

-importation of contaminated strawberries, onions

-importation of contaminated raspberries

-importation of infected  rodents  from Africa, infection of “pet” prairie dogs

4. Emergence associated with technical failings and public health breakdowns, government deregulations

-E.coli O157:H7 HUS, hemolytic colitis, hemolytic uremia

-Listeria monocytogenes

--BSE, “Mad Cow Disease”

-Hepatitis B and C

-Pertussis/whooping cough”

-Measles

-diphtheria

-MDR tuberculosis

-fecal contamination of beef/juice/fruits/veggies; lack of inadequate cooling

-fecal contamination of dairy/meat products/raw veggies

-deregulation meat rendering, use of animal tissues in animal feed, government “mis-advice” regarding consumption of contaminated beef products

-industrial concentration of blood products, exposure to contaminated needles/syringes

-changes in vaccination requirements for children

-parents choosing not to vaccinate children

-economic / public health /vaccination program “collapses”

-economic/ public health collapse

5. Emergence caused by microbial adaptations

-Mutation/evolution of bacteria associated with disease

-Mutations/evolution of viruses associated with disease

 

 

 

-Emerging antibiotic resistance

 

 

 

-“Flesh eating bacteria”-Group A Streptococcus GAS

-cholera Vibrio cholera biotype O139 pandemic

-Hantavirus

-Ebola virus

-HIV

-influenza

-MRSA /VRSA“superbugs”, nosocomial infections

-MDR tuberculosis

-acquisition of  new toxin genes from bacterial viruses

-bacterial mutations resulting in new strains

-these RNA viruses have high mutation rates because enzymes copying their RNA genetic info make many mistakes

-influenza viruses also can “re-assort”, mixing RNA segments from different influenza viruses to create new pandemic strains

-antibiotic overuse + immunocompromised hospitalized patient

-natural resistance to antibiotics because of repellant cell wall, latent stages, inadequate use of antibiotics in initial infections, public health system collapses

6. Emergence associated with increase in immunocompromised humans

-MDR TB, malaria, etc

-advances in medical technology: cancer therapy, steroid therapy for autoimmune/chronic inflammatory conditions, organ transplant recipients, -spread of HIV/AIDS

 

 

 

 

 

 

 

 

 

 

 

 

Class discussion: Add your own ideas above.

Brief history of microbiology and discovery of agents of infectious diseases

Age-old wisdom: if we do not study history, we are destined to repeat the mistakes of the past.

Most of you have been raised from childhood with some understanding of how “germs” cause disease. Early on we were taught to wash our hands after going to the bathroom, to turn away from others when we sneeze or cough, and not to spit in other peoples’ faces.  All of these learned behaviors help prevent the spread of pathogens between humans. 

So it might be difficult for us to imagine that for most of human history, people did NOT know about germs  and did not know what caused infectious diseases.

 “Miasmas” or bad air was thought responsible for some diseases such as malaria (malaria is a protozoal disease which is spread between people by a mosquito vector). Sadly many people thought that other people with “magical or evil powers” were responsible for infectious diseases such as plague. Often the poor, or minorities or anyone seen as “different” would be blamed for causing an outbreak of infectious disease. Many innocent people have been killed throughout history after being accused of causing an epidemic of disease.

So what was the problem? Why weren’t people aware of microbial pathogens? For centuries, people were unaware of microbial pathogens because they could not see them (as humans, we tend NOT to believe in things unless we can see them).

Wee animalcules discovered by Leeuwenhoek

It wasn’t until the 1600’s that microbes were first discovered by a Dutch linen merchant, Anton van Leeuwenhoek. Leeuwenhoek made his own powerful microscopes and delighted in looking at everything under his scopes. He was the first to observe and report the existence of bacteria and protozoa, his “wee animalcules”. Folks however still did not connect these wee animalcules to infectious diseases.

Edward Jenner and the smallpox vaccine

People for centuries were unaware of the immune system which protects us against pathogens. Without understanding how or why, Edward Jenner, an English country doctor, developed one of the first vaccines against smallpox in the 1700’s.. He took fluid from a cowpox vesicle and inoculated a 9 year old boy. After waiting some days, he then inoculated the boy with smallpox virus (! Yikes!). Luckily the boy survived this “challenge” with virulent smallpox but no one understood why. Today we know that the cowpox virus triggers production of “cross-reactive” or cross-protective “ antibodies”  against the smallpox virus, preventing smallpox in cowpox vaccinated people. This same type of vaccine  was used by WHO to eradicate smallpox ,the first infectious disease successfully eradicated. The modern smallpox vaccine virus is called vaccinia virus ( from root  vacca- cattle)

As Professor Meyer says: Remember Semmelweiss!!!

Ignaz Semmelweiss was a Hungarian working in a Viennese hospital in the 1800’s. He was convinced that it was NOT a good idea for medical students and doctors to perform autopsies before examining their patients on the obstetrics ward. Because no one knew that microbes caused diseases, and that the students’/doctors’ hands would become contaminated with microbial pathogens while performing the autopsies, NO ONE washed their hands after performing autopsies and before examining their patients and assisting with deliveries.  Semmelweiss guessed the students/doctors were somehow causing their pregnant patients to become  ill.  He had the audacity to suggest the students/doctors should WASH THEIR HANDS after performing autopsies. Everyone was horrified that he would make such a recommendation (suggesting the doctors and medical students were dirty???  The nerve of this guy!!!). Semmelweiss was hounded and humiliated, eventually suffering a nervous breakdown and dying in an asylum (so much for insight….).

Today lack of hand washing in hospital and medical clinics continues to cause spread of infectious diseases. Infections acquired in health care settings (hospitals, doctor’s office, dental offices, nursing homes) are called “nosocomial infections”. Many nosocomial infections are caused by health care professionals/staff who do not wash their hands before examining/treating patients. From Bauman’s Microbiology:

“ The CDC (Centers for Disease Control and Prevention) estimated that about 10% of American patients-over 2 million people-acquire a nosocomial infection each year. Nosocomial diseases…increase the duration and cost of medical care and result in some 90,000 deaths annually in the U.S.”

 

Joseph Lister vindicates Semmelweiss

Joseph Lister was a tough Scotsman who had read of Semmelweiss’ and Pasteur’s work. Lister was convinced that environmental microbes could be responsible for many wound and surgical infections. He instituted use of carbolic acid as a disinfectant and antiseptic. He would soak bandages in carbolic acid before applying to the wounds of his patients. He would wash his hands in carbolic acid and spray it in aerosols over the incision sites of his surgery patients.  Following these procedures, the number of patients developing or dying from wound or surgical infections greatly decreased. Thus Lister vindicated Semmelweiss.

 

John Snow, cholera, the Broad Street pump and the birth of epidemiology.

 

Golden Age of Microbiology: Pasteur and Koch

The accomplishments of Louis Pasteur would fill pages. We will note just a few. Pasteur was the first to prove that microbes where everywhere, even in the air. He carried out studies in fermentation and helped to lay the foundation for the germ theory of disease. He developed the first vaccine against rabies, developing the concept of “attenuated” pathogens as vaccines.

Robert Koch was a contemporary of Pasteur’s and probably had a (friendly?) competition with Pasteur’s lab. Koch developed 4 steps or pre-requisites which must be fulfilled to prove a specific microbe caused a specific disease. These 4 steps are called “Koch’s postulates”. Koch was the first to prove the germ theory of disease, which is that a specific microbe can invade another organism and cause a specific disease.

From  Robert Bauman’s Microbiology with Disease by Taxonomy, 2nd edition. 2007. Pearson Publish. Koch’s postulates: used to prove a specific microbe causes a specific disease

  1. The suspect causative agent/microbe must be isolated in every case of the diseases and be absent from healthy hosts
  2. The microbe must be isolated and grown in pure culture outside the host
  3. When the microbe is introduced into a healthy, susceptible host, the host must get the disease.
  4. The same microbe must be reisolated fro the diseases experimental host

Age of Chemotherapy: Ehrlich, Domagk and Fleming

Paul Erhlich is famous for developing the concept of “selective toxicity” or “magic bullets”. His goal was to find drugs which would specifically target, inhibit/kill a pathogen without harming the host. He identified Salvarsan, an arsenic containing compound, to treat syphilis (arsenic is also toxic for humans!).

Domagk and sulfa drugs: In the 1930’s in Germany, Gerhard Domagk discovered sulfa drugs as antibacterial chemotherapeutic agents. He found the first sulfa drug, Prontosil, was broken down in the animal body to the active agent, sulfanilamide. Sulfa drugs inhibit bacterial enzymes required (indirectly) for synthesis of nucleic acids.

Fleming, Florey and penicillin: The Scottish physician, Sir Alexander Fleming is famous for his discovery of penicillin, the first antibiotic. Antibiotics are described as chemicals produced by one (micro-) organism which harms another (micro-) organism. Antibiotics are the most famous “magic bullets” as they selectively target bacterial pathogens without harming the human host.  ( Fleming also discovered the enzyme called “lysozyme” found in eggs, tears and body secretion which can breakdown the cell walls of bacteria, causing them to die).

Large-scale production of penicillin and proof of its effectiveness treating bacterial infections was accomplished by scientists at Oxford University, led by Howard Florey (1939). During World War II, Florey brought cultures of the Penicillium mold  to the US in 1941 and coordinated  research efforts between the US government and several universities. Penicillin was first used on a relatively widespread basis during World War II. After the war, pharmaceutical companies soon identified many new antibiotics. (source: Brock Biology of Microorganisms 8th edition. 1997. Madigan et al editors. Prentice Hall publishers; see also Lax’s The Mold in Dr. Florey’s Coat)

Post- WWII, people were confident that antibiotics and vaccinations had conquered infectious diseases. Excerpts from Laurie Garrett’s The Coming Plague (p 33) illustrate the delusion of many:

            “ By 1967 US Surgeon General William H Stewart would be so utterly convinced   of imminent success that he would tell a White House gathering of state and      territorial health officers that it was time to close the book on infectious diseases          and shift all national attention (and dollars) to what he termed “the New     Dimensions” of health: chronic diseases.”

“ Boosters of the 1950s and early 1960s had some basis, born of ignorance, for their optimism: they knew comparatively little about genetics, microbial evolution, the human immune system, or disease ecology. Given the state of knowledge in the public health world of that day, it may have seemed appropriate to view infectious diseases in simple cause-and-effect terms. Seen in such a reductionist manner, problems and solutions appeared obvious and readily       conquerable, bravado warranted.”

Discovery of DNA as genetic information of cells

It wasn’t until 1944 that DNA was finally identified as the genetic information of cells Oswald Avery and Rockefeller Institute colleagues ( p 34 Garrett The Coming Plague) . The age of exploring the “ocean” of microbial genes was opened further with the discovery of the structure of DNA by Watson, Crick, and Franklin in 1953 (p 34 Garrett). As our understanding of microbial genetics expanded, so began our understanding of what “microbial trouble” we were in.

Understanding, protecting Earth's Biosphere

 

E.O Wilson: 2007 TED Talk: My Wish: Build the Encyclopedia of Life

https://www.ted.com/talks/e_o_wilson...th?language=en

E.O Wilson's "HIPPO" , how humans are threatening Life's Diversity on Earth

H=Habitat Destruction including Climate Change

I=Invasive species: from invasive plants and animals to pathogenic bacteria and viruses

P=Pollution

P= Population explosion of humans

O=Over-harvesting: hunting/fishing

 

Why/how could HIPPO cause an increase in infectious diseases in the future?

 

Ch 3 Discussion/Study guide questions Brief History of Infectious Diseases

1. From a pathogen’s point of view, humans are valuable as ______________________.

2. What is “phagocytosis”? Which cells in your body are “professional phagocytes? Why are they important?

3.Describe 3 reasons the development of agriculture caused an increase in human infectious diseases.

4. What are zoonoses? Describe 4 zoonotic diseases.

5. How do “mega-cities” contribute to the spread of infectious diseases? Name 3 “crowd” diseases.

6. What are “EID’s”, “Emerging Infectious Diseases”?

7. Describe 5 different factors contributing to evolution of “Emerging Infectious Diseases”.

8.What is “bush meat” and what is its role in EID evolution?

9. Microbiology history: Why were the following folks important? (would be matching questions on exam)

            a. Edward Jenner

            b. Ignaz Semmelweiss

            c. Joseph Lister

            d. Louis Pasteur

            e. Robert Koch

            f. Paul Ehrlich

            g. Snow

            h. Alexander Fleming

i. Florey

            j. Watson and Crick

10. What are Koch’s postulates, what do they prove?

11. What is the “Germ Theory of Disease”? Historically why was it important to prove the Germ Theory of Disease?

12. What are nosocomial infections?

-How many occur in the US each year?____    How many people die from nosocomial infections in the US each year?  ______

-What could Semmelweiss teach health care professionals which would help them reduce the number of nosocomial infections?

References

  1. Bauman, R. Microbiology with Disease by Taxonomy, 2nd edition. 2007. Pearson Publish.
  2. Brock Biology of Microorganisms 8th edition. 1997. Madigan et al editors. Prentice Hall publishers)
  3. Garrett, Laurie. The Coming Plague: Newly Emerging Diseases in a World Out of Balance. 1994. Penguin Books.
  4. Diamond, Jared. Guns, Germs and Steel: The Fates of Human Societies.1999. Norton Publishers (winner of Pulitzer Prize)
  5. Hill, Stuart. Emerging Infectious Diseases. 2006. Michael A Palladino, ed. Benjamin Cummings Special topics in Biology Series.
  6. Lax, Eric. The Mold in Dr. Flory’s Coat: The Story of the Penicillin Miracle. 2005. Henry Holt and Co. Publ.
  7. McNeill, W.H. Plagues and People. 1977. Anchor Books.