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Medical Microbiology and
Parasitology
Stijn van der Veen
Website for the course
Website: http://m-learning.zju.edu.cn
All basic course information
Course introduction and outline
Lecture slides
Basic information teachers
Online quizzes
Assessment & final mark
Attendance at lectures and lab (10%)
Online quizzes (20%)
Laboratory reports (10%)
In-class-quizzes (10%)
Final exam (50%)
Attendance
Attendance will be monitored at the beginning
of class
Being late for more than 20 minutes will be
considered as absent.
Not allowed to attend final exam when absent
for more than 70% of total lectures and lab
Online quizzes
3 quizzes
Each online quiz consists of 20-30 multiple choice questions
Students who missed the first attempt will be given one more chance to retake the quiz.
The maximum score for retaking quiz will be 60
If you missed the quiz, please contact with teacher assistants.
Kaixuan Li, [email protected]
Haili Zhou,[email protected]
Laboratory reports
Reports submitted after the deadline will be recorded as late
Late submissions will incur a penalty of 10% per day
Absence of a report will normally result in a score of 0 for that particular class
In-class-quizzes
The time and format of in-class-quiz depends
on each teacher
Final exam
Multiple choice questions （50 questions, 50 points）
True or false （20 questions, 20 points）
Short answer questions （4-5 questions, 30 points）
Introduction to
Medical Microbiology
What is a Microbe?
Microbes are (single-)cell organisms so tiny that millions can fit into the eye of a needle.
They are the oldest form of life on earth. Microbe fossils date back more than 3.5 billion years to a time when the Earth was covered with oceans that regularly reached the boiling point, hundreds of millions of years before dinosaurs roamed the earth.
Without microbes, we couldn’t eat or breathe.
Without us, they’d probably be just fine.
Understanding microbes is vital to understanding the past and the future of ourselves and our planet.
What is a Microbe?
Microbes are everywhere. There are more of them on a person's hand than there are people on the entire planet!
Microbes are in the air we breathe, the ground we walk on, the food we eat—they're even inside us!
We couldn't digest food without them—animals couldn't, either. Without microbes, plants couldn't grow, garbage wouldn't decay and there would be a lot less oxygen to breathe.
In fact, without these invisible companions, our planet wouldn't survive as we know it!
How small are microbes?
10-9
10-8
10-7
10-6
10-5
10-4
10-3
10-2
10-1
1
meter
Polio virus
Influenza virus
Pox virus
Staphylococcus
Plasmodium
Tryptanosome
Schistosome
Nematode
Tapeworm
Naked eye
Light microscope
Electron microscope
Bacillus cereus
1
101
102
103
104
105
106
107
108
109
meter
Human
Medical
school
Burj
Khalifa
Mount
Everest
Moon
Jupiter
Sun
Earth
Perspective
Thiomargarita
namibiensis
Microbes in the Tree of Life
Protista
Viruses?...not considered life!
Taxonomy (biological classification)
Carolus Linnaeus
Proposed the binomial nomenclature to standardize names for all living things.
Organisms are given two Latinized names:
Generic name (Genus)
Specific name (Species)
Names are always in Italics
Genus name is capitalized, species name not.
Second time use in text: genus name can be initialized
Carolus Linnaeus: 1707 – 1778
Examples
Bacteria Archaea Eukaryota
(not used) (not used) Animalia
Proteobacteria Euryarchaeta Chordata
Gammaproteobacteria Thermococci Mammalia
Enterobacteriales Thermococcales Carnivora
Enterobacteriaceae Thermococaceae Canidae
Escherichia Pyrococcus Canis
E. coli P. abyssi C. lupus
Types of microbes
Viruses
Unable to do much of anything on their own, viruses go into host cells to
reproduce, often wreaking havoc and causing disease. Their ability to move
genetic information from one cell to another makes them useful for cloning
DNA and could provide a way to deliver gene therapy.
Protista
Plant-like algae produce much of the oxygen we breathe; animal-like
protozoa (including the famous amoeba) help maintain the balance of
microbial life.
Fungi
From a single-celled yeast to a 3.5-mile-wide mushroom, fungi do
everything from helping to bake bread to recycling to decomposing waste.
Bacteria
Often dismissed as “germs” that cause illness, bacteria help us do an
amazing array of useful things, like make vitamins, break down some types
of garbage, and maintain our atmosphere.
Archaea
These bacteria look-alikes are living fossils that are providing clues to the
earliest forms of life on Earth.
Viruses
Acellular
Consist of DNA or RNA core
Core is surrounded by a protein coat
Coat may be enclosed in a lipid envelope
Viruses are replicated only when they are in a living host cell
Not considered life,…but this is still a debate
Bacteria
Prokaryotes
Cell wall contains peptidoglycan
Replicate by binary fission
Use organic chemicals, inorganic chemicals, or photosynthesis for energy
Come in many shapes
Archaea
Prokaryotes
No peptidoglycan (some have pseudopeptidoglycan)
Replicate by binary fission, fragmentation, or budding
Use organic chemicals, inorganic chemicals, or photosynthesis for energy
Live everywhere, including extreme environments
Methanogens
Extreme halophiles
Extreme thermophiles
Protista
Eukaryotes
Replicate sexually or by binary fission
Use sunlight or absorb or ingest organic chemicals for energy
May be motile via pseudopods, cilia, or flagella
Live mostly free, but some are parasites
Fungi
Eukaryotes
Chitin cell walls
Use organic chemicals for energy
Sexual or asexual reproduction through spores and mycelial fragmentation
Molds and mushrooms are multicellular
Yeasts are unicellular
Infectious diseases
Major impact on life expectancy
Bronze age => 26 yrs
Medieval times => 30 yrs
End of 19th century => 50 – 64 yrs
Now world average => 71 years
Infectious disease
Infectious diseases still account for 16% of all deaths worldwide, therefore it remains one of the leading causes of death
Infectious disease deaths worldwide in 2008; total 15 million.
Aristotle
Theory of spontaneous generation of life from nonliving matter.
Aristotle said: “it is readily observable that aphids arise from the dew which falls on plants, fleas from putrid matter, mice from dirty hay.”
Aristotle: 384 – 322 B.C.
First recorded perception of micro-life
Challenge of spontaneous generation
Francesco Redi: 1626 – 1697
Francesco Redi
Where do maggots come from?
Experiment
Jar 1 Jar 2 Jar 3
Left open Maggots
developed
Covered with netting
Maggots on netting
Sealed No maggots
Antonie van Leeuwenhoek: 1632 - 1723
First microscopes
Antonie van Leeuwenhoek
Grandfather of microbiology
His interests in lens making resulted in the first microscopes.
He discovered tiny organisms that were invisible to the naked eye and called these “animalcules”.
The Microscope
Anton Leeuwenhoek was Dutch.
He sold pincushions, cloth, and such.
The waiting townsfolk fumed and fussed,
as Anton’s dry goods gathered dust.
He worked, instead of tending store,
At grinding special lenses for
A microscope. Some of the things
He looked at were: mosquitoes’ wings,
the hairs of sheep, the legs of lice,
the skin of people, dogs, and mice;
ox eyes, spiders’ spinning gear,
fishes’ scales, a little smear
of his own blood, and best of all,
the unknown, busy, very small
bugs that swim and bump and hop
inside a simple water drop.
Impossible! Most Dutchmen said.
This Anton’s crazy in the head!
We ought to ship him off to Spain!
He says he’s seen a housefly’s brain!
He says the water that we drink
Is full of bugs! He’s mad, we think!
They called him dumkopf, which means dope.
That’s how we got the microscope.
Poem about Van Leeuwenhoek
Maxine Kumin:
Edward Jenner: 1749 - 1823
First vaccine
Edward Jenner
Father of immunology
Used cowpox inoculation, which causes mild symptoms, to protect against smallpox.
At that time it was estimated that 20% of the population died of smallpox, so he saved many lives.
Smallpox
Caused by the virus Variola major and Variola minor
Deadly disease with 30-35% mortality rate
Survivors often suffer from disfigurement and blindness.
Caused 300-500 million deaths in the 20th century
Through a widespread vaccination program WHO managed to eradicate smallpox in 1979
Notable victims include:Queen Mary II of EnglandEmperor Joseph I of AustriaKing Luis I of SpainTsar Peter II of RussiaKing Louis XV of France
Oliver Holmes: 1809 - 1894
Birth of the germ theory of disease
Oliver Holmes
Published in 1843 a paper on "The Contagiousness of Puerperal Fever”
Puerperal fever or childbed fever was very common and had a mortality rate of 10-35%
The paper stated that puerperal fever is passed on from patient to patient via contacts with their physician
Puerperal fever
Fever that is associated with an infection of the female reproductive organs.
Usually contracted as a result of childbirth or miscarriage.
Most common agent of the infection is Streptococcus pyogenes.
Other diseases caused by S. pyogenes: Strep Throat
Streptococcal Pneumonia
Scarlet fever
Necrotizing fasciitis
Ignaz Semmelweis: 1818 - 1865
Birth of the germ theory of disease
Ignaz Semmelweis
Investigated the cause for higher death rates due to puerperal fever in the maternity wards staffed by medical students than in those by midwives.
He linked this to the common practice of postmortem examination and the transfer of cadaverous material by the students
He introduced policy of hand washing with chlorinated lime
Hand washing is important
Hand washing is vital in healthcare settings to remove pathogenic micro-organisms!!!
The World Health Organization has "Five Moments" for washing hands
Before patient care
After environmental contact
After exposure to blood/body fluids
Before an aseptic task
After patient care
John Snow: 1813 - 1858
Birth of the germ theory of disease
John Snow
Father of epidemiology
In 1854, he investigated the source of a cholera outbreak in London.
He traced it to a water pump on Broad Street.
He had the pump disabled, which ended the outbreak.
His work resulted in changes and improvements to water (waste) systems all over the world.
Original map of the outbreak
Cholera
Infectious gastroenteritis cause by bacterium Vibrio cholerae.
Generally transmitted through contaminated water or food.
Damage of mucosal epithelium in small intestine resulting in massive diarrhea and fast dehydration.
Killed tens of millions of people in epidemics in the 19th and 20th century.
Still affects 3-5 million people annually, with an estimated 100,000 deaths.
Pasteurization & fermentation
Louis Pasteur
Father of microbiology
With his growth and fermentation experimentshe conclusively proved the theory of biogenesis.
Demonstrated that spoilage organisms could be killed by heat that was not hot enough to evaporate the alcohol in wine.
This application of a high heat for a short time is called pasteurization.
Louis Pasteur: 1822 - 1895
Attenuated vaccines
He worked on ways to prevent chicken cholera.
Due to neglect of his assistant, old culture were used to inoculate chickens. Chickens recovered and became immune.
The bacteria had become weakened (attenuated).
He named these artificially weakened infectious diseases “vaccines”.
He produced the first attenuated vaccine for rabies by drying the nerve tissue of infected rabbits.
Rabies vaccine
In 1885, a young boy, Joseph Meister, had been bitten by a rabid dog, and was brought to Pasteur. The boy almost certainly would have died an agonising death if nothing was done so Pasteur took the risk on using his untested vaccine.
"The death of this child appearing to be inevitable, I decided, not without lively
and sore anxiety, as may well be believed, to try upon Joseph Meister, the
method which I had found constantly successful with dogs. Consequently, sixty
hours after the bites, and in the presence of Drs Vulpian and Grancher, young
Meister was inoculated under a fold of skin with half a syringeful of the spinal
cord of a rabbit, which had died of rabies. It had been preserved (for) fifteen
days in a flask of dry air. In the following days, fresh inoculations were made. I
thus made thirteen inoculations. On the last days, I inoculated Joseph Meister
with the most virulent virus of rabies."
© 2000-2015 HistoryLearningSite.co.uk
Rabies
Rabies is a viral infection of the brain caused by lyssavirusses
Generally transmitted by bites from infected dogs or bats
It is almost 100% deathly unless treated with vaccines or immunoglobulin within 10 days of infection
Rabies causes about 26,000 to 55,000 deaths worldwide per year
Source: Black et al. Sci. Transl. Med. (2012) 29: 123ps5
Robert Koch: 1843 - 1910
Koch’s postulates
Robert Koch
Founder of modern bacteriology
Koch’s postulates, linking micro-organisms to disease
Identified the causative agents for cholera, anthrax, and tuberculosis, thereby proving the concept of infectious diseases.
Improved laboratory techniques and introduced bacterial agar and the Petri dish to purify bacterial colonies
Koch’s postulates
The organism must always be
present, in every case of the
disease.
The organism must be isolated
from a host containing the disease
and grown in pure culture.
Samples of the organism taken
from pure culture must cause the
same disease when inoculated into
a healthy, susceptible animal in the
laboratory.
The organism must be isolated
from the inoculated animal and
must be identified as the same
original organism first isolated from
the originally diseased host.
Anthrax
Lethal disease caused by the bacterium Bacillus anthracis.
Pulmonary or respiratory
Gastrointestinal by consumption of infected meat
Cutaneous through skin lesions
Common organism present in the soil.
B. anthracis can form dormant endospores that are able to survive for centuries.
Used for development of biological weapons.
First vaccines developed by Pasteur.
Joseph Lister: 1827 - 1912
Antiseptic surgery
Joseph Lister
Father of modern surgery
Gangrene or wound rotting was a major problem associated with surgery
Heard about work from Pasteur and promoted sterile surgery.
Introduced carbolic acid (phenol) to clean wounds and sterilize surgical instruments.
Paul Ehrlich: 1895-1964
First antimicrobial agents: arsphenamine
Paul Ehrlich
Initiating and named the concept of chemotherapy.
His lab synthesized Arsphenamine, which is also known as Salvarsan or compound 606.
Arsphenamine was the first effective medical treatment for syphilis
Arsphenamine was very unstable, oxygen sensitive and later replaced by penicilin
Syphilis
Syphilis is a highly contagious sexually transmitted disease caused by the bacterium Treponema pallidum
Syphilis develops in several different stages
Primary syphilis manifests as a single sore (chancre) at the site of infection around 10-90 days after exposure and last for 3-6 weeks.
Secondary syphilis shows as a body rash with possible fever, swollen lymph glands, sore throat, hair loss, headaches, weight loss, muscle aches, and fatigue.
Latent syphilis is without any symptoms
Tertiary syphilis develops on 1/3 of infected people and can appear 3-20 after infection. At this stage the disease is no longer contagious and it comes in many different forms such as paralysis, numbness, gradual blindness, and dementia.
Gerhard Domagk: 1895-1964
First antimicrobial agents: sulfonamides
Gerhard Domagk
Discovered the first antimicrobial agent sulfanilamide / sulfonamide
Discovered that the sulfanilamide portion of the dye Prontosil was effective against bacteria.
Sulfanilamide was later replaced by penicillin's, but it eventually led to the development of the anti tuberculosis drugs thiosemicarbazone and isoniazid.
Tuberculosis
Widespread disease caused by the bacterium Mycobacterium tuberculosis.
It is estimated that 1/3 of the world population is infected with M. tuberculosis.
Typically a lung disease but can also affect other parts of the body.
During the latent stage it is encapsulated and dormant, but it can reactivate and spread.Tuberculosis
Death from tuberculosis per 100,000 inhabitants in 2004
Alexander Fleming: 1881-1955
First antimicrobial agents: penicillin’s
Alexander Fleming
Observed that colonies of the bacterium Staphylococcus aureus disappeared on plates contaminated with a mold
He identified the mould as a Penicilliumcalled the active substance from his mold juice penicillin.
Later he had only limited success in his clinical trials and found working with the mold and extracting the penicillin to large scale quantities to difficult, so he basically abandoned it.
Staphylococcus aureus
A very versatile bacterium that is often found on the human skin and in the respiratory tract.
It is asymptomatically carried by approx. 20% of the human population.
Can cause a wide variety of diseases ranging from minor skin infections to dangerous diseases such as wound infections, sepsis, meningitis, pneumonia or bacteremia.
Notorious for hospital acquired infections and for developing antibiotic resistance (MRSA).
Howard Florey: 1898-1968
First antimicrobial agents: penicillin’s
Florey & Chain & large team
Continued research on penicillin at the Sir William Dunn School of Pathology in Oxford.
They managed to find a process for mass production
Proposed the correct chemical structure of penicillin
Ernst Boris Chain: 1906-1979
Fight against infectious diseases
Main determinants for our success of limiting infectious diseases
Improved hygiene conditions
Vaccination
Antibiotics
Next lecture
Bacterial Cell Structures
