Medical Microbiology and Parasitology. Stijn van der Veen

Transcription

1 Medical Microbiology and Parasitology Stijn van der Veen

2 Website for the course Website: All basic course information Course introduction and outline Lecture slides Basic information teachers Online quizzes

3 Assessment & final mark Attendance at lectures and lab (10%) Online quizzes (20%) Laboratory reports (10%) In-class-quizzes (10%) Final exam (50%)

4 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

5 Online quizzes 3 quizzes Each online quiz consists of 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, @qq.com Haili Zhou, @qq.com

6 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

7 In-class-quizzes The time and format of in-class-quiz depends on each teacher

8 Final exam Multiple choice questions (50 questions, 50 points) True or false (20 questions, 20 points) Short answer questions (4-5 questions, 30 points)

9 Introduction to Medical Microbiology

10 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.

11 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!

12 How small are microbes? meter Naked eye Tapeworm 1 Perspective meter Sun Nematode 10 8 Jupiter Earth 10-3 Schistosome 10 6 Moon 10-4 Thiomargarita namibiensis Light microscope 10 5 Tryptanosome 10-5 Plasmodium Bacillus cereus 10 4 Mount Everest Staphylococcus Pox virus Electron microscope Burj Khalifa 10-8 Influenza virus 10 1 Medical school 10-9 Polio virus 1 Human

13 Microbes in the Tree of Life Viruses?...not considered life! Protista

14 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) Carolus Linnaeus: Names are always in Italics Genus name is capitalized, species name not. Second time use in text: genus name can be initialized

15 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

16 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. 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. 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.

17 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

18 Bacteria Prokaryotes Cell wall contains peptidoglycan Replicate by binary fission Use organic chemicals, inorganic chemicals, or photosynthesis for energy Come in many shapes

19 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

20 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

21 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

22 Infectious diseases Major impact on life expectancy Bronze age => 26 yrs Medieval times => 30 yrs End of 19 th century => yrs Now world average => 71 years

23 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.

24 First recorded perception of micro-life 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: B.C.

25 Challenge of spontaneous generation Francesco Redi Where do maggots come from? Experiment Left open Maggots developed Covered with netting Maggots on netting Sealed No maggots Francesco Redi: Jar 1 Jar 2 Jar 3

26 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. Antonie van Leeuwenhoek:

27 Poem about Van Leeuwenhoek Maxine Kumin: 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.

28 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. Edward Jenner:

29 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 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 England Emperor Joseph I of Austria King Luis I of Spain Tsar Peter II of Russia King Louis XV of France

30 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% Oliver Holmes: The paper stated that puerperal fever is passed on from patient to patient via contacts with their physician

31 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

32 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. Ignaz Semmelweis: 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

33 Hand washing is important Hand washing is vital in healthcare settings to remove pathogenic microorganisms!!! 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

34 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. John Snow: 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

35 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 19 th and 20 th century. Still affects 3-5 million people annually, with an estimated 100,000 deaths.

36 Pasteurization & fermentation Louis Pasteur Father of microbiology With his growth and fermentation experiments he conclusively proved the theory of biogenesis. Louis Pasteur: 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.

37 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.

38 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." HistoryLearningSite.co.uk

39 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

40 Koch s postulates Robert Koch Founder of modern bacteriology Koch s postulates, linking microorganisms to disease Identified the causative agents for cholera, anthrax, and tuberculosis, thereby proving the concept of infectious diseases. Robert Koch: Improved laboratory techniques and introduced bacterial agar and the Petri dish to purify bacterial colonies

41 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.

42 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.

43 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. Joseph Lister: Introduced carbolic acid (phenol) to clean wounds and sterilize surgical instruments.

44 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. Paul Ehrlich: Arsphenamine was the first effective medical treatment for syphilis Arsphenamine was very unstable, oxygen sensitive and later replaced by penicilin

45 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 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.

46 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. Gerhard Domagk: Sulfanilamide was later replaced by penicillin's, but it eventually led to the development of the anti tuberculosis drugs thiosemicarbazone and isoniazid.

47 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

48 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 Penicillium called the active substance from his mold juice penicillin. Alexander Fleming: 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.

49 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).

50 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 Howard Florey: Proposed the correct chemical structure of penicillin Ernst Boris Chain:

51 Fight against infectious diseases Main determinants for our success of limiting infectious diseases Improved hygiene conditions Vaccination Antibiotics

52 Next lecture Bacterial Cell Structures