The Struggle with Infectious Disease. Lecture 3

Transcription

1 The Struggle with Infectious Disease Lecture 3

2 Bacterial Infectious Diseases

3 Infectious Agents Four primary types: Virus Smallpox, influenza Bacteria Tuberculosis, cholera Parasite Plague, malaria Prion CJD, Kuru

4 One of the oldest life forms Do not have a nucleus or classical membrane enclosed organelles (mitochondria, chloroplasts) There do appear to be some protein encased structures Reproduce by Binary Fusion Bacteria

5 Bacterial Reproduction

6 Eukaryotic Mitosis

7 Bacteria Bacteria introduce diversity by: Inaccurate DNA duplication Incorporation of free DNA Rapid reproduction Typically for each human generation there are approximately 30,000 bacterial generations Reproduction is even more rapid under certain conditions

8 Cholera

9 Cholera Cholera is a bacterial infection caused by Vibro Cholerae Fecal contaminated water or sometimes shellfish Results in diarrhea and vomiting of clear liquid Symptoms appear rapidly within 1 to 5 days Fluid loss in untreated patients can be litres per day, resulting in death Death rate between 25% and 40% when untreated

10 Cholera Bacteria has three distinct stages in response to local environment Survival mode through the stomach (most are killed) Flagellate stage (corkscrew) to propel the bacteria through the mucus to the wall of the small intestine Toxin production stage results in secretion of H 2 O, Na +, K +, Cl -, HCO 3- and rapid dehydration

11 Cholea Severe cases can result in fluid loss of 5-7 lites in a 2 hour period Can result in death within hours

12 Cholera Prevalent (endemic) in Ganges delta since recorded history First modern pandemic occurred in 1817 China, Japan, South East Asia Middle East, East Africa and Madagascar Spread along trade routes First Pandemic died out in 1823 in Caucuses without reaching Europe

13 Cholera Second Pandemic started in Moscow 1826 Spread through Poland and continental Europe North Africa and Eastern Seaboard of North America Seven cholera pandemics in the past 200 years First in Bengal, India Last in Indonesia in 1961

14 Cholera in England First Case in England (Sunderland) First outbreak in London (6500 die) 1842 Edwin Chadwick postulates a link between sanitary conditions and disease Second outbreak (14,000 die) Albion Terrace outbreak leads to John Snow s Treatise on sources of Cholera William Budd suggests a living organism the reproduces in large number in the gut Third outbreak in London

15 Cholera in London 1854 Outbreak of Asiatic Cholera in major cities in England Outbreak had started in 1831 but killed more than 12,00 in specific areas of the city Southwark and Lambeth were particularly affected, smaller outbreak in Soho In 3 days 127 people living around Broad Street died Only those who could not afford to stayed Death toll in this small area reach 500.

16 Cholera in London

17 Cholera in London

18 London, 1854 Dr John Snow, 1854 London England Physician who lived near the neighbourhood Had published a pamphlet in 1849 suggesting that Cholera Poison reproduced in the human body and was transmitted through contamination of food and water Opposed ridiculed and ignored by the establishment Current theory was miasma in the atmosphere

19 London, 1854

20 London, 1854

21 London, 1854 By removing the handle from the pump deaths in that neighbourhood stopped Two suppliers of water to London

22 John Snow died in 1854 without recognition or acceptance of premise for the transmission of cholera London, 1854

23 Spread of Disease From ancient times usual belief was that disease was either Act of God Spread through the air Miasma Theory

24 Spread of Disease The earliest written record suggesting that invisible living things might cause illness came from the Roman writer Marcus Terentius Varro. In the first century A.D. he wrote: "Care should be taken where there are swamps in the neighborhood, because certain tiny creatures which cannot be seen by the eyes breed there. These float through the air and enter the body by the mouth and nose and cause serious disease." Read more: Discoveries.html#ixzz2CmjdPWcM

25 Spread of Disease Girolamo Fracastro (1564): epidemic diseases were transmitted by seed-like entities that transmitted infection by direct or indirect contact or even over long distances Spontaneous Generation Theory was more popular at the time.

26 Spontaneous Generation Most clearly recorded by Aristotle Representing preceding and then current views Small living organisms could arise from inanimate objects Ticks could arise from dust Maggots could arise from dead flesh Disproved in 1668 by Francesco Redi

27 Redi s Experiment Three bottles with raw meat One uncovered One Covered with gauze One corked

28 Gauze on Top Maggots found on top of gauze, none survived Sealed top No maggots Open Top Flies entered, maggots formed on meat

29 Redi s Experiment Redi also followed maggots and determined the metamorphosed into flies Results were not accepted

30 Spread of Disease Girolamo Fracastro (1564): epidemic diseases were transmitted by seed-like entities that transmitted infection by direct or indirect contact or even over long distances Spontaneous Generation Theory was more popular at the time. Disproved in 1668 by Francesco Redi

31 Anton van Leeuwanhoek invented the microscope in 1668 He described and estimated quantities of microorganisms in water Reported his work to Royal Society of London in 1676 Microorganisms

32 Microorganisms Observations were initially ridiculed he convinced the Royal Society to send a delegation to determine if others could replicate his observations

33 Miasma Theory His observations were not taken up and were replaced by the more logical miasma theory: From the Greek for pollution; noxious, bad air Emanating from rotting organic matter Poisonous gas or mist Due to environmental factors Not passed from individual to individual

34 Developed the criteria for determining if a microorganism was a causative agent 1870 s, worked with anthrax derived from dead sheep. Extracted the material Cultured the material Injected the cultured material into mice The mice contracted anthrax Robert Koch

35 Robert Koch Koch studied 30 generations of mice before publishing his results He developed external culture media (agar) Easier to work with than liquid culture His assistant was Julius Richard Petri

36 Implications of Theory Disease has a specific cause Disease can be transmitted from person to person It is possible to eliminate the cause of a disease One does not have to move to avoid it It is possible to protect against acquiring a disease

37 Discovered, together with Koch much of foundations of microbiology Pasteur was largely responsible for popularization of the concept described the pathology of puerperal fever and suggested boric acid to kill the microorganisms Had been applied in Vienna in 1846 by Ignaz Semmelweis Louis Pasteur

38 Developed vaccines (attenuated live bacterial) against chicken cholera and then rabies Awarded a patent for anthrax vaccine before he had actually demonstrated that it worked Lab books indicate he had used another method to create original vaccine, but that method had already been published by Toussaint Louis Pasteur

39 Cholera

40 Cholera Treatment with rehydration (oral or IV) Basic antibiotics are generally effective (doxycycline) Antibiotic resistance is developing (Bangladesh) Estimated to affect 3-5 million people worldwide (2010) ~130,00 deaths Perhaps as many as 3 million per year in 1980

41 Cholera Vaccine The first Cholera vaccine was developed by Jaime Ferran (Spain) Attenuated whole cell vaccine after methods of Pasteur Results were downplayed by French Academia, but eventually accepted Replaced by oral vaccine. Both show ~65% efficacy

42 Cholera Disappeared from prominence in many countries due to water filtration and chlorination Endemic in many more countries Interesting case Pakistan vs India May re-appear due to breakdown of infrastructure or occasional carelessness

43 Haiti January 2010 earthquake Cholera appeared late 2010 Some cases were so severe individuals died within several hours of symptom onset most likely source of outbreak: UN workers from Nepal (where cholera is widespread) Exact strain match (derivative form Indonesian pandemic)

44 Haiti 650,000 cases almost 8000 deaths UN program to irradiate Cholera from Haiti (which had been Cholera free) Costed at $2.2 billion Recent case in Cuba due to contaminated food Aggressive response Rapid containment (700 cases, 3 deaths)

45 Typhoid is caused by the salmonella typhi bacteria Unique as the only known salmonella bacteria with only human host Spread through food contaminated by feces or urine Enters body through small intestine Mortality ~16% untreated 1% treated with antibiotics Typhoid

46 Typically lasts four weeks (untreated) Fever rises throughout the first week Plateaus at ~40 o during the second week with delirium and irregular pulse, enlarged liver and spleen Complication in third week include: intestinal hemorrhage or perforation, neuropsychiatric symptoms, dehyration and delirium with high fever Fever subsides during fourth week Typhoid

47 Approximately 5% who contract the disease become asymptomatic carriers who continue to carry (and shed) the bacteria after recovery Marry Mallon Cystic fibrosis may confer protection against typhoid due to changes in the small intestine (may also be true for Cholera) Interesting Facts

48 Typhoid Once transmission mechanism was understood (late 1800 s) Quarantine was used to control spread (Mary Mallon was quarantined for 26 years 1907)

49 Typhoid First vaccine: Almroth Edwin Wright (1896) Used during Boer War 10 million doses produced by UK government for WW1 estimated saving ½ million lives After Spanish American war US army set up Typhoid Board under Maj Walter Reid Sanitation, water sterilization, latrine siting 81,00 died in Civil War US Army vaccinated 1909

50 Typhoid Water treatment has effectively eliminated the disease in developed countries Vaccines are not currently used in Canada Oral and injectable vaccines are available

51 Typhoid Minor resurgence in BC due to immigration from endemic countries ~44 cases/year Manila, Philippines 2008 Typhoon Haiyan

52 Tuberculosis

53 Tuberculosis 95% of tuberculosis cases occur in the developing world Caused by the Mycobacterium tuberculosis Air borne transmission About 90% of infections are symptom free Symptomatic cases: untreated mortality rate is 50%

54 Tuberculosis Symptoms: Chronic cough Blood tinged Fever Night sweats Weight loss consumption

55 Tuberculosis

56 Latent Tuberculosis Bacteria enter pulmonary alveoli Replicate in the macrophages Macrophage envelopes bacteria Stored temporarily in a membrane bound vesicle Vesicle combines with a lysosome Lysosome tries to kill bacteria with reactive oxygen species Bacteria has thick waxy capsule that provides protection

57 Latent Tuberculosis Immune cells attack the infected macrophages Form large multinucleus granuloma cells Protect bacteria from detection by the immune system Bacteria can become dormant

58 Tuberculosis Can affect tissues other than the lungs Almost any other tissue Results in necrosis of tissue Spongy-like tissue Fibrosis and scaring as the disease waxes and wanes

59 Systemic tissue damage and weight loss led to the disease being called consumption Consumption

60 Issues Antibiotic treatment takes 6 months Ineffective treatment has resulted in multi drug resistant (MDR)TB New XMDR strain HIV infection increases risk of serious TB by 10% per year HIV patients 50 times more likely to develop HIV Only vaccine available is only effective in children Does not work for pulmonary TB