Great Ideas of Biology

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1 Great Ideas of Biology Lecture 4 Alan Mortimer PhD

2 Infectious Disease

3 Infectious Disease Where do they come from How do they move from person to person What can we do about it

4 - History of Infectious Disease - Discovery of Infectious Agents

5

6 Earliest Stages Human life is believed to have started in the warm, moist environments of the African Rift Valley and most probably similar environments in Asia Requires little protection for the human (e.g. clothes, fire etc.) Also very suitable for other species:

7 Earliest Stages Parasites do not need protection, many species can survive well without human or animal host Here warm blooded hosts become an opportunity rather than a necessity Led to populations that were chronically infected by a wide variety of infectious agents It was warmer and wetter in the rift valley

8 Early Stages As humans moved into temperate climate zones general level of infection became less Infectious agents needed more complex life cycles and structures to survive

9 Early Migration

10 As agriculture took over new means of transmission were possible Probable source of Plagues of Egypt Similar events in Asia

11 However it was the development of cities that provided to opportunity for direct transmission from person to person Start of epidemics as we know them now. Medieval London

12 Historical Perspective In fact plague kept the population at a somewhat constant level throughout more than a century

13 Case Study: Black Death Black Death or Bubonic Plague is caused by the bacteria yersinia pestis Very high fatality rate: 2/3 within 4 days Primary transmission is via rats and a rat louse Secondary transmission via droplets after lung infection. Much more contagious Much more virulent

14 Case Study: Black Death

15 Black Death Bacteria congregate in the lymph nodes and multiply rapidly leading to grossly enlarged node in groin or neck When bacteria multiply in the blood stream it leads to vascular damage Gangrene Black fingernails and toes General vascular breakdown

16 Case Study: Black Death Humans can develop lung infection and spread by coughing This is much more rapid that waiting for animal life cycles and probably led to the rapid transmission of plagues Crowded environment and no known cause or prevention measure led to incredible death rates Plague Constantinople

17 Not the first and not the last First major occurrence during the Byzantine Empire AD Developed cities Extensive trade routes Black Death Originated in Asia and followed Silk Road Cities and first instance of extensive inter-city trade in Europe

18 Case Study: Black Death After the initial outbreaks a cyclic pattern developed Outbreaks in England 1498, 1535, 1543, 1563, 1589, 1603, 1625, and 1636, and ended with the Great Plague in Plague Riot in Moscow, Wikipedia

19 Incredible Death Rates Half the population of China One third of the population of Europe One eighth of the population of Africa 25% of the entire population of the world In less than 4 years

20 Not the first and not the last Third Pandemic started in 1855 in China Killed more than 12 million in China and India Reached North America in 1900 San Francisco Current reservoir primarily in sub-saharan Africa Outbreak in Surat, India in 1994 caused 54 deaths Over 300,000 fled the area

21 Plague Today Bacteria is relatively easy to treat with several standard antibiotics Some concern with disease resistance (one case) Remains present, but is not a primary concern cases/year

22 Plague Today

23 Historical Perspective Infectious disease became prevalent when people started living in close proximity Sort of equilibrium was developed until mass movements of people began

24 Spanish conquest of Central (Aztec) and South (Inca) America Spanish were carriers of smallpox due to endemic nature in Europe Cultures were completely wiped out in 50 years Plagues and Conquest

25 Plagues and Conquest In exchange syphilis and gonorrhea were carried back from the new world to a naive population Persisted as a significant public health issues well into the 20 th century

26 Germ Theory The specific cause of disease

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

28 Religious Causes Biblical plagues Judeo-Christian Egyptian smallpox plague There is an ancient Hindu god Sitala: god of smallpox African gods such as Odinani (Nigeria) protect against famine and smallpox

29 Early Thought 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

30 Early Thought 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.

31 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

32 Redi s Experiment (1668) Three bottles with raw meat One uncovered One Covered with gauze One corked

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

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

35 Microscopic Evidence 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

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

37 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

38 Religious Arguments Primary argument from the Battle of Gideon (Joshua) causing the sun and moon to stand still Three points of argument Evidence of the senses Thousand-year consensus of men of science Authority of the Bible Not only Catholic Church but Calvin & Luther

39 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 reached 500.

40 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

41 London, 1854

42 London, 1854

43 London, 1854 By removing the handle from the pump deaths in that neighbourhood stopped Two suppliers of water to London Only one implicated

44 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

45 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

46 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

47 Developed vaccines (attenuated live bacteria) 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

48 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

49 Infectious Agents Four primary types: Virus Smallpox, Influenza Bacteria Tuberculosis, Cholera Parasite Malaria, Tropical Diseases Prion CJD, Kuru

50 Bacteria Generally single cell organism Do not contain a nucleus Can reproduce May have several different forms throughout their life cycle Most can live outside the body Antibiotics generally prevent reproduction Cholera Bacteria

51 Virus 10 to 100 times smaller than a bacteria No cell nucleus Must enter another cell to reproduce Infective agent (viron) contains only RNA or DNA (sometimes a few enzymes) Surrounded by a virus membrane Influenza Virus

52 Virus Although postulated as early as 1892 Infectious agent smaller than a bacteria The virus was not observed until 1940 Tobacco Mosaic Virus

53 Parasites Single or multicellular Multiply either within a cell (malaria) or within tissue (shistosomiasis) Some can be treated with antibiotics

54 Prions Prions are a single protein The cause misshapen proteins to be produced outside the cell Result in plaques (buildup) in the nervous system (brain) CJD (humans) Chronic wasting (cervids) Scrapies (sheep and goats

55 Ecology of Disease In most cases epidemics and plagues are caused by an infectious agent entering (finding?) an new ecological niche

56 Ecology of Disease Examples Diseases of exploration Smallpox, Tuberculosis Diseases spread through travel Spanish Flu, SARS Diseases spread due to changing conditions Cholera Diseases spread due to loss of herd immunity Polio Diseases spread when competition is removed C Difficile

57 Have we come so far?

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