Battles to Infectious Diseases: A Brief History

1. 医学史简论（7）A Brief History of Medicine 浙江大学医学院 余 海 yuhai@zju.edu.cn

2. 送瘟神：人类与传染病的斗争 Send away the Good of Plague： Battles to Infectious Diseases

3. Historyof Infectious Diseases • Infection 感染 the invasion of the body by any of various infectious agents – including bacteria, viruses, fungi, protozoan and worms，and the reaction of the body to them or their toxins.

4. Definitions • Infectious disease 感染病 (cause) The disease caused by infection and/or capable being communicable by infection • Communicable （contagious) disease 传染病 (transmission) The disease capable of being transmitted from one person to another or from animals (intermediate host) to human. • Epidemic disease流行病 (incidence) The occurrence of cases of disease in excess of what is usually expected for a given period of time. (epidemic hysteria) • Endemic disease地方病 (location) The disease that is constantly present in people living in a particular location (endemic thyroid disease-goiter)

5. Human and Infectious Diseases • Epidemics 流行 Sudden outbreak of diseases in excess of what is expected • Pandemics （全球）大流行 Sudden geographically widespread outbreak of diseases

6. History of Infectious Disease • Prehistoric period：Infectious disease rare • Agriculture society：Increased transmission • Urban civilization： Congestionof urban inhabitation, war and travelling result to outbreak of infectious diseases

7. Three factors of transmission of infectious disease • Source of infection (Typhoid Mary Mellon 1869-1938， 52/7) • Susceptible population • Transmission routes Directtouch Droplet spittle Air-borne Indirectutensils insect Indirect touch Routes of transmission Speed of sneeze: 170km/h 47.2m/s

8. Victories over infectious diseases • Smallpox • plague • Influenza • Diphtheria • Measles • Tetanus • poliomyelitis • schistosomiasis

9. 天花smallpox 天花病毒 poxviridae othopoxvirus pockmarked face，frommaculopapular rash to raised fluid-filled blisters to pustules

10. 天花smallpox • Egyptian Pharaoh Ramses V died from smallpox in1157 B.C • Frequent outbreak in the history • 300 million people died from smallpox in 20th century (100 million died from wars) Ramses V 1157BC

11. Victims of Smallpox Louis XV 1777 Elizabeth I 1533-1603 Joseph I d1711 顺治（福临） 1638-1661 Marry II 1662-1694

12. 天花smallpox Chinese invented inoculation of human smallpox (variolation) in 10th century, widely used in 14-16 century Lady Montagu brought back from Turkey to Europe in 1721 Lady Montagu variolation Blow the scab of smallpox skin lesion

13. 天花smallpox • Inspired by the fact that dairymaids infected with cowpox were immune to small-pox, Edward Jenner invented cowpox vaccine against human smallpox. Edward Jenner 1749-1823 variolation vaccination (vaccinia vacca-cow)

14. 天花smallpox • Jenner deliberately infected James Phipps, an eight year old boy, with cowpox in May 14, 1796. He then exposed Phipps to smallpox–which Phipps failed to contract. After repeating the experiment on other children, including his own son, Jenner concluded that vaccination provided immunity to smallpox without the risks of variolation. Jenner’s findings were published in 1798.

16. 天花smallpox • in 1840 Vaccination Acts were passed, the British government banned variolation and provided vaccination, free of charge. • In 1805 vaccination was introduced to China via Portugal merchants in Macao

17. 天花smallpox • 1840 British vaccination Acts • 1940 Smallpox was eradicated in Europe and North America • 1960 Last Chinese case occurred in a Yunnan-Burma border village • 1967 WHO launched smallpox eradication movement （At that time 30 million cases, 2million deaths/y 30countries 1700medical doctors 200,000 health workers mobilized in the campaign

18. 天花smallpox • Last natural infected Somalia patient cured in Oct 26 1977 • A fatal incidence occurred in Birmingham University in August 1978 a woman lab photographer Janet Parker became the last victim of smallpox, Prof Henry Bedson committed suicide. • May 8, 1980 WHO announced: Global eradication of smallpox Ali Maali

19. 天花smallpox Reasons for possible eradication of smallpox • There are no other virus reservoirs but man • Only acute infection exists, the outcome of disease: die or life-long immunity • Virus is highly immunogenic, so vaccine has been most effective

20. 鼠疫 Plague bacterium  Yersiniapestis Flea Rat Prairie dog Infection source: rodents, routs: through insects or direct

21. Bubonic and Pneumonic Plague

22. 伍连德和鼠疫 Chinese Plague Fighter Wu Lien-teh • Born in Penang, Malaya in a Chinsese family • Studied Medicine in England • 1907 Vice-Director of the Imperial Army medical College in Tientsin • In the winter 1910a endemics of plague outbroke in Manchuria which claimed 60,000 victims, the endemic was controlled under his leadership. • chaired the International Plague Conference in Mukden (Shenyang) in April 1911 • He was the first president of the China Medical Association (1916–1920) and directed the National Quarantine Service • 1937 he moved back to Ipoh as a GP Wu Lien-Teh 1879-1960

24. 伍连德和鼠疫Chinese Plague Fighter Wu Lien-teh • 1935 he was nominated as the candidate of Nobel Prize of Physiology or Medicine for work on pneumonic plaque and especially the discovery of the role played by the tarbagan in its transmission. (by Folke Henschen) 梁启超：“科学输入垂五十年，国中能以学者资格与世界相见者，伍星联（即伍连德）博士一人而已！”

25. Black death in 14th century 1346-1353 plague outbreak in Europe（black death 黑死病）,claimed 2.5million, 1/3 of European population( Threw bodies into city using trebuchet to spread plague-first biological warfare by Tartar cavalrymen) Caffa Crimea

27. Learn from plaque：contagion gown Beak fill of spices

28. Quarantenaria （40天）Quarantine （检疫） Learn from plague: quarantine

29. 血吸虫病 Schistosomiasis Schistosoma heamatobium (Bilharzia) Africa, Middle East S. Japonicum China, Phillipines S.mansoni Africa, Latin America

30. Paleopathology Findings Schistosoma eggs discovered in a well-preserved ancient lady’s body (in Changsha Mawangdui of Hunan Province, 165 BC) , and also found in another well-preserved man’s body (167 BC) in Jiangling of Hubei Province

32. 血吸虫病 Schistosomiasis Used be prevalent in 12 provinces, 400 counties, threatened 100 million people and 1 million domestic animals (buffalo) Campaign of Schistosomiasis Prevention (血防Xuefang)in 1950s Treatment of patients and animals－eradication of the sources Clearance of snails-intermediate host Water and feces control-cut the transmission routes

34. The God of Plague (Shistosomiasis) is back

35. Infection disease control-Long way to go传染病控制 - 任重而道远 • Eradicated: smallpox • Vaccine preventable: measles, poliomyelitis, diphtheria, whooping cough, tetanus • Uncontrolled：plague, cholera, tuberculosis, viral hepatitis • Re-emerging：sex-transmitted disease, Dengue fever, schistosomiasis • Newly emerging：Legionnaires’ disease, Ebola fever, SARS, MERS, bird flu, AIDS, Zika viral disease (microcephaly)

36. 流感 Influenza 1918flu pandemic (Spanish flu) spreading to nearly every part of the world. Caused by Influenza virus strain subtype H1N1. From March 1918 to June 1920, estimated 20 to 50 million people were killed (mortality rate 2.5-5%) The extreme virulence may be associated with overreaction of immune system-cytokine storm Mittelmachte (Central Power 同盟国) Entente Power (协约国）

37. Influenza versus Common Cold WHO Collaborating Centre for Influenza, Melbourne, Australia.

38. 流行性感冒（流感） Influenza (Flu) 和禽流感 Avian Influenza （Bird Flu） • Influenza（flu) is  caused byRNAviruses of theFamilyOrthomyxoviridae(正粘液病毒）(the influenza viruses) • 甲型流感病毒（Influenza A virus）:human，birds，mammalians • 乙型流感病毒（Influenza B virus）:mainly human • 丙型流感病毒（Influenza C virus）:mainly human The influenzavirus Round shape，diameter 80–120 nm

39. Hemagglutinin,H: H1～H15, Neuraminidase, N:N1～N9 , Theoretically there could be 135 subtypes, Treatment: Tamiflu (Oseltamivir phosphate) A neuraminidase inhibitor Avian Influenza Virus

40. Avian Influenza (Bird Flu) • Bird flu is influenza caused by viruses adapted to birds, which belong to Influenza virus A Influenza virus with the diameter of 80～120nm

41. Ecology of Avian Influenza Virus

42. Birdmigration

43. Viet Nam Cambodia

44. Thailand

45. Indonesia

46. Felines (tiger, leopard) can be infected with bird flue (60 tigers and 1 leopard in Thai zoo died from bird flue in 2003)

47. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO2003-2014 The overall case fatality rate 393/667=59.0%

48. 禽流感和流感发病对比 Comparisonofbirdfluwithflu TNF-a，IL-1，IL-6 Cytokinestorm“细胞因子风暴” 死亡率 ～60% vs ～1%

49. Antigenicdrift 抗原漂移 Antigenicshift 抗原转移

50. Potential risk 潜在危险 • The mutation of virus may cause the outbreak of pandemics of avian influenza (gene shift or draft, leading to transmitted from human to human) • Nature estimated：That may cause one third of world population infected , 30 million may need hospitalized, one quarter of which would die.