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Microbiology and Immun (Sci)
MIMM 465
Edith Zorychta

Lecture 1 - Dr. Briedis Unexpected outbreaks – Examples of emerging and re-emerging infectious diseases 1994-1999 - O‟nyong-nyong fever - N. America – Lyme disease, West Nile, etc - Most of the emerging viruses happen in Africa and Southern Asia  Most of the emerging viruses happens b/c of the contact b/w the humans and animals (especially avian species)  They eat smt called a „bush meat‟ - Ex. crocodile meat, higher primate (reason for the rise of HIV in Africa) Viral scare - Avian flu, swine flu, etc - The main side effects are mass hysteria and a swollen government reaction Origins of Virology: a hieroglyph from Memphis, 1400 BC - A priest called Siptah – has a withered right leg (shorter and thinner than the other leg)  A typical clinical signs of paralytic poliomyelitis The Pharaoh Ramses V – died in 1196 BC - When you look at his mummy, he has this vesicles/blisters on his face (nose and side of his head)  People punctured these blisters and done PCR analysis  It was +ve of smallpox virus Smallpox was endemic in China by 1000 BC (and very well understood) - The practice of variolation was developed  Call it variolation b/c the smallpox is developed by Variola major virus - The Chinese recognized that survivors of smallpox were protected from subsequent infection  There was an immune reaction!  People could be IMMUNIZED from getting the virus more than once - Variolation involved inhalation of the dried crusts from smallpox lesions like snuff – to inoculate the individual enough to not kill them and only give them a milder version of the disease  Primitive but the 1 type of vaccination In 1796, Edward Jenner noted that cowpox-infected bovine teats transmitted the infection to the ands of milkmaids - Blistered lesion called cowpox - Milkmaids seemed to have been completely spared by a recent smallpox epidemic - He took cowpox-infected material obtained from the hand of a milkmaid, Sarah Nemes  Then used this to vaccinate 8yr old James Phipps – vaccinated subcutaneously  Vaccination is different from variolation - Vaccination – NOT using an identical, but similar disease - Later, Jenner challenged by deliberately inoculating the boy with material from a real case of smallpox!!  They didn‟t become infected  This was the 1 real vaccination using the cowpox virus (vaccine strain) for the protection of the smallpox - Smallpox vaccine nowadays is a derivative of the original strain that Jenner used Pasteur worked extensively on the rabies disease, which he identified as being caused by: a „virus‟ (Latin for poison) - Pasteurization – killing of the bacteria residing in beverages, such as milk or wine - In spite of this, Pasteur didn‟t discriminate b/w bacteria and other agents (such as viruses)  Thought they were all just poisonous th On 12 Feb, 1892, Dmitri Iwanowski, a Russian Botanist presented a paper to the St. Petersburg Academy of science - Showing that extracts from diseased tobacco plants could transmit disease to other plants after passage through ceramic filters  Filters fine enough to retain the smallest known bacteria  He called this a filterable agent stin fact this was a tobacco mosaic virus - He identified and characterized the 1 virus  Despite this he didn‟t realize that he had discovered a distinctive agent group Obliterations of the smallpox in the wild - Discussing whether the smallpox in the lab freezers should be trashed out  Russians and Americans couldn‟t agree  WHO agreed on WT smallpox should be KEPT in Russian and American governments - So in case someone uses the virus on bio-terrorism, they could do a research on it - Brian Mahy built a category 4-virus vault in CDC to store the smallpox - Ivonovsky institute held the smallpox virus, headed by Mikhail Petrovich Chumakov  Mahy got the CIA to fund the build another vault for the virus for this institute Twort and d‟Herelle independently discovered that viruses actually infect bacteria (b/w 1915-1917) - d‟Herelle named them bacteriophages (eaters of bacteria)  Initially worked on bacteriophages of salmonella bacteria (causing diarrhea, dysentery and typhoid fever)  Predicted that if this bacteriophage is injected into ppl suffering salmonella disease, it could kill the bacteria causing the disease = therapeutic agent - He cured whole number of people - BUT antibiotic was discovered at this time (penicillin and sulfa drugs) = much simpler treatment for salmonella - Then d‟Herelle committed suicide - However the research on bacteriophage is emerging due to the resistance of antibiotic In 1881, Pasteur began studies of rabies in animals - Developed methods of producing attenuated virus preparations - Progressively drying rabbit spinal cords after experimental infection  Took this dried spinal cords and infected the rabbits  With multiple passages of the dried spinal cords through rabbits, produced virus that became more adapted to rabbits and less adapted to the natural host - These preparatists, when inoculated into animals would protect from challenge with virulent virus - This was the 1 artificially produced vaccines In 1885, nine-yr-old Meister was bitten by a rabid dog - 100% of the time, people developed rabies after bitten by a dog - Pasteur decided to treat the boy with his rabies virus vaccine – indeed the treatment was successful and the boy didn‟t develop rabies - Pasteur‟s funding was very poor and when he got this boy cured, he got a lot of funding  Even made a Pasteur institute During the Spanish-American War and the subsequent building of the Panama Canal - American deaths due to yellow fever were colossal - Walter Reed, an Army physician was sent to resolve this yellow fever - Carlos J. Finlay, a local physician, insisted that mosquitos spread yellow fever – entirely new concept of insects could act as a vector to spread the virus - James Carroll and Jesse Lazear decided to experiment on themselves using mosquitos fed on patients - Three days later, both were ill with yellow fever and Lazear died - They had proved mosquitos transmitted yellow fever - American drained swamps (where mosquitos grew), sprayed oil on the water (prevent mosquitos breathing) so they could get rid of the mosquitos Initially animal hosts were the only medium for… - Herpes and hepatitis virus DOESN‟T have animal reservoir..only human as a reservoir < Evolving and emerging viruses in a global perspective> - Dr. Gatignol ONE ESSAY Q FROM THIS LEC Historical background - 1948: US Secretary of State George Marshall: “The world now has the means to eradicate infectious diseases from earth” - 1963: Aidan Cockburn, epidemiologist, advisor at WHO: “Evolution and Eradication of Infectious Diseases” “It seems reasonable to anticipate that in ~100 years, all the major infections will have disappeared” - 1969: US Surgeon General William Steward: “The time has come to close the book on infectious diseases” - … No eradication except Smallpox in 1979… - … Emergence Ebola (76), AIDS (1980s), Plague (94), Hendra, Nipah viruses (94), SARS (2003), Influenza, viral encephalitis… - … increased Malaria, Yellow Fever, Dengue… - 1996: President Bill Clinton issued a fact sheet: “Addressing the Threat of Emerging Infectious Diseases” - 1997: World Health Organization theme: “Emerging Infectious Diseases - Global Alert, Global Response” with the lesson that in a global village, no nation is immune In terms of human deaths, what is the most dangerous animal in the world? - MOSQUITOS Mosquitos: 2-3 million fatalities per year - Before: Snakes, Scorpions, Big cats (lions, tigers, jaguars), Crocodiles, Elephants, Hippopotamus, Jellyfish, Sharks, Bears. - Mosquito is a carrier of  Malaria, Yellow fever, Dengue fever, Rift Valley Fever, Arboviral encephalitides: Japanese encephalitis, Eastern/Western Equine encephalitis, La Crosse encephalitis, St Louis encephalitis, West Nile virus… Natural weapons of mass destruction placed on a „Richter‟ scale - Viruses are among the TOP Virus evolution: constant change of a viral population in the face of selective pressures - Sources of diversity  Mutation  Recombination and reassortment (like in influenza)  Selection Emerging virus: causative agent of a new and previously unrecognized infection in a population - Manifestation of virus evolution - Result of host-virus interaction on a large scale  Viruses have co-evolved with animals Examples of emerging, re-emerging viruses - Norwalk/gastroenteritis isn‟t really an emerging virus but the spreading is increasing in some parts of the world - IVD users – IV drug users Origin of major human infectious diseases - HIV – originally transmitted from chimpanzees to humans - Dengue and yellow fever are mostly from mosquito - Stage 3 – transmission b/w humans are limited Dynamic spectrum of virus-host interactions - In some situation, you have a stable interaction b/w the virus and the host  But then the virus can evolve and have resistance and dead end - Stable interaction doesn‟t mean host absolutely survives… - We don‟t see anything in the resistant situation b/c host is resistant - Dead end is the most spectacular emerging diseases – goes from one host to another host (transmission!!)  Caused by geographical disturbance Complex virus-host relationship - Infectious cycle of Arbovirus (left)  Arbovirus means insects transmit it - Infectious cycle of the central European tick-borne flavivirus (right)  Transmitted by ticks to rodents  Ticks can infect goats and goats can infect human by the milk drinking OR ticks can directly infect human - Phylogeny of 41 influenza A
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