This document provides an outline for a presentation on tuberculosis (TB) given by Dr. James K. O'Brien for Seattle Prep High School on March 12, 2010. The outline covers TB as an ancient disease, how it spreads, its history throughout prehistory and major time periods, famous people who had TB, the sanatorium movement, Robert Koch's contributions to microbiology, antibiotics used to treat TB, public health funding, current epidemiology, and principles for treating TB. It also advertises an event for World TB Day on March 24, 2010 at the Olympic Sculpture Park in Seattle.

1. Tuberculosis After LunchJames K. O’Brien MDFor Seattle Prep High SchoolMarch 12, 2010

2. World TB DayMarch 24, 2010Pavilion at Olympic Sculpture Park6-8:30PRSVP elli.koskella@seattlebiomed.orgWebsite: www.seattlebiomed.org/event/world-tb-day

3. Tuberculosis OutlineAncient diseaseHow do we get it?HistoryPrehistoricDark agesRenaissanceFamous peopleSanitorium movementKoch and the microbiology revolutionAntibioticsTB antibioticsPublic health funding is importantEpidemiologyPrinciples for the treatment of TB

4. Everything’s worse with sharks.

5. …and crocodiles.

6. …and tuberculosis.

7. Oldest remnant of tuberculosis DNA discovered in the North American wooly mammoth, 10,000 B.C.

8. In the 19th and 20th centuries1,000,000,000 dead from TB.

9. How do we get TB?Predominately a respiratory infection. Rare in most areas of US including Seattle.Passed by microdroplets emitted by cough, talking and singing. Sneezing less effective.If not treated 50% of those infected will die often over years.Mode of death: malnutrition, inability to oxygenate blood, bleeding from lungs(hemoptysis).

10. 30-40% of close contacts to a TB patient (e.g. spouse or children) will be infected with TBApprox 90% of those infected will never develop symptoms of pulmonary TB5% infected will get sick within two years of infection.5% of those infected will develop infection in their lifetime.On average, a TB patient infects ten other people before they get treatment.It’s the unpredictability of TB that allows it’s survival through history.

12. HistoryPrehistoric Times5,000-1000 B.C.: People began gathering in “urban” areas. Egytian mummies showed evidence of TB.4,000 B.C.: Indo-europeansof the copper and bronze ages, tracked by the evolution of language, move and settle areas from Northern Europe to India.Peak occurrence of TB in Greece 700-500 BC.Indo-europeans were cattle herders. The TB bacillus that infects humans is thought to have evolved from a bacillus carried by cows.3/12/201012

13. TB in the New WorldMummy from Peru, dated 1,000 B.C., evidence of TB DNA in the spine.Prior to this DNA evidence it was believed that TB was introduced to the New World by Europeans.

14. We are unclear when tuberculosis arrived in the Western Hemisphere, but believe it accompanied animal and human movement across the Bering land bridge before 8,000 B.C or with ocean-going people after the land bridge was lost.3/12/201013

15. Dark Ages

16. Renaissance (15th century-18thcentury)1450, migration of Greek scholars to Northern Italy1540, GirolamoFracastoro, Padua, Italy, enunciates a theory of contagion.1500-1700, Southern Europe initiates public health measures, Northern Europe laughs at Southern Europe. More TB in Northern Europe and its colonies.By 1800, 1 in 3 people who died in Europe died of TB.

17. 1821 Keats wrote, “ ’Bring me the candle,’he called to Brown, with whom he was staying,‘and let me see this blood.’ He looked at the bright red spoton his pillow and then, his excitement and intoxication gone, he said calmly,‘I know the colour of that blood. It’s arterial blood…that is my death warrant.’ ” Keatsdied at age 26 of TB.

18. Some famous people with tuberculosisKing Tut, Samuel Johnson, Moliere, Maupassant, Voltaire, John Calvin, Rousseau, Goethe, Sir Walter Scott, Chopin, Immanuel Kant, Louis XIII and Louis XVII, Napoleon II, Bartholdi(Statue of Liberty), Stephen Crane, Washington Irving, Anton Chekov, Tad and Edward Lincoln (children of A. Lincoln), Edvard Munch, Paganini, Laennec (stethoscope), Shelley, John Keats, Elizabeth Barrett Browning, Charlotte/Emily/Anne Bronte, Dostoyevsky, Grieg, Robert Louis Stevenson, Alexis de Tocqueville, Henry David Thoreau, Paul Gauguin, Cecil Rhodes, “Doc” Holliday, W. Somerset Maugam, Eleanor Roosevelt, DH Lawrence, Franz Kafka, Albert Camus, George Orwell, Eugene O’Neil, W.C. Fields, Vivien Leigh(Scarlet O’Hara), Nelson Mandela, Carlos Guillien (former Mariners shortstop).

19. SanatoriumRest, fresh air, altitude and nutrition.Davos, Switzerland. est. 1880. Robert Louis Stevenson finished Treasure Island here. Thomas Mann’s Magic Mountain.Saranac Lake, NY. First US sanatorium, 1885. Edward Trudeau.Firland’s Sanatorium, est. 1911. Betty McDonald, wrote The Plague and I about experience at Firland’s.

20. Robert Koch: MicrobiologyLate 19th Century: Anthrax and choleraPopular others: Louis Pasteur, Paul Ehrlich, Rene Dubos, Alexander Fleming, Selman Waxman.Koch’s PostulatesBacteria is found all disease examinedPrepared in pure cultureReintroduced to animal, causes diseaseRetrievable in inoculated animal with diseaseIn 1908 gave a lecture contradicting the hypothesis that cow TB, Mycobacterium bovis, was related to human TB. Wrong, it was. Marred Koch’s reputation.Failed vaccine for TB.

21. AntibioticsBayer (of aspirin fame) was a manufacturer of dyes for the textile industry, with a small pharmaceutical division.In 1920s Bayer hired Dr. Gerhardt Domagk. Tested dyes with chemist Josef Klarer. Many not only killed the bugs, by ‘staining’ and destroying cell walls, but killed the inoculated animals as well.Red dye KL-730 given to mice, inoculated with bacteria, and allowed mice to live while control mice died of infection.Sulphonamide, or sulpha, drugs were discovered.In 1933, a young woman namd Heidi, was nearly dead from complications of strep throat. At Wuppertal-Elberfeld Hospital in Germany she was given Prontosil, first marketed sulpha drug, and was better in twenty four hours.These findings were repeated in larger trials. Fleming’s Penicilliumnotatum extract, penicillin, was given to a sick friend in 1936.Neither compound worked against TB.

22. Tb AntibioticsSelma Waxman PhD and Albert Schatz, a PhD student in soil microbiology, discover Streptomycin. Rutgers University.Hypothesis: soil is a battleground for microbes. They must emit chemicals to keep others ‘off their turf’.Streptomyces discovered over years of research with manure and soil. Other antibiotics discovered from the Streptomyces genus include: erythromycin, neomycin, tetracycline, vancomycin, rifamycin, and chloramphenicol.First patient got Streptomycin at the Mayo Clinic, an elderly farmer from with TB meningitis. Hinshaw and Feldman at Mayo Clinic conducted clinical trials.Jorgen Lehmann discovers PAS in Sweden, derivative of aspirin, and similar in structure to first sulpha drugs.Later drugs developed, multiple drugs at a time, for many months, needed to treat TB.

23. Public Health Funding is Important

24. New York as an exampleDecimation of the TB Control BudgetIn 1979 the New York State budget crisis led to state TB funding to NYC of $0.In 1978 NYC spent $23 million on TB control and between 1985 and 1993 it spent $2-4 million/yr.As the TB budget dropped in NYC the cases of TB rose: 1980=1514 TB cases, 1990=3520 TB cases, 1994=greater than 4000 TB cases.More than $40 million in 1994 to NYC alone from federal government to curb the epidemicBetween 1980 and 1993, estimated 20,000 extra cases of TB in NYC with each case costing $20,000 per case to treat.

26. Epidemiology2008In US 2% of cases resistant to the two best drugs, isoniazid and rifampin, and this isMultidrug resistant (MDR) TB.

27. 2007Worldwide: 2 billion infected with TB (evidence by TB skin test), 2 million die each year.

28. Previous attempts to cure TBHippocrates, honey-barley gruel-wine resin in water, and herbs grown in the gardens of temples dedicated to Aesculapius, the god of healing.In China, pith balls soaked in the blood of executed criminals.In Europe, a live trout was attached to the sufferer’s chest, a fresh catskin was wound around the body, and a piece of meat moistened with the sufferer’s urine was fed to a dog.

29. Important principles of tuberculosis treatmentFind and treat people with positive TB skin test.Most common antibiotic regimen for those with tuberculosis4 months of isoniazid, rifampin, pyrazinamide, and ethambutol each day, then 2 more months of isoniazid and rifampin each day. Total of 6 months of therapy.Use directly observed therapy (DOTS)Develop vaccine. At least 15 years away.

30. Tuberculosis OutlineAncient diseaseHow do we get it?HistoryPrehistoricDark agesRenaissanceFamous peopleSanitorium movementKoch and the microbiology revolutionAntibioticsTB antibioticsPublic health funding is importantEpidemiologyIncluding MDR and XDR TBPrinciples for the treatment of TB

34. World TB DayMarch 24, 2010Pavilion at Olympic Sculpture Park6-8:30PRSVP elli.koskella@seattlebiomed.orgWebsite: www.seattlebiomed.org/event/world-tb-day