1. DPT- From Epidemics to Immunizations- A Modern Success Story Mindy A. Schwartz, MD University of Chicago June 27, 2006

2. Outline Diphtheria Pertussis Tetanus Immunizations Modern Issues Summary

3. Diphtheria Hippocrates described this in the 4th century BCE During the epidemic in the 17th century it was called “El garatillo” - the strangler Epidemic disease in the late 19th century with case fatality rates of 42-47%

4. Corynebacterium diphtheriae- Gram positive, non motile, rod shaped bacteria Names for club shape- Koryne- Greek for club Described by Edwin Klebs and Friedrich Löffler- called the Klebs Löffler bacteria

5. Clinically Incubation period of 2-4 days, organism invades the throat and causes the development of membraneous exudate The organism then causes local invasion- may cause necrosis and discoloration of the tissue- foul odor and blackened mucous membranes The organism is also capable of causing the release of a toxin into the blood stream

6. Pharyngitis 101 Viral causes- Infectious Mononucleosis Streptococcal pharyngitis- GAS Diphtheria Pertussis Epiglottitis

7. Epidemiology Disease in fall and winter Most cases in individuals under 15 years Rates as high as 50,000 deaths per year- at the beginning of the 20th century Leading cause of death in children ages 4-10 Incidence rate of 206,939 cases in 1921- less than 5 per year in the US since 1980

8. Epidemiology On top of high endemic rates, epidemic waves were associated with an extremely high incidence and death rates Spain in early 1600’s New England in 1730’s Western Europe from 1850-1890

9. Francisco Goya - Lazarillo de Tormes- 1819

10. Emil Von Behring 1854-1917 First Nobel Prize in Physiology or Medicine in 1901 Given for his work on serum therapy on diphtheria- diphtheria anti-toxin Worked with Kitasato an in the lab of Robert Koch

11. Diphtheria Anti-toxin Toxin- causes disease Anti-toxin- neutralizes the toxin Toxoid- inactivated toxin capable of activating antibodies for an immune response but not causing the actual disease

12. The New Cure for Diphtheria- Drawing the Serum from the Horse Taken from Hansen B- New Images of a New Medicine: Visual Evidence for the Widespread Popularity of Therapeutic Discoveries in American After 1885- from the Bulletin of the History of Medicine 1999; 73.4 668

13. The New Cure for Diphtheria, Croup, etc- Injecting the Serum Taken from Hansen B- New Images of a New Medicine: Visual Evidence for the Widespread Popularity of Therapeutic Discoveries in American After 1885- from the Bulletin of the History of Medicine 1999; 73.4 668

14. Eleanor Roosevelt

15. United States Diphtheria Mortality Rates

16. The First Intubation In 1885, New York physician Joseph O'Dwyer introduced tracheal intubation for the treatment of severe diphtheria

17. Iditarod Race The Iditarod trail dog sled race is run each year to commemorate the emergency delivery in 1925 of diphtheria antitoxin to Nome, Alaska. The serum was taken from Anchorage to Nenana and then by a relay of dogs from Nenana to Nome- 674 miles away. The current race is from Anchorage to Nome – 1150 miles

18. Balto

19. Pertussis Called Whooping Cough Also referred to as the 100 day cough by Japanese and Chinese Called chincough- by Thomas Willis in 1675 Called kindhoest - a teutonic word meaning childs cough in the Middle ages

20. Pertussis First described by Guillaume de Baillou in 1578 during an outbreak in Paris Bortadella pertussis identified by Jules Bordet and Octave Gengou in 1906 Bordet won the 1919 Nobel Prize in Medicine

21. Pertussis-Epidemiology Previously a disease of childhood Transmission is airborne- via droplets Humans are the only reservoir The organism cannot survive outside of the host and is susceptible to environmental agents- heat, drying and ultraviolet light

22. Pertussis-Clinical Findings Incubation period 7-10 days Initial catarrhal stage 1-2 weeks- contagious Cough develops Third stage- it is severe, spasmodic and terminating in the characteristic whoop This lasts for weeks

23. Complications of Pertussis Chronic Cough Sleep disturbances Headache Pneumonia Seizures Encephalopathy

24. Tetanus An acute disease caused by a toxin produced by the bacterium Clostridium tetani Organism is anaerobic- living in soil Spores are resistant to heat and chemical agents Incubation period is 3-21 days- average of 8 Not spread person to person The further the site of injury the longer incubation period

25. Tetanus- Clinical Findings Symptoms Spasm of the muscles- typically jaw muscles Spasm of neck muscles, difficulty in swallowing Abdominal muscle stiffness Autonomic instability

26. Tetanus Localized Generalized Cephalic Neonatal Classic findings- risus sardonicus Trismus Opistotonus

27. Contracted body of soldier suffering from tetanus- opistotonus

28. Tetanus Tetanus toxin- tetanospasmin Blocks acetylcholine release at the motor end plate Spinal cord is the primary target organ Toxin fixation in the central nervous system may lead to seizures or involvement of the autonomic nervous system

29. Tetanus- History Described by Hippocrates in Diseases lll The aphorism- a convulsion supervening upon a wound is deadly 1884- Arthur Nicolaier produced a tetanus like symptom by injecting soil samples into animals

30. Shibasaburo Kitasato Isolated the organism in 1889 from a fatal case of a soldier in Berlin He described the anaerobic culture requirements He worked with Emil Behring on tetanus and diphtheria toxins and antitoxins

31. Tetanus Case fatality rate- approximately 10% Case to death ratio declined from 30-50% In the late 1940’s there were 500-600 cases per year In 2003- only 20 reported cases in US Seen in patients older than 50 with waning immunity of in those who have not completed their vaccination series

32. Tetanus Worldwide- neonatal tetanus is the most common form in the developing world It is caused by contamination of the umbilical stump with spores through the use of a non- sterile instrument or by application of animal dung to the cut core http://www.who.int/vaccines/en/neotetanus.shtml

33. Licensing of Childhood Vaccines in the US Whole Cell Pertussis1914 Diphtheria toxoid1926 Tetanus toxoid1937 DT1947 DPT1948 DTaP1996-1998 Baker and Katz, Pediatric Research 2004 55:2;347

34. Vaccines Whole cell pertussis Acellular pertussis Many neurological complications with the whole cell pertussis lead to its replacement by the acellular version

35. Current US Recommendations- Children 5 Immunizations of DPT- DTaP 2 months 4 months 6 months 15- 18 months 4- 6 years

36. Current US Recommendations- Adults Repeat the TdaP every 10 years Beginning in adolescence- 14-16

37. Diphtheria, Pertussis, Tetanus Modern Issues

38. Diphtheria- Around the World

39. Diphtheria in Russia Diphtheria incidence in Russia was high in the first half of the century with more than 750,000 cases in the 1950’s Immunization programs began in the 1920s were only fully implemented in 1958 with universal childhood immunizations

40. Diphtheria Rates in Russia Vitek and Wharton, Journal of Emerging Infectious Disease 1998

41. Factors Influencing the Emergence of Diphtheria in the Newly Independent States 1990-1996 Technology and Industry  Population of susceptible adults Human Demographics and Behavior  Population resistance to vaccinating children  Changes in the childhood vaccination schedule  High levels of militarization Microbial Adaptation and Change  Changes in biotype or emergence of epidemic clones Vitek and Wharton 1998: Emerging infectious Diseases 4:4: 548

42. Factors Influencing the Emergence of Diphtheria in the Newly Independent States 1990-1996 Economic Development and Land Use  Highly crowded and intense urbanization, substandard housing Breakdown of Public Health Measures  Decreased immunization in Central Asia and Caucasus due to break up of Soviet Union International Travel and Land Use  Repatriation of Russian population from republics  Refugees from Tajikistan, refugees in Georgia Vitek and Wharton 1998: Emerging infectious Diseases 4:4: 548

43. Pertussis on the Rise- 2004 http://www.pertussis.com/digest/

44. Pertussis in Cook County

45. Pertussis in Chicago Areas with the most cases- Northbrook (26) and Arlington Heights (14)

46. Neonatal Tetanus Uncommon in US - 2 cases since 1989 According to WHO- 164,000 cases and 110,000 deaths per year Of the 28 countries that account for 90% of neonatal cases- 16 are in Africa Vaccination rates in this region are stable in the low 30s- 35% in 1998

49. Summary and Food for Thought The scientific progress in infectious diseases remain one of major advances in modern medicine Immunizations have dramatically decreased the rates of infectious diseases They have been associated with reduced pediatric mortality and increased the life expectancy

50. Summary and Food for Thought The return of preventable diseases is associated with lowered immunization rates often reflecting disruptions in social networks Scientists monitor changes in the epidemiology of disease along with close evaluation of vaccine efficacy. In the west and throughout the world, vaccine recommendations continue to evolve.