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DPT- From Epidemics to Immunizations- A Modern Success Story

DPT- From Epidemics to Immunizations- A Modern Success Story. Mindy A. Schwartz, MD University of Chicago June 27, 2006. Outline. Diphtheria Pertussis Tetanus Immunizations Modern Issues Summary. Diphtheria. Hippocrates described this in the 4th century BCE

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DPT- From Epidemics to Immunizations- A Modern Success Story

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  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 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, TetanusModern 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

  47. 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

  48. 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.

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