Transcript DPT - University of Chicago

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

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%
Corynebacterium diphtheriae


Gram positive, non
motile, rod shaped
bacteria
Names for club shapeKoryne- Greek for club
Described by Edwin
Klebs and Friedrich
Löffler- called the
Klebs Löffler bacteria
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
Pharyngitis 101






Viral causesInfectious Mononucleosis
Streptococcal pharyngitis- GAS
Diphtheria
Pertussis
Epiglottitis
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
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
Francisco Goya - Lazarillo de Tormes1819
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
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
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;
The New Cure for Diphtheria, Croup, etcInjecting 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
Eleanor Roosevelt
United States Diphtheria Mortality
Rates
The First Intubation

In 1885, New York physician Joseph O'Dwyer
introduced tracheal intubation for the
treatment of severe diphtheria
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 Nome674 miles away.

The current race is from Anchorage to Nome – 1150
miles
Balto
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
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
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
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
Complications of Pertussis






Chronic Cough
Sleep disturbances
Headache
Pneumonia
Seizures
Encephalopathy
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
Tetanus- Clinical Findings





Symptoms
Spasm of the muscles- typically jaw muscles
Spasm of neck muscles, difficulty in
swallowing
Abdominal muscle stiffness
Autonomic instability
Tetanus







Localized
Generalized
Cephalic
Neonatal
Classic findings- risus sardonicus
Trismus
Opistotonus
Contracted body of soldier suffering from
tetanus- opistotonus
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
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
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
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
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 nonsterile instrument or by application of animal
dung to the cut core
http://www.who.int/vaccines/en/neotetanus.shtml
Licensing of Childhood Vaccines in the US
Whole Cell Pertussis
1914
Diphtheria toxoid
1926
Tetanus toxoid
1937
DT
1947
DPT
1948
DTaP
1996-1998
Baker and Katz, Pediatric Research 2004 55:2;347
Vaccines



Whole cell pertussis
Acellular pertussis
Many neurological complications with the
whole cell pertussis lead to its replacement
by the acellular version
Current US RecommendationsChildren

5 Immunizations of DPT- DTaP

2 months
4 months
6 months
15- 18 months
4- 6 years




Current US RecommendationsAdults


Repeat the TdaP every 10 years
Beginning in adolescence- 14-16
Diphtheria, Pertussis,
Tetanus
Modern Issues
Diphtheria- Around the World
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
Diphtheria Rates in Russia
Vitek and Wharton, Journal of
Emerging Infectious Disease 1998
Factors Influencing the Emergence of
Diphtheria in the Newly Independent States
1990-1996

Technology and Industry


Human Demographics and Behavior




Population of susceptible adults
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
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
Pertussis on the Rise- 2004
http://www.pertussis.com/digest/
Pertussis in Cook County
Pertussis in Chicago
Areas with the most cases- Northbrook (26) and Arlington Heights (14)
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
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
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.