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 shape- Koryne- 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 causes- Infectious 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 Tormes- 1819

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; 73.4 668

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

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 Nome- 674 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 non-sterile 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 USWhole 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 Recommendations- Children 5 Immunizations of DPT- DTaP

2 months 4 months 6 months 15- 18 months 4- 6 years

Current US Recommendations- Adults

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

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

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.