Welcome to the Clinical Center Grand Rounds,
a weekly series of educational lectures for physicians and
health care professionals broadcast from the Clinical
Center at the National Institutes of Health in
Bethesda, MD.
The NIH Clinical Center is the world's largest hospital totally
dedicated to investigational research and leads the global
effort in training today's investigators and discovering
tomorrow's cures.
Learn more by visiting us online at http://clinicalcenter.nih.gov
OUR TEACHER IS SARAH S. LONG AT
DREXEL SCHOOL OF MEDICINE AND AT
ST. CHRISTOPHER'S HOSPITAL FOR
CHILDREN IN PHILADELPHIA,
PENNSYLVANIA.
DR. LONG EARNED HER MEDICAL
DEGREE FROM JEFFERSON MEDICAL
COLLEGE AND COMPLETED HER
FELLOWSHIP IN PEDIATRIC
INFECTIOUS DISEASES AT
ST. CHRISTOPHER'S HOSPITAL FOR
CHILDREN FOLLOWED BY AN NIH
RESEARCHSHIP IN PHILADELPHIA.
DR. LONG IS NATIONALLY
RECOGNIZED FOR HER RESEARCH IN
VACCINE PREVENTIBLE DISEASES IN
CHILDREN.
SHE CURRENTLY PROVIDES CLINICAL
CONSULTATIVE CARE TO ENABLE THE
BEST DECISIONS FOR
PHILADELPHIA'S UNDER PRIVILEGED
CHILDREN AND MENTOR STUDENTS AND
INFECTIOUS DISEASES CLINICAL
FELLOWS.
AS AN ACADEMIC AND INSTITUTIONAL
LEADER, DR. LONG HAS SERVED AS
CHAIR OF THE FIRST SUBSPECIALTY
BOARD OF PEDIATRIC INFECTIOUS
DISEASES AT THE AMERICAN BOARD
OF PEDIATRICS.
AS CHAIR OF THE BOARD OF
DIRECTORS OF THE AMERICAN BOARD
OF PEDIATRICS, AS PRESIDENT OF
THE PEDIATRIC INFECTIOUS
DISEASES SOCIETY AND AS
PRESIDENT OF THE MEDICAL STAFF
AT ST. CHRISTOPHER'S HOSPITAL
FOR CHILDREN.
SHE IS BOTH THE FOUNDING AND
CURRENT CHIEF EDITOR OF THE
TEXTBOOK PRINCIPLES IN PRACTICE
OF PEDIATRIC INFECTIOUS DISEASES
WHICH IS NOW IN ITS SIXTH
EDITION AND IS AN ASSOCIATE
EDITOR OF THE JOURNAL OF
PEDIATRICS.
BETWEEN 2006 AND 2021, SHE WAS
AN ASSOCIATE EDITOR FOR FIVE
EDITIONS OF THE RED BOOK REPORT
OF THE COMMITTEE OF INFECTIOUS
DISEASES OF THE AMERICAN ACADEMY
OF PEDIATRICS.
AND DR. LONG SERVES AS A PAST
MEMBER OF THE VACCINES AND
RELATED BIOLOGICAL COMMITTEE OF
THE U.S. FOOD AND DRUG
ADMINISTRATION AND CURRENTLY AS
A MEMBER OF THE ADVISORY
COMMITTEE ON IMMUNIZATION
PRACTICES FOR THE CENTERS OF
DISEASE CONTROL AND PREVENTION
IN ATLANTA.
SHE'S A RECIPIENT OF NUMEROUS
NATIONAL AWARDS AND PROFESSIONAL
HONORS INCLUDING A LIFE TIME
CONTRIBUTION FROM THE AMERICAN
ACADEMY OF PEDIATRICS AND
DISTINGUISHED PHYSICIAN AWARD
FROM THE PEDIATRIC INFECTIOUS
DISEASES SOCIETY WHICH IS GIVEN
TO A PHYSICIAN WHO HAS AN
EXTENSIVE AND DISTINGUISHED
CAREER IN PEDIATRIC INFECTIOUS
DISEASES AS A CLINICIAN,
EDUCATOR AND/OR INVESTIGATOR.
THE TITLE OF DR. LONG'S
PRESENTATION IS CLINICAL
OBSERVATION CATALYZES DISCOVERY.
JOIN ME IN WELCOMING TODAY'S
GREAT TEACHER, DR. SARAH LONG.
>> YOU CAN IMAGINE HOW THRILLED
I AM TO BE ASKED TO GIVE THIS
PRESENTATION AND IT IS DAUNTING
AND TO DO IT WITH ZOOM IT'S AS
DIFFICULT AS THE WORDS THAT GO
TOGETHER.
I HAVE NO DISCLOSURES I CALLED
THIS CATALYZES DISCOVERY BECAUSE
IDEAS HAVE TO START SOMEWHERE
AND FOR ME THEY HAVE STARTED
EITHER WITH A PATIENT IN FRONT
OF ME OR SOMETHING IN THE MICRO
BIOLOGY UNDERSTOOD OR NEED TO
EXPLAIN FURTHER.
WE SEE THE LEARNING OBJECTIVES
HERE.
I HOPE WE CAN LEARN TOGETHER
TODAY TO LEARN A LITTLE BIT
ABOUT THE PATHOGENESIS OF INFANT
BOTULISM HAPPENS TO INFANTS AND
THE CHALLENGES OF PERTUSSIS AND
THE CHANGES IN THE EPIDEMIOLOGY
IN THE VACCINE EVENTS AND WHAT
THE NEXT GENERATION OF PERTUSSIS
VACCINES MIGHT NEED TO BE AND
HOPE YOU TAKE TAKEAWAY A FEW
THINGS OF THE PROCESS OF
CLINICAL REASONING AND SOMETHING
THAT MAY HELP WITH YOUR CAREER
DEVELOPMENT.
LET'S GET STARTED.
WHEN YOU GET DOWN THE LINE YOU
MAY ASK YOURSELF HOW DOES THAT
AMAZING CAREER I HAD.
YOU MIGHT AT THAT POINT HAVE
THINGS YOU WOULD LIKE TO PASS
ON.
I THOUGHT OF A FEW THINGS I
THINK INFLUENCED MY ABILITY TO
BE SUCCESSFUL I'D LIKE TO PASS
ON TO YOU.
THE FIRST IS GOING TO BE JUMP
INTO YOUR EDUCATION AND CAREER
AND FIND A MENTOR.
WELL, I GREW UP IN THE TERRITORY
OF ALASKA.
IT'S INTERESTING.
THIS LITTLE PICTURE OF ME WHEN
I'M ABOUT FIVE I THINK I HAD
ALASKAN NATIVES AND AMERICAN
INDIANS AS MY FRIEND BUT FOR
SOME REASON I WAS ALWAYS WEARING
THE DIME STORE PLASTIC HEAD
DRESS AND THIS TELLS YOU
SOMETHING ABOUT ME, THE MOST
WONDERFUL MOST LOYAL DOG THERE
WAS, I'M SURE IF I RIP UP THE
SIDES OF HIS MOUTH LIKE THAT I
CAN MAKE HIM SMILE SO I HAVE
NEVER TAKEN NO FOR AN ANSWER.
A COLLEAGUE RECENTLY SENT ME
THIS PICTURE WHEN SHE VISITED
JUNO AND TITLED IT RUSH HOUR AT
TEA HARBOR.
AS I GREW UP LOCKED BY MOUNTAINS
IN THIS GORGEOUS PLACE, THERE
WERE ABOUT 7,000 PEOPLE AND IT
WAS QUITE A REMARKABLE THING
WHEN I CAME TO PHILADELPHIA FROM
FOR MEDICAL SCHOOL AND SPENT MY
MEDICAL SCHOOL AND RESIDENCY AND
MY ENTIRE CAREER AS WAS
MENTIONED NORTH PHILADELPHIA
HOPING TO BRING THE BEST MEDICAL
POSITIONS TO CHILDREN IN THE
SECOND MOST VULNERABLE FOOD
VULNERABLE ZIP CODE IN THE
UNITED STATES.
IT'S BEEN A PRIVILEGE TO WORK
WITH AND LEARN FROM THOSE
PATIENTS AND FAMILIES.
SO HERE'S JEFFERSON ON THE DAY I
ARRIVED, 1025 WALNUT AND THIS IS
ALL ONE PICTURE ON THE LEFT AND
THERE WAS A HUGE STAIRWAY IN
FRONT OF YOU THAT LED TO THE
CLINIC AT THE TO THE STAIRS
THAT'S NOW BEEN PUT INTO MUSEUMS
BUT IT GREETED ME EVERY DAY.
I DIDN'T GO UP, I WENT DOWN TO
WHAT WAS KNOWN AS THE PIT.
HERE IS OUR CLASS AND I HAD
PHENOMENAL MENTORS AT JEFFERSON.
THERE WERE 10, 11 OF US WOMEN
AND 180 SOMETHING MEN.
I DON'T KNOW IF I GOT SPECIAL
ATTENTION BUT I FELT THESE
PEOPLE WERE THERE FOR ME AND
THEY WERE ALL DIFFERENT.
GONZALO APONTE WAS CHARISMATIC,
OPERATIC AND BIGGER THAN LIFE
AND THE ENDOCRINOLOGIST WAS
FUNNY AND JOHN TEMPLETON A FUNNY
SENSE OF RUMOR AND SOUTH
EXCELLENT AND JOE RODGERS THE
FIRST MASTER CLINICIAN I GOT TO
KNOW AND HERE'S MY GRADUATION
PICTURE.
I WAS SENT TO MY HUSBAND'S
INTERNAL MEDICINE WARD WHERE HE
WAS THE RESIDENT WHEN I I WAS A
THIRD-YEAR MEDICAL STUDENT AND
HE SAID, IF YOU GOT BEHIND ME IN
AN ELEVATOR YOU CAN'T SEE AROUND
THAT ALL HAIR SO YOU'LL SEE SOME
HAIRSTYLES AS WE GO ON AS WELL.
THEN I WENT TO ST. CHRISTOPHER'S
WHERE I HAD INNUMERABLE MENTORS
AND I HAD THE FATHER OF
PEDIATRICS AND HERE I AM WITH MY
MAJOR MENTOR MASTER CLINICIAN
DAVID SMITH AND THEN NANCY WONG
TAUGHT ME WHAT I KNEW ABOUT
ANTIBIOTICS.
SHE WAS A PULMONOLOGIST, CYSTIC
FIBROSIS AND A HEMATOLOGIST AND
TWO PATHOLOGISTS, STRIKINGLY
DIFFERENT ERA.
MOLLY DEPINA AND WHEN A CHILD
DIED AT ST. CHRISTOPHER'S ONE
WOULD GO OUT TO THE FAMILY AND
DESCRIBE AN AUTOPSY AND THEY HAD
AN AUTOPSY RATE OF OVER 80% AND
EVERY TIME THERE WAS AN AUTOPSY
YOU WOULD HERE AN OVERHEAD PAGE
THAT SAID PAGING DR. POST.
PAGING DR. POST.
WE FLED TO THE AUTOPSY SUITE
WHERE ALWAYS THESE PEOPLE AND
JOHN KIRKPATRICK, A FABULOUS
RADIOLOGIST WERE THERE AND WE
WOULD WATCH THESE INCREDIBLY
BRILLIANT PEOPLE LEARN NEW
THINGS IT'S WHERE THE DEGEORGE
SYNDROME WERE DISCOVERED AND
THEN SERENDIPITY IN MY NIH
FELLOWSHIP HERE IN MICROBIOLOGY
I WAS PLUNKED IN A SEAT NEXT TO
A BRAND NEW FACULTY MEMBER IN
INTERNAL MEDICINE AND INFECTIOUS
DISEASES AND TURNED OUT TO BE A
FABULOUS TEACHER AND I REALLY
STOLE ALL OF HIS ABILITY I COULD
TO LEARN HOW TO TEACH.
THE NEXT THING I WOULD SUGGEST
YOU COLLABORATE WITH EXPERTS.
I HAD LOTS OF LABORATORY EXPERTS
I COLLABORATED WITH AND FOR AN
INFECTIOUS DISEASE DOCTOR THE
CDC IS A WEALTH OF RESOURCE AND
THIS IS WHEN VACCINE NOT COMING
FROM ACADEMIA BUT MORE MUCH
INDUSTRY WHERE THEY HAD $100
MILLION TO THROW AT A NEW IDEA
AND BE WILLING TO FAIL WHICH
THEY DID WITH MOST OF THEM AND I
ALWAYS LEARNED A LOT FROM
COLLEAGUES.
I WAS RAISED TO BE TOUGH AND I
HAVE BEEN A TOUGH MENTOR.
I THINK SOMETIMES MEDICAL
STUDENTS DON'T UNDERSTAND THIS
IS NOT A JOB.
THEY'RE RESPONSIBLE FOR PEOPLE'S
LIVES AND I TAKE IT VERY
SERIOUSLY.
SO I TAKE THAT I'M A TOUGH
MENTOR.
SO EVERYBODY KNOWS BEFORE
PRESENTING AT LONG'S ROUNDS
WHICH WENT ON EVERY DAY I WAS ON
SERVICE, EVERY DAY FOR THE FIRST
FIVE, SIX YEARS OF MY CAREER AND
AT LEAST 50% OF THE TIME I HAVE
MAINTAINED MY ROLE AS AN IN
PATIENT CONSULTING PHYSICIAN TO
CONTINUE TO LEARN FROM MY
PATIENTS AND PARENTS AND
COLLEAGUES AND THINGS THAT CAME
TO ME.
BUT YOU DON'T PRESENT AT LONG
ROUNDS WITHOUT A FIRST PERSON
HISTORY INCLUDING PRECISE AND
CONCISE TIME LINE AND EXPOSURE
AND EXACTING PHYSICAL
EXAMINATION, STARTING WITH THE
GLOBAL OBSERVATION OF THE
PATIENT, CARDIAL FEATURES OF THE
PATIENT'S PROBLEM USING MEDICAL
TERMINOLOGY, YOU SYNTHESIZE THE
PROBLEM NOT WHO SAID WHAT TO WHO
WHERE AND WHEN BUT FIVE TO SIX
WORDS THAT DESCRIBE THE PROBLEM
AND THE FEATURES OF THE SIMPLE
LABORATORY TEST AND YOU WILL
HAVE HAD A PERSONAL EXCHANGE
WITH THE CONSULTING PHYSICIANS
TO SEE WHAT IT IS THEY'RE
WORRIED ABOUT AND WHAT THE
LABORATORY PERSONNEL ABOUT HOW
CAN WE BEST SOLVE THIS PROBLEM.
SO I JUST WANT TO INTRODUCE A
FEW OF YOU TO SOMETHING ABOUT
CLINICAL REASONING.
CLINICAL REASONING PICK ALL
THESE THINGS AND IT IS HOW AN
EXPERT THINKS.
IT'S A PROCESS WHERE WE ARRIVE
AT A DIAGNOSIS OR DECISION.
IT'S NOT TAUGHT EXPLICITLY.
I HAD ALL THESE WONDERFUL
MENTORS AND ABOUT 15 YEARS INTO
MY FACULTY POSITION I BEGAN TO
FEEL LIKE DR. SMITH.
I TALKED WITH FAMILIES, I
PURSUED PROBLEMS, I HAD AN
APPROACH AND HAD A CONFIDENCE IN
MY UNDERSTANDING MAYBE NOT OF
THE DIAGNOSIS BUT WHERE WE OUGHT
TO GO WE WOULD HAVE HAD AND TOLD
HIM I BEGIN TO FEEL LIKE YOU.
I CANNOT TELL HOW MANY
PHYSICIANS WHO WERE RESIDENTS AT
ST. CHRISTOPHER'S HAVE SENT ME A
NOTE, 15 TO 20 YEARS AFTER THEY
HAD LEFT AND SAID I SAW A
PATIENT TODAY AND I FELT I WAS
YOU.
I FELT THAT I WAS PURSUING THAT
IN THE WAY YOU MIGHT.
NOW THAT MAKES A TEACHER'S HEART
SING BUT WE NOW KNOW WE CAN GET
THERE SOONER THAN 15 YEARS.
BECOMES AN EXPERT REQUIRES
KNOWLEDGE AND EXPERIENCE.
EXPERTS TAKE CLINIC SCENARIOS,
WHAT YOU HEAR IN THE HISTORY AND
SYNTHESIZE INTO PROBLEM
REPRESENTATIONS THAT INCLUDE SOW
SOMATIC QUALIFIERS AND HERE'S A
REPRESENTATION WITH SOMATIC
QUALIFIERS.
THIS PERSON HAS THE ACUTE ONSET
OF UNREMITTING PROGRESSIVE,
EXQUISITE UPPER ABDOMINAL PAIN.
THAT'S THE SYNTHESIS OF THE
PATIENT'S PROBLEM.
THE SEMANTIC QUALIFIERS ARE ALL
THE MEDICAL ADJECTIVES I ADDED
TO THEM.
HERE'S ANOTHER ONE.
THE PATIENT HAS A SUBACUTE
REMITTING WAXING AND WANING
COURSE OF INTERMITTENT ABDOMINAL
PAIN THAT IS ASSOCIATED WITH
LOOSE STOOLS AND WEIGHT LOSS.
THAT'S A DIFFERENT PROBLEM
REPRESENTATION, ISN'T IT?
WE COMPARE THE PROBLEM
REPRESENTATIONS WITH SCRIPTS.
ACUTE PANCREATITIS AND EXQUISITE
PAIN, SUBACUTE PAIN AND I'M
LOSING THE WORD WHEN YOU LOSE
THE PAIN THAT IS EPISODIC.
AND THERE'S USUALLY WEIGHT LOSS
INVOLVED AND THERE FREQUENTLY IS
ANEMIA.
YOU MATCH THE ILLNESS TO WHAT
YOU HAVE DECIDED IS THE PROBLEM
BUT YOU HAVE TO BE CAREFUL IN
DOING THAT.
WE'RE GOING TO USE A FEW OF
THOSE THINGS TO ILLUSTRATE HOW
PAYING ATTENTION AND OBSERVING
CAN LEAD TO DISCOVERY.
HERE'S THE INFANT BOTULISM
STUDY.
IT'S ALSO GOING TO ILLUSTRATE
HOW I THINK STAYING CLOSE TO
YOUR PRIMARY PROVIDERS IS
CRITICAL AND COLLABORATE WITH
THOSE PRIMARY PROVIDERS.
SO WARREN GROVER IS A
NEUROLOGIST AT ST. CHRISTOPHER'S
AND IS SMARTER THAN ANYTHING AND
THEY DISTRIBUTED -- DESCRIBED
NINE PATIENTS WITH ACUTE
REVERSIBLE POLY NEUROPATHY AND
BEFORE YOU TELL ME THE PHYSICAL
SCHANGS -- EXAMINATION AND
HEART AND LUNGS SOUND LIKE IF
IT'S ACTIVE OR UNATTENTIVE,
UNRESPONSIVE, IRRITABLE, NOT
IRRITABLE CHILD.
THINK OF HOW YOU WOULD DESCRIBE
WHAT YOU SEE ON THE LEFT.
AFTER THEY DESCRIBED THIS AND
PUBLISHED IT, IN CALIFORNIA THE
SAME KIND OF INFANTS WERE SEEN
AND THEY HAD ELECTROMYOGRAPHY
AND THEY SAID THESE BRIEF SHORT
OVER ABUNDANT FOR THE STIMULUS
GIVEN TO ACTION POTENTIALS THAT
INCREASE WITH REPETITIVE
STIMULATION HAVE ONLY ONE
ETIOLOGY AND THEY ARE BOTULISM.
IT'S AND THEY WERE ABLE TO FIND
THE TOXIN OF BOHULINUN AND THEN
THE DEPARTMENT OF HEALTH BEGAN
TO DESCRIBE PATIENTS IN WHICH
THEY FOUND THE ORGANISMS AND THE
TOXINS IN THE PATIENT'S STOOL.
THESE WERE YOUNG INFANTS AND HAD
NOT INGESTED PREFORM TOXIN WHICH
IS BOTULISM INTOXICATION AND
WERE NOT EATING GREEN BEANS,
THEY WERE FOUR AND FIVE MONTHS
OLD SO THEY GOT BOTULISM FROM
THE CONSUMPTION OR INGESTION AND
IT WAS FROM HONEY AND THE INFANT
BOTULISM IS NOT RELATED TO HONEY
ANY MORE.
IT'S A NATURAL OCCURRENCE.
THERE WERE SOME WONDERFUL MICE
EXPERTS ASKING IF THE MICE GUT
PERMISSIVE TO OUT GROWTH OF
BOTULISM SPORES AND IF THERE'S
VEGETATION OR OUTGROWTH OF THE
SPORES IT WILL PRODUCE TOXIN AND
YOU CAN THEN HAVE THE TOXIN
ABSORBED.
HERE ON THE LEFT YOU'LL SEE THE
ANIMALS HE EXPERIMENTED WITH AND
FED THEM THE SPORES NOT THE
TOXIN AND I'M ANSWERING THE
QUESTION FOUR, DID THE ANIMALS
GET BOTULISM?
AND HERE'S DAY ONE YES, BOTULISM
AND HERE A NEONATE IN THE COLONY
FOR THREE DAYS, FED THE SPORES,
NO BOTULISM AND HERE'S GERM-FREE
WITH A LIMITED FLORA THEY'VE
BEEN FED AND GO FROM SUSCEPTIBLE
TO NOT SUSCEPTIBLE AND WITH
SUCCESSIVE POLLINATION AND YOU
CAN MAKE THEM SUSCEPTIBLE TO
INFANT BOTULISM AND WE
OCCASIONALLY SEE AN ADULT.
USUALLY WHO HAS HAD SURGERY ON
THE ABDOMEN SO THE ANTI-MOTILITY
AND ANTIBIOTIC THAT HAPPEN TO
HAVE OCCURRENCE OF THE INFANT
BOTULISM AND CALIFORNIA IS THE
HOTTEST SPOT AND WE STILL HAVE
100 PLUS CASES OF INFANT
BOTULISM.
IT'S BEEN RECOGNIZED IN 49
STATES FOR SURE.
AND A CLINICIAN STOPPED AND WAS
COLLECTING SOIL SAMPLES AND
LOOKING FOR THE CLUSTERING OF
THE BOTULINUM IN THE SOIL AND
FOUND 24% OF SAMPLES WERE
POSITIVE FOR BOTULINUM AND THE
NEUROTOXIC AND IN THE EAST WAS
ALL B AND WHEN YOU BEGAN TO GET
TO WHERE THE ROCKY MOUNTAIN
RISES OUT OF THE PLANES YOU
BEGIN TO SEE NEUROTOXINA AND
THEY MATCHED PERFECTLY THE
INFANT TYPES OF BOTULISM.
I HAD DONE MY RESEARCH ON
ANAEROBIC MICROBIOLOGY AND
DECIDED I WAS INTERESTED IN HOW
FLORA WAS ESTABLISHED AND SHOWED
ON THE FIRST DAY OF LIFE IF YOU
SCRAPE GENTLY WITH A TONGUE
DEPRESSOR THE INSIDE OF THE ORAL
MUCOSA AND PUT THAT ON A SLIDE
IN THE LABORATORY THAT ONLY
WANTS TO ADHERE THAT TURNS INTO
NORMAL FLORA.
HEALTHY PEOPLE WHO ARE OLDER DO
NOT WANT TO ADHERE E. COLI THEY
WANT THE NORMAL FLORA AND I DID
STUDIES ON THE ESTABLISHMENT OF
FECAL FLORA IN INFANTS AND FOUND
IT WAS DEPENDENT ON THE METHOD
OF BIRTH, VAGINAL, YES OR NO AND
WHAT THEY WERE FED AND FUND THAT
THAT WAS ALSO EXTREMELY
PREDICTABLE.
SO I THOUGHT MAYBE THIS MUST
HAVE SOMETHING TO DO WITH HOW
BOTULISM OCCURRED IN INFANTS.
SO WE REPORTED 44 CASES FROM
BOTULISM IN PHILADELPHIA AND
IT'S IN QUOTES REMEMBER THAT'S
IN QUOTES.
AND THEY WERE ALL 43 WERE B AND
OF AWAS SOMEONE VISITING UNDER
CALIFORNIA AND ALL UNDER 12
MONTHS AND SINCE THEN THE MORE
THAN 1,000 CHILDREN FROM INFANT
BOTULISM HAVE BEEN UNDER IS IT
MONTHS OF AGE.
INTERESTINGLY, I TOLD YOU WHERE
I WAS PRACTICING IN NORTH
PHILADELPHIA, ALL WHITE, TWO
PARENT FAMILIES, INSURANCE AND
PURELY OR PREDOMINANTLY BREAST
FED.
TWO-THIRDS HAD THEIR FIRST
NON-HUMAN SUBSTANCE LESS THAN
FOUR WEEKS BEFORE ONSET.
THAT SPECIFICALLY IS LOOKING FOR
A PIECE OF HISTORY THAT WE DID
FIND.
ANOTHER PIECE OF HISTORY, HALF
THE FATHERS HADDOCK -- HAD
OCCUPATIONS THAT HAD DAILY
INTERACTION WITH THE SOIL AND I
COLLECTED FATHERS AND FATHER'S
WORK BOOTS SAMPLES AND IN EVERY
INSTANCE FOUND BOTULINUM SPORES
OF IDENTICAL TYPE IN THE SOIL.
I ALSO DID QUANTITATIVE FECAL
FLORA WAS NOT THAT OF A FORMULA
FED BABY THAT WOULD BE
INHIBITORY AND NOT TYPICAL OF
THE FERMENTATED FLORA OF BREAST
FED BABIES WHO FLORA IS ALSO
EXPECTED TO BE INHIBITORY BUT
WAS SOMEWHERE IN BETWEEN.
WE DID A CASE CONTROL STUDY
GETTING PEDIATRICIANS FOR EACH
CASE OF INFANT BOTULISM FIND
FOUR INFANTS WHO THEY MATCHED
FOR THE BIRTH DATE AND BIRTH
HOSPITAL WITH INFANT BOTULISM TO
SEE IF THEY'RE DEMOGRAPHICS WERE
DIFFERENT OR IF THAT'S WHERE ALL
THE INFANTS WHERE THE PATIENTS
CAME FROM WERE LIKE.
WE FOUND IN FACT THESE WERE
SIGNIFICANT DIFFERENCES AND MOST
IMPORTANTLY 100% OF THE INFANTS
WITH BOTULINUM WERE BREAST FED
AND IF YOU USE YOUR PROBLEM
REPRESENTATION YOU NEVER HAVE A
PROBLEM OF THE DIAGNOSIS OF
INFANT BOTULISM.
IT'S DESCENDING AND ALWAYS
INVOLVING CRANIAL NERVES.
THERE'S ALWAYS HEAD LAG.
THE MOTHER'S THE FIRST TO NOTICE
SOMETHING ABOUT HER BABY THAT'S
WRONG AND IT'S BECAUSE IT
DOESN'T HAVE THE STRENGTH OF
FACIAL EXPRESSION AND YOU
OBSERVE THAT PATIENT WHO I
SHOWED YOU, YOU SHOULD HAVE BEEN
ABLE TO OBSERVE NOT IN THE
PICTURE BUT IN PERSON THAT THE
PATIENT IS ALERT BUT UNABLE TO
MOVE.
SO THEIR EYES, IF THEY DON'T
HAVE COMPLETE OPTHALAL PLASIA
THEY CAN'T MOVE OR MAKE AN
EXPRESSION AND I ALWAYS TELL THE
TRAINEES, RECOGNIZE HOW AN
INFANT MAKES YOU FEEL.
AN INFANT WITH SEPTOCEMIA AND
YOU WANT TO RUN AND HAVE SOMEONE
HELP YOU RESUSCITATE THE INFANT
AND THEY FEEL VULNERABLE AND YOU
DON'T WANT TO TALK LOUD BECAUSE
THEY'RE NOT DOING THAT SO I
TEACH PEOPLE TO PAY ATTENTION.
BACK TO THE BREAST FEEDING THE
HUMAN MILK AND FORMULA, ONLY IN
THE FIRST WEEK OF LIFE ARE
FORMULA FED BABIES THE ONES
GETTING INFANT BOTULISM MORE
LIKELY.
AFTER THEY RAPIDLY ALTER THEIR
FLORA AND MOST ANTIBIOTICS DON'T
SO MUCH AND LESS LIKELY TO BE
THE ONES GETTING INFANT BOTULISM
AS TIME GOES ON WHEREAS THOSE
FED HUMAN MILK PURELY WILL GET
BOTULISM UNTIL THEY BEGIN TO --
THEY'LL BE SUSCEPTIBLE TO
BOTULISM BECAUSE THEY HAVE TO
WEAN AT SOME POINT AND IT'S THAT
POINT OF WEANING WHERE THEY HAVE
FLORA PERTURBED AND PERMISSIBLE
TO THE SPORES.
AND IN PITTSBURGH THERE WERE
MANY CHILDREN AS IN PENNSYLVANIA
AND IT WAS ODD DISTRIBUTION
THOUGH WE'RE IN PHILADELPHIA
NONE OF THE CASES LIVED IN THE
HEART OF PHILADELPHIA.
ONE WAS ON THE BORDER AND THEY
WERE IN THE COUNTY SURROUNDING
PHILADELPHIA WITH NO CASES IN
THE COUNTY SURROUNDING THOSE.
WE DID A COUNTY CONTROL STUDY
THESE BEING PHILADELPHIA CASE
AND THE UPPER COUNTIES AND
YOU'LL SEE AGAIN I SOLICITED THE
HELP OF 22 PEDIATRICIANS GOT ME
700 CHARACTERISTICS FROM 700
INFANTS BORN IN THE IMMEDIATE
BIRTH DATE OF BOTULISM CASES TO
SEE IF WE CAN UNDERSTAND BETTER
HOW CASES WERE OCCURRING IN THE
UNEVEN DISTRIBUTION.
YOU'LL SEE CONSIDERATION CASE
COUNTIES AND PHILADELPHIA
COUNTIES, THERE WERE LOTS OF
DIFFERENT THE MOST IMPORTANT
BEING -- SORRY, I DIDN'T TELL
YOU THIS RIGHT, 64% OF THE CASE
COUNTY BABE YES WERE BREAST FED
AND 37% OF THE PHILADELPHIA
COUNTIES.
SO THAT MIGHT EXPLAIN SOME OF
THE UNEQUAL DISTRIBUTION OF
CASES BUT LOOK AT THE CASE
COUNTIES WHERE ALL THE CASES
WERE IN THE UPPER COUNTIES WHERE
NO CASES WERE.
AND THEY ARE IDENTICAL INCLUDING
THE AMOUNT OF BREAST FEEDING
THAT GOES ON.
WE KNOW THERE'S INFANT BOTULISM
FOR THE ANIMAL POPULATION.
LOOSE NECK IN DUCK AND HORSES
GET A FORM AND THERE'S LOTS OF
ANIMALS WITH INFANT BOTULISM.
INFANT BOTULISM OCCURS FROM IN
AVOIDABLE EXPOSURE TO SPORES IN
THE ENVIRONMENT.
BREAST FEEDING IS A RISK FACTOR
VULNERABILITY IS AT THE TIME OF
WEANING.
THERE'S AN UNEVEN DISTRIBUTION
OF SPORES IN THE SOIL MATCHING
CASE DENSITY.
THAT'S INFANT BOTULISM.
THERE'S A HAPPY ENDING.
IF YOU'RE THERE TO INTUBATE THE
BABY WHEN THEY DON'T HAVE THE
STRENGTH TO BREATHE AND HAVE
METICULOUS CARE OF THEM MOST ON
A VENTILATOR 19 TO 21 DAYS AND
DO SURVIVE.
THEY HAVE LAG FOR A LONG TIME
BUT THERE'S NO AFFECT ON THEIR
BRAIN OR INTELLECTUAL FUNCTION
OR EVENTUAL MUSCULAR FUNCTION
AND HERE HE IS NOW 42 AND I
STILL HEAR FROM HIM AND HIS
FAMILY ABOUT ONCE A CHRISTMAS.
YOU PROBABLY ALSO KNOW THERE'S
BEEN DERIVED TREATMENT FROM
INFANT BOTULISM SO THE INFANTS
DON'T HAVE TO GO THROUGH 21 DAYS
OF BEING ON A VENTILATOR.
BY USE OF ANTI-TOXIN RAISED BY
IMMUNIZING ADULTS AND THEN
PURIFYING AND GIVEN TO INFANTS.
IT WAS STUDIED IN CALIFORNIA AND
PASSIONATE RELEASE AND TREAT
MONDAY IN THE '90s AND IT'S
CLEAR MANY YEARS LATER WITH 1200
INFANTS AT LEAST TREATED IT
REDUCES THE LENGTH OF STAY FROM
FIVE WEEKS TO TWO WEEKS AND IT
HAS PREVENTED MORE THAN 65 YEARS
OF HOSPITALIZATION AND $85
BILLION IN HOSPITAL CHARGES AND
WHEN STEVE ARNON WROTE THESE TWO
ARTICLES FOR THE JOURNAL OF
PEDIATRICS I WROTE IN SAYING
WELL DONE TO A COUNTRY THAT
FEDERALLY MANDATED THE ORPHAN
DRUG ACT AND WOULD ALLOW FOR THE
DEVELOPMENT OF SUCH A MARVELOUS
PRODUCT THAT COULD BE USED IN
100, 150 CHILDREN A YEAR.
WELL DONE TO THE LEADERS AND
IMMUNIZED DON'T DEPARTMENT OF
HEALTH AND TO RECOGNIZE AN
UNCOMMON CONDITION TO PROVIDE
REMARKABLY EFFECTIVE THERAPY.
THIS IS A HAPPY STORY.
LET'S GO ON TO MY THIRD THING,
LISTEN TO YOUR PATIENTS.
WE CAN'T ABANDON THEM BECAUSE WE
DON'T UNDERSTAND THEIR PROBLEM.
AND HERE'S DR. SMITH LISTENING
TO A LITTLE PATIENT AND HERE'S
ME WITH ONE OF MY PATIENTS IN
THE '70s, EARLY 80s.
I SURMISE FROM BOTH OF OUR
HAIRDOS AND THE CHARMING LITTLE
PATIENT.
I'M ALSO GOING TO TALK A LITTLE
BIT ABOUT PURSUING WHAT WE DON'T
UNDERSTAND, THE PERTUSSIS STORY.
WHEN THE DUCKS DON'T LINE UP,
SOMETIMES YOU HAVE TO LOOK A
LITTLE BIT AND YOU'LL MAKE SOME
NEW DISCOVERY.
HERE IT WAS.
1975 I'D BEEN THE ONLY
INFECTIOUS DISEASE DOCTOR AND
CHIEF AS MY FIRST JOB FOR TWO
MONTHS WHEN A THREE--WEEK-OLD
WAS HELICOPTERED IN BECAUSE HE
HAD CONGENITAL LEUKEMIA AND HE
GOT THERE AND HIS LABORATORY
TESTS CAREFUL HOW YOU LOOK AND
INTERPRET AND THEN REPORT
LABORATORY TEST FINDINGS FINDINGS HE
DIDN'T HAVE LARGE LYMPHOCYTES
AND THERE'S A SHORT LIST OF THE
REACTION AND PERTUSSIS WAS ON
THE LIST.
WE HAD A FABULOUS LABORATORY.
WE HAD SOMEONE THAT HAD
PERTUSSIS AND HE WAS RAPIDLY
INTUBATED AND DID NOT HAVE A
COUGH.
HE HAD GAGGING AND GASPING AND
DEVELOPED STAPHOCOCCAL PNEUMONIA
AND DIED AND I SAID WHERE DID
THIS BABY GET PERTUSSIS AND WHY
DID THIS MOTHER HAVE SUCH A
TERRIBLE COUGH?
PERTUSSIS DID NOT OCCUR IN
INFANTS OR IN ADULTS IN 1975.
WELL IN THE NEXT YEAR WE SAW A
FEW MORE BABIES WITH INFANT
PERTUSSIS AND HERE'S A LITTLE
BABY THREE WEEKS OLD WHO GOT
PERTUSSIS WHOSE FATHER WAS A
PEDIATRIC RESIDENT WHO CARED FOR
AN INFANT IN INTENSIVE CARE WITH
PERTUSSIS WHOSE WIFE AT THE TIME
WAS DELIVERING AND GOT A
TERRIBLE COUGH AFTER HE HAD HAD
A TERRIBLE AWFUL COUGH AND WHERE
THEY'RE BABY GOT PERTUSSIS.
THE BABY DID WELL AND HERE THEY
ARE TWO YEARS LATER.
MEGAN IS NOW A MICROBIOLOGIST
AND THEIR BABY AND I SHOW YOU
THIS CHRISTMAS CARD PICTURE OF
THEIRS TO BE ABLE TO SAY TO YOU
THEY HAD THE SAME PEDIATRICIAN
IN NORTH PHILADELPHIA.
THEY GREW UP IN PHILADELPHIA.
HE HAD IMPECCABLE RECORDS.
TOM HAD HAD PERTUSSIS AS A CHILD
AND HIS WIFE SUE HAD BEEN FULLY
VACCINATED.
WE THOUGHT AT THE TIME DISEASE
AND VACCINE CONFER LIFE TIME
PROTECTION.
SERENDIPITY NUMBER 2, ADVANTAGE
NUMBER 2, RESOURCE WE HAD A
VIROLOGIST WHO WAS ALSO A
WONDERFUL SEROLOGIST AND SHE
SERVED MULTIPLE, MULTIPLE TIMES
FOR THE CDC AS THE SITE FOR
DETERMINING ZERO PREVALENCE OF
VACCINE PREVENTIBLE DISEASES IN
THE UNITED STATES SO WE DID
MULTIPLE, MULTIPLE IMMUNIZATION
TRIALS AND HERE I'M SHOWING
EDDIE ROTHSTEIN IN THE SUBURBS
WHO DID STUDIES WITH US.
I'M GOING TO SHOW YOU BRIEFLY WE
MADE LOTS OF DISCOVERIES ABOUT
PERTUSSIS.
ONE WAS THAT BECAUSE OUR
RESIDENTS KNEW WHAT PERTUSSIS
WAS ONE OF THE RESIDENTS EDITH
CASALES BECAME A PHYSICIAN FOR
HANDICAPPED CHILDREN AND
REALIZED THEY HAD AN OUTBREAK OF
COUGH THAT SOUNDED LIKE
PERTUSSIS TO HER AND WE CAME IN
AND STUDIED THEM AND IN FACT IT
WAS PERTUSSIS.
WE LEARNED THE ATTACK RATE IN
THE FACILITY WHERE THE CHILDREN
WERE EXQUISITELY IMMUNIZED THE
ATTACK RATE WAS 66% AND
TWO-THIRDS WERE SUBCLINICAL AND
WE LEARNED SEROLOGY WAS MORE
SENSITIVE THAN CULTURE THAN
DIRECT FLUORESCENT ANTIBIOTIC
SAMPLING AND THERE WAS A LOT OF
PERTUSSIS IN THE FACILITY SILENT
AND SOME WERE COUGHING ILLNESS
AS WELL.
WE THEN STUDIED FOUR INFANTS TO
STUDY THEIR FAMILY FOR A WHOLE
YEAR.
TURNED OUT WE DIDN'T NEED TO
THOUGH WE DID AND WE FOUND IN
THE FAMILIES 83% OF FAMILY
MEMBERS HAD EVIDENCE OF
PERTUSSIS DURING THIS SIEGE AND
ONLY A THIRD WERE CLINICAL.
ALL THE INFANTS HAD A COUGHING
ADULT IN THE HOUSEHOLD BEFORE
THEY BECAME ILL BEFORE THEY
BEGAN TO COUGH.
AND ONLY 20% OF THE INFECTED
HAVE POSITIVE CULTURE.
AGAIN, SEROLOGY WAS THE WAY TO
MAKE THE DIAGNOSIS AND ALL THE
INFECTED CONTACTS HAD DIAGNOSTIC
SEROLOGY AT THE TIME OF THE
RECOGNITION OF THE INDEX CASE.
THAT STANDS TO REASON.
THE THREE-WEEK-OLD ARE THE
VICTIM OF WHAT WAS UNRECOGNIZED
PERTUSSIS IN OLDER INDIVIDUALS.
THEN THIS ONE IS GOING TO BE THE
LAST ONE.
I'M GOING TO DESCRIBE IT'S VERY
INTERESTING BECAUSE THE CDC
WANTED TO KNOW COULD WE BE SO
AUDACIOUS AS TO GIVE TWO
INJECTIONS ON THE SAME DAY AND
HAVE THE INFANTS RESPONSES TO
ALL OF THOSE VACCINES BE AS
ROBUST AS IF THEY WERE GIVEN ON
SEPARATE DAYS.
WE DID THE STUDY OF PROVING THAT
YOU COULD GIVE MMR AND DPT
PERTUSSIS INJECTIONS ON THE SAME
DAY AND THE WAY WE DID THE STUDY
IS EVERYBODY GOT MMR ON THE
FIRST DAY AND HALF THE CHILDREN
WHO WERE THE CONTROLS RECEIVED A
PLACEBO INJECTION ON THE FIRST
DAY AND TWO MONTHS LATER THEY
REVERSED AND HALF GOT DT AND PER
TUS IS -- PERTUSSIS AND THE
OTHER GOT THE PLACEBO AND THOSE
IN THE CONTROL DID NOT GET DTP
AND THEY DIDN'T HAVE RISES IN
THEIR ANTIBIOTICS TO D OR T
BEFORE THEY GOT THEIR REAL DTP
IN THE TWO MONTHS.
JUST HAVING RECEIVED DT
WHOLESALE P AT TWO, FOUR AND SIX
MONTHS, 11% OF THE URBAN AND 3%
OF THE SUBURBAN CHILDREN HAD
SPONTANEOUS FOURFOLD RISES IN
PERTUSSIS ANTIBODIES AND NO
SYMPTOMS.
WE BEGAN TO THINK YOU GET
FREQUENT INFECTIONS THAT BOOST
YOUR PROTECTION AGAINST
PERTUSSIS AND IF YOU GET THEM
RIGHT AWAY, YOU WON'T HAVE
CLINICAL SYMPTOMS BUT AS THERE
IS MORE TIME TO RE-INFECT AND
PERTAINING TO A PAPER OF
IMMUNIZATION OF ADULTS BY
INTERNISTS WE SUGGESTED WHILE
URGING PROVIDERS FOR ADULTS TO
GET ON BOARD WITH ADULT
IMMUNIZATIONS WHICH I THINK THEY
STILL ONLY ARE 30 YEARS LATER
INCLUDING DECENNIAL PD WE SHOULD
CONSIDER WHETHER PERTUSSIS
VACCINE SHOULD BE ADDED.
HERE'S THE MAP OF WHAT HAPPENED
TO PERTUSSIS AFTER THE
INTRODUCTION OF WHOLESALE
VACCINE.
IT WAS AN INESCAPABLE PART OF
INFANCY AND BY 197 6 THE LOWEST
NUMBER WERE REPORTED IN THE
UNITED STATES BUT BY 1990s THERE
WERE MORE CASES IN TWO AGE
GROUPS.
THE YOUNG AGE GROUP IN CHILDREN
AND THE ADOLESCENTS AND YOUNG
ADULTS, NOT SO MUCH INCREASE IN
THOSE THAT WERE RIGHT AROUND THE
TIME OF RECEIVING FIVE DOSES OF
WHOLESALE VACCINE.
BY EARLY 2000s THE HIGHEST
INCIDENTS WAS IN THE AGE GROUP
UNDER SIX MONTHS WITH A
SECONDARY RISE NOTICE YOUNG
ADOLESCENT AND IN THAT YEAR MOST
CASES WERE OCCURRING IN THE
BROAD AGE GROUP FROM 10 TO 20
YEARS OF AGE.
WELL, WE WERE WRITING ABOUT THIS
AND PRESENTING POSTERS AND
TALKING TO EACH OTHER AND
APPRECIATION LITTLE OF ANYBODY
ELSE AT THAT TIME BECAUSE
PERTUSSIS WAS NOT RECOGNIZED AS
A PROBLEM.
I WAS INVITED TO THIS STORIED
PLACE IN THE MANSOUR AUDITORIUM
AT NIH TO PRESENT AT THE SIXTH
INTERNATIONAL SYMPOSIUM ON
PERTUSSIS AND PRESENTED PRETTY
MUCH WHAT I SHOWED YOU SO FAR
AND WE BECAME FRIENDS AND HE WAS
THE CHIEF AT THE INSTITUTION
DOWN THE STREET, CHILDREN'S
HOSPITAL OF PHILADELPHIA AND
STANLEY GOT UP AT THE END MIFF
TALK AND I WAS SO PROUD I WAS
PRESENTING AT THE NIH AND HE
SAID WHY IS NORTH PHILADELPHIA A
PIT OF PERTUSSIS.
WHAT IS THE MATTER WITH NORTH
PHILADELPHIA?
IT TURNED OUT IT WASN'T THE
COUNTRY WAS A PIT OF PERTUSSIS
AND AS WE UNDERSTOOD THE CHANGE
IN EPIDEMIOLOGY IS PARTIAL
CONTROL LED TO FEWER BOOSTS AND,
PARTIAL CONTROL LED TO IT STILL
BE AROUND AND THE FIRST SET OF
PARENTS DID DPT THAT LEFT MORE
PEOPLE SUSCEPTIBLE.
VACCINE FAILURE WAS VERY
IMPORTANT AND STILL IS IMPORTANT
AND PERTAINS TO CORONAVIRUS AS
WELL.
IF YOU HAVE A MUCOSAL INFECTION
WHICH PERTUSSIS IS, WHICH
CORONAVIRUS IS, YOU CAN'T EXPECT
TO PUT AN ANTIGEN INTO A MUSCLE
AND EXPECT TO GET PERFECT
MUCOSAL IMMUNITY.
SO PERTUSSIS VACCINE ON THE DAY
AFTER YOU FINISH YOUR SERIES IS
ONLY 85% PROTECTIVE AGAINST A
THREE-WEEK ILLNESS.
THAT'S NOT PERFECT AND IT'S
NEVER GOING TO BE STERILIZING
IMMUNITY.
BUT THE MAIN PROBLEM IS THERE
WAS WANING VACCINE IMMUNITY
AFTER HAVING RECEIVED THE LAST
PERTUSSIS VACCINE AT 46 YEARS OF
AGE.
WHY DID WE HAVE PERTUSSIS IN
YOUNG INFANTS?
FOR THE FIRST TIME IN MEDICAL
HISTORY, THOSE PATIENTS AND
THOSE LITTLE INFANTS WE WERE
SEEING THAT WERE DESCRIBED
NATIONALLY, THE FIRST TIME IN
MEDICAL HISTORY WAS BECAUSE WE
HAD PARTIALLY CONTROLLED
PERTUSSIS BUT MOTHER'S IMMUNITY
WAS WANING AND TRANS-PLACENTAL
ANTIBIOTICS WERE WANING AND THE
INFANTS WERE SUSCEPTIBLE.
WE MADE TWO TRUTHS.
PERTUSSIS DISEASE AND VACCINE
PROVIDE LIFE TIME PROTECTION
WERE NOT CORRECT.
WHAT WE THOUGHT WAS LIFE TIME
PROTECTION FROM EITHER WAS
REALLY ENOUGH REINFORCING
INFECTIONS WITH BORDATELLA
PERTUSSIS THAT KEEP THE PEOPLE
FROM THE DISEASE.
THAT'S WRONG.
THERE IS NOT LIFE TIME
PROTECTION.
WE INTRODUCED DTAP IN 2006 AND
FOR A WHILE IT TOOK THE EDGE OFF
THE NEW CASES.
AND THEN THE NEXT THING HAPPENED
OH, MY GOODNESS.
REMEMBER THERE WASHINGTON MANY
CASES MUCH PERTUSSIS IF THE 6 TO
10-YEAR-OLD AGE GROUP WHEN WE
HAD WHOLESALE VACCINE AND IN THE
BEGINNING OF THE PERTUSSIS
VACCINE BUT LOOK AT THE
7-YEAR-OLDS.
2006, 7 AND 8-YEAR-OLDS, AND
2008, 7, 8, 9, 10-YEAR-OLDS WITH
WERE THE MOST PREVALENT CASES IN
THAT AGE GROUP.
WHAT'S THAT ABOUT?
HERE WE SEE IT IN A DIFFERENT
WAY.
HERE WE SEE THE AGES OF THE
CASES OF PERTUSSIS.
THE FIRST IN 2010 IS THIS GROUP
HERE BEFORE WE HAD THESE THESE
WERE THE PEAK AND THEN WITH THE
VACCINE WE DON'T SEE 11 AND
12-YEAR-OLDS BUT WE SEE THE 10
AND 11-YEAR-OLDS COMING UP AND
THEY WERE VACCINATED BUT SOON
AFTER THAT BY 2014 WE HAD 59,000
CASES IN THE UNITED STATES AS
MANY AS WE HAD 50 YEARS BEFORE
THOUGH THIS PROTECTS CHILDREN,
IT PROTECTS THEM FOR A SHORT
PERIOD OF TIME AND BY THE TIME
THOSE 10 AND 11-YEAR-OLDS ARE 14
THEY'RE BACK UP AND SUSCEPTIBLE
TO PERTUSSIS.
WHAT IS THAT ABOUT?
IT'S REALLY INTERESTING.
THIS WAS A LETTER TO THE EDITOR
IN JAMA FROM AUSTRALIA THAT IS
WHAT TURNS OUT TO BE THE DEAL.
HERE IS THE DEAL.
IN AUSTRALIA THEY STARTED A
CELLULAR PERTUSSIS VACCINE ABOUT
WHEN WE DID 2000 AND GAVE IT TO
HALF THE POPULATION.
HALF CONTINUED TO GET THE
WHOLESALE VACCINE AND IN 2014
THEY HAD A PERTUSSIS OUTBREAK IS
THEY LEARNED WITH YOU WERE LEAST
LIKELY TO HAVE PERTUSSIS IF YOU
HAD HAD ALL WHOLESALE VACCINE OR
IF YOUR FIRST DOSE WAS WHOLESALE
VACCINE.
YOU WERE MOST LIKELY TO GET
PERTUSSIS IF YOUR FIRST DOSE
WITH US A CELLULAR VACCINE.
SO THE CHANGES IN THE
EPIDEMIOLOGY IN PERTUSSIS IF THE
ACELLULAR ERA ARE ANOTHER
REMARKABLE THING.
WE BEGAN DTAP REPLACING BY 1997.
EVERYBODY SINCE 2000 CAN ONLY
HAVE RECEIVED ALL ACELLULAR
VACCINES.
SO THESE GUYS HERE IN 2002 STILL
RECEIVED WHOLESALE AS THEIR
BEGIN BUT PRETTY SOON THE OLDER
ONES HAD RECEIVED ALL ACELLULAR
AND THE EPIDEMIOLOGY SHOWS THE
AFFECT OF AN AGING COHORT OF ALL
ACELLULAR VACCINE AND THOUGH
THEY'RE EFFECTIVE THEY DRIVE THE
IMMUNOLOGIC RESPONSE THAT LEADS
TO IMMEDIATE WANING AND ALSO
INABILITY TO ADEQUATELY BOOST.
SO IS THE SKY FALLING ON
PERTUSSIS VACCINE.
YES, IN FACT IT IS.
WE HAVE HAD A RESPITE AS ALL
OTHER CONTAGIOUS INFECTIOUS
DISEASES HAVE BEEN LESS COMMON
BUT IT WILL BE ROARING BACK.
UNTIL WE HAVE A BETTER MOUSE
TRAP AND VACCINE, WE ARE DOUBLED
DOWN ON PREVENTING PERTUSSIS AND
THAT'S ALL IN THE FIRST THREE
MONTHS OF LIFE SO THE
RECOMMENDATION IS TO HAVE THIS
IS SO MOTHERS HAVE
TRANSPLACENTAL ANTIBIOTIC TO
PASS TO THE INFANT TO PROTECT
THEM FOR THE FIRST TWO MONTHS OF
LIFE.
THAT'S WHAT WE CAN HOPE TO DO
WITH THE VACCINES WE HAVE.
WE NOW KNOW IT WOULD NOT BE
REASONABLE TO RECOMMEND
UNIVERSAL REVACCINATION OF THE
ENTIRE POPULATION BECAUSE WE
KNOW THE ACELLULAR VACCINE
PRIMING WHICH ALL YOUNG PEOPLE
IN THE UNITED STATES HAVE RIGHT
NOW IS NOT BOOSTABLE.
AND THAT THE VACCINE ANTIBODY
THAT YOU GET FROM A BOOSTER
DOSE, FOR INSTANCE, ONLY LASTS
ABOUT TWO YEARS.
AS IF THAT WASN'T ENOUGH AND
THERE'S MORE OBSERVATIONS TO
COME, WE CONTINUED TO TRY TO
ISOLATE AND FREEZE BORDATELLA
PERTUSSIS AND STILL HAD A BEVY
OF THIS SO WHEN J & J WANTED TO
BEGIN TO EXPLORE A NEW VACCINE
THEY ASKED US FOR OUR ISOLATES
AND THEY SAID THEY HEARD FROM J
& J AND THEY WERE ALL PERTACTIN
DEFICIENT AND IT'S A DETACHMENT
OF THE ORGANISM AND A SAID THEY
DID IT WRONG BECAUSE THERE'S NO
PERTACTIN ORGANISMS AND THEY DID
IT RIGHT NOT TO MENTION THEY DID
WHOLE GENOME SEQUENCING SO THEY
REALLY KNEW AND WE DISCOVERED
AND DR. KEENAN FROM J&J REPORTED
IN THE NEW ENGLAND JOURNAL
VARIANTS OF PERTUSSIS THAT WERE
PROTECTANT DEFICIENT AND TURNED
OUT AS WE LOOKED AT OURS THE
FIRST ISOLATE AND IT WAS THOUGHT
PERTACTIN IS A VIRULENCE FACTOR
FOR DETACHMENT OF DISEASE BUT
YOU HAVE TO THINK SOMETHING WAS
GOING ON ABOUT ESCAPE OF AN
ORGANISM FROM THE VACCINE
PRESSURE WHICH WAS WHAT'S GOING
ON RIGHT NOW.
DEF I
I HAVE TO GIVE THANKS FOR
HELPING US UNDERSTAND AND HAVE A
MODEL OF PERTUSSIS IN A BABOON.
WE DON'T HAVE A SEROLOGIC PARKER
OF PROTECTION.
THERE'S NO ANTIBIOTIC TESTS THAT
SAYS YOU'RE PROTECTED AND YOU'RE
NOT.
AND WE STILL DON'T KNOW WHAT
CAUSE THE COUGH BECAUSE IF YOU
INJECT IT INTO THE ANIMAL
THEY'LL GET LYMPHOCYTOSIS BUT
WON'T COUGH SO IT HELPS BUT
THERE'S MANY COMPANIES IN MANY
COUNTRIES LOOKING FOR THE NEXT
PERTUSSIS VACCINE.
IT'S A MUCOSAL INFECTION AND YOU
NEED SOMETHING AND IT LEECHES
OUT INTO THE MUCOSA.
THE PROBLEM WITH PURELY MUCOSAL
THEY USUALLY DON'T HAVE LONG
LEGS OR MEMORY.
SO THERE'S MULTIPLE AVENUES
BEING APPROACHED.
ONE ATTENUATED, LIVE ATTENUATED
VACCINE WITH A GENETICALLY
INACTIVATED PERTUSSIS TOXIN AND
DELETION OF OTHER VIRULENCE
GENES.
ANOTHER IS GENETICALLY MODIFIED
PT. IT TURNED OUT IN WHOLESALE
AND ACELLULAR VACCINES THE
PERTUSSIS TOXIN WAS INACTIVATED
BY A CHEMICAL PROCESS WHICH
CHANGES IT IN SUCH A WAY AND
RECOMBINANT PERTUSSIS TOXIN IS
MUCH BETTER IN THAT IT MAINTAINS
THE NATIVE EPITOPE STRUCTURE AND
IMMUNOGENICITY AND THAT WAS
LICENSED IN EUROPE AND SALES
WERE HIGH AND ANOTHER IS TO
APPROACH POTENT ADJUVANTS.
THIS IS ALL BEGINNING TO SOUND
FAMILIAR TO YOU NOW WITH WHAT
YOU ALL KNOW ABOUT CORONAVIRUS
VACCINES IN THE LAST YEAR.