>> I'LL BRING YOU UP TO DATE ON
THE LABORATORY SIDE FOR
ROTAVIRUS AND TO DIFFICULT TWO
BIRDS WITH ONE STONES, I'LL
COVER BOTH OF THESE FOR YOU NOW.
ON THE AGENDA TODAY, WE'RE GOING
TO BE SHOWING YOU THE FIRST
FINISHED VACCINE EFFECTIVENESS
RESULT FOR BOTH LICENSED
ROTAVIRUS VACCINES IN THE UNITED
STATES.
THESE ARE THE FIRST VE STUDIES
AASSESSING ROTAVIRUS VACCINES IN
CONCURRENT USE IN THE U.S.
CHILDHOOD POPULATION.
AND JUST OVERALL THIS WILL BE
FENCE ROTAVIRUS ASSOCIATED
HOSPITALIZATIONS AND THE
EMERGENCY ROOM VISIT.
WE'LL SHOW YOU AGE-SPECIFIC VE,
IN PARTICULAR ANY EVIDENCE ON
IMMUNO LOGIC WANING AND ALSO
WHAT WAS OBSERVED DURING THE
MOST RECENT YEARS.
SECONDLY, I'LL SHOW YOU THE
LABORATORY DATA INCLUDING SOME
INFORMATION ON VACCINE DRIVES
ROTAVIRUS STRENGTHS.
VERY BRIEFLY WE GO OVER THE TWO
LICENSED ROTAVIRUS VACCINES IN
THE UNITED STATES.
THE BOVINE HUMAN VACCINE, AND IN
FEBRUARY OF 2006, ACI APPROVED
THIS VACCINE FOR THREE DOSES AT
TWO, FOUR AND SIX MONTHS.
THE SECOND VACCINE WE'LL DISCUSS
IS A HUMAN VACCINE G-1P8 AND
APPROVED IN 2008 FOR TWO DOSES
AT TWO AND FOUR MONTHS.
BOTH ARE LIVE ORAL VACCINES IN
CLINICAL TRIALS, IMMUNITY WAS
OBSERVED AGAINST OTHER STRAINS
AND AS WE MENTIONED BOTH ARE
ACTUALLY IC RECOMMENDED FOR
CHILDHOOD VACCINE WITH NO
PREFERENCE.
WE'RE GOING OVER TWO PLATFORMS
AND THE RESULTS FROM BOTH AND
BOTH ARE ACTUALLY AROUND THE
SAME TIME PERIOD OF COMPLETION.
BOTH ARE CLEARED AND UNPUBLISHED
RESULTS.
SO THE FIRST IS THE NEW VACCINE
SURVEILLANCE, AND THAT WORKS.
THIS IS A CURRENTLY SEVEN SITE
NETWORK OF OF HOSPITALS AND
MEDICAL INSTITUTIONS THROUGHOUT
THE UNITED STATES.
IT'S A GREAT GEOGRAPHIC AND
DEMOGRAPHIC DIVERSITY AS YOU CAN
SEE.
OVERALL WE'RE DOING ACTIVE
SURVEILLANCE FOR ACUTE GASTRIC
ENTER
ENTERITIS.
ROTAVIRUS IS NOT A NOTIFIABLE
DISEASE.
IN ROUTINE CLINICAL PRACTICE IT
IS RARELY TESTED, AND, OF
COURSE, FOR STUDYIES LIKE OURS
WE
REQUIRE LABORATORY CONFIRMATION
OF ROTAVIRUS STATUS.
WE CONDUCT VERY TIME-CONSUMING
AND PERSONNEL-CONSUMING
SURVEILLANCE STUDIES AND WE
COLLECT PARENTAL INTERVIEWS AND
WE COLLECT THE PROVIDER VERIFIED
VACCINATION STATUS OF THE
CHILDREN.
WE COLLECT THE MEDICAL RECORDS,
INFORMATION AND, OF COURSE, WE
COLLECT THE STOOL SPECIMENS.
THE SECOND PLATFORM I'LL BE
DESCRIBING RESULTS FROM TODAY IS
FROM THE EMERGING INFECTIONS
PROGRAM.
THERE ARE TYPICALLY TEN STATES
PARTICIPATING IN EIP, AND THEY
COVER A WIDE RANGE OF ACTIVE
SURVEILLANCE FOR DIFFERENT
PATHOGEN, THIS IS A ROTAVIRUS
SPECIFIC STUDY IN CONNECTICUT
AND ATLANTA.
SO YOU CAN SEE THE DISTRIBUTION
OF THE RESULTS THAT WE'LL BE
DISCUSSING TODAY.
OKAY.
SO JUST TO GET YOU UP TO DATE
DURING THE POSTLICENSURE PERIOD
SEVERAL INDEPENDENT SMS HAVE
CONSISTENTLY REPORTED CONTINUED
STEEP DECLINES IN ROTAVIRUS AND
HOSPITALIZATION AND EMERGENCY
DEPARTMENT VISITS.
IN THE LAST FEW YEARS WE HAVE
OBSERVED THE EMERGENCE OF A
BIANNUAL PEAK IN ROTAVIRUS
ACTIVITY AND JUST FOR ONE
EXAMPLE OF THIS, HIRES THE
MODEL.
THIS IS THE PERCENT ROTAVIRUS
POSITIVE HOSPITALIZATIONS.
DURING THE PRELICENSURE PERIOD
OR JUST AT LICENSURE, 51% OF
THOSE CHILDREN COMING INTO THE
HOSPITAL WITH ACUTE ENTERITIS
SYMPTOMS WERE TESTED TO HAVE
ROTAVIRUS.
AND IN THE SECOND YEAR FOLLOWING
THAT LICENSURE, THAT DROOPED
PRECIPITOUSLY TO 6% IN THE THIS
SURVEILLANCE SYSTEMS.
WE SAW THIS BOUNCE BACK AND
BASICALLY HAS BEEN DESCRIBED IN
RECENT YEARS.
THIS IS BELIEVED TO BE THE
RESULT OF THE
IMMUNE LOGICAL SES TIBLS WHO
HAVE NOT BEEN VACCINATED, ET
CETERA, WHO THEN ARE CONSUMED
UPON EXPOSURE TYPICALLY ABOUT A
YEAR FOLLOWING WHAT WOULD HAVE
BEEN EXPECTED DURING THE
PRELICENSURE PERIOD.
SO BRAND-NEW
DATA, AND WE'RE ABOUT 90%
REDUCTION OF WHAT WE WERE
OBSERVING IN HOSPITALIZATIONS
FOR ROTAVIRUS IN THE
PRELICENSURE PERIOD.
OKAY.
SO THIS IS THE FIRST STUDY I'M
GOING TO BE PRESENTING.
THIS IS THE EFFECTIVENESS OF
BOTH VACCINES IN CONCURRENT USE
AMONG CHILDREN IN 2009 THROUGH
2011.
AND VERY BRIEFLY, THE
METHODOLOGY HERE, THESE ARE KIDS
UNDER 5 YEARS OLD, HOSPITALIZED
WITH AGE.
ALL SITES WERE INCLUDED IN THE
ROTA TECH FACILITIES I'LL BE
SHOWING YOU.
HOWEVER, VACCINATION COVERAGE
WITH ROTA RIGS THAT WAS UNDER 5%
WAS SEEN TO BE AN EFFICIENCY
DRAG, AND SO THREE SITES WERE
NOT INCLUDED IN THOSE ANALYSES.
THOSE SPECIFIC ANALYSES.
THESE ARE CASE-CONTROLLED
LOGISTIC REGRESSION MODELS
ADJUSTED SYMPTOM ONSET AND
SURVEILLANCE SITE.
AND OF COURSE, THEY WERE
CONFIRMED, VACCINATION RECORDS
CONFIRMED.
WE ARE SHOWING NEGATIVE CONTROL
RESULTS.
NOW, THESE DATA HERE HAVE NOT
BEEN PRESENTED PREVIOUSLY.
YOU CAN SEE THIS IS A
FULL-COURSE ROTA TECH VE WITH
95% CONFIDENCE INTERVALS.
YOU CAN SEE THAT THERE IS AN 84%
VACCINE EFFECTIVENESS AGAINST
HOSPITALIZATION FROM THE VISITS
FOR ROTA TECH.
AND 70% POINT ESTIMATE, THE
CONFIDENCE CLEARLY OVERLAP.
THESE ARE NOT SIGNIFICANT
DIFFERENCES HERE DESPITE
DIFFERENCES IN THE POINT
ESTIMATE.
THEY ARE NOT SIGNIFICANTLY
DIFFERENT.
ONE REASON, OF COURSE, FOR THE
WIDER CONFIDENCE INTERVALS FOR
THE ROTARICK-SPECIFIC ANALYSES
IS THAT WE HAD FAR FEW CASES IN
OUR ANALYSES AND ALSO THE
VACCINE COVERAGE FOR ROTARICKS
IN OUR JEANNETTE WORK WAS INDEED
LOWER THAN THAT FOR ROTA TECH.
THE SAMPLE SIZE HERE IS 359 WITH
1 TO 3 CASE CONTROL RATIO AND
FOR ROTA RICK, IT IS ONLY 60
CASES WITH A 1 TO 3 CASE CONTROL
RATIO.
I WOULD LIKE EVERYONE TO TAKE
THAT IN MIND AS YOU REVIEW
THESE.
THE SECOND ANALYSES THAT I'D
LIKE TO PRESENT ARE GENOTYPE
SPECIFIC.
THESE ARE THE PREDOMINANT
GENOTYPES OBSERVED DURING THE
SEASONS THAT WE HAVE ANALYZED.
YOU SEE IN BLUE ROTA TECH
ANALYSIS AND IN RED ROTA RICK
ANALYSES.
VERY CLEARLY, YOU SEE THE
INTERVALS OVERLAP ACROSS THE
BOARD.
THESE ARE NOT SIGNIFICANT
DIFFERENCES.
IN FACT, ARE VERY SIMILAR ACROSS
THE BOARD.
YOU ALSO WILL NOTE THAT FINAL
COLUMN, G12 P-8 USED TO BE
CONSIDERED AN EMERGING GENOTYPE
BUT IS NOW USED WITH INCREASING
PREDOMINANCE AND IN FACT WAS
ONCE PREDOMINANT STRAINS.
THAT HAD 83% VACCINE
EFFECTIVENESS AGAINST ROTAVIRUS.
VERY STRONG SHOWING EVEN AGAINST
G12 P8.
LOOKING NOW AT AGE-SPECIFIC
ANALYSES AND OF COURSE THE
QUESTION OF WHETHER OR NOT THERE
ISHIMNOIMMUNOLOGIC WANING.
THIS IS THE FIRST PRESENTATION
TO MY KNOWLEDGE THAT GOES ALL
THE WAY THROUGH THE FOURTH YEAR
OF LIFE.
AND WE AGAIN SEE THAT THERE IS
NO CLEAR EVIDENCE OF WANING.
EVEN THROUGH THE FOURTH YEAR OF
LIFE FOR ROTA TECH
UPIMMUNIZATION.
THESE ARE VERY STRONG SHOWINGS
EVEN THROUGH THE FOURTH YEAR OF
LIFE.
THE ROTA RICK-SPECIFIC ANALYSES,
OUR FIRST-YEAR ASSESSMENT IS NOT
SPECIFICALLY SIGNIFICANT.
THOSE CONFIDENCE INTERVALS ARE
VERY WIDE AND ONLY REPRESENT A
HANDFUL OF SUBJECTS.
HOWEVER, THE SECOND YEAR OF LIFE
IS A VERY GOOD 86% VACCINE
EFFECTIVENESS.
AND THAT WAS THE LIMIT OF OUR
STUDY POWER FOR THAT ANALYSES.
OKAY.
I'M SHIFTING OVER TO THE NEXT
SURVEILLANCE PLATFORM, THE EIP
PLATFORM.
THESE STUDIES WERE -- THIS STUDY
WAS CONDUCTED IN 2010 AND '11 AT
TWO EIP CITES, AS MENTIONED,
GEORGIA AND CONNECTICUT.
NOW, THESE ARE JUST SLIGHT
DIFFERENCES IN METHODOLOGY
OVERALL, BUT THERE ARE A FEW,
CHILDREN AGE ELIGIBLE TO RECEIVE
ROTA RICK WITH DIARRHEA WERE
ENROLLED THROUGH ACTIVE
SURVEILLANCE AND LABORATORY
CONFIRMATION VACCINE RECORDS
WERE CONFIRMED, CASE CONTROL
METHODS WERE EMPLOYED.
AND AGAIN, WE ARE JUST SHOWING
THE ROTAVIRUS NEGATIVE CONTROL
RESULT HERE.
NOW, YOU HAVE, AGAIN, ROTA TECH
IN BLUE AND ROTA RICK IN RED.
AND WE OBSERVED THAT THERE IS A
91% VERSUS AN 88% VE WITH VERY
SIMILAR CONFIDENCE INTERVAL
BOUNDS.
I WILL NOTE THAT THE -- I
BELIEVE THE SAMPLE SIZE FOR ROTA
TECH IN THIS STUDY WAS -- I
THINK IT WAS 87 CASES IN THE
ROTA TECH ASSESSMENT WITH ABOUT
A 1 TO 1 CASE CONTROL RATIO.
AND IN ROTA RICK, I BELIEVE IT
WAS 93 OR 94 CASES, AND THIS WAS
ABOUT A 1-1.5 CASE CONTROL
RATIO.
SO LET'S PUT IT ALL TOGETHER
WITH WHAT HAS PREVIOUSLY BEEN
CONDUCTED AND PUBLISHED.
AND YOU CAN SEE SPECIFICALLY
LOOKING AT ROTA TECH ANALYSES OF
VE, YOU CAN SEE THAT DR. FREITOS
ASSESSMENT.
ANOTHER ONE WAS 87%.
AND ANOTHER BY MARGARET WAS 89%.
SO YOU CAN SEE FROM THE ENVIOUS
END RESULTS THAT WE HAVE
PRESENTED HERE, A VERY
CONSISTENT FINDING OF 84% WITH
CONFIDENCE INTERVALS THAT
OVERLAPPED HERE.
AND ALSO FOR EIP RESULTS, WE CAN
SHOW YOU ALSO VERY CONSISTENT
VACCINE EFFECTIVENESS RESULTS.
THE TWO STUDIES THAT WE'VE BEEN
ABLE TO PRESENT FOR
POST-LICENSURE ROTA RICK VE WAS
70% AND FOR ROTA RICKS WAS
SLIGHTLY DIFFERENT IN TERMS OF
POINT ESTIMATE WHICH WAS 88%.
NOW, I WILL NOTE THAT WHILE
INTERNALLY EACH OF THESE STUDIES
WAS VERY WELL, VERY CLOSELY
MATCHED CASES CONTROLLED ON SUCH
CHARACTERISTICS AS RACE,
ETHNICITY
ETHNICITY, SOCIOECONOMIC STATUS,
THE INSURANCE STATUS AND SUCH,
THERE IS A POSSIBILITY THAT
THESE ARE DIFFERENT
DISTRIBUTIONS BETWEEN THE TWO
PLATFORMS.
AND MOST LIKELY THERE ARE SOME
DIFFERENCES THERE IN THAT.
SECONDLY, THE VACCINE COVERAGE
WITHIN THESE COMMUNITIES IS VERY
DIFFERENT AS WELL.
FOR INSTANCE, WE WOULD EXPECT
ABOUT A 40% VACCINE COVERAGE
ESTIMATE FOR OUR SITES THAT WE
USED FOR OUR ROTA RICK ANALYSIS,
40% ANALYSIS FOR ROTA RICK AS
OPPOSED TO ABOUT DOUBLE THAT IN
THE EIP STUDY.
SO THESE ALL MAY ADD UP TO
PROVIDE SOME DIFFERENCES AND, OF
COURSE, YOU HAVE VERY SMALL
SAMPLE SIZES IN BOTH OF THESE
STUDIES.
I WILL NOTE THAT THERE'S ONE
HIGHER INCOME ASSESSMENT THAT
LOOKED AT CONCURRENT VE FOR
THESE TWO VACCINES.
THIS WAS IN SPAIN, JUST CAME OUT
THIS SUMMER.
BY CASTILLA.
AND IT WAS DONE IN THE NAVARRE
REGION OF SPAIN WHICH IS THE
NORTHEAST SECTION OF THE
COUNTRY.
TO BE HONEST, THERE ARE VERY
CONSISTENT RESULTS THROUGH
ACTIVE SURVEILLANCE THAT THEY
WERE ABLE TO OBTAIN HERE, 81%,
ROTA TECH, 75%, ROTA RICK WITH
CONFIDENCE INTERVALS THAT
INTERSECTED GREATLY.
SO IN SUMMARY FOR THE EP
EPIDEMIOLOGIC SECTION, THE ROTA
RICK VE, STUDIES MORE INTENSELY
IN THE COMING YEAR, WANING OF
STUDY POWER WAS DETECTED FOR
EITHER VACCINE AND NO DIFFERENCE
WAS OBSERVED IN VE BY
PREDOMINANT GENOTYPE.
ROTAVIRUS STRAIN MONITORING AND
STRAINS IS THE NEXT TOPIC.
BASICALLY, I WANTED TO SHOW YOU
THAT IN OUR VERY INTENSIVE
STRAIN MONITORING THAT'S GONE ON
FOR THE LAST 15 YEARS IN THIS
SLIDE, IN THE PRELICENSURE
PERIOD, IT WAS PREDOMINANTLY A
G1 P8 DISTRIBUTION THAT
PREDOMINATED THE SAMPLES THAT
WERE TESTED.
AND YOU CAN SEE WHEN VACCINE WAS
IMPLEMENTED IN 2006 AND THERE
HAS BEEN SOME SHIFTS IN THE
DISTRIBUTION.
AND YOU CAN SEE THE G3 IS NOW
THE PREDOMINANT STRAIN IN MOST
OF OUR SURVEILLANCE SYSTEMS AND
IN THIS SURVEILLANCE SYSTEM, IN
PARTICULAR.
AND ALSO, YOU CAN SEE THE G12
HAS EMERGED TO BECOME MORE
PREDOMINANT.
NOW, WE DON'T HAVE EVIDENCE TO
SUGGEST THAT THESE CHANGES ARE
THE RESULT OF ANY VACCINES
ELECTED PRESSURE.
THEY ARE STILL NOT COMPLETELY
UNDERSTOOD, BUT IT IS ENTIRELY
POSSIBLE THAT THESE ARE THE
RESULT OF SECULAR VARIATIONS.
AND AGAIN, JUST TO BRING YOU
BACK TO THE SLIDE WE JUST LOOKED
AT, THERE APPEARS TO BE, IN THE
POST LICENSURE ANALYSIS THAT
WE'VE BEEN CONDUCTING, NO REASON
TO BELIEVE THAT THERE IS
SELECTIVE VACCINE PRESSURE UPON
THESE VACCINES OR THESE
GENOTYPES AND PREDOMINANT
CIRCULATION.
NOW, ALSO, I WANTED TO BRIEFLY
GO IN AT THE VERY END OF THIS
PRESENTATION INTO VACCINE DRIVE
STRAINS.
THESE COME IN TWO FASHIONS.
FIRST OF ALL, JUST SHED VACCINE.
SHEDDING OF A LIVE VACCINE VIRUS
IS THE PRODUCT OF THE INTENDED
REPLICATION OF THE VACCINE IN
THE INTESTINE.
SO THAT IS THE FIRST.
THE OTHER IS REASSORTMENT.
AND WE'LL TALK ABOUT THAT IN
JUST A MOMENT.
BUT SHED ROTAVIRUS VACCINE HAS
BEEN OBSERVED IN NUMEROUS
STUDIES AND CLINICAL TRIALS
AMONG APPROXIMATELY 9% TO 21% OF
THOSE RECEIVING ROTA TECH,
PREDOMINANTLY AFTER THE FIRST
DOSE, AND WITHIN A SHORT TIME
THEREAFTER.
IN ROTARICKS, VACCINATED
INFANTS, THIS WAS A LITTLE
HIGHER, 35% TO 80% OF THOSE
INFANTS ARE OBSERVED TO SHED THE
VACCINE VIRUS.
AND AT ACIP IN 2009, OF COURSE,
THIS WAS EXPECTED.
AND THERE WAS A STATEMENT MADE
TO THE MNWR REPORT AND I'LL READ
IT, THE COMPROMISED MEMBER BY
VACCINATING THE INFANT,
HOUSEHOLD OUTWEIGHS THE SMALL
RISK FOR TRANSMITTING VACCINE
VIRUS TO THE IMMUNO COMPROMISED
MEMBER.
ANY VIRUS ASSOCIATED TO THESE.
AND THAT STATEMENT HOLDS FIRM,
AND WE HAVE NO PROBLEMS WITH
THAT.
LOOKING AT THE REASSORTMENT
REPORTS THAT HAVE RECENTLY COME
OUT FROM VARIOUS COUNTRIES,
AUSTRALIA, FINLAND AND EVEN THE
UNITED STATES, I WANTED TO JUST
TAKE YOU DOWN THE ROAD OF HOW
THIS HAPPENED.
NOW, THIS IS NOT A NEW FINDING.
THIS WAS OBSERVED DURING THE
DEVELOPMENT PHASE OF THE PREROTE
THAT
PREROTATECH.
SO WHAT WE HAVE IS THE HUMAN
REASSORTMENT ROTATECH VACCINE,
YOU HAVE THE G1, G2, G3, G4 AND
G8 COMPONENTS THAT ARE
REASSORTED TO THE BOVINE P5 G6
STRAIN.
AND WHAT HAS HAPPENED, WE'VE NOW
OBSERVED IN LABORATORY ANALYSES
IS THAT THAT G1 AND P8 VACCINE
STRAIN COMPONENT REASSORT IN
VIVO AND PRODUCED A VACCINE G1
P8 REASSORTED STRAIN.
THERE IS NOT A LOT OF RESEARCH
ON THIS.
THERE ARE A LOT OF QUESTIONS
STILL.
AND IN LABORATORY ANALYSES BY
THE DOCTOR RECENTLY AND ALSO IN
EPIDEMOLOGICAL ASSESSMENTS, IT
DOES APPEAR THAT THE
TRANSMISSION OF THE
AREASSORTMENT IS POSSIBLE.
AND IN SOME CASES THAT HAVE BEEN
REPORTED, IT IS POSSIBLE THAT
SYMPTOMS ARE PRODUCED, AND WE
WILL GO THROUGH SOME OF THE
EVIDENCE ON THIS.
NOW, YOU CAN SEE HERE IN THE
SECOND COLUMN OF HOW MANY
REASSORTANTS WE'VE SEEN AN
ACTIVE SURVEILLANCE FOR FOUR
YEARS, THAT THERE TRULY ARE VERY
FEW.
THESE ARE NOT COMMON
OCCURRENCES.
INDEED, THEY ARE QUITE RARE.
YOU ALSO SEE IN THE THIRD COLUMN
THAT THESE ARE THE DENOMINATORS
THAT WE HAVE GIVEN YOU SOME
BASELINE FOR UNDERSTANDING IS
THESE ARE ACUTE GASTROENTERITIS
IN THE SURVEILLANCE PLATFORM.
YOU CAN SEE THESE ARE
EXCEEDINGLY RARE.
THE 2008/2009 SINGLE REASSORTANT
WAS DETECTED AMONG A CATCHMENT
POPULATION OF OVER 141,000
CHILDREN UNDER THE AGE OF 5.
AND IN THAT SURVEILLANCE
CATCHMENT POPULATION.
SO I WANTED TO EXPRESS THAT THIS
IS BEING PRESENTED HERE TODAY
FOR ACIP FOR TRANSPARENCY'S SAKE
AND THAT WE HAVE INDEED OBSERVED
THIS.
THAT HAS BEEN OBSERVED EVEN IN
THE DEVELOPMENT PHASES OF THIS
VACCINE.
AND THAT IT IS NOT A SERIOUS
CONCERN.
SO WE ALSO WOULD LIKE TO MENTION
THAT IN THE 2009/'10 SEASON,
THERE WAS A SINGLE ROTARICK
STRAIN THAT WAS OBSERVED IN A
CHILD WHO WAS UNVACCINATED AND
LIVING, RESIDING IN AN AREA WITH
PRACTICALLY, VERY NEARLY, 0%
ROTARICK VACCINE COVERAGE.
AND THIS CHILD UPON FURTHER
FOLLOW-UP DID NOT HAVE ANY
TRAVEL TO MEXICO, ET CETERA.
SO IT IS JUST AN INTERESTING
FINDING THAT WE WANTED TO BRING
TO YOUR ATTENTION AS WELL.
AND IN SUMMARY, WE WOULD LIKE TO
STATE THAT GP 3A, G12 P8 IS NO
LONGER CONSIDERED A STRAIN AND
THE VE IS HIGH AGAINST THE
STRAIN.
ROTATECH REASSORTANTS HAVE TRULY
BEEN OBSERVED AT LOW FREQUENCIES
IN SEVERAL VACCINATED
POPULATIONS AND TRANSMISSION
APPEARS POSSIBLE.
AND DESPITE TESTING THESE
SPECIMENS FOR THE BREADTH OF
POSSIBLE PATHOGENS, THERE
CONTINUE TO BE SOME OF THESE
CASES WHERE WE HAVE FOUND NO
OTHER PATHOGEN.
AND SO WE MAY POSTULATE THAT
THERE MAY BE SOME CAUSALITY.
EVIDENCE REGARDING ROTARICK,
SOME TRANSMISSION TO
UNVACCINATED SUBJECTS IS VERY
POTENTIALLY POSSIBLE, AND WE
FINALLY WANT TO MENTION THAT
FURTHER MONITORING OF
CIRCULATING SEROTYPES AND
CLINICAL DATA IS VERY MUCH
NEEDED, AND WE ARE ACTIVELY
ENGAGED IN THAT RESEARCH.
I WANTED TO ACKNOWLEDGE A WHOLE
HOST OF BOTH EPIDEMIOLOGICALLY,
YOU DO A GREAT DEAL OF WORK.
AND IN PARTICULAR I WANTED TO
BRING TO ATTENTION THE
CONTRIBUTIONS OF DR. VASQUEZ AND
DR. BAKER WHO ARE CO-AUTHORS IN
THESE REPORTS AS WELL.
THANK YOU.
>> QUESTIONS AND COMMENTS FOR
DR. VASQUEZ.
>> THANK YOU FOR A VERY NICE
PRESENTATION.
I HAVE TWO QUESTIONS.
GIVEN THAT IN SOME OF THESE
STATES LIKE IN CONNECTICUT, WE
WENT FROM ONE PRODUCT TO THE
OTHER, WERE YOU ABLE IN THE DATA
TO LOOK AT MIXED PRODUCT VACCINE
EFFECTIVENESS OF THE MIX
PRODUCT?
THAT'S THE FIRST QUESTION.
AND THE SECOND ONE PERTAINS TO
PARTIAL VACCINATION.
FOR THOSE WHO RECEIVED ROTATECH,
WERE YOU ABLE, IN YOUR STUDY,
WHICH IS LARGER THAN OURS, TO
LOOK AT EFFECTIVENESS AFTER TWO
DOSES?
>> YES, INDEED.
BOTH QUESTIONS, WE HAVE LOOKED
AT THAT.
FOR THE COMBINED VACCINE TYPE
CHILDREN THAT WE HAVE, THOSE
WHO, UNDER RECOMMENDATION, HAVE
RECEIVED BOTH ROTARICKS AND
ROTATECH, WE HAVE FUND OUR
ANALYSIS DATA THAT THERE WERE 5%
WHO HAD SOME SORT OF COMBINATION
ONE WAY OR ANOTHER.
AND SO THAT WAS NOT ADEQUATE
SAMPLE SIZE FOR US TO CONDUCT
THE ANALYSIS.
ON THAT.
AND WE'LL CONTINUE TO SEE IF WE
CAN REACH THAT EVEN COMPILING AN
AGGREGATE IN DATA AS WE CONTINUE
TO CONDUCT THIS WORK.
AND THEN SECONDLY, THE ANALYSIS
OF THE ROTAVIRUS VACCINE
DOSE-SPECIFIC VE RESULTS WE HAVE
CONDUCTED THOSE FOR THE NVSN.
FOR THE NVSN ROTATECH, ALL THREE
DOSES WERE SIGNIFICANTLY
DIFFERENT.
IT WAS 78% FOR TWO DOSES OF
ROTATECH.
AND THEN 84%, AS YOU SAW, FOR
THE ALL THREE DOSE, FULL COURSE.
AND FOR THE ROTARICK'S ANALYSIS,
WE DID NOT HAVE AMPLE STUDIES TO
ASSESS THE DOSE.
WE DID THE SECOND DOSE FULL
FORCE.
>> I NEED A LITTLE BIT OF HELP
UNDERSTANDING THE METHODOLOGY
WITH REGARD TO UNDERSTANDING THE
DATA ON WANING IMMUNITY.
SO AS CHILDREN GET OLDER, THEIR
DISEASE WILL BE LESS SEVERE,
PARENTS LESS LIKELY TO BRING
THEM IN FOR CARE, DOCTORS LESS
LIKELY TO TEST.
SO CAN YOU HELP ME INTERPRET
YOUR EVIDENCE THAT SUGGESTS
THERE'S NOT SIGNIFICANT WANING
IN THE CONTEXT OF THOSE
PHENOMENON.
>> YES.
THANK YOU.
THE ISSUE OF WANING IN OUR
ANALYSIS IS CENTERED AROUND
THOSE SEVERE
ROTAVIRUS-ASSOCIATED
HOSPITALIZATIONS AND VISITS.
SO PERHAPS, FOR INSTANCE, AN
OLDER CHILD IS ABLE TO REHYDRATE
ON THEIR OWN WITHOUT THAT ISSUE.
THEN PERHAPS AT A LOWER LEVEL,
THAT WOULD NOT BE AN ISSUE.
AND THAT IS NOT CAPTURED BY OUR
DATA IN TERMS OF THE WANING.
ANALYSIS.
THAT'S AN IMPORTANT DISTINCTION.
BUT IN TERMS OF SEVERE
HOSPITALIZATIONS RESULTING FROM
ROTAVIRUS, THOSE ARE VERY
OFTEN -- WE'RE CONSIDERING THOSE
TO BE VALID, YES.
>> DR. HARRISON.
>> WHAT ARE THE IMPLICATIONS FOR
THE INCREASE IN G3 CASES IN
TERMS OF ACIP?
>> THE G3 P8, THE RISE IN
PREDOMINANCE OF THAT GENOTYPE
THAT WE'VE SEEN IN MANY
SURVEILLANCE SYSTEMS DOES NOT
APPEAR TO HAVE ANY IMPLICATION
IN POLICY.
IT DOES NOT -- THERE'S NO CLEAR
EVIDENCE THAT THIS IS FROM SOME
KIND OF SELECTIVE ADAPTATION OF
A GENOTYPE IN THE PRESENCE OF A
VACCINE.
SO AS A G3 P8 SEEMS TO HAVE
EFFECTIVENESS WITH THE ANALOGY
WE PRESENTED.
>> DR. VASQUEZ.
>> CAN YOU COMMENT ON YOUR
ABILITY FOR STRAINS?
YOU USED A LICENSE FOR
INSPECTIONS.
IS THERE A POSSIBILITY THAT SOME
OF YOUR CASES WERE SHUTTING.
>> YES.
THANK YOU.
THAT IS SOMETHING THAT I COULD
DEFER THIS TO LABORATORY FOLKS
FOR GREATER DETAIL, BUT IN
GENERAL WHAT WE'VE DONE IS
TESTED ALL OF THOSE SUBJECTS
ENROLLED.
THOSE THAT ARE POSITIVE BY EIA,
WE HAVE GENOTYPED ALL OF THOSE.
AND WE HAVE GONE INTO SEQUENCING
OF THOSE USING VERY ELABORATE
PROTOCOLS LABORATORILY FOR
DETECTING WHETHER OR NOT THERE
IS A SIMILARITY WITH THE
ROTAVIRUS VACCINE STRAINS
THEMSELVES.
IF WE DO NEED FURTHER
ELABORATION, I'M SURE FOLKS HERE
WOULD BE HAPPY TO CHIME IN.
>> THANK YOU FOR YOUR
PRESENTATION.
THIS IS A LITTLE TANGENTIAL, SO
FEEL FREE TO REFUSE TO ANSWER.
I WAS FASCINATED BY YOUR
PUBLICATION SHOWING THE INDIRECT
EFFECT ON THE OLDER AGE GROUPS.
I WAS WONDERING IF YOU HAD ANY
UPDATE ON THAT AS WELL.
>> THANK YOU.
AND I DON'T THINK THAT'S
TANGENTIAL AT ALL.
ACTUALLY, IT'S VERY RELEVANT.
YOU KNOW, WE HAVE SEEN THAT --
AND THIS HAD BEEN SEEN EVEN IN
THE PRELICENSURE PERIOD IN
MODELING EXERCISES, THIS HAS
BEEN PREDICTED IN THESE VERY
STRONG MODELING EXERCISES THAT
AT A VERY GOOD VACCINE COVERAGE
LEVEL, YOU WOULD SEE A BIENNIAL
PEAK.
YOU KNOW, WE HAVE LOOKED AT
THAT.
WE'VE LOOKED AT THAT EVEN MORE
RECENTLY.
AND WE FIND THAT THE INDIRECT
BENEFIT -- AND THIS IS STILL IN
ANALYSIS PHASE, BUT IN THOSE
YEARS WHEN YOU HAVE VERY STEEP
DECLINES, THESE ARE THE 90%
REDUCTION YEARS, THAT THERE ARE
INCORRECT EFFECTS IN THOSE
YEARS.
AND THEN THE NEXT YEAR, SERVE AS
A CATCH-UP.
REMAINS TO BE IMMUNOLOGICAL.
ROTAVIRUS STILL EXISTS.
THEY MEET THAT EXPOSURE WITH
INFECTION.
PERHAPS THEY DON'T, AS THE
PREVIOUS COMMENT FROM DR.
SAWYER, WAS PERHAPS NOT ALL OF
THEM -- THEY DON'T ALWAYS HAVE
TO GO INTO -- SEEK MEDICAL CARE
PERHAPS, BUT SOME SORT OF
INDIRECT PROTECTION OCCURS
APPARENTLY SICK LICKALLY.
>> I WAS ALSO WONDERING ABOUT
THE OLDER AGE GROUPS.
YOUNG ADULTS AND EVEN OLDER
ADULTS.
>> YES.
VERY GOOD.
SO THERE'S BEEN A LOT OF
RESEARCH ON THAT, TOO, FROM SOME
OF THE MEMBERS THAT ARE IN THE
AUDIENCE HERE.
AND IF THEY WANT TO CHIME IN,
THAT WOULD BE ENCOURAGED AS
WELL.
IT DOES APPEAR THROUGH SOME OF
THESE STUDIES NOW PUBLICISHED,
IF YOU HAVE A
ROTAVIRUS-VACCINATED CHILD IN
YOUR HOUSEHOLD, POTENTIALLY
THERE ARE INDIRECT BENEFITS TO
OTHERS IN THE HOUSEHOLD, EVEN IN
ADULTS AT THE CHILD-BEARING AGE
AND EVEN PERHAPS OLDER THAN
THAT.
SO INDIRECT BENEFITS, I THINK
THE STORY HAS NOT YET BEEN
PLAYED OUT, BUT IT'S A VERY
INTERESTING ONE.
AND I THINK THERE ARE
FAR-REACHING BENEFITS.
>> AND DR. PICKERING.
>> I'VE RECEIVED SEVERAL CALLS
ABOUT MICROPREEMIES.
BY THE TIME THESE SMALL INSTANTS
ARE OLD OR STABLE ENOUGH TO
RECEIVE ROTE VA VIRUS VACCINE,
THEY'RE PAST THE FIRST DOSE THEY
RECOMMEND SHOULD BE GIVEN.
AND THEN, OF COURSE, THEY LEAVE
THE HOSPITAL AND ARE REALLY
SUSCEPTIBLE TO ROTAVIRUS
DISEASE.
IS THE WORK GROUP CONSIDERING
LIBERALIZEING THE CURRENT
ADMINISTRATION, FIRST, SECOND
AND THIRD DOSES?
>> I MAY WISH TO DEFER THAT.
OF COURSE, THERE'S A RECENT
PUBLICATION JUST OUT THIS WEEK
THAT DID LOOK AT IN LOWER INCOME
AND MODERATE INCOME COUNTRIES,
BY RELAXING THE AGE RESTRICTIONS
OVERALL, THERE DOES APPEAR TO BE
GREAT BENEFITS TO CHILDREN WHO
HAVE MISSED VACCINATIONS.
AND SPECIFICALLY DISCUSSING THIS
FOR THE MICRO -- YOU KNOW,
PREMATURE BIRTHS.
I MIGHT HAVE TO DEFER THAT TO
OTHERS.
>> JUST A QUICK COMMENT ON THAT.
I THINK THE CONCERN, OBVIOUSLY,
WITH GIVING VACCINE TO THESE
PREEMIES WAS POTENTIAL FOR
TRANSMISSION OFF THE VACCINE
STREAM AND EXPOSING OTHER BABIES
PRONE TO THE VIRUS.
BUT AS YOU SAID, BY NOT DOING
THE VACCINE UNTIL THEY ARE
DISCHARGED, SOME OF THEM BECOME
AGE INELIGIBLE IF THEY ARE NOT
DISCHARGED.
IT IS A BENEFIT RISK EVALUATION,
ONE EVALUATION WE ARE CURRENTLY
EMBARKING ON FOR INSIGHT, JUST
TO LOOK AT THIS ISSUE OF
TRANSMISSION WITH A LITTLE MORE
DETAIL TO UNDERSTAND.
DOES IT POSE A RISK.
THAT WOULD POTENTIALLY ALSO, IN
ADDITION TO INFORMATION WE ARE
GATHERING ON THE DISEASE STILL
HAPPENING, IS THERE EVIDENCE
SUGGESTING THAT PREEMIES WHO
MIGHT HAVE NOT BEEN VACCINATED
ARE INDEED THE CASES THAT ARE
OVERREPRESENTED NOW WOULD HELP
IN THESE BENEFIT CONCENTRATIONS.
>> THERE IS A DIFFERENCE BETWEEN
THE TWO VACCINES WITH THE AMOUNT
OF LIVE VIRUS IN THE STOOLS.
>> IF YOU LOOK AT THE SHEDDING
DATA AND THEN SHOW THIS, YOU DO
SEE MORE ANTIGEN SHEDDING WITH
THE VACCINE.
WHETHER THAT TRANSLATES ANY
DIFFERENT, THE ONLY THING I
WOULD ADD FOR TRANSMISSION, IN
ADDITION TO THE CASE THAT DAN
PRESENTED, GLAXO SMITH KLINE DID
DO A STUDY IN THE DOMINICAN
REPUBLIC
REPUBLIC.
AND I THINK IT'S 70% TO 80%.
SO THERE IS LIKELY SOME
TRANSMISSION OF THAT VIRUS.
>> THANKS.
DOCTOR?
>> I'D LIKE TO GENERALIZE
LARRY'S QUESTION TO ALL INFANTS
AS WE USE THE VACCINE MORE AND
LEARN ABOUT PERTUSSIS, AND AND
IF THEY'RE GOING TO CONSIDER.
>> AND THEN DR. BOCCHINI?
>> DO WE KNOW THE PERCENTAGE OF
INFANTS THAT DO NOT FINISH IT?
>> THAT'S A GOOD QUESTION.
THERE ARE TWO RESTRICTIONS.
ONE IS YOU HAVE TO ADMINISTER
THE FIRST DOSE BY 15 WEEKS AND
THE FULL SERIES BY EIGHT MONTHS
AND BOTH COULD IMPACT OVERALL
COVERAGE.
WE DON'T HAVE SPECIFIC DATA ON
HOW MANY CHILDREN ARE ACTUALLY
BEING EXCLUDED FROM VACCINATION
BECAUSE OF THESE RESTRICTIONS.
LOOKING AT THE TIMING OF
COVERAGE, WE ESTIMATED THAT
ABOUT 5% OF CHILDREN COME FOR
THEIR FIRST DOSE AFTER 15 WEEKS.
THAT POTENTIALLY WILL BE THE
LOSS.
WE ARE TRYING TO GET SPECIFIC
DATA FOR HOW THAT IMPACTS THE
ROTAVIRUS VACCINE.
THE THIRD DOSE IS ALSO AN ISSUE
AND POTENTIALLY ABOUT THE SAME
MAGNITUDE, THAT THERE ARE
CHILDREN WHO COMPLETE THEIR
SERIES AFTER EIGHT MONTHS.
>> THANK YOU VERY MUCH.
I THINK BEFORE LUNCH, WE'LL JUST
MOVE ON.
I THINK I UNDERSTAND THAT DR.