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>>TODAY WE ARE HONORED TO HOST
DR. TERRIE TAYLOR
INTERNATIONALLY RECOGNIZED
SCIENTIST AND PHYSICIAN, A
DISTINGUISHED PROFESSOR OF
SURGERY AND MSU FOUNDATION
PROFESSOR FOR THE COLLEGE OF
OSTEOPATHIC MEDICINE AT THE
COLLEGE OF MICHIGAN STATE
UNIVERSITY.
DR. TAYLOR EARNED HER DOCTOR OF
OSTEOPATHIC MEDICINE FROM THE
OSTEOPATHIC MEDICINE COLLEGE AND
COMPLETED INTERNSHIP AT THE
RIVER SIDE OSTEOPATHIC HOSPITAL
IN TRENTON, MICHIGAN.
SUBSEQUENTLY SHE PURSUED A
RESIDENCY IN INTERNAL MEDICINE
AT THE OSTEOPATHIC HOSPITAL.
DR. TAYLOR THEN EARNED A MASTERS
OF TROPICAL MEDICINE FROM THE
LIVER POOL SCHOOL OF TROPICAL
MEDICINE IN LIVER POOL UNITED
KINGDOM.
WHILE EARNING HER MASTERS SHE
MET MALCOM [INDISCERNIBLE] THE
PIONEERING RESEARCHER IN
MALARIA.
THIS PROFESSIONAL PARTNERSHIP
INSPIRED DR. TAYLOR TO COMMIT
HERSELF TO UNDERSTANDING AND
CONQUERING 1 OF THE MOST
INFECTIOUS DISEASE MALADIES IN
THE WORLD TODAY, MALARIA.
TOGETHER THEY DESIGNED A CHROMA
SCALE THAT IS USED TO ASSESS
MALARIA IN CHILDREN.
SINCE 1986 DR. TAYLOR HAS BEEN
LIVING AND WORKING IN MALAWI FOR
6 MONTHS EACH YEAR CONDUCTING
AND TREATING FOR MALARIA
RESEARCH, THE MAJORITY OF WHOM
ARE CHILDREN.
DR. TAYLOR'S RESEARCH FOCUSES ON
THE PATHOGENESIS OF CEREBRAL
MALARIA, HER TEAM PROVIDES
CLINICAL CARE FOR CHILDREN WITH
CEREBRAL MA LAIAR AND IN THAT
CONTEXT, STUDY OF THE DISEASE.
HER WORK HAS RECOGNIZED MALARIAL
RETINAL LOCATIONIN OPEN
MEETINGATHY AND ESTABLISHING
IMPORTANCE AND ORCH CHESTERATING
THE AUTOPSIES OF FATAL CEREBRAL
MALARIA AND COORDINATION OF MRI
IN MALAWI.
SHE HAS ALSO SERVED AS TD
DIRECTOR OF FOR THE CENTERS OF
EXCELLENCE RESEARCH IN MALARIA
FOR THE CENTER'S SUPPORT, SHE
HAS ESTABLISHED THE FIELD WORK
IN MALAWI.
EXECUTED CROSS PATIENTAL
SURVEYS, AND ACTIVELY CONDUCTING
LONGITUDE FLAL COHORT STUDIES,
CASE CONTROL STUDY AND A QUALITY
INQUIRY INTO BARRIERS THWARTING
MALARIA CONTROLS.
DR. TAYLOR HAS BEEN THE
RECIPIENT OF COUNTLESS HONORS
AND AWARDS INCLUDING THE
AMERICAN MEDICAL ASSOCIATION,
FOUNDATION EXCELLENCE AND
MEDICINE AWARD.
THE AMERICAN OFTIO MATHIC
ASSOCIATION, OSTEOPATHIC PIONEER
AWARD AND AMERICAN SOCIETY OF
TROPICAL MEDICINE AND THE
HIGREEN BEN KING AWARD.
SHE HAS AUTHORED OR CO AUTHORED
WELL OVER 200 PEER REVIEW
PUBLICATIONS AND HAS RECEIVED
OVER 35 MILLION IN GRANT AWARDS.
THE TITLE OF DR. TAYLOR'S
LECTURE IS THE PATHOGENESIS OF
PEDIATRIC CEREBRAL MALARIA, AN
ONGOING STORY OF SERENDIPITY AND
SURPRISES.
WELCOME DR. TAYLOR.
THANK YOU SO MUCH.
IT'S AN HONOR BEING HERE AND I
ENJOYED HAVING COFFEE WITH THE
STUDENTS EARLIER TODAY.
LET ME START BY DISCLOSING THAT
I DO SERVE IN AN ADVISORY
CAPACITY FOR A COUPLE OF
DIFFERENT ENTITIES WITHIN
NOVARTIS BUT THAT DOESN'T AFFECT
ANYTHING I WILL PRESENT AND I
HOPE THAT BY THE EPPED OF THE
HOUR, YOU WILL HAVE A BETTER
UNDERSTANDING OF HOW KIDS WITH
CEREBRAL MALARIA PRESENT AND
EVOLVE WHILE THEY'RE BEING CARED
FOR AND THAT YOU WILL UNDERSTAND
THE SIGNIFICANCE OF INCREASED
BRAIN VOLUME IN THEIR DISEASE.
I INCLUDED SERENDIPITY IN THE
TITLE.
SERENDIPITY BEING AN UNPLANNED
FORTUNATE DISCOVERY BECAUSE
REALLY IT HAS STUDDED OUR--MY
JOURNEY THROUGHOUT MY TIME IN
MALAWI.
AND I WANT TO TO TAKE A BRIEF
MOMENT IN THE BEGINNING TO TALK
ABOUT CAREERS IN GLOBAL HEALTH.
BECAUSE 1 OF THE GREAT THINGS
ABOUT THE FIELD IS THAT
EVERYBODY SORT OF ENTERS AT A
DIFFERENT POINT AND FOLLOWS
DIFFERENT TRAJECTORIES.
I STARTED IN A SMALL TOWN IN
NORTHERN MICHIGAN GRADUATING
FROM HIGH SCHOOL IN 1973 WANTING
TO DO SOMETHING INTERESTING AND
USEFUL, I HAD WONDERFUL
UNDERGRADUATE EDUCATION BUT
REALIZED I WASN'T GOING TO BE A
BENCH SCIENTIST SO I WENT ON TO
MEDICAL SCHOOL WHERE I THOUGHT
MAYBE I WOULD DO RURAL MEDICINE
BUT WHEN IT CAME TIME TO DECIDE
ABOUT A RESIDENCY WHICH WE DID
DURING OUR INTERNSHIP IN THOSE
DAYS, I COULDN'T MAKE A DECISION
AND SO, RATHER THAN JUMP
PREMATURELY, I THOUGHT LET ME
SEE THE WORLD.
I'VE GOT A SELLABLE SKILL AND AS
IT HAPPENED, I ENDED UP IN THE
SUDAN.
I ENDED UP IN SUDAN BECAUSE I
STARTED FROM MICHIGAN STATE
UNIVERSITY COLLEGE OF OFTIO
PALGTIC MEDICINE, THE DEAN THERE
HAD A VISION, NIH FUNDED
INVESTIGATORS AT MICHIGAN STATE
WERE HAVING TROUBLE GETTING
TRACTION WITH THE CLINICAL STUDY
IN SUDAN BECAUSE THEY WERE ALL
Ph.D.s AND THEY DIDN'T
HAVE--TOOK A WHILE TO WORK THEIR
WAY INTO THE CLINICAL COMMUNITY
IN SUDAN.
AND SO THE DEAN THOUGHT, AH, I
COULD BUILD CAPACITY AND MY
FACULTY AND HELP OUT THIS
PROJECT AND I SAID NO, NO, NO,
THIS IS REALLY JUST AN ADVENTURE
FOR A YEAR, MAYBE I HAVE TO
RETHINK MY DECISION ABOUT
ORTHOPEDICS AND HE SENT ME OFF
TO THE SUDAN ANYWAY KNOWING THAT
I REALLY WASN'T PLANNING ON THIS
AS A CAREER.
BUT I REALLY LIKED IT, THERE
WERE THESE DISEASES WHICH WERE
VERY UNDERSTUDIED.
THE SUDANESE CLINICIANS DO WHAT
EVERY DOCTOR DOES WHICH IS TAKE
CARE OF PATIENT.
AND THERE WERE STREAMS OF
PATIENTS, THE SUDANESE COULD
NEVER GET ON TOP OF IT ENOUGH TO
THINK ABOUT A RESEARCH PROJECT
OR REQUESTY THAT MIGHT STENCH
THE FLOW OF THOSE PATIENTS, NOT
BECAUSE THEY COULDN'T DO IT
INDLECTUALLY, THEY JUST WERE
SWAMPED WITH PATIENTS AND SO I
BEGAN TO REALLY APPRECIATE THE
UTILITY OF A WESTERN PERSPECTIVE
AND ACTUALLY ACCESS TO RESEARCH
SUPPORT AND 1 DAY I WAS LOOKING
AT THESE KIDS WHO WERE PLAYING
NEXT DOOR AND I WAS THINKING
ABOUT GOING BACK UP TO CARTU,
AND STARTING TO BONE UP ON THE
ORTHOPEDIC WORK, AND I AM LIKE
HMM, MAYBE YOU SHOULD DO THIS SO
IT WAS THIS MOMENT.
I THOUGHT, OKAY, I WILL DO IT, I
HAD TO COMMUNICATE TO THE DEAN
AT MICHIGAN STATE FROM RURAL
SUDAN, WHICH WAS TRICKY AND
PREINTERNET.
HE SAID GO TO DO A RESIDENCY, AT
THAT POINT IT WAS EASY TO CHOOSE
INTERNAL MEDICINE BECAUSE HIBEEN
SO FASCINATED BY THE PARASITIC
INFECTIONS I WAS ENCOUNTERING.
SO I CAME BACK, I DID A MEDICINE
RESIDENCY IN DETROIT ALWAYS
KNOWING I WOULD BE GETTING BACK
TO THE BUSH AND FOR THAT I
IGNORED EVERYONE'S INVITES TO
STAY IN THE U.S. AND OPTED TO
STAY IN THE LIVER POOL SCHOOL OF
MEDICINE BECAUSE IT OFFERED A
MASTER STUDENTS TO FIELD WORK
AND I REALLY WANTED TO BE IN THE
FIELD AND NOT IN THE LAB.
BEFORE A LEFT FOR LIVER POOL, I
MET AGAIN WITH THE DEAN TO
REASSURE HIM OF MY INTEREST EXPW
HE SAID, YOU KNOW IF YOU COME
BACK FROM LIVER POOL AND YOU'VE
IDENTIFIED A RESEARCH PROJECT
SOMEWHERE WHERE I COULD SEND OUR
STUDENTS ON ELECTIVE, I WILL
GIVE YOU A JOB, SO I LEFT FOR
LIVER POOL WITH THAT ADMONITION
IN MY EARS.
HERE IS THE DEAN, MIKE MEGAN AND
HERE IS HIS VISION AND MALAWI
WAS SERENDIPITOUS EEIVET NUMBER
2.
I WAS SENT THERE TO DO MY
STUDENT PROJECT BECAUSE MALCOM
CANNED WHAT 1 OF MY PROFESSORS
IN LIVER POOL HAD A LONG
STANDING CONNECTION IN MALAWI,
HE WAS REVERED, IT WAS A
HOSPITABLE PLACE FOR THE
STUDENTS TO GO AND I REALIZED IN
A NANO SECOND THAT WOULD BE
PERSPECT FOR THE MICHIGAN STATE
STUDENTS.
IT'S A SMALL LAND LOCKED COUNTRY
OF FORMER BRITISH PROTECTORATE,
IT WAS KNOWN AS [INDISCERNIBLE]
THEN AND REALLY IT'S OF NO
GEOPOLITICAL INTEREST TO ANYBODY
AND SO IT'S VERY PEACEFUL AND
VERY NICE PLACE TO WORK.
ON THIS PATH, ON THE 1 MOUNTAIN
IN MALAWI, WE STARTED DISCUSSING
RESEARCH OPPORTUNITIES AND
MALCOM HAD VISITED THE MINISTRY
OF HEALTH TO INQUIRE ABOUT
RESEARCH PRIORITIES THERE AND
THEY IDENTIFIED SEVERE MALARIA
IN CHILDREN HIS BOSS SHOWN BELOW
HIM IN THIS SLIDE, MARCEL HUMLE
HAD DONE WORK ON PRIMATE MODELS
OF MALARIA THAT SUGGESTED A
HYPOTHESIS WE COULD TEST AND I
PERSUADED MALCOM THAT EVEN
THOUGH I WAS A NOVICE, I COULD
BE IN MALAWI FOR LONGER THAN HE
COULD WITH ALL OF HIS FAMILY AND
TEACHING RESPONSIBILITIES IN THE
UK SO WE HATCHED THE IDEA FOR
THIS PROJECT AND WE'RE READY TO
START IN 1986.
WE HAD BEEN WELCOMED BY THE SOLE
PEDIATRICIAN AT THE HOSPITAL IN
AND WE KNEW IT WOULD BE AT THE
SCHOOL EVENTUALLY, THE MINISTRY
OF HEALTH HAD IDENTIFIED ITS
PRIORITY.
WE WERE JUST NAIVE, WE WERE TOTE
AMILLIO NOVICES HAVING NEVER
DONE ANY RESEARCH BEFORE THAT.
THIS IS DR. [INDISCERNIBLE] THE
PEDIATRICIAN WHO WELCOMED US
INTERNISTS INTO HER DEPARTMENT
AND THIS IS MALCOM AND ME
WORKING TO ESTABLISH INTRAVENOUS
ACCESS IN THE YOUNG PATIENT IN
THAT FIRST YEAR, THE FALL OF
1986.
SO SINCE THEN WE'VE BEEN BASED
AT THE QUEEN ELIZABETH HOSPITAL
HERE IN SOUTHERN MALAWI.
WE STARTED WITH NOT A LOT OF
MONEY, KIND OF TAKES A WHILE FOR
GRANTS TO BEAR FRUIT.
SO, I HAD 5000-POUNDS OF SEED
MONEY FROM A DEAN AT MICHIGAN
STATE AND THE WELCOME TRUST GAVE
MALCOM 5000-POUNDS SO WE START
WIDE THAT, WE WERE EVERYTHING,
WE WERE THE LAB TECH, WE WERE
NURSES, WE WERE EVERYTHING IN
THE VERY FIRST YEAR.
IT WAS VERY BUSY AND WE HAD--WE
WERE LIKING INITIALLY AT LOW
BLOOD SUGAR IN KIDS WITH
MALARIA, WE HAD TONS OF
PATIENTS.
LOTS OF DATA AND IT TURNS OUT
THAT HYPOGLYCEMIA IS VERY
IMPORTANT AND WE WROTE IT UP AND
AGAIN WITH KIND OF THE NAIVEETY
OF NOVICES AND WE SUBMITTED IT
TO THE NEW ENGLAND JOURNAL WHICH
HADN'T HAD ANYTHING ON MALARIA
IN AGES AND SO THEY PUBLISHED IT
AND WE WERE OFF TO THE RACES
AFTER THAT.
FOR THOSE OF YOU WHO ARE NOT
FAMILIAR WITH THE LIFE CYCLE OF
THE PARASITE, I WON'T BELAYOR IT
HERE EXCEPT TO SAY THAT THE FORM
OF THE PARASITE, THE STAGE AND
LIFE CYCLE THAT'S RELEVANT TO US
IS HERE, THE INTRA ARITHROUGH
ATOM SITTIC FORM WHEN THE
PARASITE INVADES CELLS, AND FOR
[INDISCERNIBLE], THE MOST
INTERESTED IN BECAUSE IT'S THE 1
ASSOCIATED WITH MOST MORBIDITY
AND MORTALITY, THAT LIFE CYCLE
IS 48 HOURS.
SO FROM 11 [INDISCERNIBLE] TO
16-32 OF THE NEXT GENERATION
TAKES ABOUT 48 HOURS AND THE RED
CELL IS DEFORMED IN THE PROCESS,
MUCH OF THE HEMOGLOBIN IS
DIGESTERRED AND THE RED CELL
BECOMES LESS DEFORMABLE AND WERE
IT TO BE REMAIN IN THE
PERIPHERAL BLOOD, IT WOULD BE
CALLED BY THE SPLEEN.
IT WOULD BE SO ABNORMAL.
SO TO AVOID THAT FATE, THE
PARASITE HAS DEVELOPED THE
CAPACITY TO CYTO ADHERE TO
ENDOTHELIAL CELLS, CAPILLARY
TISSUES THROUGHOUT THE BODY AND
IMPORTANTLY THE BRAIN BUT NOT
EXCLUSIVELY THE BRAIN.
AND THAT CYTO ADHERENCE, THE
SEQUESTRATION OF THE MATURE
ARITHROCYTE ALLOWS IT TO HIDE
FROM THE SPLEEN AND CONTINUE ITS
LIFE CYCLE.
IT ALSO IS SORT OF IRRESISTIBLE
TO ATTRIBUTE PATHOGENETIC
SIGNIFICANCE TO THIS, BECAUSE
THESE POST CAPILLARY
VENOUSLIULES ARE COMPLETELY
OBSTRUCTED OFTEN WITH THESE
PARASITIZED RED BLOOD CELLS.
ANOTHER IMPORTANT AND
DEVELOPMENTAL ENDOCRINOLOGYIOUS
FEATURE OF THIS PARASITE IF YOU
MADE A DIAGRAM WOULD BE
AFFECTED.
MANY OF THESE CAN CO EXIST WITH
THE PARASITE WITHOUT DEVELOPING
SYMPTOMS.
THIS RESERVOIR OF PARASITES IS
CENTRAL TO THE ONGOING
TRANSMISSION OF THE PARASITE TO
MOSQUITOES.
THESE ASYMPTOMATIC INDIVIDUALS
THOUGH, CAN BE DOUBLE AT
DIAGNOSIS AS YOU WILL SEE.
EVENTUALLY SOME PEOPLE DEVELOP
UNCOMLICATED MALARIA, FEVER,
CHILLS, NAUSEA, HEADACHE,
VOMITING AND A TINY PORTION GO
ON TO DEVELOP WHAT WE'RE
INTERESTED IN WHICH IS
[INDISCERNIBLE].
SO IN THE GRAND SPECTRUM OF
SEEREBERAL MALARIA IS RARE, BUT
BECAUSE SO MEAN PEOPLE ARE
INFECTED THAT ACTUALLY TOTALS
QUITE A FEW INCIDENCES OF
DISEASE AND DEATH OVER ON
AN ANNUAL BASIS.
WHEN WE STARTED THE CASE
DEFINITION OF MALARIA WERE
MOSTLY ADJECTIVES, WHICH WERE
HARD TO QUANTIFY, KIDS WERE
STIEWPEROUS, KROWZY, IT WAS
NECESSARY TO DEVELOP THE PLANTAR
[INDISCERNIBLE] SCORE WHICH
RELIES ON INFLECTING PAIN EITHER
ON A NAIL BED OR SUPER ORBITAL
RIDGE AND LOOKING TO SEE WHAT
THE RESPONSE IS, IS THERE ANY
RESPONSE, IS FROM A MOON, A
GRIMACE, CAN THE PATIENT
LOCALIZE THE PAINFUL STIMULUS OR
NOT, WHAT'S THE QUALITY OF THE
CRY AND CAN THEY FOLLOW A MOVING
OBJECT SO YOU CAN GET 5.
IF YOU CAN DO ALL OF THAT AND
SUCCESSFULLY LESS, A COMA SCORE
OF 2 OR LESS, BASICALLY
REPRESENTS SOMEONE WHO IS SO
[INDISCERNIBLE] THAT THEY CAN'T
LOCALIZE A PAINFUL STIMULUS.
IN ADDITION, THERE NEEDS TO BE
PARASITE, THERE NEEDS TO BE
PARASITES PRESENT IN NO OTHER
OBVIOUS CAUSE OF COMA AND THE 3
LEADING OTHER CAUSES OF COMA IN
THIS GROUP ARE ARE HYPOGLYCEMIA
AS WE REALIZED IN THE FIRST
YEAR, SOME KIDS CAME AROUND WITH
INTRAVENOUS, 50% DEXTROSE AND
OTHERS STAYED IN COMAS.
MENIN GIETIS CAN ALSO BE A SIDE
EFFECT OF MALARIA AND WE DO A
LUMBAR PUNCTURE FOR THAT, AND
SEIZE OURS CAN HAVE A
POST-ICTALL STATE WHICH MAY
OFTEN OBSCURE THE DIAGNOSIS.
WE DON'T DELAY TREATMENT WAITING
FOR THAT STATE OR NOT, WE TREAT
PATIENTS BUT THEY GET
CATEGORIZED AS CEREBRAL MALARIA
DEPENDING ON HOW LONG IT TAKES
THEM TO COME AROUND FROM HAVING
HAD A COMA.
THE CLINICAL ILLNESS AND OFTEN
VERY RAPID IN ITS ONSET, THESE
ARE CHILDREN WHO HAVE MANY
FEVERS OVER THE COURSE OF A YEAR
AND THE PARENTS HAVE NO WAY OF
KNOWING WHAT'S A DANGEROUS FEVER
UNTIL THE CHILD STARTS
CONVULSING OR LAPSES INTO COMA
AND THEN THEY RUSH INTO THE
HOSPITAL.
AND WE STABILIZE THEM HERE, THIS
IS THE ADMISSIONS AREA OF OUR
RESEARCH WARD.
IT'S WHERE WE CAN MACK SURE THAT
THERE ARE ADEQUATELY OX
GENERATED 8ED, WE CAN GET A
VENUS LINE, AND WE CAN GET A
COMA SCORE ASK THEN THEY'RE
MOVED TO THE WARD FOR THE REST
OF THEIR STAY.
THE PARENTS STAY THROUGHOUT HERE
AND THIS IS WHAT WE'VE ALWAYS
DONE ON OUR RESEARCH WARD IN
TERMS OF LOOKING FOREVER THE
PATIENT.
SO WE KEEP AN EYE ON THEIR
MALARIA PARASTIETS.
LET HEMEAT O CRIT IS A WAY TO
ASSESS ANEMIA RATHER THAN TO RUN
A BLOOD TEST.
GLUCOSE IS A FACTOR LACTIC
ACIDOSEISATE, CBC, SOME KIDS ARE
CONCURRENTLY BACTERIAOREMMIC AND
GENERALLY WE START ANTIBIOTIC
FIST THEY'RE BACTERIAOREMMIC AND
HYPOTENSIVE AND WE DO A LUMBAR
PUNCTURE TO CHECK FOR
MENINGITIS.
WE THEN ADMINISTER ANTIMALARIA
MEDS AND WHEN WE STARTED IT WAS
QUININE, AND NOW IS ARTESUNATE,
AND I NEED TO EXPLAIN THAT SOME
OF MY PRONOUNCEIATIONS ARE
DIFFERENT THAN THE WAY THESE
WORDS ARE PRONOUNCED IN THE
STATE AND I THOUGHT IT WAS A
POINT OF JOCKULARRITY WHEN WE
WERE FIRST STARTING.
WE WERE TREATING SEER
EASTBOUNDERAL MALARIA?
WERE WE TREATING PEOPLE VIA A
SHEDULE OR A SCHEDULE.
THERAY SO MANY DIFFERENT WORDS
IN THE ENGLISH LANGUAGE AND HE
FINALLY SAID WE COULD PRONOUNCE
THESE WORDS YOUR WAY OR WE COULD
PRONOUNCE THEM PROPERLY.
THAT'S WHY I'VE BEEN STUDYING
CEREBRAL MALARIA AND WHY WE
STARTED TREATING WITH QUININE.
WE ALSO GIVE BLOOD TRANSFUSIONS
THERE'S AN INEVITABLE LOSS OF
RED BLOOD CELLS OVER THE COURSE
OF MALARIA INFECTION AND THAT IS
VERYENTIOUS FICIENT AT OUR
HOSPITAL, WAY FASTER I THINK
THAN IN THE U.S., WE SEIZURES
AND WE KEEP AN EYE ON THE KIDS.
WE WATCH THEM.
THE NURSES DO 2 HOURLY
OBSERVATIONS FOR VITAL SIGNS AND
6 HOURLY CHECKS OF THE GLUCOSE,
LACTIC ACIDOSEISATE, HEMEAT O
CRIT AND ET CETERA.
AND WE WILL ALSO BE CHECKING THE
BLOOD VESSELS AND WE'RE
INTERESTED IN THE BACK OF THE
EYE.
WE'RE VERY INTERESTED IN
SEIZURES AND WE'RE VERY
INTERESTED IN WHAT'S HAPPENING
IN THE BRAIN.
BUT THOSE 3 WERE LATE ADD-ONS
AND THE FIRST BITS ARE WHAT
WE'VE DONE RIGHT FROM THE VERY
FIRST SEASON.
WE HAVE A CHART TAKEN--THEY WE
KEEP AN EYE--EVERYBODY TAKES
TURNS WITH THEIR OBSERVATIONS SO
WHEN WE DO OUR ROUNDS OR CALLED
TO THE BEDSIDE FOR THE CHANGE IN
THE DON DITION OF A PATIENT, WE
CAN SEE AT AN INSTANT WHAT'S
HAPPENING AND WE KEEP TRACK ON A
WHITE BOARD ON THE BOARD BECAUSE
BECAUSE TIME 0 IS DIFFERENT FOR
EVERY PATIENT.
THEY APPEAR AT ALL HOURS OF THE
DAY AND NIGHT.
THE CARE THAT WE PROVIDE IS NOT
IS HIGHLY SOPHISTICATED.
THERE'S INTRAVENOUS FLUIDS AND
NASOGASTRIC [INDISCERNIBLE] AS
WELL AS ATTENTIVE NURSING AND
CLINICAL CARE.
THE USUAL CLINICAL COURSE IS
ASTONISHINGLY RAPID CONSIDERING
THESE KIDS HAVE BEEN PLUNGED
INTO COMA, THEY'RE OFTEN
SEIZING, THAT'S LOOK LIKE
THEY'VE HAD A CLOSED HEAD INJURY
AND THE VAST MAJORITY ARE UP AND
AT THEM IN A COUPLE DAYS.
THE PARASIGNIFY TEEMIA CLEARS
QUICKLY, IF THEY DON'T WAKE UP
RIGHT AWAY WE GIVE THEM
NASOGASTRIC TUBE FEEDS, WE TREAT
THE SEIZURES, WE USE ANTIBIOTICS
ASSOCIATIONALLY, BLOOD
TRANSFUSIONS, BUT MOST KIDS GO
HOME ON DAY 3 OR 4, THE SURVIVAL
RATE AND 80-85%.
WE DO FOLLOW UP VISITS IN THE
NEUROLOGICAL SEQUEL I OF THIS
DISEASE BUT I WON'T TALK ABOUT
THAT TODAY.
BUT 15-20% DIE AND OVER THE
COURSE OF THE FIRST SEVERAL
YEARS, WE BECAME--WE BECAME ABLE
TO RECOGNIZE THIS INEVITABLE
SEQUENCE OF EVENTS.
IN ABOUT 2/3RDS OF PATIENTS THEY
WOULD HAVE RESTIER REVIEWATTORY
ARREST.
ANYTHINGLY, THE MOMS WOULD
FANATIC IT OUT FIRST AND BECOME
FRIGHTENED AND WOULD START
CRYING AND THEN THE NURSES WOULD
NOTICE THAT THE RESPIRATORY RATE
WAS BECOMING IRREGULAR, AND THEN
WE WOULD COME BECAUSE THE
PATIENT HAD REACHED THE GASPING
STAGE AND IF WE MADE IT TO THE
BEDSIDE AND WE WERE ABLE TO
START RESUSCITATING WITH A BAG
AND A MASK, WE COULD SUSTAIN
CARDIAC ACTIVITY INDEFINITELY.
SO FOR MALCOM AND ME STANDING AT
THE BEDSIDE WATCHING THIS, IT
LOOKED LIKE THE CLASSIC
DESCRIPTIONS OF WHAT'S CALLED
PERMEATION OR AS WE CALL IT IN
THE UK THEY CALL IT CONING, AND
WHAT THAT IS, IS THE INEVITABLE
OUTCOME OF A SWOLLEN BRAIN.
SO HERE'S A BRAIN CONTAINED
WITHIN THE SKULL AND AS THE
BRAIN GETS LARGER AND LARGER FOR
WHATEVER REASON BRAIN TUMOR OR
WHATEVER, IT GETS FORCED OUT BY
THE ONLY OPENING HAD WHICH IS
THE FRAME AND MAGNUM AT THE BASE
OF THE SKULL AND UNFORTUNATELY
THERE IN THE MEDULLA IS THE
RESPIRATORY CENTER AS THAT SPACE
IS ENCROACHED UPON THE REZONING
PIRATTORY CENTER HAS PRESSURE IS
APPLIED TO IT AND PEOPLE STOP
BREATHING, THERE'S RESPIRATORY
ARREST.
THAT'S WHAT IT LOOKED LIKE BUT
WE REALLY DIDN'T HAVE ANYWAY TO
KNOW.
THIS IS A PICTORIAL
DEMONSTRATION OF THAT PROCESS,
THE CEREBELLAR TONSILS EXTRUDE
THROUGH THE FRAME AND MAGNUM AND
COMPRESS THAT AND THIS IS WHAT
IT'S LIKE IN A GROSS SAMPLE OF A
BRAIN THAT'S BEEN REMOVED FROM
THE SKULL ON A PERSON WHO
PROBABLY WAS ON LIFE SUPPORT FOR
QUITE A WHILE AND THEN DIED.
BUT YOU CAN SEE DEEP GROOVING
HERE FROM THE BONY IMPRESSION OF
THE PREMIUM MAGNUM, SO THAT'S
THE OVER ALL MORTALITY WITH
ABOUT 2/3RDS OF THE KIDS GOING
32 THIS RESPIRATORY ARREST AND
THE OTHERS HAD A CARDIO
PULMONARY ARREST AND THEN, WE
HAD THE NEXT SERENDIPITOUS EVENT
WHICH IS A CURIOUS
OPHTHALMOLOGIST, I WAS THERE FOR
SUPPER 1 NIGHT.
I WAS DESCROIBING WHAT I JUST
WAS DESCRIBING TO YOU, THIS
RESPIRATORY ARREST SEEMED VERY
CURIOUS AND SHE SAID HAVE YOU
EVER LOOKED IN THE EYES, WHICH
WE KIND OF HAD BUT NOT PROPERLY,
NOT WITH FULL DILATION.
SO SHE DID THIS ON NIGHTS AND
WEEKENDS AND THERE WERE
PHENOMENAL FINDINGS WHICH THERE
WERE ALLUSIONS TO THESE FINDINGS
IN THE LITERATURE BUT THEY WERE
VERY SCATTERED SO 1 FIND SUGGEST
CALLED VESSEL CHANGES WHERE THE
COLOR OF THE COLUMN OF THE BLOOD
IN THE VESSEL ACTUALLY CHANGES
FROM RED WHICH IS NORMAL TO
ORANGE OR YELLOW, THERE ARE
AWLTS HEMORRHAGES, THAT'S SHOWN
IN THE SECOND SLIDE AND THEN
THERE WAS ANOTHER CHANGE CALLED
THE WHITENING, THERE'S A LOT OF
WHITENING AROUND THESE
HEMORRHAGES AND THEN IN THE
BOTTOM SLIDE THERE'S A PICTURE
WITH ONLY WHITENING AND THAT WAS
A CHANGE THAT WAS OBSERVED IN
BETWEEN THE BLOOD VUSESLES IN
THE FUNDUS.
AND THEY WERE NOT ALL THE SAME
BETWEEN THE PATIENTS, THEY COULD
BE DIFFERENT COMBINATIONS BUT
THEY WERE NOT IN EVERY PATIENT.
SO THIS AGAIN WAS DIFFICULT TO
FIGURE OUT BECAUSE THESE WERE
KID WHO IS ALL MET THAT STANDARD
CLINICAL CASE DEFINITION OF
CEREBRAL MALARIA, SOME HAD
COMPLETELY NORMAL EYES AND
OTHERS HAD 1 OR MORE OF THESE
FEATURES, SO THAT WAS A
CONUNDRUM.
SO AT THAT POINT IN THE MID90S
WE DECIDED THAT WE HAD TO GO BA
BEING TO SQUARE 1 AND DO
AUTOPSIESS, WHAT WERE THEY
EXPERIENCING ISSUES WHAT WAS THE
NAME OF THE SEQUESTRATION, WHAT
WAS GOING ON SO WE LAUNCHED OUR
AUTOPSIES STUDY WHICH WAS
FASCINATING AND ALL THE WORK
HERE IN THE MOTORUEARY OF THE
QUEEN ELIZABETH CENTRAL HOSPITAL
AND I PUT THE SLIDE IN BECAUSE
WHEN YOU DO A STUDY LIKE THIS,
YOU DEVELOP A VERY KIND OF DARK
GALLOWS SENSE OF HUMOR SO AFTER
A WHILE IT BECAME KIND OF FUNNY
TO US THAT ON THIS BUILDING
MARKED THE MOTORUARY IT WAS
OMINOUSLY NOTED THAT THERE WAS
ONLY 1 WAY OUT OF THE MOTORUARY.
THE AUTOPSIES WERE QUITE
EXTENSIVE, JUST SO YOU KNOW THE
PARATHYROIDS WERE THE KEY TO THE
MYSTERY AND WE TRIED TO GEM THEM
OUT OF EVERY PATIENT AND WE
SAVED THE TISSUES MANY DIFFERENT
WAYS SOPHISTICATEDY WE COULD
PROBE THEM WITH MANY DIFFERENT
TECHNIQUES TO TRY TO UNDERSTAND
WHAT WAS HAPPENING AND OVER THE
COURSE OF 14 YEARS WE DID 103
AUTOPSIES.
WE DID AUTOPSIES ON KIDS WHO MET
THE CASE DIFFERENT OF CEREBRAL
MALARIA, WE HAD KID WHO IS HAD
NO MALARIAL PARASITES AND DIED
AND WE HAD KIDS WITH MALARIAL
PARASITES AND THEY DIED FOR
OTHER REASON SAYS AND WE
COMPARED ALL OF THEM.
AND WHAT I WANT TO FOCUS ON ARE
THE FINDINGS IN THE KIDS WHO MET
THAT CASE DEFINITION OF CEREBRAL
MALARIA, SO ANYONE IN THE WORLD
IN THE WORLD WOULD HAVE CALLED
THEM CEREBRAL MALARIA, IN THAT
GROUP WE SAW 3 DIFFERENT
HISTOLOGIC FINDINGS IN THE
BRAIN.
THIS IS 1 WHERE WE HAD
SEQUESTRATION ONLY WHERE HE HAD
IT IN THE BRAIN CHOKED FULL OF
CELLS.
ANOTHER FINDING WAS
SEQUESTRATION ONLY IN OTHER
PATHOLOGY, THERE WERE DIFFERENT
THROMBY IN THE BLOOD VESES ELTS,
DIFFERENT HEMORRHAGES ON THE
PATHWAY GIVES RENK MA OF THE
BRAIN, BUT THERE WAS ALSO
SEQUESTRATION.
THE THIRD GROUP REALLY THREW US,
BECAUSE THESE KIDS HAD NO
SEQUESTRATION, NO PARASITES IN
THE BRAIN AND IN EVERY OTHER WAY
MET THE DEFINITION OF CEREBRAL
MALARIA.
AND IN THIS GROUP WE FOUND
ANOTHER CAUSE OF DEATH THAT WE
HADN'T SUSPECTED HAD WE NOT DONE
THE AUTOPSIESS.
SO THIS WAS EXTREMELY
ILLUMINATING.
WE NEVER FOUND ALTERNATIVE OR
ADDITIONAL CAUSES OF DEATH IN
THE CM1s AND THE CM2s.
WE WERE ALSO LOOKING FOR
SWELLING, ALL BRAINS WERE
SWOLLEN IRRESPECTIVE OF CAUSE OF
DEATH.
BY THE WAY IN THIS SETTING WHEN
YOU TRY TO EXAMINE THE BRAIN,
YOU HAVE TO IN THE MORTUARY PEEL
BACK THE SCALP AND TAKE A BONE
SAW AND GO AROUND THE HEAD AND
REMOVE WILL CALVARIUM AND VERY
GENTLY DISSECT DOWN THROUGH THE
SKULL, LOOSEN UP THE BRAIN,
SEVERE MITRALLER IT AT THE
SPINAL CORD, LIFT IT OUT OF THE
SKULL AND FLIP IT OVER TO SEE IF
THERE ANY SIGNS OF HERNIATION
AND WE DID THIS EAGERLY WITH
EVERY AUTOPSIES.
SO HERE'S THE FRAME AND MAGNUM,
HERE'S THE SKULL CAN THE BONE,
THIS IS NOT A REAL SKULL, WITH
THE BONE SAW AROUND IT AND THEN
WE WOULD FINGER DISSECT DOWN AND
LIFT THE BRAIN OUT OF THE SKULL.
LOOKING FOR THESE TELL TALE
SIGNS OF HERNIATION.
NOW, WE NEVER SAW IT.
SO THAT WAS FRUSTRATING.
HOWEVER, WE LEARNED A LOT, WE'VE
LEARNED THAT THEY'RE AT LEAST AT
THE HISTOLOGIC LEVEL, THERE ARE
3 DIFFERENT TYPES OF CEREBRAL
MALARIA SO THIS GROUP THAT MEETS
THE CLINICAL CASE DEFINITION IS
ACTUALLY MORE--IS NOT SO
MONOCHROMEATIC AT ALL, IT'S
ACTUALLY QUITE HETEROGENIUS AND
THERE ARE SOME KIDS IN THERE WHO
DON'T ACTUALLY HAVE SEEREBERAL
MALARIA, THOSE ARE COLORED BLUE
HERE, THEY HAVE SOMETHING ELSE
AND IT BEHOOVES US AS THE
CLINICIANS TO DETERMINE THAT.
SO WE SPENT QUITE A LOT OF TIME
LOOKING FOR CLUES IN LIFE FOR
THAT GROUP WE WANTED TO NOT
STUDY THEM AS CEREBRAL MALARIA,
THEY WERE POLLUTING OUR POOL
BIEW WE ALSO WANTED TO GIVE THEM
THE RIGHT TREATMENT AND LOW AND
BEHOLD THE RETINAL LOCATIONIN
OPEN MEETINGATHY STATUS WERE THE
KEY.
SO THE KIDS WITH NORMAL EYES
WERE NO SEQUESTRATION, THE KIDS
WITH FINDINGS OF MALARIAL
RETINAL LOCATIONIN OPEN
MEETINGATHY HAD ALL EVIDENCE OF
MALARIA INFEC IN THEIR BRAIN SO
THEN WE ALL BECAME INTENSELY
INTERESTED IN EYE EXAMS AND OVER
TIME WE WERE ABLE TO WORK OUT
WHAT THOSE EYE FINDINGS
REPRESENTED.
THE WHITENING IS IMPAIRED
PROFUSION, WE HAD TO DO INJURY
GRAMS FOR THAT BUT YOU COULD SEE
THE FLOWER ESTIMATE THADING WITH
STOP, THE BLOOD FLOW WOULD STOP
AND BEYOND THAT WAS THE
WHITENING.
SO THAT WAS INOXIC OR HIPOXIC
AREAS OF THE EYE.
THE HEMORRHAGES OF THE EYE
HISTOLOGICALLY LOOKED JUST LIKE
THE HEMORRHAGES IN THE BRAIN AND
MY PERSONAL FAVORITE OF THE EYE
FINDINGS IS THE VESSEL CHANGES.
SO WHERE THE BLOOD BECOME ORANGE
THOSE ARE ACTUALLY PARASITIZED
CELLS, WITH HEMOGLOBIN IN THEM,
THEY'RE PALER THAN YOUR AVERAGE
RED CELL AND YOU CAN SEE IT IN
THE EYES.
SO IF WE TAKE OUT THOSE THAT ARE
RED NEGATIVE, WE ARE LEFT WITH A
GROUP TO MORE TRULY LIKELY TO
HAVE SEEREBERAL MALARIA AND
THUGS THEY BECAME THE FOCUS OF
OUR WORK.
HOWEVER, YOU MAY RECALL WE STILL
DON'T KNOW WHY THEY'RE DYING.
THIS IS A VERY INTERESTING FIND,
SO WE DELVED DEEPLY INTO THE
NEURAL PATHOLOGY, THERE WAS A
LOT OF INTERESTING
NEUROPATHOLOGY, BUT NONE OF IT
WAS REALLY FATAL, SO, WE HAD TO
ADMIT THERE ARE FLAWS IN THE
AUTOPSIES, WE ARE LOAMACY BEING
AT THOSE WHO DIE, WE ARE LOOKING
AT THEM IN THE MOMENT OF DEATH,
WE HAVE NO IDEA HOW THOSE
FINDINGS COMPARED TO THE
SURVIVORS SO WE NEEDED TO DO
NEUROIMAGING, A PIPE DREAM IN
MALAWI, WE COULDN'T EVEN KEEP
THE RAG X-RAY MACHINES
FUNCTIONING.
SERENDIPITOUS EVENT NUMBER
ENOUGH WAS E. JAMES POACHIN,
VISIONARY HEAD OF RADIOLOGY AT
MICHIGAN STATE WHO PERSUADED
THEM TO DONATE A MRI MACHINE TO
US.
PHENOMENAL ARRIVED ON WORLD
MALARIA DAY 2008 AND BY 2009 WE
WERE ABLE TO IMAGE ALL OF OUR
KIDS THROUGHOUT THE COURSE OF
THEIR ILLNESS AND THE FIRST
PATIENT WHO CAME IN IN 2009,
WENT THROUGH THEIR CLINICAL
COURSE HAD 2 MRIs IN FACT,
DIED, WE GOT PERMISSION TO DO
THE AUTOPSIES THAT CASE BLUE
OPEN THE WHOLE THING.
THIS WAS A TYPICAL CEREBRAL
MALARIAL PATIENT, PARASITEMMIC,
EYE FINDINGS, NO SEIZURES HAD A
PRETTY BENIGN CLINICAL COURSE
UNTIL HE WENT THROUGH THAT
INEVITABLE RESPIRATORY CYCLE OF
EVENTS, RESPIRATORY
DESENSITIZATION AND DIED.
THIS WAS EARLY ON, HE CAME IN ON
FRIDAY AFTERNOON HAD AN MRI,
ANOTHER ON SATURDAY MORNING AND
THEN HE PASSED AWAY AND WE WERE
ABLE TO DO THE AUTOPSIES THE
SAME DAY SO WE TRY ALWAYS TO DO
THE AUTOPSIESS SHORTLY AFTER
DEATH.
THE DEATH WOULD OCCUR SHORTLY
AFTER THE RESPIRATORY ARREST, WE
WOULD TRY TO DO THE AUTOPSIES AS
QUICKLY AS WE COULD AFTER THAT
AND WE WERE JUST NERVOUS ABOUT
GOING ON, TURNING ON THE MACHINE
AND LOOKING AT THE IMAGES, THEN
WE DIDN'T, BUT NOW WE KNOW HOW
TO DO IT.
SO WE DID THAT AUTOPSIES WITHOUT
THE BENEFIT OF HAVING SEEN THE
MRI FINDINGS AND WAS JUST LIKE
EVERY OTHER 1, THE BRAIN WAS
SWOLLEN, CELL SIDE NARROWS
LOOKED AT THE BASE OF THE BRAIN,
STILL NOTHING, NO EVIDENCE OF
HERNIATION.
THEN ON MONDAY, WE REVIEWED THE
FINDINGS WITH THE RADIOLOGIST
AND JUST TO ORIENT YOU OR
ORIENITATE YOU AS MALCOM WOULD
SAY, THIS IS WHAT IT LOOKED LIKE
IN OUR MAGNET. THIS IS A T1
IMAGE EVERYTHING THAT'S BLACK IS
CEREBRAL SPINAL FLUID SO
NORMALLY THE BRAIN IS BATHED AND
BUOYANT IN CEREBRAL SPINAL
FLUID.
OUR AREA OF INTEREST IS RIGHT
HERE WE ARE LOOKING AT BRAIN
IMPINGING ON THE FRAME AND
MAGNUM.
SO HERE'S OUR PATIENT ON
ADMISSION IN FRIDAY, CLEARLY
SOMETHING DIFFERENT IS
HAPPENING, THE BRAIN IS SWOLLEN
AND BY SATURDAY, OURS BEFORE HE
DIED THERE WAS CLEAR EVIDENCE OF
HERNIATION, THE RADIOLOGIST HAD
NO DOUBT SO WE'RE LIKE WHAT?
AND THEN IT DAWNED ON US EXACTLY
WHAT HAD BEEN HAPPENING AND IT
WAS A BRILLIANT EXAMPLE OF THE
HIGHSEN BURG UNCERTAINTY
PRINCIPLE WHICH WAS THE ACT OF
MEASURING SOMETHING, IF YOU
RECALL WE EXPOSED THE SKULL, WE
HAD A BONE SAW, WE GO ALL THE
WAY AROUND AND WE LIFT OFF THE
CALVARIUM AND WHAT DOES THAT DO,
RELIEVES ALL THE PRESSURE, THE
BRAIN MOVES UP AND ALL THE SIGNS
THAT WE'RE LOOKING FOR AT THE
BRACE OF THE BRAIN WHICH DIDN'T
HAVE LONG TO APEERP BECAUSE THE
CHILD DIED AND WE WENT
IMMEDIATELY TO AUTOPSIES, THE
VERY FINDING THAT WE WERE
LOOKING FOR WAS OBLIT RATED.
WE NEVER WOULD HAVE CAUGHT THIS
WITHOUT THE MRI.
SO, FAST FORWARD SEVERAL YEARS
WE ACCUMULATE A BUNCH OF
PATIENTS AND NEARLY ALL THE
DEATHS ARE ASSOCIATED WITH
INCREASED BRAIN VOLUME.
MANY PATIENTS WITH INCREASED
BRAIN VOLUME SURVIVE, WHICH WAS
REASSURING, BUT NEARLY ALL THE
DEATHS CAN BE ATTRIBUTED IN 1
WAY SHAPE OR FORM FOCUSED ON
INCREASE BRAIN VOLUME.
THE RESOLUTION IN THOSE WHO
SURVIVE IS RAPID, CONSISTENT
WITH THE RAPID CLINICAL
IMPROVEMENT THAT WE SEE @
BEDSIDE, SO NOW OUR MARADIME AND
CLAIMED IT VIA--NOT SAYING
CAUSED YET BUT BRAIN SWELLING
AND THE RAISED INTRA CRANIAL
PRESSURE THAT IT BRINGS ALONG
WITH IT ARE STRONG PREDICTERS
EVER DEATH IN OUR PATIENT
POPULATION.
SO NOW WE'RE LIKE, OKAY, WHY ARE
THESE BRAINS SWOLLEN.
AND THERE ARE SEVERAL, ACTUALLY
POTENTIALLY 4 EXPLANATIONS FOR
THE BRAIN SWELLING.
THE BRAIN VOLUME, THE BRAIN
TISSUE ITSELF COULD BE EXPANDING
OR THE VOLUME OF BLOOD IN THE
BRAIN COULD BE INCREASING SO WE
KNOW THERE'S THE PONLT OF VASE O
GENIC, WE KNOW THERE'S A BLOOD
BARRIER BREAK DOWN, WE SAW THOSE
HISTOLOGICALLY.
WE SUSPECT THESE ARE CYTOTOXIC
EDEMA FROM THE ISCHEMIA, WE KNOW
THAT IN THE EYE, THERE'S
PROBABLY A CORRELATE TO THAT IN
THE BRAIN.
THE BRAIN ITSELF IS EXQUISITELY
CAPABLE OF ADJUSTING ITS OWN
BLOOD FLOW AND IT CAN INCREASE
BLOOD FLOW IF NECESSARY AND
THERE ARE LOTS OF REASONS IN
MALARIA WHY A BRAIN NIGHT NEED
MORE BLOOD, KIDS ARE ANEMIC,
SEIZING, FEB RILE, ALL THOSE
WOULD COMBINE TO INCREASED BLOOD
FLOW.
MY PERSONAL FAVORITE AMONG THE
POTENTIAL SOURCES OF INCREASED
BRAIN VOLUME IS THAT THE
SEQUESTERED MASS OF PARASITES IS
IMPEDING VENUS OUTFLOW AND WE
DO, HISTOLOGICALLY WE SAW LOTS
OF CONGESTION IN THE BRAIN AND I
LIKE THAT 1 BECAUSE IT'S ALSO
CONSISTENT WITH THE RAPID
RECOVERY ONCE KIDS ARE ON
TREATMENT.
BUT WE DIDN'T KNOW WHAT THEY
WERE AND IT KIND OF MATTERS
BECAUSE THE CLINICAL TREATMENT,
THE MANAGEMENT STRATEGY WOULD BE
DIFFERENT DEPENDING ON WHICH OF
THESE IT WAS.
BUT TIME IS PASSING.
KIDS ARE DYING SO WE THOUGHT,
WELL, MAYBE IT DOESN'T REALLY
MATTER BECAUSE SO MANY KIDS
SURVIVE.
MAYBE IF WE COULD JUST GRIEVE
FOR THEM INSTEAD OF STANDING AT
THE BEDSIDE BEGGING AND ASKING,
CAN'T DO THAT INDEFINITELY, IF
WE BREATHE FOR THEM AND NATURE
TOOK ITSELF COURSE AND THE BRAIN
VOLUME RESOLVED WE MIGHT BE ABLE
TO TIE THEM OVER THE VULNERABLE
PERIOD.
THAT WAS A PIPE DREAM UNTIL
SERENDIPITOUS EEIVET NUMBER 6
WHICH WAS THE ARRIVAL IN MALAWI
OF MADONNA, SHE TOOK MALAWI INTO
HER HEART AND SHE TOOK ON THE
SURGEONS AND WHOSE SURGEONS WERE
BEING COMPLICATED BY THE LACK OF
POST OPERATIVE CARE.
SO THEY WOULD DO BRILLIANT
SURGERIES BUT THERE WASN'T A
PLACE TO ALLOW THEM TO HEAL
AFTER THESE SURGERIES.
SO MADONNA BUILT A POST CARE
FACILITY, JUST WHEN WE WERE
INTERESTED IN THE POST SURGICAL
CARE OF OUR PATIENT POPULATION.
THIS IS A GORGEOUS FACILITY WE
DESIGNED A 3 ARM CLINICAL TRIAL
TO INVESTIGATE TREATMENTS THAT
MIGHT HELP THESE KIDS.
WE ORIGINALLY WERE HOPING TO
ENROLL 258 PATIENTS.
WE HAVE A GREAT STUDY TEAM OF
CLINICIANS IN MALAWI AND
RADIOLOGYSISTS AROUND THE WORLD
BECAUSE WE NEED BRAIN VOLUME
INTERPRETATIONS AT ALL HOURS OF
THE DAY OR NIGHT AND WE ARE
STUDYING THE INCREASED
ASSOCIATION OF BRAIN VOLUME FOR
OUTCOMES IN OUR KIDS WITH THE
HYPOTHESIS BEING THAT ANY
INTERVENTION THAT COULD REDUCE
THE BRAIN VOLUME OR SUPPORT
VENTILATION WOULD INL PROVE
SURVIVAL RATES.
SO 1 ARM IS IMMEDIATE VENT
LATTERY SUPPORT AND ANOTHER ARM
IS OSMOTIC THERAPY AND THERE
WERE A NUMBER OF THINGS WE COULD
HAVE CHOSEN BUT WE CHOSE 3% HYPE
OR TONIC SALINE BECAUSE IT CAN
BE ADMINISTERED THROUGH A
PERIPHERAL IV AND MORE EASILY
MANAGED THAN OTHER FORMS OF
OSMOTIC THERAPY.
THE USUAL CARE AND CONTROL ARM
AS IT WERE IS TO PUT KIDS IN A
BED WITH THE HEAD OF THE BED
ELEVATED TO ASSIST WITH THE
VENUS DRAINAGE.
THE OUTCOMES ARE TREATMENT
SUCCESS OR FAILURE AT 7 DAYS.
SO DO KIDS SURVIVE OR NOT?
AND THEN HOW WELL DO THEY
SURVIVE?
ARE THEY VERY DAMAGED AND CAN WE
IDENTIFY SOME OTHER WAY OF
PICKING UP THE KIDS WITH
INCREASED BRAIN VOLUME BECAUSE
MRIs ARE NOT UCIBOLLITIOUS,
FAR FROM IT ON THE CONTINENT SO
OTHER BIOMARKERS EVER INCREASED
BRAIN VOLUME SHOULD WE IDENTIFY
SOMETHING SUCKER ASSESSESFUL
WOULD BE EASIER TO SCALE IT UP
IF WE DIDN'T HAVE TO RELY ON
MRIs.
SO PLAN A WAS TO ENROLL OVER 6
SEASONS AND RANDOMIZE A COUPLE
HUNDRED KIDS.
THEN WE RAN INTO CHALLENGES.
ONE WAS DECREASING PATIENTS WITH
CEREBRAL MALARIA PATIENTS COMING
INTO OUR HOSPITAL.
THAT'S A GOOD THING.
IT'S HARD NOT TO BE DELIGHT WIDE
THAT.
IT'S FRUSTRATING IF YOU'RE
ENROLLING THEM BUT IT'S GOOD
OVERALL AND THIS IS A SUCCESS OF
MALAWI'S PUBLIC HEALTH SYSTEM.
THE FIRST YEAR, THE ICU WAS
STILL UNDER CONSTRUCTION SO WE
COULDN'T START.
YEARS 2 AND 3 THE MALAWI
EQUIVALENT OF THE FDA WAS VERY
CAUTIOUS ABOUT IMPORTING THE
HYPERTONIC SALINE SO WE COULD
ONLY HAVE THE VENT ARM.
AND THEN IN YEAR 4, THE MRI
CRASHED AND WE COULDN'T FIX IT
BECAUSE OF COVID.
SO THAT WAS REALLY FRUSTRATING.
SO TO RESPOND TO THAT ALL, WE
DEVELOPED A REGIONAL REFERRAL
SYSTEM WHICH WAS A LOT OF FUN
BRINGING KIDS IN FROM ALL THE
HOSPITALS WITHIN AN HOUR'S
DRIVE.
WE ULTIMATELY PERSUADED MALAWI
MEDICINE AND POISONS AND
MEDICINES SALINE WE BOUGHT THIS
VERY FUN SMALL PURPLE MRI FROM A
COMPANY CALLED HYPER FINE WHICH
HAS BEEN FANTASTIC, AND WE
CHANGED THE STUDY DESIGN A
LITTLE BIT TO ALLOW US TO GET BY
WITH FEWER PATIENTS.
SO NOW WHERE WE ARE RIGHT NOW AS
WE SPEAK IS THAT WE'VE SCREENED
187 PATIENTS.
OF THOSE 50% HAVE HAD INCREASED
BRAIN VOLUME AND ALL THE
FAMILIES AGREED TO BE HAND
ONLYIZED.
SIXTEEN HAVE GONE TO USUAL CARE,
22 TO IMMEDIATE VENT LATTERY
SUPPORT AND 12 TO HYPERTONIC
SALINE ARM.
IT IS TOO EARLY TO KNOW IF ANY
OF THEM IS WORKING OR NOT
WORKING AND IN ORDER TO GET TO
AN ANSWER, WE JUST NEED TO
RANDOMIZE THE PATIENTS NEXT AND
WE WILL HAVE AN ANSWER 1 WAY OR
OTHER.
SO, JUST TO RECAP, WE STARTED
WITH THIS POPULATION OF CHILDREN
SOME OF WHOM REMAIN UNINFECTED,
SOME ARE INFECTED AND
ASYMPTOMATIC, SOME DEVELOP
UNCOMPLICATED MALARIA, A TINY
PROPORTION TO DEVELOP INTO A
COMA AND IN THAT GROUP, THERE
ARE SOME WHO ARE UNCONSCIOUS AND
INFECT WIDE MALARIA FOR REASONS
OTHER THAN MALARIA.
THOSE ARE THE RET-NEGATIVE KIDS
BUT OUR FOCUS HAS BEEN ON THE 1S
THAT ARE RETINOPATHY POSITIVE
AND ALONG THAT GROUP, ARE THE 1S
WITH THE HIGHEST INCREASE BRAIN
VOLUME BECAUSE THE VOOF THE
MORTALITY OCCURS IN THAT.
THIS IS AS YOU CAN SEE AN
EVOLVING STORY.
SO WATCH THIS SPACE.
KEEP OUR FINGERS CROSSED WE CAN
ENROLL 20 MORE PATIENTS.
THIS HAS TAKEN A LEAP OVER THE
YEARS.
WE'VE NEEDED PATHOLOGISTS,
RADIOLOGISTS AND
OPHTHALMOLOGISTS, STATISTICIANS,
AS WELL AS THE REGULAR
[INDISCERNIBLE] SO IT'S BEEN
QUITE A JOURNEY.
THIS IS THE [INDISCERNIBLE]
PARTY CELEBRATING WITH 1 OF OUR
SURVIVORS WE'RE HOPEFUL THAT AT
THE END OF THE CLINICAL TRIAL
WITH AN ANSWER TO OUR QUESTIONS
IN A YEAR.
AND I WOULD LIKE TO CONCLUDE
WITH 1 OF MY FAVORITE
[INDISCERNIBLE] PROVERBS:
[SPEAKING FOREIGN LANGUAGE ]
WHICH TRANSLATES TO, IT'S A
LITTLE ENIGMATIC.
IT TRANSLATES TO: THE 1 WHO
DIDN'T ASK ATE THE WAX.
NOT IMMEDIATELY OBVIOUS BUT THE
BACKGROUND STORY IS THAT A
PERSON WAS GIVEN A GIFT OF A JAR
OF HONEY WITH THE BEES WAX IN IT
AND HE DIDN'T KNOW WHAT IT WAS,
AND HE DIDN'T ASK ANYBODY WHAT
IT WAS AND HE JUST ATE THE WAX
AND DIDN'T ENJOY THE HONEY.
SO THIS SAY PROVERB THAT IS VERY
USEFUL FOR ILLICITTING QUESTIONS
FROM AN AUDIENCE, I USE IT JUST
ABOUT EVERY TIME WE DISCHARGE A
PATIENT FROM THE RESEARCH WARD
BAWSES WE HAVE A LOT OF
INFORMATION TO IMPART TO THE
MOM, TAKE THESE MEDICATIONS,
COME BACK ON SUCH AND SUCH DAY
IF THE CHILD IS SICK BEFORE
THEM, COME BACK ANY TIME, BLAH,
BLAH, BLAH AND WE SAY
[INDISCERNIBLE] AND ANY MORE
QUESTIONS AND THE MOTHER WOULD
SAY OH NO AND I WOULD SAY
[SPEAKING FOREIGN LANGUAGE ] AND
THEY LAUGH BECAUSE THEY THINK
HOW DID SHE KNOW THIS BUT THEN
THEY ASK A QUESTION OR 2, SO
IT'S A VERY SUCCESSFUL PROVERB
IN TERMS OF ELICITING QUESTIONS.
SO I WOULD LIKE TO STOP AT THIS
POINT AND I WOULD BE VERY HAPPY
TO TAKE QUESTIONS.
>>THANKS DR. TAYLOR.
THAT WAS A WONDERFUL LECTURE AND
THANK YOU SO MUCH FOR SHARING
YOUR LIFE A WORK WITH US.
WE LOOK FORWARD TO THE NEXT YEAR
AS YOU HAVE A LOT OF EXCITING
RESULTS.
>>LET'S HOPE SO.
>>YEAH.
>>I GUESS I CAN START WITH A
QUESTION AS WE WAIT FOR
QUESTIONS TO COME IN.
DURING YOUR EARLY TIME IN
MALAWI, WHAT TRIALS AND
TRIBULATIONS DID YOU HAVE IN
TERMS OF CULTURAL ACCLIMATION IN
MALAWI AND THEN ALSO TO DEVELOP
TRUST WITH THE MALAWIANS TO
ALLOW THEM TO DO RESEARCH WITH
YOU?
>>EXCELLENT QUESTION.
I WAS VERY FORTUNATE TO BE
ASSOCIATED WITH RIGHT FROM THE
DEBEGINNING WITH 2 HIGHLY
REVERED CLINICIANS.
DR. [INDISCERNIBLE] AND
DR. MALCOM [INDISCERNIBLE] SO
WHEN WE STARTED THERE WASN'T A
MEDICAL SCHOOL IN MALAWI, AND
THE JOKE WAS THERE WERE MORE
MALAWI ANS BEING DOCTORS IN
MANCHESTER THAN IN MALAWI,
PEOPLE WOULD LEAVE FOR MEDICAL
TRAINING AND VERY FEW CAME BACK.
SO THERE WEREN'T PEOPLE WHO
REALLY HAD ANY MATTER IN THE
CHOICE OF THEIR CLINICAL CARE,
WE WERE IT.
SO I THINK TO A LARGE EXTENT,
THE PROOF IS IN THE PUDDING AND
PEOPLE WOULD SEE THESE KIDDINGS
GET BETTER AND GO HOME AND THAT
WAS THE--PROBABLY THE MOST
IMPORTANT DETERMINANT OF THEIR
TRUST IN US.
SO WE STARTED IN 86 AND THEN THE
MEDICAL SCHOOL STARTED IN 91 AND
IT RAMPED UP SLOWLY, 4 OR 5
GRADUATES A YEAR AND THEN 10 AND
25 AND NOW THERE ARE A LOT AND
AT THIS POINT, IT'S VERY EASY TO
BE PART OF A DEAM OF MIXED
NATIONALILITYS THAT ARE LOOKING
AFTER PATIENTS AND HONESTLY THE
CULTURAL ASPECTS OF IT HAVE
BECOME SO MUCH CLEARER NOW THAT
WE HAVE MALAWIANS WHO ARE
WORKING WITH US WHO CAN EXPLAIN
A LOT OF THE NUANCES SO IT'S
REALLY BEEN FASCINATING.
>>THAT'S GREAT.
SO TO FOLLOW UP ON THAT I KNOW
THE OFFICIAL LANGUAGE IN MALAWI
IS ENGLISH BUT UNDOUBTEDLY WITH
SUCH ENRICHMENT OF DIFFERENT
LANGUAGES THERE, I GUESS WHAT
LANGUAGES HAVE YOU PICKED UP?
>>O NO, SO THE FIRST COUPLE
YEARS I HAD A TUTOR AND I WORKED
ASSIDUOUSLY BUT AS YOU SAY,
WHILE THERE ARE 2 OFFICIAL
LANGUAGES, [INDISCERNIBLE] AND
ENGLISH AND EVERYONE WHO HAS
BEEN BEYOND SECOND ISARY SCHOOL
SPEAKS ENGLISH AND I WAS ALWAYS
AT A CENTRAL HOSPITAL SO I WAS
NEVER FORCED TO SPEAK
[INDISCERNIBLE].
SO I HAVE VERY RUDIMENTARY
[INDISCERNIBLE] AND THAT'S 1 OF
THE REASONS WHY I TRY TO LEARN
THE PROVERBS BECAUSE IF YOU DROP
THE RIGHT PROVERB IN THE RIGHT
MOMENT, PEOPLE ARE LIKE WHOA,
SHE KNOWS [INDISCERNIBLE] WHICH
I DON'T REALLY BUT I KNOW--I
KNOW TIMING OF THE MOMENT FOR
USING A PROVERB AND THERE ARE
SOME WORDS WHICH ARE EXTREMELY
USEFUL.
THERE IS--THERE ARE WORDS THAT
ARE REALLY FUN SO FOR INSTANCE,
THE WORD THAT MEANS TO BE COLD
IS [SPEAKING FOREIGN LANGUAGE ]
IT SOUNDS LIKE YOU'RE SHIVERING
WHEN YOU SAY IT.
THE WORD FOR HIPPO SOUNDS LIKE A
HIPPO IN THE WATER IT'S
[SPEAKING FOREIGN LANGUAGE ] BUT
THE 1 WORD THAT HAS REALLY
HELPED, THERE A SINGLE WORD, 1
SINGLE WORD IN [INDISCERNIBLE]
WHICH MEANS THAT YOU KNOW WHAT
HAS HIT THE FAN AND YOU CAN SAY
IT ALL IN 1 WORD AND THE WORD
IS] SPEAKING FOREIGN LANGUAGE ]
AND HONESTLY IF IT'S A CRAZY DAY
ON THE RESEARCH WARD, THE
PATIENTS ARE REALLY SICK,
THEY'RE SEIZING RIGHT AND LEFT
AND YOU CAN'T GET IVs, IF YOU
GO [SPEAKING FOREIGN LANGUAGE ],
EVERYBODY LAUGHS AND IT BREAKS
THE TENSION AND EVERYBODY MOVES
ON.
SO IT'S STRATEGIC WHAT I'VE
LEARNED.
>>THAT'S GREAT.
SO I GUESS ALSO, TOO, DURING MY
INTRODUCTION, YOU KNOW YOU SET
UP A NICE COURSE BACK IN
MICHIGAN TO TRAIN INDIVIDUALS.
YOU ALSO ALLUDED TO A MEDICAL
SCHOOL IN MALAWI, SO DO THE
STUDENTS IN THE MEDICAL SCHOOL
IN MALAWI ROTATE WITH YOU WHILE
YOU'RE OUT THERE, YOU KNOW
DURING YOUR TIME OUT THERE?
>>SO THE MSU STUDENTS ARE NOT
WITH ME PER SE.
IT'S KIND OF FEAST OR FAMINE ON
THE RESEARCH WARD, YOU NEVER
KNOW WHEN IT'LL BE BIEWZY OR
QUIET AND THE MSU STUDENTS ARE
SCATTERED AROUND THE HOSPITAL
AND THEY DO WORK SIDE BY SIDE
WITH THE MALAWI, AND THEY'RE
MALAWI AND COUNTERPARTS AND A
LOT OF SOCIALIZING WE ALL SHARE
1 BIG HOUSE AND THE MALAWI
STUDENTS ARE OFTEN OVER FOR
DINNER WITH THE MSU STUDENTS SO
THATIA BEEN EXCELLENT.
>>THAT SOUNDS LIKE A GREAT
EXPERIENCE.
SO WE'VE REACHED THE TOP OF OUR
HOUR AND I WANT TO THANK YOU FOR
GIVING US THIS EXCELLENT TALK
TODAY AND I ALSO WANT TO THANK
OUR AUDIENCE.
THANK YOU VERY MUCH AND STAY
WELL AND WE WILL SEE YOU NEXT
TIME.