Dengue and Chikungunya in Our Backyard: Preventing Aedes Mosquito-Borne Diseases

Dengue and Chikungunya in Our Backyard: Preventing Aedes Mosquito-Borne Diseases

Dengue and Chikungunya in Our Backyard: Preventing Aedes Mosquito-Borne Diseases

By Bryan Wright 0 Comment August 16, 2019


GOOD AFTERNOON.
A SEE A FEW MORE PEOPLE ARE COMING IN, BUT I’M HOPING
THEY’LL TAKE THEIR SEATS. I’M DR. PHOEBE THORPE.
IT’S MY PLEASURE TO WELCOME YOU TO CDC PUBLIC HEALTH GRAND ROUNDS FOR MAY 2015, DENGUE AND CHIKUNGUNYA IN OUR BACKYARD.
PUBLIC HEALTH GRAND ROUNDS HAS CONTINUING MEDICAL EDUCATION
CREDITS — FOR PHYSICIANS, NURSES, PHARMACIST AND OTHERS. PLEASE CHECK OUR WEBSITE TO FIND
MORE DETAILS. IN ADDITION TO THE CMEs
AVAILABLE, CDC HAS ALSO DEVELOPED A DENGUE CASE
MANAGEMENT TOOL TO HELP HEALTH CARE PROVIDERS TREAT THEIR
PATIENTS WITH DENGUE. THEY ALSO HAVE CME CREDITS
THERE, AND I WOULD CHECK IT OUT. IN ADDITION TO OUR WEBSITE, WE
ALSO HAVE SOCIAL MEDIA SITES, AND WE HAVE A FEATURED VIDEO
SEGMENT CALLED BEYOND THE DATA THAT WILL BE POSTED SHORTLY
AFTER TODAY’S SESSION. WE ARE ALSO TWEETING TODAY.
YOU CAN FOLLOW US @CDCNCEZID BY USING #CDCGRANDROUNDS.
THANK YOU. WE HAVE PARTNERED WITH THE CDC
PUBLIC HEALTH LIBRARY FOR RELATED ARTICLES.
THE FULL LISTING IS AVAILABLE AT THE WEBSITE,
CDC.GOV/LIBRARY/SCICLIPS. TO GIVE YOU A SENSE OF HOW
QUICKLY THESE DISEASES CAN SPREAD, I WANT TO SHARE WITH YOU
A RECENT OUTBREAK OF CHIKUNGUNYA IN PUERTO RICO.
THE BLUE INDICATES RESIDENTS OF A REPORTED CASE.
AS YOU CAN SEE, IN THREE SHORT MONTHS, CHIKUNGUNYA SPREAD
WIDELY WITH OVER 10,000 SUSPECTED CASES REPORTED AND
ALMOST 2,000 CASES TESTED POSITIVE.
HERE IS A PREVIEW OF THE UPCOMING PUBLIC HEALTH GRAND
ROUNDS SESSIONS. PLEASE JOIN US.
IN ADDITION TO OUR OUTSTANDING FEATURED SPEAKERS, I’D ALSO LIKE
TO TAKE A MOMENT TO ACKNOWLEDGE THE IMPORTANT CONTRIBUTIONS OF
THE INDIVIDUALS LISTED HERE. THANK YOU.
AND NOW A FEW WORDS FROM CDC’S DIRECTOR DR. TOM FRIEDEN.>>MOSQUITO-BORNE DISEASES KILL AS MANY AS 750,000 PEOPLE EVERY
YEAR, MAKING MOSQUITOS THE DEADLIEST ANIMAL ON THE PLANET
WITH THE POSSIBLE EXCEPTION OF HUMAN BEINGS.
BEFORE 1970, ONLY NINE COUNTRIES HAD EXPERIENCED SEVERE DENGUE
EPIDEMICS. NOW THE DISEASE IS ENDEMIC IN
MORE THAN 100 COUNTRIES AND AS MANY AS 3.6 BILLION PEOPLE, 40%
OF THE WORLD’S POPULATION, ARE POTENTIALLY AT RISK FOR DENGUE.
CHIKUNGUNYA IS AN EMERGING MOSQUITO-BORNE THREAT THAT’S NOW
ON OUR DOORSTEP, HAVING REACHED THE CARIBBEAN IN LATE 2013.
SINCE THEN, ALMOST 1.4 MILLION CONFIRMED OR SUSPECTED CASES
HAVE BEEN REPORTED AFFECTING 44 COUNTRIES AND TERRITORIES
THROUGHOUT THE AMERICAS. AEDES MOSQUITOS TRANSMIT BOTH
THESE VIRUSES AS WELL AS YELLOW FEVER. ONE WAY WE CAN REDUCE THE GLOBAL BURDEN AND MORTALITY FROM DENGUE
IS WITH AN EFFECTIVE VACCINE. THERE’S PROMISING RESEARCH ON
DENGUE VACCINES THAT WILL BE PRESENTED TODAY, INCLUDING ABOUT
A CANDIDATE VACCINE DEVELOPED AT CDC AT OUR FT. COLLINS CAMPUS.
THERE ARE ALSO PROMISING ADVANCES TO IMPROVE THE CONTROL
OF AEDES MOSQUITOS. IF EFFECTIVE, THESE NEW
TECHNOLOGIES COULD HELP REDUCE THE BURDEN NOT ONLY OF DENGUE
BUT ALSO OF OTHER AEDES-BORNE VIRUSES.
FOR THOSE WHO BECOME INFECTED WITH DENGUE, WE NEED BETTER
MANAGEMENT OF THEIR CARE. CURRENT TREATMENT GUIDELINES
DEVELOPED WITH OUR PARTNERS AT W.H.O. CAN NEARLY ELIMINATE
DEATH FROM DENGUE. AS MANY OF YOU KNOW, CDC HAS OUR
ORIGINS IN MOSQUITOS CONTROL. THIS REMAINS IMPORTANT WORK.
THROUGH PLANNING AND COLLABORATION, NEW VECTOR
CONTROL MEASURES, VACCINES, AND PROPER CLINICAL CASE MANAGEMENT,
WE CAN REDUCE THE BURDEN OF DENGUE AND OTHER MOSQUITOS-BORNE
DISEASES. THANK YOU FOR THE GREAT WORK
DONE IN THIS AND OTHER AREAS.>>AND NOW FOR OUR FIRST
SPEAKER, DR. MARC FISCHER.>>THANK YOU, AND GOOD
AFTERNOON. AEDES ARE MOSQUITOS SPECIES OF
GREAT PUBLIC HEALTH IMPORTANCE. AEDES AEGYPTI IS THE MAJOR
VECTOR. TAKEN TOGETHER, THESE VIRUSES
ACCOUNT FOR ALMOST 100 MILLION CASES OF MOSQUITOS-BORNE
DISEASES PER YEAR. AEDES AEGYPTI AND AEDES
ALBOPICTUS LIVE IN AND AROUND HUMAN HOUSEHOLDS.
THEIR PEAK FEEDING TIME IS DURING THE DAY. THE FEMALES BITE INDOORS.
THESE MAPS SHOW THE APPROXIMATE GEOGRAPHIC DISTRIBUTION OF AEDES
MOSQUITOS GLOBALLY AND IN THE UNITED STATES.
BOTH SPECIES ARE WIDELY DISTRIBUTED THROUGHOUT TROPICAL
AREAS IN THE AMERICAS, AFRICA, ASIA, AND OCEANIA.
AEDES MOSQUITOS-BORNE VIRUSES HAVE TWO PRIMARY TRANSMISSION
CYCLES. IN THE SYLVATIC CYCLE, VIRUSES
ARE MAINTAINED BETWEEN NON-HUMAN PRIMATES AND SPECIES IN AND
AROUND THE JUNGLE. IN THE EPIDEMIC OR URBAN CYCLE,
HUMANS ARE THE AMPLIFYING HOST AND VIRUSES TRANSMITTED DIRECTLY
FROM HUMANS TO MOSQUITOS TO HUMANS.
DENGUE IS CAUSED BY INFECTION WITH ANY OF FOUR RELATED
VIRUSES. AEDES IS THE PRIMARY VECTOR FOR
ALL FOUR OF THESE. HUMANS ARE THE PRIMARY
AMPLIFYING HOST. THE VIRUS HAVE ADAPTED SO THAT
A SYLVATIC CYCLE IS NO LONGER NEEDED TO MAINTAIN THE VIRUS IN
NATURE. THIS MAP SHOWS THE APPROXIMATE
DISTRIBUTION OF DENGUE VIRUS. SPORADIC OUTBREAKS HAVE ALSO
OCCURRED IN SOUTHERN EUROPE AND IN HAWAII, TEXAS, AND FLORIDA.
DENGUE IS THE MOST IMPORTANT MOSQUITOS-BORNE VIRAL DISEASE
GLOBALLY. IN THE LAST 50 YEARS, THE
REPORTED INCIDENTS HAS INCREASED 30 FOLD WITH EXPANSION TO NEW
AREAS. APPROXIMATELY 25% OF PEOPLE
INFECTED WITH DENGUE VIRUS DEVELOP CLINICAL SYMPTOMS.
ALTHOUGH SURVEILLANCE DATA ARE LIMITED, A RECENTLY PUBLISHED
MODEL ESTIMATED THERE WERE 96 MILLION DENGUE DISEASE CASES
WORLDWIDE IN 2010, INCLUDING 67 MILLION CASES IN ASIA, 16
MILLION IN AFRICA, AND 13 MILLION IN THE AMERICAS.
DENGUE IS AN ACUTE ILLNESS WHICH OFTEN INCLUDES HEADACHE,
MYALGIA, OR MINOR BLEEDING. SUBSEQUENT INFECTION WITH A
DIFFERENT TYPE OF DENGUE VIRUS INCREASES THE RISK FOR SEVERE
DISEASE. THE CASE FATALITY CAN BE AS HIGH
AS 10% BUT PROPER CASE MANAGEMENT REDUCES MORTALITY TO
LESS THAN 1%. CHIKUNGUNYA VIRUS IS AN ALPHA
VIRUS AN EMERGING CAUSE OF MOSQUITOS-BORNE DISEASE.
HUMANS ARE THE PRIMARY AMPLIFYING HOST FOR CHIKUNGUNYA
VIRUS DURING OUTBREAKS. SYLVATIC TRANSMISSION OCCURS IN
NON-HUMAN PRIMATES IN AFRICA. THIS MAP SHOWS COUNTRIES THAT
HAVE EVER REPORTED LOCAL TRANSMISSION OF CHIKUNGUNYA
VIRUS. THE VIRUS WAS FIRST ISOLATED IN
TANZANIA IN THE 1950s. OVER THE NEXT 50 YEARS,
OUTBREAKS OCCURRED SPORADICALLY IN PARTS OF AFRICA AND ASIA.
THEN BEGINNING IN 2004, THERE WERE LARGE EXPANSION IN THE
NUMBER OF DISEASE CASES REPORTED FROM INDIA AND ISLANDS IN THE
INDIAN AND PACIFIC OCEANS. IMPORTED CASES ALSO RESULTED IN
OUTBREAKS IN EUROPE. IN LATE 2013, THE FIRST LOCAL
TRANSMISSION OF CHIKUNGUNYA VIRUS IN THE AMERICAS WAS
IDENTIFIED IN THE CARIBBEAN. OVER THE NEXT 18 MONTHS, THE
VIRUS SPREAD THROUGHOUT MUCH OF THE WESTERN HEMISPHERE, CAUSED
OUTBREAKS ON MANY PACIFIC ISLANDS.
CHIKUNGUNYA VIRUS OFTEN CAUSES LARGE OUTBREAKS WITH HIGH
INFECTION RATES AFFECTING MORE THAN A THIRD OF THE SUSCEPTIBLE
POPULATION. THE MAJORITY OF INFECTED PEOPLE
DEVELOP CLINICAL SYMPTOMS. IN 2014, MORE THAN A MILLION
CASES OF CHIKUNGUNYA WERE REPORTED WORLDWIDE WITH MOST
OCCURRING IN THE CARIBBEAN AND CENTRAL AND SOUTH AMERICA.
THE PRIMARY CLINICAL SYMPTOMS OF CHIKUNGUNYA VIRUS INFECTION ARE
FEVER AND POLYARTHRALGIA. THE ACUTE SYMPTOMS TYPICALLY
RESOLVE IN SEVEN TO TEN DAYS. HOWEVER, SOME PATIENTS HAVE
PERSISTENT OR RECURRENT PROBLEMS FOR MONTHS FOLLOWING THEIR ACUTE
ILLNESS. THE OVERALL CASE FATALITY RATE
IS LESS THAN 1% AND OCCURRED MOSTLY IN OLDER ADULTS WITH
UNDERLYING MEDICAL CONDITIONS. YELLOW FEVER VIRUS IS ANOTHER
MOSQUITOS-BORNE VIRUS. MOST HUMAN INFECTIONS OCCUR AS A
RESULT OF SYLVATIC TRANSMISSION. URBAN OUTBREAKS OCCUR
PERIODICALLY AND MOSTLY IN WEST AFRICA.
AEDES IS THE PRIMARY VECTOR DURING THESE URBAN OUTBREAKS.
YELLOW FEVER VIRUS IS DISTRIBUTED THROUGHOUT
SUBSAHARAN AFRICA AND TROPICAL AMERICA, ALTHOUGH OUTBREAKS
OCCURRED IN EUROPE UNTIL THE EARLY 1900s.
LOCAL TRANSMISSION HAS NOT BEEN REPORTED IN THESE AREAS FOR
DECADES. LOCAL TRANSMISSION HAS NEVER
BEEN IDENTIFIED IN ASIA OR AUSTRALIA.
HOWEVER, THESE REGIONS ARE AT RISK FOR IMPORTATION AND MANY OF
THEIR URBAN AREAS HAVE AEDES AND SUSCEPTIBLE HUMAN POPULATIONS.
DURING URBAN OUTBREAKS, UP TO 30% OF THE SUSCEPTIBLE
POPULATION MAY BE INFECTED WITH YELLOW FEVER VIRUS, BUT ONLY 10%
TO 20% DEVELOP CLINICAL DISEASE. W.H.O. ESTIMATES THAT 200,000
CASES OF YELLOW FEVER OCCUR ANNUALLY WORLDWIDE WITH 85% OF
REPORTED CASES OCCURRING IN SUBSAHARAN AFRICA.
YELLOW FEVER IS AN ACUTE FEBRILE ILLNESS PRESENTING WITH
HEADACHE, MYALGIA, VOMITING. UP TO 15% OF SYMPTOMATIC
PATIENTS DEVELOP SEVERE DISEASE WITH JAUNDICE, HEMORRHAGE, OR
MULTI-ORGAN FAILURE. CASE FATALITY IS 20% TO 50% IN PATIENTS WITH SEVERE DISEASE.
ZIKA IS AN EMERGING MOSQUITOS-BORNE VIRUS.
AEDES IS THE PRIMARY VECTOR. LIKE WITH CHIKUNGUNYA, HUMANS
ARE THE PRIMARY AMPLIFYING HOST FOR ZIKA VIRUS DURING OUTBREAKS.
SYLVATIC TRANSMISSION IN NON-HUMAN PRIMATES OCCURRED IN
AFRICA, BUT THE ROLE OF OTHER ANIMALS IN MAINTAINING THE VIRUS
IS NOT KNOWN. ZIKA VIRUS WAS FIRST IDENTIFIED
IN UGANDA IN 1947. OVER THE NEXT 60 YEARS, STUDIES
SUGGESTED THE VIRUS WAS PRESENT IN MANY AFRICAN AND ASIAN
COUNTRIES. HOWEVER, LESS THAN TEN HUMAN
DISEASE CASES WERE REPORTED WORLDWIDE.
IN 2007, THE FIRST OUTBREAK OF ZIKA VIRUS WAS IDENTIFIED IN
MICRONEESIA. SINCE THEN, OUTBREAKS HAVE
INCREASINGLY BEEN RECOGNIZED IN SOUTHEAST ASIA AND THE WESTERN
PACIFIC. ZIKA VIRUS WILL LIKELY CONTINUE
TO SPREAD TO UNAFFECTED AREAS WITH AEDES.
LAST WEEK THE PANAMERICAN HEALTH ORGANIZATION REPORTED THE FIRST
CASES IN BRAZIL. THE 2007 OUTBREAK RESULTED IN AN
ESTIMATED 900 DISEASE CASES IN A POPULATION OF LESS THAN 8,000
PEOPLE. BASED ON A SURVEY, 73% OF THE
POPULATION WAS INFECTED AND 18% OF THOSE INFECTED DEVELOPED
CLINICAL ILLNESS. OVER THE PAST TWO YEARS, MORE
THAN 30,000 SUSPECTED CASES OF ZIKA VIRUS DISEASE HAVE BEEN
REPORTED FROM FRENCH POLYNESIA AND OTHER PACIFIC ISLANDS.
IN GENERAL, ZIKA VIRUS INFECTION CAUSED A MILD ACUTE ILLNESS
CHARACTERIZED BY A RASH. FEVERS ARE LOW GRADE AND 25% TO 35% OF PATIENTS MAY BE AFEBRILE. THERE HAVE BEEN A FEW REPORTS OF
POSSIBLE OTHER SEVERE DISEASE MANIFESTATIONS.
NO DEATHS HAVE BEEN REPORTED. DIAGNOSTIC TESTING IS SIMILAR
FOR DENGUE, CHIKUNGUNYA, YELLOW FEVER, AND ZIKA VIRUS
INFECTIONS. RT-PCR CAN DEFECT VIRAL RNA IN
BLOOD. NEUTRALIZING ANTIBODY TESTING
SHOULD BE PERFORMED TO CONFIRM RESULTS AND DISTINGUISH
INFECTIONS DUE TO CLOSELY RELATED VIRUSES.
FINALLY, FOR FATAL CASES, RTPCR AND STAINING CAN BE PERFORMED ON
TISSUES OBTAINED AT AUTOPSY. THERE ARE NO SPECIFIC ANTI-VIRAL
THERAPIES FOR ANY OF THESE INFECTIONS.
TREATMENT IS SUPPORTIVE AND INCLUDES FLUIDS.
PATIENTS’ HYDRATION STATUS SHOULD BE ASSESSED AND OTHER
CONDITIONS SUCH AS MALARIA AND BACTERIAL INFECTION SHOULD BE
EVALUATED FOR AND TREATED AS NEEDED.
ALL SUSPECTED CASES SHOULD BE MANAGED AS IF THEY HAVE DENGUE
UNTIL IT HAS BEEN RULED OUT. THERE ARE NO AVAILABLE VACCINES
TO PREVENT DENGUE, CHIKUNGUNYA, OR ZIKA INFECTIONS.
DENGUE VACCINES HAVE ADVANCED TO PHASE THREE CLINICAL TRIALS, BUT
DEVELOPMENT IS COMPLICATED BY THE NEED TO PROTECT AGAINST ALL
FOUR VIRUS TYPES. SEVERAL CHIKUNGUNYA VACCINES
HAVE COMPLETED PHASE ONE OR TWO SAFETY STUDIES.
LIVE ATTENUATED YELLOW FEVER VACCINE HAS BEEN LICENSED AND
AVAILABLE SINCE THE 1930s AND IS WIDELY USED IN ENDEMIC COUNTRIES
AND TRAVELERS. FROM 2007 THROUGH 2012, YELLOW
FEVER VACCINATION CAMPAIGNS LED TO AN ESTIMATED 27% REDUCTION IN
YELLOW FEVER CASES IN 11 ENDEMIC COUNTRIES IN WEST AFRICA.
OTHER THAN YELLOW FEVER VACCINE, THE BEST WAY TO PREVENT
AEDES-BORNE DISEASES IS TO REDUCE MOSQUITOS EXPOSURE.
AT A COMMUNITY LEVEL, MOSQUITOS HABITAT CONTROL AND APPLICATIONS
OF LARVACIDE MAY REDUCE SPREAD. HOWEVER, CONTROLLING AEDES
REQUIRES SUBSTANTIAL RESOURCES AND IS DIFFICULT TO SUSTAIN AT
EFFECTIVE LEVELS. FOR TRAVELERS AND OTHER
POPULATIONS WHERE FEASIBLE, USING AIR-CONDITIONING, HAVING
SCREENS ON WINDOWS AND DOORS, USING INSECT REPELLANT, AND
WEARING LONG SLEEVES AND PANTS CAN LIMIT MOSQUITOS EXPOSURE.
FINALLY, PROTECTING PEOPLE WHO ARE ALREADY INFECTED FROM
FURTHER MOSQUITOS EXPOSURE DURING THEIR FIRST WEEK OF
ILLNESS WILL PREVENT THEM FROM INFECTING NEW MOSQUITOS AND
CONTRIBUTING TO THE SPREAD OF THE VIRUS.
IN SUMMARY, AEDES IS THE MOST IMPORTANT VECTOR FOR DENGUE,
CHIKUNGUNYA, YELLOW FEVER, AND ZIKA VIRUSES DURING OUTBREAKS.
IN RECENT YEARS, THE INCIDENTS OF THESE AEDES-BORNE DISEASES
HAS INCREASED, AND THE VIRUSES HAVE SPREAD TO NEW AREAS.
THESE VIRUSES ARE FOUND IN OVERLAPPING GEOGRAPHIC AREAS AND
HAVE SIMILAR CLINICAL FEATURES. THERE ARE NO ANTIVIRAL THERAPIES
TO TREAT THESE DISEASES, BUT PROPER CLINICAL MANAGEMENT CAN
REDUCE DENGUE MORTALITY. YELLOW FEVER VACCINE IS WIDELY
USED AND EFFECTIVE. DENGUE AND CHIKUNGUNYA VACCINES
ARE IN DEVELOPMENT. UNTIL THOSE ARE AVAILABLE,
REDUCING MOSQUITOS EXPOSURE IS THE BEST PREVENTIVE MEASURE, BUT
CURRENT VECTOR CONTROL OPTIONS ARE RESOURCE INTENSIVE AND
DIFFICULT TO SUSTAIN AT EFFECTIVE LEVELS.
THANK YOU. [ APPLAUSE ]
NOW I’D LIKE TO INTRODUCE DR. DR. THOMAS SCOTT FROM THE UNIVERSITY OF CALIFORNIA DAVIS, WHO WILL BE OUR NEXT SPEAKER.>>AEDES DEVELOP, AND THE ADULTS LIVE IN CLOSE ASSOCIATION WITH
HUMANS. STORED WATER, DISCARDED ITEMS
THAT ACCUMULATE WATER CREATE ABUNDANT HABITATS FOR THE
DEVELOPMENT. THIS IS AN INCREASING PROBLEM IN
RAPIDLY GROWING URBAN SETTINGS THAT LACK ADEQUATE WATER
SUPPLIES, SOLID WASTE DISPOSAL, AND HAVE SUBSTANDARD HOUSING.
THESE CONDITIONS ARE OFTEN ASSOCIATED WITH HIGH HUMAN
POPULATION DENSITIES THAT ARE IN CLOSE, BITING CONTACT WITH HIGH
DENSITIES OF AEDES AEGYPTI. THIS CREATES A SITUATION WHERE
THERE’S A HIGH POTENTIAL FOR VIRUS TRANSMISSION.
FEMALE AEDES AEGYPTI LAY THEIR EGGS IN WATER CONTAINERS.
APPROXIMATELY ONE WEEK LATER, EGGS HATCH.
THE ADULTS REST INSIDE OF HOUSES.
MOST OFTEN IN QUIET, DARK PLACES LIKE CLOSETS OR CLOTHES RACKS.
AN IMPORTANT FEATURE OF THE ECOLOGY IS ADULTS TEND NOT TO
FLY VERY FAR, OFTEN LIVING THEIR ENTIRE LIFE IN A SINGLE HOUSE.
DURING THEIR LIFETIME, THEY SELDOM MOVE MORE THAN 100 METERS
FROM THEIR INITIAL RESTING SITE. OTHER IMPORTANT CHARACTERISTICS
COMPARED TO OTHER MOSQUITOS, THIS SPECIES HAS LOW POPULATION
DENSITY, OFTEN FEWER THAN TEN ADULT FEMALES PER HOUSE.
AND THE DISTRIBUTION OF THEIR POPULATIONS TENDS TO BE FOCAL
AND DYNAMIC SO THAT OVER TIME THERE ARE CHANGES IN THE NUMBER
OF MOSQUITOS PER HOUSE AND CHANGES IN THE DISTRIBUTION OF
INFESTED HOUSES. ONLY FEMALE AEDES AEGYPTI FEED
ON BLOOD, WHICH THEY REQUIRE TO DEVELOP THEIR EGGS.
THEY PREFER TO FEED ON HUMANS AND BITE DURING THE DAYTIME WHEN
PEOPLE ARE ENGAGED IN THEIR DAILY ACTIVITY PATTERNS.
SO COMPARED TO MANY OTHER MOSQUITOS SPECIES, AEDES AEGYPTI
BITES FREQUENTLY, WHICH INCREASES THEIR FITNESS BUT ALSO
EPIDEMIOLOLOGICALLY, FREQUENT HUMAN BITING IS ONE OF THE MOST
IMPORTANT REASONS WHY THIS IS SUCH AN EFFICIENT VECTOR OF
VIRUSES. BITING A HUMAN HOST IS REQUIRED
FOR VIRUS TRANSMISSION. AEDES AEGYPTI BITING PATTERNS
FACILITATE TRANSMISSION. SOME PEOPLE ARE BITTEN MORE THAN
OTHERS, AND FREQUENT HUMAN CONTACT CAN FACILITATE EXPLOSIVE
EPIDEMIC. BECAUSE THEY LIVE, FREQUENTLY
BITE, REPRODUCE IN CLOSE ASSOCIATION WITH HUMANS,
EPIDEMICS CAN OCCUR EVEN WHEN AEDES AEGYPTI POPULATIONS ARE
LOW. VECTOR CONTROL FOR AEDES
AEGYPTI-BORNE DISEASE AIMS TO REDUCE ADULT FEMALE POPULATIONS,
REDUCE THE HUMAN BITING RATE, AND REDUCE THE NUMBER OF
INFECTIOUS MOSQUITOS. FOR SUSTAINED REDUCTIONS IN
HUMAN INFECTION AND DISEASE, VECTOR CONTROL NEEDS TO MAINTAIN
REDUCTIONS IN MOSQUITOS POPULATIONS BELOW THE LEVELS
THAT ARE REQUIRED FOR VIRUS TRANSMISSION.
BUT DEFINING WHAT THOSE ENTOMOLOGICAL THRESHOLDS ARE HAS
BEEN A DIFFICULT THING TO DO. IN THE PAST, ENTOMOLOGICAL
INDICES BASED ON LARVAL MOSQUITOS WERE USED TO REDUCE
THE RISK OF A PERSON GETTING INFECTED.
WE NOW KNOW THEY DO NOT CORRELATE WELL WITH HUMAN
INFECTION RISK. CONSEQUENTLY, THERE’S BEEN A
SHIFT TO ADULT MOSQUITOS. BUT THAT REQUIRES UNDERSTANDING
OF COMPLEX RELATIONSHIPS AMONG THINGS LIKE THE SUSCEPTIBILITY
OF THE HUMAN POPULATION, SO HERD IMMUNITY, CONTACT RATES BETWEEN
PEOPLE AND MOSQUITOS, HUMAN DENSITY, THE INTRODUCTION OF
NOVEL VIRUSES, AND WEATHER. WITH THESE KINDS OF CONSTRAINTS
IN MIND, WHAT ARE THE VECTOR CONTROL OPTIONS?
OF THE METHODS CURRENTLY AVAILABLE, LARVAL CONTROL HAS
BEEN DIFFICULT TO USE IN A WAY THAT SUSTAINS EPIDEMIOLOGIC
IMPACT. THE MAJOR CATEGORIES CURRENTLY
AVAILABLE FOR LARVAL CONTROL INCLUDE CONTAINER CLEANING,
MANIPULATION AND TREATMENT, SOCIAL CAMPAIGNS THAT ARE BASED
ON EDUCATION, REDUCTION OF AQUATIC MOSQUITOS DEVELOPMENT
SITES, AND FINES AND PENALTIES IF LARVA OR PUPA ARE FOUND ON
THE PREMISE. FOR ADULT CONTROL, CURRENTLY
AVAILABLE METHODS INCLUDE SPACE SPRAY, WHICH NEEDS TO BE DONE
INSIDE THE HOUSE WHERE AEDES AEGYPTI REST.
OUTDOOR SPRAY OF INSECTICIDE FROM TRUCKS OR PLANES IS
INEFFECTIVE BECAUSE IT DOESN’T REACH THE MOSQUITOS THAT ARE
INSIDE HUMAN HABITATIONS. INDOOR RESIDUAL OR LONG-LASTING
INSECTICIDES THAT ARE SPRAYED ON SURFACES INSIDE HOUSES CAN BE
EFFECTIVE, AS PERSONAL PROTECTION, REPELLANTS.
BUT FOR ALL THE CHEMICAL-BASED OPTIONS, RESISTANCE TO
INSECTICIDE IS A THREAT AND IT’S A GROWING PROBLEM.
AMONG THE VARIOUS INTERVENTIONS THAT ARE CURRENTLY UNDER
DEVELOPMENT, THE FOUR MOST PROMISING INCLUDE RELEASE OF
INSECTS WHICH AIMS TO REDUCE MOSQUITOS POPULATIONS.
INFECTION WITH THE BACTERIA TO REDUCE MOSQUITOS’ CAPACITY TO
TRANSMIT VIRUS. AND NEW INSECTICIDES THAT ARE
EFFECTIVE AGAINST RESISTANT MOSQUITOS POPULATIONS.
THERE ARE TWO STRATEGIES. THE FIRST RENDERS THE ADULT
FEMALE FLIGHTLESS. MALES ARE RELEASED INTO THE
FIELD WHERE THEY MATE WITH WILD-TYPE FEMALES.
THE HETEROZYGOTE FEMALE CANNOT FLY, SO THEY CAN’T MATE, CAN’T
BITE A HUMAN, AND THEREFORE THEY CAN’T TRANSMIT THE VIRUS.
THESE HETEROZYGOUS DIE. THE SONS, HOWEVER, CAN FLY,
MATE, AND PASS ON THE FEMALE-SPECIFIC TRAIT TO THEIR
OFFSPRING. THE SECOND STRATEGY, MALES THAT
CAUSE LATE-ACTING LETHALITY ARE RELEASED INTO THE FIELD WHERE
THEY, TOO, MATE WITH WILD-TYPE FEMALES.
THE MALES AND FEMALE DIE AS PUPAE OR EARLY-STAGE ADULTS.
THIS APPROACH HAS UNDERGONE SAFETY TESTING AND FIELD TRIALS
WITH ENTOMOLOGICAL OUTCOMES IN MALAYSIA, THE CAYMAN ISLANDS,
AND BRAZIL. THE WOLBACHIA IS AN
ENDOSYMBIOTIC BACTERIA. THE FEMALE PASS THE BACTERIA ON,
AND INFECTED MOSQUITOS ARE ABOUT TWO-THIRDS TO THREE-QUARTERS
LESS LIKELY TO BECOME INFECTED WITH AND TRANSMIT DENGUE VIRUS.
THIS STRATEGY INFEARS WITH THE MOSQUITOS’ ABILITY TO TRANSMIT
THE VIRUS. THE OFFSPRING FROM INFECTED
FEMALES ARE FAVORED AND THE BACTERIA SPREAD THROUGH THE
MOSQUITOS POPULATIONS. FIELD TRIALS WITH RELEASE
INFECTED MOSQUITOS HAVE SUCCESSFULLY ESTABLISHED
WOLWACHIA INFECTION AND NATURAL POPULATIONS IN AUSTRALIA.
PRESENTLY, FIELD TRIALS ARE BEING INITIATED TO TEST THE
IMPACT OF WOLWACHIA ON REDUCING DENGUE INFECTIONS IN HUMANS.
THIS STRATEGY IS INTERESTING BECAUSE IT’S ONE THAT COULD BE
USED AGAINST OTHER VIRUSES, CURRENTLY BEING DONE WITH
DENGUE, BUT IT’S NOT LIMITED TO DENGUE.
AUTOCIDAL REMOVE EGG-LAYING AND POTENTIALLY INFECTED AEDES
AEGYPTI. FEMALES ARE ATTRACTED TO THESE
BLACK CONTAINERS. WHEN THEY ATTEMPT TO LAY THEIR
EGGS, THEY GET STUCK ON AN ADHESIVE INSIDE THE TRAP.
FIELD TRIALS IN PUERTO RICO RESULTED IN A SUSTAINED 88%
REDUCTION IN AEDES AEGYPTI POPULATION AND WAYS TO ENHANCE
THE ATTRACTIVENESS OF THE TRAPS ARE BEING EXPLORED.
BUT AS WITH OTHER INTERVENTIONS UNDER DEVELOPMENT, TRIALS NEED
TO BE CARRIED OUT TO DETERMINE THE EPIDEMIOLOGICAL IMPACT OF
THESE DIFFERENT APPROACHES. THE INNOVATIVE VECTOR CONTROL
CONSORTIUM IS PARTNERING WITH INDUSTRIES TO DEVELOP NEW
INSECTICIDES. ALTHOUGH THIS PROGRAM IS
PRIMARILY DIRECTED AT MALARIA CONTROL, IT COULD BE APPLIED TO
AEDES AEGYPTI. THIS GROUP AIMS TO DEVELOP THREE
NEW ACTIVE INGREDIENTS BY 2020, 2022.
THEY ALSO AIM TO MAKE IMPROVEMENTS IN INDOOR RESIDUAL
SPRAYS AND INSECTICIDE-TREATED MATERIALS.
DUE TO LIMITATIONS AND AEDES AEGYPTI VECTOR CONTROL AND THE
CHALLENGES OF DEVELOPING VACCINES, ESPECIALLY FOR DENGUE,
THERE’S A GROWING CONSENSUS THERE’S NOT ONE BEST STRATEGY
FOR AEDES AEGYPTI-BORNE DISEASE CONTROL.
SUPPORT IS GROWING, THEREFORE, FOR STRATEGIES THAT COMBINE
VECTOR CONTROL WITH VACCINES. THE COMPLEMENTARY FEATURES ARE
THAT ON ONE HAND, VECTOR CONTROL REDUCES THE FORCE OF THE VIRUS
INFECTION IN HUMANS, MAKING IT EASIER TO REACH VACCINE
DELIVERY. WHILE ON THE OTHER HAND,
VACCINES ARTIFICIALLY ELEVATE AND SUSTAIN HERD IMMUNITY,
MAKING IT EASIER TO SUSTAIN A VECTOR CONTROL IMPACT.
THE CURRENT EMPHASIS FOR THIS APPROACH IS TO DEFINE THE
DETAILS OF HOW TO BEST COMBINE THESE STRATEGIES AND THEN HOW
THEY WOULD BE EMPIRICALLY TESTED.
IN SUMMARY, AEDES AEGYPTI IS AN EFFICIENT VIRUS VECTOR BECAUSE
IT LIVES IN CLOSE ASSOCIATION WITH AND BITES HUMANS
FREQUENTLY. CONSEQUENTLY, EPIDEMICS CAN
OCCUR EVEN WHEN MOSQUITOS DENSITIES ARE LOW.
THE LACK OF APPROPRIATE INFRASTRUCTURE, ESPECIALLY IN
MODERN MEGACITIES, SUPPORTS INCREASING AEDES AEGYPTI
POPULATIONS WITH HIGH POTENTIAL FOR VIRUS TRANSMISSION.
INDOOR RESIDUAL INSECTICIDES HAVE THE GREATEST POTENTIAL
AMONG EXISTING TOOLS TO PREVENT DISEASE.
BUT THESE CHEMICAL-BASED INTERVENTIONS ARE CHALLENGED BY
GROWING CONCERNS ABOUT INSECTICIDE RESISTANCE.
SO WHAT ARE THE STEPS THAT WE COULD TAKE MOVING FORWARD?
ACROSS ALL VECTOR CONTROL APPROACHES WITH AEDES
AEGYPTI-BORNE DISEASE, THE EXISTING ONES AND THE NEW ONE
HAS ARE IN DEVELOPMENT. THERE’S AN URGENT NEED FOR EPIDEMIOLOGICAL ASSESSMENTS OF THOSE INTERVENTIONS.
TO WHAT EXTENT AND UNDER WHAT CIRCUMSTANCES DO THEY PREVENT
INFECTIONS AND DISEASE. INSECTICIDE PROGRAMS NEED TO
ESTABLISH EFFECTIVE RESISTANCE MONITORING PROGRAMS AND MEANS TO
MANAGE RESISTANCE ONCE IT’S DETECTED.
AMONG THE INTERVENTIONS THAT ARE UNDER DEVELOPMENT — SORRY.
THE MOST PROMISING ARE GENETIC STRATEGIES, AND THAT WOULD BE
RIDL AND WOLBACHIA. A MAJOR FORM IS SCALING UP FROM
THE SMALL-SCALE LOCAL FIELD TRIALS TO SUSTAINED COVERAGE
ACROSS LARGE AREAS IN PUBLIC HEALTH PROGRAMS.
THE FUTURE WILL REQUIRE COMBINATIONS OF INTERVENTIONS.
WE DON’T SEE A SINGLE MAGIC BULLET AMONG EXISTING TOOLS AND
STRATEGIES. FOR THOSE IN DEVELOPMENT OR
THOSE CURRENTLY AVAILABLE. MOVING FORWARD, WE NEED TO
DEFINE WHICH TOOLS PREVENT DISEASE, UNDER WHAT
CIRCUMSTANCES DO THEY WORK, AND WHEN DO THEY NOT WORK.
ONCE WE HAVE THAT KIND OF INFORMATION, WE CAN THINK MORE
CAREFULLY AND CLEARLY ABOUT HOW WE CAN COMBINE THOSE
INTERVENTIONS TO HAVE A MORE SUSTAINED IMPACT.
THAT ENDS MY TALK. THE NEXT SPEAKER WILL BE
DR. HAROLD MARGOLIS. [ APPLAUSE ]>>THANK YOU.
GOOD AFTERNOON. SO I’M LOCATED AT THE
CDC DENGUE BRANCH. FOR THOSE OF YOU THAT DON’T REALIZE IT, WE’RE IN SAN JUAN,
PUERTO RICO, WHICH IS A DENGUE ENDEMIC AREA OF THE UNITED
STATES. I’M GOING TO FOCUS ON CONTROL
AND PREVENTION OF DENGUE, WHICH AS YOU HEARD IS A SIGNIFICANT
PROBLEM FOR WHICH WE DON’T HAVE SINGLE PREVENTION STRATEGIES.
JUST TO REVIEW, DENGUE VIRUS INFECTIONS ARE PRIMARILY
ASYMPTOMATIC. IN CONTRAST TO CHIKUNGUNYA,
WHICH HAS A MUCH HIGHER SYMPTOMATIC DISEASE RATE, DENGUE
PRESENTED AS PROBLEM MAT NICK TERMS OF DIAGNOSE.
THERE ARE NO SINGLE SET OF SYMPTOMS OR SIGNS THAT IDENTIFY
THIS INFECTION OR THIS DISEASE. THE TYPICAL COURSE IS FOUR TO
FIVE DAYS OF FEVER, WHICH THEN RESOLVES, AT WHICH TIME UPWARDS
OF 10% OF INDIVIDUALS CAN GO ON TO HAVE SEVERE DENGUE, WHICH
I’LL DESCRIBE A LITTLE BIT LATER.
SO ONE OF THE ISSUES, AND YOU’VE HEARD THIS SAY BEFORE, IS THAT
SOMEBODY WITH DENGUE SHOULD NOT DIE.
SO CASE MANAGEMENT IS EXTREMELY IMPORTANT, AND THE KEY THING IN
SEVERE DENGUE IS PLASMA LEAKAGE. IT’S NOT HEMORRHAGE.
IT’S THIS SITUATION WHERE COMPENSATED SHOCK OCCURS, WHICH
GOES ON TO DECOMPENSATED SHOCK. YES, A SUBSET OF INDIVIDUALS
WILL HAVE DENGUE HEMORRHAGIC FEVER, WHICH HAS REALLY BEEN
REPLACED WITH SEVERE DENGUE, AND THIS BEING A SUBSET OF SEVERE
DENGUE. TIMELY DIAGNOSIS IS IMPORTANT IN
TERMS OF IMPROVED PROGNOSIS. IF PROPERLY MANAGED, WHICH
REALLY REQUIRES THE EARLY RECOGNITION OF COMPENSATED AND
DECOMPENSATED SHOCK AND PROPER FLUID MANAGEMENT, THE VAST, VAST
MAJORITY OF PEOPLE WILL SURVIVE. CASE FATALITY RATES ARE NOW
UNDER 0.1% IN AREAS WHERE THESE ACTIVITIES HAVE BEEN
IMPLEMENTED. AS YOU HEARD INITIALLY, CDC HAS
BEEN INVOLVED IN DEVELOPING A COURSE.
THIS WAS PRIMARILY DIRECTED AT PHYSICIANS IN PUERTO RICO, WHERE
WE ACTUALLY FOUND THAT CASE MANAGEMENT, IN SPITE OF BEING IN
AN ENDEMIC AREA, WAS NOT IDEAL. FOR THOSE WHO WANT TO TAKE CARE
OF EITHER YOUR PATIENTS THAT YOU’RE SEEING OVERSEAS IN DENGUE
ENDEMIC AREAS OR THAT YOU MAY BE SEEING AS TRAVELERS RETURNING
WITH DENGUE, I DIRECT YOU TO THIS FOUR-HOUR COURSE WHICH
GIVES YOU CASE MANAGEMENT AND CASE STUDIES.
SO WHY DO WE NEED BETTER DIAGNOSTICS?
AS I POINTED OUT, DENGUE IS AN ACUTE FEBRILE ILLNESS.
WE NOW IN PUERTO RICO SEE CHIKUNGUNYA.
IN SOME PARTS OF THE WORLD, MALARIA, AS WELL AS OTHER
ILLNESSES SUCH AS INFLUENZA IN THE TROPICS, WHICH LOOK JUST
LIKE DENGUE. CLINICAL DIAGNOSIS IS OFTEN
INCONCLUSIVE BECAUSE MANY OF THESE OTHER DISEASES HAVE FEVER,
RASH, PERIORBITAL PAIN AND FEVER.
ACCURATE DIAGNOSIS IS NEEDED. WE DON’T ALWAYS GET ALL THE
TYPOS OUT. LAB TESTS FOR DENGUE IN
CONTRAST, AGAIN, IN THINGS THAT HAVE CHANGED OVER THE LAST
SEVERAL YEARS REALLY DEPEND ON THE TIMING OF WHEN YOU SEE THE
PATIENT. WHAT I’M GOING TO DO IN THE NEXT
CARTOON IS TO GO THROUGH WHAT HAPPENS DURING THE COURSE OF
DENGUE AND HOW WE CAN NOW APPLY DIAGNOSTIC TESTS TO BETTER FIND
OUT WHAT WE HAVE IN A PATIENT WHO PRESENTS TO US.
SO IF YOU LOOK AT THE BACKGROUND, THE INCUBATION
PERIOD, THERE’S ABOUT A SEVEN-DAY INCUBATION PERIOD.
THERE’S A FEBRILE PHASE OF ABOUT FIVE DAYS.
THE CRITICAL PHASE IS WHEN THE PERSON DEFER VESZS.
FEVER GOES AWAY, AND THAT’S WHEN SEVERE DENGUE BEGINS TO OCCUR OR
OCCURS. THEN THERE’S THIS POST-FEBRILE
PHASE. IF YOU LOOK AT THE EVENTS — AND
LET’S GO TO THE LEFT-HAND SIDE OF THE CARTOON.
THERE IS VIREMIA. IT’S EASILY DETECTABLE BY
MOLECULAR TECHNIQUES, PCR, REAL-TIME PCR, OR SOME ANTIGEN
DETECTION TECHNIQUES. THE IGM ELISA IS WHAT MOST OF US
ARE PROBABLY FAMILIAR WITH. BUT YOU SEE THIS DIAGNOSTIC
EVENT DOESN’T OCCUR UNTIL THREE TO FIVE DAYS AFTER THE ONSET OF
ILLNESS. BY THAT TIME, MANY PEOPLE ARE
ALREADY ON THEIR WAY HOME AND AREN’T COMING BACK TO US.
THEY REALLY DO PRESENT EARLIER. SO IT’S PUTTING THESE TWO TESTS
TOGETHER THAT HELP US IN TERMS OF MAKING A GOOD CONFIRMATORY
DIAGNOSIS. WHAT I’VE DONE IS PUT THIS
ALGORITHM UP HIERE. IF YOU SEE SOMEBODY WITHIN THE
FIRST THREE DAYS, WHAT YOU JUST NEED IS PCR.
IF YOU SEE SOMEBODY IN THE THREE TO SEVEN-DAY PERIOD, YOU NEED
BOTH TESTS. AFTER SEVEN DAYS, YOU NEED IGM.
SO LET ME TALK A LITTLE BIT ABOUT A PREVENTION FRAMEWORK.
WHAT I’VE TALKED ABOUT IS THE BOTTOM HALF OF THIS PUZZLE,
NAMELY SECONDARY PREVENTION ACTIVITIES.
THE TOP PART, WHICH ARE INTEGRATED VECTOR CONTROL, WHICH
DR. SCOTT TALKED ABOUT,. YOU HEARD THE DIFFICULTIES WITH
IT. WHAT I’M GOING TO DO IS DRILL
DOWN ON VACCINES AND ALL OF THESE WE SEE AS BEING EVALUATED
BY SURVEILLANCE. YOU YOURSELF CAN PROTECT
YOURSELF AGAINST DENGUE BY USING REPELLANTS.
YOU’VE HEARD THIS AGAIN IN PREVIOUS TALKS.
THERE ARE A NUMBER OF ACTIVE INGREDIENTS, WHICH I’VE LISTED
HERE. THE KEY IS YOU HAVE TO PUT THEM
ON. YOU HAVE TO PUT THEM ON SEVERAL
TIMES A DAY. AND YOU HAVE TO USE THEM ALL THE
TIME. THEY DON’T HELP IN THE
COMMUNITY. SO FOR THOSE OF US WHO LIVE IN
THE TROPICS, YOU FIND IT’S SOMETIMES HARD TO DO.
THAT’S WHY, YES, IT WORKS, BUT IT DOESN’T WORK ALL THE TIME.
BUT NOW LET’S TALK ABOUT DENGUE VACCINES, WHICH YOU HEARD DR.
FRIEDEN BRING UP IN HIS COMMENTS.
THE POINTS, I THINK, ARE WELL ESTABLISHED IN TERMS OF WHY WE
WOULD LIKE TO HAVE A STRONG PRIMARY PREVENTION TOOL.
THE OTHER THING IS THAT EFFICACIOUS VIRUSES EXIST.
WE HAVE THEM AGAINST YELLOW FEVER, JAPANESE ENCEPHALITIS,
AND TICK-BORNE ENCEPHALITIS. THE CHALLENGE IS, YOU MUST
PROTECT AGAINST ALL FOUR DENGUE VIRUSES.
THEN THERE’S A LARGE IMPLEMENTATION CHALLENGE AHEAD
ONCE WE HAVE AN EFFECTIVE VACCINE.
SO HERE ARE FIVE VACCINES THAT ARE IN DEVELOPMENT.
YOU MAY BE SURPRISED THERE ARE ACTUALLY THAT MANY.
THREE OF THEM ARE LIVE ATTENUATED, BUT THEY’RE NOT DONE
BY THE CLASSICAL PASSAGE APPROACH.
THEY’VE BEEN MADE BY GENETICALLY ENGINEERING THESE VIRUSES AND
THEN COMBINING THEM INTO A SINGLE VACCINE.
THERE’S A CELL CULTURE DERIVED INACTIVATED VACCINE AND ALSO A
SUBUNIT VACCINE. THE ONE THAT DR. FRIEDEN TALKED
ABOUT IS THE ONE THAT WAS INITIALLY DEVELOPED BY CDC.
SO WHERE ARE THEY? WELL, THE SANOFI VACCINE HAS
COMPLETED PHASE THREE TRIALS. THERE ARE TWO NOW THAT ARE GOING
INTO PHASE THREE TRIALS. AND THERE ARE TWO THAT ARE
BEGINNING TO GO FROM PHASE ONE INTO PHASE TWO.
SO THERE’S A LOT IN THE PIPELINE, AND THERE’S A LOT OF
INFORMATION COMING FORWARD. NOW, ALL OF THESE TRIALS ARE
ACTUALLY BEING CONDUCTED IN A SIMILAR MANNER.
THERE WERE GUIDELINES PRODUCED IN 2008 BY W.H.O. THAT SAID,
LOOK, THESE SHOULD BE RANDOM, BLIND AND PLACEBO-CONTROLLED
TRIALS. AGE GROUPS SHOULD BE WHERE THE
HIGHEST INCIDENCE IS. THAT’S USUALLY THE 2 TO
16-YEAR-OLDS IN ALL DENGUE ENDEMIC AREAS.
THE SANOFI TRIAL HAD THREE DOSES OF VACCINE SHOWN IN PHASE TWO
TRIALS THAT THAT’S WHAT YOU NEEDED TO GET HIGH ANTIBODY
LEVELS. THEY USED A NORMAL SALINE
VACCINE. BUT SOME PLACEBO SHOULD BE USED.
AND THE END POINT, GOING BACK TO MY DIAGNOSTIC COMMENT, IS WE’RE
LOOKING FOR DENGUE AS ACUTE FEBRILE ILLNESS PLUS VIREMIA.
THAT’S GETTING PEOPLE EARLY. FOLLOW-UP HAS BEEN 25 MONTHS.
SO THAT’S 13 MONTHS AFTER THE LAST DOSE.
LOOKING FOR BOTH EFFICACY AS WELL AS ADVERSE EVENTS.
AND LONG-TERM FOLLOW-UP IS A BIG ISSUE WITH DENGUE BECAUSE OF THE
CONCERN ABOUT POTENTIAL ADVERSE EVENTS.
SO THESE TRIALS ARE ACTUALLY GOING ON FOR 48 MONTHS, AND THEY
ARE STILL BLINDED IN TERMS OF THE OUTCOMES OF THE INDIVIDUAL.
SO CROSSOVERS HAVE NOT BEEN RECOMMENDED.
SO HERE ARE THE DATA FROM THE SANOFI TRIALS.
REALIZE IT’S A LOT ON THIS SLIDE, BUT THERE WERE TRIALS IN
ASIA AS WELL AS TRIALS IN THE AMERICAS AND KIND OF GO TO THAT
AREA THAT IS CIRCLED BY THE YELLOW ELLIPSE.
YOU SEE THAT OVERALL EFFICACY WAS A LOW OF 30% TO AN AVERAGE
OF AROUND 60%. AND WHAT WAS THE CAUSE OF THAT?
WELL, GO DOWN TO DENGUE TWO. IN THE TRIAL IN THAILAND, THEY
HAD A VERY LARGE DENGUE TWO EPIDEMIC GOING ON.
THEY HAD VERY LOW EFFICACY. BUT YOU SEE THAT THE LOW
EFFICACY FOR THAT COMPONENT OF THE VACCINE CONTINUED IN THE
OTHER TRIALS. ALSO, DENGUE ONE SEEMED TO HAVE
LOWER EFFICACY AS COMPARED TO DENGUE THREE AND FOUR.
SO WHERE ARE WE TODAY? AND THIS IS ALL FAIRLY NEW DATA.
THE SANOFI VACCINE OFFERS ONLY PARTIAL PROTECTION.
CURRENT DATA HAVE NOT SHOWN ANY VACCINE SAFETY ISSUES.
AND THAT’S WITH FOLLOW-UPS NOW OUT ALMOST ANOTHER 12 MONTHS
AFTER THE TRIAL. BUT LONG-TERM FOLLOW-UP, AS I
POINTED OUT, IS NEEDED TO BE SURE THAT ANY WANING IMMUNITY
DOES NOT PRECIPITATE OR CAUSE SEVERE ADVERSE EVENTS IN PEOPLE
WHO THEN LATER ON MAY BE EXPOSED TO DENGUE, A PHENOMENA CALLED
ANTIBODY DEPENDENT ENHANCEMENT, WHICH HAS BEEN SEEN TO CAUSE A
SMALL PROPORTION OF SEVERE EVENTS IN DENGUE.
SO WHERE ARE WE? AND THIS GOES BACK TO THE
SUMMARY AND THINGS YOU’VE HEARD FROM OTHERS.
40% OF THE WORLD’S POPULATION REMAINS AT RISK FOR DENGUE.
PROPER CASE MANAGEMENT WILL LOWER DEATHS AND REDUCE CASE
FATALITY RATES. LAB DIAGNOSTICS IS REALLY
DEPENDENT ON GETTING THE RIGHT TESTS AT THE RIGHT STAGE OF
ILLNESS. WE’RE USING TWO TESTS.
VECTOR CONTROL AND VACCINE RESEARCH DO HOLD PROMISE.
BUT WE’RE INTO THIS NEW PHASE OF NEEDING TO EVALUATE THESE.
UNTIL A SAFE AND EFFECTIVE VACCINE IS AVAILABLE, ENHANCED
SURVEILLANCE, RAPID DIAGNOSIS, PERSONAL PROTECTION ARE STILL
THE BEST METHODS FOR PREVENTING DENGUE.
AND IN TERMS OF FUTURE DIRECTIONS, AS DR. SCOTT POINTED
OUT, WE NEED TO EVALUATE THE BEST WAYS TO IMPLEMENT
VACCINATION AND ALSO COMBINE THAT WITH VECTOR CONTROL THAT IS
BEING USED. THESE NEW CONTROL OPTIONS AND
WAYS TO IMPLEMENT THEM NEED TO BE PUT INTO COMMUNITY-BASED
OUTCOME STUDIES. THERE NEEDS TO BE AN IMPROVEMENT
IN DIAGNOSTIC TESTS. EVERYTHING I TOLD YOU ABOUT ARE
THINGS YOU NEED IN A FIXED LABORATORY.
BUT POINT OF CARE TESTS ARE SOMETHING THAT ARE NEEDED.
CURRENTLY THEY DON’T WORK VERY WELL.
AND INCREASE OF UNIVERSAL DENGUE CASE MANAGEMENT HAS BEEN SHOWN
TO BE EFFECTIVE, NEEDS TO BE CONTINUED, AND EDUCATION IS A
KEY PART OF THAT. AND ULTIMATELY, WE NEED TO —
EVERY TIME WE LOOK, WE FIND DENGUE WHERE WE DIDN’T THINK
DENGUE WAS. MANY OF YOU WERE SURPRISED
PROBABLY TO SEE THAT AFRICA IN THOSE EARLY MAPS WAS LIT UP WITH
A LOT OF DENGUE. WELL, THAT WAS BECAUSE IT
PROBABLY STARTED THERE AND NOW PEOPLE ARE LOOKING.
SO TIMELY DIAGNOSIS IS IMPORTANT.
SAFE AND EFFECTIVE VACCINES ARE NEEDED.
SURVEILLANCE NEEDS TO BE ENHANCED BECAUSE THAT’S HOW
WE’RE GOING TO TELL WHAT’S WORKING.
AND VECTOR CONTROL MEASURES SHOULD BE CONTROLLED AND
SUSTAINED. COORDINATION OF ALL OF THESE AND
ALL THESE VERY DIFFERENT GROUPS OF INVESTIGATORS AND PEOPLE NEED
TO BE WORKING WITH EACH OTHER IN TERMS OF GOING FORWARD.
THANK YOU. [ APPLAUSE ]
>>THANK YOU, DR. MARGOLIS. THIS SESSION IS NOW OPEN FOR
QUESTIONS. IF PEOPLE IN THE BACK CAN COME
UP TO ONE OF THE MICROPHONES, I THINK PEOPLE IN THE FRONT HAVE
MICROPHONES. IF YOU COULD RAISE YOUR HANDS
AND FOLKS COULD LIMIT THEMSELVES TO ONE QUESTION.
>>THANK YOU FOR A VERY INFORMATIVE PRESENTATION.
IT SEEMS THAT WE DON’T HAVE AN INFECTIOUS DISEASE OUTBREAK
WHERE THE QUESTION OF MOSQUITOS-BORNE TRANSMISSION
DOESN’T COME UP, EBOLA, HIV, ET CETERA.
MY QUESTION IS WHY THESE DISEASES?
WHAT IS IT WE UNDERSTAND ABOUT IT?
DOES THAT SPEAK TO OTHER APPROACHES TO MANAGING DISEASE?
SO LIKE REDUCING POPULATION VIRAL LOAD OR SOMETHING TO THAT
EFFECT. I’M NOT SURE I FULLY
UNDERSTAND THE QUESTION. WHY THESE DISEASES AND NOT
THE OTHER DISEASES THAT COME UP AND PEOPLE SAY, WELL, CAN THIS
BE TRANSMITTED BY MOSQUITOS? I MEAN, WHY THESE DISEASES
ARE TRANSMITTED BY MOSQUITOS I THINK HAS A COMBINATION TO DO
WITH OBVIOUSLY THE VECTORS WHICH I THINK THESE PEOPLE CAN SPEAK
BEST TO AS THEIR ABILITY TO BE INFECTED AND OBVIOUSLY THE
MOSQUITOS SPECIES NEED TO BE ABLE TO BE INFECTED, NOT
AFFECTED, TO THE POINT THEY CAN TRANSMIT IT.
THEN THERE NEEDS TO BE SOME HOST, IN SEVERAL OF THE CASES
WE’RE TALKING ABOUT HUMANS, AND OTHER MOSQUITOS-BORNE VIRUSES.
THOSE ARE OTHER VERTEBRAE ANIMALS THAT HAVE LEVELS HIGH
ENOUGH THAT WHEN BITTEN BY ANOTHER MOSQUITOS, THOSE
MOSQUITOS WILL BECOME INFECTED. AGAIN, THE VIRUS CAN LIVE AND BE
TRANSMITTED BY THOSE MOSQUITOS. I DON’T REALLY HAVE MUCH TO
ADD TO THAT EXCEPT THERE’S AN INTIMATE RELATIONSHIP BETWEEN
THE MOSQUITOS AND THE VIRUS BUT ALSO THE HUMAN THE HOST.
SO THIS NEEDS TO BE ABLE TO REPLICATE BETWEEN TWO DIFFERENT
HOSTS, AND THAT OFTENTIMES IS UNUSUAL.
>>FROM OUR ONLINE AUDIENCES. HOW IMPORTANT IS RAPID DIAGNOSIS
IF THERE’S NO SPECIFIC ANTI-VIRAL AGAINST DENGUE OR
CHIKUNGUNYA? THAT’S AN IMPORTANT QUESTION.
I THINK IT’S TWOFOLD. ONE IS IT DOES HELP THE
CLINICIAN, KNOWING THAT YOU REALLY HAVE A PATIENT WITH
DENGUE BECAUSE YOU HAVE MANY OTHER DISEASES THAT LOOK LIKE
IT, AND YOU MAY BE GOING, YES, YOU GO SYMPTOMATICALLY, BUT
KNOWING THIS IS DENGUE. IN THE CASE OF CHIKUNGUNYA,
WHERE BOTH OF THESE OCCUR, IT MAY ALSO HELP YOU, AND IT DOES
HELP YOU, WITH GIVING THAT PATIENT WITH CHIKUNGUNYA
ANTI-INFLAMMATORIES. YOU DON’T WANT TO GIVE THOSE TO
SOMEBODY WITH DENGUE WHO MAY START HAVING A BLEEDING EPISODE
BECAUSE YOU INTERRUPTED THEIR VASCULAR INTEGRITY.
THE OTHER PART IS SURVEILLANCE. IF YOU HAD HUGE LAGS IN KNOWING
WHAT THAT, YOU KNOW — WHAT THOSE EPIDEMIC CURVES ARE, AND
WE’VE SEEN THIS IN PUERTO RICO, WHERE WHEN H1N1 CAME OVER,
EVERYONE THOUGHT IT WAS DENGUE. THE DISEASES LOOK THE SAME.
SO IT IS IMPORTANT TO USE YOUR DIAGNOSTICS.
>>THANK YOU. IN THE BACK.
>>YES, GOOD AFTERNOON. A LITTLE OVER A YEAR AGO A —
[ INAUDIBLE ]. YES, WE ALL SAW THAT.
AND TO DATE THERE HAS NOT BEEN PUBLISHED SEQUENCE DATA.
IT WAS VERY CLOSELY RELATED TO DENGUE FOUR.
IT APPEARED TO BE FROM AN AREA WHERE SYLVATIC DENGUE WAS BEING
TRANSMITTED IN MALAYSIA AND CAME FROM A RETROSPECTIVE FREEZER
STUDY. AGAIN, TO DATE, THERE JUST
HASN’T BEEN EITHER FULL CONFIRMATION OF THAT OR NEW
TYPES. THESE ARE REALLY VIRUS TYPES
THAT HAVE BEEN IDENTIFIED. THANK YOU.
THIS IS A REALLY INTERESTING, GREAT PRESENTATION.
I THINK ONE OF THE ISSUES CLEARLY THERE’S A HUGE GLOBAL
DISEASE BURDEN FROM THESE MOSQUITOS-BORNE DISEASES, BUT WE
ALSO SAW THE DISTRIBUTION OF THE TWO VECTORS, INCLUDING PARTS OF
THE UNITED STATES AND CERTAINLY PUERTO RICO.
I THOUGHT PEOPLE MIGHT BE INTERESTED IN SOME OF YOUR
THOUGHTS, SOME OF THE EXPERIENCE WITH TRANSMISSION OF DENGUE,
BOTH IN PUERTO RICO, WHERE IT’S ENDEMIC, AND ALSO IN PARTS OF
THE SOUTHERN UNITED STATES AND WHAT YOUR THOUGHTS ARE IN TERMS
OF THE POTENTIAL FOR CHIKUNGUNYA.
>>WELL, PUERTO RICO OBVIOUSLY HAS DENGUE.
WE’VE HAD EPIDEMIC CYCLES. THIS IS A CYCLICAL DISEASE.
SO IN 2010, AT LEAST 27,000 REPORTED CASES.
YOU KNOW, THE UPS AND DOWNS. THIS VECTOR IS EVERYWHERE.
PUERTO RICO DOES NOT HAVE ONE OF THESE NEW APPROACHES TO VECTOR
CONTROL. IT’S REALLY PRETTY SPORADIC.
IT’S PRETTY HAPHAZARD. AND PEOPLE LIVE TROPICALLY.
THOSE OF YOU THAT HAVE LIVED IN THE TROPICS KNOW WHAT I MEAN.
YOU HAVE MOSQUITOS IN YOUR HOUSE, AND YOU GO WHERE
MOSQUITOS ARE. AND TO ME, THAT IS MUCH OF WHAT
GOES ON WITH DENGUE. WHAT WE’VE BEEN ABLE TO DO IN
PUERTO RICO IS REALLY CHANGE THE CASE FATALITY RATES BY BEST
CARE. I THINK THIS SPILLS OVER WITH
CHIKUNGUNYA. AGAIN, YOU SAW SOME OF THE
GRAPHICS. MY LITTLE QUIP IS THAT
CHIKUNGUNYA TELLS YOU HOW GOOD OR BAD YOUR VECTOR CONTROL
PROGRAM IS FOR AEDES AEGYPTI. BECAUSE IT JUST PICKS IT OUT
IMMEDIATELY. I THINK FOR CHIKUNGUNYA,
THE — THERE HAVE BEEN A NUMBER OF MODELS LOOKING AT RISKS OF
TRANSMISSIONS SPREAD INTO THE UNITED STATES.
I THINK DENGUE IS THE BEST MODEL WE HAVE.
OBVIOUSLY THEY’RE VERY SIMILAR ECOLOGIES, SAME VECTORS.
THERE ARE SOME DIFFERENCES. PEOPLE WITH CHIKUNGUNYA SLIGHTLY
HIGHER AND LONGER LEVELS OF VIREMIA.
YOU’RE GOING TO SEE THOSE INFECTIONS.
BUT PROBABLY DENGUE, WHERE YOU SEE HUNDREDS OF THOUSANDS IF NOT
MILLIONS OF CASES IN THE AMERICAS WITH THOUSANDS OF
TRAVEL-ASSOCIATED CASES, AND THEN A RELATIVELY, YOU KNOW,
TENS TO HUNDREDS OF LOCALLY TRANSMITTED CASES A YEAR IS
PROBABLY THE BEST MODEL OR GUESSTIMATE WE HAVE FOR WHAT
MIGHT HAPPEN IN THE CONTINENTAL UNITED STATES WITH REGARD TO
CHIKUNGUNYA. AND THAT’S WHAT WE SAW AT LEAST
IN THE FIRST YEAR OF TRANSMISSION WITH OVER A MILLION
SUSPECTED CASES IN THE AMERICAS. A FEW THOUSAND TRAVEL-ASSOCIATED
CASES AMONG RETURNING TRAVELERS TO THE U.S.
AND 11 LOCALLY TRANSMITTED CASES IDENTIFIED IN FLORIDA.
I THINK IT REMAINS TO SEE WHAT WILL HAPPEN IN THE NEXT SEASON
OR COMING YEARS. SO LIKE MARC SAID, MOST
PEOPLE THAT GET A CHIKUNGUNYA INFECTION PRESENT WITH AN
APPARENT ILLNESS. A LOT OF IT IN TERMS OF IN THE
UNITED STATES IS GOING TO DEPEND ON THE EXTENT TO WHICH MOSQUITOS
HAVE CONTACT WITH PEOPLE. SO OUR LIFESTYLE IS DIFFERENT
AND THEREFORE I WOULDN’T EXPECT — I’LL GO OUT ON A LIMB.
I WOULDN’T EXPECT THERE TO BE NEARLY AS MUCH DEPENDING ON
COMMUNITIES AND HOW PEOPLE LIVE THAT WE’RE SEEING IN OTHER PARTS
OF THE AMERICAS. MOSQUITOS AREN’T BITING US AS
OFTEN. THANK YOU.
EXCELLENT POINT. I SUFFERED FROM IT TWICE WHEN
I WAS LIVING IN THE DOMINICAN REPUBLIC.
INTERESTINGLY TO ME, I’VE SEEN A LOT OF THESE DIFFERENT SORT OF
TECHNIQUES TO PREVENT MOSQUITOS IN GENERAL.
BUT I KNOW ANECDOTALLY I HEARD — AND I JUST WANTED TO
KNOW IF THERE’S ANY REAL RESEARCH BEHIND THE FACT THAT
PERHAPS JUST A DIET, MAYBE VITAMIN SUPPLEMENTATION MIGHT BE
ABLE TO PREVENT MOSQUITOS FROM BITING CERTAIN PEOPLE JUST IN
THE FACT THAT IT’S INTERESTING TO ME THAT I WAS SURROUNDED BY
PEOPLE WHO HAD LIVED THERE IN THE DOMINICAN REPUBLIC THEIR
WHOLE LIVES AND NEVER HAD DENGUE, AND YET I COULD WALK
INTO A ROOM WHERE THERE WERE NO MOSQUITOS AND ALL THE SUDDEN
THERE WERE MOSQUITOS EVERYWHERE BITING ME.
IT JUST WAS ODD TO ME THAT NOBODY ELSE SEEM TO BE — OR
THERE WAS A CERTAIN COMPONENT OF SOMETHING THAT I HAD THAT THE
MOSQUITOS WANTED THAT THEY DID NOT WANT FROM ANYONE ELSE.
I SAW THIS HAPPENING A LOT. I JUST THOUGHT THAT WAS
INTERESTING, SOME KIND OF P.H. OR SOMETHING THAT MAKES CERTAIN
SKIN OR BLOOD MORE DESIRABLE THAN ENDEMIC.
>>THANK YOU. I THINK DR. SCOTT THERE ADDRESS
THIS. FIRST OF ALL, I’D LIKE TO
TEST THOSE PEOPLE. I BET MOST OF THEM HAD HAD
DENGUE. MAYBE NOT APPARENT INFECTIONS
AND DIDN’T KNOW IT AT THE TIME. THERE CLEARLY ARE DIFFERENCES IN
HOW SOME INDIVIDUALS ARE BITTEN MORE OFTEN THAN OTHERS.
THE BEST EXPLANATION FOR THAT PROBABLY HAS TO DO WITH
MICROFLORA BACTERIA THAT ARE ON OUR SKIN THAT EMIT CHEMICALS
THAT ATTRACT THE MOSQUITOS. THERE ARE DIFFERENCES ASSOCIATED
WITH AGE. WE TEND TO SEE MIDDLE-AGED
ADULTS GETTING BITTEN MORE OFTEN THAN CHILDREN.
EVEN WITHIN THOSE CATEGORIES, THERE ARE SOME INDIVIDUALS THAT
GET BITTEN MORE OFTEN THAN OTHERS.
THERE’S NO EVIDENCE THAT I KNOW OF THAT DIET, GARLIC, BEER, ALL
KINDS OF THINGS, HAVE ANY IMPACT ON THAT.
>>THANK YOU. IT’S BEEN WELL ESTABLISHED
THAT DENGUE HAS SPREAD THROUGHOUT THE WORLD, THROUGH
ALL THE CONTINENTS. IT’S BEEN WELL ESTABLISHED THAT
CHIKUNGUNYA HAS RECENTLY SPREAD TO THE WESTERN HEMISPHERE.
AND IT’S WELL ESTABLISHED THAT ZIKA IS NOW IN BRAZIL AND IS IN
THE PACIFIC. WHY IS IT THAT YELLOW FEVER,
WHICH HAS THE SAME VECTORS, HAS NOT SPREAD.
IT’S STABLE, AND THERE’S SO MANY AT-RISK POPULATIONS IN ASIA,
WHICH WOULD BE CATACLYSMIC IF IT SPREAD.
>>THAT’S AN EXCELLENT QUESTION. I DON’T HAVE A VERY GOOD ANSWER
FOR YOU. THERE HAS BEEN SOME SPREAD OF
YELLOW FEVER, BUT IT’S BEEN IN MUCH LIMITED WAYS.
BASICALLY CONTIGUOUS SPREAD, WITHIN THE AREAS, WITHIN SOUTH
AMERICA AND AFRICA WHERE IT’S ENDEMIC.
BUT NO SPREAD, AS YOU SAY, TO OTHER CONTINENTS, ESPECIALLY
ASIA WOULD BE OF GREAT CONCERN. I THINK THE GREATEST DIFFERENCE
THAT I CAN POINT TO IS THAT THE VIRUS HAS NOT ADAPTED TO HUMANS
AS THE PRIMARY VERTEBRAE HOST. HUMANS HAVE LEVELS HIGH ENOUGH
THEY WILL TRANSMIT TO MOSQUITOS. FORTUNATELY, ONLY IN THIS URBAN
CYCLE WHEN AEDES AEGYPTI BECOMES INVOLVED HAS THAT BEEN SEEN,
WHEREAS IN THE TYPICAL PATTERN OF YELLOW FEVER, IT HAS BEEN
LIMITED SO FAR TO THIS SYLVATIC OR JUNGLE CYCLE WHERE OTHER
MOSQUITOS AND OTHER HOSTS, MOSTLY NON-MUM PRIMATES, ARE
PLAYING A ROLE. IN ADDITION, IT DOESN’T ADDRESS
WHY IT HASN’T SPREAD TO ASIA, BUT WE HAVE A VACCINE.
THE VACCINE HAS BEEN AVAILABLE SINCE THE 1930s AND CAN BE USED
TO BASICALLY PROTECT PEOPLE WHO ARE GOING TO ENDEMIC AREAS FROM
BECOMING INFECTED AND VIREMIC, BRINGING IT TO OTHER AREAS.
THOSE ARE TWO POSSIBLE REASONS THAT HAVE REDUCED THE RISK OF
SPREAD. WHY WE HAVEN’T SEEN ANY
OUTBREAKS OR LIMITED OUTBREAKS IN THOSE AREAS, I DON’T HAVE AN
ANSWER FOR. THERE WERE THREE DIFFERENT
HYPOTHESES THAT HAVE BEEN PROPOSED.
ONE OF THEM HAD TO DO WITH DIFFERENT VECTOR COMPETENCE OF
MOSQUITOS IN DIFFERENT PARTS OF THE WORLD.
THERE WAS A GROUP AT YALE UNIVERSITY THAT EXTENSIVELY
LOOKED AT THAT AND DIDN’T SEE A DIFFERENCE.
SO THE MOSQUITOS IN ASIA WERE COMPETENT TO TRANSMIT YELLOW
FEVER. THERE WAS ANOTHER ONE THAT HAD
TO DO WITH MOVEMENT OF PEOPLE AND THAT MAYBE THEY JUST WEREN’T
MOVING FROM PLACES IN AFRICA WHERE IT WOULD INTRODUCE IT.
BUT WITH GLOBAL TRAVEL THE WAY IT IS TODAY THAT, DIDN’T SEEM
REASONABLE. AND THE THIRD ONE, WHICH WE WERE
JUST CONFERRING ON THIS, HASN’T BEEN PROVEN, SO IT’S A
HYPOTHESIS, HAS TO DO WITH NONRECIPROCAL IMMUNITY.
SO IF YOU’RE IMMUNE TO DENGUE VIRUS, YOU GET SOME PROTECTION
AGAINST YELLOW FEVER. BUT IF YOU’VE BEEN VACCINATED
FOR YELLOW FEVER, YOU’RE NOT NECESSARILY PROTECTED AGAINST
DENGUE. THAT’S NOT BEEN PROVEN.
FOR ME, THAT SEEMS LIKE THE MOST REASONABLE EXPLANATION.
SO IN ASIA, THERE’S A LOT OF PEOPLE THAT HAVE ALREADY HAD
DENGUE. THEY MAY BE PROTECTED FOR THAT
REASON. SUSAN?
>>AGAIN, FROM ONLINE AUDIENCES. ARE THERE ANY COMPLICATIONS
AFTER CHIKUNGUNYA INFECTION? I’M NOT AWARE OF ANY.
THERE HAVE BEEN VIRUSES THAT HAVE BEEN IDENTIFIED IN
OPTHALMIC TISSUES. BUT I’M NOT AWARE OF ANY
CLINICAL FINDINGS. THE CHIKUNGUNYA LITERATURE IS
CERTAINLY EXPANDING GREATLY IN THE LAST COUPLE YEARS WITH A
LARGE OUTBREAKS IN THE PACIFIC AND INDIA AND RECENTLY IN THE
AMERICAS. SO I WOULDN’T BE SURPRISED IF WE
SEE REPORTS LIKE THAT, BUT I’VE NOT — I’M NOT AWARE OF THEM.
>>THAT QUESTION WAS FROM INDIA. REBECCA HALL.
I WAS JUST WONDERING WHAT DO WE KNOW ABOUT THE PEOPLE THAT GO ON
TO HAVE MORE SEVERE FORMS OF THE DISEASES CAUSED BY THE VIRUSES?
DO THEY PRESUMABLY — HAVE THEY SUSTAINED MORE MOSQUITO BITES?
ANY OTHER UNDERLYING RISK FACTORS?
THANKS. SO FOR — I DON’T THINK IT
HAS ANYTHING TO DO WITH THE NUMBER OF MOSQUITO BITES YOU
HAVE. YOU’RE BASICALLY INFECTED AND
IT’S AN ISSUE OF YOUR BODY’S RESPONSE.
FOR DENGUE, WHICH I’LL LET HAL SPEAK TO, THERE MAY BE SOME
IMMUNE MEDIATED RESPONSE. FOR CHIKUNGUNYA, THE DATA ARE
LIMITED. WE KNOW THAT OLDER PEOPLE AND
PEOPLE WITH UNDERLYING MEDICAL CONDITIONS ARE MORE LIKELY TO
HAVE MORE SEVERE. THERE’S ONE STUDY THAT
ASSOCIATED WITH AN HLA TYPE, SO SUGGESTING A GENETIC COMPONENT.
BUT I DON’T THINK THERE’S ANYTHING MORE ABOUT THAT.
FOR YELLOW FEVER, I DON’T KNOW OF ANY SPECIFIC RISK FACTORS
THAT ARE IDENTIFIED FOR PEOPLE WHO GO ON TO HEMORRHAGE OR MORE
SEVERE DISEASE. HAL, DO YOU WANT TO SPEAK TO
DENGUE? THERE HAVE BEEN A LOT OF
HYPOTHESES WITH DENGUE. AS I POINTED OUT,
NONNEUTRALIZING ANTIBODY, AT LEAST INVITRO, AND WITH SOME EPIDEMIOLOGIC STUDIES MADE, CONFER SOME INCREASED RISK.
THE ONE THING THAT’S COME OUT IN STUDIES THAT HAVE BEEN DONE AND
WHERE YOU CAN DO IT IS VIRAL LOAD.
SO THOSE PEOPLE WITH THE HIGHEST DENGUE VIRUS TIDERS DURING THE
COURSE OF THEIR ILLNESS TEND TO BE THOSE THAT GO ON AND HAVE
SEVERE DENGUE. PAST THAT, IT’S THIS WHOLE RAFT
OF THINGS THAT NOTHING HAS BEEN PINPOINTED.
>>AND I HATE TO CUT OFF A FABULOUS DISCUSSION LIKE THIS,
BUT I THINK WE’VE REACHED THE END OF OUR TIME.
THANK YOU VERY TOUCH FOR JOINING US.
[ APPLAUSE ]

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