good afternoon.a see a few more people are coming in, but i'm hopingthey'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 educationcredits -- for physicians, nurses, pharmacist and others. please check our website to findmore details. in addition to the cmesavailable, cdc has also
developed a dengue casemanagement tool to help health care providers treat theirpatients with dengue. they also have cme creditsthere, and i would check it out. in addition to our website, wealso have social media sites, and we have a featured videosegment called beyond the data that will be posted shortlyafter today's session. we are also tweeting today.you can follow us @cdcncezid by using #cdcgrandrounds.thank you. we have partnered with the cdcpublic health library for
related articles.the full listing is available at the website,cdc.gov/library/sciclips. to give you a sense of howquickly these diseases can spread, i want to share with youa recent outbreak of chikungunya in puerto rico.the blue indicates residents of a reported case.as you can see, in three short months, chikungunya spreadwidely with over 10,000 suspected cases reported andalmost 2,000 cases tested positive.here is a preview of the
upcoming public health grandrounds sessions. please join us.in addition to our outstanding featured speakers, i'd also liketo take a moment to acknowledge the important contributions ofthe 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 everyyear, making mosquitos the deadliest animal on the planetwith the possible exception
of human beings.before 1970, only nine countries had experienced severe dengueepidemics. now the disease is endemic inmore 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 nowon our doorstep, having reached the caribbean in late 2013.since then, almost 1.4 million confirmed or suspected caseshave been reported affecting 44 countries and territoriesthroughout the americas.
aedes mosquitos transmit boththese viruses as well as yellow fever. one way we can reduce the global burden and mortality from dengueis with an effective vaccine. there's promising research ondengue vaccines that will be presented today, including abouta candidate vaccine developed at cdc at our ft. collins campus.there are also promising advances to improve the controlof aedes mosquitos. if effective, these newtechnologies could help reduce
the burden not only of denguebut also of other aedes-borne viruses.for those who become infected with dengue, we need bettermanagement of their care. current treatment guidelinesdeveloped with our partners at w.h.o. can nearly eliminatedeath from dengue. as many of you know, cdc has ourorigins in mosquitos control. this remains important work.through planning and collaboration, new vectorcontrol measures, vaccines, and proper clinical case management,we can reduce the burden of
dengue and other mosquitos-bornediseases. thank you for the great workdone in this and other areas. >> and now for our firstspeaker, dr. marc fischer. >> thank you, and goodafternoon. aedes are mosquitos species ofgreat public health importance. aedes aegypti is the majorvector. taken together, these virusesaccount for almost 100 million cases of mosquitos-bornediseases per year. aedes aegypti and aedesalbopictus 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 aedesmosquitos globally and in the united states.both species are widely distributed throughout tropicalareas in the americas, africa, asia, and oceania.aedes mosquitos-borne viruses have two primary transmissioncycles. in the sylvatic cycle, virusesare maintained between non-human
primates and species in andaround the jungle. in the epidemic or urban cycle,humans are the amplifying host and viruses transmitted directlyfrom humans to mosquitos to humans.dengue is caused by infection with any of four relatedviruses. aedes is the primary vector forall four of these. humans are the primaryamplifying host. the virus have adapted so thata sylvatic cycle is no longer needed to maintain the virus innature.
this map shows the approximatedistribution of dengue virus. sporadic outbreaks have alsooccurred in southern europe and in hawaii, texas, and florida.dengue is the most important mosquitos-borne viral diseaseglobally. in the last 50 years, thereported incidents has increased 30 fold with expansion to newareas. approximately 25% of peopleinfected with dengue virus develop clinical symptoms.although surveillance data are limited, a recently publishedmodel estimated there were 96
million dengue disease casesworldwide in 2010, including 67 million cases in asia, 16million in africa, and 13 million in the americas.dengue is an acute illness which often includes headache,myalgia, or minor bleeding. subsequent infection with adifferent type of dengue virus increases the risk for severedisease. the case fatality can be as highas 10% but proper case management reduces mortality toless than 1%. chikungunya virus is an alphavirus an emerging cause of
mosquitos-borne disease.humans are the primary amplifying host for chikungunyavirus during outbreaks. sylvatic transmission occurs innon-human primates in africa. this map shows countries thathave ever reported local transmission of chikungunyavirus. the virus was first isolated intanzania 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 thenumber of disease cases reported
from india and islands in theindian and pacific oceans. imported cases also resulted inoutbreaks in europe. in late 2013, the first localtransmission of chikungunya virus in the americas wasidentified in the caribbean. over the next 18 months, thevirus spread throughout much of the western hemisphere, causedoutbreaks on many pacific islands.chikungunya virus often causes large outbreaks with highinfection rates affecting more than a third of the susceptiblepopulation.
the majority of infected peopledevelop clinical symptoms. in 2014, more than a millioncases of chikungunya were reported worldwide with mostoccurring in the caribbean and central and south america.the primary clinical symptoms of chikungunya virus infection arefever and polyarthralgia. the acute symptoms typicallyresolve in seven to ten days. however, some patients havepersistent or recurrent problems for months following their acuteillness. the overall case fatality rateis less than 1% and occurred
mostly in older adults withunderlying medical conditions. yellow fever virus is anothermosquitos-borne virus. most human infections occur as aresult of sylvatic transmission. urban outbreaks occurperiodically and mostly in west africa.aedes is the primary vector during these urban outbreaks.yellow fever virus is distributed throughoutsubsaharan africa and tropical america, although outbreaksoccurred in europe until the early 1900s.local transmission has not been
reported in these areas fordecades. local transmission has neverbeen identified in asia or australia.however, these regions are at risk for importation and many oftheir urban areas have aedes and susceptible human populations.during urban outbreaks, up to 30% of the susceptiblepopulation may be infected with yellow fever virus, but only 10%to 20% develop clinical disease. w.h.o. estimates that 200,000cases of yellow fever occur annually worldwide with 85% ofreported cases occurring in
subsaharan africa.yellow fever is an acute febrile illness presenting withheadache, myalgia, vomiting. up to 15% of symptomaticpatients develop severe disease with jaundice, hemorrhage, ormulti-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, humansare the primary amplifying host for zika virus during outbreaks.sylvatic transmission in
non-human primates occurred inafrica, but the role of other animals in maintaining the virusis not known. zika virus was first identifiedin uganda in 1947. over the next 60 years, studiessuggested the virus was present in many african and asiancountries. however, less than ten humandisease cases were reported worldwide.in 2007, the first outbreak of zika virus was identified inmicroneesia. since then, outbreaks haveincreasingly been recognized in
southeast asia and the westernpacific. zika virus will likely continueto spread to unaffected areas with aedes.last week the panamerican health organization reported the firstcases in brazil. the 2007 outbreak resulted in anestimated 900 disease cases in a population of less than 8,000people. based on a survey, 73% of thepopulation was infected and 18% of those infected developedclinical illness. over the past two years, morethan 30,000 suspected cases of
zika virus disease have beenreported from french polynesia and other pacific islands.in general, zika virus infection caused a mild acute illnesscharacterized by a rash. fevers are low grade and 25% to 35% of patients may be afebrile. there have been a few reports ofpossible other severe disease manifestations.no deaths have been reported. diagnostic testing is similarfor dengue, chikungunya, yellow fever, and zika virusinfections.
rt-pcr can defect viral rna inblood. neutralizing antibody testingshould be performed to confirm results and distinguishinfections due to closely related viruses.finally, for fatal cases, rtpcr and staining can be performed ontissues obtained at autopsy. there are no specific anti-viraltherapies for any of these infections.treatment is supportive and includes fluids.patients' hydration status should be assessed and otherconditions such as malaria and
bacterial infection should beevaluated for and treated as needed.all suspected cases should be managed as if they have dengueuntil it has been ruled out. there are no available vaccinesto prevent dengue, chikungunya, or zika infections.dengue vaccines have advanced to phase three clinical trials, butdevelopment is complicated by the need to protect against allfour virus types. several chikungunya vaccineshave completed phase one or two safety studies.live attenuated yellow fever
vaccine has been licensed andavailable since the 1930s and is widely used in endemic countriesand travelers. from 2007 through 2012, yellowfever vaccination campaigns led to an estimated 27% reduction inyellow fever cases in 11 endemic countries in west africa.other than yellow fever vaccine, the best way to preventaedes-borne diseases is to reduce mosquitos exposure.at a community level, mosquitos habitat control and applicationsof larvacide may reduce spread. however, controlling aedesrequires substantial resources
and is difficult to sustain ateffective levels. for travelers and otherpopulations where feasible, using air-conditioning, havingscreens on windows and doors, using insect repellant, andwearing long sleeves and pants can limit mosquitos exposure.finally, protecting people who are already infected fromfurther mosquitos exposure during their first week ofillness will prevent them from infecting new mosquitos andcontributing 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 diseaseshas increased, and the viruses have spread to new areas.these viruses are found in overlapping geographic areas andhave similar clinical features. there are no antiviral therapiesto treat these diseases, but proper clinical management canreduce dengue mortality. yellow fever vaccine is widelyused and effective. dengue and chikungunya vaccinesare in development.
until those are available,reducing mosquitos exposure is the best preventive measure, butcurrent vector control options are resource intensive anddifficult 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 withhumans.
stored water, discarded itemsthat accumulate water create abundant habitats for thedevelopment. this is an increasing problem inrapidly growing urban settings that lack adequate watersupplies, solid waste disposal, and have substandard housing.these conditions are often associated with high humanpopulation densities that are in close, biting contact with highdensities of aedes aegypti. this creates a situation wherethere'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 tofly very far, often living their entire life in a single house.during their lifetime, they seldom move more than 100 metersfrom their initial resting site. other important characteristicscompared to other mosquitos, this species has low populationdensity, often fewer than ten
adult females per house.and the distribution of their populations tends to be focaland dynamic so that over time there are changes in the numberof mosquitos per house and changes in the distribution ofinfested houses. only female aedes aegypti feedon blood, which they require to develop their eggs.they prefer to feed on humans and bite during the daytime whenpeople are engaged in their daily activity patterns.so compared to many other mosquitos species, aedes aegyptibites frequently, which
increases their fitness but alsoepidemiolologically, frequent human biting is one of the mostimportant reasons why this is such an efficient vector ofviruses. biting a human host is requiredfor virus transmission. aedes aegypti biting patternsfacilitate transmission. some people are bitten more thanothers, and frequent human contact can facilitate explosiveepidemic. because they live, frequentlybite, reproduce in close association with humans,epidemics can occur even when
aedes aegypti populations arelow. vector control for aedesaegypti-borne disease aims to reduce adult female populations,reduce the human biting rate, and reduce the number ofinfectious mosquitos. for sustained reductions inhuman infection and disease, vector control needs to maintainreductions in mosquitos populations below the levelsthat are required for virus transmission.but defining what those entomological thresholds are hasbeen a difficult thing to do.
in the past, entomologicalindices based on larval mosquitos were used to reducethe risk of a person getting infected.we now know they do not correlate well with humaninfection risk. consequently, there's been ashift to adult mosquitos. but that requires understandingof complex relationships among things like the susceptibilityof the human population, so herd immunity, contact rates betweenpeople and mosquitos, human density, the introduction ofnovel viruses, and weather.
with these kinds of constraintsin mind, what are the vector control options?of the methods currently available, larval control hasbeen difficult to use in a way that sustains epidemiologicimpact. the major categories currentlyavailable for larval control include container cleaning,manipulation and treatment, social campaigns that are basedon education, reduction of aquatic mosquitos developmentsites, and fines and penalties if larva or pupa are found onthe premise.
for adult control, currentlyavailable methods include space spray, which needs to be doneinside the house where aedes aegypti rest.outdoor spray of insecticide from trucks or planes isineffective because it doesn't reach the mosquitos that areinside human habitations. indoor residual or long-lastinginsecticides that are sprayed on surfaces inside houses can beeffective, as personal protection, repellants.but for all the chemical-based options, resistance toinsecticide is a threat and it's
a growing problem.among the various interventions that are currently underdevelopment, the four most promising include release ofinsects which aims to reduce mosquitos populations.infection with the bacteria to reduce mosquitos' capacity totransmit virus. and new insecticides that areeffective against resistant mosquitos populations.there are two strategies. the first renders the adultfemale flightless. males are released into thefield where they mate with
wild-type females.the heterozygote female cannot fly, so they can't mate, can'tbite 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 theiroffspring. the second strategy, males thatcause late-acting lethality are released into the field wherethey, 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 trialswith entomological outcomes in malaysia, the cayman islands,and brazil. the wolbachia is anendosymbiotic bacteria. the female pass the bacteria on,and infected mosquitos are about two-thirds to three-quartersless likely to become infected with and transmit dengue virus.this strategy infears with the mosquitos' ability to transmitthe virus. the offspring from infectedfemales are favored and the bacteria spread through themosquitos populations.
field trials with releaseinfected mosquitos have successfully establishedwolwachia infection and natural populations in australia.presently, field trials are being initiated to test theimpact of wolwachia on reducing dengue infections in humans.this strategy is interesting because it's one that could beused against other viruses, currently being done withdengue, but it's not limited to dengue.autocidal remove egg-laying and potentially infected aedesaegypti.
females are attracted to theseblack containers. when they attempt to lay theireggs, 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 enhancethe attractiveness of the traps are being explored.but as with other interventions under development, trials needto be carried out to determine the epidemiological impact ofthese different approaches. the innovative vector controlconsortium is partnering with
industries to develop newinsecticides. although this program isprimarily directed at malaria control, it could be applied toaedes aegypti. this group aims to develop threenew active ingredients by 2020, 2022.they also aim to make improvements in indoor residualsprays and insecticide-treated materials.due to limitations and aedes aegypti vector control and thechallenges of developing vaccines, especially for dengue,there's a growing consensus
there's not one best strategyfor aedes aegypti-borne disease control.support is growing, therefore, for strategies that combinevector control with vaccines. the complementary features arethat on one hand, vector control reduces the force of the virusinfection in humans, making it easier to reach vaccinedelivery. 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 thedetails of how to best combine these strategies and then howthey would be empirically tested.in summary, aedes aegypti is an efficient virus vector becauseit lives in close association with and bites humansfrequently. consequently, epidemics canoccur even when mosquitos densities are low.the lack of appropriate infrastructure, especially inmodern megacities, supports increasing aedes aegyptipopulations with high potential
for virus transmission.indoor residual insecticides have the greatest potentialamong existing tools to prevent disease.but these chemical-based interventions are challenged bygrowing concerns about insecticide resistance.so what are the steps that we could take moving forward?across all vector control approaches with aedesaegypti-borne disease, the existing ones and the new onehas are in development. there's an urgent need for epidemiological assessments of
those interventions.to what extent and under what circumstances do they preventinfections and disease. insecticide programs need toestablish effective resistance monitoring programs and means tomanage resistance once it's detected.among the interventions that are under development -- sorry.the most promising are genetic strategies, and that would beridl and wolbachia. a major form is scaling up fromthe small-scale local field trials to sustained coverageacross large areas in public
health programs.the future will require combinations of interventions.we don't see a single magic bullet among existing tools andstrategies. for those in development orthose currently available. moving forward, we need todefine which tools prevent disease, under whatcircumstances do they work, and when do they not work.once we have that kind of information, we can think morecarefully and clearly about how we can combine thoseinterventions to have a more
sustained impact.that ends my talk. the next speaker will bedr. harold margolis. [ applause ] >> thank you.good afternoon. so i'm located at thecdc 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 unitedstates. i'm going to focus on controland prevention of dengue, which
as you heard is a significantproblem for which we don't have single prevention strategies.just to review, dengue virus infections are primarilyasymptomatic. in contrast to chikungunya,which has a much higher symptomatic disease rate, denguepresented as problem mat nick terms of diagnose.there are no single set of symptoms or signs that identifythis infection or this disease. the typical course is four tofive days of fever, which then resolves, at which time upwardsof 10% of individuals can go on
to have severe dengue, whichi'll describe a little bit later.so one of the issues, and you've heard this say before, is thatsomebody with dengue should not die.so case management is extremely important, and the key thing insevere dengue is plasma leakage. it's not hemorrhage.it's this situation where compensated shock occurs, whichgoes on to decompensated shock. yes, a subset of individualswill have dengue hemorrhagic fever, which has really beenreplaced with severe dengue, and
this being a subset of severedengue. timely diagnosis is important interms of improved prognosis. if properly managed, whichreally requires the early recognition of compensated anddecompensated shock and proper fluid management, the vast, vastmajority of people will survive. case fatality rates are nowunder 0.1% in areas where these activities have beenimplemented. as you heard initially, cdc hasbeen involved in developing a course.this was primarily directed at
physicians in puerto rico, wherewe actually found that case management, in spite of being inan endemic area, was not ideal. for those who want to take careof either your patients that you're seeing overseas in dengueendemic areas or that you may be seeing as travelers returningwith dengue, i direct you to this four-hour course whichgives 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 otherillnesses such as influenza in the tropics, which look justlike dengue. clinical diagnosis is ofteninconclusive because many of these other diseases have fever,rash, periorbital pain and fever.accurate diagnosis is needed. we don't always get all thetypos out. lab tests for dengue incontrast, again, in things that have changed over the lastseveral years really depend on
the timing of when you see thepatient. what i'm going to do in the nextcartoon is to go through what happens during the course ofdengue and how we can now apply diagnostic tests to better findout what we have in a patient who presents to us.so if you look at the background, the incubationperiod, 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 oroccurs. then there's this post-febrilephase. if you look at the events -- andlet's go to the left-hand side of the cartoon.there is viremia. it's easily detectable bymolecular techniques, pcr, real-time pcr, or some antigendetection techniques. the igm elisa is what most of usare probably familiar with. but you see this diagnosticevent doesn't occur until three to five days after the onset ofillness.
by that time, many people arealready on their way home and aren't coming back to us.they really do present earlier. so it's putting these two teststogether that help us in terms of making a good confirmatorydiagnosis. what i've done is put thisalgorithm up hiere. if you see somebody within thefirst three days, what you just need is pcr.if you see somebody in the three to seven-day period, you needboth 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, whichdr. scott talked about,. you heard the difficulties withit. what i'm going to do is drilldown on vaccines and all of these we see as being evaluatedby surveillance. you yourself can protectyourself against dengue by using repellants.you've heard this again in
previous talks.there are a number of active ingredients, which i've listedhere. the key is you have to put themon. you have to put them on severaltimes a day. and you have to use them all thetime. they don't help in thecommunity. so for those of us who live inthe 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 wewould 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 mustprotect against all four dengue viruses.then there's a large implementation challenge aheadonce 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 doneby the classical passage approach.they've been made by genetically engineering these viruses andthen combining them into a single vaccine.there's a cell culture derived inactivated vaccine and also asubunit vaccine. the one that dr. frieden talkedabout is the one that was
initially developed by cdc.so where are they? well, the sanofi vaccine hascompleted phase three trials. there are two now that are goinginto phase three trials. and there are two that arebeginning to go from phase one into phase two.so there's a lot in the pipeline, and there's a lot ofinformation coming forward. now, all of these trials areactually 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-controlledtrials. age groups should be where thehighest incidence is. that's usually the 2 to16-year-olds in all dengue endemic areas.the sanofi trial had three doses of vaccine shown in phase twotrials that that's what you needed to get high antibodylevels. they used a normal salinevaccine. but some placebo should be used.and the end point, going back to my diagnostic comment, is we'relooking 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 theconcern about potential adverse events.so these trials are actually going on for 48 months, and theyare 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 inasia as well as trials in the americas and kind of go to thatarea that is circled by the yellow ellipse.you see that overall efficacy was a low of 30% to an averageof around 60%. and what was the cause of that?well, go down to dengue two. in the trial in thailand, theyhad a very large dengue two epidemic going on.they had very low efficacy. but you see that the lowefficacy for that component of
the vaccine continued in theother trials. also, dengue one seemed to havelower 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 monthsafter the trial. but long-term follow-up, as ipointed out, is needed to be sure that any waning immunitydoes not precipitate or cause
severe adverse events in peoplewho then later on may be exposed to dengue, a phenomena calledantibody dependent enhancement, which has been seen to cause asmall proportion of severe events in dengue.so where are we? and this goes back to thesummary 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 casefatality rates. lab diagnostics is reallydependent on getting the right
tests at the right stage ofillness. 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, enhancedsurveillance, rapid diagnosis, personal protection are stillthe best methods for preventing dengue.and in terms of future directions, as dr. scott pointedout, we need to evaluate the best ways to implementvaccination and also combine
that with vector control that isbeing used. these new control options andways to implement them need to be put into community-basedoutcome studies. there needs to be an improvementin diagnostic tests. everything i told you about arethings 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 shownto be effective, needs to be
continued, and education is akey part of that. and ultimately, we need to --every time we look, we find dengue where we didn't thinkdengue was. many of you were surprisedprobably to see that africa in those early maps was lit up witha lot of dengue. well, that was because itprobably 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 howwe're going to tell what's working.and vector control measures should be controlled andsustained. coordination of all of these andall these very different groups of investigators and people needto be working with each other in terms of going forward.thank you. [ applause ]>> thank you, dr. margolis. this session is now open forquestions. if people in the back can comeup to one of the microphones, i
think people in the front havemicrophones. if you could raise your handsand folks could limit themselves to one question.>> thank you for a very informative presentation.it seems that we don't have an infectious disease outbreakwhere the question of mosquitos-borne transmissiondoesn'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 thateffect. i'm not sure i fullyunderstand the question. why these diseases and notthe other diseases that come up and people say, well, can thisbe transmitted by mosquitos? i mean, why these diseasesare transmitted by mosquitos i think has a combination to dowith obviously the vectors which i think these people can speakbest to as their ability to be infected and obviously themosquitos species need to be
able to be infected, notaffected, to the point they can transmit it.then there needs to be some host, in several of the caseswe're talking about humans, and other mosquitos-borne viruses.those are other vertebrae animals that have levels highenough that when bitten by another mosquitos, thosemosquitos will become infected. again, the virus can live and betransmitted by those mosquitos. i don't really have much toadd to that except there's an intimate relationship betweenthe mosquitos and the virus but
also the human the host.so this needs to be able to replicate between two differenthosts, and that oftentimes is unusual.>> from our online audiences. how important is rapid diagnosisif there's no specific anti-viral against dengue orchikungunya? that's an important question.i think it's twofold. one is it does help theclinician, knowing that you really have a patient withdengue because you have many other diseases that look likeit, and you may be going, yes,
you go symptomatically, butknowing this is dengue. in the case of chikungunya,where both of these occur, it may also help you, and it doeshelp you, with giving that patient with chikungunyaanti-inflammatories. you don't want to give those tosomebody with dengue who may start having a bleeding episodebecause you interrupted their vascular integrity.the other part is surveillance. if you had huge lags in knowingwhat that, you know -- what those epidemic curves are, andwe'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 beingtransmitted in malaysia and came
from a retrospective freezerstudy. again, to date, there justhasn't been either full confirmation of that or newtypes. these are really virus typesthat have been identified. thank you.this is a really interesting, great presentation.i think one of the issues clearly there's a huge globaldisease burden from these mosquitos-borne diseases, but wealso saw the distribution of the two vectors, including parts ofthe united states and certainly
puerto rico.i thought people might be interested in some of yourthoughts, some of the experience with transmission of dengue,both in puerto rico, where it's endemic, and also in parts ofthe southern united states and what your thoughts are in termsof 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 vectorcontrol. 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 wheremosquitos are. and to me, that is much of whatgoes on with dengue. what we've been able to do inpuerto rico is really change the case fatality rates by bestcare.
i think this spills over withchikungunya. again, you saw some of thegraphics. my little quip is thatchikungunya tells you how good or bad your vector controlprogram is for aedes aegypti. because it just picks it outimmediately. i think for chikungunya,the -- there have been a number of models looking at risks oftransmissions 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 slightlyhigher and longer levels of viremia.you're going to see those infections.but probably dengue, where you see hundreds of thousands if notmillions of cases in the americas with thousands oftravel-associated cases, and then a relatively, you know,tens to hundreds of locally transmitted cases a year isprobably the best model or guesstimate we have for whatmight happen in the continental
united states with regard tochikungunya. and that's what we saw at leastin the first year of transmission with over a millionsuspected cases in the americas. a few thousand travel-associatedcases 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 seasonor coming years. so like marc said, mostpeople that get a chikungunya infection present with anapparent illness.
a lot of it in terms of in theunited states is going to depend on the extent to which mosquitoshave contact with people. so our lifestyle is differentand therefore i wouldn't expect -- i'll go out on a limb.i wouldn't expect there to be nearly as much depending oncommunities and how people live that we're seeing in other partsof the americas. mosquitos aren't biting us asoften. thank you.excellent point. i suffered from it twice wheni was living in the dominican
republic.interestingly to me, i've seen a lot of these different sort oftechniques to prevent mosquitos in general.but i know anecdotally i heard -- and i just wanted toknow if there's any real research behind the fact thatperhaps just a diet, maybe vitamin supplementation might beable to prevent mosquitos from biting certain people just inthe fact that it's interesting to me that i was surrounded bypeople who had lived there in the dominican republic theirwhole lives and never had
dengue, and yet i could walkinto a room where there were no mosquitos and all the suddenthere were mosquitos everywhere biting me.it just was odd to me that nobody else seem to be -- orthere was a certain component of something that i had that themosquitos wanted that they did not want from anyone else.i saw this happening a lot. i just thought that wasinteresting, some kind of p.h. or something that makes certainskin or blood more desirable than endemic.>> thank you.
i think dr. scott there addressthis. first of all, i'd like totest those people. i bet most of them had haddengue. maybe not apparent infectionsand didn't know it at the time. there clearly are differences inhow some individuals are bitten more often than others.the best explanation for that probably has to do withmicroflora bacteria that are on our skin that emit chemicalsthat attract the mosquitos. there are differences associatedwith age.
we tend to see middle-agedadults getting bitten more often than children.even within those categories, there are some individuals thatget bitten more often than others.there's no evidence that i know of that diet, garlic, beer, allkinds of things, have any impact on that.>> thank you. it's been well establishedthat dengue has spread throughout the world, throughall the continents. it's been well established thatchikungunya has recently spread
to the western hemisphere.and it's well established that zika is now in brazil and is inthe 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 answerfor you. there has been some spread ofyellow fever, but it's been in much limited ways.basically contiguous spread,
within the areas, within southamerica and africa where it's endemic.but no spread, as you say, to other continents, especiallyasia would be of great concern. i think the greatest differencethat i can point to is that the virus has not adapted to humansas the primary vertebrae host. humans have levels high enoughthey will transmit to mosquitos. fortunately, only in this urbancycle when aedes aegypti becomes involved has that been seen,whereas in the typical pattern of yellow fever, it has beenlimited so far to this sylvatic
or jungle cycle where othermosquitos and other hosts, mostly non-mum primates, areplaying a role. in addition, it doesn't addresswhy it hasn't spread to asia, but we have a vaccine.the vaccine has been available since the 1930s and can be usedto basically protect people who are going to endemic areas frombecoming infected and viremic, bringing it to other areas.those are two possible reasons that have reduced the risk ofspread. why we haven't seen anyoutbreaks or limited outbreaks
in those areas, i don't have ananswer for. there were three differenthypotheses that have been proposed.one of them had to do with different vector competence ofmosquitos in different parts of the world.there was a group at yale university that extensivelylooked at that and didn't see a difference.so the mosquitos in asia were competent to transmit yellowfever. there was another one that hadto do with movement of people
and that maybe they just weren'tmoving from places in africa where it would introduce it.but with global travel the way it is today that, didn't seemreasonable. and the third one, which we werejust conferring on this, hasn't been proven, so it's ahypothesis, has to do with nonreciprocal immunity.so if you're immune to dengue virus, you get some protectionagainst yellow fever. but if you've been vaccinatedfor yellow fever, you're not necessarily protected againstdengue.
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 haddengue. they may be protected for thatreason. susan?>> again, from online audiences. are there any complicationsafter chikungunya infection? i'm not aware of any.there have been viruses that have been identified inopthalmic tissues. but i'm not aware of anyclinical findings.
the chikungunya literature iscertainly expanding greatly in the last couple years with alarge outbreaks in the pacific and india and recently in theamericas. so i wouldn't be surprised if wesee 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 onto 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 ithas anything to do with the number of mosquito bites youhave. you're basically infected andit's an issue of your body's response.for dengue, which i'll let hal speak to, there may be someimmune mediated response. for chikungunya, the data arelimited. we know that older people andpeople with underlying medical conditions are more likely tohave more severe.
there's one study thatassociated 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 factorsthat are identified for people who go on to hemorrhage or moresevere disease. hal, do you want to speak todengue? there have been a lot ofhypotheses 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 andwhere you can do it is viral load.so those people with the highest dengue virus tiders during thecourse of their illness tend to be those that go on and havesevere dengue. past that, it's this whole raftof 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
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