• ## Summary

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• 00:01

[MUSIC PLAYING]

• 00:11

DAVID HEYMANN: Epidemiology is the studyof a disease in humans.It tells who gets infected, when they get infected,why they get infected, and how they get infected.It also looks at people who are sick and triesto clearly define the clinical syndrome-- that means the signsand symptoms that the patient has--at every stage of disease.

• 00:40

DAVID HEYMANN [continued]: There are many different ways of approaching epidemiology.Some is descriptive, when you lookat who's being infected, how they're being infected.And you just describe a little bit what you know.If you don't know how people are getting infected,then there is further study that's required.In many times, this is done by a case control study, whichtakes cases or people who have the disease and people whohave the same age, the same sex, and the same background whodon't have disease.

• 01:13

DAVID HEYMANN [continued]: And you try to compare them with a standard questionnaire thatlooks for risk factors of disease.For example, if you're at a wedding and people get sick,and you suspect that it's the ice cream that was tainted,then you look at all the people who are sick,and you ask them a series of questions about whatthey ate at the wedding.

• 01:35

DAVID HEYMANN [continued]: And you do the same thing with the controls.And by comparing the cases and controls,you can decide whether or not ice cream was a risk factor.There are also other ways of doing epidemiological study.And that's what's called an epidemiological modeling.When you take what's known about a diseaseor you identify things through research about that disease,then you put them into a computer model,which assimilates all this informationand tells you a little bit more about the disease,about what you might expect.

• 02:10

DAVID HEYMANN [continued]: And this is especially important in projectinghow many cases of disease there might be in the future.But it's always very tricky with epidemiological modeling,because many times people take itas truth, when all it is as an estimate basedon the information that's used to createthe epidemiological model.Epidemiological studies can also bestudies that determine whether or notwhat you're doing to prevent or control the diseaseis effective and, if it isn't an effective,how to rectify the problems.

• 02:42

DAVID HEYMANN [continued]: A good example is, back in the 1980s in Malawi,where women were refusing to take the medicine thatprevented malaria.And it's very important to prevent malaria,especially in pregnant women, because if they get malariawhile they're pregnant, their child could have a lower birthweight, and they could actually become very sick.

• 03:03

DAVID HEYMANN [continued]: So women were not taking their medicine,and it was important to find out why.And so a study was done, first by focus groups sittingwith a group of women-- a woman of their own culture-- sittingwith them to determine what it was about the medicine thatwasn't suiting them.

• 03:24

DAVID HEYMANN [continued]: And what they said was that this medicine tasted bitterand it tasted like herbs that theywere using to cause abortion.Many times they wanted to have an abortion.And they took a bitter medicine that caused abortion.And they associated this medicine with an abortion.So in order to overcome the problem, it was simple.

• 03:46

DAVID HEYMANN [continued]: It was sugar-coated anti-malarial medicines,which were given to the women.And the problem was over.They took the medicine, and they prevented malaria.So research can be very simple, or it can be very complex.The research was in the focus group to begin with.Then after the chloroquine was sugar-coated,it was given to the women.

• 04:08

DAVID HEYMANN [continued]: And there was actually a test thatcould determine in their urine whether or notthey had taken the medicine.So it wasn't just focus groups.And would be wrong to just assume from a focus groupthat this would rectify the problem.Actually, you have to prove that your intervention ishaving an effect.And this was done by making sure that women were taking it,looking for the products of the chloroquine, whichwas the antimalarial drug in their urine.

• 04:35

DAVID HEYMANN [continued]: Another study that was done at the same time in neonates,children who were just born in Malawi,was a study to compare risk factors for their birth weight.Children who had low birth weightwere given a series of examinations.And also their mothers were questioned about any diseasethat they might have had during pregnancy.

• 04:60

DAVID HEYMANN [continued]: And their hospital records were also examined.A group of controls were also identified.And that was children with normal birth weight.And they were given the same questions.They were given the same examination.Their mothers were given the same questions.And the mothers' records were also searched.And by comparing the two, it became very clearthat malaria was a risk factor for low birth weight.

• 05:27

DAVID HEYMANN [continued]: Today, there's a new virus that'semerged in the Middle East.It's called the Middle East Respiratory Syndrome virus.And this virus is very similar to a virus whichemerged in 2003 called the SARS virus--Severe Acute Respiratory Syndrome virus.The virus in the Middle East causes severe diseasein people who are elderly or who have chronic diseases,such as diabetes.

• 05:53

DAVID HEYMANN [continued]: They get very sick and they die.There are two ways that this disease is transmitted.And we know this from epidemiological research.One way is in hospitals, where poor hospital practices,such as not sterilizing needles and syringesor not washing hands between patients,spreads the infection in hospitals.

• 06:14

DAVID HEYMANN [continued]: A case control study has shown that peoplewho get infected in hospitals getinfected because health workers are notmaintaining good infection control practices.There's another problem, though, with the Middle EastRespiratory Syndrome virus in that it comes from natureinto humans occasionally.And those humans who get infected from naturethen can go to a hospital.

• 06:37

DAVID HEYMANN [continued]: And that spreads into the hospital.The problem is that it's not known where this virus comesfrom in nature.There's been a lot of research comparing the genetic sequenceof this virus to other genetic sequences of virusesin animals.And it's thought that this virus haspossibly a reservoir in bats, which means that batscarry it and are healthy.

• 07:03

DAVID HEYMANN [continued]: And then bats somehow infect camels, who then get infectedand somehow infect humans.The way to determine how camels infect humansis through a case control study.Cases are persons who are infected, who are sick.A series of questions looking at what their behavior mightbe with camels is the way to identify risk factors.

• 07:25

DAVID HEYMANN [continued]: And then on the other side, you lookat people who don't have illness,who are the same age and the same sex,the same economic background, and tryto figure out if they've had this same type of contactwith camels.In order to get an idea of what the contact mightbe, of course, first of all, there'sa need for a focus group to sit down with peopleand see what their practices are as they interact with camels.

• 07:53

DAVID HEYMANN [continued]: Research such as this research on MERS coronavirus-- MiddleEast Respiratory Syndrome virus--occurs when a group of viologists--those are people who study viruses-- and epidemiologistsget together and try to identify where it's coming from,how it might be spread to humans,and a whole series of other issues around the disease.

• 08:16

DAVID HEYMANN [continued]: At the same time, clinical doctorsare also important, because they help in the studiesto identify what the signs and symptoms are of the disease,whether or not there are people whoare infected who have less severe disease,and a whole series of issues.So working together, epidemiologists, virologists,and clinicians can solve the problemof where MERS comes from in nature, how it infects humans,and what the signs and symptoms are in those people whoare infected.

• 08:47

DAVID HEYMANN [continued]: The studies around this is new and emerging virushave already shown how to stop transmission in hospitals.It's by good hospital practices.And in the Middle East, the virushas been stopped from transmitting in hospitals.However, people still occasionally getinfected from nature.And it's not known how they're getting infected.

• 09:09

DAVID HEYMANN [continued]: And those people can then travel.And what happened was one person did get infectedand went to Korea, was admitted to a hospitalin Korea-- South Korea-- where he was quite sick.And from him, others became infected,because in South Korea, hospital practices and infection controlwere not up to standard.

• 09:29

DAVID HEYMANN [continued]: Another example is the Severe Acute Respiratory Syndromevirus-- the SARS virus-- which emerged from nature probablyfrom wild animals in an animal market somewhere in China.And these viruses then infected humans.And one person was infected with a viruswhich had mutated in such a way that it was very virulent.

• 09:50

DAVID HEYMANN [continued]: We know this from backwards lookingduring the epidemiological research.What we also know about this outbreakcame from virtual networks of virologists,of clinicians, and of epidemiologists,who were working together almost around the clock virtuallywith people based at each site wherethe outbreak was occurring.

• 10:16

DAVID HEYMANN [continued]: And this was in Canada, in Asia, in the US,and many, many countries around the world whereSARS was occurring.And so by exchanging information on a daily basisthrough the internet, with occasional telephone or videoconferences, these three virtual networkswere able to work together at a global leveland provide the evidence which showedwhat caused the disease, how it was spread,and how it could be prevented.

• 10:44

DAVID HEYMANN [continued]: This evidence was then taken by the World Health Organizationand was provided as real-time policyon how the outbreak could be controlled.So if you were living in any country in the worldand were afraid of the SARS coronavirus outbreaks,you could go to the WHO website.You could find guidelines on surveillance,which means how to identify people with the illness.

• 11:07

DAVID HEYMANN [continued]: You could find guidelines on what was causing it.And you could find guidelines on a whole seriesof other activity.Emerging infections are very important today.Emerging infections are newly identified infectious diseasesin humans.These diseases, the organisms that cause these diseases,come from an animal in nature.

• 11:34

DAVID HEYMANN [continued]: So the animal-human interface is very important.What happens is an organism that'sbeing carried by an animal successfully breachesthe species barrier between animals and humansand infects a human.When a human is infected, there are three possible pathwaysfor that organism.

• 11:56

DAVID HEYMANN [continued]: For example, a human can be infected with an organismand is a dead end for that organism.That human cannot transmit the disease further.A good example is rabies.Rabies is transmitted to humans by a dog,but it doesn't go further.It's a dead end in humans, but it does cause serious illnessand death.

• 12:19

DAVID HEYMANN [continued]: Then there are emerging infectionswhich infect humans and can transmitfrom human to human but in a very localized areaand not very efficiently.They circulate for a while in human populations.And they disappear, but they can re-emerge.And a good example of this is avian influenza, bird flu,which was first identified in 1997.

• 12:44

DAVID HEYMANN [continued]: It occasionally infects humans.It then causes an outbreak.But then it disappears again.Another example is Ebola.Ebola is an outbreak, which surfaces from natureinto one human.It then spreads because of poor hospital practices,where infection control is not practiced to others.And then it causes an epidemic.

• 13:05

DAVID HEYMANN [continued]: But Ebola then eventually disappears,and it resurfaces at a future time.The third type of emergence is one that emerges in humans,finds it very easy to transmit from human to human,and becomes an endemic disease, a disease whichis with us always.And a good example of that is HIV infection or AIDS.

• 13:27

DAVID HEYMANN [continued]: And, in fact, most infections thatare endemic in humans-- like TB, like malaria, like measles--have all come from the animal kingdominto humans, successfully breaching that barrierand then causing endemic disease transmission from personto person in humans.What's important about emerging infections is not what is knownbut what is not known.

• 13:49

DAVID HEYMANN [continued]: And when a new organism enters human populations,the major concern, of course, is that itwill take that third pathway and becomean endemic disease, a disease that'sin humans for the rest of time.Influenza is a very interesting disease,because influenza comes from nature.It's thought that there are about 18 different typesof influenza virus.

• 14:12

DAVID HEYMANN [continued]: And these are harbored in wild waterfowl, wild birds thatlive in the water.Occasionally, these viruses crossthe barrier between the wild bird and humansand cause infection in humans.They can also cause infection in animals.So when they breach that barrier and cause infectionin humans or in other animals, they'rethen able sometimes to mutate in a way thatmakes them more transmissible or less transmissible.

• 14:42

DAVID HEYMANN [continued]: And when that occurs, they can then cause a pandemic.Let's go back to H5N1, which is bird flu.That first emerged in Hong Kong in 1997from some type of a duck into poultry populationsin Hong Kong.And those poultry populations-- mainlychickens that were being sold in wild markets-- became sick.

• 15:06

DAVID HEYMANN [continued]: And humans that bought those sick chickens becameinfected with this virus.This virus has been around since 1997 in chickensand still occasionally infects humans.And it's mutating slowly as it transmits to humans,because viruses have to reproduce within a living cell.

• 15:27

DAVID HEYMANN [continued]: Viruses cannot produce without taking over the machinerywithin a cell and beginning to reproduce with that machinery.So what happens is a virus that enters a human or any animalenters a cell in that animal or human,takes over the reproductive process of that cell,and reproduces itself.

• 15:49

DAVID HEYMANN [continued]: In reproducing itself, there can bemistakes made in the genetic sequencing of that organismso that they mutate.And sometimes they mutate in such a waythat they become more transmissibleand then cause a pandemic.At other times, they don't.They just become a virus which periodicallyinfects humans like bird flu.

• 16:11

DAVID HEYMANN [continued]: The big concern of an emerging infectionis to know what the outcome will be.Is it a one-time event?Will it reoccur?Or will it become an endemic disease?A good example of this is the first outbreakof Ebola, which occurred in 1976.In 1976, the study, the epidemiological study,of that outbreak showed clearly that this was an outbreak whichshouldn't have occurred.

• 16:39

DAVID HEYMANN [continued]: It occurred because a patient got into a hospitalwhere needles and syringes were not being sterilized.And from the initial patient, womenin the maternity in the hospital gotinfected by non-sterilized needles and syringes.This outbreak occurred.But by the time the teams got there to investigate it--I was a part of those initial teams.

• 17:02

DAVID HEYMANN [continued]: By the time the teams got there to investigate it,the outbreak had already stopped,because this virus is its own worst enemy.It's too virulent.It kills people too rapidly to beable to sustain itself in human populations, fortunately.So what was known after that outbreak wasthat the outbreak occurred because of poor infectioncontrol in the hospital.

• 17:25

DAVID HEYMANN [continued]: The question was, would it reoccur?And if it reoccurred, would it cause another outbreak?Well, it took only a year to find outthat, yes, it would reoccur.It did reoccur.It reoccurred in a hospital about 250 kilometersfrom the original hospital.But in that hospital, the doctor who was heading the hospitalhad actually been at the Yamkuku outbreak and seen cases.

• 17:49

DAVID HEYMANN [continued]: So he knew he seeing Ebola.He isolated that patient immediately,and there was no further transmission, no outbreak.And then through a study done for five yearsat that hospital, it was found that Ebolaemerges every year during the rainy seasoninto human populations.But the humans understand this disease.

• 18:10

DAVID HEYMANN [continued]: They understand that it's very serious.And to them, it's a human who's beeninfected with evil spirits, and they stay away.They stay away.They take care so that they don't get infected,because they've seen this many, many times.And they know they have to stay away.So the outbreaks never occur.So that's why it's important to do a complete studyat the beginning, and gradually more and more informationis known.

• 18:34

DAVID HEYMANN [continued]: After that outbreak that occurredin 1977, the second outbreak of Ebola,there were a whole series of animal studiesthat were conducted by epidemiologists to look and seewhether or not it could be found where that virus was in nature.It was found, for example, the pygmies livingin the Congo basin had antibody evidencethat they might have been infected with the Ebola virus.

• 18:59

DAVID HEYMANN [continued]: So a study was set up by a group of epidemiologiststo work with those pygmies so that they could go out and dotheir hunting every day; bring back the animals that theyusually bring back; provide them to a team, which includedan expert from the Smithsonian who could identify the animals,and then a group of virologists and epidemiologistswho could harvest the organs from those animals,put them in liquid nitrogen, send them offto a laboratory in the US, where that could be studied,looking for a virus in animals, hoping to find the reservoir,that virus in nature.

• 19:36

DAVID HEYMANN [continued]: It was not possible.It didn't occur.But what did occur a few years laterwas that Bob Swanepoel, one of the virologistswho had been working to try to find outwhere Ebola was harbored in nature, reversed the process.It was highly suspect that bats and small rodentscould be carrying this virus.And so he took those animals into his laboratoryin South Africa, a maximum security laboratory, infectedthem with the Ebola virus to see which animals could surviveinfection and which could possibly be carriers,and he founded fruit bats could be infectedand didn't get sick, whereas all the other animals got sickand died.

• 20:15

DAVID HEYMANN [continued]: So the hypothesis today is that fruit bats carry that virus.A whole series of research projects to better understandthe disease.And this is important so we can prevent infectionsfrom occurring if possible.So what needs to be done is the maximum amount of informationmust be collected whenever an outbreak occurs.

• 20:36

DAVID HEYMANN [continued]: Following onto the networks that were establishedduring the SARS outbreak back in 2003, a group at Oxfordhas set up what's called ISARIC, an international groupof clinicians and epidemiologistswho have protocols ready to move out immediatelywhen there's a new disease.

• 20:57

DAVID HEYMANN [continued]: They go out.They study the disease with the World Health Organizationand try to identify where it's coming from,how it's infecting humans, what the signs and symptoms areof the disease, and what to expect in the futureand, most importantly, how to prevent it from reoccurring.

• 21:17

DAVID HEYMANN [continued]: Each new emerging infectious diseaseis really a detective story.It's a mission to be accomplished.And it's a mission to be accomplished usingmost up-to-date technologies.What needs to be understood is what the organismis that's causing the infection, what it looks like genetically,what it looks like as it infects humansand what the signs and symptoms are that occur,and a whole series of other information about the organismthat causes the infection and the way it manifests itselfin humans.

• 21:52

DAVID HEYMANN [continued]: Also important is to understand where it comes fromand how it can be prevented from comingfrom there in the future.When a new infectious diseases is identified,the goal is prevention.That's always the goal from any infectious diseasesis prevention or at least control earlyin the course of infection.

• 22:13

DAVID HEYMANN [continued]: And so what needs to be done is bringing togetherdifferent types of researchers to understand moreabout that disease.Each disease is different.Each infection comes from a different source.But each can be investigated using the same basic outbreakinvestigation principles.

• 22:34

DAVID HEYMANN [continued]: In the first people outbreak in 1976,nothing was known about this virus.It was important to get all the information possible.So there were studies looking at howtransmission might have occurred,and that was understood.What was also important was to understandwhere the disease had been.And that was done by taking bloodsfrom people who lived in communities surroundingthe hospital where the outbreak occurred.

• 23:02

DAVID HEYMANN [continued]: Collecting blood from those peoplethen was a means of identifying whether or notthey had antibody to the Ebola virus, whichwould tell whether or not they were infected.So when you do a study like this, called a serosurvey,you collect blood from persons who you feel you need to study.But you also have to have a detailed questionnaireto see whether or not, if they do have antibody,they had signs and symptoms.

• 23:29

DAVID HEYMANN [continued]: So every person who studied fills inor is asked to answer questions for a questionnaire,a standard questionnaire.Then can do this of their own well.But they can't be forced to do this.So if a person doesn't want to answer those questions,they should not be forced to answer those questions.If they answer them, understandingwhy they're answering those questions,and you collect a blood from that person,then you can begin to correlate whether or notthey had infection with what their signs and symptoms were.

• 24:01

DAVID HEYMANN [continued]: You can then take people who have antibody in their bloodand compare them to the group that didn't have antibody.Back in the 1960s, smallpox was a diseasewhich was killing almost 2.7 million people each year.It was a very serious infectious disease.

• 24:23

DAVID HEYMANN [continued]: And it was one for which there was a vaccine.The problem was that that vaccinewasn't equitably distributed.And so the disease was occurring in developing countries.And occasionally it came into an industrialized country,with a person who came there to work or to live or to visit.So smallpox was a very serious infectious disease,which was able to spread around the world.

• 24:48

DAVID HEYMANN [continued]: And an eradication program began whichwas successful in getting rid of that infectionby the year 1980.After that, there was an attempt to find another disease whichcould be eradicated.And the scientific community focused on polio.Now, polio is a different disease from smallpox.

• 25:09

DAVID HEYMANN [continued]: And it was quite a big challenge to set up an eradicationprogram for polio.Smallpox is caused by a virus.Every person infected shows clinical signs and symptomsof smallpox.So if you find that person, if you isolate that person,if you identify all people who had contact with that personand vaccinated them or isolate them if they get sick,you can stop smallpox very easily.

• 25:37

DAVID HEYMANN [continued]: It was a very easy program to run,because everybody that had smallpox had the virus.In polio, for every person who gets paralyzed by polio,there are up to 500 people who are infectedand don't get polio, but that polio virusis still circulating.So to stop polio, you can't just findthe persons who are infected, youhave to make sure that everybody is vaccinated.

• 26:01

DAVID HEYMANN [continued]: So whereas in smallpox you could dowhat's called ring containment-- find a person,isolate that person, vaccinate all contacts and all peopleliving near that person.In polio, you have to vaccinate the whole population,because you don't know where the virus is.So it's an entirely different program whichdepends on mass vaccination.

• 26:22

DAVID HEYMANN [continued]: Vaccination is required until you reacha level called herd immunity.Herd immunity is when there's enough people in the populationimmune from vaccination that the virus can no longer passfrom human to human and pass to those who aren't vaccinated.So herd immunity is a very high coverage of vaccine--maybe 90%, 95%-- which protects not only those who arevaccinated but those who are unvaccinated because the virusstops transmitting to those people in the environment.

• 26:60

DAVID HEYMANN [continued]: Polio eradication therefore was a very different programfrom smallpox, depending on mass vaccination.And it's been a very costly program.To date, the program has cost about $12 billion US dollars.And it will cost at least$15 to \$20 billionbefore polio is eradicated.Smallpox eradication back in the '60s and '70scost 300 million US dollars.

• 27:24

DAVID HEYMANN [continued]: So you can see there's a very big difference today becauseof a difference in strategy and because thingsare more expensive today than they were in '67.I've been a medical epidemiologist from the Centersfor Disease Control in Atlanta since the early 1970s.My first assignment was to smallpox eradication in India.

• 27:46

DAVID HEYMANN [continued]: Second assignment was for 13 years in sub-Saharan Africaworking with diseases such as malaria and Ebola.In fact, my first assignment in Africawas the Ebola outbreak in 1976.And then I was seconded by the Center for Disease Controlto the World Health Organization, whereI headed various infectious disease controlprograms, including polio eradication,including emerging infectious diseases,and finally including all infectious diseases.

• 28:15

DAVID HEYMANN [continued]: In polio, I led the Global Partnership to eradicate polio.That required constant interactionwith many, many different partnersaround the world working on polio eradication, includingcountries.So if countries had a difficulty with polio,we would try to work with those countriesto help them identify the problemsthrough epidemiological research and overcome those problems.

• 28:41

DAVID HEYMANN [continued]: At the same time, there were many problemswhich had nothing to do with public healthbut which were political problems.We also had to work with them.A good example is in 2003, when northern Nigeria stoppedvaccinating against polio.Nigeria was almost free of polio in 2003.And all the other countries in West Africa were free of polio.

• 29:04

DAVID HEYMANN [continued]: But Nigeria stopped vaccinating because there was a feelingby some of the political leaders that this vaccine wasa Western plot to sterilize young Muslim girls.So vaccination was stopped.Rumors were rife throughout northern Nigeria.And children begin to develop polio.

• 29:25

DAVID HEYMANN [continued]: And in addition, the virus spreadto 18 polio-free countries, from Nigeriathrough Saudi Arabia all the way into Indonesian.So by a difficulty, a political difficulty in northern Nigeria,because this had nothing to do with public health.It was a political issue in northern Nigeria.

• 29:47

DAVID HEYMANN [continued]: The rest of the world became reinfected with polio.So in order to stop that, it was a whole seriesof activities that needed to be done,including getting religious leaders engagedin helping get rid of the myths and, more importantly,getting the governor of Kano State, who was promulgatingthis myth to stop doing that.

• 30:10

DAVID HEYMANN [continued]: And to do that, it required helping himunderstand the problem.One of the problems was that 82% of all children with poliowere living in his part of Nigeria.To get him to understand the problem and to help themget out of that problem in a way that could save face for him.And so that was part of the activities as well.

• 30:30

DAVID HEYMANN [continued]: So those are some of the activitiesthat you must do as a leader of a polio program.But others include making sure that the program'sworking properly technically.And this was very important in India,where it was found that the polio vaccine thathad worked in countries around the worldwas not working properly in India.It was found that this vaccine, whichcontains three viruses-- type 1, type 2, type 3 polio vaccine--and is a living virus vaccine, for some reasonwas not causing immunity in children.

• 31:02

DAVID HEYMANN [continued]: They were given up to 10 doses of vaccineand still didn't have immunity.By looking at literature from the past-- whichhad done some studies in India with polio vaccination--and also by doing some epidemiological studiesat the present, it was found that this vaccine wasn'tworking probably because each of the types of viruswere different in their ability to cause immunity in humans.

• 31:29

DAVID HEYMANN [continued]: Type 2 was the most efficient.Type 1 and type 3 were not efficient.And they were competing with each otherfor the same receptor sites in the intestine,which permitted the virus to enter the bodyand cause immunity.So the solution was to break up this vaccineinto three different vaccines-- a type 2 vaccine, a type 2vaccine, and a type 3 vaccine.

• 31:53

DAVID HEYMANN [continued]: That was done with funding from the Gates Foundation, the Billand Melinda Gates Foundation.And the vaccine, the monovalent vaccines-- type 1, type 2,type 3 vaccines-- were put into study, epidemiological study,to see if they were effective, and they were.So those vaccines were then adopted within India,and polio was eliminated from India.

• 32:15

DAVID HEYMANN [continued]: Research on polio was of several different types.One was to look at what's called backgroundimmunity in countries, to look at how many childrenare infected.Because if polio isn't being eliminated or eradicatedin that country, it may be because children are nothighly enough protected.

• 32:35

DAVID HEYMANN [continued]: Remember, to eradicate a disease,you must reach herd immunity.So looking at the level of immunity in childrenis a good way of determining how close you are to reachingeradication or elimination.So that was a very important study-- taking bloodfrom children under the age of five years,looking to see if they were protectedand how well they were protected.

• 32:57

DAVID HEYMANN [continued]: If they weren't being protected in one part of the countryor another, then it was important to go and furtherstudy to find out why they weren't being infected.Was it because the vaccine was not goodand had not been kept cold?Was it because vaccination techniqueswere not being done properly?Or was it just because there was a false registration of peoplebeing vaccinated or thinking that people were vaccinatedwhen they weren't?

• 33:22

DAVID HEYMANN [continued]: A whole series of issues that hadto be investigated to put the program back on track.In addition, there were children whohad been vaccinated up to 10 times whowere still getting polio.That required additional study.And we just talked about that study.There were other studies that were needed in polio programsaround the world.And one of those was a study to determine whether or notthere could be a vaccine which could replace the vaccine beingused in polio eradication.

• 33:53

DAVID HEYMANN [continued]: The vaccine being used in polio eradicationis a live virus vaccine.But those viruses are attenuated.They don't cause disease, but they causethe body to produce antibody.Those viruses also unfortunately canmutate once they are in nature, passing from human to human,because they pass from human to human just like other polioviruses.

• 34:17

DAVID HEYMANN [continued]: They can mutate in such a way that they becomeviruses which cause paralysis.And so that vaccine is not a safe vaccineto continue using after polio eradication has been completed.So it's necessary to study other vaccines, vaccinesthat are made from viruses which have been killed,to see whether or not they can be effectively usedin developing countries.

• 34:39

DAVID HEYMANN [continued]: So that's some of the other studiesthat need to be done, studies looking at the future.And finally, once polio is eradicated,that virus will still be present in some laboratorieswhere they're studying the virus or whereit's been accidentally stored with bloods thatare stored for other reasons.And so it's necessary that an inventoryis known of every laboratory which might have polio virus.

• 35:04

DAVID HEYMANN [continued]: And they must either destroy that virusor provide it to a safekeeping laboratory, wherethe virus can be stored.The polio eradication program began in 1988.And the initial target was to complete eradicationby the year 2000.That program began by building on routine vaccinationprograms, because polio vaccine was alreadybeing used in routine immunization programsthroughout the world.

• 35:32

DAVID HEYMANN [continued]: Those countries that had good immunization programshad very little difficulty in increasing herd immunityby having what they called campaignsto go door to door to give vaccine to all children,hoping that they could increase the coverage to a level itthere was herd immunity and stop transmission.So by the year 2000, most countries,through routine programs and supplemental immunizationcampaigns going door to door, were able to get rid of polio.

• 36:03

DAVID HEYMANN [continued]: In 2000, though, there were six countries that still had polio.And they had polio because their routine immunization programshad not been strong enough to permit easy attainment of herdimmunity and eradication.So solutions had to be found for those countries.And those solutions included more campaignsand strengthening of their routine programs.

• 36:29

DAVID HEYMANN [continued]: The polio eradication program depends on one strategy.And that strategy is identifying wherepolio is occurring and then havinga mass campaign around that polioand increasing the strength of the routine immunizationprograms.That surveillance system is quite a phenomenal system,because it's in every country of the world.

• 36:52

DAVID HEYMANN [continued]: And it's looking for people who havewhat's called acute flaccid paralysis, which is paralysiscaused by polio and by other organisms as welland other phenomena.But if you find every person who has flaccid paralysisand collect a specimen of stool, a feces specimenfrom that person, send it to a laboratory,it can be determined whether that is polio or notby a laboratory analysis.

• 37:21

DAVID HEYMANN [continued]: That surveillance system, which is throughout the world,requires certain standards.It requires that, within a period of two weeks,a person who has been shown to have flaccid paralysisis examined and does have a specimen collectedand another specimen collected after two weeks.

• 37:41

DAVID HEYMANN [continued]: And it also requires that there isa certain level of flaccid paralysisthat's reported by countries.Because if they're not reporting flaccid paralysis, eventhough it might not be polio, they'renot doing the job as well as they should be.So there have been the standards set in the worldthat there should be at least 1 child per 10,000 reportedwith acute flaccid paralysis during each week.

• 38:09

DAVID HEYMANN [continued]: At the same time, that child shouldhave been examined within the time set out.This information is collected in countries,provided to WHO regional offices,and provided to the World Health Organizationin Geneva, where every week there'sa meeting that looks to determine where there areproblems where countries aren't doing this surveillance, whichunderpins polio eradication.

• 38:31

DAVID HEYMANN [continued]: If they're not doing it, then remedies are found,and they're encouraged to increase their activity.That surveillance system depends on genetic sequencingof the polio virus once it's found.And through that genetic sequence,it's possible to determine where that virus camefrom by linking it to its predecessors,because this virus mutates but on a regular basis.

• 38:59

DAVID HEYMANN [continued]: So you can take a virus today and,through its genetic sequence and comparisonwith a database of genetic sequencesfrom throughout the world, determine where it came fromand how long it's been circulated.A good example of this is polio that entered Angola backin 2007 or 2008.

• 39:21

DAVID HEYMANN [continued]: It entered Angola, which was a polio-free country.And the genetic sequence showed that,if it come to Angola from India, where polio was stillcirculating, and the hypothesis isthat it came in a worker who had cometo Angola from India to work on the oil platforms there.

• 39:43

DAVID HEYMANN [continued]: Back in the 1970s, when I was working in Cameroon,there was a question they had come upthat was very important as people begin to thinkabout eradicating polio.That question was, did the polio virus and vaccine spreadfrom person to person?And if it did, did it cause immunity in the personsto whom it spread?

• 40:08

DAVID HEYMANN [continued]: And so we designed a study that lookedat children who were vaccinated that took a blood from a childwhen vaccinated and then two weeks after vaccination to seewhether or not they had had a seroconversion, whichmeans antibody production due to the vaccine.The initial specimen must be negative for antibody.

• 40:31

DAVID HEYMANN [continued]: The specimen two weeks later mustbe positive at a certain level.At the same time, looking at family members, parents,other children in the household whoweren't given polio vaccine, blood specimens and specimensof their feces were collected to see whether or notthey had been infected or were carrying the polio vaccinevirus, because it was very important to knowwhether that virus was circulating.

• 40:59

DAVID HEYMANN [continued]: Through that study and through a comparison,it was found that family members did get infected,did carry the virus, and could carry it for up to a monthafter the child in their family had been vaccinated.This was very important to know, because many of these peoplehad had polio as children, yet they were still carryingthat virus in their intestines.

• 41:23

DAVID HEYMANN [continued]: This then led on to further studies,which were done by others to look at polio vaccine.Another example of research whichwas developed to answer a questionwas in Malawi, when I was working in Malawi.In Malawi, the basic medication, chloroquine,that was being used to treat children with malaria,was not successfully treating all children.

• 41:48

DAVID HEYMANN [continued]: And it was known that that parasite wasmutating in such a way that it was becomingresistant to chloroquine.The question was, when should the governmentchange from this medication, which was very inexpensive-- Itonly cost about 1 US cent a dose--when should they change from this medicationto another medication to protect their children?

• 42:11

DAVID HEYMANN [continued]: And so discussions with the governmentdecided that they could accept if 10% of their childrenweren't successfully treated the first time with chloroquine,because then they would be treated againwith another drug.But they didn't want more than 10% of their childrento become infected with malaria and not be successfully treatedwith chloroquine.

• 42:34

DAVID HEYMANN [continued]: So by looking at research and epidemiological methods thathad been used around the world, wecame upon a method which is used by the car industryto determine the quality of their vehicles.This is called Lot Quality Assurance Sampling.

• 42:54

DAVID HEYMANN [continued]: And what the industry does is they set a thresholdof acceptance for a defect.For example, they might set a threshold of 2% for a dentsomewhere in the body of the car before it's put on the market.So they could accept if 2% of their cars had a dentbut no more.To do this, they had developed a technologywhich looked at a series of vehiclesand examined them closely for dents.

• 43:21

DAVID HEYMANN [continued]: And by doing a certain number of vehicles in a sequence,they could determine whether that 2% thresholdhad been passed.And then they would begin to look for problemsin the production line.This was adapted to use in Malawi in malariaby looking at a sequence of children who had malaria.

• 43:43

DAVID HEYMANN [continued]: In fact, looking at just 37 children,taking a blood from them, giving themchloroquine-- which was the drug that they were usingat that time-- and then two weeks later seeingif they still have malaria or not.In that 37-child sample, there wasa sequence of children coming in with malaria.

• 44:04

DAVID HEYMANN [continued]: If two or fewer of those childrenhad malaria two weeks later, then that 10% thresholdhad not been passed, and the governmentdid not change its medication.But if that 10% threshold were passed,then the government wanted to do further studiesto put a new drug into that same testing methodologyto see whether that was effective at lowerthan 10% level.

• 44:31

DAVID HEYMANN [continued]: And so by using this methodology in very local areas--because resistance is a local phenomenon.It's not a national phenomenon.It occurs in various places.By using this methodology throughout the country,they were able to adapt their malaria program appropriately.They still use that technology 30 years later,as do many other countries in determining whether or nottheir chosen antimalarials are still effective.

• 45:00

DAVID HEYMANN [continued]: In studying a disease, there are many different epidemiologicalmethods that are used.And these are used both for infectious diseasesand non-communicable diseases-- those diseasesthat aren't infectious.These methods include identifying risk factorsfor infection.They include understanding whether or not populationsare immune to infections.

• 45:26

DAVID HEYMANN [continued]: In other words, whether or not theyhave antibody to infections.And in the case of non-communicable diseases,it's looking to see what people are doingthat are causing their disease.So if you look at non-communicable diseasesinstead of having infectious disease organisms like HIVor TB, what you have is risk factors,which are also acting very much like infectious organisms.

• 45:53

DAVID HEYMANN [continued]: For example, smoking is a risk factorthat causes eventually lung disease and possibly cancer.Too much sugar is a risk factor which canresult in obesity and diabetes.So treating risk factors as if they're infectious agents,you can design epidemiological studies,which are very similar to those for infectious diseases,with one caveat.

• 46:20

DAVID HEYMANN [continued]: And that caveat is that they must be long-term studies,because non-communicable diseases develop overa very long period of time.A smoker today will possibly have no symptomsuntil-- if a smoker's 18 years old today,they may have no signs and symptoms of smokinguntil they're 30 or 40.But they will be guaranteed to havesome signs and symptoms by then, either a cigarettecough or chronic bronchitis.

• 46:47

DAVID HEYMANN [continued]: And eventually, unfortunately, many of themwill go on to develop cancer.So to test the intervention of stopping smoking,it takes quite a while to see the impact of thatin the immediate, in the mid-term, and in the long term.Methods used to do epidemiological studieshave been with us for many years.

• 47:08

DAVID HEYMANN [continued]: What's happening though is we're becoming more powerfulin our ability to use those basic epidemiological toolsbecause of things such as genetic sequencing.So whereas 30 years ago, an outbreakwould be investigated looking to see who was infectedand how they were becoming infected,why they were becoming infected, today you can go even furtherand, in some instances, through genetic sequences,determine where that infection actually came from.

• 47:39

DAVID HEYMANN [continued]: And you can then begin to link people with a genetic sequenceso that you can see where that virus has gonein a chain of transmission and whereit might have mutated and gone along a different chainof transmission.So the basic epidemiologic tools have always existedor have existed for many years.

• 48:01

DAVID HEYMANN [continued]: And they include excellent statistical analysisafter the studies are done.But what's important today is the new technologies--the IT technologies, the genetic technologies--which put even more powerful tools in our hands.Influenza is a disease which occurs every year in epidemics.

• 48:21

DAVID HEYMANN [continued]: But the influenza virus mutates each year.It does what it calls drifts antigenically.It drifts a little bit.It mutates a little bit so that the vaccinethat you use this year for influenzaisn't effective next year for next year's influenza epidemic.There's a network of laboratoriesaround the world that are constantly collecting influenzaviruses and looking at their genetics,at their genetic sequence.

• 48:47

DAVID HEYMANN [continued]: And from that information each year, there'sa technical meeting which determineswhich are the most prevalent mutated strains of virusand which ones should be used to develop the next season'sinfluenza vaccine.That would not be possible without the abilityto use basic epidemiology supplemented by genomics,by genetic sequencing.

• 49:15

DAVID HEYMANN [continued]: I joined the Centers for Disease Control,which is the Public Health Agency of the United States,in 1976.My first assignment from the CDC wasto the outbreak of a new emerginginfection in the US called Legionnaires' disease.And my second assignment was to a new emerging infectioninternationally called Ebola in 1976.

• 49:38

DAVID HEYMANN [continued]: Both those infections occurred within a period of six monthsafter I joined the Center for Disease Control.And I was able to participate in investigationsof both of those outbreaks.From there, my career led me to Africa,where I was based for about 13 years,from the Centers for Disease Control,working in epidemiological research activities thathelped better design infectious diseasesurveillance, prevention, and control programs.

• 50:07

DAVID HEYMANN [continued]: So during that 13 years, I workedwith many infectious diseases-- Ebola, yellow fever,a disease called yaws, and many childhood diseasesand other diseases such as malaria, measles,diarrheal diseases-- a whole series of infectious diseases,which we studied, which we developed a betterunderstanding on, and which we thenapplied to better prevention and control in the countrieswhere the research was done and globally.

• 50:40

DAVID HEYMANN [continued]: What was very interesting in the 1970swas that there was very little capacityfor countries to participate in researchbecause their laboratories had run down.This was 20 years post the colonial system.Their laboratories had run down.They hadn't been able to maintain the public healththat they had had during the colonial era,because it was a very difficult financial situationthat these countries faced.

• 51:07

DAVID HEYMANN [continued]: So early on, it was very difficult to workwith countries in doing epidemiological research.And many times, laboratories had to be set up in the fieldto accompany the research projects that were going on.Today, that's changed dramatically.And countries can participate fully and do all the laboratoryinvestigations and the other investigationswithin their countries, with a little bit of supportexternally and especially in training and provisionof equipment and supplies and various other things.

• 51:39

DAVID HEYMANN [continued]: So what we've seen is, from a periodwhen countries were not able to participatevery well in research to today, whenthey can be equal to the European and North Americancollaborators and do the studies that are needed to be donewithin the country themselves.Now, this isn't occurring in all countries.And it was clear in the Ebola outbreakthat those countries weren't ready.

• 51:59

DAVID HEYMANN [continued]: But in other countries, capacities are increasing.And countries in the next 30 yearswill develop those capacities to befull equal partners with research partnersfrom industrialized countries.Doing epidemiological research in developing countriesis always a challenge.And the biggest challenge is to get the national public healthpeople involved in those studies,because just doing those studies without involvementof national researchers doesn't help the country at all.

• 52:31

DAVID HEYMANN [continued]: So it's very important and very frustrating at timesnot to be able to get developing country researchers fullyinvolved because of the lack of resources,a lack of training within the country.And so the goal of epidemiological researchis not only to better understand infectionsbut also to permit developing country researchersto develop the skills to do these studies eventuallyon their own.

• 52:55

DAVID HEYMANN [continued]: So our obligation in working on epidemiological researchin developing countries is two-fold--get answers and help the countriesthemselves develop the skills to get those answers themselves.Ethics must always be in the mind of a researcher.

• 53:16

DAVID HEYMANN [continued]: At any time that you're doing research on human,that human needs to understand whatis being done, whether there are any risks,and must then make an informed decision of whether or notthey want to participate.In many institutions in industrialized countries,there are what's called ethics reviewcommittees or committees that review the ethics of a study.

• 53:40

DAVID HEYMANN [continued]: They review the questionnaires to seethat those questionnaires are prepared in the right manner.They also review informed consent formsto make sure that those forms are informing the person sothat they can decide with the information necessary whetheror not to participate in the study.Indispensable in research.

• 54:07

DAVID HEYMANN [continued]: It's important in epidemiological researchto look at what you're really doingas a collection of evidence.Collecting evidence that can be usedto develop sound disease prevention and controlstrategies and policies.So all epidemiological research and all research in generalgives the information necessary sothat the political leaders of countries can develop the rightpolicies and the right strategies.

• 54:38

DAVID HEYMANN [continued]: Many times, they don't listen to the evidence becauseof political pressures or lobbyingor other activities that are going on.But it's the responsibility of a researcherto provide that evidence in a format that political leaderscan understand and hope they will use that information.

• 55:04

DAVID HEYMANN [continued]: What attracted me to epidemiological researchwas a series of events.But most importantly was the factthat I saw that I could myself do more in public health,in epidemiology and public health,than in clinical medicine.Because in clinical medicine, you treat one patient.Now you treat another patient in another half-hour.

• 55:25

DAVID HEYMANN [continued]: But in public health, you can treat or preventa whole population from becoming sick or help them get better.So it's just a different approach.And I prefer the latter, which was a group approach.Having developed the skills necessary,when an outbreak occurs, there's essentiallyan epinephrine rush, a rush of hormones, which tell you,I want to go out there and do this.

• 55:51

DAVID HEYMANN [continued]: Just like a journalist or anyone else,when there's a good story, there'sa rush of hormones, a rush of adrenaline,which sends that person out to do the studies.So once you have the skills, once youhave the understanding of how to protect yourself,then when an outbreak occurs, the adrenalin rushpushes you out to do what you cando to prevent other people from becoming infected or becomingsick and also to learn how to prevent it in the long term.

• 56:21

DAVID HEYMANN [continued]: Nothing's more satisfying than to be able to find a problem,study that problem, and find solutions.And that occurs many, many times in disease preventionand control programs.A vaccine's not working as it should.Another intervention that you're usingis not having the effect you thought it would have.

• 56:44

DAVID HEYMANN [continued]: So epidemiological study of this situationcan help identify the tools that youneed to rectify the situation and to put preventionand control back on target.What I most enjoy about the role that Ihave is being able to find solutionsto problems, whether or not it's findinga solution to preventing and controlling a new and emerginginfection or whether it's a solutionto help a developing country investigator develop the skillsthey need to do that job.

• 57:19

DAVID HEYMANN [continued]: Research, especially research whichis associated with an investigationof the new disease, is very satisfying if you'veprepared yourself, if you've taken the timeto obtain the skills that are necessary to investigateand to do the research necessary to understand a new disease,and also if you've learned how to protect yourselfwhile you're doing that research.

• 57:45

DAVID HEYMANN [continued]: If you go into a country to do researchand don't wash your hands, for example, between patientsor whatever you're doing, you're a failure to yourself and alsoto those people who you're studying.So there are two things you must obtain-- the skills in researchand also the understanding of howto protect yourself and protect others during that research.

• 58:10

DAVID HEYMANN [continued]: The future is really bright for epidemiological research.There are many new techniques that can be used.We talked about genetic sequencing.There will be further developmentsin genetic sequencing.There will be better understanding of whatthat genetic sequence means.It may be that one day we can predictwhich organisms will spread, which organisms will notspread.

• 58:35

DAVID HEYMANN [continued]: There's a whole series of new toolsgenetically that may help us.But in addition, there are communication toolswhich will also help us.Now, in the world, there are mobile telephones everywhere.People can report when there's somethingunusual in their community, and they do.They're beginning to report that to their health systemso that we can detect and respond much,much earlier to disease outbreaksor to anything which is irregular,which occurs in communities.

• 59:03

DAVID HEYMANN [continued]: So the future is bright on all sides.And what we need to do is make surethat, as new technologies are developed,they're applied immediately as best theycan be applied within research.Research is very important, whether it'sepidemiological research to betterunderstand and characterize a diseaseor whether it's clinical trials to test new medicinesor vaccines.

• 59:31

DAVID HEYMANN [continued]: Each one of these areas of researchis very, very important.To get into research, it's very important to earn your wings.And to earn your wings, you must participatein the basic types of research that you want to create.So the first step is to obtain the skillsthrough formal education, the skills and the understanding.

• 59:55

DAVID HEYMANN [continued]: But that's not enough.These skills must then be appliedin a situation where the research that's going onis research that you want to participate in, whether it'sepidemiological research in developingcountries or clinical trials of a new vaccine in the UnitedKingdom.Whatever, you must begin to do that research probablyinitially as a junior investigator, whichis sometimes frustrating, but then as timegoes on, developing the skills to write the grant proposalsor to write the protocols necessaryand to become a principal investigator.

### Video Info

Publisher: SAGE Publications Ltd.

Publication Year: 2017

Video Type:Interview

Methods: Epidemiology

### Segment Info

Segment Num.: 1

Persons Discussed:

Events Discussed:

Keywords:

## Abstract

Dr. David Heymann discusses epidemiological research and his career as an investigator with the CDC and the WHO. He reflects on his work with MERS, the Ebola virus, and polio. He says some of the biggest challenges to disease eradication come from a lack of understanding, so strong evidence and clear communication are essential.