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Harden: We will stop here today. But I want to say that your entire coverage of this is most interesting, because, of course, we are back, then, to the differences in mission of the NIH to do research and the CDC to do the epidemiology and to be the liaison to the public as to what is happening.
Harden: And the words that we use. Tony Fauci got himself in lots of problems over his attempt to be very scientific...
Harden:...and say that they were 99 percent sure that it was not casually transmitted, and then the newspaper said that Dr. Fauci says it can be casually transmitted, because there was a one percent chance that it could be...
Quinn:...transmitted, because a doctor will never say never.
Harden: That is right.
Quinn: That is the bottom line. We will not.
Harden: But I think this whole linguistic problem in terms of research and medicine and the public, and the translation of information from one to the other is an extremely important part, and this epidemic has just highlighted it.
Quinn: Yes. In my work, the divisions between the NIH, the CDC, and so forth, were gray divisions. We overlapped immensely. And I am epidemiologically trained from my time in Seattle. But I am also laboratory trained to do basic research from my time at the NIH. I try to put the two together. And the CDC has laboratory people there that do basic research. We all overlap one another. When that overlap is beneficial and we are complementary to a certain degree, working together to solve a problem, then that is fine. When it causes lots and lots of friction that is antagonistic and does not solve the problem, that is bad.
In the case of Projet SIDA, it was complementary. There was friction because of the two institutions. I think it is the history of the institutions. But it was complementary. We put people together there that wanted to come up with answers to questions, solve questions, I should say, and it paid off, I think, in the long run. It was, to me, a very rewarding and satisfying type of project, one that I, for the rest of my life, will be extremely proud of. When people bring up the friction, I say, “Yes. But when do not we have friction?” I have friction down in the laboratory next to me. The NIH has it from laboratory to laboratory. Life is filled with frictions. But do not focus on the frictions. Focus on the products that came out, and whether they hold the test of time.
Of everything that Projet SIDA published, none of it has ever been retracted. It all holds true. The data are there. The specimens are there. The Africans worked with the Americans and with the Europeans. It was a truly international collaborative arrangement that worked. It shows that if you have a big enough problem and enough interested parties, they can work together. Yes, they will have their fights, but they will still work together. So when people say that the CDC is to do this and–yes, that is their goals and their mission. But the individuals within that can overlap one another and complement each other, and to me, that has been the exciting part.
Harden: Very good. Let us stop here for today.
This is the second interview with Dr. Thomas Quinn. The date is 16 December 1996. The interview is being conducted in a conference room, Building 31, National Institutes of Health, Bethesda, Maryland. The interviewers, again, are Dr. Victoria A. Harden, Director, NIH Historical Office, and Dr. Caroline Hannaway, NIH Historical Consultant.
Harden: In our first interview, Dr. Quinn, you were summarizing the activities of Projet SIDA and the African experience. We have a couple more follow-up questions on that before we move into a discussion of your later work.
You noted that there was a problem with the ELISA [enzyme-linked immunosorbent assay] assays in Africa because of people who had malaria, and that this caused problems with ascertaining the prevalence of AIDS. Could you give a fairly non-technical but specific explanation for what was going on and how these kinds of tests work? People do not perhaps understand why a test might not be specific.
Quinn: Early on, as the test was developed, it became clear that there were a number of biological entities that could give a reaction in the ELISA test but would not definitely reflect HIV infection. In the United States, it was learned that pregnancy, for example, would give you a false positive ELISA. Then you would do what is called a Western blot, and that would show whether viral antibody was present to viral proteins, so it would differentiate the false positives from the true positives. The ELISA was made to be exquisitely sensitive so that it would not miss any positive tests or positive infected people. But this was at the expense of its not being as specific; that is, it would give false-positive reactions so that it would not miss any true positives. So it became clear that you had to take a Western blot, an immunoblot, and run the same patient sera on the immunoblot. If there were specific antibodies to the virus, they would react to the proteins, and that would then confirm that the initial ELISA test was positive and reflect a true infection.
On the other hand, if there was a false-positive reaction, then those viral proteins would not become visible on the immunoblot, and you would tell the person that they had a false-positive test and they were not truly infected. It pretty much became clear very early, within the first six months of licensure of the assay, that it was very sensitive but not that specific, and that you needed a two-tiered test to confirm the result.
When this test was brought over to Africa, the problem was compounded several-fold, because there were a lot of endemic diseases that caused an immunologic reactivity that would come up positive on the ELISA test. But then when you went to do the Western blot, it would be clear that these were false positives, not true positives.
Harden: May I ask just one quick question? When you did an ELISA test on someone, did you tell them that they had a positive result and that a second test had to be done?
Harden: Or did you just go ahead and do the second test?
Quinn: You had to go ahead and do the test. Especially in the early days when we were really just getting our feet wet with the ELISA. We wanted to be sure that when we told someone they were HIV-infected, that it was a confirmed positive. So everyone that we informed that they were infected went through the two-step process. Their sera was first tested by ELISA and then tested by the immunoblot, Western blot, and if both tests were positive, they were told they were positive for HIV.
There are a number of endemic diseases in Africa that will tip off the ELISA but not the immunoblot to be positive. We could go down a whole list of parasitic diseases, but malaria was the most notable one. There were even several papers written about that. There was also trepanosomiasis, there was filariasis, you name it, there was a long list. Even endemic bacterial infections, tuberculosis, things like that, could make the ELISA go positive. So you needed the Western blot. It became sort of a standard for scientific conduct there, that you had to do both tests. You could not get away with just doing the ELISA.
Later down the road, it became clear that this was too expensive for African countries. They could not afford to do both tests. For research purposes you could, because that was funded just as it was in the United States, with the same kind of standards. But really to screen the blood supply in Africa, which was critically important since 10 percent of blood donors were positive, you had to have another way of ruling out those that were truly infected and those that were not. I became very closely interested in this whole question of what was the best sort of testing to do there. I will take you through a couple of steps.
The very first thing that we found out was that the blood in Zaire was being transfused within an hour of its being donated. You did not even have time to do the ELISA, never mind the Western blot. So what we did was work with some manufacturers to come up with rapid tests that could be done in 10 minutes and which could tell you whether the person was infected or not. It turned out that these tests were very, very good. In fact, they were actually a little better than the ELISA up front. But you still could not tell the person they were infected on the single rapid test–there were several rapid tests that we used–and there were at least three or four that we tried out.
Harden: What kinds of tests?
Quinn: The very first one that we used was called–I am blocking on its name now. It was made by Du Pont, and I keep wanting to say HIV. It was HIV something, HIVNET or something like that.
Harden: Was this the latex test?
Quinn: That was not yet. The latex test was actually the second one. Then the third one was called the Testpack, which was made by Abbott. The latex was made by Cambridge Bioscience, and the HIVNET–it is not HIVNET but it is similar to that; I am sorry I cannot think of the name; I could find out for you–and that was made by Du Pont.
What we did in a couple of different African settings, actually, was to utilize these rapid-screening tests and see whether they worked, and, in fact, they did. But what was a nice algorithm was that, since you did not have time to get the Western blot or even the ELISA done, you could use two separate rapid tests in tandem. If one was positive, then you confirmed this with the other one. That was equal to doing an ELISA and a Western blot, and yet you had your answer in 15 minutes and the blood could be transfused if the result was negative; if it was positive, the blood would be discarded.
The other part of trying to limit the amount of infected blood that was getting transfused to people was to teach the physicians that you should not transfuse individuals unless they desperately needed that transfusion because of the high risk of getting infected with HIV. We set criteria that you should not transfuse the blood until a person’s hematocrit or their anemia was at a certain level. That, in fact, cut the numbers of transfusions by 50 percent; just by doing that, we cut the need for the blood transfusions. Then we told them how to bank the blood. The Germans came in and wanted to work with us on this, and they built a brand new blood bank at Mama Yemo. We set up the rapid test, and so the blood could be banked while the testing was completed. In fact, during, I would say, 1988 to 1991, towards the latter years of Projet SIDA, we had a complete, effective blood-screening program in Kinshasa, so that infection was being transmitted in very few cases due to blood transfusion.
Hannaway: Was this organization of testing then moved to other African countries or elsewhere?
Quinn: It was, yes. Nairobi, of course, could afford it, and so could Zimbabwe and Harare, and a few other countries clearly had some financial support to help get these into place. The Swedes were interested in working with African countries. And so were the Germans and the British. It became an international effort. This was one thing the international community could do for Africa–to get down there and start screening the blood supply–because up to 10 to 15 percent of all HIV infections in Africa were due to blood transfusions. That became very clear early on. The rest was all heterosexual transmission, but 15 percent was through blood transfusions.
So the international community reacted to that either by building blood banks so that the blood could be banked while it was properly screened, or going in with these rapid tests. I became very interested in the rapid-test format, and our laboratory was the first one actually to bring the rapid test into blood-banking scenarios in Africa.
Later, we were to take the rapid tests into epidemiologic studies; that is, a lot of people that we enrolled into our prospective studies wanted to know the results of their test right away. They did not want to come back several weeks or months later. In some cases, we were afraid we would lose them. If they had a positive test or a negative test, we could counsel them immediately, before they left the clinic setting. So we went into this tandem screening process: screen with one rapid test, confirm with the other, give the patient the result.
We have subsequently, although we have not published this yet, done this in emergency rooms here in the United States, so that people who have a tendency to come in for medical care but may not come back for the results of tests can get an answer right away.
Then, of course, we would always, even with these two rapid tests, still go to a Western blot eventually. But we would tell the person preliminarily if they were positive for this infection.
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