guidelines will be presented to the NIAID Council in September for review and approval.

ASTHMA

Question. Dr. Fauci, what progress have you been able to make through your Asthma and Allergic Disease Centers and Centers for Interdisciplinary Research on Immunologic Disease effort for Asthma and Allergic Diseases?

Answer. During the present year we have begun the process of converting these Centers to Cooperative Agreements in order to enhance our ability to centrally direct and coordinate selected activities. This year we will be concentrating on implementation of asthma education and treatment outreach and demonstration activities in those centers where this does not currently exist. Our hope is that these 16 cooperative research centers will provide the framework for a nationally oriented treatment program for asthma.

Question. Dr. Fauci, last year you told us about your Institute's effort to develop asthma treatment programs for our inner-city children with asthma. What have you accomplished?

Answer. I am pleased to report that in February 1991 we announced the awarding of eight grants to fund the National Cooperative Inner-City Asthma Study. The awards were made to eight universities in Detroit, Cleveland, Chicago, St. Louis, Washington, D.C, Baltimore and two in New York City and is to be conducted over a four-year period. The goal of the study is to reduce recurrent asthmatic episodes and asthma-related deaths among Black and Hispanic children living in the inner city. In the initial months of this study, investigators will be collecting information relevant to developing a common treatment protocol which will be implemented during the subsequent months. We hope this will provide a meaningful and uniform approach to the treatment of our adolescent children with asthma.

Question. Dr. Fauci, what progress have you made in the treatment of asthma?

Answer. During the past two years we have been collaborating closely with the NHLBI to develop guidelines for the treatment of asthma under their National Asthma Education Program. As this information is disseminated to the health care community at large, it should provide an important link in insuring that modern treatment of asthma reaches each and every person in the United States.

Question. Dr. Fauci, for several years we have been concerned about environmental pollution and its role in causing/contributing to asthma and allergic disease. Do you have any progress to report?

Answer. The NIAID supported investigators have recently reported on the importance of the house dust mite as a precipitin cause of asthma attacks responsible for many emergency room visits. Control of environment in the homes of afflicted individuals, particularly in the bedroom, has led to a significant reduction in attacks. Because of the importance of indoor air pollution and indoor allergens as precipitating factors in allergic diseases and asthma, we are supporting an Institute of Medicine Task Force whose

aim is to identify all potential factors and to develop the means to control them.

Question. Asthma deaths are rising steadily in the U.S. with the highest rates found in Black male children. The problem is particularly acute in New York City and Chicago. Given the alarming increases recently in deaths due to asthma among young children, is your Institute supporting research studies to identify the cause of the increase in mortality as well as what can be done to reverse the trend?

Answer.

We have been very concerned about the increase in asthma morbidity and mortality rates among Black and Hispanic children, especially after a period of several years of steady decline in the rates overall. In response to that concern, in February, 1991 we launched the National Cooperative Inner-City Asthma Study. Of the eight awards made, two will be conducted in New York City and one will be conducted in Chicago.

The study is to be conducted over a four year period and is specifically focused to identify factors contributing to the increased incidence of asthma and will enable us to develop modalities to reduce recurrent asthmatic episodes and asthma-related deaths among inner city Black and Hispanic children.

TROPICAL MEDICINE

Question. I understand that recent scientific developments in the area of molecular biology have opened up many new areas of inquiry within the field of tropical medicine. These advances have created many exciting new research opportunities but the NIAID cannot fund many excellent and outstanding grant proposals due to limited resources. Could you comment on the opportunities we are missing by being unable to fund all of these excellent proposals?

Answer. The field of tropical medicine focuses on the health of populations that live principally in underdeveloped countries who are exposed to a variety of diseases caused by parasites. Since the size of the populations affected by these infections is enormous, these diseases are significant impediments to social and economic progress. Despite the application of biotechnology to the study of these diseases, much remains to be done to enhance methods for prevention and control. Additional support would fund the following proposals:

Diagnosis. It is essential that new diagnostic methods be developed. For many of these diseases, the available methods are crude, inefficient, time consuming and costly. Biotechnology,

including molecular biology, could make possible the rapid, sensitive and specific identification of parasites. This will facilitate the determination of populations at risk as well as the identification of the clinical course of infection.

Drug development. Chemotherapeutic approaches for prevention and treatment of parasitic infections have lagged far behind other infectious diseases. With a few exceptions, there have been no new compounds introduced for these diseases in decades. Existing drugs are often toxic and/or less than completely effective. Recent advances in parasitology have demonstrated that parasites have distinct biochemical pathways from those of their hosts. Additional

molecular biological studies could enable investigators to determine sites, unique and essential to the parasite, which are potentially subject to inhibition. Such studies will lead to the rational design of new drugs which will selectively kill the parasite without harming the host.

Vaccine development. In terms of cost-benefit ratios the most successful method to prevent disease by infectious agents has been achieved by means of vaccination, as witnessed by smallpox eradication and polio control. Similar control of parasitic agents does not exist. Simply put there are no vaccines for any human parasitic infection. Much work needs to be done to increase our understanding of man's immune response to parasites. Further molecular biological research, combined with immunological knowledge, could lead to the identification of parasite constituents useful as vaccines. The ability of biotechnology to produce these candidate vaccines holds great promise for future control efforts.

Vector biology. Many of the tropical diseases are transmitted by vectors such as mosquitoes and snails. The initiation of molecular biological studies would lead to the identification of vectors responsible for disease transmission. Further, novel approaches to alter the genes of these vectors may lead to new methods of preventing infection in man.

Question. If you had additional resources to support activities in tropical medicine, could you describe what you believe to be the greatest unmet need with respect to training specialists either in the U.S. or in overseas locations?

Answer. The training of tropical medicine specialists would be greatly enhanced by providing additional institutional support to academic groups of tropical disease investigators and practitioners associated with schools of medicine and/or public health. The groups would provide training for specialists interested in clinical and public health as well as biomedical research aspects of tropical medicine. According to a recent Institute of Medicine report, "The U.S. Capacity to Address Tropical Infectious Disease Problems", such groups" are needed to sustain a core of U.S. expertise and leadership to deal with tropical disease problems." Such sustained support would provide the basis for the development of multidisciplinary approaches needed to control these diseases. The support would provide visibility and stability to the field and would thus be useful in recruiting new professionals.

Question. How is the NIAID responding to last year's report language requiring some of the new monies in the FY 1991 appropriation to be allocated to tropical medicine?

Answer. The NIAID has focused its efforts on enhancing the support for tropical disease research by funding unsolicited, investigator initiated research grants in the areas of drug and vaccine development, diagnosis and vector control, on the assumption that this will allow scientists the opportunity to follow up on leads as they arise. The NIAID will expand the number of Tropical Disease Research Units, our domestic centers for research on tropical diseases, from three to four in 1991. In addition, the Institute is expanding research opportunities for individuals working in endemic areas through the support of Tropical Medicine Research Centers

(TMRC) and International Collaboration in Infectious Disease (ICIDR) programs. During FY 1991 the NIAID established three TMRCs in endemic areas. These centers provide both U.S. and foreign scientists an opportunity to investigate and collaborate on these problems which are of major public health importance.

AIDS VACCINES

Question. Dr. Fauci, I was contacted recently about the AIDS vaccine which has been developed by MicroGeneSys. I understand that the drug is ready to move into Phase II clinical trials to determine whether or not the drug is effective. Dr. Fauci, what is the status of clinical trials for the AIDS vaccine developed by MicroGeneSys?

Answer. The NIAID has conducted two trials, one at the NIH itself and at one of its vaccine evaluation units, to test this vaccine for safety and ability to induce an immune response. Enrollment in the second trial was completed this month, and it will be months before the data are complete. The MicroGeneSys vaccine has also been used as a booster in some individuals that had first been immunized with a different product, HIVAC-le, which is based on vaccinia, and this seems to be a very promising combination. The criteria for moving into trials of protection against HIV infection in man are still under discussion. However, some leading scientists believe that vaccine candidates should be shown to protect monkeys against simian immunodeficiency virus (SIV) or chimpanzees against human immunodeficiency virus (HIV), and the MicroGeneSys vaccine has not yet been proven to do this. We are now arranging for a trial in monkeys for the SIV equivalent of this vaccine. Our current trials will tell us more about how much of this vaccine should be given, and how often it must be given, to induce the long-lasting and vigorous response that any vaccine must produce before it can be tested for efficacy.

Question. Please tell the Committee the overall status of work to develop AIDS vaccines. How many are now being tested? you expect to have a safe and effective vaccine?

When do

Answer. There are three areas that we are working especially diligently on to further our chances of developing an effective AIDS vaccine. The first is the issue of the genetic variation of the virus. Studies that explore the immunologic consequences of HIV genetic variation in terms of vaccine development are important because the production of a vaccine for AIDS is made much more difficult by the frequency with which HIV mutates. These mutations can result in subtle but significant changes in viral structure, which could render a vaccine ineffective. Investigation into the rate and extent of viral genetic mutation will provide scientists with critical knowledge needed for developing an effective AIDS vaccine.

The second is the area of adjuvant development. Several subunit vaccines which utilize proteins or peptides of the virus are likely to be candidates for clinical trials. Thus, an effective adjuvant, or a compound that enhances the immune response to a vaccine, may be critical to boosting the host response to the vaccine. Moreover, effective adjuvants may be necessary to induce long-term immunological memory, thereby decreasing the number of booster immunizations required to elicit protective immunity.

The third area includes basic immunological issues, such as identifying the components of the immune response needed for an effective vaccine. This issue is vital because HIV/SIV vaccines may require both antibody and cellular components of the immune system to be effective. Research into mechanism of protective immunity should provide insights into optimal strategies for vaccine design.

Currently, seven vaccines are in clinical trial in uninfected volunteers, and six vaccines are being evaluated in HIV-positive asymptomatic volunteers.

These preliminary studies are addressing safety and ability of the vaccine to induce immune responses. The goal of these first studies is to obtain comprehensive immunologic analyses on each candidate, and to compare these data to comparable animal model studies. In addition, there are currently several other candidate vaccines in preclinical development, and it is anticipated that a number of these will enter clinical studies in 1991.

QUESTIONS SUBMITTTED BY SENATOR ROBERT C. BYRD

AIDS VACCINES

Question. Dr. Fauci, there have been a number of newspaper reports that several AIDS vaccines have been found to be safe for use in humans. What vaccines hold out the most promise at this time?

Answer. It is true that several candidate vaccines have been shown to be safe in uninfected individuals, but it is impossible for us to judge which of the several vaccine candidates is most promising at this time. We are pressing ahead to determine what kinds of immune reactions each vaccine elicits, so that we can make such

determinations.

Question. What plans are underway to expand human clinical trials of AIDS vaccines which have been found safe in humans to determine the effectiveness of those vaccines in both preventing and treating AIDS?

Answer. The NIAID is developing protocols to test several candidate AIDS vaccines in infected individuals. One such trial is currently underway and is sponsored by the AIDS Clinical Trial Group. This is a small trial to investigate the end points necessary to determine efficacy in this study population. Expansion of human clinical trials will take place as more and more safe AIDS vaccine candidates become available and as more is learned about the end

points necessary to judge effectiveness. The NIAID is in the process of putting in place the infrastructure necessary to carry out such trials.

Question. Given the mortality rates of those infected with HIV, what plans does the NIH have to begin efficacy tests on AIDS vaccines which have proven to be safe for use in humans?

Answer. No vaccine candidate will be tested in large scale efficacy tests until it is proven safe and capable of eliciting a vigorous immune response. We are searching diligently for clues as