THE ARMED FORCES EPIDEMIOLOGICAL BOARD
Its First Fifty Years
by
Theodore E. Woodward, M.D.
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PART III The End of the Decade The activities of the AFEB continue. Some diseases have been conquered or have become less significant militarily, for example, enteric diseases such as the dysenteries, rickettsial diseases such as the typhus fevers, and the encephalitides, as well as poliomyelitis. New diseases such as AIDS appear and raise the specter of catastrophic debilitation in both the military and the civilian populations. Other diseases such as malaria have not been conquered, only partially controlled with our current best knowledge. Pathogenic microorganisms continue to plague mankind and the best minds in military and civilian medicine will continue to combat them. The section that follows summarizes some of the military and medical problems that the Board confronted and advised upon during 1989. Streptococcal Infections Beginning in 1983 and peaking during 1987 and 1988, the Army Medical Service and the Department of the Navy reported a significant increase in streptococcal pharyngitis, particularly among recruits. Approximately one percent of those patient shown to have pharyngitis developed acute rheumatic fever. No obvious cases of streptococcal-induced pharyngitis occurred among Air Force personnel during this time, and there were also no cases of acute rheumatic fever. The prompt use of penicillin, or Erythromycin in those persons with a history of penicillin sensitivity, led to a sharp decrease in the incidence of streptococcal pharyngitis and its sequelae in Army and Navy personnel. The AFEB was kept informed of these developments; the problem was discussed in considerable detail at the meeting of the Subcommittee on Infections at WRAIR on 16 February 1989. The three recommendations that the Board formulated on penicillin prophylaxis for streptococcal diseases, which were effectively applied, were that:
264 3. Studies should be undertaken in areas with high rates, such as Marine Corps recruit depots, to (a) examine the desirability of administering a second dose of Bicillin four weeks after the first to prevent a second peak of streptococcal illness during recruit training; and (b) determine the occurrence of streptococcal skin infections, particularly in the summer months, as a justification for Bicillin prophylaxis. Hepatitis Vaccines The Board has been identified with the development and use of hepatitis vaccines for several decades. Hepatitis is a serious military medical problem with significant morbidity and loss of time from work. (The problem had become quite apparent in 1986, with a high incidence of hepatitis among military personnel stationed in Korea.) Discussions among the members of the Subcommittee on Infections and the military's Preventive Medicine Officers made it apparent that immunization of the entire military force against hepatitis B infection was advisable. Because of significant fiscal constraints, however, such a program was not feasible. A regimen other than the standard subcutaneous injection of vaccine, such as the intradermal route, was suggested as a way to reduce the costs and still provide appropriate protection. Screening trials were conducted using a two-dose intradermal injection of 0.1 ml vaccine. When it became apparent that adequate antibody protection resulted, recommendations were made for all military personnel assigned to Korea and other areas of high incidence to be so immunized. The conventional full-dose regimens were recommended whenever they were feasible. The AFEB also recommended, in a separate action, that hepatitis B vaccine be administered to all health-care workers and to inmate personnel in U.S. disciplinary barracks. During its meeting of 28-29 September 1989, the AFEB responded to questions relating to reduceddose regimens for recombinant hepatitis vaccines. Recombinant hepatitis vaccines are not generic, and reduced doses of hepatitis B vaccines prepared by different manufacturers may or may not be equally immunogenic. Studies by various investigators had revealed that one-fourth (2.5 mcg) to one-half (5 mcg) of the currently recommended 10 mcg doses of Merck, Sharp and Dohme's recombinant vaccine (Recombivax-HB) are highly immunogenic for adults up to the age of 30. As of this date, reduced-dose data of the Smith, Kline, Beecham vaccine (Engerix B) are not available. Accordingly, the AFEB recommended:
During these discussions, the Board leaned heavily on Dr. Saul Krugman for advice and guidance. His broad and authoritative experience in the fields of hepatitis and its control by hepatitis vaccines has made him an important resource, not only for the Board, but also for the nation. Problem with the Jet Injector Gun During a Board meeting in June 1986, Captain Michael Stek, Jr., MC, USN, presented data and press clippings that suggested that a contaminated jet injector gun, which had been used at a private clinic in California in 1985, was responsible for causing hepatitis in sixty-four patients. The possibility was also raised that HIV infection might be transmitted by the jet gun when biological products, such as gamma globulin, were administered. After numerous meetings, the Board recommended, in March 1988,
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266 Furthermore, the Board stated that the chance of transmitting HIV infection through gamma globulin given by jet injector was too remote to be significant. Those persons most responsible for formulating these decisions and recommendations had previously had extensive experience with the jet injector; Dr. Abram Benenson had worked with it since it was developed. Continuing Recommendations on Malaria During the September 1986 meeting of the Board, and during subsequent meetings of the Disease Control Subcommittee and the Board, the problem of malaria was always discussed. In view of the complexity of the problem, the Board recommended that military medical research on malaria concentrate on two major research areas: (a) the search for effective drugs for chemoprophylaxis and treatment, and (b) the development of effective vaccines. At the request of the Department of Defense's Office of Health Affairs, the Board studied malaria-research programs currently underway in both the military and civilian sectors, and determined that the military malaria-research programs were appropriately integrated with other federally sponsored programs. There had been, for awhile, the appearance that the efforts were not appropriately coordinated. It became clear that the United States Agency for International Development (USAID) and the military groups had somewhat differing objectives, and thus were not in conflict. The search for an effective vaccine continues and is greatly needed. At the request of the Army Surgeon General, the AFEB considered the matter of Mefloquine prophylaxis during its 28-29 September 1989 meetings. The questions posed to the Board related to (a) confusion that might arise from a complicated prophylaxis schedule, and (b) the potential side effects such as dizziness and psychotic behavior that might occur in patients taking the medication. The Subcommittee on Disease Control discussed the problem in considerable detail and was aided by Dr. Hans O. Lobell of the Centers for Disease Control and other expert consultants. Based on expert consideration of the relevant data, the AFEB recommended that:
In addition, the AFEB made the following recommendations regarding the use of Mefloquine for military personnel in flight status:
The Encephalitides Japanese B Encephalitis. In 1986, a U.S. Air Force general stationed in the Far East became ill with Japanese B encephalitis. Better control measures, particularly with the use of vaccines, promptly attracted attention. The potential for Japanese B encephalitis applied particularly to those military 267
Armed Forces Epidemiological Board and Committee Directors
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Armed Forces Epidemiological Board and Committee Directors
269 personnel stationed in Korea, Thailand, the Philippines, and China. Inactivated vaccines used extensively by the Japanese were reputed to cause minimal side reactions and to have a protective efficacy rate of 90 to 95 percent. Attenuated Japanese B vaccines had been under development in Japan for a number of years, although the degree of protection and the potential for vaccine virus conversion were not fully known. In 1986 and in subsequent years, the Subcommittee on Infections and the Board concluded that both inactivated and attenuated Japanese B vaccines should be used selectively, as determined by local command decisions. Military scientists were advised to continue trying to work out the details until more reliable data became available. California Virus Encephalitis. In April, 1987, the Board was apprised of the prevalence of California virus (LaCross) encephalitis (CVE), which occurs in the mid-United States. Other forms of arthropod-borne encephalitis (arbor viruses) are western and eastern equine encephalitides and St. Louis encephalitis. Chikungunya, dengue, and yellow fever are related viral illnesses that differ in their clinical expressions. Dr. Thomas Monath, a very capable entomologist from the Arbor Virus Center in Denver, reported on the importance and prevalence of Aedes albopictus, a good transmitter of CVE. This mosquito is found in about twelve states, including Mississippi, Alabama, Louisiana, Texas, Illinois, Florida, and California. A. albopictus transmits CVE horizontally and transovarially more avidly than does A. aegypti. This mosquito was apparently imported into the United States via old tires acquired from various parts of the world, particularly the Far East. Approximately 16 percent of such tires hold water that is contaminated with either ova or larvae of A. albopictus. Viable ova in tires can be inactivated with methyl bromide gas fumigation, but the most cost-effective method to inactivate the ova is to heat the tires to 100° C. The reason that the old tires were imported into the United States was never elucidated. A Historical Footnote. An attenuated Venezuelan equine encephalitis vaccine that was developed at USAMRIID under AFEB and the Commission of Epidemiological Survey sponsorship was used in a massive field control program in Central America, Mexico, and Texas in 1971. The vaccine stopped an eipzootic of encephalitis. This epidemic, if uncontrolled, not only would have destroyed much of the horse population in the United States but also would have infected large numbers of humans. Board Briefing on Lyme Disease At its meeting on 25 February 1988, Major (P) Donald Driggers, MSC, USA, and Commander David Trump, MC, USN, briefed the AFEB on Lyme disease. This affliction is potentially of massive importance to both the military and the public in many areas of the continental United States. Many epidemiologists believe that, were it not for the advent of AIDS, Lyme disease would now be the nation's primary infectious disease problem. Incidence of the disease is steadily rising in the United States, more commonly among males, and with widespread distribution. Rodents and deer are the favorite hosts of the tick vector, Ixodes dammini. Birds may be responsible for the widespread distribution of the infected ticks. Central nervous system signs are often early manifestations of this infectious disease, and troublesome arthritis is a common late sign. The need for early specific treatment was emphasized. Due to the extreme importance of this disease, the Board will continue to monitor progress and events in this area. Continuing Recommendations on Human Immunodeficiency Virus On 20 September 1989, the Surgeon General of the Army requested that the AFEB discuss Zidovudine (AZT) and make recommendations regarding its use in the armed forces. In particular, the Surgeon General asked that the Board consider AZT as it is used to treat patients in the early stages of Human Immunodeficiency Virus (HIV) infections, both now and in the immediate future. 270 At its 28-29 September 1989 meeting, the AFEB considered in some detail the issue of AZT chemotherapy in military patients infected with HIV-1. The Board's experts presented the current knowledge. AZT is an expensive drug that, according to the limited information available, may prolong the lives of patients with AIDS But the drug may also be associated with additional problems, such as developing resistance to AZT and other drugs or developing other adverse effects from long-term usage. The use of AZT signals the advent of antiviral chemotherapy for this deadly infection. When the Food and Drug Administration (FDA) approved its use in the treatment of certain patients with AIDS, some in the medical profession were prompted to adopt this drug as the standard of care. The FDA gave its approval based on significantly different outcomes of 281 patients. Currently, no subsequent promising studies with confirmatory data have been released or published. By virtue of the unavailability of complete data, the Board made the following statement:
In its deliberations, the Board recognized that a few strains of HIV-1 that are resistant to AZT have been isolated, and that this resistance appears to develop when the drug is administered over long periods of time. Furthermore, the virus's drug-resistance appears to cross over to other promising experimental drugs. Hence, the AFEB recommended that:
The AFEB further noted the implementation of the so-called "parallel track" program for drug evaluation, wherein control preparations are omitted from studies on medications of potential use in the treatment of patients infected with HIV-1. The Board was deeply concerned that this development might make it difficult to assess newer drugs that might be effective. The Board therefore recommended that:
Important scientific contributions of the WRAIR group that included Lt. Colonel John Brundage, Lt. Colonel Robert Redfield, Colonel Edmund Tramont, and Colonel Donald Burke assisted the Board in fulfilling its advisory role on HIV-control in the military. They developed clinical and epidemiological data on HIV infections, formulated a helpful clinical classification based on the stages of the illness, and sharpened the laboratory diagnostic procedures. Military Readiness Issues Related To Worldwide Deployment In March of 1984, Dr. William Mayer, the Assistant Secretary of Defense for Health Affairs, had requested that the AFEB evaluate the current worldwide reporting systems of epidemiological data, with reference to the prevalence of diseases and their incidence. The Board was asked to direct its attention to the epidemiological information relating to potential trouble-areas of the world and to comment about 271 those preventive measures best suited to insuring preventive control measures. (The complete report of the ad hoc Committee, chaired by Dr. Paul Densen, that addressed these problems is found on pages 211-220. One of the Board's important recommendations pertaining to the medical problems of rapid deployment was that a physician-epidemiologist be appointed and assigned to the Armed Forces Medical Intelligence Center (AFMIC) at Fort Detrick, whose major responsibilities would be to (a) designate the diseases prevalent in a country, (b) rank them in order of their military importance, and (c) list the preventive measures necessary to deal with them. The Board periodically addressed these important issues, but fiscal and other constraints caused some delays. In the interim, Colonel Robert Wells, the Board's Executive Secretary, and I visited AFMIC at Fort Detrick. At this meeting, during the fall of 1988, the Board's views and wishes in terms of the desired objectives were discussed. As a consequence of that preliminary discussion, during the February 1989 meeting of the Board, Lt. Colonel H. Jack Baghdassarian, MC, USAF, gave an objective and complete report directly related to the aforementioned subject. In his report, Colonel Baghdassarian detailed the important epidemiological diseases country by country. The report described the topography, climate, water sources, animal threats, prevalent arthropods, plant threats, hospital and other medical-treatment sites, location of major air fields, and included a complete listing and description of the diseases of operational importance. His exhaustive document represented a resource of considerable importance; the Board unanimously recommended its adoption. The following description of Kuwait is excerpted from Colonel Baghdassarian's excellent report:
Location
Topography
Climate
272 Kuwait International Airport (prepared 12 May 1980). [NOTE: Colonel Baghdassarian's report contained a detailed weather chart here, which I have omitted. T.E.W.] Water Supply
Electricity
Animal Threats
Snakes
Marine Invertebrates
Arthropods
Plant Threats
Immunizations vaccination requirements for any international traveler. Military Requirements: Routine immunizations. Note: State Department recommends gamma globulin. HIV Screening Requirements. The Kuwaiti government requires proof of negative AIDS testing from individuals applying for resident visas. Results of tests performed in the United States are accepted. Additional Information of Operational Importance
Kuwaiti Hospitals in Kuwait City (2920N 4800E)
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U.S. Medical Facilities: None identified. Major Airfields
Short-term Incubation Periods (Usually Less Than 15 Days)
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Long-term Incubation (Usually More Than 15 Days)
Additional Epidemiological Notes
AFEB Support of the Medical Follow-Up Agency The Board met at Parson's Island, Maryland on 28-29 September 1989. The following agenda shows the topics discussed, together with the participants, and provides a glimpse at the wide scope of Board concerns: 275
276 One of the most important agenda items for this meeting was a discussion of the activities of the Medical Follow-up Agency of the Institute of Medicine of the National Academy of Sciences. Throughout the past several decades, the AFEB has emphasized the need for a longitudinal, long-term, follow-up system that would provide continuing information relating to current health-care practices, not only for the treatment of the individual patient but also to provide information on changing trends and practices in the various fields of medicine. The ensuing comprehensive discussion at this meeting of the Board led to the following memorandum, which was transmitted on 3 November 1989, and follows: MEMORANDUM FOR
SUBJECT: Support for the Medical Follow-up Agency of the National Academy of Sciences 1. Throughout its distinguished history, the Medical Follow-up Agency (MFUA) has served the Armed Forces by providing critical medical data of eminent practical importance. This information has been essential not only to the military, but has also served the long-term interests of the civilian health care community as well. This agency is, in fact, a national resource which ultimately impacts on both our defense posture and the well-being of every American. 2. Due to the realities of an ever-shrinking Federal budget, the existence of this key organization is now threatened. Through a Congressional mandate last year, a panel, under the auspices of the Office of Technology Assessment evaluated the status of the MFUA. As a result of the panel's recommendations, the agency is to be continued for a five-year period with a budget of $0.5 million per year in core support-providing that these funds will, in fact, be available. It is ironic that there may be difficulty in funding this relatively small amount for an organization that has done so much good over the years. In the words of the Office of Technological Assessment (OTA) working group, "There is a little dispute that the MFUA is the clear choice for studying long-term-effects of military experiences (whether war-associated or incidental)." 3. The facts speak for themselves. The resources of the MFUA provide essential information to many long-term studies of major importance. For example, the National Heart, Lung, and Blood Institute (NHLBI) of the NIH collaborated with this agency in establishing twin registries for WWII and Vietnam veterans. These data have been utilized on multiple occasions and have yielded scientific data on the genetic relationships of cardiovascular diseases and pertinent risk factors. There are many other examples which could be readily referenced, describing work by the MFUA on coronary disease, cancer and stress, and related epidemiological studies which impact on the wellbeing of us all. 4. At its recent meeting, the Armed Forces Epidemiological Board (AFEB) and its panel of experts devoted considerable time to discussing the contributions of the Medical Follow-up Agency and the relevance of the information to the military as well as to the public. The Board was unanimous in its strong recommendation that funds must be committed to keep this agency viable. The AFEB, therefore, strongly encourages ongoing support for the continued funding of the MFUA. It is imperative that collaborative studies with this organization be expanded so that there be a continuum in the utilization of this key medical information on into the future. FOR THE ARMED FORCES EPIDEMIOLOGICAL BOARD Theodore E. Woodward, M.D. Robert A. Wells, Ph.D. 277 The Fiftieth Anniversary The AFEB held its winter meeting in February 1990 at WRAIR. Because of the publication deadlines for this volume, it was not possible to include details of the meeting. It is fitting, however, to close with the agenda for the Fiftieth Anniversary Celebration of the Board, to be held at WRAIR on 28 June 1990. That agenda (tentative) follows:
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Theodore E. Woodward, M.D. Text of a talk delivered on the occasion of the Fiftieth Anniversary of the AFEB
The strength of any enterprise, whether a business, a corporation, a medical center, or a scientific institution, is not its buildings, its plush surroundings, or its modern laboratories. Rather, it is the people who work within its walls. Perhaps more than anything else, this is why the AFEB, with its system of Commissions and advisory Committees, has been so successful. The founders built the AFEB on rock by selecting and recruiting the right people to assist the military services in their mission to maintain good health among the troops. They initially conceived that all of the Board's activities would be directed toward the goals of better understanding and prevention of diseases, thereby insuring a healthy military service. One of the important and enriching experiences in my life was the opportunity to mature and develop during the five years I spent in the military. After World War II, there was an even greater chance for intellectual growth through the privilege of participating in the scientific activities of several Commissions of the Board, and later with the Board itself. This is not the time to review the many activities of the Board and its Commissions; those remarkable events are now a matter of historical record. A history of the AFEB's first fifty years is now available and is presented in book form today. Individual Commission reports are also in preparation by directors of those Commissions, and some are nearly at the printing stage. This prompts me to thank wholeheartedly those who undertook the important task of writing and recording these activities of medical and historical importance. For my own part, preparation of the Board's history has been a privilege because it is a report of the accomplishments of many persons whose work is an achievement almost beyond measure. It is to those persons who contributed so much and to this organization that I feel such a sense of indebtedness. I plan to speak in my own way for a few minutes. So relax, you are neither to be guided nor misguided. My favored life as a medical-school teacher, clinical observer, practitioner, and sometimes a doer, has enriched me far beyond that which I have contributed. In searching through the memories of my experiences these past fifty years, I came across a number of unpaid IOUs to several persons who, by virtue of their stature, professional example, and teaching, unwittingly allowed me to borrow from them. It is not possible to make proper repayment, but I take some solace in realizing that others, too, have borrowed heavily from those special persons. Their help to me was incalculable. Their contribution through the AFEB to the cause of epidemiology is a bright light in the history of public health. Each of you has special heroes; permit me to have mine. The persons about whom I have chosen to comment are but a small sample of a large group, all with strong roots in the health and welfare of the military services. Stanhope Bayne-Jones set an example by the conduct of his productive life and by his insistence that a professional person should accept the responsibility for any role of benefit to society and then should complete the assignment. My dear friend Joe Smadel taught me much about science and helped me sift out difficult medical problems. He clarified for me the importance of the bridge between the bench and the patient and showed that bench and field work, rather than armchair philosophy, were essential. When I was a young 279 departmental chairman, he helped me to formulate my criteria for selecting good people. Good training, teaching ability, interest in teaching, and creativity are not enough; the creative person must also have shown documented evidence of that creativity by publishing something decent and readable. Ken Goodner, my most irascible, unpredictable, and sensitive friend, was not soft, sentimental, patronizing, or scornful of medical students. Rather, he was their friend. He encouraged young men and women to achieve their potential as fine physicians and never ceased to impart the glow of his enthusiasm, which was fed by the rich tradition of medical history, one of his constant preoccupations. He appreciated the lessons of the old masters of medicine. Colin M. MacLeod and Thomas Francis, Jr., themselves close friends, were leaders with versatility, wisdom, absolute insistence on scientific accuracy, and little tolerance for stupidity. Each knew so well how to properly evaluate the important characteristics of people, how to analyze important scientific issues, and how to spend public funds intelligently. To see them in action was to learn. K. F. Meyer was sincerely respected by those who knew and learned from him. His ability as a field scientist, coupled with his picturesque turns of phrase, gave me, a neophyte, a clearer view of why a problem is a problem, and the route to take to find the solution. I am indebted to John H. Dingle and there are many others who feel the same way. One of his creeds, "One must take time to design the study of a problem," he applied to his early work on acute respiratory diseases. Others of his creeds, "Utilize the natural setting when possible; don't manipulate nature's way; don't force results; have adequate data; temper your conclusions by possessing full knowledge of the earlier accomplishments of others, and acknowledge their findings and views," are important for all of us to understand and practice. When my wartime boss Leon A. Fox had confidence in anyone, he expressed his wishes succinctly and then watched, rather than directed, as long as the issue seemed to be progressing well and heading toward its solution. He accomplished his objectives by taking action rather than by issuing memoranda. One of his basic principles was, "Know the subject or shut up," which is not a bad rule. All one has to do is to peruse the historical data: the documents, minutes, accounts of events, and letters, to understand that the activities of these pioneers and many others shaped, and helped to shape, the military health standards and the practice of preventive medicine during World War II and thereafter. A small sample of their scientific "firsts" and contributions to the medical literature is displayed in the foyer outside this hall. My purpose today has been to relate how a few men strove for-and achieved-excellence in their chosen fields. In so doing, they favored the AFEB and its Commissions, and they, along with others, were pillars of strength. By the conduct of their lives and their wise counsel, they enhanced our profession and inspired us. In addition to building solid foundations in the basic and clinical sciences, they provided us the opportunity to associate closely with informed professionals, a link of immeasurable value. This is what the AFEB has done for me. It is not possible for me to measure the extent of my indebtedness to those I have named, but in no way do I exclude the many others who have helped and enriched my growth, and who are still with us today. A stanza from Kipling's "Spies March" is a fitting tribute to mark these fifty years of epidemiological science: There are no leaders to lead us to honor,
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