That said, it is hard not to be envious of the bright, dedicated, indeed courageous EIS officers who have been able directly or indirectly to remove pump handles. In contrast, most of my activities as an EIS officer were related to influenza epidemiology. Although I was in the amazing position of being the only EIS officer who was assigned to this area in 1967-1969 and as a result got the opportunity to play a major role in documenting the last U.S. epidemic of H2N2 influenza (“Asian flu”) and the first U.S. epidemic, indeed pandemic, of H3N2 influenza (“Hong Kong flu”), there was no simple control measure and no opportunity to remove a pump handle. Nonetheless, as Mark Pendergrast documents, I had the good fortune to participate in a series of controlled trials of influenza vaccines in both the 1967-1968, Asian flu, and the 1968-1969 Hong Kong flu epidemics. I worked closely with the late Steve Mostow, a young physician who served for three years in the respiratory viral diseases laboratory at CDC; and we both worked under the expert leadership and guidance of Walter Dowdle, then head of the viral diseases laboratories at CDC and later deputy director of CDC, and Marion Coleman, the head of the respiratory viral diseases laboratory. Both were excellent virologists. Unfortunately Marion died at a young age of a brain tumor. I consider Walt, who retired many years ago from CDC but continues as a consultant to WHO’s Task Force on Global Health and for many years worked on polio eradication at the Carter Center in Atlanta, to be one of the most level-headed thinkers and best teachers I have ever encountered. I had the good fortune to be able to learn from occasional interactions with him even a few decades after I was no longer affiliated with CDC.

Until the late 1960s, commercially-prepared influenza vaccines employed the Sharples centrifugation process to try to purify viral particles from the embryonated egg fluids in which the vaccine virus was grown. When electron micrographs became available it was apparent that these products were not very pure. The number of inactivated viral particles in a given amount of vaccine varied, and the impurities were associated with a high reaction rate, which limited the total dose that could be given. Efficacy, while said to be on the order of 70 percent for a vaccine made with a virus similar to the prevailing epidemic strain, was often much less and could be zero. New zonal ultracentrifugation methods led to much purer vaccine preparations, and a larger amount of virus could be given without so many reactions. Demonstrating the properties of the new vaccines vs. the old – reactions, efficacy – was the object of the vaccine trials being conducted by us in those years.

Having an influenza vaccine with reasonable efficacy, which actually was only on the order of about 70 percent, is just the first step in achieving control of the disease. Getting it to people in time, especially in the years in which it is most needed such as an anticipated pandemic, involves a whole process ranging from the mechanics of manufacturing a new vaccine to organizing an immunization program at the national and all local levels. In our complex health system, this is a formidable task and one that had not been considered systematically back in the 1960s. “Inside the Outbreaks” documents the “over-reaction” to swine flu in 1976. Others have called it the “Swine Flu Fiasco”; but in my opinion it represented a reasonable approach to a problem given what was known at the time and was an important milestone. Going into that issue would require much more discussion that is possible here. I raise it, however, because some of the fall-out from 1976, such as concern about possible future association of influenza vaccine with Guillain-Barré syndrome and general apathy about influenza immunization among the public and health care professionals, led to persistence of very low immunization rates even in the so-called “high-risk” population for whom vaccine was particularly recommended – i.e., persons age 65 and over and persons with various chronic conditions, especially heart disease, lung disease, and diabetes.

In the early 1980s, Alan Kendal, then head of the influenza laboratory at CDC, decided that it was important to revise the influenza recommendations. At the time, I and Fred Ruben, a former EIS officer then at the University of Pittsburgh who had done a lot of work on influenza and influenza vaccine over the years, were both members of the Immunization Practices Advisory Committee (ACIP). Alan asked Fred and I to join him and EIS officer Peter Patriarca who worked on influenza to join him in drafting revised recommendations. We recognized that it was important not just to have recommendations that were “sensible”, which the old ones were, but ones that were likely to be followed. In addition, the objective was to assure that people who needed it got into the habit of annual influenza immunization. Why? At one time, it was thought that influenza A epidemics occurred in the U.S. only every two to three years; but with the advent of H3N2 (Hong Kong) influenza in 1968-1969 and the return of H1N1 (Russian) influenza in 1977, and careful analysis of mortality data, it was now apparent that on average influenza A was leading to 30-40,000 excess deaths in the U.S. each year!

In drafting the revisions to ACIP’s influenza vaccine recommendations, we focused first on “highest risk” persons – e.g., older people with chronic conditions who were most likely to be hospitalized or die during an influenza epidemic. Our reasoning was that one needed target groups for whom one could set high, but achievable immunization goals. The “highest risk” group consisted of persons most likely to be seeing physicians regularly – i.e., persons who could be immunized during office visits. We went a step further and recommended that the medical personnel caring for them, physicians, office nurses, and hospital workers, be immunized since they would be most exposed to influenza at a time that they most needed to be healthy and help others. I confess that there was not, at that time, any evidence, just “common sense”, to support the recommendation for health care workers, and such evidence only developed later. But, there was evidence to show that commercially-available influenza vaccines could be effective at decreasing major morbidity due to influenza such as hospitalization; and that evidence was first developed in the 1970s by former EIS officer William H. Barker who teamed up with John P. Mullooly to study members of Kaiser Permanente in Portland, Oregon. So, there was major morbidity such as hospitalization and mortality that could be prevented with more effective immunization recommendations and practices.

Anyway, starting with the revised influenza immunization recommendations from ACIP, the efforts of CDC to track immunization and suggest ways to improve it, and a series of international conferences called “Options for the Control of Influenza” which Alan Kendal initiated in about 1984, some attention began to be paid to influenza. As annual immunization rates increased in the U.S., albeit still relatively low, more and more evidence accumulated about who might benefit from influenza immunizations, ACIP considered more and more evidence, and immunization recommendations again became more inclusive.

That said, only a handful of people in the U.S. and around the world seemed interested in how a next pandemic – the last being the Hong Kong (H3N2) pandemic of 1968-1969 – might be blunted. Influenza may not be predictable from year to year, but the idea that it will disappear and not trouble us again is unthinkable. Yet, we were doing relatively little about it. When the first outbreak of “Avian flu” (H5N1) occurred in Hong Kong in 1997, we would have been totally unprepared as a nation to develop and apply widespread control efforts had a pandemic occurred. That outbreak was controlled in Hong Kong by killing the large populations of live chickens and ducks that were harboring the virus. With the reappearance of H5N1 a few years later, the world as a whole and the U.S. paid more attention. Significant resources have been devoted to influenza control, developing and testing new vaccines and antivirals, and formulating plans for deployment of control efforts of many types. Although scientific “breakthroughs” are still needed, promising avenues are being pursued, and there is now a large group of scientists working on influenza and influenza control.

The recent H1N1 (swine flu – “again”) pandemic has been a fortunate test of pandemic planning. Though the country and world are still far from prepared, and there is still no chance to remove the pump handle completely, we are much better prepared than just a decade ago and because H1N1 has been “relatively mild”, it has provided an opportunity to find holes and consider ways to plug them rather than providing a tragic relearning of the lesson that influenza epidemics can cause massive societal disruption.

On a personal level, I was involved as an “amateur” in influenza control for many of the past 40 years. I say “amateur” since it was not my main activity at any time after leaving CDC and I never was supported to do work in the field. I realized a year or two ago that there are now enough “professionals” in the field that I can think of the tide in the battle to control influenza having turned and turn my personal attention to other pressing problems. Influenza control isn’t as instantly gratifying as pump handle removal, but the progress is satisfying nonetheless. And, while it is common to think of EIS officers arriving at epidemics or getting involved with diseases after they have peaked and “riding the downhill tail of the epidemic curve to glory”, in fact, it is remarkable to see the degree to which EIS officers have, sometimes alone and more often in concert with teams even huge numbers of others, successfully participated in both short-term and long-term disease control efforts.

The Ogemaw County epidemic has been well described first in a story that Berton Roueche did for the New Yorker, which I found particularly exciting since I had originally been attracted to epidemic investigations and the EIS by reading some of Roueche’s collected stories in “Eleven Blue Men”. The description of Ogemaw remains in print in another collection of Roueche stories, “Medical Detectives”, and is entitled “The West Branch Study” – West Branch being the largest town in Ogemaw County. It is described more formally/scientifically in the following reference: Schoenbaum SC, Baker O, Jezek Z. “Common-source epidemic of hepatitis due to glazed and iced pastries.” American Journal of Epidemiology. 1976; 104:74-79.

Back in 1968, Ogemaw County had a population of about 12,000. A worker in the local bakery and another local resident who happened also to be a food handler at an ice-cream stand had had hepatitis in early April. Then over one month from late April to late May, there were 61 more cases of hepatitis. Since hepatitis A, which in those days was called infectious hepatitis, has an incubation period of about 15-45 days, the whole outbreak was consistent with a common source of exposure back in the early part of April – i.e., sometime in the first two weeks.

Now, cohort studies are based on the idea that the investigator wants to find out if exposure to something causes disease. So, to do a cohort study you start with a group of people who are well but have an exposure of interest – for example, smoking. You find a similar group of people who are well and do not have that exposure – i.e., are non-smokers. Then you follow both groups over time and determine how many in each group become ill from various illnesses. That allows you to calculate the “relative risk” of developing a specific illness, e.g., lung cancer, heart disease, etc, if you are exposed (a smoker) vs. non-exposed (a non-smoker). An advantage of cohort studies is that they allow you to study the occurrence of multiple illnesses in relation to a single type of exposure. Since you start with people who are well and the illnesses develop over time, cohort studies take a lot of time. They are “prospective” studies. It is also the model for clinical trials, i.e., for drugs or other medical interventions. One starts with a group of people and gives some of them a drug, or “exposure”, and compares what happens to the treated group over time vs. the non-treated or non-exposed group.

In contrast, case-control studies are “retrospective”. They work backwards in time. One starts with a group of people who have an illness, the cases, and a group who do not have it, the controls. Then one determines if the members of each group might have or have had a variety of exposures. By comparing the frequency of each exposure in each group one can calculate a statistic known as the “relative odds” of getting the illness in the face of each specific exposure.

When I started the EIS course back in July 1967, the first case study was a church supper or pot-luck supper in Oswego County, New York. The epidemic was due to staphylococcal enterotoxin which has a very short incubation period between the time its victims eat it and the time they become ill. In a church supper in a small town it is possible to determine who was present, who became ill or stayed healthy, and what each person ate. That actually makes it possible to approach the analysis of the information either from a cohort approach – i.e., consider each food on the buffet table an exposure, calculate, and compare the relative risk of illness for those who consumed the food and those who didn’t – or pursuing the case-control approach one could start with the groups of people who got ill vs. those who didn’t, calculate the frequency with which the persons in each group ate each food and then calculate the relative odds of illness for eaters of each food. The cohort approach to analysis is preferred in this situation; and a study in which all the data about the exposures and illness can be obtained at one time is called a “cross-sectional” study.

OK – so back to Ogemaw County: Hepatitis has a relatively long incubation period, especially compared to staph enterotoxin. By the time the epidemiologist learns about the outbreak it really isn’t possible to know the cohorts of persons who were exposed to each possible source of such outbreaks – foods of various types from various sources, water, etc. But, it is easy to know who is sick, the cases. Then one has to pick a suitable group of controls and try to find out from each group what they might have been exposed to. In short, evaluation of such epidemics fits quite naturally into the case-control methodology. There is an issue, however, and it involves selection of an “appropriate” group of controls. This isn’t trivial, and sometimes one even picks a couple of different kinds of controls. Also, one can just pick a group of suitable controls for the group of cases as a whole, or one can try to match a specific control to each case or patient. The theory is that one wants the controls to be as similar as possible to the cases except for the exposures that might have been associated with the development of the illness. So if the cases were all young women, one wouldn’t pick a group of controls that were all old men. On the other hand, if one matches each ill woman who is a specific age with a healthy woman of exactly the same age, then one can no longer study whether gender or age are factors in developing the illness. In Ogemaw County we took a chance in picking the controls. Forty-one of the 61 cases were age 10-19. To have a control group that came close to the case group in demographics, we chose all the household members of cases who were age 10-19 and ended up with 56 of them. The chance that we took was that not everyone who gets infected with the hepatitis A virus becomes ill. So, it was possible that by picking household members of cases we were picking some people who actually had had exposure to the hepatitis virus. In considering them controls we were increasing the likelihood that a high rate of exposure to the culprit would occur in the control group and we wouldn’t be able to identify the culprit since there wouldn’t be enough difference in reported exposure between cases and controls. Nonetheless, it was convenient to be able to interview the cases and controls about exposures on just one contact with a household. So we took the chance. And, it worked out: 92 percent of the patients 10-19 years old had eaten glazed or iced pastries from the local bakery during the first two weeks of April 1968, the likely time of exposure given the body of the epidemic occurring in late April/May; whereas, only 47 percent of the controls reported a similar exposure. The only other frequent exposure reported by cases was West Branch’s municipal water, but the controls reported consuming water from the municipal supply even more frequently than the cases. So, it was just a frequent exposure for anyone living in the Ogemaw County area.

There were many other interesting features to the epidemic in Ogemaw County; and since they are well-described in the journal article and story in Roueche’s “Medical Detectives” I won’t go into them here. What I would like to mention is that like most epidemic investigations, Ogemaw was a team effort. I was sent out from Atlanta where I had been working on influenza. In line with some of the stories in “Inside the Outbreaks”, I needed to learn about the epidemiology of hepatitis A on the flights up to Michigan. I got to work closely with the county health officer, Ophelia Baker; and two other EIS officers were sent up after a few days to help in the investigation – Jim Gardner, the EIS officer in my class who had been assigned to the state of Michigan, and Eugene Page, the EIS officer in Florida. Then one day I got a call from Atlanta. There was a visitor at CDC, a seasoned infectious disease epidemiologist from Czechoslovakia, Dr. Zdenek Jezek. He had had several times as much experience as the three of us EIS officers combined! In fact, at the time he came to visit CDC, he was working for WHO and had just come back from a couple of year assignment in Mongolia. Without the team and Zdenek Jezek’s experience, I doubt we would have been able to pin down the exposure quite so neatly to the worker in the bakery who had become ill in early April. When we observed the bakery operations directly, we saw that he would dip pastries with his bare hands into a pan of glaze, a thick sugar-water mix, and put icing onto other pastries with his hands. Dr. Baker, in her role as the health officer, instituted some food-handling rules for the local businesses that prepared foods on site such as the bakery, and proceeded to inspect them over time. Michigan, which used to manufacture immune serum globulin, had a large supply, and Dr. Baker ran clinics to give globulin to anyone who wanted it which turned out to be the majority of residents of the county. There was no newly reported case of hepatitis in Ogemaw County for over a year after the epidemic.

Early on in “Inside the Outbreaks”, Alex Langmuir’s description of epidemiology as the science of long division gets mentioned as does the classic four-fold table (e.g., in the context of common source epidemics such as pot-luck suppers, a matrix for each food item served would have two columns – “ill”, “not ill” – and two rows – “ate the item”, “did not eat the item”). What comes through by implication in the book is the extraordinary inventiveness that EIS officers and other epidemiologists have exhibited over the years in getting usable numerators and denominators. The method may sound simple, but there are several varieties of epidemiologic studies – the book predominantly mentions cohort and case-control – and one can spend a lifetime coming to an understanding of how best to use epidemiologic methods to address important issues. And, the fact that the EIS has been able to foster so many contributions from people who start out with a two-year term of service and a one-month introductory course, generally taught by peers who have been in the program for just a year themselves, speaks to the robust organization of the program itself including to mention a few, its selection process, development of tools such as the course itself including its use of the case-method type of teaching that Karen Starko describes in her blog post (June 23, 2010), as well as software and other resources EIS officers can use in the field, consultative backup, and development of reports that do not just lead to publications about the issue at hand but also provide the basis for program evaluation.

Some years ago Alex Langmuir was asked to participate in an oral history project, I believe by the National Library of Medicine. When his contribution was completed, there was a ceremony in Boston at the Countway Medical Library, and several of his associates and friends were asked to speak in his honor. I, in turn, was honored to be one of those. At that point, most of my activities were related to management in a large HMO. I had left academia and had taken my first major management position after almost a decade and a half of being an epidemiologist. It was beginning to dawn on me that my work and experiences as an epidemiologist were informing my management career. Indeed, I believe that most epidemiologic projects require developing and managing teams – a theme that is nicely and plentifully illustrated in “Inside the Outbreaks”. In preparing remarks for Alex’s ceremony, I was able to reflect on the fact that in my opinion he was an excellent manager. None of us is perfect; and “Inside the Outbreaks” does a nice job at painting a portrait of Alex both at home and in the workplace “warts and all”. But, I think that readers of the book will recognize that the EIS was a classic start-up/entrepreneurial venture and that its founder was able to grow it into a significant enterprise, many of whose activities and processes have proven durable for decades.

One thing that goes back to the earliest days of the EIS and Alex’s influence, and comes across well in the book, is the notion of translating epidemiologic information into action. Alex had a strong bias towards action, a characteristic of good managers, and that bias fortunately has also persisted over the decades. I believe it has also been injected into many EIS officers, or if already present in our personalities, enhanced by the EIS experience and the opportunities to act that it presents.

In my opinion, Mark Pendergrast has done an excellent job in showcasing the EIS and its history without overly confounding it with the “co-history” of the Centers for Disease Control or the US government as a whole. Yet, these larger forces not only provided the environment in which the EIS did and does function, but also directly affected programs, decisions, and possibly attitudes. The book describes some of the issues around public disclosure of information learned by EIS officers, but it would take a separate analytic vs. an historical approach to really get at the degree to which some of the specific incidents recounted, e.g., what gets included in the MMWR, how to handle the (dis)continuation of a clinical trial, etc, reflect decisions at the level of the EIS vs. CDC vs. some higher level of government. CDC programs and thus the experiences of EIS officers have certainly been affected by higher level decisions. Although CDC still published abortion surveillance reports, I believe that activities recounted in the book that are related to abortion surveillance in the period following Roe v. Wade (1973) changed dramatically as a result of U.S. government policies related to family planning and abortions. Similarly, I suspect that CDC could have, and EIS officers could be involved in, more activities related to injuries resulting from handgun use were it not a controversial area of public policy. CDC is not the only federal agency that is tractable to pressures from strong outside interests. Some readers of this blog may recall that the former Agency for Health Care Policy and Research (AHCPR) was threatened with total loss of funding and almost went out of existence in the mid-1990s because of controversy about its clinical guidelines activities, particularly one for management of back pain, and was reorganized into what is now the Agency for Healthcare Research and Quality (AHRQ), an agency that funds the development of evidence about clinical practices but does not synthesize that evidence into clinical guidelines.

Another theme that comes across well in “Inside the Outbreaks” is that while it is now trendy to talk about globalization, the EIS has had a global perspective since its earliest days in the 1950s and continues to operate and have a global influence directly or through its alumni and “friends” in other countries. That said, I also sensed, probably reflecting my EIS experience, the objective of epidemiologists mentioned in the book about going upstream to find problems that need addressing at their source, and the incidents described in the book, an opportunity for action that has not yet been taken: Beginning with CDC’s assistance in the 1950s for a tidal wave or tsunami to the malnutrition evaluations in what had been Biafra to very recent involvement in the earthquake in Haiti, not described in the book, it has been common to include epidemiologists in aid efforts when responding to disasters around the world. Yet, as Hurricane Katrina showed within this country and as appears to be the case with events in other countries, both the national and international responses appear to be developed ad hoc and often appear uncoordinated. Just as we finally began to recognize a little more than a decade ago with the appearance of H5N1 (Avian) influenza that it was likely that someday there would be another influenza pandemic and that general pandemic preparedness/planning was an important priority, in reading through “Inside the Outbreaks” it dawned on me that international planning for responses to various types of disasters – e.g., floods and earthquakes – makes enormous sense. We may not know when the next will occur, but we know there will be another; and it would be prudent to have designated leaders of the relief efforts. Epidemiologic analysis of prior events would make it clear what the priorities would be for providing certain types of services in a logical order – e.g., arranging for control of air, sea and land traffic to the affected area, handling the press that will predictably arrive, assuring that the type of goods sent are appropriate to the type of disaster and local conditions (hot/cold climate, etc, etc).

I could go on, but I suspect that readers have already gotten my main messages that “Inside the Outbreaks” is an excellent recounting of the history of the EIS, an important U.S. government-sponsored activity that has influenced the lives of a few thousand persons lucky enough to have been in it, and also a highly provocative book. Readers get an extremely clear picture of the contributions possible from the social science of epidemiology and how that science is applied by its practitioners. I would recommend it as interesting, informative, even entertaining, reading.