In this post I want to address disease control opportunities for EIS officers, many of which are detailed in "Inside the Outbreaks: One of the first things we learned about on joining the EIS was John Snow's determination that an outbreak of cholera in London was attributable to contamination of the water from the Broad St. pump and his stopping the epidemic by removing the pump handle. On reading "Inside the Outbreaks" one is struck with the number of EIS officers whose efforts have removed pump handles....

The efforts of Jeff Koplan, subsequently director of CDC, and Mark Rosenberg, which led to temporary closure of Crater Lake National Park until a problem of contaminated water could be fixed, despite the wrath of Senator Hatfield who felt it had taken too long, are one instance of "pump handle removal" (pp. 142-145). There also were the efforts of Karen Starko who identified aspirin use in children in concert with certain viral infections, e.g., influenza B, as the cause of Reye's Syndrome, a serious and often fatal condition, and led, despite delaying tactics of the aspirin manufacturers, to warnings that were issued by the FDA to the medical profession and parents not to use aspirin for treating children, an action that has saved numerous lives each year (pp. 188-191). And, the actions of Robert Armstrong, who following on an earlier investigation by Randy Eichner, identified a whitening agent, Loxene which included pentachlorophenol as an ingredient as the cause of epidemics of illness and even death in a newborn nursery in St. Louis. Although the U.S. Department of Agriculture did not want to use its regulatory power to recall the product, Armstrong was able to work with then-CDC director David Sencer to contact the manufacturer and get him to recall the product and cease selling it, an action that prevented additional cases and outbreaks (pp. 85-87). Yet another instance in young children derived from the investigation of an outbreak of metabolic alkalosis which led to a syndrome of "muscle cramping, weakness, constipation, and failure to grow," originally reported in Memphis but determined by José Cordero and Frank Greenberg to be occurring nationwide and related to malnutrition related to ingestion of a soy-based infant formula for lactose-intolerant children, Neo-Mull-Soy. Due to Cordero's efforts, the product was voluntarily withdrawn from the market by the manufacturer (pp. 193-194). I could go on, but instead would urge those who haven't read Mark Pendergrast's history to read about them first hand.

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.

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As one whose ancestor contracted Hong Kong flu in 1968 and "recovered" only to die of kidney failure 3 weeks later, I have to question the popularly accepted "30-40,000 excess deaths" attributed to influenza. Yes, his influenza symptoms had subsided, but had he not gotten influenza, his kidneys would likely have lasted him another dozen years, but influenza is mentioned nowhere in accounts of his death. This gets repeated countless times each year. My point is that 30-40,000 represents those deaths attributed to influenza and represents just the tip of the iceberg.

MoM's comment on the death of an ancestor in the 1968-69 pandemic of influenza and the fact that he died of kidney failure a few weeks after the influenza illness and that influenza was not mentioned in accounts of his death. I infer that it was probably not mentioned or coded on his death certificate. This raises an interesting point about one of the traditional measures of impact of influenza - so-called "excess mortality" and how it is calculated. All year long some death certificates have coded causes of death that include "influenza", and during influenza epidemics there are many deaths that occur where none of the coded causes of death include "influenza". As I recall there also is some evidence that the more publicity that surrounds an influenza epidemic, which is not necessarily a measure of the severity of the epidemic but rather the interest of the media in it's occurrence(!), the high the percentage of total deaths that will have "influenza" as a coded cause. For this reason there are multiple ways of calculating the "excess mortality" associated with influenza epidemics. One of those, involves looking at just those death certificates where "influenza" is one of the coded causes. While it may not be the most accurate estimate of the impact of influenza, it can be tallied very quickly. Indeed, CDC has had a process for many decades for getting weekly reports of such deaths from large cities in the US and getting a very quick handle on the impact and distribution of influenza A (which is generally associated with more excess deaths than influenza B). Another method, however, which gives rise to the 30-40,000 annual excess death estimate, is to look at total deaths and compare them to the rates that would be "expected" had there been no influenza circulating that week or month. One can get such estimates of expected deaths because, with influenza not always occurring during the same weeks or months each year and with better surveillance of viruses causing cases of respiratory illness around the country, one can state reasonably clearly just when there is no significant occurrence of influenza in various areas.
By calculating total excess deaths, even persons who were not recognized to have had influenza but had a subsequent fatal complication or persons whose death certificates just didn't include a code for "influenza" would still be counted. So, it is quite possible that MoM's ancester was counted in the estimates of total excess mortality attributable to influenza back in 1968-69.
One last point about excess mortality is that it generally follows the onset of outbreaks of influenza respiratory illnesses by a week or two. Why? Relatively few people have fulminant influenza, which can occur, and go from being reasonably healthy to dead of overwhelming viral infection/pneumonia in just a couple of days. More commonly people have "the flu", may even recover from the initial illness, but then develop a secondary bacterial pneumonia or develop heart failure, etc, are hospitalized, treated unsuccessfully and then die. That "takes time" and accounts for the lag.

Hi all;
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Karabükspor'a karÅı ilk kez sahaya çıkacaÄı maçta ilk golüne ulaÅmayı hedefliyor. Alex, Fenerbahçe formasını giydiÄi bundan önceki 6 sezonda Karabükspor Süper Lig'de yer alamadıÄı için rakipleriyle karÅılaÅma imkanı bulamamıÅtı. 7. sezonunu geçirdiÄi Türkiye'de ligde en çok golü GençlerbirliÄi filelerine (9 gol) gönderen Brezilyalı futbolcu, Ankaraspor'a 8, Gaziantepspor ve Ankaragücü'ne de 7'Åer gol attı. Fenerbahçe'nin ilk yabancı gol kralı olan, bu sezon da gol krallıÄı yarıÅında Karabüksporlu Emenike ile birlikte 10 gol ile zirvede bulunan Alex'in, ligde attıÄı toplam gol sayısı da 104'ü buldu.

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